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A new study published in Diabetes Technology and Therapeutics showed that one of the main causes of postprandial and nocturnal hyperglycemia in hospitalized inpatients is delayed insulin delivery after meals and snacking before bed without insulin administration.

For those with diabetes, controlling blood glucose levels is essential, and timing insulin boluses during meals and eating before bed are important factors in this process. Better decisions about insulin dosing and glucose stability at night are made possible by continuous glucose monitoring (CGM), which offers real-time insights into glucose changes.

Optimizing glycemic regulation and lowering the risks of hyperglycemia (high blood sugar) and hypoglycemia (low blood sugar) can be achieved by comprehending how these variables interact. It might be difficult to provide prandial insulin with meals on time for hospitalized inpatients. Moreover, no prior research has examined the glycemic effects of post-dinner snacking, sometimes known as “bedtime snacking,” in the absence of prandial insulin treatment. This study was by Sara Alexanian and colleagues examined the effects of bedtime eating and delayed insulin delivery on inpatient glycemic control.

The In-Fi study, compared Fiasp with insulin aspart (Novolog) in inpatients with type 2 diabetes, was the subject of a post hoc analysis by researchers. The Dexcom G6 PRO continuous glucose monitoring (CGM) device was used to measure the glucose results. A total of 122 randomized participants who finished the primary trial protocol (which involved wearing a CGM for at least 4 meals) had their CGM and insulin delivery data examined. This study assesses the effects of bedtime eating and postponed insulin injection on glucose regulation.

Insulin boluses given before meals (n = 149) had a 4-hour postprandial time in range (TIR70–180) of 48%, while those given more than 5 minutes after a meal had a TIR70–180 of 24%. When controlling for bedtime sensor glucose, eating between 9 p.m. and 12 a.m. was linked to a considerably lower overnight (9 p.m. and 6 a.m.) TIR70–180 and a significantly higher fasting glucose the following morning.

After controlling for initial bedtime sensor glucose, bedtime eating was linked to greater overnight glucose percentage coefficient of variation and higher overnight glucose standard deviation. Overall, one of the main cause of post-meal and nocturnal hyperglycemia in hospitalized patients is the delayed administration of insulin during meals and the consumption of insulin-free snacks before bed. 

Reference:

Alexanian, S. M., Cheney, M. C., Bello Ramos, J. C., Spartano, N. L., Wolpert, H. A., & Steenkamp, D. W. (2025). Impact of meal insulin bolus timing and bedtime snacking on continuous glucose monitoring-derived glycemic metrics in hospitalized inpatients. Diabetes Technology & Therapeutics. https://doi.org/10.1089/dia.2025.0027

A new study published in the Journal of the American College of Cardiology showed that the patients with atrial fibrillation (AF) on oral anticoagulation, which includes NT-proBNP and high-sensitivity troponin outperforms clinical ratings in predicting stroke.

The risk of ischemic stroke is a major factor in stroke prevention therapy recommendations for people with atrial fibrillation (AF). It is known that a patient receiving direct oral anticoagulant treatment today still has a chance of having a stroke, which might range from 0.3% to 0.9% annually.

The true vision for the future was that if patients treated with a direct oral anticoagulant still had a high risk of stroke, they might benefit from additional treatment such as left atrial appendage occlusion [LAAO] devices, or perhaps have a more liberal indication for ablation to eliminate A-fib or lessen the burden of A-fib as a stroke risk indicator.

This was because the risk of stroke still varies during oral anticoagulant treatment. Thus, this study was to assess the biomarker-based Age, Biomarkers, Clinical history (ABC)-AF-stroke risk score. Lars Wallentin and colleagues also created a modified ABC-AF-istroke risk score to predict total stroke and ischemic stroke in AF patients, respectively.

The ABC-AF-stroke score and the modified ABC-AF-istroke score were calculated using data clinical history of stroke, on age, and levels of N-terminal pro B-type natriuretic peptide and troponin in 26,452 AF patients who were assigned to direct oral anticoagulants (DOACs) or warfarin.

There were 756 incidents of stroke or systemic embolism (SEE) throughout the follow-up period, including 534 cases of ischemic stroke/SEE. In comparison to the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) score of 0.632 and the CHA2DS2-VASc score of 0.614, the ABC-AF-stroke score, C-index, demonstrated greater discrimination of total stroke/SEE. With a C-index for ABC-AF-istroke of 0.677 when compared to 0.642 for the ATRIA and 0.624 for the CHA2DS2-VASc score, the outcomes for ischemic stroke/SEE were comparable (P < 0.001 for both).

For both total and ischemic stroke, the ABC-AF-stroke scores demonstrated satisfactory calibration. In the pertinent subgroups, the results were consistent. Analysis of decision curves revealed a net advantage with regard to decision thresholds for stroke prevention. Overall, when it came to predicting total and ischemic stroke, the biomarker-based ABC-AF risk scores were well-calibrated, demonstrated superior discrimination over clinical risk scores, and offered significant decision assistance for stroke-prevention therapies in AF patients.

Reference:

Wallentin, L., Lindbäck, J., Hijazi, Z., Oldgren, J., Carnicelli, A. P., Alexander, J. H., Berg, D. D., Eikelboom, J. W., Goto, S., Lopes, R. D., Ruff, C. T., Siegbahn, A., Giugliano, R. P., Granger, C. B., & Morrow, D. A. (2025). Biomarker-based model for prediction of ischemic stroke in patients with Atrial Fibrillation. Journal of the American College of Cardiology, 85(11), 1173–1185. https://doi.org/10.1016/j.jacc.2024.11.052

Analgesic management for pain following proximal femur fractures is critical to enhancing patient recovery. In a recent controlled study involving 60 adult trauma patients scheduled for surgical fixation of proximal femur fractures, the effectiveness of three analgesic techniques was compared: the continuous fascia iliaca plane block using a suprainguinal approach (SFICB), the continuous fascia iliaca plane block using an infrainguinal approach (IFICB), and a femoral nerve block (FNB). Participants were randomized into one of the three groups, receiving ultrasound-guided blocks with 0.2% ropivacaine for postoperative analgesia, followed by a continuous infusion at 10 mL/h for the first 24 hours.

Study Objectives

The primary aim was to assess the number of rescue analgesic (RA) doses required within the first 24 hours post-surgery to maintain a visual analogue scale (VAS) pain score below 4. Secondary objectives included total morphine consumption, duration of analgesia, pain scores over time, quality of pain relief, and the assessment of any adverse effects.

Results Overview

Results showed that patients in the SFICB group had a significantly lower need for RA doses: only 15% required additional morphine, compared to 40% in the IFICB group and 50% in the FNB group. Furthermore, median morphine consumption was notably less in the SFICB group (3 mg) than the IFICB (6.5 mg) and FNB (9.0 mg) groups, indicating better analgesic efficacy. SFICB patients reported lower median VAS scores and higher quality of pain relief, with a significant proportion noting excellent pain relief compared to those in the other two groups.

Methodological Considerations

Methodologically, patients were carefully selected based on specific criteria to ensure reliability. Those with any prior analgesic therapies, infections, pregnancy, or other relevant comorbidities were excluded. Each block’s feasibility and performance time were recorded along with patient-reported side effects. Patients in all groups underwent monitoring for hemodynamic stability during the procedure.

Efficacy of SFICB

Results demonstrated the superior analgesic efficacy of the SFICB approach due to its more extensive local anesthetic spread, successfully covering the femoral, lateral femoral cutaneous, and obturator nerves. While both the FNB and IFICB techniques were effective, they lagged behind SFICB in terms of overall effectiveness and patient satisfaction.

Clinical Implications

The findings emphasize the clear advantage of using a continuous suprainguinal fascia iliaca compartment block as a preferred technique for postoperative pain management in patients with proximal femur fractures. The implications suggest that implementing SFICB can lead to reduced opioid consumption and better pain management, providing a more effective strategy for enhancing recovery in surgical patients. This study supports the notion that optimized regional anesthesia techniques can play a pivotal role in improving postoperative care outcomes and patient satisfaction. Further investigations could expand to assess long-term effects and explore the potential for additional adjunct therapies to augment analgesic strategies.

Key Points

– A controlled study with 60 adult trauma patients evaluated three analgesic techniques for postoperative pain management following proximal femur fractures: continuous fascia iliaca plane block using a suprainguinal approach (SFICB), continuous fascia iliaca plane block using an infrainguinal approach (IFICB), and femoral nerve block (FNB). Each participant received ultrasound-guided blocks with 0.2% ropivacaine followed by a continuous infusion for the first 24 hours post-surgery.

– The primary objective was to analyze the number of rescue analgesic doses needed within the first 24 hours to maintain a visual analogue scale (VAS) pain score below 4. Secondary objectives assessed total morphine consumption, duration of analgesia, pain scores over time, quality of pain relief, and side effects.

– Results indicated that only 15% of patients in the SFICB group necessitated additional morphine for pain relief, significantly lower than 40% in the IFICB group and 50% in the FNB group, suggesting superior effectiveness of the SFICB technique.

– Median morphine consumption was significantly reduced for the SFICB group (3 mg), compared to the IFICB (6.5 mg) and FNB (9.0 mg) groups, demonstrating the SFICB’s enhanced analgesic efficacy.

– The superior analgesic performance of SFICB is attributed to its broader local anesthetic spread, covering essential nerves including the femoral, lateral femoral cutaneous, and obturator nerves, resulting in lower median VAS scores and improved patient satisfaction in pain management.

– The findings suggest that SFICB is a preferred postoperative pain management technique for proximal femur fractures, potentially leading to reduced opioid consumption and improved patient recovery outcomes. The study indicates a need for further exploration of long-term effects and adjunct therapies to enhance analgesic strategies.

Reference –

Nidhi Bhatia et al. (2025). Continuous Peripheral Nerve Block In Patients With Proximal Femur Fracture: A Randomised Comparison Of Three Techniques. *Indian Journal Of Anaesthesia*. https://doi.org/10.4103/ija.ija_1095_24.

Clinical research has long focused on ways to harness the actions of the immune system. From vaccines to immunotherapies, researchers have used their knowledge of the immune system to develop therapies to treat or prevent diseases from influenza to autoimmune disease and cancer.

Now, researchers from Penn’s School of Dental Medicine and international collaborators have investigated the effects of training the innate immune system in experimental models of two chronic inflammatory diseases, periodontitis and arthritis. They found that this “trained” immunity, or TRIM, led to increased bone loss in these models. This study is published in Developmental Cell.

Previous approaches have largely focused on the adaptive immune system, that branch of the immune system that “remembers” previous threats and launches specific attacks when it encounters them again. The body also has an innate immunity branch, which, for a long time, was just considered the first-line, general attack arm of the immune system with no ability to remember prior assaults or respond differently when rechallenged.

“If you go and look at an immunology textbook-even today-it will likely tell you that innate immunity has no memory; its response doesn’t get improved the second time,” says George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Basic & Translational Sciences at Penn Dental Medicine.

This belief, Hajishengallis notes, has been challenged over the past decade. Studies have shown that the innate immune system can respond more strongly when challenged again with the same or different stimulus-in other words, it can be “trained.”

And importantly, these studies have also shown that “training” the innate immune system has beneficial effects, such as anti-tumor activity and an increased response to fighting infections in certain experimental models.

But inflammation—the innate immune system’s natural response to harmful stimuli-can also exacerbate symptoms or even cause diseases, demonstrating the need to better understand the immune system when developing immune-based therapies. An increased response may not always be beneficial.

“Trained innate immunity (TRIM) has emerged as a major immunological principle that challenges the dogma that memory is restricted to adaptive immunity,” says Hajishengallis. “So, a better understanding of TRIM is imperative to appropriately harness it for therapeutic gain in human disease.”

The Hajishengallis team along with a collaborative lab led by Triantafyllos Chavakis at the Dresden University of Technology, induced TRIM using ß-glucan, a compound found in certain fungi, and measured the generation of osteoclasts, which resorb bone during growth and healing, in models of inflammatory periodontitis and arthritis.

“We found that this treatment primed osteoclast precursors to differentiate into osteoclasts more readily if presented with an inflammatory challenge like arthritis,” says Chavakis.

“So, although TRIM can have beneficial effects-protecting against infections and cancer-our results indicate that the memory of a previous infection may also contribute to inflammatory diseases and the comorbidity between inflammatory bone loss disorders,” adds Hajishengallis.

Their work, however, showed that ß-glucan only increases the opportunity for bone loss to occur-it does not cause actual bone loss. That only occurs if a second inflammatory stimulus, such as arthritis or periodontitis, is present.

“This requirement [for a secondary challenge] epitomizes the concept of trained immunity-the training stimulus causes a state of preparedness for future events,” says Hajishengallis.

Importantly, these results argue against the idea that it is the initial stimulus that is driving TRIM to be beneficial or maladaptive (harmful), as ß-glucan caused beneficial TRIM (for example, tumor growth inhibition) in previous studies by Hajishengallis and Chavakis.

“Our findings suggest that the context in which TRIM emerges dictates whether the functional outcome is protective or harmful,” says Chavakis.

“The double-edged sword nature of TRIM acquires special relevance when considering the preventive or therapeutic application of TRIM-inducing agents,” adds Hajishengallis.

Reference:

Nora Haacke, Hui Wang, Shu Yan, Marko Barovic, Xiaofei Li, Kosuke Nagai, Adelina Botezatu, Aikaterini Hatzioannou, Bettina Gercken, Giulia Trimaglio, Anisha U. Shah, Jun Wang, Ling Ye, Mangesh T. Jaykar, Martina Rauner, Ben Wielockx, Kyoung-Jin Chung, Mihai G. Netea, Lydia Kalafati, George Hajishengallis, Triantafyllos Chavakis, Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice, Developmental Cell, https://doi.org/10.1016/j.devcel.2025.02.001