During the COVID-19 pandemic, Johns Hopkins Medicine Media Relations is focused on disseminating current, accurate and useful information to the public via the media. As part of that effort, we are distributing our “COVID-19 Tip Sheet: Story Ideas from Johns Hopkins” every Tuesday throughout the duration of the outbreak.

We also want you to continue having access to the latest Johns Hopkins Medicine research achievements and clinical advances, so we are issuing a second tip sheet every Thursday, covering topics not related to COVID-19 or the SARS-CoV-2 virus.

Stories associated with journal publications provide a link to the paper. Interviews with the researchers featured may be arranged by contacting the media representatives listed. 

PLASTICS-BONDING CHEMICAL MAY BE TIED TO NEURODEVELOPMENTAL PROBLEMS FOLLOWING INFANT HEART SURGERY

Media Contact: Michael E. Newman

Researchers at Johns Hopkins Medicine and the Medical University of South Carolina (MUSC) have shown in a new study that cyclohexanone, an industrial solvent often used to bind together plastic parts in medical equipment, such as stopcocks and intravenous (IV) tubing, can be found in the blood of babies after surgery for congenital heart disease (CHD) at more than three times the level seen before the operation.

The researchers, reporting in the May 6, 2020, issue of the journal JAMA Network Open, say this finding may help explain why as many as 65% of all neonatal CHD patients suffer lifelong neurodevelopmental problems after their cardiac defect is repaired.

These include developmental delays and functional deficits in speech and language, attention, memory, executive function, visual-spatial skills, and gross and fine motor function.

Decades of animal studies revealed that inhalation of cyclohexanone results in toxic effects on the central nervous system, as well as liver and kidney dysfunction. Kidney failure compounds the neurologic impacts of cyclohexanone because it prevents toxins from being removed from blood and allows them to travel to the brain.

“Based on these findings, exposure limits for cyclohexanone were established to protect adults who could come in contact with it on their jobs, yet we had not determined if IV medical exposure, especially to a very vulnerable population — tiny babies with heart defects — were at risk from the same chemical,” says Allen Everett, M.D., professor of pediatrics at the Johns Hopkins University School of Medicine, director of the Pediatric Proteome Center at the Johns Hopkins Children’s Center, and lead author of the new study.

“Previous research indicated that cyclohexanone can migrate from polyvinyl chloride [PVC] tubing and connections into IV fluids, so we designed our study to see if this happened after neonatal cardiac surgery, and if so, whether or not it was associated with the poor neurodevelopmental outcomes measured after a year’s time,” he explains.

Using blood samples collected by MUSC in an earlier clinical trial testing the impact of steroid therapy on 85 pediatric CHD patients after corrective surgery, the researchers looked for cyclohexanone at three time points: immediately before and after the operation, and 12 hours later. They then compared the relationship of cyclohexanone with neurodevelopmental evaluations of these patients at 12 months following surgery.

What they found was a more than threefold increase in the amounts of cyclohexanone in the neonates’ blood immediately after cardiac surgery with cardiopulmonary bypass — when a heart-lung machine mechanically maintains circulatory function — and where the infant is connected with plastic tubing and connectors suspected of containing residual cyclohexanone.

Patients with cyclohexanone still present at 12 hours postoperatively had lower developmental scores for cognitive, language and motor ability at 12 months following surgery, even after adjusting for potential confounding variables such as gender, severity of the heart defect and length of the surgery. This provided solid evidence that cyclohexanone exposure was independently involved, Everett says.

To confirm the suspected link between cyclohexanone and neurodevelopmental problems after neonatal CHD repair surgery, Everett and his colleagues are planning a follow-up study with blood samples and neurological evaluations previously obtained from a larger group of patients in the United States and Canada. The researchers also hope to work with industry to quickly reduce cyclohexanone contamination of medical plastics.

“As more and more infants with CHD get corrective surgery and survive, any neurodevelopmental impacts as a result of that surgery will present a significant challenge to their adult quality of life,” Everett says. “However, few potential causes for these problems have been researched. We have suggested one, cyclohexanone exposure, and based on that work, we can now better define the hazard and then look for ways to remove it.”

ONE IN 10 PATIENTS WITH VASCULAR EVENT, INFECTION OR CANCER SYMPTOMS WILL BE MISDIAGNOSED

Media Contact: Danny Jacobs

One in 10 patients with symptoms caused by a major vascular event, infection or cancer will be misdiagnosed, and about half of those will be seriously harmed or die as a result, according to a research team led by a Johns Hopkins Armstrong Institute for Patient Safety and Quality expert.

The researchers reviewed more than 90,000 patients documented in 28 published studies. Diagnostic error for 15 diseases from the “Big Three” categories ranged from 2% for heart attacks to 62% for a spinal abscess. Misdiagnosis-related harm rates ranged from 1% for heart attacks to 36% for a spinal abscess. The findings were published online on May 14, 2020, in the journal Diagnosis.

“Tracking diagnostic errors and harms for these 15 ‘Big Three’ diseases is a novel way to measure total diagnostic errors that really hasn't been brought to the foreground,” says David Newman-Toker, M.D., Ph.D., director of the Johns Hopkins Armstrong Institute Center for Diagnostic Excellence. “One of the key insights from this phase of the work is that we now know we have to be careful about just looking at raw diagnostic error rates without knowing the rate of serious harms. That’s because it's a little too subjective whether you call a missed opportunity a ‘diagnostic error,’ but it's not subjective whether the patient suffered permanent disability or death as a result.”

The research team, which includes Dana Siegal, R.N., director of patient safety at CRICO Strategies, is constructing a national estimate of serious misdiagnosis-related harms. Previously, the researchers used medical malpractice claims data to identify the “Big Three” that accounted for nearly three-fourths of all serious harm from diagnostic errors. CRICO Strategies is a division of CRICO, the medical malpractice insurance program associated with Harvard Medical School and its affiliates.

The 15 diseases analyzed in the study were four vascular events: stroke, heart attack, venous thromboembolism (a blood clot from a vein in the extremities that lodges in the lungs), aortic aneurysm (enlargement of the aorta, the main blood vessel delivering blood to the body) and dissection, and arterial thromboembolism (a clot from an artery that most often interrupts intestinal blood flow); six infections: sepsis, meningitis, encephalitis, spinal abscess, pneumonia and endocarditis; and five types of cancer: lung, breast, colorectal, prostate and melanoma.

Some of the rarer diseases, such as spinal abscesses, are necessarily going to be harder to diagnose, Newman-Toker acknowledges, but multiple studies have shown how often clear diagnostic red flags are missed at the bedside of many of these patients. How little has been done for most of these disorders compared to the decades of research, education and advances in medicine that have gone into more accurately diagnosing heart attacks is an example of what is possible, he adds.

“We should look at heart attacks as a success story that we should try to replicate for the other diseases,” Newman-Toker says. “It's not that it's impossible to diagnose these dangerous diseases. For several of them, including stroke and spinal abscess, we already know how to improve bedside diagnosis; we just haven’t fully disseminated these approaches.

He adds: “It will take effort, teamwork, resources and research to get it done and sustained over time. We're going to have to apply the same kind of thought and energy to addressing diagnosis for these other conditions as we did with heart attacks, and, were we to do that, I believe that we could fix these problems too.”

ERECTILE DYSFUNCTION DRUG SHOWS PROMISE AS THERAPY FOR CHRONIC PELVIC PAIN SYNDROME

Media Contact: Michael E. Newman

Tadalafil molecules (with orange shadows) flowing through an artery alongside red blood cells. A new Johns Hopkins Medicine study shows that the drug, commonly used to treat erectile dysfunction, also has promise as a treatment for chronic pelvic pain syndrome, a common urinary tract problem in men. Credit: M.E. Newman, Johns Hopkins Medicine, using public domain images

Chronic prostatitis, also known as chronic pelvic pain syndrome (abbreviated as CP/CPPS), is a nonbacterial inflammation of the prostate gland that results in pain and discomfort lasting three or more months. According to the National Institute of Diabetes and Digestive and Kidney Diseases, it is the most common urinary tract problem in men younger than 50, ranks as the third most common urological condition in men older than 50, and accounts for about two million medical visits in the United States each year.

Because the cause of CP/CPPS is unknown, treating it can be a difficult task for health care providers. Furthermore, none of the commonly used medical therapies have been beneficial beyond the time they were administered.

Now, researchers at Johns Hopkins Medicine have reported that a class of drugs commonly used to treat erectile dysfunction also may provide sustained relief of symptoms among patients with CP/CPPS.

The finding was published on May 6, 2020, in the journal Translational Andrology and Urology.

Phosphodiesterase type 5 (PDE5) inhibitors, such as the generic drug tadalafil (also known by its trade name Cialis), have been successfully used for years to treat men with benign prostate hyperplasia, pulmonary arterial hypertension and erectile dysfunction by relaxing smooth muscle cells lining the blood vessels supplying the prostate, lungs and penis, respectively.

Non-bacterial CP/CPPS is believed to be caused by elevated tissue pressures and reduced blood flow within the prostate.

“Because there hasn’t been an adequate, long-term therapy for symptoms and management of CP/CPPS, we decided to see if a PDE5 inhibitor could provide symptom relief by lowering pressure within the prostate, improving oxygenation and reducing oxidative stress,” says Amin Herati, M.D., assistant professor of urology at the Johns Hopkins University School of Medicine and director of male infertility and men’s health at the school’s Brady Urological Institute.

In their study, Herati and his colleagues gave tadalafil to 25 men between the ages of 18 and 66 who had been diagnosed with CP/CPPS and then evaluated them after three months for changes in pain, urinary symptoms and quality of life.

“There was marked improvement in all three categories: a sixfold average reduction in pain, a two-and-a-half fold average relief from previous urinary difficulties and a nearly fivefold average upturn in perceived quality of life,” Herati says.

Although the study population was small, Herati says that the data suggest that PDE5 inhibitor therapy is promising for CP/CPPS and that patients would likely continue showing positive results after one year. He and his team plan further trials to confirm this.

STUDY SHOWS SEPSIS PATIENTS LIVING IN DISADVANTAGED AREAS MORE LIKELY TO RETURN TO HOSPITAL

Media Contact: Brian Waters

According to a recent study led by Johns Hopkins Medicine researchers, patients who reside in more disadvantaged neighborhoods have a significantly higher risk for readmission within 30 days following a hospitalization for sepsis. Sepsis is a potentially deadly condition that occurs when the body’s immune system overresponds to an existing infection, triggering an imbalance of chemicals that can damage multiple organ systems.

The study was published on April 8, 2020, in the journal Critical Care Medicine.

Surviving sepsis can present significant health care consequences for the patient, including readmissions for additional treatment. Repeated hospitalizations, in turn, can lead to long-term health problems or even generate new symptoms and disabilities. Johns Hopkins Medicine researchers investigated whether or not patients from underserved neighborhoods experienced more rehospitalizations than other groups within 30 days of completing the initial inpatient care for sepsis.           

The researchers used the area deprivation index (ADI) — a measure constructed from socioeconomic factors such as income, poverty, education and housing — to define the level of disadvantage for the neighborhoods in which the study patients lived. For example, 110 of the patients resided in the most disadvantaged neighborhoods of Baltimore City and the United States, ranking in the 90th to 99th percentile on the ADI scale.

In collecting their data, the researchers adjusted for tobacco use and the severity of sudden or chronic illnesses. The findings still showed that patients who live in the most underserved neighborhoods — defined as ones having the highest ADI — were those most frequently rehospitalized following sepsis treatment. Even when these patients received equal care to others in the hospital, living in a disadvantaged neighborhood increased their likelihood of readmission.

“We believe that conditions in more disadvantaged neighborhoods, such as exposure to unsanitary environments or lack of healthy food, provide more challenges for a person’s immune system, which may compromise them during their recovery from sepsis,” says Panagis Galiatsatos, M.D., M.H.S., assistant professor of pulmonary and critical care medicine at the Johns Hopkins University School of Medicine and lead author of the study.

Based on their findings, Galiatsatos and his colleagues recommend that ADI be used to identify vulnerable populations at greatest risk for readmissions following hospitalization for sepsis. They believe that doing so can help health care providers to better address the disparity and implement ways to mitigate it.