Archive for month: December, 2024

Supplementation with probiotics may improve glycemic control in women with gestational diabetes suggests a study published in the BMC Endocrine Disorders.

Tourniquet-induced hypertension (TH) is still a challenging problem, and different strategies like peripheral nerve blocks, peri-femoral artery blocks, and subcutaneous infiltration have been investigated to manage it. Recent study aimed to compare the efficacy of peri-femoral artery block (P-FAB) and subcutaneous infiltration, both combined with femoral and sciatic nerve blocks, in reducing tourniquet-induced hypertension (TH) during lower-limb surgery under general anesthesia. The primary objective was to compare the incidence of TH between the two groups. Secondary objectives included intraoperative use of intravenous fentanyl and antihypertensive medications, as well as postoperative pain scores.

The study was a single-center, double-blind, randomized controlled trial involving 58 patients scheduled for elective lower-limb surgery. Participants were randomly assigned to the P-FAB or subcutaneous infiltration (SI) groups. All patients received general anesthesia with femoral and sciatic nerve blocks. TH was defined as a 30% increase in systolic blood pressure from baseline. The results showed no significant difference in the incidence of TH between the P-FAB and SI groups (51.9% vs 51.9%, p=1.00). Similarly, there were no significant differences in intraoperative fentanyl (p=0.459) or antihypertensive use (p=0.992). Pain scores at the thigh and surgical sites, measured using a numerical rating scale, were also not significantly different between the two groups (p>0.05).

Conclusion

In conclusion, adding a peri-femoral artery block to general anesthesia with femoral and sciatic nerve blocks did not reduce the incidence of tourniquet-induced hypertension compared to subcutaneous infiltration in patients undergoing lower-limb surgery. The findings suggest that the use of combined femoral and sciatic nerve blocks may be sufficient to mitigate the effects of tourniquet-induced hypertension, and the addition of a peri-femoral artery block does not provide further benefits.

Key Points

1. The study aimed to compare the efficacy of peri-femoral artery block (P-FAB) and subcutaneous infiltration, both combined with femoral and sciatic nerve blocks, in reducing tourniquet-induced hypertension (TH) during lower-limb surgery under general anesthesia.

2. The primary objective was to compare the incidence of TH between the P-FAB and subcutaneous infiltration (SI) groups. Secondary objectives included intraoperative use of intravenous fentanyl and antihypertensive medications, as well as postoperative pain scores.

3. The study was a single-center, double-blind, randomized controlled trial involving 58 patients scheduled for elective lower-limb surgery. Participants were randomly assigned to the P-FAB or SI groups.

4. The results showed no significant difference in the incidence of TH between the P-FAB and SI groups (51.9% vs 51.9%, p=1.00). There were also no significant differences in intraoperative fentanyl use or antihypertensive use.

5. Pain scores at the thigh and surgical sites, measured using a numerical rating scale, were not significantly different between the two groups (p>0.05).

6. The findings suggest that the use of combined femoral and sciatic nerve blocks may be sufficient to mitigate the effects of tourniquet-induced hypertension, and the addition of a peri-femoral artery block does not provide further benefits.

Reference –

Chonruethai Tangkittithaworn et al. (2024). Efficacy Of Local Anaesthetic Peri-Femoral Artery Injection Compared To Subcutaneous Infiltration In Combination With Femoral And Sciatic Nerve Blocks For Reducing Thigh Tourniquet-Induced Hypertension During Lower-Limb Surgery Under General Anaesthesia: A Randomised Controlled Double-Blinded Trial. *Indian Journal Of Anaesthesia*. https://doi.org/10.4103/ija.ija_968_24.

A new study published in the journal of Sleep and Breathing showed that a higher risk of moderate-to-severe obstructive sleep apnea (OSA) in children may be linked to male gender and the presence of allergic rhinitis (AR). The most prevalent sleep-disordered breathing (SDB) is obstructive sleep apnea. In healthy adults and children, OSA prevalence ranged from 3.5% to 20.4% and 1% to 5%, respectively, and was considerably greater for SDB. Prolonged partial upper airway obstruction and/or occasional full blockage are characteristics of OSA which interferes with regular breathing and sleep cycles.

Also, these respiratory conditions may raise the chance of metabolic, neurological, and cardiovascular problems. The people frequently suffer from eczema, asthma, allergic rhinitis (AR), and other allergic illnesses. AR is a widespread illness that impacts 10% to 40% of people worldwide. Another frequent sleep-related respiratory condition that affects kids is obstructive sleep apnea. Therefore, Bo Yang and team conducted this study to characterize the variables linked to the onset and advancement of severe types of pediatric OSA.

Children having a discharge diagnosis of OSA who were hospitalized between January 2020 and December 2020 to the Children’s Hospital of Chongqing Medical University, China, were included in this study. Following evaluations of the apnoea-hypopnea index (AHI) and lowest oxygen saturation (LSaO2) using established methods, each patient had a polysomnography test. The computerized medical records of the hospital were used to gather clinical and demographic data. A univariate logistic model was used to investigate the relationships between OSA severity and other covariates. Multivariate analysis was then used to further discover independent risk factors.

During the research period, 263 children in all were identified. Standardized recommendations indicate that 48.7% of people with OSA had moderate to severe symptoms, whereas 51.3% had mild symptoms. In this population, 39.2% of people had mild hypoxemia, and 60.8% had moderate to severe hypoxemia. After controlling for variables, moderate-to-severe OSA was significantly linked with male gender and allergic rhinitis (all P-values < 0.05). P < 0.05 indicated that AR was the sole significant predictor of hypoxemia.

Overall, in order to lower the risk of severe OSA and associated consequences, our findings highlight the need for early identification and care of AR in children. For children with OSA, especially those with AR, tailored treatment strategies may enhance results and slow the course of the illness to more advanced stages.

Reference:

Yang, B., Zou, Q., Wang, F., Pang, Y., Wei, P., & Xing, Y. (2024). Allergic rhinitis as a predictor of moderate-to-severe paediatric obstructive sleep apnoea. In Sleep and Breathing (Vol. 28, Issue 3, pp. 1303–1310). Springer Science and Business Media LLC. https://doi.org/10.1007/s11325-024-03011-6

A simple dietary supplement may provide a new approach to boost CAR T cell function, according to a study from researchers in the Perelman School of Medicine at the University of Pennsylvania and Penn Medicine’s Abramson Cancer Center. While the approach needs to be assessed in clinical trials, the early research, shared in a press briefing today at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 4), hints at a potentially cost-effective strategy to improve CAR T cell function and cancer-fighting abilities.

CAR T cell therapy is a personalized treatment approach, pioneered at Penn Medicine, that reprograms patients’ own immune cells to kill their cancer.

“Thousands of patients with blood cancers have been successfully treated with CAR T cell therapy, but it still doesn’t work for everyone,” said co-lead author Shan Liu, PhD, a postdoctoral fellow who presented the study at ASH. “We took an outside-the-box approach to improve CAR T cell therapy, by targeting T cells through diet rather than further genetic engineering.”

Liu co-led the study with Puneeth Guruprasad, PhD, who earned his PhD at Penn and is now a medical student in the Perelman School of Medicine. The lead authors worked under the mentorship of co-senior authors Marco Ruella, MD, an assistant professor of Hematology-Oncology, a researcher with the Center for Cellular Immunotherapies and the scientific director of Penn Medicine’s Lymphoma Program; and Maayan Levy, PhD, an assistant professor of Microbiology.

CAR T cells prefer BHB as a fuel source

First, the research team tested the effect of several different diets, including ketogenic, high-fiber, high-fat, high-protein, high cholesterol, and a control diet, on CAR T cell’s tumor-fighting capabilities using a mouse model of diffuse-large B-cell lymphoma. They found improved tumor control and survival in the mice receiving a ketogenic diet compared to all other diets. In subsequent studies, they found higher levels of beta-hydroxybutyrate (BHB), a metabolite produced by the liver in response to a ketogenic diet, was a key mediator of this effect.

The research builds on previous work from Levy’s team, which found that BHB strongly suppressed the growth of colorectal tumors in lab experiments.

“Our theory is that CAR T cells prefer BHB as a fuel source rather than standard sugars in our body, such as glucose,” Guruprasad said. “So, increasing the levels of BHB in the body gives the CAR T cells more power to take out the cancer cells.”

Translational studies in patient samples and healthy volunteers

Next, the research team tested a BHB supplement combined with CAR T cell therapy in laboratory models of human cancer (on a standard diet); the results showed complete obliteration of the cancer in the vast majority of mice and resulted in higher CAR T cell expansion and activation. To see if BHB, which occurs naturally at various level in our bodies, had a similar effect in humans, the team assessed blood samples from patients who had recently received CAR T cell therapy and found that greater BHB levels were associated with better CAR T cell expansion in patients. They also looked at T cells of healthy volunteers who took a BHB supplement and found similar changes in how normal T cells generated energy after exposure to BHB.

Past studies across several cancer types have looked at the impact of dietary interventions, such as a high-fiber diet, on the response to cancer immunotherapy, however the mechanism behind the BHB effect in this study appears to stem from metabolic changes in the blood, rather than via the gut microbiome, as in the case of a high-fiber diet.

Next steps and potential impact

The theory that BHB supplementation could improve response to CAR T cell therapy is being tested in a Phase I clinical trial at Penn Medicine’s Abramson Cancer Center.

“We’re talking about an intervention that is relatively cheap and has low toxicity potential,” Levy said. “If the clinical trial data pans out, I’m excited to think about how a fairly simple approach like this could be combined with dietary interventions or other, more traditional approaches, to enhance the anti-cancer effect.”

The clinical trial, led by principal investigator Elise Chong, MD, an assistant professor of Hematology-Oncology, will soon begin enrolling patients with relapsed or refractory large B-cell lymphoma who are receiving commercially available anti-CD19 CAR T cell therapy as part of their treatment.

“As a physician and scientist, I share my patients’ excitement for potential new strategies to better treat their cancer, and I’m thrilled to see this research move from the lab bench to translational studies and now to a clinical trial,” Ruella said. “However, we want to emphasize that, at this point, the research is still preliminary, and we’re not making any dietary or supplement recommendations to patients based on this study until we have definitive clinical evidence.”

Reference:

Keto diet metabolite may power up CAR T cells to kill cancer, University of Pennsylvania School of Medicine, Meeting: 66th American Society of Hematology (ASH) Annual Meeting and Exposition.