Indocyanine green fluorescence guided resection of parathyroid adenoma of the carotid sheath: a case report and review of the literature.

Background: Ectopic parathyroid tissue can pose difficulties in diagnosis, management, and resection of adenomas in patients with hyperparathyroidism. The use of multimodal pre-operative imaging is recommended due to the diverse anatomic presentation of parathyroid adenomas and the potential presence of multiple adenomas. Resection failure still can occur, however, indocyanine green (ICG) fluorescence imaging is an intraoperative tool that has potential to help address this challenge. In the case which follows we demonstrate the use of ICG fluorescence imaging to assist in successful resection of a parathyroid adenoma located within the carotid sheath. Case Description: We present the case of a 75-year-old woman with primary hyperparathyroidism due to a parathyroid adenoma localized to the left carotid sheath, posterior to the carotid artery. Careful resection was aided by ICG fluorescence guidance allowing for complete resection and immediate postoperative restoration of normal parathyroid hormone and calcium levels. The patient had no peri-operative complications and had an unremarkable post-operative course. Conclusions: The anatomical heterogeneity of parathyroid gland adenomas within and around the carotid sheath presents a unique diagnostic and surgical scenario; however, the use of intra-operative ICG, as presented in this case, has important implications for endocrine surgeons and surgical trainees alike. This tool provides improved intra-operative identification of the parathyroid tissue allowing for safe resection, especially in cases involving critical anatomical structures.

Prevalence and Severity of Burn Scars in Rural Mozambique.

BACKGROUND: Burn injuries are common in low- and middle-income countries (LMICs) and their associated disability is tragic. This study is the first to explore burn scars in rural communities in Mozambique. This work also validated an innovate burn assessment tool, the Morphological African Scar Contractures Classification (MASCC), used to determine surgical need. METHODS: Using a stratified, population-weighted survey, the team interviewed randomly selected households from September 2012 to June 2013. Three rural districts (Chókwè, Nhamatanda, and Ribáuè) were selected to represent the southern, central and northern regions of the country. Injuries were recorded, documented with photographs, and approach to care was gathered. A panel of residents and surgeons reviewed the burn scar images using both the Vancouver Scar Scale and the MASCC, a validated visual scale that categorizes patients into four categories corresponding to levels of surgical intervention. RESULTS: Of the 6104 survey participants, 6% (n = 370) reported one or more burn injuries. Burn injuries were more common in females (57%) and most often occurred on the extremities. Individuals less than 25 years old had a significantly higher odds of reporting a burn scar compared to people older than 45 years. Based on the MASCC, 12% (n = 42) would benefit from surgery to treat contractures. CONCLUSION: Untreated burn injuries are prevalent in rural Mozambique. Our study reveals a lack of access to surgical care in rural communities and demonstrates how the MASCC scale can be used to extend the reach of surgical assessment beyond the hospital through community health workers.

Pediatric basilar skull fractures from multi-level falls: A systematic review and retrospective analysis.

OBJECTIVE: Multi-level fall (MLF) accounts for 26.5%-37.7% of traumatic pediatric basilar skull fractures (BSFs). There is a dearth of information concerning recommendations for work-up, diagnosis, treatment, and otolaryngological follow-up of pediatric basilar skull fractures secondary to MLFs. Through a systematic literature review and retrospective review of an institution's trauma experience, we sought to identify clinical findings among pediatric MLF patients that indicate the need for otolaryngological follow-up. METHODS: A two-researcher team following the PRISMA guidelines performed a systematic literature review. PubMed, Web of Science, and EBSCO databases were searched August 16th, 2020 and again on November 20th, 2021 for English language articles published after 1980 using search terms Pediatric AND (fall OR "multi level fall" OR "fall from height") AND ("basilar fracture" OR "basilar skull fracture" OR "skull base fracture" OR "skull fracture"). Simultaneously, an institutional trauma database and retrospective chart review was performed for all patients under age 18 who presented with a MLF to a pediatric tertiary care center between 2007 and 2018. RESULTS: 168 publications were identified and 13 articles reporting pediatric basilar skull fracture data and MLF as a mechanism of injury were selected for review. MLF is the most common etiology of BSF, accounting for 26.5-37.7% of pediatric BSFs. In the retrospective review, there were 180 cases of BSF from MLF in the study period (4.2%). BSF and fall height were significantly associated (p < 0.001), as well as presence of a CSF leak and fall height (p = 0.02), intracranial hemorrhage (ICH) (p = 0.047), and BSF fracture type (p < 0.001). However, when stratified by age, these associations were only present in the younger group. Of those with non-temporal bone BSFs (n = 71), children with hemotympanum (n = 7) were approximately 18 times more likely (RR 18.3, 95% CI 1.89 to 177.02) than children without hemotympanum (n = 64) to have hearing loss at presentation (28.6% vs. 1.6% of patients). CONCLUSIONS: MLF is the most common cause of pediatric basilar skull fractures. However, there is limited information on the appropriate work-up or otolaryngologic follow-up for this mechanism of injury. Our retrospective review suggests fall height is predictive for BSF, ICH, and CSF leak in younger children. Also, children with non-temporal bone BSFs and hemotympanum may represent a significant population requiring otolaryngology follow-up.

Remote telesurgery in humans: a systematic review.

BACKGROUND: Since the conception of robotic surgery, remote telesurgery has been a dream upon which incredible technological advances haven been built. Despite the considerable enthusiasm for, there have been few published studies of remote telesurgery on humans. METHODS: We performed a systematic review of the English literature (PubMed, EMbase, Inspec & Compendex and Web of Science) to report studies of remote telesurgery in humans. Keywords included telesurgery, remote surgery, long-distance surgery, and telerobotics. Subjects had to be human (live patients or cadavers). The operating surgeon had to be remote from the patient, separated by more than one kilometer. The article had to explicitly report the use of a long-distance telerobotic technique. Articles that focused on telepresence or tele-mentoring were excluded. RESULTS: The study included eight articles published from 2001 to 2020. One manuscript (1 subject) described remote surgery on a cadaver model, and the other seven were on live humans (72 subjects). Procedure types included percutaneous, endovascular, laparoscopic, and transoral. Communication methods varied, with the first report using a telephone line and the most recent studies using a 5G network. Six of the studies reported signal latency as a single value and it ranged from 28 ms to 280 ms. CONCLUSIONS: Few studies have described remote telesurgery in humans, and there is considerable variability in robotic and communication methods. Future efforts should work to improve reporting of signal latency and follow careful research methodology.

An electronic, unsupervised patient-reported Expanded Disability Status Scale for multiple sclerosis.

BACKGROUND: In persons with multiple sclerosis (MS), the Expanded Disability Status Scale (EDSS) is the criterion standard for assessing disability, but its in-person nature constrains patient participation in research and clinical assessments. OBJECTIVE: The aim of this study was to develop and validate a scalable, electronic, unsupervised patient-reported EDSS (ePR-EDSS) that would capture MS-related disability across the spectrum of severity. METHODS: We enrolled 136 adult MS patients, split into a preliminary testing Cohort 1 (n = 50), and a validation Cohort 2 (n = 86), which was evenly distributed across EDSS groups. Each patient completed an ePR-EDSS either immediately before or after a MS clinician's Neurostatus EDSS evaluation. RESULTS: In Cohort 2, mean age was 50.6 years (range = 26-80) and median EDSS was 3.5 (interquartile range (IQR) = [1.5, 5.5]). The ePR-EDSS and EDSS agreed within 1-point for 86% of examinations; kappa for agreement within 1-point was 0.85 (p < 0.001). The correlation coefficient between the two measures was 0.91 (<0.001). DISCUSSION: The ePR-EDSS was highly correlated with EDSS, with good agreement even at lower EDSS levels. For clinical care, the ePR-EDSS could enable the longitudinal monitoring of a patient's disability. For research, it provides a valid and rapid measure across the entire spectrum of disability and permits broader participation with fewer in-person assessments.

Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis.

Changes in gut microbiota composition and a diverse role of B cells have recently been implicated in multiple sclerosis (MS), a central nervous system (CNS) autoimmune disease. Immunoglobulin A (IgA) is a key regulator at the mucosal interface. However, whether gut microbiota shape IgA responses and what role IgA+ cells have in neuroinflammation are unknown. Here, we identify IgA-bound taxa in MS and show that IgA-producing cells specific for MS-associated taxa traffic to the inflamed CNS, resulting in a strong, compartmentalized IgA enrichment in active MS and other neuroinflammatory diseases. Unlike previously characterized polyreactive anti-commensal IgA responses, CNS IgA cross-reacts with surface structures on specific bacterial strains but not with brain tissue. These findings establish gut microbiota-specific IgA+ cells as a systemic mediator in MS and suggest a critical role of mucosal B cells during active neuroinflammation with broad implications for IgA as an informative biomarker and IgA-producing cells as an immune subset to harness for therapeutic interventions.

Silent progression in disease activity-free relapsing multiple sclerosis.

OBJECTIVE: Rates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation. METHODS: Disability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0-5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (±1 year) and sustained to year 10 (±1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA-DRB1*15:01 as covariates. RESULTS: Relapses were associated with a transient increase in disability over 1-year intervals (p = 0.012) but not with confirmed disability progression (p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable (p < 0.05). INTERPRETATION: Long-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS. Ann Neurol 2019;85:653-666.

Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by adaptive and innate immune system dysregulation. Recent work has revealed moderate alteration of gut microbial communities in subjects with MS and in experimental, induced models. However, a mechanistic understanding linking the observed changes in the microbiota and the presence of the disease is still missing. Chloroform-resistant, spore-forming bacteria, which primarily belong to the classes Bacilli and Clostridia in the phylum Firmicutes, have been shown to exhibit immunomodulatory properties in vitro and in vivo, but they have not yet been characterized in the context of human disease. This study addresses the community composition and immune function of this bacterial fraction in MS. We identify MS-associated spore-forming taxa (primarily in the class Clostridia) and show that their presence correlates with impaired differentiation of IL-10-secreting, regulatory T lymphocytes in vitro. Colonization of antibiotic-treated mice with spore-forming bacteria allowed us to identify some bacterial taxa favoring IL-10+ lymphocyte differentiation and others inducing differentiation of proinflammatory, IFN-γ+ T lymphocytes. However, when fed into antibiotic-treated mice, both MS and control-derived spore-forming bacteria were able to induce similar IL-10-expressing Treg immunoregulatory responses, thus ameliorating symptoms of experimental allergic encephalomyelitis (EAE). Our analysis also identified Akkermansia muciniphila as a key organism that may interact either directly or indirectly with spore-forming bacteria to exacerbate the inflammatory effects of MS-associated gut microbiota. Thus, changes in the spore-forming fraction may influence T lymphocyte-mediated inflammation in MS. This experimental approach of isolating a subset of microbiota based on its functional characteristics may be useful to investigate other microbial fractions at greater depth. IMPORTANCE To address the impact of microbiome on disease development, it is essential to go beyond a descriptive study and evaluate the physiological importance of microbiome changes. Our study integrates computational analysis with in vitro and in vivo exploration of inflammatory properties of spore-forming microbial communities, revealing novel functional correlations. We specifically show that while small differences exist between the microbiomes of MS patients and healthy subjects, these differences are exacerbated in the chloroform-resistant fraction. We further demonstrate that, when purified from MS patients, this fraction is correlated with impaired immunomodulatory responses in vitro.