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SGLT2 Inhibitors Linked to Lower Hyperkalemia Risk and Improved RAASi Continuation suggests a new study published in the JAMA .

In a new National Institutes of Health-funded study led by scientists at the Wilmer Eye Institute, Johns Hopkins Medicine researchers say they have determined that low blood sugar, or hypoglycemia, may promote a breakdown of the blood-retinal barrier, an important boundary that regulates the flow of nutrients, waste and water in and out of the retina.

The research, which investigated the phenomenon in diabetic mice, provides insights into the origin of diabetic retinopathy, specifically in patients with episodes of hypoglycemia. Diabetic retinopathy, a severe complication of both type 1 and type 2 diabetes, can cause permanent vision damage if left untreated.

The full study, published in Science Translational Medicine on April 30, explains that a specific protein known as hypoxia-inducible factor (HIF) accumulates in certain cells in the retina during periods of low blood sugar.

HIF has been implicated in diabetic retinopathy and other eye diseases before. The protein can trigger a chain reaction, switching on overproduction of other proteins which lead to overgrowth and leakage of blood vessels in the retina. Now, scientists have found that HIF is a player in how the blood-retinal barrier breaks down during hypoglycemia.

Researchers tested HIF’s role in hypoglycemia by inducing periods of low blood sugar in mice with and without diabetes. Their experiments showed that mice with diabetes had higher levels of HIF during hypoglycemia, enough to promote the breakdown of the blood-retinal barrier and cause leakage in retinal blood vessels, while mice without diabetes did not experience higher levels of HIF. This breakdown in diabetic retinopathy contributes to irreversible damage to the retina and vision loss.

The team investigated further by testing an experimental drug known as 32-134D, which inhibits the HIF protein. Some diabetic mice received an injection of 32-134D prior to induced episodes of low blood sugar, and researchers observed lower HIF levels, in turn preventing the expression of proteins that promote the breakdown of the blood-retinal barrier and blood vessel leakage.

“These studies help explain why patients with diabetes who are initially started on tight glucose control, the cornerstone of diabetic management, or those who have high glycemic variability (transient episodes of very low-followed by very high-serum glucose levels), experience worsening of their diabetic eye disease,” says corresponding author Akrit Sodhi, M.D., Ph.D., associate professor of ophthalmology and the Branna and Irving Sisenwein Professor of Ophthalmology at the Johns Hopkins University School of Medicine and the Wilmer Eye Institute. “Our findings underscore why therapies targeting HIF will be an effective approach to prevent or treat diabetic retinopathy.”

Researchers are planning future studies on HIF, the breakdown of the blood-retinal barrier and 32-134D, and hope to conduct clinical studies of 32-134D in patients with diabetic retinopathy.

Reference:

Chuanyu Guo et al. ,Hypoglycemia promotes inner blood-retinal barrier breakdown and retinal vascular leakage in diabetic mice.Sci. Transl. Med.17,eadq5355(2025).DOI:10.1126/scitranslmed.adq5355.

Recently published study focuses on the implications of acute normovolemic hemodilution (ANH) on red blood cell (RBC) transfusion rates and the occurrence of short-term complications in patients undergoing cardiac surgery. Recognizing that bleeding is a critical complication during heart surgeries, which often leads to the necessity of allogeneic blood transfusions, the investigation highlights the need for alternative strategies like ANH to potentially mitigate adverse transfusion-related outcomes.

Methodology

An extensive quasi-experimental design was employed, encompassing 2,271 patients at a referral hospital, with a rigorous propensity-score matching approach applied to balance the cohort effectively. This matching resulted in 778 patients divided into two groups: those receiving ANH (389 patients) and those not receiving it (389 patients). The matching was successful as there were no significant differences in demographic, clinical, and procedural variables between the two groups.

Results

The results revealed that ANH led to a statistically significant reduction in both the rate and volume of RBC transfusions. Specifically, the RBC transfusion rate dropped from 60.9% to 50.9% in the ANH group (risk ratio: 0.84; P = 0.006) and the number of transfused RBC units was decreased by an average of 0.24 units. However, the study did not identify any differences in the transfusion of fresh frozen plasma (FFP) and platelets between groups.

Complications

In terms of complications, the incidence of lactic acidosis—a condition defined as elevated serum lactate levels—was notably reduced by 53%, from 11.3% in the non-ANH group to 6.8% in the ANH group (risk ratio: 0.47; P < 0.001). This observation suggests that ANH could enhance tissue perfusion and reduce blood viscosity, possibly leading to improved coronary blood flow and efficiency in oxygen delivery.

Postoperative Outcomes

Conversely, the study found no significant differences in various short-term postoperative outcomes, including mortality, incidences of re-intubation, re-exploration due to bleeding, delayed sternal closure, length of ICU stays, or duration of mechanical ventilation. Despite the apparent benefits regarding RBC transfusions and lactic acidosis, the lack of other adverse effects underscores the potential safety of ANH as a blood conservation method in cardiac surgeries.

Limitations

The authors pointed out several limitations to their findings. Even with rigorous propensity score matching, there may still be residual confounding factors that were not accounted for, including variations in individual patient characteristics and other technical aspects of the surgeries performed. Additionally, the study did not assess certain postoperative outcomes, such as infections or acute kidney injury. In conclusion, the findings of this large, rigorously matched study substantiate that mild-volume ANH could significantly decrease both the rate and volume of RBC transfusions along with the incidence of lactic acidosis in cardiac surgery patients, while not adversely affecting other short-term outcomes. These implications suggest that ANH can be an effective blood conservation technique. Nonetheless, further randomized clinical trials are recommended to validate these results and explore the broader implications of ANH in diverse patient populations.

Key Points

– The study investigates the impact of acute normovolemic hemodilution (ANH) on red blood cell (RBC) transfusion rates and short-term complications in patients undergoing cardiac surgery, aiming to address the complications arising from bleeding and the need for allogeneic blood transfusions.

– A quasi-experimental design involving 2,271 patients at a referral hospital was utilized, with propensity-score matching resulting in 778 patients evenly divided into two groups: those receiving ANH and those not receiving it, effectively balancing demographic, clinical, and procedural variables.

– ANH significantly reduced the RBC transfusion rate (from 60.9% to 50.9%; risk ratio: 0.84; P = 0.006) and the average number of transfused RBC units by 0.24 units, although no significant differences were observed in the use of fresh frozen plasma (FFP) and platelets between the two groups.

– The incidence of lactic acidosis decreased by 53% in the ANH group (from 11.3% to 6.8%; risk ratio: 0.47; P < 0.001), indicating possible improvements in tissue perfusion and oxygen delivery efficiency due to ANH.

– No significant differences in short-term postoperative outcomes were reported, such as mortality, re-intubation, re-exploration for bleeding, delayed sternal closure, ICU stay duration, or mechanical ventilation time, suggesting the potential safety of ANH in cardiac surgeries.

– Limitations acknowledged include potential residual confounding factors not accounted for despite matching, as well as the lack of assessment for specific postoperative complications like infections or acute kidney injury, highlighting the need for further randomized clinical trials to validate the findings and assess broader applications of ANH.

Reference –

Vala Sebt et al. (2025). Acute Normovolemic Hemodilution Significantly Reduces RBC Transfusion And Lactic Acidosis Following Cardiac Surgery-A Propensity-Matched Study.. *Annals Of Cardiac Anaesthesia*, 28 2, 136-142. https://doi.org/10.4103/aca.aca_192_24.

Anal cancer has been steadily increasing in the United States, with the biggest jumps among older women, especially white and Hispanic women-a shift that challenges assumptions about high-risk groups and who should be screened, according to a study to be presented today at Digestive Disease Week® (DDW) 2025.

“Rates of anal cancer are rising fastest among white and Hispanic women over 65-groups not traditionally considered high risk,” said lead author Ashley Robinson, MD, a second-year internal medicine resident at Advocate Lutheran General Hospital. “While the exact reasons behind this trend remain unclear, most older women were beyond the recommended age for human papillomavirus vaccination when it first became widely available.”

Human papillomavirus, known as HPV, causes 90% of anal cancers.

Researchers analyzed data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results database, known as SEER, from 2017 to 2021. They found anal cancer increased by 2.9% for women and 1.6% for men. Anal cancers increased fastest among white women over 65, who saw a 4.3% increase during the five-year study period, reaching 11.4 cases per 100,000 in 2021. If the trend continues, the incidence of anal cancer in women over age 65 would double in less than 17 years.

Hispanic women over age 65 had the second-highest rate of anal cancer, with 7.5 cases per 100,000 people in 2021 and a slower annual increase of 1.7%.

“It’s crucial that we promote HPV vaccination as a key tool for preventing anal cancer, while also keeping health care providers informed as screening guidelines evolve,” Dr. Robinson said. “These findings highlight specific patient groups who may benefit from targeted screening for anal HPV and anal cancer.”

Still considered rare, anal cancer makes up approximately 1% of all gastrointestinal cancers, with more than 90% of cases linked to chronic HPV infection. While screening for anal HPV, dysplasia and cancer is recommended for high-risk groups-identified as individuals with HIV, bone marrow transplant recipients and other immunocompromised populations-older women addressed in this study are not included.

Reference:

Anal cancer rates rising most among older, white and Hispanic women, Digestive Disease Week, Meeting, Digestive Disease Week.

Eating a healthy diet as a child is linked to girls having their first menstrual period at an older age than those who consumed a less healthy diet, according to a new study published today (Wednesday) in Human Reproduction, one of the world’s leading reproductive medicine journals.

The findings remained unaltered by the girls’ body mass index (BMI) or height, both of which have been associated with the earlier onset of periods.

The study has implications for health in later life as it is well known that women who started their periods at an early age may be at higher risk for diabetes, obesity, breast cancer and diseases of the heart and blood vessels.

Holly Harris, MPH, ScD, an associate professor at the Fred Hutchinson Cancer Center in Seattle, Washington, USA, who led the study, said: “I think our findings highlight the need for all children and adolescents to have access to healthy meal options, and the importance of school-based breakfasts and lunches being based on evidence-based guidelines.”

The findings come from a large, prospective study of more than 7,500 children, aged between 9 and 14, who were enrolled in the Growing Up Today Study (GUTS) in the USA in two waves in 1996 and 2004. The researchers followed them through to 2001 and 2008, respectively.

For the first time, the researchers investigated the link between particular diets and the age that periods first started (menarche). They are also the first to examine whether BMI might have a modifying effect on the association between diet and age of menarche. Previous studies have only looked at BMI as something that needs to be considered when analysing results (a confounding factor).

Prof. Harris said: “In previous work that we had conducted in the Nurses’ Health Study II, an ongoing prospective cohort, we observed a higher risk of breast cancer among people who consumed an inflammatory-promoting diet during adolescence and early adulthood. Following these results we were interested in understanding whether earlier life dietary intake might influence breast cancer through impact on risk factors for breast cancer that occur between early life and breast cancer, such as age at menarche. This led to the current study where we examined the impact of dietary patterns on age at menarche.”

Before their periods started, the children completed questionnaires about their diet when they joined the study and then every one to three years thereafter. They also reported their age when their first period started.

The researchers assessed the girls’ diets against two established dietary patterns: the Alternative Healthy Eating Index (AHEI), and the Empirical Dietary Inflammatory Pattern (EDIP). The AHEI awards more points for healthier foods, including vegetables, legumes and whole grains, while unhealthy foods such as red and processed meats, trans fats and salt are awarded fewer points. The EDIP scores diets in a way that reflects their overall potential for causing inflammation in the body. Foods that are linked to greater inflammation include red and processed meat, meat from animal organs, refined grains and high-energy drinks.

A total of 6,992 girls (93% of the whole group) had their first period during the study. Analysis of data from the questionnaires showed that the 20% of girls with the highest AHEI score and who, therefore, had the healthiest diets, were eight percent less likely to have their first period within the next month compared to the 20% of girls who had the lowest AHEI score. The 20% percent of participants with the highest EDIP score, which meant they had the most inflammatory diet, were 15% more likely to have their first period in the next month compared to the 20% who had the lowest EDIP score.

Prof. Harris said: “We observed that these two dietary patterns were associated with age at menarche, indicating that a healthier diet was linked to menstrual periods starting at an older age. Importantly, these results were independent of BMI and height, demonstrating the importance of a healthy diet regardless of body size. As earlier age at menarche is associated with multiple later life outcomes, including higher risk of diabetes, obesity, cardiovascular disease and breast cancer, this may be an important period for trying to reduce the risk of these chronic diseases.”

The researchers believe that these results suggest the type of food eaten by girls during childhood and adolescence and its impact on inflammation may be what is influencing the time of menarche, rather than height and BMI.

“As this is the first study to look at these specific dietary patterns it is important to examine the association in other populations. It also highlights that eating a healthy diet, which we know is associated with chronic disease outcomes in later life, could also have benefits in adolescence. Generally, eating fruits, vegetables, whole grains, fatty fish, nuts and legumes, polyunsaturated fatty acids, while limiting intake of red and processed meats, refined grains, sugar-sweetened beverages and added salt, benefits everyone regardless of age,” said Prof. Harris.

The researchers now plan to look at childhood and adolescence dietary patterns and body size to see how they may relate to characteristics of menstrual cycles in adulthood.

Strengths of the study include that it collected data on diet in a prospective manner, and it was able to see whether or not BMI and height influenced the association with age at menarche. Limitations include information on diet, weight, height and age at menarche was collected via questionnaires and may be subject to error; the researchers were not able to adjust directly for body fat, as measured by dual-energy X-ray absorptiometry; and the participants were predominately white and so the researchers were not able to see if results varied by race.

Reference:

C P Davis, S Fest, K Cushing-Haugen, T W Kensler, J E Chavarro, H R Harris, Dietary patterns and age at menarche in a prospective study of girls in the USA, Human Reproduction, 2025;, deaf072, https://doi.org/10.1093/humrep/deaf072