Archive for month: December, 2024

A widely accessible drug commonly used to control blood glucose levels in diabetic patients has the potential to strengthen the effects of immunotherapy and improve recurrence-free survival in people with lung cancer who are overweight or obese, new research published in the Journal of the National Cancer Institute shows. Sai Yendamuri, MD, MBA, FACS, Chief Strategy Officer and Chair of Thoracic Surgery at Roswell Park Comprehensive Cancer Center, led the retrospective study as co-senior author.

Over the past 20 years, researchers have seen evidence suggesting that metformin might slow cancer progression, but the results of clinical trials have largely failed to confirm the connection. Based on prior findings, Dr. Yendamuri and his colleagues from Roswell Park hypothesized that the anticancer benefits of the drug might be experienced in a specific group of lung cancer patients-Diabetes Drug Appears to Fight Lung Cancer-But Only in Overweight or Obese Patientsthose who are overweight or obese. They further suspected that strong evidence of these effects may have been obscured in past clinical trials that included normal-weight patients.

To test that theory, the team looked at data from two groups of patients who had non-small cell lung cancer (NSCLC). One group included 511 patients with a body mass index (BMI) of 25 or higher, considered overweight/obese, and 232 with a BMI of less than 25, not considered overweight-all of whom underwent surgery. Data from a second group were used to evaluate the drug’s effect on progression-free survival in 284 overweight vs. 184 non-overweight patients with NSCLC who received a type of immunotherapy called an immune checkpoint inhibitor. Additionally, the team documented metformin’s effects on tumor progression, antitumor immunity and response to immune checkpoint inhibitors in the lab in preclinical lung cancer models.

“Our work shows that the anticancer effect of metformin is active only in the context of obesity,” says Dr. Yendamuri. “We observed longer recurrence-free survival in overweight patients who took metformin and underwent surgery.”

The preclinical studies in animal models showed that metformin slowed tumor growth and reversed obesity-driven suppression of the immune system. Combined treatment with metformin plus an immune checkpoint inhibitor (anti-PD-1 antibody therapy) achieved even better tumor growth control — but this effect was essentially seen only in obese models, paralleling the improved progression-free survival seen only in overweight patients receiving immune checkpoint inhibitors.

Joseph Barbi, PhD, Assistant Professor of Oncology in Roswell Park’s Department of Immunology, and co-senior author on the new work, adds that the team’s findings show that in obese or overweight patients, metformin appears to shift the balance between immune-suppressing mechanisms and those that activate tumor-killing processes.

“By calling attention to the potential of metformin-containing treatment regimens to improve clinical outcomes for obese and overweight patients, we hope to inspire future studies,” says Dr. Barbi. “We believe our findings provide a rationale for testing drug combinations that might have the potential for preventing or treating lung cancer more effectively in this growing pool of patients.”

Based on their clinical and preclinical observations, Drs. Yendamuri and Barbi designed a phase 2 clinical trial (NCT04931017) to evaluate the drug’s potential for preventing lung cancer in overweight or obese people at high risk for the disease. Roswell Park is one of only three sites in the U.S and Canada to offer the trial, which is funded by the National Cancer Institute.

“Metformin has been used for 30 years and has a long record of safety-and it’s one of the most widely accessible and affordable drugs of any kind,” says Dr. Yendamuri. “If we can repurpose it to fight cancer, that’s very exciting.”

Reference:

Randall J Smith, Robert Zollo, Sukumar Kalvapudi, Yeshwanth Vedire, Akhil Goud Pachimatla, Cara Petrucci, Garrison Shaller, Deschana Washington, Vethanayagam Rr, Stephanie N Sass, Aravind Srinivasan, Eric Kannisto, Sawyer Bawek, Prantesh Jain, Spencer Rosario, Joseph Barbi, Sai Yendamuri, Obesity-Specific improvement of lung cancer outcomes and immunotherapy efficacy with metformin, JNCI: Journal of the National Cancer Institute, 2024;, djae295, https://doi.org/10.1093/jnci/djae295

Vitamin D supplementation associated with significantly increased incidence of remission of chronic anterior uveitis suggests a study published in the Ocular Immunology and Inflammation.

According to a study to be presented at next week’s RSNA meeting in Chicago, Levothyroxine use  may be associated over time with bone loss,

Levothyroxine is the second most commonly prescribed medication among older adults in the U.S. It is marketed under multiple brand names including Synthroid and is a synthetic version of a hormone called thyroxine and is commonly prescribed to treat the condition hypothyroidism, or underactive thyroid. In people with hypothyroidism, the thyroid gland does not produce enough thyroxine on its own, often resulting in fatigue, weight gain, hair loss and other symptoms. If left untreated, hypothyroidism can lead to serious and potentially fatal complications.

Approximately 23 million Americans-about 7% of the U.S. population-take levothyroxine daily. Sometimes, patients have been taking levothyroxine for many years, but it is not clear why it was initially prescribed or if it is still required.

“Data indicates that a significant proportion of thyroid hormone prescriptions may be given to older adults without hypothyroidism, raising concerns about subsequent relative excess of thyroid hormone even when treatment is targeted to reference range goals,” said the study’s lead author Elena Ghotbi, M.D., postdoctoral research fellow at Johns Hopkins University School of Medicine in Baltimore, Maryland.

Though there are some variables, a normal reference range for thyroid-stimulating hormone (TSH) is typically around 0.4 – 5.0 microunits per milliliter. Excess thyroid hormone has been associated with increased bone fracture risk.

For this study-a multidisciplinary collaboration between the Russell H. Morgan Department of Radiology and Radiological Science and Endocrinology Department at Johns Hopkins Medical Institutions, Dr. Ghotbi and colleagues aimed to determine whether levothyroxine use and higher thyroid hormone levels within the reference range are associated with higher bone loss over time in older “euthyroid” adults, meaning adults with normal thyroid function.

The researchers used the Baltimore Longitudinal Study of Aging (BLSA), a prospective observational cohort study of community-dwelling older adults. Participants aged 65 and older who had at least two visits and thyroid function tests consistently within the reference ranges were included in Dr. Ghotbi’s study.

“This research is a collaboration between Johns Hopkins and the BLSA, the longest-running study on aging conducted by the Intramural Research Program of the National Institute on Aging,” said co-author Eleanor Simonsick, Ph.D., epidemiologist and BLSA co-director. “The BLSA’s extensive data include repeated DEXA measurements at each study visit, which provides valuable insight into the progression of bone density and bone mass changes over time, offering a more comprehensive understanding of aging-related osteoporosis.”

The study group included 81 euthyroid levothyroxine users (32 men, 49 women) and 364 non-users (148 men, 216 women), with a median age of 73 and TSH levels of 2.35 at the initial visit. Other risk factors like age, gender, height, weight, race, medications, smoking history and alcohol use were considered in propensity score matching of levothyroxine users versus non-users.

The results showed that levothyroxine use was associated with greater loss of total body bone mass and bone density-even in participants whose TSH levels were within the normal range-over a median follow-up of 6.3 years. This remained true when taking into account baseline TSH and other risk factors.

“Our study suggests that even when following current guidelines, levothyroxine use appears to be associated with greater bone loss in older adults,” said Shadpour Demehri, M.D., co-senior author and professor of radiology at Johns Hopkins.

Jennifer Mammen, M.D., Ph.D., co-senior author and associate professor of endocrinology at Johns Hopkins, advises that adults taking levothyroxine should discuss their treatment with their health care provider and regularly monitor their thyroid function tests. “A risk-benefit assessment should be conducted, weighing the strength of the indications for treatment against the potential adverse effects of levothyroxine in this population,” she said.

Reference:

Common thyroid medicine linked to bone loss, Radiological Society of North America, Meeting: 110th Scientific Assembly and Annual Meeting of the Radiological Society of North America.

Since the introduction of mifepristone, a progesterone blocker, the rate of medication-based abortions has consistently increased in both the United States and worldwide. In 2020, 53% of abortions in the United States were medication-based, and in most Western European countries, more than half of the abortions were also medication-based according to the most recent data. Recent study examined whether mental health disorders increased in the shorter and longer-term after a medication or procedural abortion using Danish population data.

The researchers followed 72,424 females who had a first-trimester abortion between 2000 and 2018, analyzing the risk of any first psychiatric diagnosis, mood disorder diagnosis, and anxiety/stress disorder diagnosis. They compared the risk in the year after the abortion to the year before, as well as over longer time periods. The key findings were: 1. Females having medication (n=37,155) and procedural abortions (n=35,269) had the same risk of any first psychiatric diagnosis in the year after their abortion relative to the year before (medication abortion adjusted incidence rate ratio=1.02; procedural abortion adjusted incidence rate ratio=0.94). 2. As more time passed after the abortion, the risk of psychiatric diagnoses actually decreased relative to the year before the abortion for each method. For example, 5+ years after the abortion, the adjusted incidence rate ratios were 0.58 for medication abortions and 0.54 for procedural abortions. 3. These findings were consistent when examining specific diagnoses like mood disorders and anxiety/stress disorders, as well as in sensitivity analyses.

Conclusion

The researchers conclude that neither medication nor procedural abortions increase the risk of mental health disorders in the shorter or longer-term. These findings provide evidence that abortions do not negatively impact mental health. The results suggest policies or practices based on the idea that abortion methods increase psychological problems are not supported by the data.

Key Points

1. The study examined whether mental health disorders increased in the shorter and longer-term after a medication or procedural abortion using Danish population data.

2. The researchers followed 72,424 females who had a first-trimester abortion between 2000 and 2018, analyzing the risk of any first psychiatric diagnosis, mood disorder diagnosis, and anxiety/stress disorder diagnosis.

3. Females having medication (n=37,155) and procedural abortions (n=35,269) had the same risk of any first psychiatric diagnosis in the year after their abortion relative to the year before.

4. As more time passed after the abortion, the risk of psychiatric diagnoses actually decreased relative to the year before the abortion for both medication and procedural abortions. For example, 5+ years after the abortion, the adjusted incidence rate ratios were 0.58 for medication abortions and 0.54 for procedural abortions.

5. The findings were consistent when examining specific diagnoses like mood disorders and anxiety/stress disorders, as well as in sensitivity analyses.

6. The researchers conclude that neither medication nor procedural abortions increase the risk of mental health disorders in the shorter or longer-term, and that policies or practices based on the idea that abortion methods increase psychological problems are not supported by the data.

Reference –

Steinberg JR, Laursen TM, Lidegaard Ø, Munk-Olsen T. Medication and procedural abortions before 13 weeks gestation and risk of psychiatric disorders. Am J Obstet Gynecol 2024;231:437.e1-18