Archive for category: News

A study published in Diabetes Care has found that transepidermal water loss (TEWL) is a strong predictor of diabetic foot ulcer recurrence. Involving over 400 adults, the study revealed that individuals with high TEWL were 2.7 times more likely to experience ulcer recurrence compared to those with low TEWL.

A research team funded by the National Institutes of Health (NIH) has identified a diagnostic aid that has the potential to accurately predict the recurrence of diabetic foot ulcers that appear to be fully healed. By measuring the skin’s barrier function through a process known as trans-epidermal water loss, or TEWL, scientists were able to determine which wounds were more likely to reopen. TEWL measurements are a major factor in burn care, where deep layers of the skin are often damaged. The findings suggest that full restoration of skin barrier function should be incorporated into existing wound treatment standards to ensure complete wound closure and to better identify patients at risk of wound recurrence.

“This study is an important initial step to give clinicians treating diabetic foot ulcers a reliable diagnostic aid for the first time to assess an individual’s risk of ulcer recurrence,” said Teresa Jones, M.D. program director for the Division of Diabetes, Endocrinology, & Metabolic Diseases at NIH’s National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK). “Foot ulcers are such a confounding issue with diabetes and being able to determine which wounds are at highest risk for recurrence could save many lives and limbs.”

Scientists, working together through the NIDDK Diabetic Foot Consortium, evaluated over 400 study participants who had a diabetic foot ulcer that visually appeared to be closed or healed. They measured TEWL at the site of the foot ulcer and found that 35% of participants with high TEWL (more water loss) reported a wound recurrence by 16 weeks, compared to just 17% for those with low TEWL (less water loss). Participants with higher TEWL were 2.7 times more likely to experience a wound recurrence than participants with low TEWL.

Diabetic foot ulcers are a major complication of diabetes where a break in the skin of the foot is often unnoticed by a patient due to nerve damage, known as neuropathy. They are the leading cause of non-traumatic lower-limb amputations, and untreated or unhealed ulcers significantly increase the risk of death. Wounds that appear to be healed on the surface may not be fully closed below the superficial surface of the skin, hampering the effectiveness of the skin’s barrier function to keep in water and keep out pathogens, such as bacteria.

Reference:

Chandan K. Sen, Gayle M. Gordillo, Sashwati Roy, Jordan Jahnke, Mithun Sinha, Lava Timsina, Shomita S. Mathew-Steiner, Michael S. Conte, Crystal Holmes, Teresa L.Z. Jones, Rodica Pop-Busui, Giselle Kolenic, Cathie Spino, Geoffrey C. Gurtner, NIDDK Diabetic Foot Consortium TEWL Study; High Transepidermal Water Loss at the Site of Wound Closure Is Associated With Increased Recurrence of Diabetic Foot Ulcers: The NIDDK Diabetic Foot Consortium TEWL Study. Diabetes Care 2025; dc250300. https://doi.org/10.2337/dc25-0300

Acute myeloid leukemia (AML) is an aggressive cancer affecting the blood and bone marrow that progresses rapidly, making immediate treatment essential. While chemotherapy and targeted drugs have improved outcomes for some patients, many forms of AML remain resistant to treatment, and relapses are common.

A new study sheds light on why certain types of AML are so challenging to treat and how outcomes for patients might be improved. Researchers from Japan, including scientists from Chiba University, have discovered that an epigenetic enzyme called SETD1B plays a critical role in supporting the growth of a particularly aggressive form of AML—especially in patients with the Fms-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD) mutation, a genetic change associated with poor prognosis and high relapse rates. By targeting SETD1B, the researchers believe, it may be possible to develop more effective treatments that prevent leukemia cells from multiplying.

The study was led by Associate Professor Takayuki Hoshii and included Dr. Shintaro Izumi and Professor Atsushi Kaneda from the Graduate School of Medicine, Chiba University, Japan. The findings were published online in the journal Leukemia on May 8, 2025.

“Patients with AML, especially with the FLT3-ITD mutation, often respond poorly to current therapies. Our findings are that the epigenetic regulator SETD1B protein supports aggressive cell proliferation in AML by promoting oncogenic MYC expression,” says Dr. Hoshii.

Previous research has shown that FLT3-ITD mutations are detected in patients with mixed-lineage leukemia-rearranged (MLL-r) AML, a subtype of leukemia characterized by genetic abnormalities. MLL-r AML cells exhibit high levels of histone H3 lysine 4 trimethylation (H3K4me3), an epigenetic modification that affects which genes are turned on or off without changing the DNA sequence. Though the link between MLL-r AML and H3K4me3 has been established, the association between FLT3-ITD and H3K4me3 remains unclear.

Using advanced genetic screening tools, the team identified Setd1b as the gene responsible for producing a protein that adds methyl groups to histone H3 at lysine 4, resulting in the H3K4me3 epigenetic modification, and upregulation of Myc genes, which plays a critical role in regulating cell growth, division, and metabolism and can contribute to cancer development if altered.

To understand the role of SETD1B, the researchers performed CRISPR screening and then genetically engineered leukemia cells with altered versions of SETD1B, specifically deleting its catalytic domain, which is the active part of the protein responsible for the epigenetic modification of the DNA. They then used RNA sequencing and chromatin mapping to identify which genes and pathways were most affected.

Their experiments revealed that removing SETD1B’s catalytic domain significantly slowed cancer growth, particularly in leukemia cells with FLT3-ITD or NrasG12D mutations. It also caused a drop in the activity of genes in the MYC pathway. This suggests that without the epigenetic function of SETD1B, MYC cannot remain fully active, weakening the ability of the cancer cells to grow and divide.

“The breadth of H3K4me3 is crucial for transcriptional consistency, and MYC expression appears highly dependent on both the quality and quantity of transcriptional elongation,” says Dr. Hoshii. “Understanding SETD1B’s role in maintaining this epigenetic mark is critical for developing biomarkers and therapies for leukemia subtypes and other MYC-driven cancers.”

Interestingly, when the researchers reintroduced the Myc gene back into leukemia cells lacking SETD1B, the cancer cells began to grow again, but only partially, suggesting that SETD1B plays a broader role in MYC’s cancer-promoting activity.

This discovery paves the way for new treatment strategies. By targeting SETD1B or its epigenetic functions, scientists may be able to develop therapies that are especially effective for patients with FLT3-ITD mutations. As a possible next step, the researchers point to Chaetocin, an existing compound known to inhibit enzymes related to SETD1B. This could serve as a foundation for developing more selective SETD1B-targeted drugs. Measuring SETD1B activity in patients might also help doctors predict who would benefit most from these therapies.

As the search for better treatments continues, this study reveals how targeting the cancer’s epigenetic machinery could provide a new strategy to treat the disease, giving hope to patients with aggressive forms of AML.

Reference:

Izumi, S., Ohtani, K., Matsumoto, M. et al. Regulation of H3K4me3 breadth and MYC expression by the SETD1B catalytic domain in MLL-rearranged leukemia. Leukemia 39, 1627–1639 (2025). https://doi.org/10.1038/s41375-025-02638-y.

A group led by the Department of Neurosurgery at the Brain Research Institute, Niigata University, has successfully treated a patient with a brainstem glioma harboring a rare IDH2 mutation. The patient initially presented with a gradual loss of hearing in the left ear, and MRI showed a lesion at the left side of the brainstem, near the root exit zone of the left acoustic nerve. Initially, a brainstem glioma with H3K27M mutation was suspected. However, the gradual clinical course and unusual location of the brainstem glioma were considered atypical.

The patient underwent magnetic resonance spectroscopy in which 2-hydroglutarate, a marker for IDH mutation, was evident. Subsequently, the patient underwent a surgical biopsy, and pathological analysis revealed a rare IDH2 mutation. Although most brainstem gliomas with H3K27M mutation have an unmethylated MGMT promoter and thus are resistant to temozolomide, about 70% of IDH-mutant astrocytomas are known to have a methylated MGMT promoter and are sensitive to temozolomide.

A team led by Dr. Manabu Natsumeda successfully treated the patient with temozolomide and radiation, and the tumor dramatically shrank, and surprisingly, the patient’s hearing improved. The patient has been off treatment after 1 year of maintenance temozolomide treatment, but the tumor has not relapsed. “We were fortunate to detect IDH mutation in this patient, or else we would not have used temozolomide. This case illustrates the importance of screening by MRS for IDH mutation and a safe biopsy to determine the optimal treatment.” explains Dr. Natsumeda. The case report was published online in the journal Frontiers in Oncology on July 8, 2025.

Reference:

Takuya Okada, Case Report: Improved hearing in a rare, adult IDH2-mutant brainstem astrocytoma successfully treated with radiation and temozolomide, Frontiers in Oncology, https://doi.org/10.3389/fonc.2025.1555986

France: A new study has found that using a combination of multiplex PCR (mPCR) testing and serum procalcitonin levels to guide antibiotic management in critically ill patients with community-acquired pneumonia (CAP) did not significantly reduce antibiotic exposure or improve outcomes when compared to standard care. The findings of the MULTI-CAP randomized controlled trial were published on July 15, 2025, in Intensive Care Medicine by Dr. Guillaume Voiriot of Sorbonne Université, Assistance Publique – Hôpitaux de Paris, and his research team.

Researchers have identified in a new study published in JAMA that repeated low-dose treatment with lysergic acid diethylamide (LSD) is safe but not substantially symptom-reducing in adults with attention-deficit/hyperactivity disorder (ADHD). A randomized controlled trial evaluated the safety and efficacy of microdosing LSD among patients with moderate to severe ADHD, with no difference in improvement in symptoms between LSD and placebo. The study was conducted by Lorenz M. and fellow researchers.