Nevin Manimala

Spine (Phila Pa 1976). 2025 Aug 22. doi: 10.1097/BRS.0000000000005480. Online ahead of print.

ABSTRACT

STUDY DESIGN: A retrospective cohort analysis.

OBJECTIVE: This study investigates the association between initial postoperative gabapentinoid prescription and long-term opioid use following long-segment posterior lumbar instrumentation.

SUMMARY OF BACKGROUND DATA: Gabapentinoids have gained traction for their neuropathic pain-relieving properties and potential synergy with opioids. However, their long-term efficacy in minimizing postoperative opioid consumption remains uncertain, particularly in patients undergoing extensive spinal surgery.

METHODS: The TriNetX Research Network was queried to identify patients with preoperative diagnoses of lumbar spinal stenosis, spondylolisthesis or scoliosis who underwent posterior lumbar instrumentation spanning 3 to 12 vertebral segments. The study population was stratified by based on the extent of instrumentation, defined as either 3-6 or 7-12 spinal segments. These patients were further divided into two cohorts: those who were prescribed a gabapentinoid (gabapentin or pregabalin) within 30 days postoperatively and those who were not. To address potential confounders, 1:1 propensity score matching (PSM) was performed, adjusting for demographics, comorbidities, and preoperative prescriptions of opioids and gabapentinoids. Presence of select postoperative opioid prescriptions were assessed at 1 to 3 months, 3 to 6 months, 6 to 12 months, and 12 to 24 months.

RESULTS: A total of 28,827 patients met all initial inclusion criteria. Following 1:1 PSM, the 3-6 segment group included 1,816 patients per cohort and the 7-12 segment group consisted of 344 patients per cohort. Among 3-6 level instrumentations, patients who received gabapentinoids within 30 days of surgery demonstrated significantly lower odds of being prescribed non-codeine-based and strong opioids at all postoperative intervals. In contrast, these gabapentinoid-treated patients exhibited higher odds of weak opioid prescriptions at 3 to 6 months. No statistically significant difference in opioid prescribing was observed among 7-12 segment instrumentation patients at any period.

CONCLUSION: This study demonstrates that early postoperative gabapentinoid prescription is associated with a sustained reduction in chronic non-codeine-based and strong opioid use following 3-6 segment lumbar fusion. These findings underscore the utility of gabapentinoids as part of a multimodal analgesia strategy, potentially minimizing the need for more potent opioids and reducing the risk of long-term dependence in spine surgery patients.

PMID:40844769 | DOI:10.1097/BRS.0000000000005480

Proc Natl Acad Sci U S A. 2025 Aug 26;122(34):e2507516122. doi: 10.1073/pnas.2507516122. Epub 2025 Aug 22.

ABSTRACT

Humans can implicitly learn about multistep sequential relationships between events in the environment from their statistical co-occurrence. Theoretical work has suggested that neural replay is a candidate mechanism that aids such learning. Here, we used functional MRI (fMRI) to test whether replay is related to implicit learning of higher-order sequential relationships. Human participants viewed sequences of images that followed probabilistic transitions determined by ring-like graph structures. Behavioral modeling of response times revealed that participants acquired multistep transition knowledge in a manner consistent with gradual updating of an internal successor representation (SR) model. Yet, half of participants did not report being aware of any sequential task structure, and most participants failed to provide meaningful transition probability ratings in a posttask test. Analyses of temporal dynamics of multivariate fMRI patterns during brief 10 s pauses from the ongoing statistical learning task indicated backward sequential replay of multistep sequences in visual cortical areas. Variations in model parameters between participants that captured response time patterns related to strength of neural replay. No corresponding relations between replay and measures of explicit awareness were found. These findings indicate that implicit learning of higher-order relationships establishes an internal SR-based map of the task and is accompanied by cortical on-task replay.

PMID:40844766 | DOI:10.1073/pnas.2507516122

Eur Radiol. 2025 Aug 22. doi: 10.1007/s00330-025-11859-9. Online ahead of print.

NO ABSTRACT

PMID:40844754 | DOI:10.1007/s00330-025-11859-9

Eur Radiol. 2025 Aug 22. doi: 10.1007/s00330-025-11960-z. Online ahead of print.

NO ABSTRACT

PMID:40844753 | DOI:10.1007/s00330-025-11960-z

Eur Radiol. 2025 Aug 22. doi: 10.1007/s00330-025-11959-6. Online ahead of print.

NO ABSTRACT

PMID:40844752 | DOI:10.1007/s00330-025-11959-6

Eur Radiol. 2025 Aug 22. doi: 10.1007/s00330-025-11877-7. Online ahead of print.

NO ABSTRACT

PMID:40844751 | DOI:10.1007/s00330-025-11877-7

Eur Radiol. 2025 Aug 22. doi: 10.1007/s00330-025-11875-9. Online ahead of print.

NO ABSTRACT

PMID:40844750 | DOI:10.1007/s00330-025-11875-9

Cardiovasc Drugs Ther. 2025 Aug 22. doi: 10.1007/s10557-025-07759-1. Online ahead of print.

ABSTRACT

PURPOSE: The optimal dosing strategy for direct oral anticoagulants (DOACs) in extended treatment of venous thromboembolism (VTE) remains debated, particularly in balancing efficacy and bleeding risk.

METHODS: A systematic review and meta-analysis was performed to compare reduced-dose versus full-dose DOACs for extended VTE treatment. Databases including PubMed, Embase, and Cochrane Library were searched from inception to March 2025 for randomized controlled trials (RCTs) involving adult patients treated with different DOAC doses for VTE. Primary outcomes were recurrent VTE, major or clinically relevant non-major bleeding, and all-cause mortality. Subgroup analysis was conducted by DOAC type (apixaban vs. rivaroxaban).

RESULTS: Pooled data from 4 studies involving 8421 patients showed no statistically significant difference in recurrent VTE risk between reduced-dose and full-dose DOACs (RR = 0.94; 95% CI, 0.64-1.37; p = 0.75). Bleeding events were significantly lower in the reduced-dose group compared to the full-dose group (RR = 0.71; 95% CI, 0.61-0.82, p < 0.00001). All-cause mortality did not differ significantly between groups (RR = 0.80; 95% CI, 0.54-1.18; p = 0.25). Subgroup analysis showed consistent findings across DOAC type, with no significant interaction effects.

CONCLUSION: Reduced-dose DOACs appear to be as effective as full-dose DOACs in preventing VTE, with a favorable safety profile due to reduced bleeding risk. These findings support reduced-dose DOACs as a viable option for extended anticoagulation in VTE patients.

PMID:40844745 | DOI:10.1007/s10557-025-07759-1

J Neurol. 2025 Aug 22;272(9):587. doi: 10.1007/s00415-025-13328-1.

ABSTRACT

BACKGROUND: Primary Lateral Sclerosis (PLS) is a rare, adult-onset neurodegenerative disease that predominantly affects upper motor neurons. Despite being considered mostly sporadic, familial cases and rare genetic variants in genes associated with amyotrophic lateral sclerosis, hereditary spastic paraplegia and other neurological disorders have been reported in some PLS cases. Due to its rare prevalence among general population, large genetic studies of PLS are lacking.

METHODS: Fifty patients diagnosed with PLS based on consensus criteria were enrolled between 2013 and 2022 for comprehensive phenotypic and genotypic analysis using whole genome sequencing. We analyzed rare single nucleotide variants (SNVs), deemed pathogenic, likely pathogenic or of uncertain significance (VUS) based on the American College of Medical Genetics and Genomics criteria, and repeat expansions (REs) exceeding the pathogenic threshold, in 290 genes involved in neurological disorders.

RESULTS: We identified mutations in 7 patients (13.7%), specifically SNVs in CAPN1 (Spastic paraplegia 76), TBK1 (amyotrophic lateral sclerosis/frontotemporal dementia, ALS4/FTD), LITAF (Charcot-Marie-Tooth disease 1C), POLG (chronic progressive external ophthalmoplegia), APP (Alzheimer’s disease) and OPTN (ALS12 ± FTD), and one RE in ATXN8OS (spinocerebellar ataxia 8). Additionally, two VUS were found in ANTXR2, a candidate gene for PLS recently identified via truncating variant collapsing analysis, but none of them was loss-of-function (one synonymous and one in-frame insertion).

CONCLUSIONS: Our study demonstrates a notable genetic intersection between PLS and various neurological disorders, including motor neuron diseases, neuropathies, mitochondrial disorders, ataxias, and dementias. These findings underscore the relevance of further investigation in larger cohorts to fully elucidate PLS genetic architecture and highlight the need to reconsider the role of genetic testing in its diagnostic criteria.

PMID:40844737 | DOI:10.1007/s00415-025-13328-1

J Health Popul Nutr. 2025 Aug 21;44(1):304. doi: 10.1186/s41043-025-01041-8.

ABSTRACT

BACKGROUND: Uncontrolled type 2 diabetes mellitus warrant the utilization of different combination antidiabetic therapies, however, the addition of these newer agents as add-on therapy increases the risk of side effects and needs to be further investigated in terms of their risk to benefit to the patient. Therefore, the current study aims to evaluate the clinical and safety outcomes in patients taking empagliflozin and Sitagliptin in addition to metformin.

METHOD: A cross-sectional study was conducted using a non-probability consecutive sampling technique to gather data at the Diabetes and Foot Care Clinic in Abbottabad from July 2023 to December 2023. This is an exploratory observational study in which a total of 155 study participants were selected and divided into two groups: Group A, treated with Sitagliptin add-on Metformin (n = 79), and Group B, treated with Empagliflozin add-on Metformin (n = 76), Biochemical parameters (HbA1c, serum creatinine) were collected and eGFR was calculated at baseline and after a 3-month follow-up. All statistical analyses were performed using IBM SPSS version 23.

RESULTS: Among the participant’s majority (53.5%) were males whereas the mean age of the participants was 51.7 ± 10.5 years. Baseline HbA1c and serum creatinine of all the patients were found to be 9.5 ± 1.8% and 1.02 ± 0.2 mg/dL respectively. There was a statistically significant decrease in mean HbA1c values in both the groups at baseline and follow-up (p < 0.001) whereas both the groups were found to be similar in their ability to reduce HbA1c (p = 0.25). Furthermore, there was a statistically significant decrease in serum creatinine values in both the groups at baseline and follow-up (p = 0.002) whereas Empagliflozin add-on Metformin was found to have more ability to reduce serum creatinine (p = 0.01) as compared to Sitagliptin add-on Metformin (p = 0.06). As a result, Empagliflozin add-on Metformin improved the patients’ eGFR significantly (p = 0.001).

CONCLUSION: Empagliflozin as add on therapy in uncontrolled T2DM provided improvements in patients HbA1c, serum creatinine, and eGFR hence improving overall clinical outcomes and patient safety.

PMID:40842035 | DOI:10.1186/s41043-025-01041-8