Body

Researchers at Rutgers Robert Wood Johnson Medical School have reported the first instance of COVID-19 triggering a recurrence of Guillain-Barré Syndrome - a rare disorder where the body's immune system attacks nerves and can lead to respiratory failure and death.

While there have been several reports of Guillain-Barré Syndrome following COVID-19, this is the first in which COVID-19 actually triggered a recurrence of the condition - in a 54-year-old man who had suffered with Guillain-Barré Syndrome twice and had a third occurrence after testing positive for COVID-19, according to the Rutgers case report published in the journal Pathogens.

"The patient came to the emergency room with complaints of progressive difficulty swallowing, then had a fever for three days, followed by weakness in the arms, legs and face," said Erin McDonnell, a medical student who made the discovery. "His symptoms were worse this time than in previous episodes. He has since recovered."

Researchers looked at about 1,200 hospital patients diagnosed with COVID-19 who were admitted and discharged between March and May of 2020 and this was the only instance where COVID-19 triggered the recurrence of Guillain-Barré Syndrome.

Guillain-Barré Syndrome can follow acute viral and bacterial infections, causing symptoms including weakness and tingling in the extremities. As the condition worsens, the weakness quickly spreads, eventually sometimes paralyzing the whole body. While most people recover from the condition, about 5 percent of people experience a recurrence, McDonnell said.

"We recommend that patients who develop COVID-19 and have a history of autoimmune [demyelinating] disorders in which the body's immune system attacks the myelin that insulates and protects their nerves be closely observed for several weeks for neurologic symptoms," said Payal Parikh, assistant professor at Rutgers Robert Wood Johnson Medical School, who led the study along with Martin Blaser, director of the Center for Advanced Biotechnology and Medicine.

The findings will improve the understanding of the spectrum of Guillain-Barré Syndrome, which may be trigged by acute viral or bacterial infection, and help create treatments for COVID-19 patients.

A large study of patients in the United States who contracted coronavirus disease 2019 (COVID-19) confirms many complications of the disease, according to new research in CMAJ (Canadian Medical Association Journal).

"Understanding the full range of associated conditions can aid in prognosis, guide treatment decisions and better inform patients as to their actual risks for the variety of COVID-19 complications reported in the literature and media," writes Dr. William Murk, Jacobs School of Medicine & Biological Sciences, University at Buffalo, Buffalo, New York, with coauthors from Aetion, Inc., HealthVerity, Inc. and the University of Toronto.

Using de-identified outpatient and inpatient medical claims from a United States health database, researchers identified 70 288 patients who had a COVID-19-related health visit between March 1 and April 30, 2020. More than half of all patients were admitted to hospital, and approximately 5% were admitted to the intensive care unit. The median age was 65 years, and 55.8% were female. The authors looked at all possible diagnostic codes and identified those that increased in frequency after the onset of COVID-19.

The most common complications associated with COVID-19 were pneumonia, respiratory failure, kidney failure, and sepsis or systemic inflammation, consistent with other studies. The absolute risk of someone with COVID-19 having these serious conditions was 27.6% for pneumonia, 22.6% for respiratory failure, 11.8% for kidney failure and 10.4% for sepsis or systemic inflammation.

The researchers also found associations with a range of other lung and cardiovascular conditions, such as collapsed lung, blood clotting disorders and heart inflammation, although the risk of these was relatively low. Contrary to results of other studies, COVID-19 did not appear to be associated with a higher risk of stroke.

"This study provides estimates of absolute risk and relative odds for all identified diagnoses related to COVID-19, which are needed to help providers, patients and policy-makers understand the likelihood of complications," write the authors.

A team of biologists from RUDN University developed a hibiscus-based dietary supplement for trout that makes the fish less sensitive to ammonia pollution and more stress-resistant. The results of the study were published in the Aquaculture journal.

Rainbow trout (from the genus of Pacific salmons) is one of the most popular species in fish farms. When bred on a farm, a trout can grow up to 6-8 kg, while in nature they are usually smaller. In the course of their lives, all fish produce ammonia, and because of an unbalanced diet, high density, and lack of fresh water the pools at fish farms are often rich in it. In these concentrations, ammonia becomes poisonous: it suppresses the immune systems of the fish and provokes inflammations, making the fish susceptible to various diseases. A team of biologists from RUDN University found out that the toxicity of ammonia can be reduced with the help of a natural supplement made of hibiscus powder.

"Our goal was to analyze the immune-stimulating and anti-inflammatory effect of Hibiscus sabdariffa for rainbow trout Oncorhynchus mykiss. The tests were carried out both in regular conditions and after the addition of ammonia," said Yuri Vatnikov, a Ph.D. in Veterinary Medicine, and the Head of the Department of Veterinary Medicine at RUDN University.

Roselle or Hibiscus sabdariffa is a shrub of the family Malvaceae. It is known for its antispastic, diuretic, and antifebrile properties. Its flowers are used to make carcade, and the leaves are edible with their sepals rich in organic acids, sugars, vitamins, and nutrients. That is why the team from RUDN University chose hibiscus as a dietary supplement for rainbow trout.

To test its effect on the fish, the team conducted an experiment: 480 young rainbow trouts weighing about 8 g each were divided into three groups and put into 12 60-liter aquariums (40 fish in each). The first group got no hibiscus in its diet; the second received 0.5% and the third 1% of the natural supplement. The dietary regime was maintained for 60 days. After that, the trouts were moved to aquariums with 0.3 mg/l ammonia concentration (0.52 mg/l being lethal for the fish) for 24 hours.

Ammonia increased the activity of inflammation agents (plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and the production of inflammatory proteins in the liver of all fish. At the same time, the levels of lysozyme, immunoglobulins. and other protective molecules in their bodies decreased. However, by the end of the experiment, the fish that received 0.5% of hibiscus powder gained the most weight and grew the fastest among all three groups (showing 471% growth compared to 385% and 395% in the first and third group, respectively). The fish that received the supplement also turned out to have healthier livers and stronger immune systems, and their blood contained less inflammation marker proteins and more immunoglobulins. Moreover, their skin mucus was more effective against bacteria.

"Our study confirms that hibiscus is capable of improving the immune response and reducing inflammation in rainbow trout thus supporting the health of the fish after it is exposed to the toxic influence of ammonia. We recommend adding 0.5-1% of this supplement to the diet of the trout," added Yuri Vatnikov.

ABSTRACT 464

A study led by The University of Texas MD Anderson Cancer Center showed that first-line treatment with a regimen of chemotherapy combined with the monoclonal antibody blinatumomab resulted in increased survival and achieved a high rate of measurable residual disease (MRD) negativity for patients who were newly diagnosed with a high-risk form of acute lymphoblastic leukemia (ALL) known as Philadelphia chromosome-negative B-cell ALL (Ph-negative B-ALL).

Findings from the study were presented by Nicholas Short, M.D., assistant professor of Leukemia, at the virtual 2020 Annual Meeting of the American Society of Hematology. The study was led by Elias Jabbour, M.D., professor of Leukemia.

"The best opportunity to cure any acute leukemia is by giving the most effective therapy in the front-line setting," Short said. "We are very encouraged that every patient on the study achieved a complete remission and 97% achieved MRD negativity, which is highly associated with better outcomes."

Advancing treatment options and improving quality of life for ALL patients

Standard treatment for patients with Ph-negative B-ALL is combination chemotherapy, which has a high rate of treatment failure and complications. Current therapies for ALL have high remission rates of up to about 90%. However, many patients relapse, leading to long-term survival rates of 50% or less. Finding new treatment options that can improve response and survival for these patients is critical.

Immunotherapy using monoclonal antibodies, such as blinatumomab, encourages changes in the body's immune system and interferes with the ability of tumor cells to grow and spread. Blinatumomab has two components, one targets CD3, on the T-cells, and one targets CD19, which is overexpressed in most cases of B-cell ALL. Previous clinical trials have shown blinatumomab to be effective in improving overall survival in the relapsed or refractory setting and it has been proven to clear up MRD, as well.

"Although the survival data is early, it is promising, with a two-year survival of 80%. This is particularly important as about a third of these patients had high-risk features," Jabbour said. "We are encouraged that we can decrease the amount and duration of chemotherapy for patients and hope that these results will translate to long-term survival and increased cure compared to standard chemotherapy regimens."

Evaluating patient response and adding a new study arm

The trial enrolled 38 patients, ages 14 to 59, with newly diagnosed Ph-negative B-ALL, 34 of whom were able to be evaluated in the study. Patients could not have received more than one prior cycle of chemotherapy and were required to have a performance status of ?3, total bilirubin ?2 mg/dl and creatinine ?2 mg/dl.

Trial participants were 55% Caucasian, 32% Hispanic, 5% Black, 3% Asian and 5% other. At least one high-risk feature was present in 19 patients (56%), including TP53 mutation in 10 patients (17%), CRLF2+ in 6 patients (19%), and an adverse-risk karyotype in 12 patients (32%).

Patients received two cycles of hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) chemotherapy alternating with two cycles of high-dose methotrexate and cytarabine, followed by four cycles of blinatumomab at standard doses. The maintenance phase consisted of 12 monthly cycles of daily mercaptopurine, monthly vincristine, weekly methotrexate, and monthly pulses of prednisone (POMP) with three additional cycles of blinatumomab.

All patients in the study experienced at least one adverse event, which was expected with the hyper-CVAD regimen. Four patients developed cytokine release syndrome, which resolved with corticosteroids and interruption of blinatumomab.

Thirty-one percent of patients had a blinatumomab-related neurological event, including a grade 2 seizure in one patient, a grade 1 tremor in two patients, a grade 3 ataxia in one patient and a grade 2 encephalopathy and dysphasia in one patient. All other neurological events were easily manageable, reversible and did not alter the planned treatment.

Relapses occurred in 13% of patients, but no relapses were observed in patients without baseline high-risk features or in any patients beyond two years. Twelve patients underwent an allogenic stem cell transplant and 17 patients remain in continuous remission.

The next stage of this study will incorporate inotuzumab ozogamicin into the regimen for the next 40 patients enrolled in the trial. Inotuzumab ozogamicin is an anti-CD22 antibody drug that attaches to the CD22, which is highly expressed in B lymphoblasts, and then delivers the toxin directly to the ALL cells. While these findings need to be confirmed in larger studies, the data suggests that blinatumomab can improve treatment response for Ph-negative B-ALL patients.

"Our goal now is to see if we can do hyper-CVAD with blinatumomab and adding inotuzumab ozogamicin to get even better results," Short said. "We believe this will decrease chemotherapy-related toxicity, minimize MRD, further decrease reliance on stem cell transplants and improve long-term outcomes for these patients."

First study to assess the global impact of travel restrictions on the pandemic suggests they are effective in countries with low numbers of COVID-19 cases, or that have strong travel links with countries experiencing high rates of infection.

The measures are unlikely to be effective when the virus is already spreading rapidly within a country.

Travel restrictions may have been most effective during the early stages of the pandemic.
International travel restrictions may only be effective at controlling the spread of COVID-19 when applied in a targeted way, according to research published in The Lancet Public Health journal.

The measures may have limited impact on the epidemic within individual countries except those with low levels of the virus or that have strong travel links with countries experiencing high rates of infection.

The new study also suggests that travel restrictions can be effective in countries close to a tipping point for exponential growth - with a reproduction number, or R number, between 0.95 and 1.05 -but not in those where it is already spreading rapidly among the population.

Every country in the world had imposed some form of travel restrictions - which have high economic and social costs - by late April 2020 as part of efforts to control the spread of the COVID-19. However, until now, no studies had produced global estimates of how the risk of importing cases relates to local transmission levels. Findings from this study could enable policymakers to determine where travel restrictions will have a major impact on slowing local transmission, and where they will have little effect.

Professor Mark Jit from the London School of Hygiene and Tropical Medicine, who led the study, said: "We recognise that these measures carry a high economic and social cost, so it's important that governments use travel restrictions in a targeted way. Before introducing restrictions, they should take into account local infection figures, epidemic growth rates, and the volume of travellers arriving from countries heavily-affected by the virus." [1]

The authors used detailed flight data to compare the number of expected COVID-19 cases arriving from international flights (assuming no travel restrictions) with the number of infections arising from transmission within individual countries. The authors produced estimates of international travellers in May and September 2020 based on two scenarios. One scenario used flight data for the same months in 2019 (assuming no reduction in travel numbers) and the other scenario was based on the expected reduction in passenger numbers. Numbers of COVID-19 cases and infection rates were estimated using a mathematical model that adjusts recorded cases to take account of asymptomatic and unreported infections.
Results were determined based on how imported COVID-19 cases would affect local epidemic growth rates, using country-specific R number estimates. Where imported cases accounted for more than 10% of infections within individual countries, they were considered to have a major impact on growth of the epidemic. The work estimated that when imported cases accounted for less than 10%, their impact on the growth of the epidemic is usually small, while those below 1% would have an almost undetectable effect on epidemic size. Publicly available country-specific R number estimates were used to identify countries close to their tipping point for exponential growth (R number between 0.95 and 1.05).

Had there been no travel restrictions or reduction in travel volumes in May 2020, the imported COVID-19 cases would account for more than 10% of infections in the majority of countries (102/136 countries included in the analysis). Imported cases would account for no more than 10% of infections in 34 out of 136 countries, and less than 1% in four. According to the estimates based on expected passenger numbers in May 2020, imported cases would have contributed to more than 10% of total incidence in 74 countries, less than 10% of total incidence in 62 countries, and to less than 1% in eight countries.

However, by September 2020, had there been no travel restrictions or reduction in travel volumes, imported cases would account for more than 10% of infections in only a small number of countries (56/162 countries). Imported cases account for less than 10% of infections in 106 out of 162 countries, and less than 1% in 21. According to the estimates based on expected passenger numbers in September 2020, travel restrictions would have contributed to more than 10% of infections in only 37 countries, less than 10% in 125 countries and less than 1% in only 44 countries (see appendix for country-level data).

In September 2020 with an expected reduction in passengers, of the 44 countries where imported cases would account for less than 1% of local infections in, 22 have R number estimates outside their tipping point (ie, R1.05), meaning that lifting travel restrictions in these countries is unlikely to cause local outbreaks (see appendix for country-level data). In May 2020 with an expected reduction in passengers, there are only five countries with R numbers estimates outside their tipping point where imported cases would account for less than 1% of local infections.

The findings indicate that international travel restrictions were most effective at limiting local transmission of the virus during earlier stages of the pandemic. This is because imported cases led to outbreaks in countries with very few - or no - existing cases.

The authors conclude that recommendations about international travel restrictions should not be applied uniformly. Countries must first consider local infection figures and epidemic growth rates, as well as the volume of travellers arriving from countries heavily-affected by COVID-19. For instance, in September 2020, the measures would be effective in New Zealand and China because the virus had been supressed to such low levels in both countries that the expected number of imported cases is similar to the local rate, meaning arrivals could trigger a new local wave of infections.

Estimates produced in the study assume that the COVID-19 rate among international travellers was the same as the general population of their country of origin. However, infected arrival rates are likely to be lower because people with symptoms are less likely to travel in the first place, and those who do may be detected during routine screening. People in the incubation period while traveling may develop symptoms and be detected, or self-declare illness upon arrival to their destination. This could mean that the number of imported COVID-19 cases that would occur without travel restrictions is overestimated in this study.

The authors also assessed only international flight data, meaning their analysis may not accurately capture the risk of COVID-19 spreading between countries with high volumes of land traffic (such as rail and road travel between countries in continental Europe).

Binge drinkers increased their alcohol consumption by nearly 20% during COVID-19 stay-at-home orders, according to new research by public health experts at The University of Texas Health Science Center at Houston (UTHealth). Their study, published in the American Journal of Drug and Alcohol Abuse, is one of the first to analyze the association of stress caused by the pandemic and dangerous alcohol consumption.

The study team surveyed nearly 2,000 adults in the United States in the spring of 2020. Their questions aimed to understand any stressors participants were experiencing stemming from COVID-19 lockdown orders, including amount of time spent at home, how many individuals were living in the participants' household, any current or previous instances of depression, and any job impacts related to the pandemic such as decreased pay. They also surveyed participants about their drinking habits, classifying them as either binge drinkers, non-binge drinkers, or nondrinkers.

Based on the self-reported data, the team was able to determine that 32% of all the participants reported binge drinking during stay-at-home orders, and 60% of those classified as binge drinkers said they had increased alcohol consumption during the pandemic compared to 28% of non-binge drinkers. Binge drinking is defined for men as consuming five or more drinks and for women as consuming four or more within a two-hour period.

In addition, binge drinkers with a history and current diagnosis of depression were more likely to report consuming more alcohol during the pandemic, compared to those with no previous or current diagnosis. The study authors also found that the longer participants spent sheltering at home, the greater the odds of harmful consumption of alcohol.

Those who binge-drank shared they consumed a maximum of roughly seven drinks in one sitting during the pandemic. In comparison, non-binge drinkers reported consuming roughly two drinks maximum during stay-at-home orders, with approximately 56% of non-binge drinkers reporting drinking about the same amount they would prior to the pandemic.

Respondents answered they spent an average of four weeks in lockdown and at least 21 hours a day at home. Those who lived with children were 26% less likely to binge-drink compared to those who did not have children in their household.

The study team shared that their findings point to the concern that the COVID-19 pandemic will have lasting public health consequences, even for those who never contracted the virus.

"Our results indicate that those who spent more time at home during the early stages of the pandemic were more likely to consume alcohol at unhealthy levels. This was particularly concerning for those with a previous diagnosis of depression and current depressive symptoms," said Sitara Weerakoon, MPH, first and corresponding study author and a doctoral candidate at UTHealth School of Public Health.

According to the U.S. Centers for Disease Control and Prevention, prolonged heavy alcohol consumption can lead to liver disease, cancer, cardiovascular disease, and alcohol use disorders.

"We hope that public health and clinical experts consider these additional associations of the pandemic and develop programs and opportunities to overcome them. This may include increasing awareness and access to virtual counseling sessions and mental health services. Additionally, public health organizations should prioritize providing healthy alternatives for stress relief, such as virtual meetups and social activities," Weerakoon said.

Researchers have developed a potential new treatment for the eye disease glaucoma that could replace daily eye drops and surgery with a twice-a-year injection to control the buildup of pressure in the eye. The researchers envision the injection being done as an office procedure that could be part of regular patient visits.

The possible treatment, which could become the first non-drug, non-surgical, long-acting therapy for glaucoma, uses the injection of a natural and biodegradable material to create a viscous hydrogel -- a water-absorbing crosslinked polymer structure -- that opens an alternate pathway for excess fluid to leave the eye.

"The holy grail for glaucoma is an efficient way to lower the pressure that doesn't rely on the patient putting drops in their eyes every day, doesn't require a complicated surgery, has minimal side effects, and has a good safety profile," said Ross Ethier, professor and Georgia Research Alliance Lawrence L. Gellerstedt Jr. Eminent Scholar in Bioengineering in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "I am excited about this technique, which could be a game-changer for the treatment of glaucoma."

The research, which was supported by the National Eye Institute and the Georgia Research Alliance, was published Dec. 7 in the journal Advanced Science. The research was conducted in animals, and shows that the approach significantly lowered the intraocular pressure.

As many as 75 million people worldwide have glaucoma, which is the leading cause of irreversible blindness. Glaucoma damage is caused by excess pressure in the eye that injures the optic nerve. Current treatments attempt to reduce this intraocular pressure through the daily application of eye drops, or through surgery or implantation of medical devices, but these treatments are often unsuccessful.

To provide an alternative, Ethier teamed up with Mark Prausnitz, professor and J. Erskine Love Jr. Chair in the School of Chemical and Biomolecular Engineering at Georgia Tech, to use a tiny hollow needle to inject a polymer preparation into a structure just below the surface of the eye called the suprachoroidal space (SCS). Inside the eye, the material chemically crosslinks to form the hydrogel, which holds open a channel in the SCS that allows aqueous humor from within the eye to drain out of the eye through the alternative pathway.

There are normally two pathways for the aqueous humor fluid to leave the eye. The dominant path is through a structure known as the trabecular meshwork, which is located at the front of the eye. The lesser pathway is through the SCS, which normally has only a very small gap. In glaucoma, the dominant pathway is blocked, so to lessen pressure, treatments are created to open the lesser pathway enough to let the aqueous humor flow out.

In this research, the hydrogel props open the SCS path. A hollow microneedle less than a millimeter long is used to inject a droplet (about 50 microliters) of the hydrogel-precursor material. That gel structure can keep the SCS pathway open for a period of months.

"We inject a viscous material and keep it at the site of the injection at the interface between the back of the eye and the front of the eye where the suprachoroidal space begins," Prausnitz said. "By opening up that space, we tap a pathway that would not otherwise be utilized efficiently to remove liquid from the eye."

The injection would take just a few minutes, and would involve a doctor making a small injection just below the surface of the eye in combination with numbing and cleaning the injection site. In the study, the researchers, including veterinary ophthalmologist and first author J. Jeremy Chae, did not observe significant inflammation resulting from the procedure.

The pressure reduction was sustained for four months. The researchers are now working to extend that time by modifying the polymer material -- hyaluronic acid -- with a goal of providing treatment benefits for at least six months. That would coincide with the office visit schedule of many patients.

"If we can get to a twice-a-year treatment, we would not disrupt the current clinical process," Prausnitz said. "We believe the injection could be done as an office procedure during routine exams that the patients are already getting. Patients may not need to do anything to treat their glaucoma until their next office visit."

Beyond extending the time between treatments, the researchers will need to demonstrate that the injection can be repeated without harming the eye. The procedure will also have to be tested in other animals before moving into human trials.

"The idea of having a 'one-and-done' treatment that lasts for six months would be particularly helpful for those whose access to healthcare is non-optimal," Ethier said. "Having a long-acting therapy would have an additional advantage during times of pandemic or other disruption when access to healthcare is more difficult."

PHILADELPHIA (December 7, 2020) - Cocaine continues to be one of the most commonly abused illicit drugs in the United States. Pre-clinical literature suggests that targeting glucagon-like peptide-1 receptors (GLP-1Rs) in the brain may represent a novel approach to treating cocaine use disorder. Specifically, GLP-1R agonists, which are FDA-approved for treating diabetes and obesity, have been shown to reduce voluntary drug taking and seeking in preclinical models of cocaine used disorder. However, the exact neural circuits and cell types that mediate the suppressive effects of GLP-1R agonists on cocaine-seeking behavior are mostly unknown.

New research from the University of Pennsylvania School of Nursing (Penn Nursing) has discovered that GLP-1Rs are expressed on specific cell types and neural circuits in the brain that reduce cocaine-seeking behavior. Investigators have also discovered that GLP-1Rs are expressed primarily on GABAergic neurons in the hindbrain and that the efficacy of the GLP-1R agonist exendin-4 to reduce cocaine seeking depends, in part, on activation of these GABA circuits. Moreover, activating these endogenous anti-craving circuits in the brain using viral-mediated gene delivery methods was sufficient to reduce cocaine-seeking behavior. These findings highlight GLP-1R-expressing anti-craving circuits in the brain that could serve as potential targets to reduce cocaine craving-induced relapse. The findings are published in the journal Molecular Psychiatry.

"Overall, the translational implications of these findings are profound in that they support GLP-1R-focused therapeutic approaches for the treatment of cocaine craving and relapse," says lead investigator Heath D. Schmidt, PhD, Associate Professor of Nursing at Penn Nursing.

Firearm injury is a major public health crisis in the United States. In 2017, more than 39,000 deaths were caused by firearms, but the incidence of cases in which people survive after a trip to the emergency department, known as cases of nonfatal injuries, has not been well established. Therefore, it has proven elusive to answer this simple question: "What is the total number of cases of firearm injury per year in the U.S.?"

A new study by a team of researchers in the Perelman School of Medicine at the University of Pennsylvania and Columbia University's Mailman School of Public Health expands research on trends of fatal and nonfatal firearm injuries in the U.S.. Their findings, published today in JAMA Internal Medicine, show that between 2009-2017, there has been an average of 120,232 firearm injuries each year, or 329 per day, and that cases of nonfatal injury are twice as prevalent as deaths from firearms. The study signifies the importance of evaluating the impact of firearm prevention policies and strategies not just on injuries that ultimately result in death, but also the more common cases in which people survive after emergency care.

The researchers, led by Elinore J. Kaufman, MD, MSHP, an assistant professor of Surgery in Traumatology, Surgical Critical Care, and Emergency Surgery, used data pulled from death certificates by the Centers for Disease Control and Prevention (CDC) that ranged from 2009 until 2017 and combined it with data on emergency room visits for nonfatal firearm injuries from the Nationwide Emergency Department Sample.

The team of researchers categorized firearm injuries and deaths in the following ways: unintentional, self-harm, assault, legal intervention, or of undetermined intent. During the period examined, there were an average of 34,538 deaths per year, of which 77 percent occur outside hospital. In total, there were an average of 85,694 emergency department visits per year for nonfatal injuries. The likelihood of survival varied dramatically when it came to intent. Roughly 90 percent of self-harm injuries resulted in death versus approximately 25 percent for those injured in either assaults or legal intervention, such as police-involved shootings, and 1 percent of those injured unintentionally, such as through an accidental discharge of a firearm.

Self-harm caused the most deaths per year (21,128) with the vast majority occurring outside the hospital. However, after taking nonfatal injuries into account, assaults were the most common cause of firearm injury (39 percent of all injuries) followed closely by unintentional injuries (37 percent of all injuries).

"Research has shown that suicide is the most common form of firearm deaths, and suicide prevention is of preeminent importance. But looking at these numbers of nonfatal injuries can raise concern in other areas needing their own forms of prevention," said Kaufman. "After two decades of progress, rates of firearm injuries are now increasing, and effective prevention strategies are urgently needed."

Kit Delgado, MD, an assistant professor of Emergency Medicine and Epidemiology, said the study fills some "major" gaps in what is known about firearm injury in the United States and could provide an approach for putting together a more complete picture.

"By combining fatal and nonfatal injury data, we can identify major differences in injury rates by mechanism and age group and geography," Delgado said. "For example, assaults among 15 to 34-year-olds account for the highest injury rates in urban areas, whereas unintentional injuries in this age group account for the highest rate of injury in rural areas. Just like there isn't only one cure for cancer, better characterization of the nuanced causes and mechanisms of firearm injury has the potential to lead to more effective implementation of public health prevention strategies."

Having this full picture is necessary to develop effective strategies for gun violence prevention and treatment. For example, while unintentional firearm injury rarely causes death, it accounts for half of all nonfatal injuries, and was the most common among children.

Prevention strategies such as child access prevention laws and gun lock distribution have the potential to prevent many of these injuries, but their true impact will remain unknown if only deaths are counted. To that end, Rinad S. Beidas, PhD, an associate professor of Psychiatry at Penn was recently granted $3.6 million from the National Institute of Mental Health to research the implementation of nudge-based programs for safer storage of firearms among parents.

In addition, the Penn Injury Science Center received funding from the National Collaborative for Gun Violence Research, examining U.S. counties in which firearm injury death rates have gone down the most over the last two decades, comparing their preventive strategies to counties in which firearm injury death rates have gone up the most. But more efforts are needed.

"A firearm injury can have a major impact on a survivor's long-term health and well-being, as well as on their family and community." Kaufman said. "We need to look beyond deaths when we evaluate injury prevention initiatives."

The team aims to expand their prior work on firearm policy to also measure the impact of policy on nonfatal injuries.

Philadelphia, December 7, 2020--Despite early reports suggesting a decline in preterm births during the COVID-19 pandemic period, an analysis by researchers at Children's Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania has found no change in preterm births or stillbirths at two Philadelphia hospitals in the first four months of the pandemic. The findings, published today in JAMA, resulted from the examination of an ongoing, racially-diverse pregnancy cohort that assesses both spontaneous and medically-indicated preterm birth.

"Preterm birth is highly complex, with a diverse set of presentations and unknown causes," said Heather H. Burris, MD, MPH, an attending physician in CHOP's Division of Neonatology and senior author of the study. "Because we have two independent reviewers assessing every preterm birth at two Penn Medicine hospitals, we were able to complete a rigorous analysis of multiple types of preterm birth for the first four months of the pandemic and compare that data to the same period in previous years."

The cohort, known as GeoBirth, includes more than 100,000 births at two Penn Medicine hospitals in Philadelphia since 2008. Each preterm birth, characterized as any birth occurring before 37 weeks' gestation, is manually classified by two independent, blinded reviewers as either a spontaneous preterm birth or a medically-indicated preterm birth. The former includes preterm labor or early rupture of the membranes, and the latter includes conditions that necessitate an early delivery for the health of the mother or baby, such as preeclampsia or intrauterine growth restriction.

The researchers analyzed 2,992 live births from March through the end of June 2020 and compared those births to 5,875 over the same four-month period in 2018 and 2019. Making use of the robust GeoBirth data set, the research team compared rates of overall preterm birth, spontaneous preterm birth, medically-indicated preterm birth, and stillbirth, defined as intrauterine demise after 20 weeks.

The data did not show any significant change in preterm or stillbirth rates during the COVID-19 pandemic. Even when breaking down the preterm birth data by spontaneous and medically-indicated preterm births, the researchers still did not detect differences between the pre-pandemic and pandemic period. These findings differ from European studies that have reported a decrease in preterm birth and increase in stillbirth during the first few months of the pandemic.

"While particular mechanisms that lead to preterm birth remain elusive, we know that various individual and environmental factors are linked to poor birth outcomes, and that those factors vary by demographic groups. Our years of work in this field led us to question other reports that suggested preterm births and stillbirths had decreased across the board over this extremely stressful and uncertain pandemic period," said Michal Elovitz, MD, director of the Maternal and Child Research Center and the Hilarie L. Morgan and Mitchell L Morgan President's Distinguished Professor in Women's Health at Penn. "The power of the GeoBirth cohort will allow us with the opportunity to query how individual, societal and environmental factors affect pregnant women and how those factors may be heightened by all the varying effects of a pandemic. It is imperative that we have rigorous tools to study how these different factors may harm pregnant people and how the pandemic may exacerbate those factors so we can target appropriate strategies to improve the lives of women and their babies."

Handley et al. "Changes in preterm birth phenotypes and stillbirth at two Philadelphia hospitals during the SARS-CoV-2 pandemic from March-June 2020," JAMA, online December 7, 2020, DOI: 10.1001/jama.2020.20991

In a recent study published in the British Journal of Dermatology, individuals with atopic dermatitis, or eczema, were more likely to also have various autoimmune diseases, especially those involving the skin, the gastrointestinal tract, or the connective tissue.

For the study, researchers analyzed Swedish national health care registers and compared 104,832 cases of atopic dermatitis with 1,022,435 controls.

Additional studies are needed to identify subsets of patients with atopic dermatitis at higher risk for autoimmune diseases, and to explore whether the severity and treatment of atopic dermatitis may affect its association with these conditions.

"Greater awareness, screening, and monitoring of autoimmune comorbidities may relieve the disease burden in patients with atopic dermatitis and may give deeper insight into its pathogenesis," said lead author Lina U. Ivert, of the Karolinska Institutet, in Sweden.

In an analysis of women with early breast cancer, Black women had higher rates of obesity and other health conditions that can affect survival, compared with white women. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS).

Obesity is a known risk factor for various cancers, and its rise over the past few decades has contributed to a rise in breast cancer rates that is greater in Black women than white women. At the same time, as breast cancer mortality rates have declined, the decline has been less pronounced in Black women, producing a 40% mortality gap.

To investigate further, Kirsten Nyrop, PhD, of the University of North Carolina at Chapel Hill, and her colleagues analyzed information concerning 548 patients treated at their hospital for early breast cancer. The team found that 62% of Black patients and 33% of white patients fell within the obese weight range, and higher percentages of Black women had obesity-related comorbidities, such as hypertension, diabetes, and high cholesterol, than white women. Yet, despite significant differences in the prevalence of obesity and comorbidities, there were no differences between Black and white patients in treatment decisions with regard to type of surgery, chemotherapy, radiation, or endocrine therapy.

"Early breast cancer is highly treatable, and survival rates have improved steadily due to treatment advances and early detection through mammograms; however, the high rates of obesity, overall comorbidities, and obesity-related comorbidities observed among women with early breast cancer--especially among Black women--can contribute to disparities in overall survival of these patients," said Dr. Nyrop. "Findings from this study need to be considered within the larger context of the cancer-obesity link and the disparate impact of the obesity epidemic on communities of color in the United States."

Dr. Nyrop noted that rates of many cancers that are impacted by obesity are higher in Black women as are rates of numerous obesity-related conditions such as diabetes and hypertension. "As the COVID-19 pandemic has glaringly underscored, there is an urgent need to address the systemic and socioeconomic aspects of obesity that disproportionately affect minority communities in the U.S. if we are to reverse health disparities."

An accompanying editorial stresses that clinicians should "take advantage of the breast cancer diagnosis as an opportunity for interventions that can be far-reaching." The authors note that several lifestyle interventions can not only address obesity but also potentially prolong survival in patients with cancer.

Harmful drinking among adults increases the longer they spend at home in lockdown, according to a study published in the peer-reviewed American Journal of Drug and Alcohol Abuse.

The research, based on a survey of nearly 2,000 over-18s in the US, is the first to highlight the relationship nationally between hazardous drinking and life stresses triggered by the COVID-19 pandemic and the associated 'lockdowns'.

The findings show the odds of heavy alcohol consumption among binge drinkers - those who, within two hours, consumed five or more drinks for men and four and above for women - rose an extra 19% for every week of lockdown.

The odds of increased alcohol intake overall for binge drinkers was more than double that of people who did not drink excessively (60% vs 28%), especially those with depression or a history of the disease.

Carried out by experts at the University of Texas Health Science Center School of Public Health, in Dallas, the study also highlights that:

During the pandemic, binge drinkers on average drank four drinks per occasion, compared to two drinks among non-binge drinkers.

Participants who drank at harmful levels during the pandemic would consume seven drinks maximum on one occasion. This is compared to a maximum of two per session during the pandemic for those who did not.

Living with children in lockdown minimally reduced the odds (by 26%) of turning to the bottle for people in general.

The researchers are now calling for new intervention and prevention strategies for people in isolation at risk of hazardous drinking. Otherwise, they say there could be long-lasting health consequences.

"Increased time spent at home is a life stressor that impacts drinking and the Covid-19 pandemic may have exacerbated this stress," says Sitara Weerakoon, a PhD candidate from the University of Texas.

"Future research should consider the potential for depressive symptoms acting as a moderator (a factor that changes the impact) in the relation between the time spent under a shelter-in-place mandate (lockdown) and binge drinking.

"Additional research is (also) needed to develop best treatment for people with substance use disorders who may be more susceptible to adverse health outcomes."

The study aim was to identify a link between COVID-19-related stress factors and changes in alcohol consumption and binge drinking since the pandemic began.

The data was from an online survey completed by 1,982 adults from mid-March to mid-April, which coincided with the first US state-wide stay-at-home order on March 19. The average age of participants was 42 and the majority were white (89%) and female (69%).

Based on survey responses, the researchers categorised participants as binge drinkers, non-binge drinkers and non-drinkers. Among the factors analysed were length of time spent in lockdown, how many adults or children they were living with, current or previous episodes of depression, and job status related to lockdown such as decreased pay.

On average, every respondent had been in lockdown for four weeks, and spent 21 hours a day at home, with the majority (72%) not leaving for work.

Overall, nearly a third (32%) of participants reported binge drinking during the pandemic with binge drinkers increasing their intake. However, non-binge drinkers consumed about the same amount of alcohol than before lockdown.

Limitations of the study include the survey data being self-reported, and the fact the question on binge-drinking did not specify a time within which the alcohol was consumed.

In addition, the majority (70%) of participants were relatively high earners, a factor already associated with hazardous alcohol use. The authors say future research is needed in a more 'generalizable population'.

LOS ANGELES (EMBARGOED UNTIL DEC. 7, 2002 AT 5 A.M. EST) - A new approach to cancer therapy shows potential to transform the commonly used chemotherapy drug gemcitabine into a drug that kills cancer cells in a specialized way, activating immune cells to fight the cancer, according to a study led by Cedars-Sinai Cancer investigators. The findings, made in human and mouse cancer cells and laboratory mice, were published today in the peer-reviewed journal Nature Communications.

The investigators discovered that when they added the Food and Drug Administration-approved anti-inflammatory medication celecoxib (Celebrex) to gemcitabine chemotherapy, it converted gemcitabine from a non-immunogenic drug-unable to activate a patient's own immune response-to an immunogenic drug, which triggered the immune response in the mice. The combination of drugs delivered a "one-two punch" of killing tumor cells and activating immune cells, said Keith Syson Chan, PhD, a Cedars-Sinai Cancer translational scientist and corresponding author of the study. Kazukuni Hayashi, PhD, is the first author.

"I believe that our study has significant clinical potential, as cancer immunotherapy continues to emerge as an important pillar for treating cancer patients," Chan said. "This discovery, if confirmed in clinical trials, may potentially increase the percentage of patients who respond to cancer immunotherapy."

Currently, about 70% to 85% of patients taking immunotherapy drugs fail to respond to them, he added.

Since the 1940s, the main treatment for killing cancer cells has involved chemotherapy drugs, which kill the cells directly. But many of the current drugs fail to induce the most efficient form of cell death, known as "immunogenic" cell death, which activates the release of a protein called a "go" or "danger" signal. The "go" signal prompts immune cells-called dendritic cells-to spur T cells to eradicate tumors. Instead, most current chemotherapies for pancreatic, bladder, breast, ovarian and non-small cell lung cancers not only are non-immunogenic-they suppress the immune system.

In recent years, immunotherapy drugs have been added to chemotherapy regimens, or used alone, to help a patient's own immune cells attack cancer, but the response rate is low.

Certain chemotherapy drugs such as gemcitabine do kill cancer cells and release the "go" signal for an immune response. Scientists, therefore, have believed that those drugs are immunogenic. That is not entirely the case, though, Chan said.

In a surprise discovery, the study investigators-from Cedars-Sinai, Baylor College of Medicine in Houston, and Taipei Medical University in Taiwan-found that while gemcitabine does release the "go" signal, it also prompts the release of an inhibitory signal, or brake, that stops dendritic cells from activating cancer-killing T cells. If the brake is on, "the T cells don't go anywhere," Chan explained. It is necessary, therefore, to find a balance between the "go" and "brake" signals to prompt an effective immune response.

The solution to that balance, the investigators discovered, is the anti-inflammatory drug celecoxib, which removed the brake so that only the "go" signal remained. The dendritic and T cells then were better able to perform their immune responses. Gemcitabine was transformed into an immunogenic drug.

"Rather than focusing on stepping down harder on the gas pedal-releasing proteins that are "go" signals-we removed the impeding brake pedal, allowing the dendritic cells to induce T cells to kill tumors," Hayashi said.

Chan and Hayashi said they believe that the immune response will perform even better with an immunotherapy drug added to a gemcitabine and celecoxib treatment regimen. A study is underway in Chan's lab to test that hypothesis. They look forward, they said, to testing the efficacy of the new treatment in randomized, placebo-controlled human trials in collaboration with their Cedars-Sinai clinical colleagues.

"Harnessing the patients' immune system to attack patients' tumor cells has become an important tool for physicians treating cancer," said Dan Theodorescu, MD, PhD, director of the Cedars-Sinai Cancer enterprise. "Unfortunately, our current efforts fail in a significant number of patients. This study unveils at least one potential mechanism explaining these failures, and more importantly, provides a potential solution."

A CAR T-cell therapy known as axicabtagene ciloleucel (axi-cel) drove cancer cells to undetectable levels in nearly 80% of patients with advanced non-Hodgkin lymphoma (NHL) in a phase 2 clinical trial, Dana-Farber Cancer Institute investigators report at the virtual 62nd American Society of Hematology (ASH) Annual Meeting.

While NHL tends to be a slow-growing disease, patients frequently relapse after standard treatment, underscoring the need for new therapies. Axi-cel's effectiveness in trial participants who had either relapsed or become resistant to other drugs is especially encouraging, according to investigators.

"We were very impressed with the magnitude of the responses, and also the durability," said Dana-Farber's Caron Jacobson, MD, MMSc, who led the trial and will present the findings at ASH. "This treatment has meaningfully impacted high-risk patients with these diseases. I was also struck early on by how favorable the safety profile was compared to what we've been seeing in the fast-growing lymphomas."

Axi-cel is made by collecting some of a patient's disease-fighting T cells and genetically altering them to deploy a specialized receptor on their surface. The receptor enables the modified T cells - called chimeric antigen receptor, or CAR T cells - to latch onto cancer cells and destroy them. The CAR T cells are then infused into the patient. In previous trials in patients with large B cell lymphoma, the therapy reduced cancer cells below detectable levels, achieving a "complete response," in many patients.

In the current trial, dubbed ZUMA-5, investigators administered axi-cel to 146 patients with follicular lymphoma or marginal zone lymphoma - two slow-growing forms of non-Hodgkin leukemia - at multiple U.S. medical centers. All the participants had active lymphoma despite undergoing multiple previous treatments.

A median of 17.5 months after treatment with axi-cel, 92% of the trial participants had an objective response - a detectable reduction in their cancer - and 76% had a complete response. At the cutoff date for data collection, responses continued in 62% of all treated patients.

Almost all patients experienced adverse side effects, with 86% experiencing adverse events of grade 3 or higher. Seven percent experienced grade 3 or higher cytokine release syndrome and 19% experienced grade 3 or higher neurologic events. Response rates were slightly higher and adverse effect rates were slightly lower for patients with follicular lymphoma than for those with marginal zone lymphoma.

Jacobson will present findings on this study at the "Advancing New Frontiers: Genome Editing & Cellular Therapy" press briefing on Saturday, Dec. 5, at 12:30 p.m. EST. Further details will be presented during Session 623, Abstract 700, on Monday, Dec. 7 at 4:30 p.m. EST.