Faculty Bibliography

BACKGROUND/UNASSIGNED:"Never Events" (<1/1000) likely never occur without a breach in the standard of care (SOC), while "Near Never Events" (<1/100) are typically not far behind. METHODS/UNASSIGNED:"Never Events" are described as "Harmful hospital-acquired conditions that the Center for Medicare and Medicaid Services identified in 2008." Here, we focused on wrong-site spine surgery (WSSS)/wrong-level spine surgery (WLSS), 3 select cases of Caspar Distraction Screws causing hematomas, and one medicolegal case involving multiple simultaneous "Never Events." RESULTS/UNASSIGNED:The spine literature documented the following frequencies of wrong-site spine surgery WSSS/"Never Events" as occurring in 4.5/10,000 lumbar, 6.8/10,000 cervical, and 2.2/10,000 cranial procedures; other series focused on the incidence of wrong-level spine surgery (WLSS). Three "Never Events" consisting of cervical epidural hematomas were attributed to Caspar Distraction Screws. A medicolegal case is also presented in which a spine surgeon caused multiple simultaneous "Never Events" (i.e., ipsilateral surgical errors) during an anterior cervical fusion. Finally, the definition of "Never Events" was newly expanded to better assess "Near Never Events", as the latter applied to varied frequencies of esophageal perforations, plate/screw migration/erosions/displacement, cerebrospinal fluid leaks, infection, and other factors. CONCLUSION/UNASSIGNED:"Never Events" (<1/1000) likely never occur without a breach in the SOC, while "Near Never Events" (<1/100) are typically not far behind.

The atopic dermatitis (AD) Yardstick articles aim to provide an up-to-date review of AD therapy for clinicians. The first two AD Yardstick articles were published in 2018 and 2023. Since the last update, multiple medications have been added to armamentarium of AD. These include roflumilast cream, tapinarof cream, lebrikizumab and nemolizumab. In the current AD Yardstick article, we aim to provide evidence-based information on these new treatments, as well as updated information on previously reviewed therapy. A new feature of the AD Yardstick article is the addition of patient vignettes, which provide practical guide and clinical pearls for clinicians.

BACKGROUND/UNASSIGNED:The placement of Spinal Cord Stimulator (SCS) trial or permanent electrodes carries a 31.9-43% morbidity/adverse event (AE) rate. Most AEs are attributed to electrode migration (EM: device-related AE 26.7% older cohort vs. 9.7% newer cohort), spinal epidural hematomas (SEHs: 0.81-2.6%), infection (3.4% older vs. 1.9% recent cohort), SCI (spinal cord injury: percutaneous 0.45% vs. 0.36% paddle electrodes), dural tears (DT/ cerebrospinal fluid leaks (CSF leaks)), foreign body/fibrous reactions, or syrinx formation. METHODS/UNASSIGNED:SCSs are typically applied to address chronic neuropathic pain syndromes. Here, we evaluated 20 articles focusing on patients who developed postoperative myelopathy/radiculopathy, variously attributed to MR-documented AE warranting medical or surgical intervention. RESULTS/UNASSIGNED:Postoperative symptoms/signs of AE typically included the acute development of new/increased weakness, sensory loss, and/or sphincter dysfunction. Requisite STAT MR scans usually confirmed the etiology of AE including electrode migration, SEH, DT, SCI, and/or postoperative scarring/fibrosis. Most patients warranted STAT surgery, while a small subset could be managed conservatively. CONCLUSION/UNASSIGNED:The AE rate for spinal cord stimulators ranges from 31.9 to 43%. While the majority are due to electrode migration, other etiologies include SEH, SCI, DT, and foreign body reactions. Those who become acutely myelopathic usually warrant STAT MR scans with the majority additionally necessitating STAT surgical intervention to limit short/long-term neurological morbidity.

BACKGROUND/UNASSIGNED:Intraoperative Neural Monitoring (IONM) is mandatory for performing anterior (i.e., transthoracic) or lateral extracavitary approaches to significant anterior/anterolateral thoracic ossification of the posterior longitudinal ligament (TOPLL) (i.e. often misdiagnosed as calcified Thoracic Disc Herniations) (TDH). Notably, the remaining "posterior procedures" (i.e. laminectomy, transpedicular, and costotransversectomy) are contraindicated for treating significant anterior/anterolateral TOPLL as they result in unacceptably high frequencies of spinal cord injury (SCI) typically correlated with significant intraoperative IONM losses. METHODS/UNASSIGNED:A review of multiple studies documented that IONM (i.e. especially Tc-MEP (Transcranial Motor Evoked Potentials)) is mandatory when performing anterior transthoracic or lateral extracavitary approaches to TOPLL. This is because IONM alerts signaling the onset of SCI may likely be remediated (i.e. minized vs. limited) utilizing appropriate resuscitative maneuvers. Alternatively, extremely high frequencies of significant IONM losses occurring with "posterior procedures" carried a much higher risk of permanent/irreversible neurological injury. RESULTS/UNASSIGNED:Multiple studies documented that IONM should be used with anterior transthoracic or lateral extracavitary approaches to anterior/anterolateral TOPLL surgery, and that "posterior procedures" were largely contraindicated. In one series, significant amplitude Tc-MEP losses occurred in 73% of posterior decompressions; 39% developed Tc-MEP amplitude losses, that correlated with new SCI. In another study of 249 TOPLL patients undergoing "posterior only operations", 50 developed new significant IONM alerts (i.e. of deterioration); only 40% (20/50) were successfully resuscitated. Overall, initiating immediate resuscitative maneuvers in response to IONM occurring during various types of TOPLL surgery can avert SCI in up to 10.4%, to 40%, to 57% of cases. CONCLUSION/UNASSIGNED:IONM is mandatory for anterior/anterolateral TOPLL surgery utilizing anterior transthoracic or lateral extracavitary approaches.

IntroductionBipolar depression is disabling and often inadequately responsive to medication alone. The current efficacy evidence of transcranial magnetic stimulation (TMS) for bipolar depression is conflicting. Therefore, we synthesized randomized controlled trials (RCTs) that tested the efficacy, safety, and tolerability of TMS for bipolar depression.MethodsWe searched MEDLINE/EMBASE/Cochrane/PsycINFO/gray literature (01/10/2025) for RCTs comparing any TMS protocol with sham. Co-primary outcomes were depressive symptoms, all-cause discontinuation; secondary outcomes were response, remission. Risk of bias (RoB) was assessed with RoB-2. Random-effects models estimated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95%CI), alongside sensitivity, subgroup, and meta-regression analyses.ResultsNineteen comparisons from 17 RCTs (N = 563; TMS = 293, sham = 270; mean N TMS = 15.4, sham = 15.9; mean duration = 2.40 weeks; RoB "low" = 35%, "some concerns" = 65%) were included. Among trials reporting subtypes (k = 13), 41.8% of participants had bipolar I disorder, and 58.2% had bipolar II disorder. The left dorsolateral prefrontal cortex was the most common target (k = 12). TMS reduced depressive symptoms versus sham (SMD = -0.34; 95%CI = -0.58 to -0.11), with no difference in all-cause discontinuation. TMS was favoured for response (RR = 1.41; 95%CI = 1.10 to 1.80) and remission (RR = 1.54; 95%CI = 1.06 to 2.23). However, these effects were not consistently confirmed in sensitivity or subgroup analyses by RoB, TMS type, stimulation site, or treatment resistance. Overall, 15 comparisons (88.2%) did not show superiority of TMS over sham for depressive symptoms at the individual trial level. No seizures or serious adverse events occurred; adverse events did not differ from sham. Meta-regression suggested a greater number of total pulses was associated with greater depressive symptom reduction (β = -0.018; p = .00017).ConclusionsTMS shows a small meta-analytic antidepressant effect and acceptable tolerability in bipolar depression despite most individual trials being negative. However, subgroups and sensitivity findings did not support TMS as an efficacious treatment at current doses. Further testing via larger RCTs with higher-dose protocols is warranted.

In the phase 3 CEPHEUS study, daratumumab plus bortezomib/lenalidomide/dexamethasone (D‑VRd) increased overall MRD-negativity rates versus VRd in transplant-ineligible/transplant-deferred patients with NDMM. We present an expanded MRD analysis of CEPHEUS. Patients who were transplant-ineligible, or deferred transplant as initial therapy, were randomized 1:1 to receive D-VRd or VRd. Overall MRD negativity (NGS) was defined as the proportion of patients achieving ≥CR and MRD-negative status assessed at 10-5 (primary endpoint) and 10-6 thresholds. A total of 395 patients were randomized (D-VRd, n=197; VRd, n=198). With 58.7-months median follow-up, overall MRD-negativity rates were significantly higher with D-VRd versus VRd (10-5, 60.9% vs 39.4%; OR, 2.37; 95% CI, 1.58-3.55; 10-6, 46.2% vs 27.3%; OR, 2.24; 95% CI, 1.48-3.40; P<0.0001 and P=0.0001, respectively). Sustained MRD negativity (≥12 months) was also significantly higher with D-VRd versus VRd (10-5: 49.2% vs 27.3%; 10-6: 34.0% vs 16.2%; each P<0.0001), with similar benefits at ≥24 and ≥36 months. MRD-negativity rates were higher at all pre-specified timepoints, and cumulatively, with D-VRd versus VRd (10-5 and 10-6). Among patients who achieved MRD negativity, PFS trended in favor of D-VRd versus VRd (10-5, HR, 0.61; 95% CI, 0.35-1.06; P=0.0755; 10-6, 0.66; 95% CI, 0.31-1.41; P=0.2811). Responses with D-VRd are deeper and more durable versus VRd, increasing overall, sustained, and landmark MRD-negativity rates, translating into improved overall PFS for patients treated with D-VRd versus VRd (intent-to-treat), with the potential to improve PFS even among patients who achieve MRD negativity. D-VRd is therefore a new standard-of-care treatment for transplant-ineligible/transplant-deferred NDMM. Registered at www.clinicaltrials.gov: NCT03652064.

INTRODUCTION/BACKGROUND:The oral microbiome may influence brain health and contribute to cognitive decline. However, little evidence exists on the potential modifying role of the oral microbiome in the relationship between tooth loss and cognitive performance. This study aimed to investigate the interaction effects between tooth loss and oral dysbiotic status on cognitive performance. METHODS:Data were from the 2011-2012 National Health and Nutrition Examination Survey. The sample included 677 adults aged 60 to 69 y. Cognitive performance was assessed by the Consortium to Establish a Registry for Alzheimer's Disease, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test. Significant tooth loss was defined as a loss of ≥10 permanent teeth out of 28. A high dysbiotic index was defined as being in the upper tertile of the ratio of periodontal disease-associated bacteria (Treponema, Porphyromonas, and Tannerella) to healthy bacteria (Rothia and Corynebacterium). RESULTS:A multivariable linear regression model showed a significant interaction effect between tooth loss and dysbiotic index on the AFT (b = -1.87, P = 0.03), indicating that participants with a higher dysbiosis index and fewer missing teeth scored lower on the AFT. CONCLUSIONS:The effect of tooth loss on verbal fluency depends on oral bacterial imbalances: if there is significant tooth loss, bacterial imbalances may not be important. However, when fewer teeth are lost, high bacterial imbalances may account for lower verbal fluency. These findings suggest that maintaining periodontal health aimed at decreasing oral dysbiosis should be promoted among older adults in the community.Knowledge Transfer Statement:Our findings highlight the importance of preserving the health of the teeth and not just retaining the teeth. Oral health awareness and good oral hygiene practice should be further promoted among older adults in the community.

INTRODUCTION/BACKGROUND:Hemispherotomy is an effective treatment for children with drug-resistant epilepsy (DRE). While hemispherotomy techniques and indications have evolved, access remains predominantly constrained to high-resource settings. METHODS:We performed a retrospective analysis of children who underwent hemispherotomy from 2011 to 2023 by a hybrid team, including local Panamanian and US neurologists, neurosurgeons, and EEG technicians and analyzed surgical, epilepsy, and quality of life (QoL) parameters. Follow-up data were collected according to the International Consortium for Health Outcomes Measurement (ICHOM) guidelines for children with epilepsy. RESULTS:Twenty-three children underwent hemispherotomy. The median age at surgery was 10 years (range 2-20). The median follow-up time was 6 years (range 1-13). The etiology of DRE included malformations of cortical development in 14 children (60.8%), including 8 (34.8%) with schizencephaly, and secondary causes in 9 children (39.1%). Seizure frequency improved for all 23 children (100%): Engel I was achieved in 15 children (65.2%), Engel II (26.1%) in six children, and Engel III (8.7%) in two children. Patients with seizure freedom had significantly fewer preoperative seizures per day than patients with seizure recurrence. Complications occurred in six children (26.1%): 2 wound infections, 2 meningitis, 1 femoral vein thrombosis, and 1 wound hematoma with return to OR. There were no perioperative mortality and no postoperative hydrocephalus or CSF diversion. QoL-related outcomes were available for 16 children: 16/16 (100%) reported that the surgery was a worthwhile and repeatable choice, 14 (87.5%) reported improved cognitive function, the median QOLCE-16 score was 62.5 ± 21. CONCLUSION/CONCLUSIONS:Hemispherotomy for DRE in selected children is a safe and effective surgery in a public children's hospital in a low-resource setting. At last follow-up, the majority of children were seizure-free, and all children had decreased seizure frequency. Families reported improved cognitive function, improved QoL and high satisfaction with their decision to pursue this surgery.

OBJECTIVE:We implemented and evaluated a novel score called the blunt thoracic trauma score (BTTS) for the triage of chest wall injury (CWI) patients to optimize utilization of the intensive care unit (ICU). METHOD/METHODS:or Fisher's exact test for categorical variables. Logistic/negative binomial regression models were used to find predictors for ICU admission and length of stay (LOS). RESULTS:Six hundred thirty-three patients were included; 407 pre-BTTS/226 post-BTTS. Pre-BTTShigher median ISS (p < 0.001), more rib fractures (p < 0.001). Post-BTTS older (p < 0.001), more comorbidities (coronary artery disease [p = 0.028], hyperlipidemia [p = 0.004], pulmonary disease [p = 0.038]). Post-BTTS cohort had lower rates of ICU admission (p = 0.008), shorter ICU-LOS (p < 0.001), and Hospital-LOS (p < 0.001). Post-BTTS cohort was associated with shorter Hospital-LOS after adjusting for other factors (p = 0.004). CONCLUSIONS:Implementation of a novel BTTS for triage of CWI was associated with decreased ICU admission rates and shorter ICU-LOS and Hospital-LOS. The decreased Hospital-LOS persisted even after controlling for other factors.