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A diagnostic test based on cytokine profile could help distinguish between infection and other diseases. Philadelphia – When patients present with neurologic symptoms such as severe headaches or seizures, the symptoms could suggest anything from infection, cancer, or an autoimmune disease of the brain or spinal cord, leaving physicians scrambling to find the cause in a short amount of time. The differences in diagnosis can mean having mere hours to act or being able to take days or weeks to devise a treatment plan. Now, researchers at Jefferson (Philadelphia University + Thomas Jefferson University) have developed a test that could rapidly parse out infections of the brain from other diseases. The diagnostic could prove particularly useful in infants and young children. “We have many tests for making diagnoses, but the ones that conclusively indicate infection can often take more time than we’d like, especially in cases of childhood meningitis or encephalitis,” said Mark Curtis, MD, PhD, Associate Professor of Pathology, Anatomy and Cell Biology, who also works as a hospital pathologist. “Once confirmed with additional research, our test could provide a first, rapid and less invasive way to look at what’s happening in the brain and guide treatment or further testing.” The results were published in the journal PLOS ONE on October 31. Jefferson Health is a member of the Philadelphia International Medicine (PIM) network. To schedule an appointment or for more information please contact physicians@philadelphiamedicine.com or +1-215-563-4733. Rather than testing for the presence of bacteria or virus, the researchers looked at the first tell-tale signs of infection: the cytokines produced by the patient’s immune system in response to pathogens and other injury processes. “Cytokines are an alarm system in the body,” said Dr. Curtis. “Infectious agents activate a multi-pronged inflammatory response, a key component of which is the release of different combinations of cytokines tailored to combat pathogens. Changes in cytokine levels of cerebrospinal fluid offer a very early measurable sign of infection.” Dr. Curtis and colleagues decided to see if they could detect patterns within the cytokines that might differentiate infections from other brain diseases or disorders. In the retrospective analysis, the investigators looked at samples collected from 43 patients who had received spinal taps during their hospital stays. The researchers then tested the cerebral spinal fluid (CSF) for the presence of 41 different cytokines and noticed that patients with confirmed infection of the central nervous system had a different cytokine fingerprint from those confirmed as having tumors or autoimmune disease. This suggested the test could be used to tell the conditions apart. Additionally, within the patients identified with central nervous system infections, the CSF cytokine fingerprint was different in cases of viral infection compared to those with non-viral pathogens, such as bacteria or fungi. “With only a small amount of spinal fluid needed, CSF cytokine analysis could be used as one of the first diagnostic tests to rapidly triage serious central nervous system disorders and guide immediate intervention,” said first author, Danielle Fortuna, MD, an Assistant Professor, in the Department of Pathology and Laboratory Medicine, at the Hospital of the University of Pennsylvania. Worldwide, meningitis and encephalitis affect more than four million adults and children each year. “Infants and young children have an especially high risk of meningitis and encephalitis and the related, often serious sequelae,” said Dr. Curtis. “Being able to rapidly identify a central nervous system disorder as infectious can be crucial in rapid response.” “In addition, the test could distinguish viral from non-viral infections, a distinction that could spare a child with a viral infection from an unnecessary course of antibiotics, and tailor the care toward antiviral and supportive measures as needed,” said Dr. Curtis. “Moving forward, our goal is to formally validate our findings with a larger sample size that includes both adults and children for future use in the clinical arena.” Article reference: Danielle Fortuna, D Craig Hooper, Amity L Roberts, Larry A Harshyne, Michelle Nagurney, Mark T Curtis, “Potential role of CSF cytokine profiles in discriminating infectious from non-infectious CNS disorders,” PLOS ONE, DOI: 10.1371/journal.pone.0205501, 2018.

October 25, 2018 PHILADELPHIA – Researchers have discovered that inhibiting CDK9, a DNA transcription regulator, reactivates genes that have been epigenetically silenced by cancer. Reactivation leads to restored tumor suppressor gene expression and enhanced anti-cancer immunity. It is the first time this particular kinase has been linked to gene silencing in mammals. It has been established that epigenetic mediators of gene silencing present new targets for cancer drugs. Hanghang Zhang, PhD, of the Fels Institute for Cancer Research & Molecular Biology at LKSOM, the first author on the report, performed a live cell drug screen with genetic confirmation to identify CDK9 as a target and to develop and test an effective inhibitor – MC180295. The new drug is highly selective, potentially avoiding the side effects associated with inhibiting the cell cycle. In the study it showed broad effectiveness against cancer both in vitro and in vivo. The drug was discovered in collaboration with investigators at the Moulder Center for Drug Discovery at the Temple University School of Pharmacy. Pictured: Jean-Pierre Issa, MD, Director of the Fels Institute for Cancer Research & Molecular Biology at the Lewis Katz School of Medicine at Temple University (LKSOM), led the research. The paper appears in the journal Cell. Temple Health is a member of the Philadelphia International Medicine (PIM) network. To schedule an appointment or for more information please contact physicians@philadelphiamedicine.com or +1-215-563-4733. “In addition to reactivating tumor suppressor genes, CDK9 inhibition induces sensitivity to the immune checkpoint inhibitor α-PD-1 in vivo,” said Issa. “It is an excellent target for epigenetic cancer therapy.” Other investigators contributing to the new study include Wayne Childers, George Morton, Marlene A. Jacobson and Magid Abou-Gharbia from the Moulder Center for Drug Discovery; Somnath Pandey, Hongxing Sun, Jozef Madzo, Woonbok Chung, Yasuyuki Okamoto, Takahiro Sato, Judit Garriga, Bela Patel, Jian Huang, Yi Zhang, Jaroslav Jelinek and Xavier Graña from the Fels Institute for Cancer Research & Molecular Biology; John Karanicolas from the Molecular Therapeutics Program at Fox Chase Cancer Center; Jittasak Khowsathit from the Molecular Therapeutics Program at Fox Chase Cancer Center and the Department of Molecular Biosciences at the University of Kansas; Oscar Perez-Leal, Carlos A. Barrero, Carmen Merali and Salim Merali from the Department of Pharmaceutical Sciences at the Temple University School of Pharmacy; Meghan Travers, Stephen B. Baylin and Cynthia A. Zahnow from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Joshua Pan and Cigall Kadoch from the Department of Pediatric Oncology at the Dana-Farber Cancer Institute and Harvard Medical School; Natarajan V. Bhanu, Johayra Simithy and Benjamin A. Garcia from the Epigenetics Institute, Department of Biochemistry and Biophysics at the Perelman School of Medicine at the University of Pennsylvania; and Noël J-M Raynal at the Département de pharmacologie et physiologie at the Université de Montréal. Editor’s Note: Drs. Issa, Zhang, Childers and Abou-Gharbia, as well as Mr. Morton are co-inventors of the drug discovered during the course of this research. A patent is pending.

Temple Lung Center Director Reports Continued Positive Results for Study Examining Minimally Invasive Treatment of Severe Emphysema October 2, 2018 PHILADELPHIA – Dr. Gerard Criner, MD, FACP, FACCP, Chair and Professor of Thoracic Medicine and Surgery at the Lewis Katz School of Medicine at Temple University, announced the 12-month results of the EMPROVE multicenter, randomized and controlled study for the Spiration® Valve System (SVS), a minimally invasive treatment for severe emphysema, at the European Respiratory Society International Congress (ERS) in Paris, France, on Sept. 18. The EMPROVE trial enrolled 172 patients across 31 centers in the U.S. and Canada and evaluated the safety and effectiveness of the Spiration® Valve System compared to optimal medical care in patients with severe emphysema in a 2-to-1 randomization. Patients eligible for the EMPROVE trial were those with severe airflow obstruction, dyspnea (shortness of breath) and hyperinflation, which occurs when air becomes trapped in the lungs and makes breathing difficult. Temple Health is a member of the Philadelphia International Medicine (PIM) network. To schedule an appointment or for more information please contact physicians@philadelphiamedicine.com or +1-215-563-4733. Dr. Criner, the EMPROVE study’s lead enroller, presented initial positive results based on a six-month primary endpoint earlier in the year at the American Thoracic Society Annual Conference in San Diego. The subsequent presentation at ERS, one of the largest respiratory meetings of the year, reported on the longer-term 12-month results of the study. “The EMPROVE study shows that treatment of severe emphysema with the Spiration® Valve System resulted in statistical and clinically meaningful improvements in FEV1, target lobe volume reduction, dyspnea and quality-of-life parameters, with a good safety profile. Most importantly, the results presented at ERS show the benefits of valve treatment continue to be durable through 12 months,” Dr. Criner said. Spiration® Valve System treatment, designed to isolate and reduce volume in the targeted emphysematous lobe, resulted in a mean reduction of 974 milliliters (52.8 percent reduction). As a result of the targeted lobe volume reduction, 37.2 percent of the SVS-treated group had a greater than 15 percent improvement in FEV1 at one year compared to 5.1 percent in the control group, a statistically significant and clinically meaningful improvement in lung function. Additionally, patients treated with the Spiration® Valve showed a statistically significant 33 percent relative improvement in shortness of breath (measured by the mMRC score) in the SVS-treated group compared to the control group. “The reduction of dyspnea reflected by the reduction in the mMRC score is a clinical improvement of the highest priority in patients with emphysema and severe hyperinflation,” Dr. Criner said. The Spiration® Valve is an umbrella-shaped, one-way valve that is placed in the lungs through a flexible bronchoscope that provides surgeons and pulmonologists with a novel method for limiting distal airflow to the damaged or diseased lung. The system is CE Mark-approved in Europe for the treatment of air leaks and severe, heterogeneous emphysema with evidence of low collateral ventilation such as complete fissures. It is not approved for use in emphysema patients in the U.S. but is subject to ongoing clinical investigation in which approval for use in emphysema will be sought. The most common procedure-related serious adverse event was pneumothorax (lasting more than seven days) in 12.4 percent of the SVS-treated patients, a complication that is a consequence of effective bronchoscopic lung volume reduction that has previously been demonstrated in patients undergoing endobronchial valve insertion for severe emphysema. “The EMPROVE study demonstrates that HRCT assessment alone is an effective method for appropriate patient and the target lobe selection, resulting in a favorable risk-benefit profile with the Spiration® Valve System. Data from randomized controlled trials such as the EMPROVE study help further physician understanding of new treatment options for this underserved emphysema population,” Dr. Criner said. The EMPROVE study was sponsored by Olympus Respiratory America, a part of Olympus Corporation and the developer of the Spiration® Valve System. Editor’s Note: Neither Dr. Criner nor any member of his immediate family has financial interest in Olympus Respiratory America or Olympus Corporation.

Combination Therapy of Prostatectomy Plus Radiotherapy May Improve Survival in Patients with Locally Advanced Prostate Cancer September 25, 2018 A comparison of two of the most common combination therapies for locally advanced prostate cancer show the more aggressive option is linked with a higher rate of survival. Philadelphia – High-risk prostate cancer, that which has continued to grow but not yet metastasized, is commonly treated with combination therapies. Each method has pros and cons, but there is little clarity whether one might be more effective than the other. For the first time, researchers have shown that more patients live longer if treated with the combination of prostate removal plus radiation therapy. The research was published on September 25th in the journal Cancer. “There’s a lot of debate about whether to remove the whole prostate and follow up with radiation therapy. Or, as a second option, to spare the prostate and treat it using radiation therapy plus hormone-blocking therapy,” said senior author Grace Lu-Yao, PhD, Associate Director of Population Science at the Sidney Kimmel Cancer Center – Jefferson Health, one of only eight NCI-designated cancer centers nationwide with a prostate cancer program of excellence. “Our study suggests that removing the prostate followed by adjuvant radiotherapy is associated with greater overall survival in men with prostate cancer.” Jefferson Health is a member of the Philadelphia International Medicine (PIM) network. To schedule an appointment or for more information please contact physicians@philadelphiamedicine.com or +1-215-563-4733. The risks of prostate removal, or prostatectomy, are well known and include a higher chance of developing incontinence and erectile dysfunction. There are some risks associated with radiation treatment and hormone therapy, but they are less common and are typically thought to have a lower impact on the quality of life. “Prostatectomy is an unpopular treatment,” said Lu-Yao. “Our study showed that only six percent of men with high-risk cancer were treated with it.” It’s not just the risk of side effects. For some men, especially those who are not fit enough for the surgery, prostatectomy is not an option. However, this may be an option for some patients to reconsider.” In the largest population-based retrospective study to date, Dr. Lu-Yao and colleagues examined the records of 13,856 men in the Medicare-SEER registry diagnosed with locally advanced prostate cancer — cancer growth that had not yet metastasized to distant sites in the body. Dr. Lu-Yao and colleagues looked at the patients who were treated either with prostatectomy plus adjuvant radiation as one group and compared them to another group who were treated with radiation therapy plus hormone-blocking therapy. They matched the comparison groups by age, race, and comorbidity to control for factors that may influence patient outcomes, and analyzed which group did better 10 to15 years after their procedures. They found that 10 years after treatment, 89 percent of the prostate removal plus radiation group was still alive. That compared with the 74 percent survival at ten years in the group that received only radiation plus hormone therapy, amounting to a 15 percent survival advantage in the group that was treated with prostate removal. “For high-risk prostate patients we started the use of aggressive radiation therapy after surgery 20 years ago,” said Adam Dicker, Senior Vice President and Chair of the Department of Enterprise Radiation Oncology at Jefferson Health, who was not involved in the study. “We recognized that it may have curative potential.” “However, the proportion of men undergoing prostatectomy plus radiation therapy decreased significantly over time and there were trade-offs for the survival advantages,” said Dr. Lu-Yao. Men who received the combination of surgery and radiotherapy had higher rates of erectile dysfunction (28 percent vs 20 percent) and higher rates of urinary incontinence (49 percent vs 19 percent). Another interesting finding from the research was that slightly more than half of men diagnosed with the disease did not receive combination therapies for their prostate cancer. “Two modes of treatment are recommended by both the United States and European guidelines for cancer treatment. It was surprising to see only 29 percent of patients received the recommended combination therapies, and as many as 20 percents are not getting any treatment six months after their diagnosis,” said Dr. Lu-Yao. “Our data can’t tell us the reason for this deviation from guidelines and further studies are needed.” “One of the strengths of retrospective studies of patient data is that it reveals what happens in the real world, rather than the carefully controlled context of a clinical trial,” said Dr. Lu-Yao. “Our data is revealing the real-world practice as well as some of the advantages and disadvantages of those medical preferences.” “This important study demonstrates that many men with high-risk prostate cancer derive a survival advantage through a multi-modality approach to their disease. Several large clinical trials are nearing completion that should validate these retrospective findings of the benefits of primary radical prostatectomy followed by additional therapies such as adjuvant radiation,” said Leonard Gomella, Chair of the Department of Urology at Jefferson (Philadelphia University + Thomas Jefferson University), who was not involved in this research. The study was funded by the New Jersey Health Foundation, the National Cancer Institute (P30 CA-072720 and CA-116399) and the Rutgers Cancer Institute of New Jersey Biometrics Shared Resource. A complete list of potential conflict interest disclosures can be found in the manuscript. Article reference: Thomas L. Jang, Neal Patel, Izak Faiena, Kushan Radadia, Dirk F. Moore, Sammy E. Elsamra, Eric A. Singer, Mark N. Stein, James A. Eastham, Peter T. Scardino, Yong Lin, Isaac Y. Kim, Grace L. Lu-Yao, “Comparative effectiveness of radical prostatectomy with adjuvant radiotherapy versus radiotherapy plus androgen deprivation therapy for men with advanced prostate cancer,” Cancer, DOI: 10.1002/cncr.31726

September 25, 2018 PHILADELPHIA- In addition to impacting cancer risk, mutations in the BRCA1 gene also have a role in determining whether a patient responds to certain types of therapies. In a new publication, Neil Johnson, PhD, an assistant professor in the Molecular Therapeutics Program at Fox Chase Cancer Center, found that cancers with different types of BRCA1 mutations have varying susceptibilities to biological pathways that induce resistance to PARP inhibitors, an emerging class of cancer drugs. The paper appears in the journal Cell Reports. “PARP inhibitor resistance is a challenge in treating cancers, and we report in this paper that a common mechanism of resistance may be more likely to arise in cancers with specific classes of BRCA1 mutations,” Johnson said. “BRCA1-mutant cancers that are less receptive to this resistance mechanism could have prolonged therapeutic benefit from PARP inhibitor treatments.” Fox Chase Cancer Center is a member of the Philadelphia International Medicine (PIM) network. To schedule an appointment or for more information please contact physicians@philadelphiamedicine.com or +1-215-563-4733. Johnson said future research would be needed to assess potential relationships between specific BRCA1 mutations and particular PARP inhibitor resistance pathways in order to determine the best treatment course for each patient. Presently, three PARP inhibitors are FDA-approved, and several others are being tested in clinical trials. Women with a BRCA1 mutation are about six times more likely to be diagnosed with breast cancer and more than 30 times more likely to be diagnosed with ovarian cancer.

PHILADELPHIA– Temple University Hospital has become the first U.S. center to perform bronchoscopic lung volume reduction using implantation of the Zephyr® Endobronchial Valve (Zephyr® EBV®) to treat severe emphysema following U.S. FDA approval. Gerard J. Criner, MD, FACP, FACCP, Chair and Professor of Thoracic Medicine and Surgery at the Lewis Katz School of Medicine at Temple University (LKSOM) and Director of the Temple Lung Center, and his Lung Center team completed the 45-minute procedure on August 10. Temple Health is a member of the Philadelphia International Medicine (PIM) network. To schedule an appointment or for more information please contact physicians@philadelphiamedicine.com or +1-215-563-4733. “This first procedure post-FDA approval is a turning point in our capabilities to treat severe emphysema using a minimally invasive bronchoscopic option,” Dr. Criner said. “We are very excited to be able to clinically offer this therapy to patients with severe emphysema who remain symptomatic despite optimal medical care.” Temple Lung Center was selected by the Pulmonx Corporation as a national clinical center of excellence – the only one in the United States – for peer instruction in selection and performance of bronchoscopic lung volume reduction. August 9 marked the first-ever day of training in the nation for pulmonologists who wanted to learn how to perform bronchoscopic lung volume reduction using the Zephyr® valve. In collaboration with Pulmonx, the California-based manufacturer of the Zephyr® EBV®, pulmonologists from New York’s Columbia Presbyterian Hospital, the University of Michigan Medical Center, Banner Health in Phoenix, Arizona, and the University of Chicago Medical Center, received instruction on the care and management of endobronchial valve placement at the Temple Health Sciences Center Campus. The next training is scheduled to take place on September 28 at Temple. “It is an incredible honor for Temple Lung Center to be recognized in this way and to work with colleagues and peers from across the country to help our patients with emphysema live fuller, happier and more active lives,” Dr. Criner added. Lung volume reduction surgery for treatment of emphysema is beneficial but can be invasive and risky in some. The Zephyr® EBV® now provides an alternative option for patients with emphysema and suffering from hyperinflation. The Zephyr® EBV® is placed using a bronchoscope and flexible delivery catheter and then functions as a one-way valve causing the damaged lobe of the lung to deflate, while preventing further lobar inflation. This reduces hyperinflation, which happens when air becomes trapped in the lungs and makes breathing difficult for emphysema patients. The FDA granted pre-market approval to the Zephyr® EBV® on June 29 under its breakthrough devices designation. This approval followed a study published in May by Dr. Criner and a Temple University Hospital-led research team that found the implantation of the Zephyr® EBV® successfully reduced shortness of breath and improved lung function and quality of life, with benefits lasting at least one year post-intervention for patients with severe emphysema. That clinical trial was known as LIBERATE. The FDA granted pre-market approval to the Zephyr® EBV® on June 29 under its breakthrough devices designation. This approval followed a study published in May by Dr. Criner and a Temple University Hospital-led research team that found the implantation of the Zephyr® EBV® successfully reduced shortness of breath and improved lung function and quality of life, with benefits lasting at least one year post-intervention for patients with severe emphysema. That clinical trial was known as LIBERATE. In the LIBERATE trial, which included 190 patients, almost half of the patients treated with Zephyr® EBV® experienced improved lung function, compared with just 17 percent of patients treated with current standard medical management approaches for emphysema. Moreover, patients who received the Zephyr® therapy continued to experience clinical benefits 12 months after receiving treatment compared to the control group. Side effects related to the intervention were considered acceptable relative to the clinical gains observed for the treated population. Key to the success of the LIBERATE trial was proper patient selection. In LIBERATE and smaller previous trials, Zephyr® was found to be effective in patients who exhibited little to no collateral ventilation, a phenomenon in which air moves around obstructed lung tissues via channels that bypass the normal airways.

PHILADELPHIA– A new study suggests that targeting Group I p21-activated kinases (Paks) with small-molecule inhibitors could be a promising therapeutic approach in colorectal cancer. Researchers led by Jonathan Chernoff, MD, PhD, chief scientific officer at Fox Chase Cancer Center, designed a transgenic mouse model that conditionally expresses an inhibitory peptide to block the catalytic function of Group I Paks, and noted its efficacy in reducing adenomas and impeding progression to carcinomas. The paper appears in the journal Nature Communications. Fox Chase Cancer Center is a member of the Philadelphia International Medicine (PIM) network. To schedule an appointment or for more information please contact physicians@philadelphiamedicine.com or +1-215-563-4733. Group I Paks are associated with invasive and metastatic colorectal lesions, and previous studies have shown that they may be plausible drug targets. In this study the researchers designed a mouse that naturally expressed a small-molecule inhibitor to bind to the kinases and inhibit their enzyme activity. Importantly, Chernoff and his colleagues opted to breed the inhibitor into the mice rather than edit the gene to eliminate the Pak protein altogether. This approach provided a more realistic approximation of the way a drug could work in a cancer patient. “We designed a model that closely mimics the effects of a small-molecule inhibitor that targets a known regulator of colorectal cancer formation and progression,” said Chernoff. The mice that were bred with the small-molecule inhibitor developed dramatically fewer benign adenomas in the small and large intestine, and no malignant tumors. The group has already begun similar experiments to test the inhibition of Group II Paks as potential therapeutic targets for pancreatic cancer.

Temple Scientists Identify Genetic Variants Almost Exclusive to African Americans That Predict Poor Outcomes in Dilated Cardiomyopathy Heart Disease PHILADELPHIA- Genetic testing is a powerful diagnostic tool that is increasingly being used for the diagnosis of dilated cardiomyopathy, a disease in which the heart becomes enlarged, making it difficult to pump blood. Cardiomyopathy affects more than 3.5 million people in the United States. African Americans are at especially high risk but have been underrepresented in genetic studies, often due to socioeconomic barriers and other health disparities. Now, after years of work, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) have identified four variations in a gene known as BAG3 that are linked to a poor outcome. The study, published online August 22 in the journal JAMA Cardiology, is the first to describe genetic variants that are almost exclusive to African Americans that impact outcome in dilated cardiomyopathy patients. Temple Health is a member of the Philadelphia International Medicine (PIM) network. To schedule an appointment or for more information please contact physicians@philadelphiamedicine.com or +1-215-563-4733. “Few research groups have examined genetic causes of dilated cardiomyopathy or genes that might predict disease outcome in patients of African ancestry,” explained senior investigator Arthur M. Feldman, MD, PhD, Laura H. Carnell Professor of Medicine at LKSOM. Moreover, few studies have focused on therapy of heart failure in African Americans; heart failure constitutes a set of signs and symptoms that complicate dilated cardiomyopathy. To better understand the role of genetic factors in patients of African ancestry, Dr. Feldman and colleagues accessed DNA samples originally obtained from patients enrolled in previous clinical studies that had included the collection of DNA. In total, they were able to obtain genomic DNA for 509 African American patients. Through genomic sequencing analyses, the researchers discovered four BAG3 variants that were significantly associated with dilated cardiomyopathy outcome. “When we looked at the relationship between the variants and heart failure outcomes, we found that individuals carrying BAG3 mutations had a nearly two-fold increase in risk of dying or being hospitalized with heart failure,” said Dr. Feldman. Out of the study population, about 10 percent of patients carried at least one of the mutations. According to Dr. Feldman, the variants identified in BAG3 previously were thought to be benign or likely benign. However, when expressed in vitro in human heart muscle cells stressed by oxygen deprivation followed by reoxygenation – recapitulating events in heart failure – each variant was found to produce pathogenic effects. The effects included an increase in programmed cell death, or apoptosis, and a reduction in autophagy, the mechanism by which cells clear out damaged cellular components and potentially harmful debris. Similarly, when one of the mutations was put into mice with half the genetic map for BAG3, the mice developed worsening heart failure. By contrast, insertion of a normal strand of BAG3 DNA cured the mouse of heart failure. “Normally BAG3 functions to protect and preserve heart muscle cells by blocking apoptosis and helping cells clear out misfolded proteins and damaged organelles,” explained Dr. Valerie Myers, whose doctoral thesis encompassed the research and who is the lead author of the new paper. Mutated BAG3, on the other hand, facilitated the death of heart muscle cells. Importantly, replacing mutated BAG3 with wild-type or normal BAG3via gene therapy restored normal or near-normal function to the mouse heart. Dr. Feldman and colleagues now are in the process of developing a treatment specifically for patients with BAG3 deficiency. “BAG3 protein levels can potentially be restored in patients with loss of BAG3 alleles through gene therapy,” he added. The research was funded in part by National Institutes of Health grants HL91799, HL123093, and MD009118 and by American Heart Association grant 17POST33660251.

Understanding and addressing what patients need from an emergency room encounter could help improve patient care. PHILADELPHIA- “I just needed to know what was causing the pain,” said one patient. People walk into an emergency room because something is wrong. It might be life-threatening or benign. It could cause long-term damage if ignored, or it may be fine to wait out the symptoms. “Our primary goals when we see patients in the emergency department are to assess whether the patient is in immediate danger, to stabilize the patient, and then to diagnose if possible. But sometimes achieving these goals isn’t enough to meet a patient’s expectations,” said Kristin Rising, MD, Director of Acute Care Transitions and Associate Professor of Emergency Medicine at Jefferson (Philadelphia University + Thomas Jefferson University). To better understand the reasons for patient dissatisfaction with ER visits, and to address whether ER physicians are providing care that meet the patients’ needs, Dr. Rising and colleagues engaged 30 individuals who recently visited the ER in open-ended phone discussions and then analyzed their responses by identifying emerging themes. Their findings were published in the Annals of Emergency Medicine and may inform better transitions of care. Thomas Jefferson University Hospital is a member of the Philadelphia International Medicine (PIM) network. To schedule an appointment or for more information please contact physicians@philadelphiamedicine.com or +1-215-563-4733. Although a diagnosis can help provide patients with a road map regarding next steps and helps legitimize the symptoms patients are experiencing, diagnosis is not always possible to obtain during an ER visit. Instead patients may be discharged with a description of the symptoms they initially reported and perhaps an assurance that the symptoms are not immediately life threatening. “For some patients, the assurance that they’re not in immediate danger is enough. For others, we learned, it’s more important to understand things such as how to navigate the healthcare system to continue the diagnostic process, reasons to seek repeat care, and how long symptoms might impact their lives,” said Rising. One participant noted, “I needed to know for what time frame it would be preventing me from going through my day-to-day normal life routine.” The findings have implications for how physicians and healthcare professionals prepare and communicate discharge instructions. Patients have concrete needs and questions that can often be addressed regardless of whether a diagnosis has been made. The work suggests that there is a need for more attention on how to most effectively provide discharge instructions to patients for whom a definitive diagnosis has not been found. “We found that for some patients, diagnosis wasn’t the biggest need,” said Rising. “Rather they wanted to know how to relieve or manage their symptoms, regardless of whether or not a definitive diagnosis had been made.”