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Scientists from Russia and Italy studied a new axis of the pathway that prevents the development of liver fibrosis. The role of GILZ protein in curbing the disease progression was shown in a study using mice models and confirmed by clinical data. These findings can be used in the treatment of liver fibrosis in humans. The research was published in the journal Cell Death & Disease.

Fibrosis combines an overgrowth of connective tissue and a decline in the liver function that can be caused by a viral infection, alcohol intoxication, autoimmune diseases or other liver disorders. If left untreated, fibrosis can lead to cirrhosis and even death. Inflammatory processes ? complex cascades of molecular interactions between the cells of the immune system ? play an important role in the progression of fibrosis, therefore, its treatment requires thorough understanding of those processes at the molecular level. The most common anti-inflammatory agents, such as glucocorticoids, are widely used in the treatment of autoimmune diseases and other problems, however, in the case of liver fibrosis, they are likely to cause severe side effects.

In their recent study, researchers from Skoltech, the University of Perugia, and the University of Florence (Italy) focused on the GILZ protein. GILZ expression leads to changes in cellular processes similar to those triggered by glucocorticoids. The team experimented with a model of liver fibrosis induced in GILZ knockout mice and observed rapid progression of the disease. The scientists verified their hypothesis about the effect of GILZ on the progression of fibrosis using gene expression data on patients with liver fibrosis and obtained evidence of lower GILZ levels in those patients. Downregulation of the upstream CCR2 protein restored resistance to the progression of liver fibrosis.

The team's findings suggest that GILZ is a promising anti-hepatic fibrosis drug target.

"Importantly, there is a strong correlation between our data on mice and clinical data on humans, which is rarely the case with lab results obtained using model objects and even mammals that may never be confirmed in human. Now we have every reason to expect that by controlling the signaling pathway which involves GILZ one could treat inflammatory liver diseases in humans," professor Timofei Zatsepin of the Skoltech Center for Life Sciences (CLS) explains.

New Haven, Conn. -- A Yale-led study reveals that new medicines and vaccines approved for use in the United States are often unavailable in countries that hosted their clinical trials, suggesting that the benefits of drug research are not being shared equitably among populations that participate in testing.

The study, published May 5 in JAMA Network Open, covers 34 novel drugs sponsored by large pharmaceutical companies that the U.S. Food and Drug Administration (FDA) approved between 2012 and 2014. Approvals were made on the basis of a total of 898 trials that were held in the United States and 70 other countries worldwide.

By analyzing the 563 trials for which location data was available, the researchers found that, five years after approval in the United States, only 15% of the drugs (5 of 34) were approved in every country that hosted trials. Among the 70 countries that contributed research participants, 7% (five countries) received market access to the drugs they helped test within a year of FDA approval and 31% (22 countries) did so within five years. Approvals happened faster in high-income countries, such as Germany and Canada, while access was lowest in Africa, where none of the drugs were available anywhere except in South Africa, which had access to just 24% of the drugs after five years.

"We discovered substantial gaps in access to new medications that raise concerns about the equitable distribution of research benefits," said Jennifer Miller, assistant professor at Yale School of Medicine, founder of Bioethics International -- a nonprofit advocate for patient-centered medical innovation -- and the study's lead author. "Ensuring market access to medicines for the countries helping to develop them can help effectuate a bedrock principle of research ethics: that the benefits and burdens of research should be shared equitably among the people affected by it."

Clinical research for medicines and vaccines seeking FDA approval is largely conducted outside the United States, and increasingly in lower-income countries. While FDA-approval is necessary for drugs to become available in the United States, it does not ensure market access in other countries. Research sponsors, such as pharmaceutical companies, must submit marketing approval applications to make the medicines and vaccines accessible in countries that hosted trials. While marketing access does not guarantee a patient can afford a medicine or vaccine, or that there is a reasonably sufficient supply of a pharmaceutical product, it is a critical precondition for access to new drugs, the researchers explained.

The 34 drugs were grouped into six treatment areas: infectious disease; cardiovascular disease and diabetes; autoimmune, musculoskeletal, and dermatology; neurology; and psychiatry. The study found that only one of the 34 medications was approved for marketing in all the countries where it was tested a year after FDA approval.

"We found that the typical drug approved by the FDA was tested in 25 different countries," said Dr. Cary Gross, professor of medicine at Yale School of Medicine and a co-author of the paper. "If the citizens of those countries never gain access to the new drug, then one has to ask why are they participating in the research in the first place? Just to see if it's safe for use in the United States and other wealthy countries?"

Even five years after FDA approval, only 5 of 34 of the drugs, or 15%, were approved in all the countries, according to the study.

"Drug research across international boundaries provides U.S. patients access to new medications and vaccines, and could, in theory, maximize benefits for all: The U.S. contributes capital that other countries lack, while those countries contribute human volunteers and a workforce necessary to complete clinical trials expeditiously," said Peter Bach, director of the Center for Health and Policy Outcomes at Memorial Sloan Kettering Cancer Center, and a co-author of the study. "For these partnerships to be truly equitable, then the host countries must benefit from the research by quickly gaining access to the new medications after FDA approval."

To make the process more equitable, the researchers suggest that, as a condition of running clinical trials, governments of host countries require that pharmaceutical companies commit to submitting a marketing approval application within a designated timeframe after FDA approval. They recommend that companies should consider adopting policies through which they will not test drugs in countries where they do not intend to sell the tested product. The researchers also call for transparent tracking, auditing, and reporting on product registrations in countries that host trials to assist in expanding access to new medicines and vaccines globally.

A new mutation found in a gene associated with an increased risk of atrial fibrillation poses a significantly increased risk for heart failure in Black people.

The discovery, made by researchers at the University of Illinois Chicago, could change current guidelines that recommend against genetic testing in people with atrial fibrillations, also known as AFib.

"We found that this new variant confers a significantly increased risk in African Americans, and this mutation has a 50% chance of being passed on to offspring," said Dr. Dawood Darbar, UIC professor of medicine and pharmacology at the College of Medicine. "Since it increases risk for heart failure, it would be wise to test people with atrial fibrillation to see if they carry this dangerous gene."

AFib is the most prevalent heart rhythm disorder worldwide and increases the risk of stroke, heart failure and even dementia.

Previous research from Darbar's lab identified several genes with variations or mutations that increased the risk of early-onset AFib in white people. One of these variants is in a gene called Titan -- the largest gene in the human genome.

Darbar and colleagues sequenced the genes associated with increased risk of early-onset AFib in 227 Black and Latino patients with early-onset AFib who were seen at UI Health, UIC's health care system.

"With early-onset AFib, which we defined in our research as younger than age 65, the likelihood that AFib is genetic, or familial in its cause, is much higher," Darbar said.

They found that 7% of these patients had at least one genetic variation associated with an increased risk of AFib. Among these patients, 50% had a mutation in the Titan gene.

"The Titan mutation is very strongly associated with an increased risk for heart failure as well as AFib, which suggests that African Americans and Hispanic/Latinos with early-onset AFib be screened for this dangerous gene," Darbar said.

Darbar and colleagues also discovered a new genetic variation they think might be associated with an increased risk of early-onset AFib.

"The new gene we discovered was present in six families with two or more individuals with early-onset AFib, making this gene very suspicious," Darbar said. "We will be looking into the significance of this variation in our future studies."

According to a new study published in the journal Research in Social and Administrative Pharmacy, hospitals that participate in the 340B Drug Pricing Program provide more medication access services -- which are services that help remove barriers to accessing necessary medications -- than comparably sized non-340B hospitals.

The University of Illinois Chicago researchers who conducted the study, which included a survey of available services sent to a nationally representative sample of hospitals across the U.S., suggest that 340B participating hospitals may be better positioned to create and administer programs that support patients who are uninsured or underinsured and those who may have job, transportation and other social insecurities.

"Medication access services are an important way that hospitals support patients whose health and wellbeing are dependent on medications but who otherwise may struggle to afford or access drugs. This includes patients with a range of illnesses, from chronic health conditions such as diabetes or hypertension to people who have required life-saving transplants," said Sandra Durley, a clinical assistant professor at the UIC College of Pharmacy in the pharmacy practice and pharmacy systems, outcomes and policy departments.

According to Durley, a contributing author of the study, for low-income patients, the availability of medication access services like prior authorization assistance and provision of free or discounted drugs, for example, at their site of care "can mean the difference between receiving prescribed drug therapy and going without, due to delays or unaffordability of medications."

For the study, researchers collected primary questionnaire response data from pharmacy directors at non-federal acute care hospitals from March 2019 to May 2019. They then assessed the availability of nine medication access service offerings.

There was a significant difference in the average number of services offered between 340B and non-340B hospitals. 340B hospitals offered, on average, 6.2 services while non-340B hospitals offered 3.9 services, after an adjustment for hospital size.

For all nine services that were assessed, a higher percentage of 340B hospitals reported providing the service compared to non-340B hospitals. This difference was statistically significant for six out of the nine services: assistance with prior authorizations (89.7% for 340B hospitals vs. 63.0% for non-340B hospitals), discharge prescription services (85.3% vs. 44.4%), free immunizations (58.8% vs. 33.3%), free or discounted outpatient medications (83.8% vs. 48.2%), medication therapy management (52.9% vs. 11.1%) and patient assistance programs (83.8% vs. 51.9%). There was no statistically significant difference for the other three services: free prescription delivery, free medications from the emergency department and transitions of care.

In addition, the researchers looked at general health care services. For the four services analyzed, an equivalent or higher percentage of 340B hospitals compared with non-340B hospitals reported providing the service. The difference was statistically significant for two of the services: the provision of drug/alcohol outpatient treatment services (37.5% vs. 9.5%) and HIV/AIDS outpatient services (39.3% vs. 9.5%). There was no significant difference for providing free or discounted transportation to health services or providing housing support for homeless patients.

Durley said the data published in this study provides important information for policymakers about how participation in the 340B program translates into expanded services for patients who seek care at safety net and public hospitals.

The authors write, "At a time when 79% of Americans believe that the cost of prescription drugs is unreasonable, and 19% of Americans report not filling a prescription at least once in the last two years due to cost, services that facilitate medication access are imperative for favorable health outcomes. While the 340B Program is not designed in its intent as a direct patient benefit program, its savings can be utilized in a variety of different ways to provide more comprehensive services. The findings of this study suggest that 340B hospitals play a critical role in facilitating medication access."

Durley says that while the survey was conducted before the onset of the COVID-19 pandemic, the data presented in the study is likely just as relevant, if not more relevant, today.

"We've seen increased job loss and social insecurity over the last year that has essentially compounded the barriers experienced by underserved communities who are also bearing the brunt of COVID illness. The pandemic is highlighting that there is a greater need for services that support vulnerable communities, not a lesser need," said Durley, who also is senior associate director of ambulatory care pharmacy services at the University of Illinois Hospital, which participates in the 340B program as a disproportionate share provider.

CLEVELAND, Ohio (May 5, 2021)--Vitamin D is a critical part of a healthy diet. Among other benefits, it has been shown to protect against bone disease and maintain soft tissue health. A new study suggests that it may also play a role in the degree of postoperative pain postmenopausal women experience after undergoing total knee replacement. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Vitamin D deficiency is a major issue globally. It is estimated that 60% of adults have insufficient levels of the bone-building vitamin. Estrogen deficiency in perimenopausal women has been associated with decreased levels of vitamin D. A sedentary lifestyle and lack of sun exposure have also been shown to contribute to vitamin D deficiency in perimenopausal women.

In this new study, researchers sought to investigate the effect of vitamin D levels on function outcomes and risk factors of moderate to severe pain in postmenopausal women after total knee replacement. The procedure is frequently recommended for treating advanced knee osteoarthritis when nonsurgical treatment is no longer effective. Although the procedure is safe, many women experience postoperative pain.

Previous studies have sought to identify factors that play a role in determining the amount of pain women feel after undergoing knee replacement surgery. Among other factors, these studies pinpointed postmenopausal status and low estrogen levels as being associated with joint paint primarily in women aged 50 to 59 years. This new study suggests a link between vitamin D deficiency and a greater risk of postoperative pain. It identified vitamin D deficiency, smoking, and a high body mass index (BMI) as independent risk factors for moderate to severe pain after knee replacement surgery.

The new study additionally found that there was a high prevalence (67.3%) of vitamin D deficiency in postmenopausal women scheduled for total knee replacement. These study results are in line with previous studies that suggested that vitamin D deficiency is associated with the development of osteoarthritis, as well as muscle cramps, bone pain, walking difficulty, decreased bone mineral density, and fractures. The results of studies like these could provide valuable insights to clinicians evaluating postmenopausal women before major joint surgeries.

Results are published in the article "Effects of preoperative serum vitamin D levels on early clinical function outcomes and the moderate-to-severe pain prevalence in postmenopausal women after primary total knee arthroplasty."

"This study found that high body mass index, smoking, and vitamin D deficiency were independent risk factors for moderate to severe postoperative pain after knee replacement in postmenopausal women. Additionally, those with preoperative vitamin D deficiency had poorer functional outcomes. These findings highlight opportunities for clinicians to address these modifiable factors before postmenopausal women undergo joint replacement surgeries," says Dr. Stephanie Faubion, NAMS medical director.

A new study published in Arthritis Care & Research indicates that few individuals with the autoimmune disease lupus who were publicly insured through Medicaid received recommended vaccines in 2000-2010. Also, those who were unvaccinated needed more acute care for vaccine-preventable illnesses.

From 2000-2010, there were 1,290 patients who visited the emergency department or were hospitalized for vaccine-preventable illness, and 93% of these visits occurred in patients without billing codes for related vaccinations. Patients who were Black had a 22% higher risk of needing such care than those who were white.

"These episodes represent missed opportunities to deliver essential preventive care to our patients, and particularly to patients with heightened vulnerabilities," said lead author Candace H. Feldman, MD, ScD, of Brigham and Women's Hospital.

Untreated mental health disorders can be a serious problem for women and their children during pregnancy and after giving birth, during the postpartum period. A recent analysis funded by the Agency for Healthcare Research and Quality (AHRQ) and published in Psychiatric Research & Clinical Practice notes that few studies have examined the benefits of medications for mental health disorders in pregnant and postpartum women. And while many studies have reported on potential harms, the large majority could not separate the effect of medications from the effect of the underlying disorder. As a result, it is not clear that these medications caused harms to pregnant or postpartum women.

A total of 164 studies were included in the analysis. Study results indicate that brexanolone and sertraline likely lessen depressive symptoms, and mood stabilizers may reduce recurrence of bipolar disorder.

"It's vital for patients and providers to make informed decisions during pregnancy and postpartum, and our study shows a need for more and higher quality research in regards to mental health treatments," said Meera Viswanathan PhD, of the AHRQ Evidence-based Practice Center at RTI International - University of North Carolina.

Erythropoietin (EPO) is a medication used to stimulate the production of new red blood cells, which is impaired in individuals with kidney failure. Unfortunately, however, the treatment may increase the risk of hip fractures.

In an analysis published in the Journal of Bone and Mineral Research that examined 1997-2013 records from two large U.S. databases, investigators found that EPO doses administered to patients with kidney failure on hemodialysis fluctuated widely over time, and hip fracture rates closely tracked the average dose of EPO doses used in patients.

"Patients with renal failure can benefit from EPO treatment; however, as with all medications, a full understanding of potential drug-associated risks favors the likelihood that a positive risk-benefit balance can be achieved with EPO treatment," senior author Constance Tom Noguchi, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases.

An analysis of published studies indicates that Twitter may be a useful learning tool in dental education.

The analysis, which is published in the Journal of Dental Education, included 7 studies. Studies indicated that the real-time question and answer sessions using Twitter work well in an educational setting. Also, the semi-anonymous interactions on Twitter can be beneficial for students unwilling to speak in front of their peers. Twitter can also make lectures more engaging, and it can be used to ask questions that assess student comprehension.

The investigators noted that there are significant barriers to Twitter's use in dental education, however, including privacy and concerns about professionalism.

"We live in a dynamic world where the use of social media such as Twitter has become part of our daily life. It is amazing that many dentists and dental students from all over the world use Twitter as a live platform in discussing clinical cases and sharing news, knowledge, and experiences," said senior author Omar Kujan, DDS, PhD, of The University of Western Australia. "Our study is the first to collate the current evidence regarding the use of Twitter in dental education. Our findings supported the potential for Twitter as a useful learning tool in dental education, but there were some barriers. Future research would help in refining Twitter's use and improve its efficacy in dental education."

A study involving researchers at Karolinska Institutet and Gothenburg University in Sweden has found that low levels of a protein called PDGFRb are associated with particularly good results of radiotherapy in women with early-stage breast cancer. The study, which is published in the journal Clinical Cancer Research, also suggests that the efficacy of radiotherapy can be improved with drugs that block this protein.

Some 900 women in Sweden are diagnosed with DCIS (ductalcarcinoma in situ), the earliest possible form of invasive breast cancer. Standard treatment is surgery and subsequent radiotherapy. Although the prognosis is generally good, some ten per cent of patients suffer a recurrence within ten years of diagnosis.

"It is well-known that the benefits of radiotherapy are individual, so we need to find predictive markers that can be used to avoid unnecessary or ineffective radiotherapy," says the study's co-last author Fredrik Wärnberg, professor at the Department of Clinical Sciences at Gothenburg University's Sahlgrenska Academy.

While previous studies have focused mainly on markers in the tumour cells themselves, recent findings show that supporting tissue around the tumour cells can affect the therapeutic effect of DCIS. Studies in cell and animal models have demonstrated that the efficacy of radiotherapy can be influenced by fibroblasts, which are a type of supporting cell in the breast cancer tissue.

Arne Östman's research group at Karolinska Institutet and Professor Wärnberg's group have now analysed a large tissue collection from a randomised radiotherapy study (SweDCIS). Their analyses showed that low levels of a particular fibroblast protein, PDGFRb, are associated with especially high radiotherapeutic efficacy for women with DCIS.

Several new studies have been launched, one a collaboration with the US company PreludeDx on breast cancer diagnostics.

"The treatment guidelines of DCIS might need to be changed if these studies confirm our original findings," says the study's first author Carina Strell, researcher at the Department of Immunology, Genetics and Pathology, Uppsala University, and the Department of Oncology-Pathology, Karolinska Institutet.

The results of this newly published study also indicate that the efficacy of radiotherapy can be improved if combined with the blocking of PDGFRb. The researchers now plan to interrogate this further in experimental cell and animal models before any studies on patients can begin.

The majority of top-rated fertility apps collect and even share intimate data without the users' knowledge or permission, a collaborative study by Newcastle University and Umea University has found.

Researchers are now calling for a tightening of the categorisation of these apps by platforms to protect women from intimate and deeply personal information being exploited and sold.

For hundreds of millions of women fertility tracking applications offer an affordable solution when trying to conceive or manage their pregnancy. But as this technology grows in popularity, experts have revealed that most of the top-rated fertility apps collect and share sensitive private information without users' consent.

Dr Maryam Mehrnezhad, of Newcastle University's School of Computing and Dr Teresa Almeida, from the Department of Informatics, Umeå University, Sweden, explored the privacy risks that can originate from the mismanagement, misuse, and misappropriation of intimate data, which are entwined in individual life events and in public health issues such as abortion, infertility, and pregnancy.

Dr Mehrnezhad and Dr Almeida analysed the privacy notices and tracking practices of 30 apps, available at no cost and dedicated to potential fertility. The apps were selected from the top search results in the Google Play Store and let a user regularly input personal and intimate information, including temperature, mood, sexual activity, orgasm and medical records.

Once the apps were downloaded, the researchers analysed GDPR requirements, privacy notices and tracking practices. They found out that the majority of these apps are not complying with the GDPR in terms of their privacy notices and tracking practices. The study also shows that these apps activate 3.8 trackers on average right after they are installed and opened by the user, even if the user does not engage with the privacy notice.

Presenting their findings at the CHI 2021 Conference, taking place on May 8-13, Dr Mehrnezhad and Dr Almeida warn that the approach of these apps to user privacy has implications for reproductive health, and rights.

Dr Mehrnezhad said: "Users of these apps are normally women who are considered marginalised user groups and the data concerning these groups is personal, more sensitive, and identified by GDPR legislation as 'special category data' requiring extra protection."

Dr Almeida added: "Data are kept in such a vulnerable condition, one in which a default setting allows not only for monetizing data but also to sustain systems of interpersonal violence or harm, such as in cases of pregnancy loss or abortion, demands a more careful approach to how technology is designed and developed.

"While digital health technologies help people better manage their reproductive lives, risks increase when data given voluntarily are not justly protected and data subjects see their reproductive rights challenged to the point of e.g. personal safety."

The study shows that majority of these fertility apps are classified as 'Health & Fitness', a few as 'Medical', and one as 'Communication'. The authors argue that miscategorising an unsecure app which contains medical records as 'Health & Fitness' would enable the developers to avoid the potential consequences, for example, of remaining in the app market without drawing significant attention to it. This means that fertility app data could continue to be sold to third parties for a variety of unauthorised uses, such as advertising and app development.

The team is currently looking into the security, privacy, bias and trust in IoT devices in Femtech. In light of their research, these researchers are calling for more adequate, lawful, and ethical processes when dealing with this data to ensure women get protection for the intimate information that is being collected by such technologies. They advise to seek to improve the understanding of how marginalised user groups can help to shape the design and use of cybersecurity and privacy of such technologies.

University of Bristol research into octopus vision has led to a quick and easy test that helps optometrists identify people who are at greater risk of macular degeneration, the leading cause of incurable sight loss.

The basis for this breakthrough was published in the latest issue of the Journal of Experimental Biology and describes new technology developed by lead researcher, Professor Shelby Temple, to measure how well octopus- which are colour-blind - could detect polarized light, an aspect of light that humans can't readily see. Using this novel technology, the research team showed that octopus have the most sensitive polarization vision system of any animal tested to date. Subsequent research used the same technology in humans and led to the development of a novel medical device that assesses the risk factor for sight loss later in life.

Prof Shelby Temple, who holds honorary positions at the School of Biological Sciences, University of Bristol and the School of Optometry, Aston University, explained the impact of the team's findings. He said: "We knew that octopus, like many marine species, could see patterns in polarized light much like we see colour, but we had no idea that they could do so when the light was only 2% polarized - that was an exciting surprise, but even more surprising was when we then tested humans and found that they were able to see polarization patterns when the light was only 24% polarized.

"Humans can perceive polarized because macular pigments in our eyes differentially absorb violet-blue light depending on its angle of polarization, an effect known as Haidinger's brushes. It's like a super sense most of us don't even know we have, revealing a faint yellow bow-tie shape on the retina. The more of these pigments a person has, the better protected they are against sight-loss.

"By inventing a method to measure polarization vision in octopuses, we were able to use the core technology to develop a novel ophthalmic device that can quickly and easily screen people for low macular pigments, a strong risk factor for increased susceptibility to macular degeneration."

Macular pigments are the body's natural protection against damaging violet-blue light. This new testing approach enables optometrists to provide preventative advice to patients. Empowering patients to make simple lifestyle choices, like wearing sunglasses or eating more dark green and brightly coloured fruits and vegetables that can help them protect their sight through life.

Prof Temple said, "I am so happy this work has been published, as it was the foundation upon which we developed our exciting new technology for measuring macular pigments."

Macular pigments are the carotenoids lutein, zeaxanthin and meso-zeaxanthin that we can only acquire from our diet. They provide long term protection to the retina and this helps prevent age-related macular degeneration by acting as antioxidants and by strongly absorbing the most damaging high energy visible (violet-blue) wavelengths (380-500 nm) of light that reach our retina. A challenge to the eye care industry is that it is not possible to determine someone's macular pigment levels without measurement, and until now most techniques have been too time consuming, difficult, or expensive to become part of regular eye exams. The new technology developed by Prof Temple through his start-up company Azul Optics Ltd, enables rapid screening of macular pigment levels and can be used on patients from 5 -95 years of age. Prof Temple added: "We are all living longer and expecting to do more in our older age, so I hope this serendipitous invention will help empower people to do more to look after our eyes, so they don't suffer from this devastating disease."

FINDINGS

A new study by researchers at the UCLA Jonsson Comprehensive Cancer Center has identified a novel combination therapy to potentially help overcome resistance to immunotherapy in people diagnosed with advanced lung cancer. The combination approach uses immune checkpoint inhibitors with ATRA, a safe medication that is widely used to treat leukemia. The team found the combination therapy led to eradication of over 70% of tumors when tested in mice with LKB1-deficient lung cancer. It also generated durable tumor-specific immunity.

BACKGROUND

Immune checkpoint inhibitors have substantially improved the outcomes for people with lung cancer. The five-year survival rate for patients with advanced disease on this therapy is more than 13% compared to 5% in patients with conventional chemotherapy. Although immunotherapy has been successful for many patients, a majority of patients still do not respond to the therapy.

To help increase the number of patients who benefit from this therapy, researchers have sought to identify mechanisms for treatment resistance. The tumor suppressor gene LKB1 are found mutated in 20% of patients with non-small cell lung cancer and 30% of KRAS-mutant non-small cell lung cancers. It also is a major gene associated with resistance to immune checkpoint inhibitors. By identifying aberrant pathways caused by LKB1 mutation, researchers are figuring out a novel therapy that targets the pathway and sensitizes LKB1-deficient tumors to immunotherapy.

METHOD

To assess the response of the combination therapy, researchers tested the therapy in mice that were injected with LKB1-deficient lung tumors.

IMPACT

The study provides evidence that using ATRA in combination with checkpoint inhibitors could potentially help patients with advanced lung cancer who carry LKB1 mutation to have a positive response to immunotherapy.

AUTHORS

Lead authors are Rui Li, MD, PhD, currently a resident physician of internal medicine at UCLA, and Ramin Salehi-Rad, MD, PhD, a physician scientist in pulmonary and critical care medicine. The senior authors are Bin Liu, PhD, an adjunct professor of pulmonary and critical care medicine, and Steven Dubinett, MD, a professor of pulmonary and critical care medicine, pathology and laboratory medicine, and molecular and medical pharmacology at the Geffen School of Medicine and physician-scientist in the UCLA Jonsson Comprehensive Cancer Center.

JOURNAL

The study was published online in Cancer Research, a journal of the American Association for Cancer Research.

FUNDING

The research was supported in part by funding from the National Cancer Institute, the National Heart Lung and Blood Institute and the Department of Veteran Affairs.

May 4, 2021 - From the very beginning of the AIDS epidemic in 1981, nurses have been at the forefront of patient care, advocacy, and research. But even in the age of antiretroviral therapy and pre-exposure prophylaxis, many challenges remain in reducing the impact of HIV and AIDS, according to the special May/June issue of The Journal of the Association of Nurses in AIDS Care (JANAC). The official journal of the Association of Nurses in AIDS Care, JANAC is published in the Lippincott portfolio by Wolters Kluwer.

Assembling nine "state of the science" reviews invited from leading clinical scientists, the special issue of JANAC summarizes 40 years of nursing science throughout the HIV epidemic - highlighting "lessons learned and the way forward" in improving clinical care and quality of life for people living with HIV. "The HIV epidemic has been shaped, for the better, by dedicated nurses, nurse practitioners, and midwives who have provided direct care, questioned the status quo, advocated for patients' rights, taught the next generation of HIV clinicians, and advanced the science," according to an introduction by Editor-in-Chief Michael V. Relf, PhD, RN, AACRN, ANEF, FAAN and other members of the JANAC editorial team.

Nurse researchers lead the way in improving HIV prevention and patient care

Several of the special-issue papers focus on groups that face disproportionately high burdens of HIV disease. Schenita D. Randolph, PhD, MPH, RN, CNE, of Duke University School of Nursing and colleagues review the evidence on HIV prevention and treatment among cisgender women in the United States. In 2018, women accounted for 19 percent of new cases of HIV in the United States. The rate of new HIV cases is 14 times higher in Black women and three times higher in Latina women, compared to white women.

Dr. Randolph and colleagues discuss risk factors driving the HIV epidemic among US women, including interpersonal, community, and societal factors. They also provide an overview of evidence-based HIV risk reduction interventions, combining behavioral, biomedical, and structural strategies. However, to end the epidemic of HIV among women, a primary focus on prevention must incorporate the unique needs of women at risk for HIV.

"Nurses have a unique role in developing and carrying out HIV interventions....particularly the recognition that the root causes of HIV include both social and biomedical factors," Dr. Randolph and colleagues write. They outline priorities and recommendations to make HIV interventions for women more sustainable, including efforts to engage women throughout the research process and incorporating technology approaches.

Carmen J. Portillo, PhD, RN, FAAN, of Yale University School of Nursing and colleagues present a review of HIV prevention approaches in Black and Hispanic/Latinx communities. In 2018, Black/African American people accounted for 37 percent of new HIV cases and Hispanic/Latinx people for 30 percent.

Structural racism and social inequities embedded in the economic, education, health care, and criminal justice systems are major contributors to the "overwhelmingly disparate" HIV-related health disparities in Black and Hispanic/Latinx populations. "[M]ulti-level interventions that address individual, structural, and social level components have demonstrated more sustainable outcomes," according to the authors.

Nurse scientists can play a major role in addressing racism as "the fundamental reason for health disparities," the researchers believe. Dr. Portillo and coauthors call for "updating antiquated curriculums in nursing, medicine, and public health that perpetuate racial, structural-level inequities and also increasing the pipeline for Black and Hispanic/Latinx persons to pursue research or clinical-focused doctorate degrees."

Other papers in the special issue address vulnerabilities to HIV among adolescents and young adults and people with differences in sexual orientation or gender identity/expression; important problems of aging patients with HIV, including cognitive changes and comorbid chronic diseases; and other key issues along the continuum of care including medication adherence, HIV-related stigma, and the future of HIV prevention. Dr. Relf and colleagues conclude: "This body of work reflects an optimism that perhaps, in the next 40 years, we will be reviewing the key role that nursing played to help end the AIDS epidemic once and for all."

WASHINGTON, DC -- A new case report, detailed in Annals of Emergency Medicine, is the first known case of a patient with VITT (vaccine-induced thrombotic thrombocytopenia) treated with a heparin alternative following the Centers for Disease Control and Prevention (CDC) guidance.

An otherwise healthy female patient in her 40s came to the emergency department at UCHealth University of Colorado Hospital twelve days after receiving the Johnson & Johnson vaccine with a headache, dizziness, and vision changes. The patient was treated on April 13, 2021, the same day that the Centers for Disease Control and Prevention (CDC) announced a pause in the administration of the Johnson & Johnson vaccine. CDC guidance recommended treatment with heparin alternatives but did not recommended any specific alternative in that announcement.

Bivalirudin was given to the patient and the authors write that, "this patient's early outcomes suggest that bivalirudin may be a safe alternative to heparin in patients demonstrating a presentation consistent with VITT."'

"Our experience shows us that these clot reactions are very rare, but they can be treated," said R. Todd Clark, MD, MBA, lead co-author and assistant professor of emergency medicine at the University of Colorado School of Medicine. "Americans can feel comfortable getting vaccinated and should discuss any vaccination concerns with their doctor. Getting vaccinated is a critical step in combatting this pandemic so we can return to our normal lives."

While more research is needed on the efficacy of this medicine, the early outcomes of this case may inform the decision making of other health professionals who may be selecting heparin alternatives for patients with VITT, the authors said.