A specialized population of monocyte-derived tracheal macrophages promote airway epithelial regeneration through a CCR2-dependent mechanism.

Macrophages are critical for maintenance and repair of mucosal tissues. While functionally distinct subtypes of macrophage are known to have important roles in injury response and repair in the lungs, little is known about macrophages in the proximal conducting airways. Single-cell RNA sequencing and flow cytometry demonstrated murine tracheal macrophages are largely monocyte-derived and are phenotypically distinct from lung macrophages at homeostasis. Following sterile airway injury, monocyte-derived macrophages are recruited to the trachea and activate a pro-regenerative phenotype associated with wound healing. Animals lacking the chemokine receptor CCR2 have reduced numbers of circulating monocytes and tracheal macrophages, deficient pro-regenerative macrophage activation and defective epithelial repair. Together, these studies indicate that recruitment and activation of monocyte-derived tracheal macrophages is CCR2-dependent and is required for normal airway epithelial regeneration.

De novo hematopoiesis from the fetal lung.

Hemogenic endothelial cells (HECs) are specialized cells that undergo endothelial-to-hematopoietic transition (EHT) to give rise to the earliest precursors of hematopoietic progenitors that will eventually sustain hematopoiesis throughout the lifetime of an organism. Although HECs are thought to be primarily limited to the aorta-gonad-mesonephros (AGM) during early development, EHT has been described in various other hematopoietic organs and embryonic vessels. Though not defined as a hematopoietic organ, the lung houses many resident hematopoietic cells, aids in platelet biogenesis, and is a reservoir for hematopoietic stem and progenitor cells (HSPCs). However, lung HECs have never been described. Here, we demonstrate that the fetal lung is a potential source of HECs that have the functional capacity to undergo EHT to produce de novo HSPCs and their resultant progeny. Explant cultures of murine and human fetal lungs display adherent endothelial cells transitioning into floating hematopoietic cells, accompanied by the gradual loss of an endothelial signature. Flow cytometric and functional assessment of fetal-lung explants showed the production of multipotent HSPCs that expressed the EHT and pre-HSPC markers EPCR, CD41, CD43, and CD44. scRNA-seq and small molecule modulation demonstrated that fetal lung HECs rely on canonical signaling pathways to undergo EHT, including TGFß/BMP, Notch, and YAP. Collectively, these data support the possibility that post-AGM development, functional HECs are present in the fetal lung, establishing this location as a potential extramedullary site of de novo hematopoiesis.

Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models.

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient's pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions.

Durotomy- and Irrigation-Related Serious Adverse Events During Spinal Endoscopy: Illustrative Case Series and International Surgeon Survey.

BACKGROUND: Durotomy during endoscopic spine surgery can cause a patient's neurological or cardiovascular status to deteriorate unexpectedly intra- or postoperatively. There is currently limited literature regarding appropriate fluid management strategies, irrigation-related risk factors, and clinical consequences of incidental durotomy during spinal endoscopy, and no validated irrigation protocol exists for endoscopic spine surgery. Thus, the present article sought to (1) describe 3 cases of durotomy, (2) investigate standard epidural pressure measurements, and (3) survey endoscopic spine surgeons on the incidence of adverse effects believed to result from durotomy. MATERIALS AND METHODS: The authors first reviewed clinical outcomes and analyzed complications in 3 patients with intraoperatively recognized incidental durotomy. Second, the authors conducted a small case series with intraoperative epidural pressure measurements during gravity-assisted irrigated video endoscopy of the lumbar spine. Measurements were conducted on 12 patients with a transducer assembly that was introduced through the endoscopic working channel of the RIWOSpine Panoview Plus and Vertebris endoscope to the decompression site in the spine. Third, the authors conducted a retrospective, multiple-choice survey of endoscopic spine surgeons to better understand the frequency and seriousness of problems they attributed to irrigation fluid escaping from the surgical decompression site into the spinal canal and neural axis. Descriptive and correlative statistical analyses were performed on the surgeons' responses. RESULTS: In the first part of this study, durotomy-related complications during irrigated spinal endoscopy were observed in 3 patients. Postoperative head computed tomographic (CT) images revealed massive blood in the intracranial subarachnoid space, the basal cisterns, the III and IV ventricle, and the lateral ventricles characteristic of an arterial fisher grade IV subarachnoid hemorrhage, and hydrocephalus without evidence of aneurysms or angiomas. Two additional patients developed intraoperative seizures, cardiac arrhythmia, and hypotension. The head CT image in 1 of these 2 patients had intracranial air entrapment.In the second part, epidural pressure measurements in 12 patients who underwent uneventful routine lumbar interlaminar decompression for L4-L5 and L5-S1 disc herniation showed an average epidural pressure of 24.5 mm Hg.In the third part, the online survey was accessed by 766 spine surgeons worldwide and had a response rate of 43.6%. Irrigation-related problems were reported by 38% of responding surgeons. Only 11.8% used irrigation pumps, with 90% running the pump above 40 mm Hg. Headaches (4.5%) and neck pain (4.9%) were observed by nearly a 10th (9.4%) of surgeons. Seizures in combination with headaches, neck and abdominal pain, soft tissue edema, and nerve root injury were reported by another 5 surgeons. One surgeon reported a delirious patient. Another 14 surgeons thought that they had patients with neurological deficits ranging from nerve root injury to cauda equina syndrome related to irrigation fluid. Autonomic dysreflexia associated with hypertension was attributed by 19 of the 244 responding surgeons to the noxious stimulus of escaped irrigation fluid that migrated from the decompression site in the spinal canal. Two of these 19 surgeons reported 1 case associated with a recognized incidental durotomy and another with postoperative paralysis. CONCLUSIONS: Patients should be educated preoperatively about the risk of irrigated spinal endoscopy. Although rare, intracranial blood, hydrocephalus, headaches, neck pain, seizures, and more severe complications, including life-threatening autonomic dysreflexia with hypertension, may arise if irrigation fluid enters the spinal canal or the dural sac and migrates from the endoscopic site along the neural axis rostrally. Experienced endoscopic spine surgeons suspect a correlation between durotomy and irrigation-related extra- and intradural pressure equalization that could be problematic if associated with high volumes of irrigation fluid LEVEL OF EVIDENCE: 3.

Personalized Interventional Surgery of the Lumbar Spine: A Perspective on Minimally Invasive and Neuroendoscopic Decompression for Spinal Stenosis.

Pain generator-based lumbar spinal decompression surgery is the backbone of modern spine care. In contrast to traditional image-based medical necessity criteria for spinal surgery, assessing the severity of neural element encroachment, instability, and deformity, staged management of common painful degenerative lumbar spine conditions is likely to be more durable and cost-effective. Targeting validated pain generators can be accomplished with simplified decompression procedures associated with lower perioperative complications and long-term revision rates. In this perspective article, the authors summarize the current concepts of successful management of spinal stenosis patients with modern transforaminal endoscopic and translaminar minimally invasive spinal surgery techniques. They represent the consensus statements of 14 international surgeon societies, who have worked in collaborative teams in an open peer-review model based on a systematic review of the existing literature and grading the strength of its clinical evidence. The authors found that personalized clinical care protocols for lumbar spinal stenosis rooted in validated pain generators can successfully treat most patients with sciatica-type back and leg pain including those who fail to meet traditional image-based medical necessity criteria for surgery since nearly half of the surgically treated pain generators are not shown on the preoperative MRI scan. Common pain generators in the lumbar spine include (a) an inflamed disc, (b) an inflamed nerve, (c) a hypervascular scar, (d) a hypertrophied superior articular process (SAP) and ligamentum flavum, (e) a tender capsule, (f) an impacting facet margin, (g) a superior foraminal facet osteophyte and cyst, (h) a superior foraminal ligament impingement, (i) a hidden shoulder osteophyte. The position of the key opinion authors of the perspective article is that further clinical research will continue to validate pain generator-based treatment protocols for lumbar spinal stenosis. The endoscopic technology platform enables spine surgeons to directly visualize pain generators, forming the basis for more simplified targeted surgical pain management therapies. Limitations of this care model are dictated by appropriate patient selection and mastering the learning curve of modern MIS procedures. Decompensated deformity and instability will likely continue to be treated with open corrective surgery. Vertically integrated outpatient spine care programs are the most suitable setting for executing such pain generator-focused programs.

The Changing Environment in Postgraduate Education in Orthopedic Surgery and Neurosurgery and Its Impact on Technology-Driven Targeted Interventional and Surgical Pain Management: Perspectives from Europe, Latin America, Asia, and The United States.

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work-life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur-investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management.

A review of the roles of constituent minerals and residual bitumen in the solid-liquid separation of oil sands tailings.

The efficient dewatering of fluid fine tailings (FFT) generated from warm-water extraction of Canadian oil sands is a major challenge that has limited the timely reclamation of the tailings. It is generally recognized that both chemical amendments and physical/mechanical solid-liquid separation treatments are required to speed up FFT dewatering. Significant efforts have been made to enhance the rate of solid-liquid separation of FFT in the past several decades. The fact that these efforts have met with limited successes calls for a better fundamental understanding of the solid-liquid separation process. In this work, we reviewed and critically analyzed the factors that contribute to the difficult dewatering of FFT, including the role of constituent minerals and residual bitumen. In particular, the effects of mineralogical composition, mineral particle size, and the role of residual bitumen on settling rate, hydraulic conductivity, and filtration rate are reviewed and discussed. This review also points out directions to accelerate the dewatering of FFT, such as reducing the effective volume fraction of swelling clays and releasing bitumen coating from clay surfaces, that may significantly increase the filtration rate of oil sands tailings.

Joint International SILACO, SICCMII, ISASS Symposium as a Model for a Collaborative Framework to Create Literature on Advances in Spine Surgery, Patient Care, and Policy.

International collaborations can be the key to overcoming innovation implementation hurdles. The authors report on a joint symposium between the International Society For The Advancement of Spine Surgery (ISASS) and La Sociedad Iberolatinoamerica de Columna (SILACO), and La Sociedad Interamericana de Cirurgia de columna de Minima invasión (SICCMII) aimed at improving joint surgeon education programs. The symposium highlighted that patient-related spine care issues are similar across geographical, cultural, and language barriers. The sustainability of such programs depends on funding and mutually respectful relationships orchestrated by multi-lingual leaders who will bridge gaps created by geographical, cultural, and language barriers to effectively develop clinical research content focused on advancing surgeon education and improving patient outcomes across the Americas.

A Proposed Personalized Spine Care Protocol (SpineScreen) to Treat Visualized Pain Generators: An Illustrative Study Comparing Clinical Outcomes and Postoperative Reoperations between Targeted Endoscopic Lumbar Decompression Surgery, Minimally Invasive TLIF and Open Laminectomy.

Background: Endoscopically visualized spine surgery has become an essential tool that aids in identifying and treating anatomical spine pathologies that are not well demonstrated by traditional advanced imaging, including MRI. These pathologies may be visualized during endoscopic lumbar decompression (ELD) and categorized into primary pain generators (PPG). Identifying these PPGs provides crucial information for a successful outcome with ELD and forms the basis for our proposed personalized spine care protocol (SpineScreen). Methods: a prospective study of 412 patients from 7 endoscopic practices consisting of 207 (50.2%) males and 205 (49.8%) females with an average age of 63.67 years and an average follow-up of 69.27 months was performed to compare the durability of targeted ELD based on validated primary pain generators versus image-based open lumbar laminectomy, and minimally invasive lumbar transforaminal interbody fusion (TLIF) using Kaplan-Meier median survival calculations. The serial time was determined as the interval between index surgery and when patients were censored for additional interventional and surgical treatments for low back-related symptoms. A control group was recruited from patients referred for a surgical consultation but declined interventional and surgical treatment and continued on medical care. Control group patients were censored when they crossed over into any surgical or interventional treatment group. Results: of the 412 study patients, 206 underwent ELD (50.0%), 61 laminectomy (14.8%), and 78 (18.9%) TLIF. There were 67 patients in the control group (16.3% of 412 patients). The most common surgical levels were L4/5 (41.3%), L5/S1 (25.0%), and L4-S1 (16.3%). At two-year f/u, excellent and good Macnab outcomes were reported by 346 of the 412 study patients (84.0%). The VAS leg pain score reduction was 4.250 ± 1.691 (p < 0.001). No other treatment during the available follow-up was required in 60.7% (125/206) of the ELD, 39.9% (31/78) of the TLIF, and 19.7% (12/61 of the laminectomy patients. In control patients, only 15 of the 67 (22.4%) control patients continued with conservative care until final follow-up, all of which had fair and poor functional Macnab outcomes. In patients with Excellent Macnab outcomes, the median durability was 62 months in ELD, 43 in TLIF, and 31 months in laminectomy patients (p < 0.001). The overall survival time in control patients was eight months with a standard error of 0.942, a lower boundary of 6.154, and an upper boundary of 9.846 months. In patients with excellent Macnab outcomes, the median durability was 62 months in ELD, 43 in TLIF, and 31 months in laminectomy patients versus control patients at seven months (p < 0.001). The most common new-onset symptom for censoring was dysesthesia ELD (9.4%; 20/206), axial back pain in TLIF (25.6%;20/78), and recurrent pain in laminectomy (65.6%; 40/61) patients (p < 0.001). Transforaminal epidural steroid injections were tried in 11.7% (24/206) of ELD, 23.1% (18/78) of TLIF, and 36.1% (22/61) of the laminectomy patients. The secondary fusion rate among ELD patients was 8.8% (18/206). Among TLIF patients, the most common additional treatments were revision fusion (19.2%; 15/78) and multilevel rhizotomy (10.3%; 8/78). Common follow-up procedures in laminectomy patients included revision laminectomy (16.4%; 10/61), revision ELD (11.5%; 7/61), and multilevel rhizotomy (11.5%; 7/61). Control patients crossed over into ELD (13.4%), TLIF (13.4%), laminectomy (10.4%) and interventional treatment (40.3%) arms at high rates. Most control patients treated with spinal injections (55.5%) had excellent and good functional outcomes versus 40.7% with fair and poor (3.7%), respectively. The control patients (93.3%) who remained in medical management without surgery or interventional care (14/67) had the worst functional outcomes and were rated as fair and poor. Conclusions: clinical outcomes were more favorable with lumbar surgeries than with non-surgical control groups. Of the control patients, the crossover rate into interventional and surgical care was 40.3% and 37.2%, respectively. There are longer symptom-free intervals after targeted ELD than with TLIF or laminectomy. Additional intervention and surgical treatments are more often needed to manage new-onset postoperative symptoms in TLIF- and laminectomy compared to ELD patients. Few ELD patients will require fusion in the future. Considering the rising cost of surgical spine care, we offer SpineScreen as a simplified and less costly alternative to traditional image-based care models by focusing on primary pain generators rather than image-based criteria derived from the preoperative lumbar MRI scan.

Differential Agnostic Effect Size Analysis of Lumbar Stenosis Surgeries.

STUDY DESIGN: A meta-analysis of 89 randomized prospective, prospective, and retrospective studies on spinal endoscopic surgery outcomes. OBJECTIVE: The study aimed to provide familiar Oswestry Disability Index (ODI), visual analog scale (VAS) back, and VAS leg effect size (ES) data following endoscopic decompression for sciatica-type back and leg pain due to lumbar herniated disc, foraminal, or lateral recess spinal stenosis. BACKGROUND: Higher-grade objective clinical outcome ES data are more suitable than lower-grade clinical evidence, including cross-sectional retrospective study outcomes or expert opinion to underpin the ongoing debate on whether or not to replace some of the traditional open and with other forms of minimally invasive spinal decompression surgeries such as the endoscopic technique. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 31 December 2019 identified 89 eligible studies on lumbar endoscopic decompression surgery enrolling 23,290 patient samples using the ODI and VAS for back and leg pain used for the ES calculation. RESULTS: There was an overall mean overall reduction of ODI of 46.25 (SD 6.10), VAS back decrease of 3.29 (SD 0.65), and VAS leg reduction of 5.77 (SD 0.66), respectively. Reference tables of familiar ODI, VAS back, and VAS leg show no significant impact of study design, follow-up, or patients' age on ES observed with these outcome instruments. There was no correlation of ES with long-term follow-up (P = 0.091). Spinal endoscopy produced an overall ODI ES of 0.92 extrapolated from 81 studies totaling 12,710 patient samples. Provided study comparisons to tubular retractor microdiscectomy and open laminectomy showed an ODI ES of 0.9 (2895 patients pooled from 16 studies) and 0.93 (1188 patients pooled from 5 studies). The corresponding VAS leg ES were 0.92 (12,631 endoscopy patients pooled from 81 studies), 0.92 (2348 microdiscectomy patients pooled from 15 studies), and 0.89 (1188 open laminectomy patients pooled from 5 studies). CONCLUSION: Successful clinical outcomes can be achieved with various lumbar surgeries. ESs with endoscopic spinal surgery are on par with those found with open laminectomy and microsurgical decompression. CLINICAL RELEVANCE: This article is a meta-analysis on the benefit overlap between lumbar endoscopy, microsurgical decompression, laminectomy, and lumbar decompression fusion.

Challenges in Spinal Endoscopy.

The advent of any new technology or technique is fraught with challenges in the early stages of development and adoption. This situation is no different for spinal endoscopy, which has been continuously developing for decades and has only recently gained significant traction in North America. Patient selection can be challenging for even expert endoscopic surgeons, given the limited abilities of current technology for patients with multilevel disease. Anatomic limitations, such as iliac crest location and small foraminal dimensions, can restrict application of the transforaminal approach, considered the "workhorse" of endoscopic techniques. A paucity of dedicated training opportunities has led many to become late adopters or preclude exposure entirely, limiting the next generation of surgeons and expansion of the field. Finally, economic constraints, including capital expenses and issues with insurance reimbursement, have generated difficulties to widespread acquisition. Nonetheless, the future is bright for spinal endoscopy, with potential solutions to these issues already generating progress. In the present report, we have summarized these challenges and discussed some of the current steps underway to help alleviate their impact.

CPHEN-013: Comprehensive phenotyping of hematopoietic stem and progenitor cells in the human fetal liver.

Hematopoietic stem cells (HSCs) reside at the top of the hematopoietic hierarchy and can give rise to all the mature blood cell types in our body, while at the same time maintaining a pool of HSCs through self-renewing divisions. This potential is reflected in their functional definition as cells that are capable of long-term multi-lineage engraftment upon transplantation. While all HSCs meet these criteria, subtle differences exist between developmentally different populations of these cells. Here we present a comprehensive overview of traditional and more recently described markers for phenotyping HSCs and their downstream progeny. To address the need to assess the growing number of surface molecules expressed in various HSC-enriched fractions at different developmental stages, we have developed an extensive multi-parameter spectral flow cytometry panel to phenotype hematopoietic stem and multipotent progenitor cells (HSC/MPPs) throughout development. In this study we then employ this panel to comprehensively profile the HSC compartment in the human fetal liver (FL), which is endowed with superior engraftment potential compared to postnatal sources. Spectral cytometry lends an improved resolution of marker expression to our comprehensive approach, allowing to extract combinatorial expression signatures of several relevant HSC/MPP markers to precisely characterize the HSC/MPP fraction in a variety of tissues.

Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment.

The human hematopoietic stem cell harbors remarkable regenerative potential that can be harnessed therapeutically. During early development, hematopoietic stem cells in the fetal liver undergo active expansion while simultaneously retaining robust engraftment capacity, yet the underlying molecular program responsible for their efficient engraftment remains unclear. Here, we profile 26,407 fetal liver cells at both the transcriptional and protein level including ~7,000 highly enriched and functional fetal liver hematopoietic stem cells to establish a detailed molecular signature of engraftment potential. Integration of transcript and linked cell surface marker expression reveals a generalizable signature defining functional fetal liver hematopoietic stem cells and allows for the stratification of enrichment strategies with high translational potential. More precisely, our integrated analysis identifies CD201 (endothelial protein C receptor (EPCR), encoded by PROCR) as a marker that can specifically enrich for engraftment potential. This comprehensive, multi-modal profiling of engraftment capacity connects a critical biological function at a key developmental timepoint with its underlying molecular drivers. As such, it serves as a useful resource for the field and forms the basis for further biological exploration of strategies to retain the engraftment potential of hematopoietic stem cells ex vivo or induce this potential during in vitro hematopoietic stem cell generation.

A Differential Clinical Benefit Examination of Full Lumbar Endoscopy vs Interspinous Process Spacers in the Treatment of Spinal Stenosis: An Effect Size Meta-Analysis of Clinical Outcomes.

STUDY DESIGN: A design-agnostic standardized effect meta-analysis of 48 randomized, prospective, and retrospective studies on clinical outcomes with spinal endoscopic and interspinous process spacer (IPS) surgery. OBJECTIVE: The study aimed to provide reference set of Oswestry Disability Index (ODI) and visual analog scale (VAS) effect size data for back and leg pain following endoscopic and IPS decompression for lumbar herniated disc, foraminal, or lateral recess spinal stenosis. BACKGROUND: Mechanical low back pain following endoscopic transforaminal decompression may be more reliably reduced by simultaneous posterior column stabilization with IPS. METHODS: A systematic search of the PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 2 April 2020, identified 880 eligible endoscopy and 362 IPS studies varying in design and metrics. The authors compared calculated standardized effect sizes (Cohen's d) for extracted ODI, VAS-back, and VAS-leg data. RESULTS: The pooled standardized effect size combining the ODI, VAS-back, and VAS-leg data for the total sample of 19862 data sets from the 30 endoscopy and 18 IPS was 0.877 (95% CI = 0.857-0.898). When stratified by surgery, the combined effect sizes were 0.877 (95% CI = 0.849-0.905) for endoscopic decompression and 0.863 (95% CI = 0.796-0.930; P = 0.056) for IPS implantation. The ODI effect sizes calculated on 6462 samples with directly visualized endoscopic decompression were 0.917 (95% CI = 0.891-0.943) versus 0.798 (95% CI = 0.713-0.883; P < 0.001) with indirect IPS decompression (P < 0.001). The VAS-back effect sizes calculated on 3672 samples were 0.661 (95% CI = 0.585-0.738) for endoscopy and 0.784 (95% CI: 0.644-0.923; P = 0.187) for IPS. The VAS-leg effect sizes calculated on 7890 samples were 0.885 (95% CI = 0.852-0.917) for endoscopic decompression and 0.851 (95% CI = 0.767-0.935; P = 0.427). CONCLUSION: Lumbar IPS implantation produces larger reduction in low back pain than spinal endoscopy. On the basis of this meta-analysis, the combination of lumbar transforaminal endoscopy with simultaneous IPS has merits and should be formally investigated in higher grade clinical studies. CLINICAL RELEVANCE: Meta-analysis on the added clinical benefit of combining lumbar endoscopic decompression with an interspinous process spacer.

TikTok and Attention-Deficit/Hyperactivity Disorder: A Cross-Sectional Study of Social Media Content Quality.

OBJECTIVES: Social media platforms are increasingly being used to disseminate mental health information online. User-generated content about attention-deficit/hyperactivity disorder (ADHD) is one of the most popular health topics on the video-sharing social media platform TikTok. We sought to investigate the quality of TikTok videos about ADHD. METHOD: The top 100 most popular videos about ADHD uploaded by TikTok video creators were classified as misleading, useful, or personal experience. Descriptive and quantitative characteristics of the videos were obtained. The Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-A/V) and Journal of American Medical Association (JAMA) benchmark criteria were used to assess the overall quality, understandability, and actionability of the videos. RESULTS: Of the 100 videos meeting inclusion criteria, 52% (n = 52) were classified as misleading, 27% (n = 27) as personal experience, and 21% (n = 21) as useful. Classification agreement between clinician ratings was 86% (kappa statistic of 0.7766). Videos on the platform were highly understandable by viewers but had low actionability. Non-healthcare providers uploaded the majority of misleading videos. Healthcare providers uploaded higher quality and more useful videos, compared to non-healthcare providers. CONCLUSIONS: Approximately half of the analyzed TikTok videos about ADHD were misleading. Clinicians should be aware of the widespread dissemination of health misinformation on social media platforms and its potential impact on clinical care.

Rompiendo el efecto ''techo de cristal'' en la generación de evidencia clínica de alto nivel en ortopedia y traumatología / Breaking the "glass ceiling" effect in the generation of high-level clinical evidence in orthopedics and traumatology

Introduction: In clinical studies involving common orthopedic problems and traumatic injuries, randomization methods are difficult to orchestrate. The lack of high-level clinical evidence based on prospective, randomized, double-blind studies is often cited as a major reason for rejecting proposed therapeutic advances in orthopedic surgery. Materials and methods: This opinion document summarizes the limitations of clinical trials in surgical subspecialties. A consensus is presented about how the practicing orthopedic surgeon can produce high-quality clinical evidence and thus make changes to their clinical practice protocols. Results: This literature review revealed that level of evidence classifications vary among surgical subspecialties. Research in orthopedics and traumatology is primarily directed toward diagnosis, preferred treatment, and economic decision analysis, while other prognostic classifications are preferred in other areas, such as plastic surgery. In orthopedics, double-blind controlled studies are rare and often impractical or even unethical. Crossover between randomized surgical trials of study groups is more common. Other difficulties in surgical trials range from: lack of organizational and financial support, institutional approval or ethics committee and registration requirements for clinical trials, and to insufficient time outside of an already busy clinical program to dedicate to this laborious task. uncompensated task. Conclusion: Orthopedic surgery is a subspecialty based on experience and skill. Many innovations begin with enterprising surgeons reporting opinion reports or retrospective cohort studies, many of which are biased. Prospective observational cohort studies with consistent results may offer higher grade clinical evidence than poorly executed randomized trials.

Natural Language Processing as an Emerging Tool to Detect Late-Life Depression.

Late-life depression (LLD) is a major public health concern. Despite the availability of effective treatments for depression, barriers to screening and diagnosis still exist. The use of current standardized depression assessments can lead to underdiagnosis or misdiagnosis due to subjective symptom reporting and the distinct cognitive, psychomotor, and somatic features of LLD. To overcome these limitations, there has been a growing interest in the development of objective measures of depression using artificial intelligence (AI) technologies such as natural language processing (NLP). NLP approaches focus on the analysis of acoustic and linguistic aspects of human language derived from text and speech and can be integrated with machine learning approaches to classify depression and its severity. In this review, we will provide rationale for the use of NLP methods to study depression using speech, summarize previous research using NLP in LLD, compare findings to younger adults with depression and older adults with other clinical conditions, and discuss future directions including the use of complementary AI strategies to fully capture the spectrum of LLD.

Correlating natural language processing and automated speech analysis with clinician assessment to quantify speech-language changes in mild cognitive impairment and Alzheimer's dementia.

BACKGROUND: Language impairment is an important marker of neurodegenerative disorders. Despite this, there is no universal system of terminology used to describe these impairments and large inter-rater variability can exist between clinicians assessing language. The use of natural language processing (NLP) and automated speech analysis (ASA) is emerging as a novel and potentially more objective method to assess language in individuals with mild cognitive impairment (MCI) and Alzheimer's dementia (AD). No studies have analyzed how variables extracted through NLP and ASA might also be correlated to language impairments identified by a clinician. METHODS: Audio recordings (n=30) from participants with AD, MCI, and controls were rated by clinicians for word-finding difficulty, incoherence, perseveration, and errors in speech. Speech recordings were also transcribed, and linguistic and acoustic variables were extracted through NLP and ASA. Correlations between clinician-rated speech characteristics and the variables were compared using Spearman's correlation. Exploratory factor analysis was applied to find common factors between variables for each speech characteristic. RESULTS: Clinician agreement was high in three of the four speech characteristics: word-finding difficulty (ICC = 0.92, p<0.001), incoherence (ICC = 0.91, p<0.001), and perseveration (ICC = 0.88, p<0.001). Word-finding difficulty and incoherence were useful constructs at distinguishing MCI and AD from controls, while perseveration and speech errors were less relevant. Word-finding difficulty as a construct was explained by three factors, including number and duration of pauses, word duration, and syntactic complexity. Incoherence was explained by two factors, including increased average word duration, use of past tense, and changes in age of acquisition, and more negative valence. CONCLUSIONS: Variables extracted through automated acoustic and linguistic analysis of MCI and AD speech were significantly correlated with clinician ratings of speech and language characteristics. Our results suggest that correlating NLP and ASA with clinician observations is an objective and novel approach to measuring speech and language changes in neurodegenerative disorders.

Full-Endoscopic Oblique Lateral Lumbar Interbody Fusion: A Technical Note With 1-Year Follow-Up.

BACKGROUND: Oblique lateral lumbar interbody fusion (OLLIF) is a minimally invasive lumbar interbody fusion procedure using a bullet-shaped polyetheretherketone (PEEK) nonexpandable fusion cage modified to diminish risk to the exiting nerve root during posterolateral implantation through the Kambin safe zone under fluoroscopic guidance. The objective of this study was to present feasibility of this procedure and 1-year clinical outcome data. METHODS: The authors present a prospective cohort study of 20 patients who underwent fluoroscopy-guided and full-endoscopic OLLIF in 22 segments allowing protection of the exiting nerve root from January 2018 to March 2019. The foraminoplasty, discectomy, endplate preparation, placement of bone graft and insertion of the fusion cage was done under continuous full-endoscopic visualization. The OLLIF fusion was backed up with bilateral percutaneous posterior supplemental pedicle screw fixation. Primary clinical outcome measures were the visual analog scale (VAS) of low back and leg pain, and Oswestry disability index (ODI) at 1 week, 3 months, 6 months, and 1 year after the operation. At final follow-up, the Macnab score was also evaluated. Secondary outcome measures were computed tomography (CT) assessment fusion using the Mannion classification of spinal fusion and adverse events related to the device as well as magnetic resonance imaging (MRI) assessment of nerve root decompression. RESULTS: All patients had significant relief of low back pain and leg pain, by VAS and ODI scores that improved significantly (P < .01). There were no complications. Postoperative lumbar MRI of all patients showed sufficient direct nerve decompression. At 1-year follow-up, excellent Macnab outcomes were obtained 13 patients, good in six, and fair in one. Impaired sensation and muscle strength of the involved nerve root significantly recovered in all but 2 patients (P < .05). According to the Mannion CT-based classification of spinal fusion, CT showed complete interbody fusion achieved in all 22 segments. CONCLUSIONS: Full-endoscopic OLLIF is a safe, effective, minimally invasive, economical, practical, and widely applicable minimally invasive interbody fusion technique in the lumbar spine. LEVEL OF EVIDENCE: 3.

Dural Tears During Lumbar Spinal Endoscopy: Surgeon Skill, Training, Incidence, Risk Factors, and Management.

BACKGROUND: Incidental dural tears during lumbar endoscopy can be challenging to manage. There is limited literature on their appropriate management, risk factors, and the clinical consequences of this typically uncommon complication. MATERIALS AND METHODS: To improve the statistical power of studying durotomy with lumbar endoscopy, we performed a retrospective survey study among endoscopic spine surgeons by email and chat groups on social media networks, including WhatsApp and WeChat. Descriptive and correlative statistics were done on the surgeons' recorded responses to multiple-choice questions. Surgeons were asked about their clinical experience with spinal endoscopy, training background, the types of lumbar endoscopic decompression they perform by approach, the decompression instruments they use, and incidental durotomy incidence with routine lumbar endoscopy. RESULTS: There were 689 dural tears in 64 470 lumbar endoscopies, resulting in an incidental durotomy incidence of 1.07%. Seventy percent of the durotomies were reported by 20.4% of the surgeons. Eliminating these 19 outlier surgeons yielded an adjusted durotomy rate of 0.32. Endoscopic stenosis decompression (54.8%; P < .0001), rather than endoscopic discectomy (44.1%; 41/93), was significantly more associated with durotomy. Medium-sized dural tears (1-10 mm) were the most common (52.2%; 48/93). Small pinhole durotomies (less than 1 mm) were the second most common type (46.7%; 43/93). Rootlet herniations were seen by 46.2% (43/93) of responding surgeons. The posterior dural sac injury during the interlaminar approach (57%; 53/93) occurred more frequently than traversing nerve-root injuries (31.2%) or anterior dural sac (23.7%; 22/93). Exiting nerve-root injuries (10.8%;10/93) were less common. Over half of surgeons did not attempt any repair or closure (52.2%; 47/90). Forty percent (36/90) used sealants. Only 7.8% (7/90) of surgeons attempted an endoscopic repair or sutures (11.1%; 10/90). DuralSeal was the most commonly used brand of commercially available sealant used (42.7%; 35/82). However, other sealants such as Tisseal (15.9%; 13/82), Evicel (2.4%2/82), and additional no-brand sealants (38; 32/82) were also used. Nearly half of the patients (48.3%; 43/89) were treated with 24-48 hours of bed rest. The majority of participating surgeons (64%; 57/89) reported that the long-term outcome was unaffected. Only 18% of surgeons reported having seen the development of a postoperative cerebrospinal fluid (CSF)-fistula (18%;16/89). However, the absolute incidence of CSF fistula was only 0.025% (16/64 470). Severe radiculopathy with dysesthesia; sensory loss; and motor weakness in association with an incidental durotomy were reported by 12.4% (11/89), 3.4% (3/89), and 2.2% (2/89) of surgeons, respectively. CONCLUSIONS: The incidence of dural tears with lumbar endoscopy is about 1%. The incidence of durotomy is higher with the use of power drills and the interlaminar approach. Stenosis decompression that typically requires the more aggressive use of these power instruments has a slightly higher incidence of dural tears than does endoscopic decompression for a herniated disc. Most dural tears are small and can be successfully managed with mechanical compression with Gelfoam and sealants. Two-thirds of patients with incidental dural tears had an entirely uneventful postoperative course. The remaining one-third of patients may develop a persistent CSF leak, radiculopathy with dysesthesia, sensory loss, or motor function loss. Patients should be educated preoperatively and reassured. LEVEL OF EVIDENCE: 3.