Body

New research indicates that a prior induced abortion poses only a very small risk of negative effects on births from subsequent pregnancies, but the risk is higher if the abortion is performed later in the pregnancy.

The Acta Obstetricia et Gynecologica Scandinavica study included 418,690 first-time mothers with singleton births between 1996 and 2013 in Finland. Investigators observed an increased risk of extremely preterm birth and very low birthweight among women with late abortion(s) when compared with those with early abortion(s).

When the analysis was restricted to only one abortion, women who had had a late abortion showed a higher risk of only extremely preterm birth compared with women who had experienced an early abortion.

In an Acta Paediatrica study, exclusive breastfeeding for the first 3 months was linked with a lower risk of respiratory allergies and asthma when children reached 6 years of age.

In the study of 1,177 mother-infant pairs, a third of the children were exclusively breastfed until the age of 3 months. By the age of 6 years, 20.8% of children had been diagnosed with respiratory allergies and 11.3% with asthma.

Exclusive breastfeeding for 3 months was associated with a 23% lower relative risk of respiratory allergies at the age of 6 years. It was also associated with a 34% lower relative risk of asthma, but only if the children did not have a family history of asthma.

Breastfeeding for 3 months, but not exclusively, was insufficient to reduce the risk of respiratory allergies or asthma.

"Airway disorders such as respiratory allergies and some asthma may be prevented in some cases by encouraging exclusive breastfeeding for at least 3 months, as human milk was potentially beneficial in reducing the risk of airway disorders among children," said author Galya Bigman, PhD, of the University of Maryland, Institute of Human Virology, School of Medicine.

Individuals who undergo weight loss surgery may face an elevated risk of bone fractures, according to a study published in the Journal of Internal Medicine.

The study included 2,007 Swedish patients with obesity who were treated with weight loss surgery (either gastric bypass, gastric banding, or vertical banded gastroplasty) and 2,040 matched patients who did not undergo surgery. Over a median follow-up of between 15 and 18 years for the different treatment groups, the highest incidence rate for fractures was seen in the gastric bypass group. Rates were 22.9 per 1,000 person-years in this group, compared with 10.4, 10.7, and 9.3 per 1,000 person-years for the vertical banded gastroplasty, gastric banding, and control groups, respectively. (These rates translate to 229, 104, 107, and 93 people experiencing a fracture per 10,000 people over one year.)

The fracture risk in the gastric bypass group was 2.58-times higher than in the control group, 1.99-times higher than in the gastric banding group, and 2.15-times higher than in the vertical banded gastroplasty group.

"Our results show that gastric bypass surgery increases the long-term risk of fracture, both compared with non-surgical obesity care and compared two other bariatric surgery methods used in our study," said lead author Sofie Ahlin, MD, PhD, of the University of Gothenburg, in Sweden. "Increased risk of fracture is a serious side effect that should be taken into account when selecting surgical procedures and it should also be kept in mind during post-operative follow-up in patients who have undergone gastric bypass."

Researchers at the National Institutes of Health and the University of Wisconsin have demonstrated that using artificial intelligence to analyze CT scans can produce more accurate risk assessment for major cardiovascular events than current, standard methods such as the Framingham risk score (FRS) and body-mass index (BMI).

More than 80 million body CT scans are performed every year in the U.S. alone, but valuable prognostic information on body composition is typically overlooked. In this study, for example, abdominal scans done for routine colorectal cancer screening revealed important information about heart-related risks - when AI was used to analyze the images.

The study compared the ability of automated CT-based body composition biomarkers derived from image-processing algorithms to predict major cardiovascular events and overall survival against routinely used clinical parameters. The investigators found that the CT-based measures were more accurate than FRS and BMI in predicting downstream adverse events including death or myocardial infarction, cerebrovascular accident, or congestive heart failure. The results appeared in The Lancet Digital Health.

"We found that automated measures provided more accurate risk assessments than established clinical biomarkers," said Ronald M. Summers, M.D., Ph.D., of the NIH Clinical Center and senior author of the study. "This demonstrates the potential of an approach that uses AI to tap into the biometric data embedded in all such scans performed for a wide range of other indications and derive information that can help people better understand their overall health and risks of serious adverse events."

The study used five AI computer programs on abdominal CT scans to accurately measure liver volume and fatty change, visceral fat volume, skeletal muscle volume, spine bone mineral density, and artery narrowing. Researchers found that not only did the combination of automated CT-based biomarkers compare favorably with the FRS and BMI for predicting cardiovascular events and death before any symptoms were present but in fact, the CT measure of aortic calcification, that is buildup of calcium deposits in the aortic valve, alone significantly outperformed the FRS for major cardiovascular events and overall survival.

The researchers also observed that BMI was a poor predictor of cardiovascular events and overall survival, and all five automated CT-based measures clearly outperformed BMI for adverse event prediction.

"This opportunistic use of additional CT-based biomarkers provides objective value to what doctors are already doing," said Perry J. Pickhardt, M.D., of the University of Wisconsin School of Medicine & Public Health, lead and corresponding author of the study. "This automated process requires no additional time, effort, or radiation exposure to patients, yet these prognostic measures could one day impact patient health through presymptomatic detection of elevated cardiovascular or other health risks."

This research builds on prior efforts designing AI algorithms that Dr. Summers has undertaken in his lab in the NIH Clinical Center's Radiology and Imaging Sciences Department and his previous collaboration with Dr. Pickhardt to develop, train, test, and validate fully automated algorithms for measuring body composition using abdominal CT. The researchers plan to test the approach in other studies, including more racially diverse populations.

Boston, Mass. - Commonly known as the breast cancer genes, the BRCA gene family plays a role in repairing damaged DNA. Inherited mutations in the genes BRCA1 or BRCA2 raise the risk of developing breast, ovarian, prostate and other cancers. Led by clinician-researchers at Beth Israel Deaconess Medical Center (BIDMC), a first-of-its-kind study provided new evidence about the optimal way to treat patients who carry BRCA mutations - also known as BRCA carriers - who have been diagnosed with breast cancer. The new data come from the INFORM trial, the results of which appeared in the Journal of Clinical Oncology.

Designed to settle a question raised by previous studies, INFORM is the largest prospective randomized clinical trial to compare the efficacy of a platinum agent to a standard treatment regimen. The INFORM trial was led by Nadine Tung, MD, Director of the Cancer Risk and Prevention Program and head of Breast Medical Oncology at Beth Israel Deaconess Medical Center (BIDMC).

"Previous studies reported that the platinum-based therapy cisplatin was effective in BRCA carriers with breast cancer," said Tung. "Those findings left clinicians uncertain whether to use cisplatin - an unconventional drug for treating early stage breast cancer - or whether to use the same chemotherapy regimen used for other women with breast cancer. Prior to INFORM, no randomized prospective data existed comparing platinum to standard chemotherapy in this population of patients. Our study found that platinum-based therapy was actually no more effective than the standard first-line treatment."

Linked to five percent of breast cancer cases among the general population, BRCA mutations are responsible for a larger proportion of breast cancer in younger women, Jewish women, and those with a family history of breast cancer. BRCA mutations are identified in 10 to 20 percent of women with the type of breast cancer known as triple negative breast cancer.

As part of the INFORM trial, Tung and colleagues at 13 medical centers recruited 117 patients newly-diagnosed with but not yet treated for breast cancer who were also known to carry one or both of the two known BRCA mutations. Fifty-seven of these patients were treated with the standard first-line chemotherapy, doxorubicin combined with cyclophosphamide (AC), while 60 patients were treated with cisplatin. All participants underwent mastectomy or lumpectomy, followed lymph node biopsy or dissection after completing their respective courses of treatment.

The results of the INFORM trial demonstrate that, while cisplatin is an active agent for treating breast cancer in BRCA carriers, it is not more effective than the standard chemotherapy regimen AC. Tung and colleagues reported that among participants treated with cisplatin, the overall pathologic complete response rate - the disappearance of all cancer at surgery - was 18 percent compared with 26 percent with the AC regimen.

"We demonstrated that both regimens can be effective and treatment choice may need to incorporate an individual's other health concerns and anticipated side effects with each regimen," Tung said.

Further analysis of the data revealed that, among women with triple-negative breast cancer, pathologic complete response rates were 22 percent and 28 percent, respectively. Among patients with another subtype of breast cancer known as hormone receptor-positive breast cancer, response rates were six percent and 21 percent, respectively.

The number of patients with complete or near complete disappearance of cancer, termed Residual Cancer Burden 0 or 1, was also numerically but not statistically higher with AC than cisplatin, for all breast cancer subtypes.

"Given the previously reported impressive activity of platinum agents in BRCA-associated breast cancer, these results were surprising," Tung noted. "The INFORM trial underscores the importance of confirming results from single arm trials with randomized trials."

New Haven, Conn. -- People can carry hazardous compounds from cigarette smoke that cling to their bodies and clothes and then release those compounds into non-smoking environments -- exposing people nearby to cigarettes' adverse effects, a new study shows.

For the last decade, third-hand smoke has been described as the residual contamination from cigarette smoking that adheres to walls and other surfaces in places where smoking has previously occurred. For example, hotels and rental car companies have implemented smoking restrictions to limit this contaminating odor from their rooms and cars.

A team of researchers led by Yale's Drew Gentner shows for the first time that this third-hand smoke can travel in large quantities into indoor, non-smoking environments by way of humans. The research suggests that even if someone is in a room where no one has smoked, that person could still be exposed to many of the hazardous chemical compounds that make up cigarette smoke, depending on who else had entered the room or previously visited it. The results were published March 4 in Science Advances.

"In real-world conditions, we see concentrated emissions of hazardous gases coming from groups of people who were previously exposed to tobacco smoke as they enter a non-smoking location with strict regulations against indoor smoking," said Gentner, associate professor of chemical & environmental engineering. "People are substantial carriers of third-hand smoke contaminants to other environments. So, the idea that someone is protected from the potential health effects of cigarette smoke because they're not directly exposed to second-hand smoke is not the case."

The researchers brought highly sensitive analytical instrumentation into a movie theater to track thousands of compounds, present as either gases or particles, over the course of a week. A diverse range of volatile organic compounds found in tobacco smoke spiked dramatically when certain audiences arrived for the movies. These increases were minor for G-rated movies, while audiences for R-rated movies -- which included moviegoers more likely to smoke or to be exposed to smoke -- consistently released much larger quantities of these compounds into the theater. The relative proportions of these emitted compounds confirmed that they were from slightly aged cigarette smoke.

"Despite regulations preventing people from smoking indoors, near entryways, and near air intakes, hazardous chemicals from cigarette smoke are still making their way indoors," said Roger Sheu, a Ph.D. student in Gentner's lab and lead author of the study.

The amount of these hazardous and reactive gases wasn't trivial, the researchers said. The gas emissions were equal to that of being exposed to 1-10 cigarettes of secondhand smoke in a one-hour period. These emissions and air concentrations peaked upon audience arrival and decreased over time, but not completely, even when the audiences left. In many cases, the movie-goers left a persistent contamination observable the following days in the unoccupied theater. The researchers said that is because the chemicals don't remain entirely in the air, but are also adsorbed onto various surfaces and furnishings, just as it does with third-hand smoke contamination in places where smoking has occurred.

The researchers also found a predominance of nitrogen-containing compounds from cigarettes, which would have migrated from people to other indoor surfaces.

"In particular, we noticed that nicotine was the most prominent compound by far," said co-author Jenna Ditto, a Ph.D. student in Gentner's lab.

The researchers said these results on human transport of third-hand smoke now help to explain why previous studies had found notable quantities of nicotine on surfaces in numerous non-smoking environments.

The researchers emphasized that avoiding movie theaters is not the solution to avoiding third-hand smoke. In fact, the theater used for the study is modern, large, and well-ventilated, which reduced the effect of the emissions on concentrations of hazardous compounds in the room. In less well-ventilated spaces -- such as public transit, bars, offices, and homes -- similar third-hand smoke emissions would likely result in considerably higher concentrations of many of these compounds.

BALTIMORE, MD - March 4, 2020 - Using a combination of magnetic resonance imaging (MRI) to target and sample suspicious prostate tissue along with a standard prostate biopsy is significantly more likely to detect the most aggressive prostate cancers than standard biopsy alone. This finding, published today in the New England Journal of Medicine, could allow a higher percentage of prostate cancer patients to avoid unnecessary treatment for slow-growing prostate cancers that are not likely to spread.

The new study was conducted by National Cancer Institute (NCI) researchers including one who is now at the University of Maryland School of Medicine (UMSOM).

"This study demonstrated that using a combination of both types of biopsies leads to more detection of prostate cancers and is less likely to miss aggressive cancers that can spread and kill," says study co-author M. Minhaj Siddiqui, MD , FACS, an associate professor of surgery at UMSOM and a collaborating member of the NCI research team. "This is an important finding that will be practice-changing as we see more cancer centers adopting both types of biopsy methods. Those of us who have already adopted this cutting-edge technology can now give physicians and patients alike the confidence that their prostate cancer diagnosis is accurate and that hard-to- diagnose aggressive cancers are not being missed."

About one in nine men will be diagnosed with prostate cancer during his lifetime, according to the American Cancer Society. Most men diagnosed with prostate cancer do not die from it, and many have milder forms of the disease that do not require immediate treatment but can instead be carefully monitored, called active surveillance, to make sure the tumor is not growing or becoming more aggressive.

Traditional biopsies, that use ultrasound imaging to locate the gland and randomly remove 12 core tissues samples, have been known to miss aggressive cancers, however, so doctors have not felt comfortable relying on them for treatment guidance for fear of under-treating patients with deadly tumors. As a result, many men with milder forms of the disease have been over-treated with surgery or radiation which often leads to side effects such as impotence and incontinence.

In a targeted biopsy, MRIs of the suspected cancer are fused with real-time ultrasound images, creating a map of the prostate that enables doctors to pinpoint and test suspicious areas.

"With greater confidence in our ability to make an accurate diagnosis, we are better able to use more conservative approaches, such as active surveillance, to manage patients sparing them adverse side effects," says Dr. Siddiqui, who is also Director of Urologic Oncology and Robotic Surgery at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC). The NCI-designated comprehensive cancer center offers MRI-targeted biopsy, with expanded treatment options, including focal therapy to surgically remove only the tumor, sparing the prostate.

For the study, Dr. Siddiqui and his colleagues evaluated 2,103 men who all had both traditional biopsies using ultrasound and targeted biopsies guided by MRIs to check for prostate cancer. They then examined the prostate glands of 404 of these patients who were diagnosed with prostate cancer and had their gland surgically removed; they found that aggressive cancers went undetected in 16.8 percent of the standard biopsies compared to 8.8 percent of MRI-targeted biopsies; when the two biopsy methods were combined, only 3.5 percent of aggressive cancers were missed.

"These findings suggest that combined biopsy provides improved diagnostic accuracy over either systemic or MRI-targeted biopsy alone and better predicts the result of final histopathological analysis," the researchers wrote in the study.

The NCI conducted the study with data collected from June 2007 to January 2019. In 2015, the same group of researchers published a study in JAMA that found that 30 percent more high-risk prostate cancers were diagnosed with MRI-targeted biopsy than with the traditional approach. In addition, 17 percent fewer low-risk cancers were diagnosed with the MRI-targeted biopsy, compared to the standard method. Dr. Siddiqui was the first author of the JAMA article. It led to large cancer institutions, such as UMGCCC, adopting both biopsy methods as the standard of care.

Los Angeles, Calif. - The AIDS Clinical Trials Group (ACTG), the world's largest and longest-established HIV research network, will make 28 presentations at the Conference on Retroviruses and Opportunistic Infections (CROI 2020) held in Boston, March 8-11. ACTG investigators will present data in oral presentations and themed discussions on the impact of chronic antiretroviral therapy (ART) on a novel metric of the HIV reservoir, predictors of multidrug resistant tuberculosis (MDR-TB) in resource-limited settings, findings from the first HIV cure trial that exclusively enrolled women, and interactions between contraceptives and TB drugs and the vaginal microbiome.

"The ACTG has led research on HIV and its co-infections and comorbidities since the beginning of the epidemic, more than 30 years ago," said ACTG Chair Judith Currier, M.D., MSc, of the University of California, Los Angeles. "The studies being presented at CROI this year reflect the diversity of ACTG's research portfolio and demonstrate our commitment to addressing the full range of issues affecting people living with HIV. These studies provide insights into HIV cure, TB, the interaction between contraception and HIV treatment, sex differences, and co-morbidities in people living with HIV."

The 28 ACTG presentations at CROI 2020, a premier global HIV research conference, demonstrate ACTG's continued impact on the understanding of HIV pathogenesis, clinical interventions, clinical care, and the health of people living with HIV. Presentations are listed below:

ORAL PRESENTATIONS AND THEMED DISCUSSIONS

INTACT PROVIRAL DNA LEVELS DECLINE IN PEOPLE WITH HIV ON ANTIRETROVIRAL THERAPY (ART) (ACTG 5321; Oral Abstract Session 0-06: Targeting the Persistent HIV Reservoir, Tuesday, March 10 10:00 am - 12:00 pm) Rajesh T. Gandhi, et al. (rgandhi@mgh.harvard.edu) Topic: HIV Cure, the Reservoir, and Persistence

The intact proviral DNA assay is a novel metric of the HIV reservoir. This study shows that intact proviral DNA levels decline for people on chronic ART and examines the relationship of that decline to other metrics of HIV persistence and immune activation.

PREDICTORS OF TUBERCULOSIS INFECTION IN MDR-TB HOUSEHOLD CONTACTS ?15 YEARS OLD (ACTG 5300/IMPAACT2003; Oral Abstract Session 0-12: Tuberculosis, Opportunistic Infections, and HIV Testing, Wednesday, March 11 10:00 am - 12:00 pm) Soyeon Kim, et al. (skim@sdac.harvard.edu) Topic: Tuberculosis

This presentation provides insights into predictors of active TB infection among household contacts of individuals with MDR-TB.

EFFECT OF TAMOXIFEN ON VORINOSTAT-INDUCED HIV RNA EXPRESSION IN WOMEN ON ART (ACTG 5366; Themed Discussion Session TD-06: Curative Strategies: Trials and Tribulations, Tuesday, March 10 1:30 pm - 2:30 pm) Eileen Scully, et al. (escully1@jhmi.edu) Topic: HIV Cure, the Reservoir, and Persistence

A5366 is the first study to examine a strategy to reduce the HIV reservoir exclusively in women using a hormone-modulating approach. Since estrogen in women blocks the expression of HIV when researchers try to 'turn on' the latent reservoir in women living with HIV, A5366 examines whether tamoxifen and vorinostat can reverse latency.

A COMBINED ESTROGEN/PROGESTIN VAGINAL RING IMPROVES VAGINAL MICROBIAL COMMUNITIES (ACTG 5316; Themed Discussion Session TD-15: Making Sense of it All: HIV Susceptibility in the Female Genital Tract, Wednesday, March 11, 1:30 pm - 2:30 pm) Nicole H. Tobin, et al. (ntobin@mednet.ucla.edu) Topic: Contraception

This presentation explores the relationship between the use of hormone-base intravaginal rings and vaginal flora.

ANTIRETROVIRAL AND RIFAMPICIN CO-TREATMENT AFFECTS DMPA EXPOSURE: DOSING IMPLICATIONS (ACTG 5338; Themed Discussion Session TD-13: The Long and Short of it: What's Next for Long-Acting Drugs, Wednesday, March 11, 1:30 pm - 2:30 pm) Jose Francis, et al. (jose.francis@uct.ac.za) Topic: Contraception

Because TB coinfection among pregnant women living with HIV is associated with poor outcomes, effective contraception to prevent unintended pregnancy is important. This study examines the impact of HIV and rifampicin-based TB therapy on depot medroxyprogesterone acetate (DMPA) levels when used as an injectable contraceptive.

POSTER PRESENTATIONS

HIV Cure, the Reservoir, and Persistence

RISK AND PREVALENCE OF RESIDUAL VIREMIA AFTER cART IN RESOURCE-LIMITED COUNTRIES (NWCS 425; Poster Session P-E02: Measuring the HIV Reservoir, Monday, March 9, 2:30 pm - 4:00 pm) Sivaporn Gatechompol, et al. (sivaporn.k@hivnat.org)

This study compares factors associated with residual single copy viremia in people living with HIV who are virally suppressed on ART between the United States and resource-limited settings.

TELMISARTAN DECREASES MONOCYTE CX3CR1 EXPRESSION IN TREATED HIV INFECTION (ACTG 5317; Poster Session P-M02: Adipose Tissue and Obesity, Tuesday, March 10, 2:30 pm - 4:00 pm) Jordan E. Lake, et al. (jordan.e.lake@uth.tmc.edu)

Telmisartan is an angiotensin receptor blocker with anti-inflammatory properties, especially in adipose tissue. This presentation evaluates whether telmisartan improves inflammatory and obesity markers in patients on ART.

AMINOBISPHOSPHONATES REVERSE LATENCY IN HIV-SEROPOSITIVE INDIVIDUALS (NWCS 464; Poster Session P-E07: HIV Curative Strategies: In Vitro Studies, Tuesday, March 10, 2:30 pm - 4:00 pm) Natalia Soriano-Sarabia, et al. (nataliasorsar@email.gwu.edu)

Aminobisphosphonates, which are used to treat osteoporosis, may reverse latency in chronic HIV infection due to disruptions in cell signaling. This study examines that association for the first time.

TH2 CYTOKINES ARE ASSOCIATED WITH HIGHER LEVELS OF INTACT PROVIRUSES ON ART (ACTG 5321; Poster Session P-E10: Immune Pressure on the HIV Reservoir, Wednesday, March 11, 2:30 pm - 4:00 pm) Joshua C. Cyktor, et al. (jcc114@pitt.edu)

This study examines the relationship between levels of various cytokines among people on ART and different metrics of the HIV-1 reservoir.

MODELING HIV RESERVOIR DECLINE AFTER ART INITIATION AS A FUNCTION OF NK CELL FEATURES (NWCS 441; Poster Session P-E10: Immune Pressure on the HIV Reservoir, Wednesday, March 11, 2:30 pm - 4:00 pm) Elena Vendrame, et al. (elenaven@stanford.edu)

HIV DNA levels decline after ART initiation, and this study examines factors associated with that decline, including natural killer cells.

Viral Control with or without Structured Treatment Interruptions

FACTORS ASSOCIATED WITH VIRAL CONTROL AFTER STRUCTURED TREATMENT INTERRUPTION (NWCS 470; Poster Session P-E04: Insights from Analytical Treatment Interruptions, Monday, March 9, 2:30 pm - 4:00 pm) Nikolaus Jilg, et al. (njilg@partners.org)

Structured treatment interruptions (STIs) will be a critical strategy to determine if HIV remission or cure efforts are successful. This study examines the factors immediately following STIs that predict longer periods of virologic control.

HIV POST-TREATMENT CONTROL DESPITE PLASMA VIRAL EVOLUTION AND DUAL INFECTION (NWCS 470; Poster Session P-E04: Insights from Analytical Treatment Interruptions, Monday, March 9, 2:30 pm - 4:00 pm) Behzad Etemad, et al. (betemad@bwh.harvard.edu)

HIV post-treatment controllers (PTCs) serve as models for sustained HIV remission and may provide clues for HIV remission or cure studies. This study examines plasma virus composition and diversification within HIV PTCs.

FREQUENCY OF POST-TREATMENT CONTROL VARIES BY ART RESTART AND VIRAL LOAD CRITERIA (NWCS 380; Poster Session P-E04: Insights from Analytical Treatment Interruptions, Monday, March 9, 2:30 pm - 4:00 pm) Jesse M. Fajnzylber, et al. (jesse_fajnzylber@dfci.harvard.edu)

Analytic treatment interruptions (ATI) are critical strategies to examine the efficacy of HIV remission or cure strategies. This study examines an interactive tool for estimating viral rebound timing in the setting of an ATI.

Tuberculosis

GEOGRAPHIC AND INDIVIDUAL RISK FACTORS FOR TB OR DEATH IN THE BRIEF-TB TRIAL (ACTG 5279; Poster Session P-N02: Latent TB Infection: Risk Factors, Treatment, and Prevention, Monday, March 9, 2:30 pm - 4:00 pm) Cynthia Riviere, et al. (criviere@ghesiko.org)
The original A5279 trial compared one month of isoniazid and rifapentine to nine months of isoniazid for TB prevention in resource-limited settings. This follow-up presentation explores clinical, demographic, and geographic factors associated with TB acquisition, TB-related death, and death in each group.

Comorbidities

ADVANCED GLYCATION END PRODUCTS ASSOCIATED WITH CARDIOMETABOLIC RISK ON ART (ACTG 5260; Poster Session P-L01: Inflammatory Biomarkers and Cardiovascular Outcomes, Monday, March 9, 2:30 pm - 4:00 pm) Vanessa El Kamari, et al. (Vanessa.ElKamari@UHhospitals.org)

This study evaluates changes in serum advanced glycation end products (AGEs), usually associated with aging, in the ACTG 5257 trial after ART initiation with one of three NNRTI-based regimens.

TRICARBOXYLIC ACID METABOLITES PREDICT METABOLIC COMORBIDITIES AND DEATH IN AGING PWH (NWCS 447; Poster Session P-M03: Metabolic Complications, Monday, March 9, 2:30 pm - 4:00 pm) Corrilynn O. Hileman, et al. (chileman@metrohealth.org)

Monocyte activation may contribute to inflammatory and metabolic changes among people aging with HIV. This study analyzes associations between concentrations of monocyte activation markers and comorbidities in the HIV Infection, Aging, and Immune Function Long-Term Observational (HAILO) study.

PREDICTIVE VALUE OF THE CD8 COUNTS AND CD4/CD8 RATIO AT TWO YEARS OF SUCCESSFUL ART (DACS 322.1; Poster Session P-Q05: T Cell Patterns, Monday, March 9, 2:30 pm - 4:00 pm) Sergio Serrano-Villar, et al. (sergio.serrano@salud.madrid.org)

Although CD4 cell counts predict clinical events, there is variability in the predictive power of CD8+ T cell counts and CD4/CD8 ratios on clinical outcomes in HIV. This study examines these factors in relation to clinical events on suppressive ART.

GUT INTEGRITY MARKERS AND ASSOCIATIONS WITH ADIPOSITY IN PEOPLE WITH AND WITHOUT HIV (ACTG 5260s; Poster Session P-M02: Adipose Tissue and Obesity, Tuesday, March 10, 2:30 pm - 4:00 pm) Allison Ross Eckard, et al. (eckarda@musc.edu)

Fat accumulation after ART initiation remains a serious problem among people living with HIV, but little is known about the pathophysiology of this process, especially with Integrase Strand Transfer Inhibitors. This presentation assesses the relationship between gut integrity markers and body composition for the first time.

A CROSS-SECTIONAL ANALYSIS OF ANTIRETROVIRAL REGIMEN ACTIVITY IN CEREBROSPINAL FLUID (ACTG 5321; Poster Session P-G03: Pharmacokinetics and Pharmacodynamics in Special Populations and Body Sites, Tuesday, March 10, 2:30 pm - 4:00 pm) Courtney V. Fletcher, et al. (cfletcher@unmc.edu)

This study analyzes the distribution of different antiretrovirals (ARVs) in cerebrospinal fluid and the relationship between that distribution and biomarkers of HIV persistence and inflammation in the cerebrospinal fluid.

T-CELL AND MONOCYTE ACTIVATION CORRELATE AND DECLINE DURING HCV THERAPY FOR HCV-HIV (ACTG 5329; Poster Session P-J06: HCV After the SVR: Gone but Not Forgotten, Tuesday, March 10, 2:30 pm - 4:00 pm) Ann Auma, et al. (awa28@case.edu)

Successful hepatitis C (HCV) therapy has been associated with partial or complete normalization of immune activation during mono-HCV infection. This presentation shows that successful therapy for HCV among patients with HIV-HCV co-infection similarly leads to a decline in markers of immune activation, despite the ongoing HIV.

PLASMA CITRATE AND SUCCINATE PREDICT NEUROCOGNITIVE IMPAIRMENT IN OLDER PWH (NWCS 447; Poster Session P-F02: Neurocognition: Biomarkers, Therapies, and Outcomes, Tuesday, March 10, 2:30 pm - 4:00 pm) Corrilynn O. Hileman, et al. (chileman@metrohealth.org)

This study evaluates the effect of specific neuroinflammatory markers on neurocognitive impairment among older people living with HIV.

PREVALENCE OF PHYSICAL FUNCTION IMPAIRMENT AND FRAILTY IN MIDDLE-AGED PWH (ACTG 5361; Poster Session P-M08: Functional Status and Frailty, Wednesday, March 11, 2:30 pm - 4:00 pm) Triin Umbleja, et al. (tumbleja@sdac.harvard.edu)

People living with HIV have an increased risk of falls, hospitalizations, and mortality due to frailty. This study evaluates the risk factors for physical function impairment among patients with HIV at low to moderate cardiovascular risk.

PRINCIPAL COMPONENTS ANALYSIS TO IDENTIFY BIOMARKERS PREDICTIVE OF NON-AIDS EVENTS (NWCS 411; Poster Session P-B08: Non-AIDS Consequences of HIV Infection, Wednesday, March 11, 2:30 pm - 4:00 pm) Carlee Moser, et al. (cmoser@sdac.harvard.edu)

In this presentation, biomarkers of monocyte and macrophage activation are examined in relationship to non-AIDS events among individuals living with HIV.

TOTAL HIV DNA LEVELS DO NOT PREDICT NON-AIDS-DEFINING EVENTS (NWCS 411; Poster Session P-B08: Non-AIDS Consequences of HIV Infection, Wednesday, March 11, 2:30 pm - 4:00 pm) Colline Wong, et al. (cwong22@bwh.harvard.edu)

While total HIV DNA levels predict the size of the HIV reservoir, this study shows that this biomarker is not associated with non-AIDS defining events among people living with HIV.

Sex Differences

SEX-SPECIFIC ANALYSES IN ORAL ABSTRACTS FROM CROI 2019 (A5001; Poster Session P-Q02: HIV in Key Populations, Monday, March 9, 2:30 pm - 4:00 pm) William R. Short, et al. (wshort@pennmedicine.upenn.edu)

Globally, women account for more than half of all people living with HIV yet remain underrepresented in research. CROI guidelines (starting in 2018) specifically recommend reporting sex distribution and sex-adjusted analyses, but adherence to these guidelines has been relatively poor. This updated analysis examines adherence to these guidelines among oral abstracts from CROI 2019.

DYNAMICS OF HIV-SPECIFIC T-CELLS ON DURABLE ART DIFFER BY ANTIGEN

RECOGNIZED & BY SEX (ACTG 5321; Poster Session P-D08: Impact of Antiretrovirals on the Immune Response, Wednesday, March 11, 2:30 pm - 4:00 pm) Eva M. Stevenson, et al. (ems2200@med.cornell.edu)

In order to advance understanding toward HIV cure, sex differences must be examined to determine whether cure strategies will differ by sex. This study examines differences in HIV-specific T cell responses by sex among chronically treated patients on ART.

HIV Diagnosis/Predictors of Clinical Outcomes

INFLAMMATION AND MITOCHONDRIAL DYSFUNCTION NOT NRTIS DRIVE EVENTS IN ACTG A5241 (NWCS 423; Poster Session P-M10: Epigenetic and Mitochondrial Toxicities, Tuesday, March 10, 2:30 pm - 4:00 pm) Carl J. Fichtenbaum, et al. (fichtecj@ucmail.uc.edu)

A recent ACTG study found that among people living with HIV experiencing treatment failure, the treatment arm that added an NRTI to a regimen of two or more ARVs had more deaths and clinical events than the arm that did not. However, inflammation and mitochondrial dysfunction seem to drive these events (not the NRTIs) in this study.

NOVEL CRITERIA FOR DIAGNOSING ACUTE HIV IN A MULTI-NATIONAL ART INITIATION STUDY (ACTG 5354; Poster Session P-R06: Diagnosing Early HIV Infection, Wednesday, March 11, 2:30 pm - 4:00 pm) Trevor A. Crowell, et al. (tcrowell@hivresearch.org)

ART initiation during acute HIV infection (AHI) limits the size of the HIV reservoir, but identifying patients with AHI can be logistically challenging. This presentation evaluates a novel way to diagnose AHI incorporating modern diagnostic algorithms to facilitate early treatment.

Only two days after Latin America’s first case of coronavirus was confirmed in São Paulo, the largest Brazilian city, researchers at Adolfo Lutz Institute (IAL), the University of São Paulo (USP) in Brazil and the University of Oxford in the UK have published the complete genome sequence for the virus, which they call severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).

The report was published on February 28 on Virological.org, a forum for discussion and data sharing used by virologists, epidemiologists and public health specialists. This kind of information helps understand how the virus is spreading around the world, and is useful for the development of vaccines and diagnostic tests.

“By sequencing the genome, we’ve come closer to finding out the origin of the epidemic. We know the confirmed cases in Brazil came from Italy, but the Italians don’t yet know the origin of the outbreak in Lombardy as they have yet to sequence their samples. They haven’t identified patient zero and don’t know whether he or she came from China directly or via other countries,” Ester Sabino, head of USP’s Tropical Medicine Institute (IMT), told Agência FAPESP.

According to Sabino, the first Brazilian sequence closely resembles the samples sequenced in Germany on January 28 and differs from the genome sequenced in Wuhan, the epicenter of the epidemic in China. “This virus mutates relatively little, once a month on average, so there’s no point in sequencing small pieces of the genome. To understand how the virus is spreading and evolving, we have to map the whole genome,” she said.

The researchers at IAL also sequenced the whole genome of the coronavirus isolated from the second Brazilian patient diagnosed with COVID-19, as the disease is officially called, on February 29. Completed only 24 hours after confirmation of the case in Brazil, the study shows that there are differences between the genomes of the viruses isolated from the first and second patients.

“The second Brazilian genome is more similar to the genome sequenced in the United Kingdom, and both differ from the Chinese sequences. This suggests the COV-19 epidemic is maturing in Europe in the sense that internal transmission is already occurring in European countries,” Sabino said.

The ongoing monitoring process, she added, will enable scientists to identify the regions of the viral genome that mutate least, an essential step in developing vaccines and diagnostic tests. “If the tests target a region that mutates frequently, the probability of loss of sensitivity will be high,” she said.

Epidemiological surveillance

Sabino and Nuno Faria, a professor at Oxford University, are co-principal investigators of the Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE). The project, supported by FAPESP, the UK Medical Research Council and the Newton Fund, aims to conduct real-time epidemiological analysis of arboviruses such as dengue and zika.

“This project has created a network of researchers dedicated to responding to epidemics and analyzing epidemiological data in real time,” Sabino said. “The aim is to provide genuine assistance to health services and not just publish information months after the problem occurs.”

According to Sabino, as soon as China confirmed the first outbreak of COVID-19 in January, the project team mobilized to obtain the resources necessary to sequence the virus as soon as it arrived in Brazil.

“We began partnering with the IAL team and training researchers to use MinION, a portable, low-cost sequencing technology. We used this methodology to monitor the evolution of zika virus in the Americas, but in that case we were able to trace the origin of the virus and the dissemination route only a year after the epidemic ended. This time the team went into action as soon as the first case was confirmed,” Sabino said (read more at: agencia.fapesp.br/25472).

The main advantage of real-time epidemic monitoring, she added, is the possibility of identifying exactly where viruses that arrive in Brazil have come from. This information is useful to guide containment actions and help reduce dissemination of the disease.

“It’s a new tool for epidemiological surveillance. So far it’s been tested only in Africa during the Ebola epidemic,” Sabino said. “We wanted to publish this second sequence right away to help colleagues in Italy analyze their data. We shared the protocol used by our team with the Italians and put them in touch with the CADDE group in the UK.”

Breaking down barriers

The first case of COVID-19 in Brazil (BR1) was diagnosed by molecular biology on February 26 by the IAL team. The patient was infected in Italy, possibly between February 9 and 21. The viral genome was sequenced by a team led by Claudio Tavares Sacchi, who heads IAL’s Strategic Laboratory (LEIAL), and Jaqueline Goes de Jesus, a postdoctoral fellow of USP’s Medical School (FM-USP) and holder of a scholarship from FAPESP.

“We were expecting the virus to arrive in São Paulo State, and as soon as we had confirmation I got in touch with our partners at IMT-USP. We’d been working with them for months on the use of MinION to monitor dengue,” Sacchi told Agência FAPESP.

“We were able to break down a few barriers with this study. The university trained teams and transferred technology so that the virus can be sequenced in the right place, which is the center responsible for epidemiological surveillance. That’s how things should be done,” Sabino said.

Besides IAL and USP, the participants in CADDE include members of the Center for Control of Endemic Diseases (SUCEN) and the Center for Epidemiological Surveillance (CVE), both of which are agencies of the São Paulo State Department of Health.

Containment plan

Since mid-January infectious disease specialist Esper Kallás, a professor at FM-USP, has helped the São Paulo State Department of Health develop a care strategy for patients infected by SARS-CoV-2. The Emilio Ribas Institute and FM-USP’s general hospital (Hospital das Clínicas) have been designated referral centers for severe cases in the state.

“Hospital das Clínicas follows an emergency response and disaster containment protocol called HICS [hospital incident command system], which was triggered to care for victims of the school shooting in Suzano [a city in metropolitan São Paulo where ten people were killed in 2019] and during the yellow fever epidemic in 2018. We’ve now established all the care flows in anticipation of the imminent coronavirus epidemic,” Kallás said.

A working group has been set up, he added, to discuss protocols for clinical trials to be held with patients diagnosed and treated by the state’s health system.

“This strategic planning and rapid publication of the viral genome demonstrate São Paulo State’s capacity to respond with high-quality science and contribute to the understanding of threats to public health,” Kallás said.

ROCHESTER, Minn. -- A protein known to help cells defend against infection also regulates the form and function of mitochondria, according to a new paper in Nature Communications.

The protein, one of a group called myxovirus-resistance (Mx) proteins, help cells fight infections without the use of systemic antibodies or white blood cells. The authors report that MxB, which is associated with immune response to HIV and herpes virus, is key to mitochondrial support.

"Our work provides new insights into how this dynamin MxB protein assists in fighting viral infections, which could have substantial health implications in the future," says Mark McNiven, Ph.D., a Mayo Clinic cell biologist and senior author.

Viral infection

In response to infection, a cell releases interferon and neighboring cells ramp up Mx protein production. The authors replicated previous findings that MxB blocks nuclear pores and MxB increases markedly when cells are treated with interferon. But they also show that some MxB is present in most immune tissues, such as tonsil, prior to a "red alert" and that it has another role.

"We were surprised to see MxB present on, and in, mitochondria," says Hong Cao, Ph.D., a Mayo Clinic research scientist and first author. "That it is both induced in response to infection and vital to mitochondrial integrity is exciting, considering that HIV and herpes alter mitochondria during infection."

Protecting the generator

The authors report that during infection, MxB dynamically condenses, dissolves and reforms over time, and traced MxB's travels to the nuclear pores, as well as to the tips and along mitochondria. They also show, via a cell line that can't make MxB in response to interferon, that mitochondrial cristae are affected by MxB, as well.

"Without active MxB protein, mitochondria become nonfunctional, no longer produce energy, and kick out their DNA genome into the cytoplasm," says Dr. Cao. "These cells are not happy, but may have the capacity to survive a viral infection."

History of mitochondrial investigation

The work of Dr. Cao and team builds on the findings of mitochondrial investigators at Mayo.

"Over two decades ago, our lab discovered a set of proteins that perform mechanical work to shape and pinch mitochondria," says Dr. McNiven. That discovery led to a variety of research initiatives across the international mitochondria field into not only basic research questions, but also into clinical areas. This work shows that mitochondrial dynamics, such as fission and fusion, are vital functions. They regulate cell death needed to retard cancer cell growth and the turnover of damaged mitochondria needed to prevent neurodegenerative disorders, and contribute to antiviral cell immunity, to name a few.

The next steps, Dr. McNiven says, are to continue to investigate how MxB is targeted to and internalized by mitochondria, and how its association induces such drastic changes to biology of this organelle.

MALVERN, PA, March 3, 2020 (GLOBE NEWSWIRE) - Ocugen, Inc. (NASDAQ: OCGN), a clinical-stage company focused on discovering, developing and commercializing transformative therapies to treat rare and underserved ophthalmic diseases, announced today the publication in Nature Gene Therapy of preclinical data of nuclear hormone receptor gene NR2E3 as a genetic modifier and therapeutic agent to treat multiple retinal degenerative diseases. OCU400 (NR2E3-AAV) has received two orphan drug designations targeting two distinct inherited retinal diseases (IRDs): NR2E3 mutation-associated retinal diseases and CEP290 mutation-associated retinal diseases.

The publication details efficacy results in five unique mouse models of retinitis pigmentosa (RP) that underwent administration of NR2E3-AAV by subretinal injection. The five RP models tested were rd1 (PDE6 β associated RP), Rho-/- and RhoP23H (both Rhodopsin associated RP), rd16 (Leber Congenital Amaurosis) and rd7 (Enhanced S-cone Syndrome). The study demonstrates the potency of a novel modifier gene therapy to elicit broadspectrum therapeutic benefits in early and intermediate stages of RP.

Please refer to Nature Gene Therapy's online publication for additional results from this study.

"This represents an important milestone for the development of this therapy. I am impressed by the protection that was elicited in multiple animal models of degeneration caused by different mutations. A treatment for inherited retinal degenerations that is mutation independent would have wide reaching implications," said Mark Pennesi, M.D., Ph.D., Associate Professor of Ophthalmology at the Oregon Health & Science University (OHSU) School of Medicine and Division Chief of the Ophthalmic Genetics Service at the OHSU Casey Eye Institute.

"Dr. Haider and her vision research team have successfully demonstrated proof of principle in their elegant study by rescuing 5 animal models of RP by resetting homeostasis. This is the foundation work for the development of the first broad spectrum therapy for inherited retinal degeneration diseases and is a game changer for rescue even after disease onset," said Cheryl Mae Craft, Ph.D., Professor of Ophthalmology, USC Keck School of Medicine at USC Roski Eye Institute Los Angeles, CA.

"One of the biggest advantages of our modifier gene therapy platform is that it has the potential to eliminate the need for individual gene replacement and gene editing strategies and may revolutionize gene therapy treatments for eye diseases. Inherited retinal degenerations such as RP affect over 1.5 million people worldwide. Over 150 gene mutations have been associated with RP and this number represents only 60% of the RP population. The remaining 40% of RP patients cannot be genetically diagnosed, making it difficult to develop individual treatments. Our modifier gene therapy has potential to eliminate the need for developing more than 150 individual products and provide one treatment option for all RP patients," said Rasappa Arumugham, Ph.D., Ocugen's Chief Scientific Officer. "We are completing preclinical studies for OCU400 and anticipate commencing a Phase 1/2a clinical trial in patients in 2021."

March 3, 2020 - Cannabis use is much more common among pregnant women with depression and pregnant women with depression are more than 3 times more likely to use cannabis than those without depression, according to a new study at Columbia University Mailman School of Public Health. Despite data linking cannabis and depression in many populations, this is the first study to examine this relationship among pregnant women in a nationally representative sample. The findings are online in the journal Drug and Alcohol Dependence.

Data were drawn from the 2005-2018 National Survey on Drug Use and Health (NSDUH), an annual survey of persons ages 12 and older in the US. Pregnant women were categorized as a current cannabis user if they responded they has used marijuana at least once during the past 30 days. The study, conducted with colleagues at The City University of New York, also investigated whether the relationship between depression and cannabis use differed by age, other sociodemographic characteristics, and perception of risk associated with cannabis use.

"Our findings are timely given rapidly shifting perceptions about risks associated with cannabis use and its legalization," said Renee Goodwin, PhD, in the Department of Epidemiology at Columbia Mailman School. "We found the prevalence of cannabis use was much higher among those with depression who perceived no risk (24 percent) relative to those who perceived moderate-great risk associated with use (5.5 percent)."

Among pregnant women without depression, those who perceived no risk had higher levels of use (16.5 percent) compared with those who perceived moderate-great risk (0.9 percent), though both these levels were substantially lower than among women with depression.

Depression appears to increase vulnerability to cannabis use even among pregnant women who perceive substantial risk. "Perception of greater risk associated with regular use seems to be a barrier to cannabis use, though pregnant women with depression who perceived moderate-great risk associated with regular cannabis use were more than 6 times as likely to use cannabis than those without depression. This suggests that depression may lead to use even among those who perceive high risk," noted Goodwin. "With legalization, the degree to which dangers are thought to be linked with cannabis use appear to be declining in the U.S. overall, and this may also apply to pregnant women."

Cannabis use was significantly more common among pregnant women with, compared to without, depression. Over one in ten (13 percent) pregnant women with a major depressive episode reported past-month cannabis use compared with 4 percent without depression who reported using cannabis. This was the case across all sociodemographic subgroups.

Approximately one in four pregnant teens with depression used cannabis in the past month. "As brain development is ongoing until age 25, cannabis use in this group may increase risks for both mother and offspring," she noted." "Our results provide recent nationally representative estimates
suggesting that education and intervention efforts should be targeted at pregnant teens."

"Education about risks associated with cannabis use during pregnancy for both mother and offspring, especially among women with prenatal depression, are needed as cannabis is rapidly being legalized across the U.S. and increases among pregnant women have previously been reported," suggested Goodwin.

Currently, 50% of the adult population worldwide is overweight or obese. Obesity has been shown to increase the severity of influenza infection.

This new study demonstrates that obesity not only enhances the severity of influenza infection but also impacts viral diversity, likely due to an impaired interferon defense response in individuals who are obese.

Obesity may be one factor explaining why there is so much variation in the influenza virus each year, necessitating the creation of yearly influenza vaccines.

Washington, DC - March 3, 2020 - Obesity promotes the virulence of the influenza virus, according to a study conducted in mice published in mBio, an open-access journal of the American Society for Microbiology. The finding could explain, in part, why the influenza virus varies greatly from year to year. This is concerning given that the obesity epidemic is an ever-expanding threat to public health, with currently 50% of the adult population worldwide considered overweight or obese.

"We want to be careful about extrapolating too much from a mouse experiment, but the study does suggest that because of the problem with how cells respond to flu in an obese environment, individuals who are obese don't have good antiviral responses. They are delayed. They are blunted," said principal study investigator Stacey Schultz-Cherry, PhD, a faculty member at St. Jude Children's Research Hospital and Deputy Director, World Health Organization Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds. Dr. Schultz-Cherry is Chair of ASM's Public and Scientific Affairs Committee (PSAC). "Obesity allows the virus to get in, replicate faster and make more mistakes. Some of those mistakes are potentially beneficial for the virus."

Previous research has shown that individuals who are obese have higher influenza viral loads in exhaled breath and that they shed virus longer. Animal studies have demonstrated that the influenza virus can spread deeper into the lungs for longer periods of time when obesity is present. Each year a new influenza vaccine is created because the virus continues to drift and change.Dr. Schultz-Cherry and colleagues hypothesized that the obese microenvironment may allow the influenza virus to change more rapidly.

To find out, the researchers infected lean and obese mice with influenza for 3 days, allowing time for the virus to replicate. They then recovered the viruses from the obese or lean mice and provided them to obese and lean mice respectively, allowed 3 days for replication and then repeated this process. "Basically, we wanted to mimic what would happen during an epidemic where the virus goes from one person to the next," said Dr. Schultz-Cherry. "What happens if a virus goes from a lean person to a lean person to a lean person versus an obese person to an obese person to an obese person."

The researchers found that as the virus went from obese mouse to obese mouse, the virus underwent changes. Minor variants rapidly emerged in the obese mice and these variants exhibited increased viral replications resulting in enhanced virulence in wild-type mice. "When you get infected with flu, it's not just one virus, it's a population. It's like a little cocktail party and in this case, the cocktail party in the obese mice was a whole different matter," said Dr. Schultz-Cherry. "There were different populations and some of those viruses were more virulent than the strains that went from lean mouse to lean mouse."

When cells interact with influenza, the body typically mounts an interferon response to stop the virus from replicating and spreading. The new research showed that this emergency response was blunted in obese mice. The increased diversity of the influenza viral population in obese mice correlated with decreased type I interferon responses and treatment of obese mice with recombinant interferon reduced viral diversity, suggesting that the delayed antiviral responses exhibited in obesity may permit the emergence of a more virulent influenza virus population.

The researchers said they would next like to study what is happening at the population level in humans. "Do we see this increased viral diversity in obese people in what they are shedding? Is obesity part of why we now see so much viral drift each season and why we have to continually update our vaccines?" said Dr. Schultz-Cherry. The researchers will also tease apart what is happening at the cellular level to impact the virus itself.

OAK BROOK, Ill. - The first study to examine both chest X-ray and CT imaging findings in teenagers with electronic (e-)cigarette or vaping product use-associated lung injury (EVALI) was published today in the journal Radiology.

"This population is particularly vulnerable to e-cigarette use and its potentially life-threatening consequences," said the study's lead author, Maddy Artunduaga, M.D., assistant professor of pediatric radiology at UT Southwestern Medical Center in Dallas.

First introduced in the U.S. around 2007, e-cigarettes are now the most used tobacco product among U.S. youth. The 2018 National Youth Tobacco Survey reported that in 2018 more than 3.6 million middle and high school students were using e-cigarettes.

Although vaping has been often marketed as a safer alternative to smoking traditional cigarettes, e-cigarette liquids and aerosols contain a variety of chemicals that can result in ill health effects. When these potentially harmful chemicals are inhaled, acute lung injury may occur. EVALI has emerged as a serious and sometimes fatal complication of vaping. Patients under 18 years of age account for 15% of reported U.S. hospitalizations due to EVALI.

Imaging plays a key role in the evaluation of suspected EVALI. Accurate identification of the condition allows for prompt medical treatment, which may decrease the severity of injury in some patients.

Dr. Artunduaga and colleagues retrospectively reviewed chest CT images and X-rays of 14 patients (7 boys and 7 girls) ranging in age from 13 to 18 years old. All patients included in this study used an e-cigarette or engaged in dabbing--the practice of inhaling small quantities of a concentrated and vaporized drug, such as cannabis oil--in the 90 days before symptom onset. Four patients had a history of exposure to both tetrahydrocannabinol (THC) and nicotine-containing vaping products. Nine patients had a history of exposure to THC-containing vaping products only. One patient had a history of exposure to nicotine-containing vaping products only.

All 14 patients had respiratory symptoms. Symptoms varied among patients but most commonly included shortness of breath, cough and chest pain. Twelve patients also had gastrointestinal symptoms, such as vomiting, nausea, diarrhea or abdominal pain. Four patients initially had isolated gastrointestinal symptoms and later developed respiratory symptoms after hospital admission. Other symptoms included fever, chills, weight loss and fatigue.

"In some cases, the initial symptoms may lead clinicians to suspect a gastrointestinal origin for the patient's presentation, and the radiologist may be the first to suggest EVALI as a diagnostic consideration," Dr. Artunduaga said.

The results showed characteristic chest X-ray and CT findings. Bilateral and symmetric ground-glass opacity in the lungs, frequently associated with consolidation, often of lower lobe predominance, was the key imaging finding. On CT, subpleural sparing was also visualized in 79% of patients.

"Another imaging feature observed on CT in 36% of our pediatric patients with EVALI, was the reversed halo sign, which is characterized by the presence of a central ground-glass opacity surrounded by denser consolidation of crescentic shape or complete ring," Dr. Artunduaga said.

Dr. Artunduaga noted that chest X-ray alone does not allow the sufficient characterization of the patterns of EVALI in pediatric patients and, therefore, CT is needed for a complete assessment.

"CT provides a better evaluation of the extent and degree of involvement, as well as a better assessment of the characteristics of abnormal pulmonary findings. This can lead to the early diagnosis of EVALI, which would ultimately allow the timely management of this entity in the pediatric population," she said.

Recent advances in low-dose CT techniques have yielded diagnostic exams that have decreased radiation dose up to 93%. Thus, the radiation dose associated with low-dose CT is justified in the evaluation of suspected EVALI in pediatric patients, according to Dr. Artunduaga.

"Radiologists will continue to play an important role in the initial detection and follow-up of pediatric patients with EVALI," she said. "When these imaging findings are observed in pediatric patients, with or without the history of exposure to e-cigarette or vaping products, EVALI should be included as a diagnostic possibility."

PITTSBURGH, March 3, 2020 - The net cost of prescription drugs -- meaning sticker price minus manufacturer discounts -- rose over three times faster than the rate of inflation over the course of a decade, according to a study published today in JAMA. It's the first analysis to report trends in net drug costs for all brand-name drugs in the U.S.

The study is one of three manuscripts by researchers in the Center for Pharmaceutical Policy and Prescribing (CP3) at the University of Pittsburgh's Health Policy Institute published in this week's special issue of the journal, which focuses on prescription drug costs.

"Previously, we were limited to studying list prices, which do not account for manufacturer discounts. List prices are very important, but they are not the full story," said lead author Inmaculada Hernandez, Pharm.D., Ph.D., assistant professor of pharmacy at Pitt. "This is the first time we've been able to account for discounts and report trends in net prices for most brand name drugs in the U.S."

Hernandez and colleagues showed in past research that list prices for prescription drugs have increased steadily over the past decade.

In the new analysis, the team used revenue and usage data for 602 brand-name drugs to track list and net prices from 2007 to 2018. Inflation-adjusted list prices increased by 159%. Net prices, which account for rising manufacturer discounts, including rebates, coupon cards and 340B discounts, increased by 60%. That's 3.5 times general inflation.

In 2015, net prices began leveling off. Still, the authors caution that stable net prices don't automatically mean that prescription drug costs are affordable for consumers.

"Net prices are not necessarily what patients pay," said senior author Walid Gellad, M.D., M.P.H., associate professor of medicine and health policy at Pitt and director of the CP3. "A lot of the discount is not going to the patient."

That's because the vast majority of the discount likely consists of rebates paid directly to public and private insurers. Rebates don't usually affect the amount patients pay through copays or coinsurance, which are based on list price, not net.

Beneath the overall trends, there was large variability across different drug classes. In some cases, such as insulins or TNF inhibitors, there was a widening gap between list and net prices. In others, such as cancer drugs, list and net prices increased in parallel. Multiple sclerosis treatments were an exceptional case, where even after discounts, net prices more than doubled over the decade in inflation-adjusted dollars.

The study also shows that discounts are much larger for Medicaid than for other payers, likely reflecting regulation, including the mandatory Medicaid rebate based on price increases over inflation. Discounts for other payers are based on negotiations.

The Senate Finance Committee is considering a bill that would add price inflation-based rebates to Medicare, similar to Medicaid.

"We're seeing a lot of discussion that net prices have stabilized over the last few years, and that does appear to be the case," said Gellad, who also is a physician and researcher with the VA Pittsburgh Healthcare System. "But the stabilization of net price comes on top of large increases over the last decade, many times faster than inflation, for products that have not changed over this time period. In addition, this net price is an average, with substantial variability across payers and drugs."