Complications of Implanted Vagus Nerve Stimulation: A Systematic Review and Meta-analysis.

INTRODUCTION: Vagus Nerve Stimulation (VNS) has emerged as a promising tool in ischemic stroke rehabilitation. However, there has been no systematic review summarizing its adverse effects, critical information for patients and providers when obtaining informed consent for this novel treatment. This systematic review and meta-analysis reports the adverse effects of VNS. METHODS: A systematic review was performed in accordance with PRISMA guidelines to identify common complications after VNS therapy. The search was executed in: Cochrane Central Register of Controlled Trials, Embase, and Ovid MEDLINE. All prospective, randomized controlled trials using implanted VNS therapy in adult patients were eligible for inclusion. Case studies and studies lacking complete complication reports were excluded. Extracted data included technology name, location of implantation, follow-up duration, purpose of VNS, and adverse event rates. RESULTS: After title-and-abstract screening of 4933 studies, 21 were selected for final inclusion. Across these studies, 1474 patients received VNS implantation. VNS was used as a potential therapy for epilepsy (9), depression (8), anxiety (1), ischemic stroke (1), chronic heart failure (1), and fibromyalgia (1). The 5 most common post-implant adverse events were voice alteration/hoarseness (n=671, 45.5%), paresthesia (n = 233, 15.8%), cough (n = 221, 15.0%), dyspnea (n = 211, 14.3%), and pain (n = 170, 11.5%). CONCLUSIONS: Complications from VNS are mild and transient, with reduction in severity and number of adverse events with increasing follow-up time. In prior studies, VNS has served as treatment option in several instances of treatment-resistant conditions, such as epilepsy and psychiatric conditions, and its use in stroke recovery and rehabilitation should continue to be explored.

Body Mass Index Impacts Indication But Not Outcomes of Thoracic Endovascular Aortic Repair.

BACKGROUND: There are limited studies looking at thoracic endovascular aortic repair (TEVAR) outcomes in obese and overweight patients. Our objective was to determine the rate of complications, reintervention, and short-term mortality in normal weight, overweight, and obese patients undergoing TEVAR. METHODS: Patients undergoing TEVAR at a large tertiary hospital from October 2007 to January 2020 were analyzed. Patients were stratified into 3 cohorts based on body mass index (BMI): normal (18.5-25 kg/m2), overweight (25-30 kg/m2), and obese (>30 kg/m2). Primary outcomes were 30-day and 1-year survival. Intraoperative, in-hospital, and postdischarge complications were assessed as secondary outcomes using the Clavian-Dindo classification system. In addition, reinterventions associated with the index TEVAR procedure as a secondary outcome. RESULTS: Among 204 patients fitting the study criteria, we identified 65 with normal BMI, 78 overweight, and 61 obese patients. Obese patients were younger than the overweight and normal BMI patients (mean age 62.2 vs. 66.7 vs. 70.7, respectively, P = 0.003). In terms of TEVAR indication, the obese cohort had the highest percentage of patients with type B aortic dissection (36.4%), while the normal BMI cohort had the higher proportion of patients undergoing TEVAR for isolated thoracic aortic aneurysm (63.9%). Intraoperative complications did not significantly differ between cohorts. Postoperatively, in-hospital complications, postdischarge complications and 30-day return to the operative room did not differ significantly between study cohorts. Odds of reintervention did not differ significantly between cohorts, both on univariate and multivariate analysis. Log-rank test of Kaplan Meier analysis revealed no difference in reintervention-free survival (P = 0.22). Thirty-day mortality and 1-year overall survival were similar across cohorts. Both univariate and multivariate logarithmic regression revealed no difference in likelihood of 30-day mortality between the obese and normal cohort. CONCLUSIONS: There were no measurable differences in complications, reinterventions, or mortality, suggesting that vascular surgeons can perform TEVAR across a spectrum of BMI without compromising outcomes.

Evaluation of patient health outcomes of a student-run free clinic in East Harlem.

BACKGROUND: Most United States medical schools have affiliated student-run free clinics, but the quality of services provided in such contexts compared to national metrics is unknown. This study determines whether a student-run, attending-supervised free clinic servicing a low-income and minority race patient population in New York City can meet national metrics of care. METHODS: Through chart review from January 1, 2020 to December 31, 2020, patient outcomes and service utilization in the Healthcare Effectiveness Data and Information Set were examined and compared to national rates of patients using Medicaid HMO or Medicare. Patients are ≥ 21 years of age, residents of East Harlem, and ineligible for health insurance because of legal residency requirements. The majority identify as Hispanic and speak Spanish as their primary language. All patients who were seen in the clinic during the 2020 calendar year were included. The primary study outcome is the number of Healthcare Effectiveness Data and Information Set measures in which patients, seen in a student-run free clinic, meet or exceed national comparisons. RESULTS: The healthcare outcomes of 238 patients, mean age 47.8 years and 54.6% female, were examined in 18 Healthcare Effectiveness Data and Information Set measures. The student-run free clinic met or exceeded national metrics in 16 out of 18 categories. CONCLUSIONS: The student-run free clinic met or exceeded the national standard of care according to national metrics. Evidence-based priorities have been clarified for future improvement. Other student-run free clinics should similarly evaluate the quality of their services.

How Are We Doing? A Scoping Review of Published Patient-Centered Outcomes Research in United States Student-Run Free Clinics.

Phenomenon: Student-run free clinics (SRFCs) serve an integral role in most United States (US) medical schools and contribute substantially to literature on the quality of care to uninsured persons. There has been substantial growth over the past decade of scholarly work produced by SRFCs as they have increased in size and number. Research on patient care outcomes informs better care structures for patients, however there is no current synthesis of patient care outcomes research among SRFCs. This article provides an overview of SRFC research on patient outcomes to understand current research domains and to identify gaps in the literature. Approach: We completed a scoping review by searching Scopus, PubMed, and Journal of Student Run Clinics in June 2021. All peer-reviewed, English-language articles focused on patient-centered outcomes at SRFCs in the US were included. Two independent reviewers performed title, abstract, and full-text screening of relevant works, and eight reviewers conducted data extraction. Descriptive data analysis was performed along with relevant content analysis of patient-centered outcomes. Findings: The search strategy identified 784 studies, of which 87 met inclusion criteria. Most studies were published within the last six years (81.6%), located in California, New York, or Florida (43.7%), and intervention based (33.3%). Many studies (46.0%) had a specific disease of focus of which diabetes was the most researched(19.5%). Patient-centered studies were the leading focus of the study aims (40.2%), where key findings demonstrated primarily improved outcomes in clinic metrics post-intervention (36.8%) or equivalent/better clinical performance than national metrics (20.7%). Insights: This review brings to light gaps in the literature reporting research in SRFCs and can be applied to other low-resource settings. Future efforts to expand SRFC outcomes research should focus on community relationship building, understanding institutional support, and ensuring education on best practices for research within SRFCs. Doing so informs patient care improvement as SRFCs continue to operate as safety net clinics for marginalized populations.

Vagal Nerve Stimulation: A Bibliometric Analysis of Current Research Trends.

BACKGROUND: Vagal nerve stimulation (VNS) has become established as an effective tool for the management of various neurologic disorders. Consequently, a growing number of VNS studies have been published over the past four decades. This study presents a bibliometric analysis investigating the current trends in VNS literature. MATERIALS AND METHODS: Using the Web of Science collection data base, a search was performed to identify literature that discussed applications of VNS from 2000 to 2021. Analysis and visualization of the included literature were completed with VOSviewer. RESULTS: A total of 2895 publications were identified. The number of articles published in this area has increased over the past two decades, with the most citations (7098) occurring in 2021 and the most publications (270) in 2020. The h-index, i-10, and i-100 were 97, 994, and 91, respectively, with 17.0 citations per publication on average. The highest-producing country and institution of VNS literature were the United States and the University of Texas, respectively. The most productive journal was Epilepsia. Epilepsy was the predominant focus of VNS research, with the keyword "epilepsy" having the greatest total link strength (749) in the keyword analysis. The keyword analysis also revealed two major avenues of VNS research: 1) the mechanisms by which VNS modulates neural circuitry, and 2) therapeutic applications of VNS in a variety of diseases beyond neurology. It also showed a significant prevalence of noninvasive VNS research. Although epilepsy research appears more linked to implanted VNS, headache and depression specialists were more closely associated with noninvasive VNS. CONCLUSION: VNS may serve as a promising intervention for rehabilitation beyond neurologic applications, with an expanding base of literature over the past two decades. Although epilepsy researchers have produced most current literature, other fields have begun to explore VNS as a potential treatment, likely owing to the rise of noninvasive forms of VNS.

Accuracy of artificial intelligence for the detection of intracranial hemorrhage and chronic cerebral microbleeds: a systematic review and pooled analysis.

BACKGROUND: Artificial intelligence (AI)-driven software has been developed and become commercially available within the past few years for the detection of intracranial hemorrhage (ICH) and chronic cerebral microbleeds (CMBs). However, there is currently no systematic review that summarizes all of these tools or provides pooled estimates of their performance. METHODS: In this PROSPERO-registered, PRISMA compliant systematic review, we sought to compile and review all MEDLINE and EMBASE published studies that have developed and/or tested AI algorithms for ICH detection on non-contrast CT scans (NCCTs) or MRI scans and CMBs detection on MRI scans. RESULTS: In total, 40 studies described AI algorithms for ICH detection in NCCTs/MRIs and 19 for CMBs detection in MRIs. The overall sensitivity, specificity, and accuracy were 92.06%, 93.54%, and 93.46%, respectively, for ICH detection and 91.6%, 93.9%, and 92.7% for CMBs detection. Some of the challenges encountered in the development of these algorithms include the laborious work of creating large, labeled and balanced datasets, the volumetric nature of the imaging examinations, the fine tuning of the algorithms, and the reduction in false positives. CONCLUSIONS: Numerous AI-driven software tools have been developed over the last decade. On average, they are characterized by high performance and expert-level accuracy for the diagnosis of ICH and CMBs. As a result, implementing these tools in clinical practice may improve workflow and act as a failsafe for the detection of such lesions. REGISTRATION-URL: https://www.crd.york.ac.uk/prospero/ Unique Identifier: CRD42021246848.

Portable stroke detection devices: a systematic scoping review of prehospital applications.

BACKGROUND: The worldwide burden of stroke remains high, with increasing time-to-treatment correlated with worse outcomes. Yet stroke subtype determination, most importantly between stroke/non-stroke and ischemic/hemorrhagic stroke, is not confirmed until hospital CT diagnosis, resulting in suboptimal prehospital triage and delayed treatment. In this study, we survey portable, non-invasive diagnostic technologies that could streamline triage by making this initial determination of stroke type, thereby reducing time-to-treatment. METHODS: Following PRISMA guidelines, we performed a scoping review of portable stroke diagnostic devices. The search was executed in PubMed and Scopus, and all studies testing technology for the detection of stroke or intracranial hemorrhage were eligible for inclusion. Extracted data included type of technology, location, feasibility, time to results, and diagnostic accuracy. RESULTS: After a screening of 296 studies, 16 papers were selected for inclusion. Studied devices utilized various types of diagnostic technology, including near-infrared spectroscopy (6), ultrasound (4), electroencephalography (4), microwave technology (1), and volumetric impedance spectroscopy (1). Three devices were tested prior to hospital arrival, 6 were tested in the emergency department, and 7 were tested in unspecified hospital settings. Median measurement time was 3 minutes (IQR: 3 minutes to 5.6 minutes). Several technologies showed high diagnostic accuracy in severe stroke and intracranial hematoma detection. CONCLUSION: Numerous emerging portable technologies have been reported to detect and stratify stroke to potentially improve prehospital triage. However, the majority of these current technologies are still in development and utilize a variety of accuracy metrics, making inter-technology comparisons difficult. Standardizing evaluation of diagnostic accuracy may be helpful in further optimizing portable stroke detection technology for clinical use.

Early feeding after free flap reconstruction of the oral cavity: A systematic review and meta-analysis.

BACKGROUND: Traditionally, patients undergoing free flap reconstruction for oral cavity defects have been given nothing by mouth for 6-14 days post-operatively due to concern for orocutaneous fistula development. METHODS: Multiple databases were screened for studies assessing the rate of orocutaneous fistula formation in early (≤5 days) versus late (>5 days) feeding groups following oral cavity free flap reconstruction. Fixed- and random-effects meta-analyses were used. RESULTS: One randomized controlled trial, one prospective cohort, and three retrospective cohort studies were included. The early feeding group displayed no significant increase in orocutaneous fistula formation (RD = -0.02, p = 0.06) or free flap failure (RD = -0.01, p = 0.39), with a significantly shorter hospital length of stay (mean difference [days] = -2.43, p < 0.01). CONCLUSIONS: While further prospective trials are necessary, initiation of oral intake before post-operative day 5 may be appropriate in properly selected patients following oral reconstruction.

Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance.

OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.

Application of the Robotic-Assisted Digital Exoscope for Resection of Posterior Fossa Tumors in Adults: A Series of 45 Cases.

BACKGROUND AND OBJECTIVES: Complete safe resection is the goal when pursuing surgical treatment for posterior fossa (PF) tumors. Efforts have led to the development of the exoscope that delineates tumors from non-neoplastic brain. This investigation aims to assess patient outcomes where PF tumor resection is performed with the exoscope by a retromastoid or suboccipital approach. METHODS: A retrospective analysis was conducted for patients with PF tumors who underwent exoscope resection from 2017 to 2022. Patient demographics, clinical, operative, and outcome findings were collected. Extent of resection studies were also performed. Associations between perioperative data, discharge disposition, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: A total of 45 patients (22 male patients) with a median age of 57 years were assessed. Eighteen (40%) and 27 patients (60%) were diagnosed with malignant and benign tumors, respectively. Tumor neurovascular involvement was found in 28 patients (62%). Twenty-four (53%) and 20 (44%) tumors formed in the cerebellum and cerebellopontine angle cistern, respectively. One tumor (2%) was found in the cervicomedullary junction. The mean extent of resection was 96.7% for benign and malignant tumors. The PFS and OS rate at 6 months (PFS6, OS6) was 89.7% and 95.5%, respectively. Neurological complications included sensory loss and motor deficit, with 11 patients reporting no postoperative symptoms. Of the neurological complications, 14 were temporary and 9 were permanent. CONCLUSION: The exoscope is an effective intraoperative visualization tool for delineating PF tumors. In our series, we achieved low postoperative tumor volumes and a high gross total resection rate.

Exosome-Based Therapy for Ischemic Stroke: A Bibliometric Analysis of Current Trends and Future Directions.

BACKGROUND: Stroke is a leading cause of mortality and disability worldwide. Exosomes, or small extracellular vesicles with signaling properties, have recently been identified as novel mechanisms for stroke treatment. This study aims to use bibliometric techniques to identify current research trends and future directions of exosome-based stroke therapy. METHODS: The Web of Science Core Collection was searched using terms that included "exosome" and all stroke types. Bibliometric data, including authors, publication years, citations, countries/regions, institutions, journals, and Keywords Plus, were extracted directly from the Web of Science Core Collection. Keywords were mapped using VOSviewer. RESULTS: From 2010 to 2021, 424 documents were identified with a total of 12,708 citations. The number of publications increased yearly from 2012 to 2021, the majority of which were research and review articles. China and the United States produced the most publications with Henry Ford Hospital and Oakland University serving as the 2 most highly published research institutions. Documents were published most frequently in the journal Stroke. Keywords Plus analyses revealed 3 main research areas: exosomes as pathogenic mediators, biomarkers, and treatments of stroke. Ischemic stroke was the most prevalent type of stroke included in these studies. CONCLUSIONS: Using bibliometric techniques, this study identified a current and growing interest in the research of exosomes in stroke, particularly in their pathogenic, biomarker, and potential minimally invasive therapeutic properties. Given the high prevalence of ischemic stroke in the current literature, further characterization of exosomes in other stroke types, such as intracerebral hemorrhage, emerges as a future direction for this field of research.

Exosomes in subarachnoid hemorrhage: A scoping review.

INTRODUCTION: Vasospasm is a common complication following subarachnoid hemorrhage (SAH), causing increased ischemia and tissue injury, and is implicated as a major risk factor for poor outcomes. The success of current treatments for vasospasm is limited, with limited efficacy and unclear clinical benefits. Exosomes, vesicles that carry small molecules such as miRNA, have been theorized as a potential vasospasm treatment. In this study, we aim to survey the current literature discussing the role of exosomes in the setting of SAH. METHODS: Following PRISMA guidelines, we performed a scoping review evaluating the role of exosomes in the treatment of SAH. The search was conducted using PubMed and Scopus, and all original research papers studying exosomal profiles of SAH research subjects or SAH therapy were eligible for inclusion. RESULTS: After screening and full text review, seven papers were selected for final inclusion. Of these, two studies analyzed the expression profile of endogenous exosomes after SAH. Four papers identified and characterized miRNA-based exosomal therapies to attenuate early brain injury (EBI) after SAH. One paper discussed the role of protein overexpression in exosome delivery of miRNA for EBI after SAH. Interestingly, all identified papers studying exosomal therapy demonstrated anti-apoptotic or anti-inflammatory effects of miRNA exosomes acting via the BDNF/TrkB/CREB or HDAC3/NF-κB pathways. CONCLUSION: Identified studies demonstrate potential neuroprotective benefits of miRNA-based exosomal treatment of EBI and SAH. Findings warrant further research investigating the anti-inflammatory and anti-apoptotic role of exosomal miRNA delivery in SAH models, specifically targeting the common pathway identified by the authors.

Prehospital Stroke Detection Devices: A Bibliometric Analysis of Current Trends.

BACKGROUND: Stroke represents the second highest disease burden worldwide. It is well documented that rapid stroke identification and treatment are associated with improved outcomes. In particular, prehospital stroke detection (PSD) devices have emerged as possible tools to facilitate more rapid and accurate stroke triage. Bibliometric analyses offer a powerful tool to characterize the entire field from an interdisciplinary perspective. This bibliometric analysis aims to analyze current themes and identify future trends within the PSD space. METHODS: The Web of Science collection database was surveyed for PSD literature. Search terms focused on stroke diagnostic techniques, clinical indicators for ischemia/hemorrhage, and prehospital timing. Subsequently, VOSviewer was used for visual mapping analyses. RESULTS: A total of 237 documents were identified between 1995 and 2021 from 1190 different authors. Publication volume has increased greatly in recent years. Publications were spread across 156 journals with the largest journal, Stroke, contributing just 7 studies over 26 years. Keywords analysis showed that stroke, near-infrared spectroscopy, and electroencephalography were the most common keywords. CONCLUSIONS: Novel PSD devices are promising tools for the early detection and characterization of stroke. This study identifies recent increased attention to PSD technology, a trend that will likely continue in the coming years. Devices using near-infrared spectroscopy, ultrasonography, microwave, and electroencephalography represent the central areas of future PSD research. The multidisciplinary, and therefore fractured, nature of the PSD space requires those interested in the field to maintain active search habits across multiple journals to remain up to date on PSD innovations.

Blood pressure management through application-based telehealth platforms: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Hypertension management has several challenges, including poor compliance with medications and patients being lost to follow-up. Recently, remote patient monitoring and telehealth technologies have emerged as promising methods of blood pressure management. We aimed to investigate the role of application-based telehealth programs in optimizing blood pressure management. METHODS: Searches were performed in December 2020 using three databases: Cochrane Central Register of Controlled Trials, Embase and Ovid MEDLINE. All randomized controlled trials that included remote blood pressure management programmes were eligible for inclusion. Studies were included if blood pressure data were available for both the intervention and control groups. Following PRISMA guidelines, data were independently collected by two reviewers. Data were pooled using a random-effects model. The primary study outcomes were mean SBP and DBP changes for the intervention and control groups. RESULTS: Eight hundred and seventy-nine distinct articles were identified and 18 satisfied inclusion and exclusion criteria. Overall, a mean weighted decrease of 7.07 points (SBP) and 5.07 points (DBP) was found for the intervention group, compared with 3.11 point (SBP) and 3.13 point (DBP) decreases in the control group. Forest plots were constructed and effect sizes were also calculated. Mean change effect sizes of 1.1 (SBP) and 0.98 (DBP) were found, representing 86 and 85% of the intervention group having greater SBP or DBP changes, respectively, when compared with the control group. DISCUSSION: Remote patient monitoring technologies may represent a promising avenue for hypertension management. Future research is needed to evaluate the benefits in different disease-based patient subgroups.

Phenotypic profiling of mGlu7 knockout mice reveals new implications for neurodevelopmental disorders.

Neurodevelopmental disorders are characterized by deficits in communication, cognition, attention, social behavior and/or motor control. Previous studies have pointed to the involvement of genes that regulate synaptic structure and function in the pathogenesis of these disorders. One such gene, GRM7, encodes the metabotropic glutamate receptor 7 (mGlu7 ), a G protein-coupled receptor that regulates presynaptic neurotransmitter release. Mutations and polymorphisms in GRM7 have been associated with neurodevelopmental disorders in clinical populations; however, limited preclinical studies have evaluated mGlu7 in the context of this specific disease class. Here, we show that the absence of mGlu7 in mice is sufficient to alter phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep. Moreover, Grm7 knockout mice exhibit an attenuated response to amphetamine. These findings provide rationale for further investigation of mGlu7 as a potential therapeutic target for neurodevelopmental disorders such as idiopathic autism, attention deficit hyperactivity disorder and Rett syndrome.