Advances in the treatment of cervical rheumatoid: Less surgery and less morbidity

Rheumatoid arthritis is a chronic systemic inflammatory disease that often affects the cervical spine.While it was initially thought that cervical involvement was innocuous,natural history studies have substantiated the progressive nature of untreated disease.Over the past 50 years,there has been further elucidation in the pathophysiology of the disease,as well as significant advancements in medical and surgical therapy.The introduction of disease modifying drugs and biologic agents has reduced the amount of patients with advanced stages of the disease needing surgery.Advancement in instrumentation techniques has improved patient outcomes and fusion rates.The introduction of endoscopic approaches for ventral decompression may further lower surgical morbidity.In this review,we give a brief overview of the pertinent positives of the disease.A discussion of historical techniques and the evolution of surgical therapy into the modern era is provided.With improved medical therapies and lessinvasive approaches,we will likely continue to see less advanced cases of disease and less surgical morbidity.Nonetheless,a thorough understanding of the disease is crucial,as its systemic involvement and need for continued medical therapy have tremendous impact on overall complications and outcomes even in patients being seen for standard degenerative disease with comorbid rheumatoid.

Reconstruction of complex orbital fracture with titanium implants

AIM: To evaluate the effectiveness and safety of complex orbital fracture reconstruction with titanium implants. METHODS: A retrospective review of 46 patients treated with complex orbital fractures reconstruction using titanium implants from January 2005 to December 2008 was conducted. The following data were recorded: age, gender, mechanism of injury, preoperative and postoperative orbital CT, visual acuity, diplopia, ocular motility and Hertel exophthalmometer. RESULTS: The most common cause was motor vehicle accident (47.8%), followed by industrial injury (30.4%). All patients had improved appearance after operation and CT scan at one week after operation showed the fracture defects of orbit and neighboring areas had been reconstructed. Forty-six cases had various degrees of enophthalmos before operation. Among them, 32 cases were completely corrected, 11 cases improved obviously and 3 cases had no improvement after operation. Thirty-six patients with visual acuity =20/60 revealed diplopia of various degrees, including 26 patients had diplopia in right ahead and/or reading positions. At the sixth month after operation, diplopia disappeared in five patients, 7 patients still had diplopia in right ahead and/or reading positions, 14 patients had diplopia in positions rather than right ahead and reading positions (<20 degrees) and ten patients had diplopia only at peripheral gazing (>20 degrees). All patients had various degrees of ocular motility disorders before operation. At the sixth month after operation, eyeball movement disorder disappeared in 9 patients, 31 patients showed improvement and 6 patients had no improvement. Complications of implant infection, rejection and displacement were not reported after operation. CONCLUSION: The application of titanium implants in the repair of complex orbital fractures greatly improves the appearance and functional results, which is a favorable material for plastic surgery of complex orbital fracture.

Time-to-enrollment in clinical trials investigating neurological recovery in chronic spinal cord injury:observations from a systematic review and Clinical Trials.gov database

Currently,large numbers of clinical trials are performed to investigate different forms of experimental therapy for patients suffering from chronic spinal cord injury(SCI).However,for the enrollment process,there are different views on how the time period between injury and interventions should be determined.Herein,we sought to evaluate the impact of time-to-enrollment in chronic SCI clinical trials.A data set comprising 957 clinical studies from clinical Trials.gov was downloaded and analyzed focusing on the eligibility criteria for post-injury time-to-enrollment.We also aggregated individual patient data from nine clinical trials of regenerative interventions for chronic SCI selected by a systematic literature search from 1990 to 2018.Characteristics of the studies were assessed and compared by dividing into three groups based on time-to-enrollment(group 1≤12 months,group 2=12-23 months and group 3≥24 months).In Clinical Trials.gov registry,445 trials were identified for chronic SCI where 87%(385)were unrestricted in the maximum post-injury time for trial eligibility.From systematic literature search,nine studies and 156 patients(group 1=30,group 2=55 and group 3=71)were included.The range of time-to-enrollment was 0.5 to 321 months in those studies.We also observed various degrees of motor and sensory improvement in between three time-to-enrollment groups.Our results indicate that enrolling wide ranges of time-to-enrollment in a group may present imprecise outcomes.Clinical trial designs should consider appropriate postinjury time frames to evaluate therapeutic benefit.

The proteome of distal nerves: implication in delayed repair and poor functional recovery

Chronic denervation is one of the key factors that affect nerve regeneration.Chronic axotomy deteriorates the distal nerve stump,causes protein changes,and renders the microenvironment less permissive for regeneration.Some of these factors/proteins have been individually studied.To better delineate the comprehensive protein expression profiles and identify proteins that contribute to or are associated with this detrimental effect,we carried out a proteomic analysis of the distal nerve using an established delayed rat sciatic nerve repair model.Four rats that received immediate repair after sciatic nerve transection served as control,whereas four rats in the experimental group(chronic denervation)had their sciatic nerve repaired after a 12-week delay.All the rats were sacrificed after 16 weeks to harvest the distal nerves for extracting proteins.Twenty-five micrograms of protein from each sample were fractionated in SDS-PAGE gels.NanoLC-MS/MS analysis was applied to the gels.Protein expression levels of nerves on the surgery side were compared to those on the contralateral side.Any protein with a P value of less than 0.05 and a fold change of 4 or higher was deemed differentially expressed.All the differentially expressed proteins in both groups were further stratified according to the biological processes.A PubMed search was also conducted to identify the differentially expressed proteins that have been reported to be either beneficial or detrimental to nerve regeneration.Ingenuity Pathway Analysis(IPA)software was used for pathway analysis.The results showed that 709 differentially expressed proteins were identified in the delayed repair group,with a bigger proportion of immune and inflammatory process-related proteins and a smaller proportion of proteins related to axon regeneration and lipid metabolism in comparison to the control group where 478 differentially expressed proteins were identified.The experimental group also had more beneficial proteins that were downregulated and more detrimental proteins that were upregulated.IPA revealed that protective pathways such as LXR/RXR,acute phase response,RAC,ERK/MAPK,CNTF,IL-6,and FGF signaling were inhibited in the delayed repair group,whereas three detrimental pathways,including the complement system,PTEN,and apoptosis signaling,were activated.An available database of the adult rodent sciatic nerve was used to assign protein changes to specific cell types.The poor regeneration seen in the delayed repair group could be associated with the down-regulation of beneficial proteins and up-regulation of detrimental proteins.The proteins and pathways identified in this study may offer clues for future studies to identify therapeutic targets.

Creation of an optic nerve sheath diameter ultrasound model for Neuro ICU education

Background: Using ultrasound to measure optic nerve sheath diameter(ONSD) is an emerging bedside technique to noninvasively assess intracranial pressure(ICP) in patients with brain injury. This technique is unique among bedside ultrasonography and is often performed by providers who have no formal ultrasound training. We sought to create a low-cost, 3 D, reusable ONSD model to train neurology, neurosurgery, and critical care providers in measuring ICP.Results: We identified 253 articles, of which 15 were associated with models and 2 with simulation. One gelatin model was reported, upon which we based our initial design. We could not validate the visual findings of this model;however, after constructing multiple beta models, the design most representative of human eye anatomy was a globe made of ballistics gel and either a 3 mm, 5 mm, or 7 mm×50 mm 3 D-printed optic nerve inserted into a platform composed of ballistics gel, all of which sat inside a 3 D-printed skull. This model was used to teach ONSD measurements with ultrasound at a continuing medical education event prior to training on a live human model.Conclusions: A simple 3 D ballistic ONSD model allows learners to practice proper hand placement and pressure, basic landmarks, and ONSD measurement prior to operating on a human eye. This model is replicable and sustainable given that the globe and platform are composed of ballistics gel.

Peripheral nerve injury induced changes in the spinal cord and strategies to counteract/enhance the changes to promote nerve regeneration

Peripheral nerve injury leads to morphological, molecular and gene expression changes in the spinal cord and dorsal root ganglia, some of which have positive impact on the survival of neurons and nerve regeneration, while the effect of others is the opposite. It is crucial to take prompt measures to capitalize on the positive effects of these reactions and counteract the negative impact after peripheral nerve injury at the level of spinal cord, especially for peripheral nerve injuries that are severe, located close to the cell body, involve long distance for axons to regrow and happen in immature individuals. Early nerve repair, exogenous supply of neurotrophic factors and Schwann cells can sustain the regeneration inductive environment and enhance the positive changes in neurons. Administration of neurotrophic factors, acetyl-L-carnitine, N-acetyl-cysteine, and N-methyl-D-aspartate receptor antagonist MK-801 can help counteract axotomy-induced neuronal loss and promote regeneration, which are all time-dependent. Sustaining and reactivation of Schwann cells after denervation provides another effective strategy. FK506 can be used to accelerate axonal regeneration of neurons, especially after chronic axotomy. Exploring the axotomy-induced changes after peripheral nerve injury and applying protective and promotional measures in the spinal cord which help to retain a positive functional status for neuron cell bodies will inevitably benefit regeneration of the peripheral nerve and improve functional outcomes.

Key changes in denervated muscles and their impact on regeneration and reinnervation

The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle＇s residual receptivity by time alone. Other sensitive markers that closely correlate with the extent of denervation should be found. After a denervated muscle develops a fibrillation potential, muscle fiber conduction velocity, muscle fiber diameter, muscle wet weight, and maximal isometric force all decrease; remodeling increases neuromuscular junction fragmentation and plantar area, and expression of myogenesis-related genes is initially up-regulated and then down-regulated. All these changes correlate with both the time course and degree of denervation. The nature and time course of these denervation changes in muscle are reviewed from the literature to explore their roles in assessing both the degree of detrimental changes and the potential success of a nerve repair. Fibrillation potential amplitude, muscle fiber conduction velocity, muscle fiber diameter, mRNA expression levels of myogenic regulatory factors and nicotinic acetylcholine receptor could all reflect the severity and length of denervation and the receptiveness of denervated muscle to regenerating axons, which could possibly offer an important clue for surgical choices and predict the outcomes of delayed nerve repair.

Acute retinal arterial ischemia

Acute retinal arterial ischemia,which includes transient monocular vision loss(TMVL),branch retinal artery occlusion(BRAO),central retinal artery occlusion(CRAO)and ophthalmic artery occlusion(OAO),is most commonly the consequence of an embolic phenomenon from the ipsilateral carotid artery,heart or aortic arch,leading to partial or complete occlusion of the central retinal artery(CRA)or its branches.Acute retinal arterial ischemia is the ocular equivalent of acute cerebral ischemia and is an ophthalmic and medical emergency.Patients with acute retinal arterial ischemia are at a high risk of having further vascular events,such as subsequent strokes and myocardial infarctions(MIs).Therefore,prompt diagnosis and urgent referral to appropriate specialists and centers is necessary for further work-up(such as brain magnetic resonance imaging with diffusion weighted imaging,vascular imaging,and cardiac monitoring and imaging)and potential treatment of an urgent etiology(e.g.,carotid dissection or critical carotid artery stenosis).Since there are no proven,effective treatments to improve visual outcome following permanent retinal arterial ischemia(central or branch retinal artery occlusion),treatment must focus on secondary prevention measures to decrease the likelihood of subsequent ischemic events.

少突神经胶质细胞瘤的磁共振波谱检查与组织病理学及遗传亚型之间的相关性

Background: Oligodendroglial neoplasms with combined loss of chromosomes 1p a nd 19q may have a good prognosis and respond to procarbazine- lomustine (CCNU) - vincristine (PCV)- chemotherapy. Objective: To determine whether single voxe l magnetic resonance spectroscopy (SV- MRS) obtained through routine clinical p ractice distinguishes between histopathologic and genetic subtypes of oligodendr oglial tumors. Methods: Forty- eight patients with oligodendroglial tumors (19 oligodendrogliomas and 29 oligoastrocytomas) underwent molecular genetic analysis to determine allelic imbalance in chromoso mes 1p36 and 19q13. SV- MRS was obtained pretherapy to determine tumor metaboli te ratios. Results: Grade III oligodendroglial tumors had higher choline (Mann- Whitney; p=0.002), methyl lipid (Mann- Whitney; p=0.002), and combined methyle ne lipid and lactate ratios (Mann- Whitney; p < 0.001)- than grade II tumors. Lactate did not distinguish between tumor types (Fisher exact test; p=0.342) or grade (Fisher exact test; p=0.452). There were no significant associations when tumors were analyzed according to histopathology or genetic subtypes. Conclusion : As a noninvasive diagnostic tool used in routine clinical practice, SV- MRS h as the potential benefit of determining oligodendroglial tumor grade but not sub types classified by histopathology or molecular genetics. MRS may be useful for determining the timing of therapy but is unlikely to predict chemosensitivity.

Three-hundred and sixty degrees of surgical approaches to the maxillary sinus

Objectives:To demonstrate three-hundred and sixty degrees of maxillary sinus(MS)surgical approaches using cadaveric dissections,highlighting the step-by-step anatomy of each procedure.Methods:Two latex-injected cadaveric specimens were utilized to perform surgical dissections to demonstrate different approaches to the MS.The procedures were documented with macroscopic images and endoscopic pictures.Results:Dissections were performed to approach the MS medially(endoscopic maxillary antrostomy and ethmoidectomy),anteriorly(Caldwell-Luc),superiorly(transconjunctival/transorbital approach),inferiorly(transpalatal approach),and posterolaterally(preauricular hemicoronal approach).Conclusion:A number of approaches have been described to address pathology in the MS.Surgeons should be familiar with indications,limitations,and surgical anatomy from different perspectives to approach the MS.This paper illustrates anatomic approaches to the MS with detailed step-by-step cadaveric dissections and case examples.

3D-printed scaffolds with 2D hetero-nanostructures and immunomodulatory cytokines provide pro-healing microenvironment for enhanced bone regeneration

Three-dimensional (3D) printing technology is driving forward the progresses of various engineering fields, including tissue engineering. However, the pristine 3D-printed scaffolds usually lack robust functions in stimulating desired activity for varied regeneration applications. In this study, we combined the two-dimensional (2D) hetero-nanostructures and immuno-regulative interleukin-4 (IL-4) cytokines for the functionalization of 3D-printed scaffolds to achieve a pro-healing immuno-microenvironment for optimized bone injury repair. The 2D hetero-nanostructure consists of graphene oxide (GO) layers, for improved cell adhesion, and black phosphorous (BP) nanosheets, for the continuous release of phosphate ions to stimulate cell growth and osteogenesis. In addition, the 2D hetero-nanolayers facilitated the adsorption of large content of immuno-regulative IL-4 cytokines, which modulated the polarization of macrophages into M2 phenotype. After in vivo implantation in rat, the immuno-functioned 3D-scaffolds achieved in vivo osteo-immunomodulation by building a pro-healing immunological microenvironment for better angiogenesis and osteogenesis in the defect area and thus facilitated bone regeneration. These results demonstrated that the immuno-functionalization of 3D-scaffolds with 2D hetero-nanostructures with secondary loading of immuno-regulative cytokines is an encouraging strategy for improving bone regeneration.

Insula and the Immune System:More than mere Co-existence?

Does the Brain Regulate the Immune System?While long considered to be separate entities,increasing evidence has demonstrated that thebrain and theperipheral immune system interact through bidirectional feedback[1].The brain hosts a vibrant immune environment(e.g.microglia and perivascular macrophages)that is responsible for maintaining the integrity of the central nervous system[2].In addition,the brain is the central regulator of the rest of the body and its homeostasis.

Burnout and well-being in otolaryngology trainees:A systematic review

Objective:To comprehensively review the recent published literature to characterize current trends of burnout and well-being among otolaryngology trainees.Methods:Study design:systematic review and meta-analysis.A comprehensive literature review from 2000 to 2021 of studies related to otolaryngology resident burnout and well-being,as well as the general topic of well-being among surgical residents was completed.All included studies were summarized qualitatively.For the quantitative analysis,only articles reporting a Maslach burnout inventory(MBI),modified MBI or Mini-Z-Burnout assessment were included.Results:Twenty-five articles were included in the qualitative summary and nine articles in the quantitative analysis.In the qualitative summary,trainees were reported to have increased levels of distress and emotional hardening compared to attending otolaryngologists.Total hours worked per week and female gender were associated with worsened well-being.Residency program strategies to improve trainee well-being include program-sponsored wellness activities,dedicated wellness champions,and assistance with clerical burden.Implementation of protected nonclinical time has been shown to decrease burnout and increase well-being among trainees.Moreover,formal trainee mentorship programs have also been shown to reduce trainee burnout and stress.In the quantitative analysis,rates of trainee burnout ranged from 29.7%to 86%with an overall trend towards reduced rates of burnout from 2006 to 2021.Utilizing a weighted average,the overall burnout among otolaryngology residents was 58.6%.Conclusions:Rates of burnout remain high among otolaryngology trainees.Implementing formal mentorship programs and providing protected time during regular work hours appear to be effective tools to improve resident well-being.