Combining Image similarity and Predictive AI Models to Decrease Subjectivity in Thyroid Nodule Diagnosis and Improve Malignancy Prediction.

OBJECTIVES: To evaluate the efficacy of combining predictive artificial intelligence (AI) and image similarity model to risk stratify thyroid nodules, using retrospective external validation study. METHODS: Two datasets were used to determine efficacy of the AI application. One was Stanford dataset ultrasound images of 192 nodules between April 2017 to May 2018 and the second was private practice consisting of 118 thyroid nodule images between January 2018 to December 2023. The nodules had definitive diagnosis by cytology or surgical pathology. The AI application was used to predict the diagnosis and American College of Radiology Thyroid Imaging and Data System (ACR TI-RADS) score. RESULTS: In the Stanford dataset, the AI application predicted malignancies with sensitivity of 1.0 and specificity of 0.55. Positive predictive value (PPV) was 0.18 and negative predictive value (NPV) was 1.0. The Area Under the Curve - Receiver Operating Characteristic (AUC-ROC) was 0.78. ACR TI-RADS based clinical recommendation had a polychoric correlation of 0.67. In the private dataset, the AI application predicted malignancies with sensitivity of 0.91 and specificity of 0.95. PPV was 0.8 and NPV was 0.98. AUC-ROC was 0.93 and accuracy was 0.94. ACR TI-RADS based score had a polychoric correlation of 0.94. CONCLUSION: The AI application showed good performance for sensitivity and NPV between the two datasets and demonstrated potential for 61.5% reduction in the need for fine needle aspiration (FNA) and strong correlation to ACR TI-RADS. However, PPV was variable between the datasets possibly from variability in image selection and prevalence of malignancy. If implemented widely and consistently among various clinical settings, this could lead to decreased patient burden associated with an invasive procedure and possibly to decreased health care spending.

Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities.

Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the TME exhibit substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAFs) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLC's adaptable nature, opening possibilities for reprogramming the TME-tumor communications that shape SCLC tumor states.

Sex and gender differences in lower limb chronic exertional compartment syndrome: a systematic review.

OBJECTIVES: Chronic exertional compartment syndrome (CECS) is a cause of exertional leg pain and has been reported in varying frequencies in males and females. Currently, it is unclear whether there are significant sex and gender differences in lower-limb CECS. Delineating sex and gender differences is vital in determining the causes of CECS and best treatments. This systematic review aimed to determine the sex/gender distribution of CECS and to assess for sex and gender differences in CECS diagnosis and outcomes. METHODS: PubMed (Medline), Cochrane Library, and EMBASE databases were searched for studies that were published from January 2000-March 2022 and reported lower-limb CECS data in males and/or females. Data on CECS diagnosis (intracompartmental pressures) and outcomes (e.g. post-surgical return-to-sport, need for re-operation) with sex/gender breakdowns were extracted. The sex/gender distribution of CECS and prevalence of CECS by sex/gender were calculated. RESULTS: Forty-one studies were included in the systematic review; there were 27 retrospective reviews, 8 prospective studies, and 6 retrospective studies with prospective follow-ups. Thirty studies involved surgical populations. Sex/gender distribution of CECS was calculated using data from 24 studies; 51% were female. Prevalence of CECS was available in five studies and ranged widely for males (54%-73%) and females (43%-65%). Intracompartmental pressure data varied by sex/gender. Male athletes were more likely than female athletes to return to sport following surgery for CECS, but variations in all other post-surgical outcomes were observed between sexes and genders in the general population. CONCLUSION: Females represented 51% of the patients who were diagnosed with CECS among studies. Most CECS diagnosis and outcomes data varied by sex/gender, except for post-surgical outcomes data in athletes, which demonstrated that males had higher rates of return to sport than females. Future studies are needed to examine factors contributing to sex and gender differences in CECS diagnosis and outcomes.

Treatment of Interspinous Pain With Extracorporeal Shockwave Therapy: A Case Report.

ABSTRACT: The interspinous region is an atypical source of low back pain, and it can often be difficult to identify. There are many structural components in the interspinous region that can contribute to interspinous pain, including the interspinous ligament, which plays a role in providing stabilization to the spine. Successful treatments of interspinous pain have not been well characterized in the literature. This case presents the first documentation of the use of extracorporeal shockwave therapy as a noninvasive treatment for refractory interspinous-related low back pain. Extracorporeal shockwave therapy has previously been shown to facilitate regeneration and tissue healing in tendons and ligaments but has not previously been used to treat interspinous pain. A 24-yr-old former collegiate softball player presented with 5 mos of low back pain; the interspinous ligament was clinically suspected as a pain generator, and this was confirmed via an ultrasound-guided injection. She underwent a course of physical therapy that improved function but did not improve pain, and nonsteroidal anti-inflammatory drugs only provided minimal and temporary relief. Three consecutive extracorporeal shockwave therapy treatment sessions provided 90% improvement in pain and function, and she was able to return to exercise and recreational sports. At more than 6 mos after extracorporeal shockwave therapy treatment, she reported no recurrences or functional limitations.

A Tale of Bilateral Rapidly Progressive Osteoarthritis of the Hip-It Is Not Always the Steroid Injection: A Case Report.

ABSTRACT: Rapidly progressive osteoarthritis of the hip is an unusual subset of hip osteoarthritis in which a >2 mm/yr rate of joint space narrowing occurs. Rapidly progressive osteoarthritis of the hip has been associated with intra-articular steroid injection, with the incidence of rapidly progressive osteoarthritis of the hip after intra-articular steroid injection ranging from 2.8% to 21%. The occurrence of rapidly progressive osteoarthritis of the hip unrelated to intra-articular steroid injection is rare, and not frequently reported. This report presents a unique case of rapidly progressive osteoarthritis of the hip in the bilateral hips of one patient. The first hip developed rapidly progressive osteoarthritis of the hip within 6 mos after an intra-articular steroid injection. Three years later, the second hip developed rapidly progressive osteoarthritis of the hip within 4 mos without any injection or use of systemic steroid medication. The etiology of rapidly progressive osteoarthritis of the hip in the absence of intra-articular steroid injection is unclear, and this case presents the opportunity to observe the development of rapidly progressive osteoarthritis of the hip due to different causes within the same individual.

Relationship of Chronic Systemic Inflammation to Both Chronic Lifestyle-Related Diseases and Osteoarthritis: The Case for Lifestyle Medicine for Osteoarthritis.

Systemic inflammation is a root cause of lifestyle-related chronic diseases and may also play a role in the development and progression of osteoarthritis (OA). Lifestyle medicine seeks to treat, prevent, and reverse lifestyle-related chronic disease via 6 pillars: nutrition, sleep health, stress management, physical activity, social connections, and risky behavior avoidance/reduction. This article presents a review of the literature in which we assess the connections between the 6 pillars of lifestyle medicine, chronic systemic inflammation, and OA. We also discuss the whole-person approach that lifestyle medicine interventions can provide to reduce chronic systemic inflammation and affect the development or progression of OA.

Non-operative Treatment Options for Osteoarthritis in the Hip.

With the increased disability associated with osteoarthritis (OA) progression, and the significant socioeconomic burden of joint replacement surgeries, there is a need for more reliable conservative treatments for patients presenting with hip OA. Most studies of OA treatments involve the knee. We conducted a literature search and reviewed non-operative hip OA treatment recommendations by the Osteoarthritis Research Society International, the American College of Rheumatology, American Academy of Orthopedic Surgeons, and European Alliance of Associations for Rheumatology, as well as Cochrane Reviews. Non-steroidal anti-inflammatory drugs and corticosteroid injections are the most supported and recommended options for hip OA; other medications with potential benefits for short-term pain relief include acetaminophen and tramadol. Most societies recommend against the use of glucosamine, typical opioids, and viscosupplementation injections. Platelet-rich plasma has potential benefits, but evidence of its effectiveness is incomplete. Further research is needed to better inform and guide clinicians who create treatment plans for patients with symptomatic hip OA.

Evaluation of sleep health documentation and sleep-related intervention by physiatrists treating musculoskeletal disorders: A retrospective investigation.

BACKGROUND: Sleep health is linked to pain, function, and global health. Unfortunately, sleep health may not be consistently addressed as a part of musculoskeletal care. OBJECTIVE: To describe the frequency of sleep health documentation and intervention by musculoskeletal physiatrists. Additionally, patient-reported outcome measures were compared between patients with and without sleep impairment. We hypothesized that sleep health is documented and addressed in less than half of initial patient encounters and that patients with a sleep impairment have worse patient-reported outcomes scores compared to those without sleep impairment. DESIGN: Retrospective study. SETTING: Tertiary orthopedic hospital. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Frequency of provider documentation of sleep health, frequency and characteristics of sleep health intervention provided, and Patient-Reported Outcome Measurement Information System (PROMIS)-10 mental health and physical health scores. RESULTS: Initial visits for a musculoskeletal condition of 39,452 patients from January 1, 2020 to October 1, 2022 were included. Documentation of sleep health was found in 33.0% (13,002/39,452) of patients. Of those with sleep health documentation, 59.2% (7697/13,002) were classified as having a sleep impairment. Only 19.0% of patients were provided with sleep-related education or other intervention. Patients with a sleep impairment had worse PROMIS-10 mental health and physical health scores (p < .001), as compared to those without a sleep impairment. CONCLUSIONS: Patients with sleep impairment had worse mental and physical health scores than those without sleep impairment, and only 19.0% received sleep health intervention. These data suggest that sleep impairment is common in patients presenting for evaluation of a musculoskeletal condition, and advanced provider education and tools to help patients improve their sleep health are needed.

Using pre-surgical suspicion to guide insula implantation strategy.

Rationale: Insular epilepsy can be a challenging diagnosis due to overlapping semiology and scalp EEG findings with frontal, temporal, and parietal lobe epilepsies. Stereotactic electroencephalography (sEEG) provides an opportunity to better localize seizure onset. The possibility of improved localization is balanced by implantation risk in this vascularly rich anatomic region. We review both safety and pre-implantation factors involved in insular electrode placement across four years at an academic medical center. Methods: Presurgical data, operative reports, and invasive EEG summaries were retrospectively reviewed for patients undergoing invasive epilepsy monitoring on the insula from 2016 through 2019. EEG reports were reviewed to record the presence of insula ictal and interictal involvement. We recorded which presurgical findings suggested insular involvement (insula lesion on MRI, insula changes on PET/SPECT/scalp EEG, characteristic semiology, or history of failed anterior temporal lobectomy). The likelihood of pre-sEEG insular onset was categorized as low suspicion if no presurgical findings were present ("rule out"), moderate suspicion if one finding was present, and high suspicion if two or more findings were present. Results: 76 patients received 189 insular electrodes as part of their implantation strategy for 79 surgical cases. Seven patients (8.9%) had insular ictal onset. One clinically significant complication (left hemiparesis) occurred in a patient with moderate suspicion for insular onset. There were 38 low suspicion cases, 36 moderate suspicion cases, and 5 high suspicion cases for pre-sEEG insula ictal onset. Two low suspicion (5.3%), three moderate suspicion (8.6%), and two high suspicion (40%) cases had insular ictal onset. Conclusions: The insula can safely receive sEEG. Having two or more presurgical factors indicating insular onset is a strong, albeit incomplete, predictor of insular seizure onset. Using pre-implantation clinical findings can offer clinicians predictive value for targeting the insula during invasive EEG monitoring.

Golfing after Orthopaedic Surgery: A longitudinal follow-up (GOLF) study protocol.

Aims: The primary aim of this prospective, multicentre study is to describe the rates of returning to golf following hip, knee, ankle, and shoulder arthroplasty in an active golfing population. Secondary aims will include determining the timing of return to golf, changes in ability, handicap, and mobility, and assessing joint-specific and health-related outcomes following surgery. Methods: This is a multicentre, prospective, longitudinal study between the Hospital for Special Surgery, (New York City, New York, USA) and Edinburgh Orthopaedics, Royal Infirmary of Edinburgh, (Edinburgh, UK). Both centres are high-volume arthroplasty centres, specializing in upper and lower limb arthroplasty. Patients undergoing hip, knee, ankle, or shoulder arthroplasty at either centre, and who report being golfers prior to arthroplasty, will be included. Patient-reported outcome measures will be obtained at six weeks, three months, six months, and 12 months. A two-year period of recruitment will be undertaken of arthroplasty patients at both sites. Conclusion: The results of this prospective study will provide clinicians with accurate data to deliver to patients with regard to the likelihood of return to golf and timing of when they can expect to return to golf following their hip, knee, ankle, or shoulder arthroplasty, as well as their joint-specific functional outcomes. This will help patients to manage their postoperative expectations and plan their postoperative recovery pathway.

otpb functions in a Lef1-dependent transcriptional network required for expression of the stress response inhibitor crhbp in the zebrafish hypothalamus.

The vertebrate hypothalamus regulates physiological and behavioral responses to environmental stimuli through the function of evolutionarily-conserved neuronal subpopulations. Our previous work found that mutation of zebrafish lef1 , which encodes a transcriptional mediator of the Wnt signaling pathway, leads to the loss of hypothalamic neurons and behavioral phenotypes that are both associated with stress-related human mood disorders However, the specific Lef1 target genes that link neurogenesis to behavior remain unknown. One candidate is otpb , which encodes a transcription factor with known roles in hypothalamic development. Here we show that otpb expression in the posterior hypothalamus is Lef1-dependent, and that like lef1 , its function is required for the generation of crhbp + neurons in this region. Transgenic reporter analysis of a crhbp conserved noncoding element suggests that otpb participates in a transcriptional regulatory network with other Lef1 targets. Finally, consistent with a role for crhbp in inhibiting the stress response, zebrafish otpb mutants exhibit decreased exploration in a novel tank diving assay. Together our findings suggest a potential evolutionarily-conserved mechanism for the regulation of innate stress response behaviors through Lef1-mediated hypothalamic neurogenesis.

COVID-19-induced headache in Boston and the vicinity.

Headache is a common neurological symptom of Coronavirus disease 2019 (COVID-19) patients. However, the prevalence, comorbidities, and ethnic susceptibilities of COVID-19-induced headaches are not well-defined. We performed a retrospective chart review of patients who tested positive for SARS-CoV2 by reverse transcriptase-polymerase chain reaction (RT-PCR) in March and April 2020 at Massachusetts General Hospital, Boston, Massachusetts, USA. In the study, we identified 450 patients, 202 (44.9%) male, and 248 (55.1%) female, who tested positive for COVID-19. Headache is a significant painful symptom affecting 26% of patients. Female predominance is determined in sore throat, nasal congestion, hypogeusia, headache, and ear pain. In contrast, pneumonia and inpatient hospitalization were more prevalent in males. Younger patients (< 50) were more likely to develop sore throat, fatigue, anosmia, hypogeusia, ear pain, myalgia /arthralgia, and headache. In contrast, older (> 50) patients were prone to develop pneumonia and required hospitalization. Ethnic subgroup analysis suggests Hispanic patients were prone to headaches, nausea/vomiting, nasal congestion, fever, fatigue, anosmia, and myalgia/arthralgia compared to non-Hispanics. Headache risk factors include nausea/vomiting, sore throat, nasal congestion, fever, cough, fatigue, anosmia, hypogeusia, dizziness, ear pain, eye pain, and myalgia/arthralgia. Our study demonstrates regional gender, age, and ethnic variabilities in COVID symptomatology in Boston and the vicinity. It identifies mild viral, painful, and neurological symptoms are positive predictors of headache development in COVID-19.

Variability in Patient-Incurred Costs and Protocols of Regenerative Medicine Procedures for Musculoskeletal Conditions in the United States.

Background: The use of regenerative medicine as an "off label" treatment for musculoskeletal conditions has increased in recent years. However, the literature is sparse regarding the costs of these treatments to patients. Purposes: We sought to determine the patient-incurred costs for regenerative medicine treatments performed by physicians for musculoskeletal conditions in the United States, according to primary specialty, geographic region, practice setting, and years in practice. We also sought to characterize pre- and posttreatment protocols and image guidance use. Methods: We performed a cross-sectional study with data collection occurring between April 2020 and April 2021. It began with the distribution of an online survey through an email campaign by the American College of Sports Medicine to its members. Approximately 90 emails were sent by our research team as well. Throughout the year, various participant recruitment methods were used (through Twitter, for example). Survey data included physician demographics, practice/training information, types/costs of regenerative medicine treatments performed, and pre-/postprocedure protocols. Results: One hundred physicians who self-reported performing standalone regenerative medicine procedures participated in this online survey. According to the responses, the most common treatments performed were platelet-rich plasma (PRP; 100%), bone marrow concentrate (BMC; 41%), microfragmented adipose grafting (36%), prolotherapy (33%), and bone marrow aspirate (BMA; 21%) administered to the peripheral joints, tendons/muscles, ligaments, and/or spine. Overall, the respondents reported large variations in treatment costs to patients; BMA and BMC were the most expensive and had the largest ranges in costs for all anatomical locations. Costs for PRP were lower than those for BMA and BMC, with less variation. Physicians in private practice reported higher PRP, BMC, and BMA costs in the peripheral joints than those in academic settings. Most physicians recommended avoiding non-steroidal anti-inflammatory drugs pre- and postprocedure, and 74% recommended physical therapy postprocedure. Conclusions: Findings from a survey of physicians who provide regenerative medicine procedures as off-label treatment for musculoskeletal conditions suggest that there is variation in related patient-incurred costs. Future studies should explore associations between treatment costs and outcomes.

Prevalence of rapidly progressive osteoarthritis of the hip following intra-articular steroid injections.

INTRODUCTION: Numerous studies have indicated that intra-articular steroid injections to the hip are beneficial for short-term pain relief. However, recent studies have drawn concerns of rapidly progressive osteoarthritis of the hip (RPOH) following intra-articular steroid injections. The prevalence of RPOH following intra-articular steroid injections varies widely in the literature. OBJECTIVE: To identify the prevalence of RPOH following intra-articular steroid injections, and to compare baseline characteristics between patients with and without RPOH. DESIGN: Case series. SETTING: Tertiary academic hospital. PATIENTS: A total of 924 patients (median [interquartile range; IQR] age: 59 [45-70] years; 579 female) who received an intra-articular hip steroid/anesthetic injection from January 2016 to March 2018 and had available pre- and post-injection imaging (prior to surgical intervention) were included in the study. INTERVENTIONS: Baseline and injection-related data-including demographics, age, body mass index, medical history, laterality, and steroid type-were collected from electronic medical records. MAIN OUTCOME MEASURES: Post-injection RPOH was determined via imaging review by a physiatry fellow, followed by an attending physiatrist and a musculoskeletal radiologist to confirm findings. RESULTS: The majority of patients received unilateral injections into the hip, and the most common steroids used were triamcinolone and methylprednisolone. Review of pre- and post-injection imaging revealed 26 cases of RPOH, for an overall prevalence of 2.8% (95% confidence interval [CI] 1.9%-4.1%). Compared to those without RPOH, patients with RPOH were significantly older (median age [IQR]: 64 [60-73] vs. 59 [44-70] years, p = .003) and had a shorter duration of symptoms prior to their injections (median [IQR]: 3 vs. 12 [6-36] months, p < .001). Adjusted regression analyses showed that age was associated with greater odds of RPOH (odds ratio [OR], 95% CI: 1.04, 1.01 to 1.07; p = .003). CONCLUSIONS: The prevalence of RPOH following intra-articular steroid injections into the hip was lower than previously reported but still clinically relevant. This should be considered when counseling patients prior to intra-articular hip steroid injections.

Return to sport in elite gymnastics: Unprecedented training interruptions provide lessons for the future.

INTRODUCTION: Year-round training is standard for elite gymnasts in the United States, but the coronavirus disease 2019 (COVID-19) pandemic led to unprecedented training interruptions. The effect of these training disruptions is unknown. OBJECTIVE: This study aimed to describe and compare training interruptions in elite gymnasts before and during the pandemic, the time it took to return to the prior level of gymnastics training, the development of injuries during return to gymnastics training, and gymnast-reported difficulty in and nervousness about returning to prior level of gymnastics training. DESIGN: Retrospective study. SETTING: Anonymous online surveys distributed to elite gymnasts in the United States. PARTICIPANTS: A total of 184 current elite gymnasts who completed the surveys were included. This represented an overall response rate of 52.3% (184/352). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Information was collected about training interruptions and time, nervousness, difficulty, and injury during return to gymnastics. RESULTS: Gymnasts reported significantly longer training interruptions due to COVID-19 than before the pandemic (8.7 ± 4.4 vs. 4.4 ± 7.9 weeks, p < .001), but duration of return to prior gymnastics level was similar (4.6 ± 2.7 vs. 3.7 ± 4.8 weeks, p = .106). Of the 137 gymnasts who had returned to training by the time of the survey, 46 (33.6%) reported an injury during their return to gymnastics. A high degree of nervousness to return to gymnastics was significantly associated with greater risks of injury upon return (risk ratio [RR] 2.7, 95% confidence interval [CI]: 1.6-4.7; p < .001) and difficulty returning to prior level (RR 3.4, 95% CI: 1.7-6.6; p < .001). CONCLUSION: Pandemic-related training interruption was significantly greater in duration than prior interruptions, but time required for return to gymnastics was similar. Gymnasts may be at increased risk of injury during return to gymnastics if experiencing nervousness about returning following a break in training. These findings provide guidance for gymnasts' return from training interruptions and may refute the long-held belief that gymnasts should not take time away from training due to fear of injury or difficulty regaining skills.

Rate and Timing of Return to Golf After Hip, Knee, or Shoulder Arthroplasty: A Systematic Review and Meta-analysis.

BACKGROUND: The physical and mental health benefits of golf are well recognized, and as a moderate-intensity activity, it is an ideal sport for patients after joint arthroplasty. PURPOSE: To assess the rate and timing of returning to golf and the factors associated with these after hip, knee, or shoulder arthroplasty. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: A search of PubMed and Medline was performed in March 2021 in line with the 2009 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Search terms included sport, golf, and arthroplasty. The criterion for inclusion was any published research article studying return to golf after arthroplasty. Random-effects modeling was used to measure rates of returning to golf for each type of arthroplasty. RESULTS: A total of 23 studies were included for review. All studies were retrospective in their methodology. The mean age of patients was 66.8 years (SD, 3.37). Four studies reported on hip arthroplasty, 6 on knee arthroplasty, and 13 on shoulder arthroplasty. Among 13 studies, the mean rate of returning to golf was 80% (95% CI, 70%-89.9%). Hip, knee, and shoulder arthroplasty had mean return rates of 90% (95% CI, 82%-98%), 70% (95% CI, 39%-100%), and 80% (95% CI, 68%-92%), respectively. Among 9 studies, the mean time to return to golf was 4.4 months (95% CI, 3.2-6). Change in handicap was reported in 8 studies (35%) with a mean change of -0.1 (95% CI, -2.4 to +2.2). There were no studies presenting factors associated with return to golf. CONCLUSION: This is the first meta-analysis of returning to golf after joint arthroplasty. The study reports a high rate of returning to golf, which was greatest after hip arthroplasty. However, the study highlights the paucity of prospective data on demographic, surgical, and golf-specific outcomes after arthroplasty. Future prospective studies are required to eliminate response bias and accurately capture golf and patient-specific outcomes.

Source-sink connectivity: a novel interictal EEG marker for seizure localization.

Over 15 million epilepsy patients worldwide have drug-resistant epilepsy. Successful surgery is a standard of care treatment but can only be achieved through complete resection or disconnection of the epileptogenic zone, the brain region(s) where seizures originate. Surgical success rates vary between 20% and 80%, because no clinically validated biological markers of the epileptogenic zone exist. Localizing the epileptogenic zone is a costly and time-consuming process, which often requires days to weeks of intracranial EEG (iEEG) monitoring. Clinicians visually inspect iEEG data to identify abnormal activity on individual channels occurring immediately before seizures or spikes that occur interictally (i.e. between seizures). In the end, the clinical standard mainly relies on a small proportion of the iEEG data captured to assist in epileptogenic zone localization (minutes of seizure data versus days of recordings), missing opportunities to leverage these largely ignored interictal data to better diagnose and treat patients. IEEG offers a unique opportunity to observe epileptic cortical network dynamics but waiting for seizures increases patient risks associated with invasive monitoring. In this study, we aimed to leverage interictal iEEG data by developing a new network-based interictal iEEG marker of the epileptogenic zone. We hypothesized that when a patient is not clinically seizing, it is because the epileptogenic zone is inhibited by other regions. We developed an algorithm that identifies two groups of nodes from the interictal iEEG network: those that are continuously inhibiting a set of neighbouring nodes ('sources') and the inhibited nodes themselves ('sinks'). Specifically, patient-specific dynamical network models were estimated from minutes of iEEG and their connectivity properties revealed top sources and sinks in the network, with each node being quantified by source-sink metrics. We validated the algorithm in a retrospective analysis of 65 patients. The source-sink metrics identified epileptogenic regions with 73% accuracy and clinicians agreed with the algorithm in 93% of seizure-free patients. The algorithm was further validated by using the metrics of the annotated epileptogenic zone to predict surgical outcomes. The source-sink metrics predicted outcomes with an accuracy of 79% compared to an accuracy of 43% for clinicians' predictions (surgical success rate of this dataset). In failed outcomes, we identified brain regions with high metrics that were untreated. When compared with high frequency oscillations, the most commonly proposed interictal iEEG feature for epileptogenic zone localization, source-sink metrics outperformed in predictive power (by a factor of 1.2), suggesting they may be an interictal iEEG fingerprint of the epileptogenic zone.

Postponed depth electrode placement due to seborrheic dermatitis of the scalp: illustrative case.

BACKGROUND: Seborrheic dermatitis is a common fungal infection of the scalp that may potentially affect depth electrode placement for intracranial seizure monitoring. No cases documenting the safety of proceeding with depth electrode placement in the setting of seborrheic dermatitis have been reported. OBSERVATIONS: A 19-year-old man with a history of drug-resistant epilepsy was taken to the operating room for placement of depth electrodes for long-term seizure monitoring. Annular patches of erythema with trailing scales were discovered after shaving the patient's head. Dermatology service was consulted, and surgery was cancelled because of the uncertainty of his diagnosis and possible intracranial spreading. He was diagnosed with severe seborrheic dermatitis and treated with topical ketoconazole. Surgery was rescheduled, and the patient received successful placement and removal of depth electrodes without any complications. LESSONS: Seborrheic dermatitis is a common skin infection that, in the authors' experience, is unlikely to lead to any intracranial spread after treatment. However, surgeons should use clinical judgment and engage dermatology colleagues regarding any uncertain skin lesions.

A novel RBD-protein/peptide vaccine elicits broadly neutralizing antibodies and protects mice and macaques against SARS-CoV-2.

The development of safe and effective vaccines to respond to COVID-19 pandemic/endemic remains a priority. We developed a novel subunit protein-peptide COVID-19 vaccine candidate (UB-612) composed of: (i) receptor binding domain of SARS-CoV-2 spike protein fused to a modified single-chain human IgG1 Fc; (ii) five synthetic peptides incorporating conserved helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from SARS-CoV-2 structural proteins (three from S2 subunit, one from membrane and one from nucleocapsid), and one universal Th peptide; (iii) aluminum phosphate as adjuvant. The immunogenicity and protective immunity induced by UB-612 vaccine were evaluated in four animal models: Sprague-Dawley rats, AAV-hACE2 transduced BALB/c mice, rhesus and cynomolgus macaques. UB-612 vaccine induced high levels of neutralizing antibody and T-cell responses, in all animals. The immune sera from vaccinated animals neutralized the SARS-CoV-2 original wild-type strains and multiple variants of concern, including Delta and Omicron. The vaccination significantly reduced viral loads, lung pathology scores, and disease progression after intranasal and intratracheal challenge with SARS-CoV-2 in mice, rhesus and cynomolgus macaques. UB-612 has been tested in primary regimens in Phase 1 and Phase 2 clinical studies and is currently being evaluated in a global pivotal Phase 3 clinical study as a single dose heterologous booster.