© MedPage Today Neurology
Having a residual shunt after percutaneous patent foramen ovale (PFO) closure was associated with an elevated risk of stroke or transient ischemic attack (TIA) recurrence years after the procedure, researchers found in a prospective cohort study.
The incidence of these events reached 2.32 per 100 patient-years with a shunt on transthoracic echocardiography (TTE) compared with 0.75 per 100 patient-years with a complete seal. The elevated risk persisted after adjustment for other factors (adjusted HR 3.01, 95% CI 1.59-5.69).
Whereas small residual shunts were not significantly linked to increased risk (HR 2.02, 95% CI 0.87-4.69), moderate or large residual shunts were (HR 4.50, 95% CI 2.20-9.20), reported MingMing Ning, MD, MMSc, of Massachusetts General Hospital and Harvard Medical School, and colleagues. Their findings were published online in the Annals of Internal Medicine.
Noting that stroke and TIA recurrence most often occurred within the first few years after PFO closure, Ning's team suggested that patients with moderate or large residual shunts undergo long-term follow-up of at least 5 years with a multidisciplinary team, with TTE with bubbles performed every 3 to 6 months during the first year and every 6 to 12 months thereafter to evaluate shunt size.
And because shunts can be expected to diminish over time as the closure device gets further epithelialized, stepping up antithrombotic treatment is reasonable until the shunt stabilizes, they added.
A 3D bioengineered human brain tissue model developed features of Alzheimer's disease -- including amyloid-beta plaque formation, neuronal loss, neuroinflammation, and reduced neural network functionality -- when infected with herpes simplex virus-1. (Science Advances)
An artificial intelligence model accurately predicted Alzheimer's risk by assessing MRIs, cognitive scores, age, and sex, besting 11 practicing neurologists. (Brain)
Even psychiatry residents are being recruited to care for COVID-19 patients in the hospitals. (STAT)
According to geotagged Twitter data, Michigan was the top state for COVID-19-related depression and anxiety tweets, followed by Missouri and Louisiana. (MLive)
The European ADHD Guidelines Group released additional guidance on initiating ADHD treatment in patients during the pandemic who haven't had an in-person baseline cardiovascular assessment. (The Lancet Child & Adolescent Health)
Mind Medicine announced it's entering into a phase IIa clinical trial testing LSD micro-dosing in adults with ADHD.
People with schizophrenia who switched to lurasidone (Latuda) after 12 months of treatment on risperidone (Risperdal) saw an improvement in symptoms along with reductions in weight, metabolic parameters, and prolactin levels. (BMC Psychiatry)
Dopaminergic progenitor cells derived from a Parkinson's disease patient's own skin cells and injected into his putamen showed evidence of survival and were associated with improved motor scores and quality of life measures.
The cells were implanted into the 69-year-old Parkinson's patient's putamen in two procedures, left hemisphere followed by right hemisphere, 6 months apart. PET imaging with a dopaminergic activity tracer up to 24 months suggested graft survival, reported Jeffrey Schweitzer, MD, PhD, of Massachusetts General Hospital, and colleagues, in the New England Journal of Medicine.
Over 24 months, the patient's MDS-UPDRS, part III (evaluating parkinsonian motor signs) and PDQ-39 (assessing Parkinson's disease-related quality of life) scores also improved. His Parkinson's drug regimen at 24 months was similar to his pre-procedure treatment, but his levodopa equivalents were reduced from 904 mg to 847 mg.
The patient required no immunosuppression. "We have shown for the first time in this study that these reprogrammed cells are still recognized as self by the patient's immune system and won't be rejected," senior author Kwang-Soo Kim, PhD, of McLean Hospital in Belmont, Massachusetts, said in a statement.
"The study is interesting and promising, but should be interpreted with caution given that it reports on only one patient with limited and incomplete clinical data," noted Malin Parmar, PhD, of Lund University's Developmental and Regenerative Neurobiology department in Sweden, who wasn't involved with the research.
Widespread connectivity loss was seen in early Alzheimer's brains, researchers reported.
Positron emission tomography (PET) imaging with [11C]UCB‐J showed a broad pattern of synaptic density reductions in all medial temporal and neocortical brain regions analyzed, wrote Adam Mecca, MD, PhD, of Yale University in New Haven, Connecticut, and co-authors in Alzheimer's & Dementia.
These reductions largely were maintained after correcting for volume loss and were more extensive than decreases in gray matter volume, Mecca and colleagues noted. Lower tracer uptake also correlated with lower cognitive performance.
The researchers used [11C]UCB‐J, a relatively new in vivo PET tracer, to visualize synaptic vesicle glycoprotein 2A (SV2A) binding in 34 people with early Alzheimer's disease and 19 cognitively normal older adults. SV2A is expressed in virtually all synapses and is located in synaptic vesicles in the presynaptic terminal.
The group's earlier work with the tracer looked at synaptic alterations in early Alzheimer's disease, but didn't identify their extent or determine an optimal reference region for SV2A Alzheimer's studies.
"We still predominately test if you are being admitted or, now, if you need an elective surgery or admission to a skilled nursing facility. Outpatient is still chaos." -- An anonymous infectious diseases specialist, responding to a MedPage Today benchmark survey about challenges healthcare workers face during the COVID-19 pandemic.
"They are a harbinger of what is to come. In several decades, these conditions will start affecting large regions and for longer periods of time." -- Matthew Huber, PhD, of Purdue University in West Lafayette, Indiana, about potentially fatal heat and humidity mixtures recorded at weather stations throughout the world.
"Don't buy any fancy cars." -- Andrew Freedman, MD, program director of the urology residency program at Cedars-Sinai Medical Center in Los Angeles, on his advice to medical trainees in the current uncertain economic climate.
"It's actually incredibly complicated." -- Alysse Wurcel, MD, of Tufts Medical Center in Boston, on the logistics of testing prison and jail inmates for coronavirus infection.
"It is an important milestone in the field as it reports on survival of stem cell-derived dopamine neurons in a human brain." -- Malin Parmar, PhD, of Lund University in Sweden, discussing a novel brain cell transplant performed in a Parkinson's disease patient.
There was no trade-off of impaired cognition when evolocumab (Repatha) was added to statin therapy for LDL cholesterol lowering, according to patient-reported outcomes from the FOURIER trial.
Similar proportions of patients in the evolocumab and placebo groups reported cognitive decline over a median 2.2 years (3.7% vs 3.6%, P=0.62), as shown on a 23-item survey on memory and executive domains using the Everyday Cognition (ECog) scale.
The survey revealed no differences in total scores and subdomain scores among the 82.2% of the FOURIER trial population who answered questions about their everyday function at the beginning and the end of trial participation, reported Robert Giugliano, MD, SM, of Brigham and Women's Hospital in Boston, and colleagues in the May 12 issue of the Journal of the American College of Cardiology.
Even people who achieved very low LDL cholesterol levels (<20 mg/dL) at week 4 had similar declines in total cognitive score as those whose LDL remained at or above 100 mg/dL.
Study results were consistent across prespecified baseline subgroups, including patients above age 75.
While scores of Americans have had to postpone elective surgeries, sometimes for serious conditions, at least eight professional athletes have gone ahead with procedures including elbow and knee ligament reconstruction and groin surgery.
Some names are familiar to sports fans: Major League Baseball pitchers Justin Verlander had groin surgery and Noah Syndergaard and Chris Sale had "Tommy John" surgery; Major League Soccer star Josef Martinez had anterior cruciate ligament (ACL) reconstruction.
Many sports medicine providers support these athletes' surgical endeavors, citing their need to support their livelihood, as well as the absence of major restrictions at their surgery locale at surgery time (most of these occurred in mid to late March), and the potential for further harm if the athletes waited until after the pandemic.
Yet others question the safety and ethics of undergoing what they deemed non-essential surgeries when the U.S. Surgeon General, state governors, and the Centers for Medicare and Medicaid Services (CMS) have cautioned against them.
"It's this question of what's essential and what's not essential," said Lee Igel, PhD, a medical ethicist with the New York University Tisch Institute for Global Sport.
A case report in Italy suggests breakthrough seizures may be a sign of COVID-19 infection.
"We describe the first patient to develop a focal status epilepticus as a presenting symptom of SARS-CoV-2 infection," reported Catello Vollono, MD, PhD, of Fondazione Policlinico Universitario Agostino Gemelli in Rome, and co-authors in Seizure.
The patient was a woman who had a previous episode of herpes encephalitis with seizures that had been well controlled for 2 years. She developed focal myoclonus suddenly and required hospitalization and intravenous (IV) anti-seizure medications; 12 hours later, she had a fever and tested positive for SARS-CoV-2, the virus that causes COVID-19 infection.
This suggests the patient had an unmasking of her underlying seizures, said Avindra Nath, MD, senior investigator of nervous system infections at the NIH's National Institute of Neurological Disorders and Stroke, who was not involved with the case.
"The importance of this case is that all patients who present with unmasking of seizures in the setting of exposure to the virus should be tested for SARS-CoV-2 during the pandemic and should be isolated until results are available," Nath told MedPage Today.
More than a third of 214 confirmed COVID-19 cases in China had neurologic symptoms, researchers said.
Acute cerebrovascular events, impaired consciousness, and muscle injury were seen in 36.4% of patients and were more common (45.5%) in patients with severe infection who required mechanical ventilation, reported Bo Hu, MD, PhD, of Union Hospital and Huazhong University of Science and Technology in Wuhan, and colleagues.
Neurologic symptoms included central nervous system (CNS) manifestations such as dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, or seizure; peripheral nervous system manifestations such as taste and smell impairment, vision impairment, or nerve pain; and skeletal muscular injury manifestations.
"For those with severe COVID-19, rapid clinical deterioration or Worsening could be associated with a neurologic event such as stroke, which would contribute to its high mortality rate," the team wrote in JAMA Neurology. "During the epidemic period of COVID-19, when seeing patients with these neurologic manifestations, clinicians should consider SARS-CoV-2 [the virus that causes COVID-19] infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and prevention of transmission."
COVID-19 and severe acute respiratory syndrome (SARS), which first appeared in China in late 2002, are similar in many ways clinically, noted S. Andrew Josephson, MD, of the University of California San Francisco, and colleagues, in an accompanying editorial.
As the federal government took steps to ease shortages of some critical sedatives and other drugs used in the ICU, pharmacy and anesthesiology groups say more needs to be done.
On Tuesday, the Drug Enforcement Administration loosened restrictions on controlled substances needed for the ICU treatment of COVID-19, increasing by 15% the allowed production volumes of fentanyl, morphine, hydromorphone, codeine, ephedrine, pseudoephedrine, and certain intermediates for their production. The agency also boosted the amount of ketamine, diazepam, midazolam, lorazepam, and phenobarbital that can be imported.
More action is being sought, though.
The American Society of Anesthesiologists (ASA), for example, is calling for the FDA to work with manufacturers to extend expiration dates of critical products.
The ASA threw the spotlight most urgently on the ICU sedative propofol. "With the increased demand for this drug and the number of COVID-19 positive patients needing ventilators, we can only anticipate that this will soon be in shortage," the group said in an open letter to the FDA.
WASHINGTON -- The FDA approved selumetinib (Koselugo) on Friday for the treatment of plexiform neurofibromas in children with neurofibromatosis type 1 (NF1).
NF1 is a genetic condition that leads to the growth of tumors throughout the body, that while benign can affect patients' organs and be painful and debilitating. Selumetinib, a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor, is indicated for children 2 years and older with symptomatic and inoperable plexiform neurofibromas, tumors of the nerve sheaths.
"[I]n this critical time we want patients to know that the FDA remains committed to making patients with rare tumors and life threatening diseases, and their unique needs, a top priority," Richard Pazdur, MD, the FDA's top oncology/hematology official, said in a statement. "For the first time, pediatric patients now have an FDA-approved drug to treat plexiform neurofibroma, a rare tumor associated with NF1."
Approval was based on a phase II study of 50 NF1 patients with inoperable plexiform neurofibromas who received the drug's recommended oral dose (25 mg/m2 twice daily) until disease progression or unacceptable toxicity. Two-thirds of patients achieved a partial response to selumetinib, defined as a 20% reduction in tumor volume on MRI at 6 months, and 82% of these patients had responses lasting a year or more.
Patient-reported quality-of-life scores also improved for 29 patients during treatment, as did parent-reported scores for 45 patients.
"You have an attending physician who knows what she's doing directing fish-out-of-water physicians who have been conscripted into service beyond their specialties." -- Scott Weavil, JD, on redeployment terms being written into physicians' contracts during COVID-19.
"We're used to dealing with horrific situations and we're used to dealing with death. But now it's coming at an accelerated rate." -- Vincent Variale, president of the Uniformed EMS Union Local 3261 in New York, on the impact of the COVID-19 crisis on EMS workers.
"When you pay doctors for performance, you have to be able to measure how sick their patients are, because a hospital or doctor with sicker patients is going to have worse performance and you don't want to penalize them for that." -- Kenton Johnston, PhD, of St. Louis University, discussing the idea of incorporating a "frailty index" into Medicare pay.
"I find it very hard to justify firing anybody who is trying to tell stories for the right reasons." -- Nisha Mehta, MD, a radiologist in Charlotte, on providers who face punishment for publicly discussing PPE shortages at their hospitals.
"The more you take it, the more you lose respiratory reserves, and you may not be able to fight this infection." -- Samer Narouze, MD, PhD, of Western Reserve Hospital in Ohio, discussing opioid treatment for chronic pain during the COVID-19 pandemic.
A phase III study of the nerve growth factor and monoclonal antibody tanezumab showed positive results in a refractory patient population with knee or hip osteoarthritis (OA) -- good enough that this agent may finally be approved after a long and rocky development road.
Among 849 patients enrolled from 104 sites from 2016 to 2018 who had not responded to other oral or injectable treatments, those randomized to 5-mg tanezumab had a change on the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscale of -2.85 at week 24 compared with -2.24 for those receiving placebo, for a mean difference of -0.62 (P=0.0006), according to Francis Berenbaum, MD, PhD, of the Sorbonne Université in Paris, and colleagues.
Patients receiving tanezumab 2.5 mg also had significantly greater reductions in pain compared with placebo, with a mean difference of -0.46 (P=0.0088), the researchers reported online in Annals of the Rheumatic Diseases.
"This study demonstrates subcutaneous tanezumab at a dose of 5 mg every 8 weeks statistically significantly improves pain, physical function, and patient global assessment of OA at 24 weeks in patients with moderate-to-severe OA who have not responded to or could not tolerate standard-of-care analgesics," wrote Berenbaum and colleagues.
The FDA decided last month to accept a regulatory submission for tanezumab given subcutaneously in doses of 2.5 for moderate-to-severe OA that has not responded to conventional treatments, according to developers Pfizer and Eli Lilly.
The specific symptom pattern in depressed adolescents was associated with likelihood of improvement with fluoxetine (Prozac), a secondary analysis of the Treatment for Adolescents with Depression Study (TADS) indicated.
Among 426 children with moderate-to-severe depression, those with "cardinal" symptoms such as anhedonia, sleep problems, and social withdrawal had significantly improved scores on the Children's Depression Rating Scale-Revised (CDRS-R) with fluoxetine alone (4.1 points, 95% CI 1.1-7.1) or with added cognitive behavioral therapy (CBT) (5.8 points, 95% CI 2.8-8.9) compared with a placebo arm at 12 weeks, reported Christian Kieling, MD, PhD, of the Hospital de Clínicas de Porto in Porto Alegre, Brazil, and colleagues.
In contrast, teens on fluoxetine with a second cluster of symptoms such as physical complaints, appetite changes, and suicidal ideation showed no significant improvements on the CDRS-R scale, with or without CBT, compared with the placebo arm, the researchers wrote in The Lancet Psychiatry.
However, among adolescents with this second symptom cluster, those on fluoxetine and CBT had significantly improved scores compared with those on fluoxetine or CBT alone, the researchers added.
"Our results confirm that response to treatment is heterogeneous and suggest the clinical profile for which a given therapeutic modality might be more or less beneficial," Kieling and co-authors wrote, adding that the two clusters selected in the study have previously been identified in adults as playing an important role in treatment effects.