Citations

Microglia actively survey the brain and dynamically interact with neurons to maintain brain homeostasis. Microglial Gi protein–coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, the impact of temporally activating microglial Gi signaling on microglial dynamics and neuronal activity in the homeostatic brain remains largely unknown. In this study, we used Gi-based designer receptors exclusively activated by designer drugs (Gi-DREADD) to selectively and temporally modulate microglial Gi signaling pathway. By integrating this chemogenetic approach with in vivo two-photon imaging, we observed that exogenous activation of microglial Gi signaling transiently inhibited microglial process dynamics, reduced neuronal activity, and impaired neuronal synchronization. These altered neuronal functions were associated with a decrease in interactions between microglia and neuron somata. Together, this study demonstrates that acute, exogenous activation of microglial Gi signaling regulates neuronal circuit function, offering a potential pharmacological target for the neuromodulation through microglia.

Transcatheter aortic valve replacement (TAVR) was introduced in 2002 and has become integral in the management of aortic stenosis. As an alternative to surgical aortic valve replacement, it relies heavily on safe access to the aortic annulus for implantation of a valve prosthesis. Throughout its development and in current practice, the transfemoral (TF) arterial route for retrograde valve delivery has been the primary approach. However, this route is not appropriate for all patients, which has led to the development of multiple alternate access options. This review discusses the development of access for TAVR, followed by a thorough discussion of TF access. The commercially available products, preprocedural planning, closure techniques, and procedural complications are all discussed. We also describe the various alternate access routes with particular emphasis on the most recently developed route, transcaval access (TCv), with focus on procedural indications, technical considerations, and comparative outcomes. As TAVR technology, indications, and availability all expand, the knowledge and implementation of safe access are of utmost importance.

Background Intra-articular corticosteroid (IACS) injection and peri-articular corticosteroid injection are commonly used to treat musculoskeletal conditions. Results vary by musculoskeletal region, but most studies report short-term benefit with mixed results on long-term relief. Publications showed adverse events from single corticosteroid injections. Recommended effective doses were lower than those currently used by clinicians. Methods Development of the practice guideline for joint injections was approved by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine and the participating societies. A Corticosteroid Safety Work Group coordinated the development of three guidelines: peripheral nerve blocks and trigger points; joints; and neuraxial, facet, and sacroiliac joint injections. The topics included safety of the technique in relation to landmark-guided, ultrasound-guided, or radiology-aided injections; effect of the addition of the corticosteroid on the efficacy of the injectate; and adverse events related to the injection. Experts on the topics were assigned to extensively review the literature and initially develop consensus statements and recommendations. A modified version of the US Preventive Services Task Force grading of evidence and strength of recommendation was followed. A modified Delphi process was adhered to in arriving at a consensus. Results This guideline focuses on the safety and efficacy of corticosteroid joint injections for managing joint chronic pain in adults. The joints that were addressed included the shoulder, elbow, hand, wrist, hip, knee, and small joints of the hands and feet. All the statements and recommendations were approved by all participants and the Board of Directors of the participating societies after four rounds of discussion. There is little evidence to guide the selection of one corticosteroid over another. Ultrasound guidance increases the accuracy of injections and reduces procedural pain. A dose of 20 mg triamcinolone is as effective as 40 mg for both shoulder IACS and subacromial subdeltoid bursa corticosteroid injections. The commonly used dose for hip IACS is 40 mg triamcinolone or methylprednisolone. Triamcinolone 40 mg is as effective as 80 mg for knee IACS. Overall, IACS injections result in short-term pain relief from a few weeks to a few months. The adverse events include an increase in blood glucose, adrenal suppression, detrimental effect on cartilage lining the joint, reduction of bone mineral density, and postoperative joint infection. Conclusions In this practice guideline, we provided specific recommendations on the role of corticosteroids in joint, bursa, and peritendon injections for musculoskeletal pain.

AbstractBackgroundColon cancer patients have inferior overall survival than a matched general population (MGP). It is unknown if physical activity is associated with a reduction in this survival disparity.MethodsData were analyzed from two National Cancer Institute–sponsored postoperative treatment trials in stage III colon cancer, Cancer and Leukemia Group B (CALGB) 89803 and 80702, with 2876 patients who self‐reported physical activity. Physical activity was converted to metabolic equivalents (MET‐hours/week). The MGP was derived from the National Center for Health Statistics and matched on age, sex, and year.ResultsIn CALGB 89803, among patients who were alive at 3 years, those with <3.0 and ≥18.0 MET‐hours/week had subsequent 3‐year overall survival rates that were −17.1% (95% confidence interval [CI], −22.4 to −11.8) and −3.5% (95% CI, −7.7 to 0.3) lower than MGP, respectively. In CALGB 80702, among patients who were alive at 3 years, those with <3.0 and ≥18.0 MET‐hours/week had subsequent 3‐year overall survival rates that were −10.8% (95% CI, −15.4 to −6.9) and −4.4% (95% CI, −7.6 to −1.6) lower than MGP, respectively. In pooled analyses, among patients who were alive and did not have tumor recurrence by year 3 (n = 1908), those with <3.0 and ≥18.0 MET‐hours/week had subsequent 3‐year overall survival rates that were −3.1% (95% CI, −6.2 to −0.3) lower and 2.9% (95% CI, 1.5–4.2) higher than MGP, respectively.ConclusionsPhysical activity is associated with an attenuation of the survival disparity between patients with stage III colon cancer participating in clinical trials and MGP. Colon cancer survivors who are physically active may achieve survival that approximates the MGP.

AbstractDevelopmental and epileptic encephalopathies (DEEs) are a group of rare, severe, early-onset epilepsies characterized by pharmacoresistance, marked electroencephalographic abnormalities, and delayed or regressive psychomotor development. DEEs are associated with poor long-term outcomes and increased mortality; however, early recognition and targeted treatment can impact neurodevelopmental outcomes and overall quality of life. Treatment with antiseizure medication is often challenging given drug resistance, chronic polypharmacy, and medication interactions. With advances in genetic testing and increased understanding of the neurobiological mechanisms of DEEs, the treatment approach is evolving and includes repurposed antiseizure medications and targeted therapies, as well as early surgical intervention in select patients. In addition to high seizure burden and neurodevelopmental delay, DEEs are associated with comorbidities affecting a range of body systems; these can include intellectual disability, psychiatric disorders, motor dysfunction, and respiratory and gastrointestinal problems. Over time, these comorbidities increase the complexity of management and have important implications on the disease burden and quality of life for both patients and their caregivers. Multidisciplinary care in DEEs is paramount. We summarize the current evidence on the management of specific DEEs, focusing on targeted therapies and optimizing outcomes.

BACKGROUND: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging–detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach. METHODS: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left ventricular arrhythmias undergoing catheter ablation procedures were randomly assigned to a transseptal puncture approach compared (1:1) with a retrograde aortic approach. The primary outcome was the presence of an acute brain lesion detected by magnetic resonance imaging. Secondary outcomes included clinically manifest complications, procedural efficacy, and 6-month neurocognitive assessments. RESULTS: Among the 62 patients randomly assigned to a retrograde aortic approach with postoperative brain magnetic resonance imaging, 28 (45%) exhibited an acute brain lesion compared with 19 of the 69 (28%) of those randomized to a transseptal puncture ( P =0.036). No differences in clinically manifest complications or procedural efficacy were observed. More patients in the retrograde aortic arm were categorized as having a high likelihood of cognitive impairment at 6 months (33% compared with 19% of those in the transseptal arm), but substantial loss to follow-up was present. CONCLUSIONS: Among patients undergoing left ventricular catheter ablation procedures, a transseptal approach reduced the risk of acute brain lesions by nearly half compared with a retrograde aortic approach without sacrificing safety or efficacy. Given a likely embolic pathogenesis, the brain magnetic resonance imaging findings may reflect a propensity to other organ damage; these findings may extend to other procedures requiring left ventricular entry. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03946072.

Importance Semaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D). Objective To investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network. Design, Setting, and Participants This was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non–GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion and rate of NAION were calculated. Association between semaglutide and NAION was assessed using 2 approaches: an active-comparator cohort design comparing new users of semaglutide with those taking other GLP-1RAs and non–GLP-1RA drugs, and a self-controlled case-series (SCCS) analysis to compare individuals’ risks during exposure and nonexposure periods for each drug. The cohort design used propensity score–adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). Network-wide HR and IRR estimates were generated using a random-effects meta-analysis model. Exposures GLP-1RA and non–GLP-1RAs. Main Outcomes and Measures NAION under 2 alternative definitions based on diagnosis codes: one more inclusive and sensitive, the other more restrictive and specific. Results The study included 37.1 million individuals with T2D, including 810 390 new semaglutide users. Of the 43 620 new users of semaglutide in the Optum’s deidentified Clinformatics Data Mart Database, 24 473 (56%) were aged 50 to 69 years, and 26 699 (61%) were female. The incidence rate of NAION was 14.5 per 100 000 person-years among semaglutide users. The HR for NAION among new users of semaglutide was not different compared with that of the non–GLP-1RAs using the sensitive NAION definition—empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25). The risk was higher only compared with patients taking empagliflozin (HR, 2.27; 95% CI, 1.16-4.46; P = .02) using the specific definition. SCCS analysis of semaglutide exposure showed an increased risk of NAION (meta-analysis IRR, 1.32; 95% CI, 1.14-1.54; P &amp;lt; .001). Conclusions and Relevance Results of this study suggest a modest increase in the risk of NAION among individuals with T2D associated with semaglutide use, smaller than that previously reported, and warranting further investigation into the clinical implications of this association.

BACKGROUND AND OBJECTIVES: Transforaminal lumbar interbody fusion (TLIF) allows for direct and indirect decompression and segmental lordosis in sagittal plane correction. This study compares the effectiveness of “Bullet” type and “Banana” type devices for sagittal plane correction. METHODS: Patients who underwent 1-level or 2-level TLIF for degenerative pathology at a single tertiary care center were identified. Details were extracted on demographics, interbody dimensions, and preoperative and postoperative lumbopelvic parameters from upright radiographs. Cages were categorized as “Bullet” or “Banana” type based on morphology and manufacturer description of optimal position. Univariable comparisons between levels treated with “Bullet” and “Banana” type interbodies were performed. Multivariable linear regression was performed to identify independent predictors of postoperative segmental lordosis and change in segmental lordosis. RESULTS: One hundred and ninety eight unique patients (median 66.6 years; [IQR 59.5, 73.7]; 56.6% female) were included with 241 levels treated, of which 114 (52.7%) were treated with “Banana” type interbodies and 127 (47.3%) with “Bullet” type. “Banana” type interbodies afforded both greater postoperative segmental lordosis (8.1 [6.2, 10.7] vs 7.5 [5.2, 9.6]; P = .048) and greater increase in segmental lordosis (3.3 [0.7, 7.0] vs 2.3 [0.1, 4.2]; P = .015). On multivariable linear regression, only preoperative segmental lordosis (β = 0.322 per degree; [0.244, 0.399]; P < .001), implant listed lordosis (β = 0.146 per degree; 95% CI [0.048, 0.244]; P = .004), preoperative pelvic incidence (0.072 per degree; [0.034, 0.111]; P < .001), and use of bilateral TLIF windows (β = 3.133; [1.213, 5.053]; P = .001) were predictive of postoperative segmental lordosis. CONCLUSION: The present analysis suggests that baseline lumbopelvic anatomy, interbody lordosis, and the use of bilateral TLIF windows are the most important predictors of postoperative segmental lordosis. Use of “Banana” vs “Bullet” type interbodies was not predictive of segmental lordosis achieved on immediate postoperative upright radiographs. Further work is merited to determine whether the 2 interbody types demonstrate differences regarding subsidence risk or maintenance of correction.

Objective: To assess patient radiation exposure as reflected by cumulative air kerma (CAK) and dose area product (DAP) during fenestrated-branched endovascular aortic repair (FB-EVAR). Background: Patient radiation exposure during FB-EVAR has been reported inconsistently. Methods: Data from 2,111 patients enrolled in 10 physician-sponsored investigational device exemption studies (2012-2022) were analyzed from the United States Aortic Research Consortium database. Procedures were performed using seven fixed imaging systems (A to G). Patients were classified into three groups by imaging era: 2012-2015 (Group 1), 2016-2018 (Group 2), and 2019-2022 (Group 3). Primary endpoints were CAK and DAP risk factors, assessed using linear mixed-effect models. Secondary endpoints were diagnostic reference levels (DRL) for FB-EVAR. Results: Of the 2,111 patients (71% males; mean 74±9 years years-old) treated by FB-EVAR; 263 (12%) were in Group 1, 541 (26%) in Group 2, and 1,307 (62%) in Group 3. Use of ≥4 vessel stent-graft designs increased from 69% (Group 1) to 79% (Group 3) ( P <0.001). Median CAK decreased from 3,644 mGy (Group 1) to 1,753 mGy (Group 3), and DAP from 441 Gy.cm² to 208 Gy.cm² ( P <0.001). Higher BMI, iliac branch device (IBD) use, and longer fluoroscopy time (FT) were associated with increased CAK and DAP, while experienced operators and systems D, F, and G were protective ( P <0.05). DRLs for Group 3 were 2,800 mGy (CAK) and 340 Gy.cm² (DAP). Conclusions: Radiation exposure during FB-EVAR significantly decreased over time. Higher BMI, IBD use, and FT were linked to increased exposure, while experienced operator and System D, F or G were protective. Trial registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02043691 NCT00583817 NCT00483249 NCT01937949 NCT02050113 NCT02323581 NCT01874197 NCT01654133 NCT02266719.

OBJECTIVE It is not clear whether smoking impacts patient-reported outcomes (PROs) in patients with cervical spondylotic myelopathy (CSM). The aim of this study was to explore the impact of smoking status on baseline symptom severity and the rate of achieving satisfaction and the minimal clinically important differences (MCIDs) for PROs in patients with CSM. METHODS This study was an analysis of the prospective Quality Outcomes Database CSM module. Patients aged ≥ 18 years diagnosed with primary CSM who underwent elective surgery were included. PROs (visual analog scale [VAS] neck and arm pain, Neck Disability Index [NDI], modified Japanese Orthopaedic Association [mJOA], and EQ-5D scores and North American Spine Society [NASS] patient satisfaction) were collected at baseline and 24 months of follow-up. RESULTS Of the 1141 patients with CSM, 202 (17.7%) were smokers and 939 (82.3%) were nonsmokers. Compared with the nonsmokers, smokers were younger (56.3 ± 11.3 years vs 61.5 ± 11.7 years, p < 0.01) and had a lower BMI (29.3 ± 6.8 vs 30.3 ± 6.3, p = 0.04). A higher proportion of smokers had depression, anxiety, and chronic obstructive pulmonary disease (all p < 0.01). At baseline, smokers had worse pain (VAS neck pain score: 6.0 ± 3.2 vs 5.1 ± 3.3; VAS arm pain score: 5.7 ± 3.2 vs 4.7 ± 3.5), disability (NDI score: 45.2 ± 20.0 vs 37.1 ± 20.6), myelopathy (mJOA score: 11.5 ± 2.9 vs 12.2 ± 2.8), and quality of life (EQ-5D score: 0.51 ± 0.23 vs 0.57 ± 0.22) (all p < 0.01). At the 24-month follow-up, a higher proportion of smokers achieved the MCID in mJOA (69.4% vs 56.6%, p < 0.01) compared with nonsmokers. However, after accounting for significant covariates, there was no significant difference in the baseline disease severity. There was also no difference between the PROs at the 24-month follow-up. The two groups also achieved similar MCIDs for most PROs and were similarly satisfied (NASS score of 1 or 2: smoker 81.2% vs nonsmoker 84.6%, p = 0.29) 24 months after surgery. CONCLUSIONS Smokers and nonsmokers with CSM had similar baseline disease severity and 24-month PROs. They also achieved similar rates of MCIDs for PROs and satisfaction after surgery. Numerous previous studies have documented the association between tobacco usage and inferior clinical outcomes after spine surgery. However, in the context of severe and debilitating spinal disorders such as cervical myelopathy, meaningful and impactful improvements are still seen in properly selected patients.