As the COVID-19 pandemic spread and cases climbed, authorities and public health officials encouraged people to stay home to avoid spreading COVID-19. While this type of message was an essential part of the public health campaign, one of the results was an apparent drop in routine visits to the emergency department for serious health conditions, such as heart attacks, appendicitis, broken bones, and strokes. A study conducted by Yale University and the Mayo Clinic and published in JAMA confirmed that a sample of emergency departments in states with spiking COVID-19 cases did experience a significant drop in emergency room visits.

This study was conducted in Colorado, Connecticut, Massachusetts, New York, and North Carolina during the spring (March and April), when COVID-19 cases were rising rapidly in these states. All five states experienced at least a 40% drop in emergency department visits and hospital admissions, with a full 63.5% drop in New York’s emergency department visits. This drop mirrors the increase in COVID-19 cases and government orders to stay at home.

While staying home can save lives during COVID-19, avoiding the emergency department for true health emergencies most certainly does not save lives. This analysis proves that public health messaging needs to specify that emergency medical care is an essential reason to leave home. Further research is needed to determine the true toll on human health and suffering of medical care avoidance during the COVID-19 pandemic.

As immunotherapy has become the standard of care for a variety of cancers, one powerful type of immunotherapy has emerged for the treatment of blood cancers: CAR T-cell therapy. CAR T-cell therapy involves the removal and alteration of a patient’s own T-cells (immune system cells) to attack cancer cells in the blood. Once altered in a lab to recognize the cancer cells, the CAR T-cells are infused back into the patient’s bloodstream. While CAR T-cell therapy is approved for several forms of lymphoma, a study by Dana-Farber Cancer Institute led to the first FDA approval of CAR T-cell therapy for mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin’s lymphoma that is often not caught and diagnosed until the blood cancer has advanced to later stages. Curing MCL has historically been difficult or impossible with traditional cancer therapies. For this reason, the disease can be life-threatening, especially if the disease is resistant to chemotherapy, and the approval of CAR T-cell therapy is a major step forward for the treatment of MCL.

In the study conducted by Dana-Farber, the results showed CAR T-cell therapy to be a highly effective treatment for resistant forms of MCL. Of the 74 patients treated with the CAR T-cell therapy, 93% responded to the first infusion, and all signs of cancer disappeared in 67% of patients. Since these patients had exhausted other therapies, these results showed promise for patients with an otherwise poor prognosis.

The CAR T-cell treatment, called KTE-X19, can now be used to treat patients who have treatment-resistant or relapsed forms of MCL. Dana-Farber, which conducted the clinical trial used for FDA-approval, will now administer the treatment to MCL patients.

Genetic testing offers valuable insight into cancer-linked genes and genetic mutations that may be precursors to the development of cancer. However, with increased insight into the genetic mutations associated with cancer, there is an increased need to understand which mutations are problematic and which only warrant careful monitoring for changes. A new genomic test developed by researchers at Dana-Farber Cancer Institute helps doctors to determine whether patients who have smoldering multiple myeloma (an early form of multiple myeloma) are at high risk for subsequently progressing to full-blown multiple myeloma.

Smoldering multiple myeloma (SMM) is a plasma-cell disorder, which is a disease of a specific type of white blood cell (plasma cell) found in bone marrow. This condition is asymptomatic but can progress into multiple myeloma (MM), a cancer of the plasma cells in bone marrow. However, with no treatment for SMM, doctors must monitor SMM to watch for the symptoms of myeloma. Current treatment is commonly known as “watchful waiting.” This new study at Dana-Farber was designed to help doctors determine which mutations in the bone marrow of SMM patients carried the highest risk of disease progression.

Researchers identified three mutations in tissue samples that were associated with an increased rate and speed of disease progression: certain genetic mutations in the MAPK pathway, amplification or translocation of the MYC gene and a mutation or deletion in the TP53 gene. Both in the study and in a validity test, these three variations were all associated with progression to multiple myeloma.

By testing tissue samples in SMM patients for these three mutations, doctors can identify the highest risk patients and schedule regular monitoring for disease progression. This added insight can enable physicians to provide the best possible care after an SMM diagnosis, whether a patient has high-risk mutations or not.

The ability of cancerous cells to evade immune response can be instrumental in the growth of cancer within the body. For this reason, researchers examine the ways in which cancer is able to block a normal immune response and aim to develop immunotherapy drugs that target those mechanisms of action. In a new study published in Nature, researchers found that a vital immune protein called interleukin-18 (IL-18) was blocked by tumors, allowing the tumor to evade the human immune system. However, the researchers were able to find a synthetic form of IL-18, known as a decoy receptor, that was unaffected by the tumor’s blocking signals in studies.

Interleukin-18 is a pro-inflammatory protein that is part of the body’s cytokines. IL-18 works to mobilize the T cells and NK cells that attack and kill damaged or infected cells. A tumor that blocks the function of IL-18 can essentially continue to grow unchecked by the NK cells that would typically neutralize or inhibit tumor cells. Many tumors are particularly adept at evading IL-18 by releasing a protein that binds with IL-18 before it can reach the tumor.

Previous research tested IL-18 as an immunotherapeutic treatment for tumors, but this was ineffective because the IL-18 binding protein released by the tumor worked on both the natural IL-18 and the added IL-18 used in immunotherapy. The fact that added pro-inflammatory IL-18 resulted in no effect alerted researchers to the presence of IL-18 binding protein and motivated the search for a form of IL-18 that would be able to resist tumor-released IL-18 binding protein.

This new study by Yale researchers has tested a synthetic form of IL-18 with a specific mutation that prevents the tumor’s IL-18 binding protein from inhibiting the function of the IL-18. Scientists hope that this potential new treatment may work against tumors that have historically been resistant to immunotherapy. Researchers hope that clinical trials for this new form of IL-18 may begin next year.

Survival rates for cancer differ based on the type of cancer, the stage of cancer at diagnosis and several other factors. Cancer researchers look for treatment options that improve survival rates in cancer patients, but especially seek options that provide high disease-free survival odds. While survival rates only indicate the likelihood of death, disease-free survival (DFS) rates indicate the likelihood of cancer recurrence or death. For this reason, DFS rates provide valuable information about the effectiveness of each cancer therapy.

Scientists seeking treatment options with high DFS rates for non-small cell lung cancer (NSCLC) launched a trial for osimertinib, an oral medication that has been approved by the FDA for treatment of advanced lung cancer with EGFR mutations since 2015. The drug works by inhibiting genetic mutations that feed the growth and development of EGFR mutation-positive cancer. However, osimertinib was previously only approved to treat advanced cancer rather than early-stage NSCLC.

In the Yale Cancer Center osimertinib study, researchers aimed to show that the drug provided an equal alternative to chemotherapy for patients with early stage, non-small cell lung cancer with certain EGFR gene mutations. However, the researchers found that osimertinib provided 89% of study participants with DFS at the two-year mark, compared to 53% of study participants who were randomized to other treatments.

This discovery may provide an alternative option for a different standard of care than traditional treatment with chemotherapy. Therapy with osimertinib is highly targeted, making it more effective and reducing some of the unpleasant side effects of chemotherapy. However, researchers will need to continue to monitor study participants to ensure that treatment provides the same or better long-term benefits than the current standard of care.

While much of our collective focus is on enhancing the functions of the immune system, the human immune system can be the human body’s own “worst enemy.” Rheumatoid arthritis, multiple sclerosis, allergies, cytokine storms and celiac disease are all caused by the immune system’s overreaction to foreign bodies. However, one of the most dangerous immune system overreactions is that due to organ transplants.

Scientists work painstakingly to identify the most exact transplant matches in an effort to prevent dangerous and costly transplant rejections. This involves a process known as tissue typing, and the goal is to match the antigens on the tissue of the donor organ as closely as possible to the recipient’s tissue. This can prevent the immune system from sensing that the antigens on the donor organ are foreign and attacking the new organ. Then, doctors prescribe immunosuppressive medications to temper the immune system and further prevent an attack of the replacement organ.

Together, tissue typing and immunosuppressive medications are relatively successful in preventing hyperacute rejection, which can happen immediately after a transplant, and acute organ rejection, which can happen up to three months following the surgery. However, chronic rejection, in which the body slowly attacks the new organ, is much more difficult to treat, because it occurs over years of immune activity. Scientists have been searching for a way to prevent this slow breakdown of chronic rejection.

This was the driving force behind a study by Jordan Pober, the Bayer Professor of Translational Medicine at Yale University, and his team, who have recently identified a molecule of crucial importance in the chronic rejection of transplants. The immune response against transplanted tissue largely takes place in the endothelial cells of the blood vessels, home of the HLA antigens that most often instigate aggressive immune responses in transplant cases. Through a process called membrane attack complex (MAC), the endothelial cells produce molecules that spur T cells to attack. By inhibiting one of those molecules, this aggressive immune response can potentially be prevented.

Preventing chronic rejection without prolonged use of immunosuppressants can potentially save the lives of transplant recipients, as well as minimizing the number of organ transplants that any one patient needs and freeing up those organs for other recipients.

Most Americans under the age of 65 receive health insurance coverage through their employer, or through a parent’s employer. This means that Americans who lose their job also typically lose their health insurance. For people fighting cancer and their family members, losing health insurance coverage can be a devastating blow. In addition, Americans may miss expensive preventative screenings and treatment that may otherwise be fully covered under a typical health insurance plan, such as mammograms and the HPV vaccine.

Disruptions in access to health insurance can cause several problematic outcomes for patients diagnosed with cancer and for people who routinely miss preventative care. According to a study published in the Journal of the National Cancer Institute, uninsured persons were significantly more likely to present with an advanced stage of cancer than people with health insurance. Uninsured cancer patients were also significantly less likely to receive any or all recommended cancer treatment and experienced worse outcomes, including decreased chances of survival.

Because of the out-of-pocket cost of medical tests and treatments without insurance, uninsured people often avoid seeking treatment until cancer symptoms are severe. Advanced cancer is generally more difficult to treat than early-stage cancer, especially if it has metastasized from its location of origin. This alone could cause decreased chances of survival, but when coupled with the fact that some uninsured cancer patients avoid treatment in part or in full due to the cost, odds of survival are significantly impacted.

This situation is true for the chronically uninsured and for those who experience gaps in coverage during job losses or loss in Medicaid coverage. Understanding the potential implications of health insurance status can help doctors to best treat patients, with and without cancer.

Immunotherapy is becoming the standard of care for many cancers, utilizing the body’s own immune system to fight cancer cells. Checkpoint inhibitors, one form of immunotherapy, allow the immune system to find and fight cancerous cells. Cancers of the bladder, breast, cervix, colon, esophagus, head, neck, kidney, blood, liver, lung, prostate and skin can all be treated with various forms of immunotherapy. One type of cancer that has proven very difficult to treat with immunotherapy is brain cancer, especially gliomas (glioblastoma multiforme or GBM). As cancers mutate, they often can become easier for the immune system to recognize with immunotherapy, but this is not the case for gliomas.

A glioma analysis published in the journal Nature looked at 10,200 cases of gliomas and found that immunotherapy is largely ineffective at treating this form of brain cancer. Typically, as a cancer mutates, it loses some resistance to the human immune system, which allows checkpoint inhibitor treatments to expose the cancer. However, even after several mutations, glioma cells still evaded the immune system after checkpoint inhibitor immunotherapy. Researchers believe that several immunosuppressive activities in the brain may help shelter gliomas from the immune system. Further research will be needed to discover how to expose gliomas to more cytotoxic lymphocytes, which are key cells in fighting disease.

This study also showed that the standard chemotherapy treatment for gliomas, temozolomide, becomes less effective if the glioma mutates, making the cancer harder to treat. Temozolomide is largely ineffective on hypermutated gliomas, as is immunotherapy. Ultimately, this analysis explains why gliomas, and especially glioblastomas, are known for their resistance to traditional cancer therapies and provides further insight into the treatment of gliomas with standard and new cancer therapies, paving the way for additional research.

Diagnosing and treating early cancers is a priority for both physicians and researchers because treating late stage cancers is often difficult or impossible. Cancers with a genetic link can allow for the identification of high-risk individuals and about 5-10% of cancers are inherited. If a person is diagnosed with a cancer with a potential genetic link, family members can be tested to see if they also have a mutated gene and are at increased risk to develop cancer. 

Now, more genetic mutations with a potential link to cancer are under investigation, including genetic mutations leading to acute myeloid leukemia (AML). Acute myeloid leukemia is a type of blood cancer found in both children and adults. According to new research on AML by Dana-Farber Cancer Institute, blood cells need more than one genetic mutation or “hit” to turn cancerous. That window between the first genetic “hit” and the second mutation is a potential treatment window to prevent leukemia from developing in the first place.

In one animal study conducted at Dana-Farber, mice who experienced the first genetic mutation, called clonal hematopoiesis of indeterminate potential (CHIP), and then a second mutation ultimately developed leukemia. However, when treated after the first mutation with a compound called VTP-50469, the problematic mutated blood cells stopped reproducing and leukemia never developed. If doctors can treat the mutations that cause AML rather than treating the resulting leukemia with traditional cancer therapies, this could potentially improve patient outcomes. Scientists still need to prove that the compound has a high level of safety and efficacy in patients, but this research could lead to the early treatment of patients with AML.

One of the most dangerous side effects of a stroke or brain injury is uncontrolled brain swelling, which can block blood flow to the brain and lead to further brain damage. Currently, doctors can fight swelling by removing a part of a skull or by installing a shunt to drain cerebrospinal fluid, but both carry risks, primarily of infection. A drug capable of reducing swelling without invasive procedures may potentially also reduce the high morbidity rate of complications caused by brain swelling.

In the study led by the University of Exeter, a group of researchers from around the world discovered that a malfunction in the transportation of key proteins in one brain pathway can lead to the dangerous swelling. The proteins in this pathway regulate water composition in and out of the brain, but the new ZT-1a compound is able to target that specific pathway. In lab tests of mice and rats with stroke or hydrocephalus, ZT-1a was able to stop the enzymes from activating proteins that led to increased water in the brain. This mechanism was able to reduce swelling by 50% in the study. Further human studies are needed to confirm these initial findings.

A previous study examined the potential use of multiple drugs to reduce swelling, but none of those drugs were able to concentrate the reduction of swelling to just the brain, which made the drugs too dangerous to use in humans. The ability of this compound to target specific enzymes in a specific pathway is a unique characteristic that may make the compound a safer alternative to high-risk surgeries and devices, like shunts.

Despite the fact that strokes are a major health concern in the United States, affecting nearly 800,000 people and killing approximately 140,000 each year, treatments are largely outdated, with high rates of complications. Finding ways to improve the treatment of strokes and stroke complications through non-invasive methods could potentially save the life and quality of life of future stroke patients.