Two type 2 diabetes medications outperformed others in NIH-funded clinical trial

In a large clinical trial comparing four drug medications approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes, researchers found that insulin glargine and liraglutide performed the best to maintain blood glucose levels in the recommended range. All four medications evaluated were added to treatment with metformin, which is the first-line drug to treat type 2 diabetes. Of the 37 million Americans who have diabetes, approximately 90% to 95% of them have type 2 diabetes, and people with diabetes who keep their blood glucose levels in the near-normal range have a lower risk of developing diabetes complications such as nerve, kidney, and eye diseases. While there is general agreement that a combination of metformin, diet, and exercise is the best early approach in diabetes care, there is no consensus on what to do next to best keep high blood glucose in check.

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The study enrolled over 5,000 people with type 2 diabetes from diverse racial and ethnic groups who were already taking metformin. Three groups took metformin plus a medicine that increased insulin levels, sitagliptin, liraglutide, or glimepiride. The fourth group took metformin and insulin glargine U-100, a long-acting insulin. After an average of four years of follow-up, the study found that participants taking metformin plus liraglutide or insulin glargine achieved and maintained their target blood levels for the longest time compared to sitagliptin or glimepiride. Sitagliptin was found to be the least effective in maintaining target levels.

Source: asamonitor.pub/3VG7EAN

New gene therapy could prevent blindness in children with rare ciliopathy

In a National Institutes of Health (NIH)-funded study, National Eye Institute researchers developed a gene therapy that rescues cilia defects in retinal cells affected by a type of Leber congenital amaurosis (LCA). LCA is a rare genetic disease that leads to degeneration of the light-sensing retina at the back of the eye. Most forms of the disease have no treatment. The type of LCA caused by mutations in NPHP5 is relatively rare. It causes blindness in all cases, and in many cases, it can also lead to failure of the kidneys, a condition called Senior-Løken syndrome.

Stem cell samples from two patients with NPHP5 deficiency were used to generate retinal organoids, also called retinas-in-a-dish. These retinal organoids showed defects in the photoreceptors, including loss of the “outer segments,” which, in a healthy retina, contain light-sensing molecules called opsins that initiate a nerve signal that travels to the brain and mediates vision. The photoreceptor outer segment is a special type of primary cilium, and researchers discovered that a type of LCA caused by mutations in the NPHP5 (also called IQCB1) gene leads to severe defects in the primary cilium.

The findings not only shed light on the function of the NPHP5 protein in the primary cilium but also led to a potential treatment for this blinding condition. When the researchers introduced an adeno-associated viral vector containing a functional version of NPHP5 as a gene therapy vehicle, the retinal organoids showed a significant restoration of opsin protein concentrated in the proper location in outer segments. The new gene therapy approach could prevent blindness in children with LCA and help treat others with the disease.

Source: asamonitor.pub/3ftXwdO

Mitigating graft-vs-host disease and cancer relapse after leukemia treatment

Researchers from Baylor College of Medicine have engineered immune cells to control complications that emerge after treating leukemia, such as graft-vs-host disease (GvHD) and cancer relapse, with allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Researchers wanted to protect patients from both GvHD and cancer resurgence without eliminating their normal immunity that helps fight leukemia but also protects against serious disease-causing viruses, which frequently emerge post-transplant.

In their treatment post-chemotherapy, the patient receives an infusion of stem cells from a healthy donor, which repopulate the patient and restore the normal blood-making process. The transplanted stem cells also usually contain a small amount of donor immune cells called T cells, which can recognize normal organs and tissues as foreign and mount an immune rejection-like process called GvHD. The team developed a way to identify the T cells that cause GvHD using the protein OX40 that is found in abundance in those T cells. The researchers then engineered a receptor named alloimmune defense receptor, or ADR, a molecule they expressed on therapeutic T cells that enables them to recognize and kill cells that express OX40 protein. ADR-armed T cells very effectively suppressed T cells, mediating GvHD in animal models. T cells outfitted with both ADR and a leukemia-specific chimeric antigen receptor protected animal models from both GvHD and leukemia relapse.

Source: asamonitor.pub/3BSssfb

Advanced melanoma survival improves by 20% when immunotherapy is given before targeted therapy

The multicenter, phase III clinical trial DREAMseq, from the Georgetown Lombardi Comprehensive Cancer Center, showed a 72% two-year overall survival rate for people with advanced melanoma who received pembrolizumab immunotherapy both before and after, rather than just after, surgery to remove tumor tissue, versus the 52% survival rate of those who initially received targeted therapies. Progression-free survival, where the cancer is stable or improving, was also trending in favor of those who started on immunotherapy.

265 trial participants with metastatic melanoma were randomly assigned to two groups. One group received a targeted drug combination followed by an immunotherapy combination if their cancer resisted the first combination. The other group received the immunotherapy combination first and the targeted therapy if necessary. The DREAMseq trial was stopped early due to the clear evidence that – for patients with melanoma who have a mutation in the BRAF gene, specifically a BRAF V600 mutation – immunotherapy is the better initial approach compared to giving drugs that specifically target this mutated pathway. According to the National Cancer Institute, there will be an estimated 99,780 new cases diagnosed and 7,650 deaths due to melanoma in 2022, but advances in treatment attributed to a 4% drop in melanoma deaths from 2015 to 2019.

Source: asamonitor.pub/3xZDiyY

Frozen embryo transfers linked with risk of dangerous hypertensive disorders

In vitro fertilization (IVF) using frozen embryos may be associated with a 74% higher risk of hypertensive disorders, including preeclampsia, gestational hypertension, eclampsia (the onset of seizures in those with preeclampsia), and chronic hypertension with superimposed preeclampsia than during naturally conceived pregnancies or with fresh embryo transfer.

Researchers examined national data from medical birth registries in Denmark, Norway, and Sweden of nearly 2.4 million women 20 to 44 years old who had single deliveries and gave birth between 1988 and 2015. Of the more than 4.5 million pregnancies in the study, 4.4 million were naturally conceived, more than 78,000 pregnancies were fresh embryo transfers, and more than 18,000 pregnancies were frozen embryo transfers. The data included 33,000 cases of women who had both an IVF pregnancy and a naturally conceived pregnancy, called sibling comparison, to isolate if the potential reason for the hypertensive disorders was attributable to parental factors or to the IVF treatment. The findings of the sibling comparison indicate that higher risk for hypertensive disorders results not from parental factors, but in relation to some IVF treatments.

Source: asamonitor.pub/3CjiR2D

Knockout of protein TXNIP improves diabetes-associated hyperglycemia and hyperglucagonemia

Research from the University of Alabama at Birmingham has shown that the protein TXNIP regulates survival and function of beta cells, the pancreatic cells that produce the hormone insulin to lower levels of glucose in the blood. Downregulation or inhibition of TXNIP in beta cells protects against diabetes in mouse models, and a repurposed clinical drug that inhibits TXNIP shows promising results in people with recent-onset type 1 diabetes.

Research now shows that TXNIP alpha-cell knockouts, known as aTKO, improved diabetes-associated hyperglycemia and hyperglucagonemia in a mouse model of streptozotocin-induced diabetes. When aTKO mice were fed a high-fat diet for 30 weeks to create glucose intolerance, they had a reduced high-fat diet-induced glucose intolerance, compared to control mice on the high-fat diet. In the knockout mice, there was no change in the architecture of the aTKO islets, and the alpha cell numbers were unchanged. Furthermore, the expression levels of the glucagon gene and key islet transcription factors showed no change. However, glucagon secretion was decreased more than twofold in the aTKO islets compared to controls.

Thus, it appears that downregulation of alpha cell TXNIP can inhibit alpha cell glucagon secretion, which in turn may help explain the improvement in hyperglucagonemia and hyperglycemia observed in diabetic aTKO mice.

Source: asamonitor.pub/3SsZ32s

Bridge2AI program expands use of artificial intelligence in biomedical and behavioral research

The National Institutes of Health will invest $130 million over four years to accelerate the use of artificial intelligence (AI) by the biomedical and behavioral research communities. The Bridge to Artificial Intelligence (Bridge2AI) program is assembling team members from diverse disciplines and backgrounds to generate tools, resources, and richly detailed data that are responsive to AI approaches while ensuring its tools and data do not perpetuate inequities or ethical problems that may occur during data collection and analysis. AI is already used in biomedical research and health care, but its widespread adoption has been limited in part due to challenges of applying AI technologies to diverse data types, partly due to insufficient biomedical and behavioral data sets that lack important contextual information about the data type, collection conditions, or other parameters. Bridge2AI researchers will create guidance and standards for the development of ethically sourced, state-of-the-art, AI-ready data sets that have the potential to help solve some of the most pressing challenges in human health – such as uncovering how genetic, behavioral, and environmental factors influence a person’s physical condition throughout their life. Bridge2AI will also produce diverse data types to identify abnormal changes in the body, make new connections between complex genetic pathways and changes in cell shape or function, and help improve decision-making in critical care settings to speed recovery from acute illnesses.

Source: asamonitor.pub/3SmQwx9

New wireless surgical camera has first successful human use

The ArthroFree Wireless Surgical Camera System from Lazurite and Minnetronix Medical is the first wireless surgical camera system to receive FDA market clearance for arthroscopy and general endoscopy. The camera has recently had its first successful human use and the completion of its transfer to manufacturing.

The system, first used in surgery on September 13 at NYU Langone, enables real-time, high-quality images without the intrusion of cords. Additional surgeries with the use of the wireless camera are scheduled to be held at NYU Langone and other orthopedic centers. The Minnetronix optics team contributed to the ArthroFree System’s reduced latency and enhanced imaging, as well as the development of the image signal processing chain that an image takes to travel from initial capture on a sensor to a screen.

The device has a lightweight engine and a handpiece that increases production speed and efficiency by developing a modular strategy of batch assembling subassemblies and finishing assembly inside a clean room. The finalization of the product comes despite increased supply chain challenges, and with the help of the Minnetronix and Lazurite teams’ creative solutions.

Source: asamonitor.pub/3SEiW6i

Seer Medical at-home epilepsy monitoring system coming to the U.S.

With recent FDA approval, Seer Medical is preparing to launch its most recent epilepsy diagnostic monitoring technology in the U.S. With the green light, Seer has begun forging partnerships with hospitals and health care providers to identify potential patients with epilepsy who are waiting for a long-term monitoring option to confirm the diagnosis.

The Seer Home epilepsy monitoring system uses a wearable device and monitoring hub to track the health of people suspected of having epilepsy for up to a week at a time. The Seer Sense device features a series of electrodes that are attached to the chest and forehead, kept in place by wearable pieces that rest across the shoulders and at the crown of the head, respectively. The electrodes capture both electroencephalograph readings of brain activity and electrocardiogram readings from the heart. The hub is equipped with cameras to monitor patients, with footage of their body movements synced to the electrode data to provide doctors with additional context about their conditions.

The artificial intelligence algorithms are also able to parse through the data, looking for signs of epilepsy and potential triggers of the condition. Though epilepsy affects more than 65 million people around the world, about one-third of diagnoses are incorrect. Seer Medical hopes its at-home monitor will increase the efficiency and accuracy of the diagnostic process.

Source: asamonitor.pub/3SC5obm