Citations

Interest in the potential applications of artificial intelligence in medicine, anesthesiology, and the world at large has never been higher. The Anesthesia Research Council steering committee formed an anesthesiologist artificial intelligence expert workgroup charged with evaluating the current state of artificial intelligence in anesthesiology, providing examples of future artificial intelligence applications and identifying barriers to artificial intelligence progress. The workgroup’s findings are summarized here, starting with a brief introduction to artificial intelligence for clinicians, followed by overviews of current and anticipated artificial intelligence–focused research and applications in anesthesiology. Anesthesiology’s progress in artificial intelligence is compared to that of other medical specialties, and barriers to artificial intelligence development and implementation in our specialty are discussed. The workgroup’s recommendations address stakeholders in policymaking, research, development, implementation, training, and use of artificial intelligence–based tools for perioperative care.

Abstract Studies assessing genetic associations with neuropathological features in Lewy body disease (LBD) have been limited to candidate gene investigations, and therefore, information is lacking regarding the genetic architecture of the neuropathology of LBD. In the current study, we examined a large series of neuropathologically confirmed LBD cases (n = 980 in the discovery series, n = 503 in the replication series) and performed genome-wide association studies of 11 different neuropathological outcome measures. The 11 neuropathological outcomes included Braak neurofibrillary tangle (NFT) stage, Thal amyloid phase, LBD subtype, Lewy body (LB) counts in five different brain regions, dorsolateral and ventromedial putaminal tyrosine hydroxylase immunoreactivity and neuronal loss in the ventrolateral part of the substantia nigra. Associations between variants and outcomes were assessed using regression models appropriate for the nature of the given neuropathological outcome and that were adjusted for age at death, sex and top principal components of genetic data. In the discovery series, APOE rs429358 (i.e. APOE ε4) was associated with a greater severity of each of Braak NFT stage [odds ratio (OR) = 3.07, P = 2.34 × 10−32], Thal amyloid phase (OR = 3.57, P = 3.28 × 10−29) and LBD subtype (OR = 1.78, P = 9.85 × 10−9), with similar findings observed in the independent replication series (Braak NFT stage, OR = 2.30, P = 2.70 × 10−11; Thal amyloid phase, OR = 3.17, P = 6.39 × 10−18; LBD subtype, OR = 2.68, P = 3.85 × 10−10). In the subgroup of cases with lower levels of Alzheimer's disease pathology (Braak NFT stage ≤ III and Thal amyloid phase ≤2), there was a strong association between APOE rs429358 and LBD subtype even when adjusting for Braak stage and Thal phase in the discovery series (n = 218, OR = 2.47, P = 0.007) and the replication series (n = 141, OR = 3.60, P = 0.006). Although additional genome-wide significant associations were identified in the discovery series between LINC01581/MCTP2 rs547411734 and lower middle frontal LB counts, between TLE3 rs3743309 and lower cingulate LB counts, and between GRIN2A/ATF7IP2 rs1097915 and lower parahippocampal LB counts, these findings were not observed in the replication series. Our results indicate that the APOE ε4 allele is the most prominent genetic determinant of severity of neuropathology in LBD. These findings represent a key step forward in our understanding of genetic drivers of neuropathological features in LBD. Future studies utilizing meta-analytical approaches will be important to more precisely assess other associations that were not quite genome-wide significant in the discovery series.

Abstract Objective Dravet syndrome (DS) is a developmental and epileptic encephalopathy. Diagnosis is clinical, but ~90% of patients have pathogenic variants in SCN1A . ATP6V0C has recently been proposed as a novel candidate gene for epilepsy, with or without developmental delay. Here we describe two adult patients with a clinical diagnosis of DS associated with ATP6V0C variants. Methods Patients with developmental and epileptic encephalopathies were evaluated by physicians who are experts in DS, and their clinical diagnosis was correlated with genetic findings. A subgroup of those patients with DS but without known genetic causes were evaluated through gene panels, whole exome sequencing, and chromosome microarray. Phenotype was determined by pediatric and adult chart reviews, interviews, and physical examinations. Results Of 753 patients with DS, two unrelated individuals with classic features of DS during childhood and adulthood were identified with heterozygous de novo missense variants in ATP6V0C (c.319G > C, p.(Gly107Arg) and c.284C > T, p.(Ala95Val), respectively). Both variants were absent in normal populations and computational prediction algorithms suggested deleterious effects on protein structure and/or function. No disease‐causing variants in other genes previously associated with DS were found. Significance Here we describe two adult patients with Dravet‐like syndrome and pathogenic/likely pathogenic variants in ATP6V0C . We propose that abnormal ATP6V0C function can, at the severe end of the clinical spectrum, be associated with Dravet‐like phenotype. This is relevant, as these patients would not qualify for disease‐modifying antisense nucleotide or gene therapies targeting SCN1A .

ABSTRACTOf the many burdens cancer patients face, the impact on personal finances is often invisible to clinicians. Financial toxicity refers to the negative impact on patients’ and families’ quality of life due to a combination of high out‐of‐pocket costs of medical treatment, diminished savings, and psychological distress as a result of diminished finances. Financial toxicity in cancer care has been more closely examined in the standard‐of‐care setting. Financial toxicity in the early phase clinical trial setting, and the ethical implications of making patients pay out of pocket to access experimental interventions that may not have therapeutic benefit, have yet to be explored. This article seeks to highlight hidden costs of clinical trial participation in the U.S., and to illustrate how patients are susceptible to financial toxicity from nonmedical direct costs and indirect costs even though a trial intervention itself is not charged to the patient. We argue that not informing prospective participants of the potential costs of trial participation threatens their autonomy and interferes with researchers’ prima facie duties to beneficence and nonmaleficence.

Abstract Chronic headache is a common complication after mild traumatic brain injury (mTBI), which affects close to 70 million individuals annually worldwide. This study aims to test the utility of a unique, early predictive magnetic resonance imaging (MRI)-based classification model using structural brain MRI scans, a rarely used approach to identify high-risk individuals for post-mTBI chronic pain. We recruited 227 patients with mTBI after a vehicle collision, between March 30, 2016 and December 30, 2019. T1-weighted brain MRI scans from 128 patients within 72 hours postinjury were included and served as input for a pretrained 3D ResNet-18 deep learning model. All patients had initial assessments within the first 72 hours after the injury and performed follow-ups for 1 year. Chronic pain was reported in 43% at 12 months postinjury; remaining 57% were assigned to the recovery group. The best results were achieved for the axial plane with an average accuracy of 0.59 and an average area under the curve (AUC) of 0.56. Across the model's 8 folds. The highest performance across folds reached an AUC of 0.78, accuracy of 0.69, and recall of 0.83. Saliency maps highlighted the right insula, bilateral ventromedial prefrontal cortex, and periaqueductal gray matter as key regions. Our study provides insights at the intersection of neurology, neuroimaging, and predictive modeling, demonstrating that early T1-weighted MRI scans may offer useful information for predicting chronic head and neck pain. Saliency maps may help identify brain regions linked to chronic pain, representing an initial step toward targeted rehabilitation and early intervention for patients with mTBI to enhance clinical outcomes.

Abstract Objectives Sleep disturbance is a key symptom of fibromyalgia and a risk factor for chronic widespread pain. This systematic review and meta-analysis aims to assess the effectiveness of pharmacological treatments and cognitive behavioural therapy (CBT) in improving sleep quality in fibromyalgia patients. Methods A systematic search of PubMed, MEDLINE, Embase, Cochrane CENTRAL and CINAHL was conducted for randomized controlled trials (RCTs) published up to April 2023. Studies assessing pharmacological or CBT interventions with sleep-related outcomes were included. Data were extracted, and meta-analyses were performed where applicable. Study quality and bias were evaluated using the Cochrane Risk of Bias tool. Results Forty-seven RCTs, including 11 094 participants, were reviewed. CBT for insomnia (CBT-I) showed a significant improvement in sleep quality (SMD −0.63, 95% CI −0.98 to −0.27), while CBT for pain (CBT-P) had no significant impact. Pharmacological agents such as pregabalin and sodium oxybate moderately improved sleep, but there was uncertainty around this evidence. Amitriptyline, milnacipran and duloxetine showed no significant benefit for sleep. Study heterogeneity was moderate, and no publication bias was detected. Conclusion CBT-I is a promising treatment for enhancing sleep quality in fibromyalgia. Pharmacological treatments like pregabalin may be beneficial but should be used cautiously due to potential risks. Future research should prioritize trials focusing on sleep as a primary outcome and explore the comparative effectiveness of pharmacological treatments and CBT-I in fibromyalgia. Understanding the mechanisms linking sleep and fibromyalgia will also help guide future therapies.

ABSTRACTOverviewSex and gender have emerged as central modifiers of disease biology, phenotype, and clinical outcomes in myeloproliferative neoplasms (MPNs). This review will uniquely highlight issues affecting women with MPN and articulate their relevant determinants.Epidemiology and DiagnosisA higher overall prevalence of MPN has been established in women. The incidence of essential thrombocythemia (ET) predominates, while, conversely, polycythemia vera (PV) and myelofibrosis (MF) are seen in lower frequencies as compared to men. Diagnostic criteria are dictated by sex‐driven physiological variances in hemoglobin and hematocrit levels in PV, mandating separate diagnostic thresholds, respectively: > 16.0 g/dL and > 48% in women vs. > 16.5 and > 49% in men.Genetic Framework and PhenotypeWomen with MPN harbor fewer acquired somatic mutations and a lower frequency of high‐risk mutations than their male counterparts; lower JAK2V617F driver variant allele frequency and attenuated allele burden kinetics have also been reported. Women with MPN are younger at diagnosis than men and, contingent on subtype, display more indolent disease features. Importantly, validated symptom burden assessments consistently disclose higher scores in women vs. men.Thrombosis and OutcomesWomen with MPN have a unique thrombotic diathesis with respect to men, more frequently involving the splanchnic venous system in those ultimately diagnosed with PV. Outcomes data depict female sex as a variable associated with more favorable clinical trajectories, including lower rates of MF/leukemic transformation and secondary cancers, as well as improved overall survival rates vis‐à‐vis men.Life‐Cycle Windows, Pregnancy, and PostpartumPotential challenges at each significant life stage will be addressed: puberty, preconception and fertility, and perimenopause; these include issues surrounding oral contraceptives and hormone use. Prospective studies suggest overall favorable maternal and fetal outcomes with pregnancy in women with MPN. Full details on risks and reported outcomes will be discussed, as well as a risk‐adapted approach to management informed by obstetric and thrombosis history. Recommendations include aspirin 81 mg daily in all patients and cytoreduction with interferon‐α in those with antecedent thrombosis, as well as in low‐risk cases with higher‐risk features (e.g., poorly controlled hematocrit and recurrent fetal loss). Antepartum anticoagulation with low molecular weight heparin (LMWH) is recommended in cases with previous venous thromboembolism.Conclusions and Future DirectionsThis review highlights female sex and gender as critical drivers of MPN incidence, presentation, and natural history. It further outlines the impact and management of MPN as related to unique female reproductive phases. A sex‐informed lens will be required in order to recalibrate current prognostic tools, a requisite to refining patient counselling and clinical decision‐making in line with precision medicine. Moreover, while several mechanisms underpinning sex‐defined discrepancies have been defined, these mandate further prospective study. Finally, sex and gender‐based differences must be weighted in clinical trials with systematized procedures to correct participation imbalances in favor of sex and gender equity.

Abstract Hip arthroscopy is a technically demanding procedure that can require a substantial volume of irrigation fluid. Techniques should be explored to optimize fluid use while ensuring satisfactory surgical instrumentation and labral repair. In this technical note, we present a method for performing a dry arthroscopic labral repair. This technique can be used in the treatment of a variety of labral pathologies, including primary labral repair with knotless or hand‐tied anchors, revision labral repair, and labral reconstruction, without the need for irrigation fluid. Additionally, we discuss supplemental techniques that can be used during other portions of the arthroscopic hip procedure to limit irrigation fluid use. Technique Video video See video under supplementary data.

Abstract The standard of care for hip labral tears is arthroscopic repair, with labral reconstruction performed more commonly for irreparable tears in order to avoid isolated labral debridement. However, labral reconstruction can be technically demanding. We provide a concise step‐by‐step guide for performing labral reconstruction or augmentation using a modified retrograde pull‐through technique, including tips, tricks, and surgeon pearls, and pitfalls. Despite the procedure's technically challenging nature, we believe our technique highlights several important steps to improve the practicality and efficiency of the case and produce satisfactory patient outcomes. Technique Video video See video under supplementary data.