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

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

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

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

Non-operative Treatment Options for Osteoarthritis in the Hip.

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

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

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

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

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

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

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

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

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

Clinical outcomes following intradiscal injections of higher-concentration platelet-rich plasma in patients with chronic lumbar discogenic pain.

PURPOSE: This study aimed to assess clinical outcomes following intradiscal injections of higher-concentration (> 10 ×) platelet-rich plasma (PRP) in patients with chronic lumbar discogenic pain and to compare outcomes with a historical cohort. METHODS: This retrospective study included 37 patients who received intradiscal injections of higher-concentration (> 10 ×) PRP and had post-procedure outcomes data (visual numerical scale pain score, Functional Rating Index [FRI], and NASS Patient Satisfaction Index). Outcomes were compared to a historical cohort of 29 patients who received intradiscal injections of < 5X PRP. RESULTS: Pain and FRI scores significantly improved by 3.4 ± 2.5 and 46.4 ± 27.6, respectively, at 18.3 ± 13.3 months following intradiscal injections of > 10 × PRP (p < 0.001). These improvements were greater than those reported by the historical cohort (1.7 ± 1.6 and 33.7 ± 12.3; p = 0.004 and 0.016, respectively). Additionally, the satisfaction rate was higher in patients receiving > 10 × PRP compared to those receiving < 5 × PRP (81% vs. 55%; p = 0.032). CONCLUSIONS: Findings from this study suggest that clinical outcomes can be optimized by using PRP preparations that contain a higher concentration of platelets. Further research is needed to continue to optimize the composition of PRP used to treat patients with lumbar disc disease.

Correlation of femoral version measurements between computed tomography and magnetic resonance imaging studies in patients presenting with a femoroacetabular impingement-related complaint.

Computed tomography (CT) is considered the gold standard for femoral version measurement. However, recent data have shown magnetic resonance imaging (MRI) as another modality to measure femoral version. This study aimed to correlate MRI and CT femoral version measurements in patients presenting with a femoroacetabular impingement (FAI)-related complaint. Patients (18-35 years old) who presented to the hip preservation clinic and radiology department with a suspected FAI diagnosis from 26 December 2018 to 4 March 2020 were included. All patients had a CT and MRI of the hip, with images including both hips and knees, as per our institution's protocol for possible hip preservation surgery. Patients were excluded if they were missing views of the knees, or if they had a history or imaging appearance of any condition affecting femoral version at the femoral head (e.g. slipped capital femoral epiphysis). Femoral version was measured by three reviewers. Fifty-eight patients were included, and 36 (62%) were female. Femoral version averaged 6.1° ± 11.8° on CT and 6.5° ± 10.8° on MRI. A strong positive correlation was reported between the two imaging modalities (r: 0.81; P < 0.001). Inter-rater reliability among the three reviewers was excellent and statistically significant for measurements on both MRI [intraclass correlation coefficient (ICC): 0.95; 95% CI: 0.85, 0.99; P < 0.001] and CT (ICC: 0.97; 95% CI: 0.92, 0.99; P < 0.001). Our finding suggests that MRI is a sufficient method for measuring femoral version to determine disease etiology and treatment progression. To avoid exposing patients to ionizing radiation, physicians should not obtain CT scans to evaluate femoral version.

sEH promotes macrophage phagocytosis and lung clearance of Streptococcus pneumoniae.

Epoxyeicosatrienoic acids (EETs) have potent antiinflammatory properties. Hydrolysis of EETs by soluble epoxide hydrolase/ epoxide hydrolase 2 (sEH/EPHX2) to less active diols attenuates their antiinflammatory effects. Macrophage activation is critical to many inflammatory responses; however, the role of EETs and sEH in regulating macrophage function remains unknown. Lung bacterial clearance of Streptococcus pneumoniae was impaired in Ephx2-deficient (Ephx2-/-) mice and in mice treated with an sEH inhibitor. The EET receptor antagonist EEZE restored lung clearance of S. pneumoniae in Ephx2-/- mice. Ephx2-/- mice had normal lung Il1b, Il6, and Tnfa expression levels and macrophage recruitment to the lungs during S. pneumoniae infection; however, Ephx2 disruption attenuated proinflammatory cytokine induction, Tlr2 and Pgylrp1 receptor upregulation, and Ras-related C3 botulinum toxin substrates 1 and 2 (Rac1/2) and cell division control protein 42 homolog (Cdc42) activation in PGN-stimulated macrophages. Consistent with these observations, Ephx2-/- macrophages displayed reduced phagocytosis of S. pneumoniae in vivo and in vitro. Heterologous overexpression of TLR2 and peptidoglycan recognition protein 1 (PGLYRP1) in Ephx2-/- macrophages restored macrophage activation and phagocytosis. Human macrophage function was similarly regulated by EETs. Together, these results demonstrate that EETs reduced macrophage activation and phagocytosis of S. pneumoniae through the downregulation of TLR2 and PGLYRP1 expression. Defining the role of EETs and sEH in macrophage function may lead to the development of new therapeutic approaches for bacterial diseases.

Network radiofrequency ablation for drug resistant epilepsy.

Radiofrequency ablation (RFA) is a minimally invasive procedure for drug-resistant focal epilepsy. Although well tolerated, seizure outcomes are less favorable than standard resection. RFA is commonly performed following stereoencephalography (sEEG) identification of the seizure onset zone (SOZ). We hypothesized RFA outcomes can improve by adding RFA of seizure spread regions to the SOZ as identified by sEEG, an approach we term network RFA. Four patients underwent network RFA at our institution from 8/2017 to 9/2019. There were two Engel IB outcomes and two Engel III outcomes. The median follow-up length was 25.5 months (range 17-35). No permanent neurological deficits occurred. Etiologies consisted of polymicrogyria (1), mixed malformation of cortical development (MCD) (2), and cryptogenic (1). This study provides descriptive results regarding the efficacy and safety of network RFA. Network RFA can be considered in patients with focal epilepsies with large MCDs that may not be amenable to standard resection.

sEEG for expansion of a surgical epilepsy program: Safety and efficacy in 152 consecutive cases.

OBJECTIVE: Stereoelectroencephalography (sEEG) is an intracranial encephalography method of expanding use. The need for increased epilepsy surgery access has led to the consideration of sEEG adoption by new or expanding surgical epilepsy programs. Data regarding safety and efficacy are uncommon outside of high-volume, well-established centers, which may be less applicable to newer or low-volume centers. The objective of this study was to add to the sEEG outcomes in the literature from the perspective of a rapidly expanding center. METHODS: A retrospective chart review of consecutive sEEG cases from January 2016 to December 2019 was performed. Data extraction included demographic data, surgical data, and outcome data, which pertinently examined surgical method, progression to therapeutic procedure, clinically significant adverse events, and Engel outcomes. RESULTS: One hundred and fifty-two sEEG procedures were performed on 131 patients. Procedures averaged 10.5 electrodes for a total of 1603 electrodes. The majority (84%) of patients progressed to a therapeutic procedure. Six clinically significant complications occurred: three retained electrodes, two hemorrhages, and one failure to complete investigation. Only one complication resulted in a permanent deficit. Engel 1 outcome was achieved in 63.3% of patients reaching one-year follow-up after a curative procedure. SIGNIFICANCE: New or expanding epilepsy surgery centers can appropriately consider the use of sEEG. The complication rate is low and the majority of patients progress to therapeutic surgery. Procedural safety, progression to therapeutic intervention, and Engel outcomes are comparable to cohorts from long-established epilepsy surgery programs.

A retrospective analysis of a commercially available platelet-rich plasma kit during clinical use.

INTRODUCTION: Point-of-care analyses of platelet-rich plasma (PRP) are not routine in the orthopedic regenerative medicine field. Therefore, many physicians rely on the manufacturer's reported content for commercial preparation kits. This contributes to a knowledge gap between injectate content and patient outcome. OBJECTIVE: To assess whether the EmCyte PurePRP II 60-mL preparation kit returns PRP content that meets the manufacturer's expectations when used during routine clinical care for a heterogenous patient population, and to determine whether a change in PRP yield volume affects injectate content. Protocol A (exclusion of granulocytes and low hematocrit) and Protocol B (inclusion of granulocytes and higher hematocrit) were evaluated. DESIGN: Retrospective review. SETTING: Private practice. PARTICIPANTS: One hundred five patients (118 preparations) treated for orthopedic conditions over an 8-month period via PRP injection. Thirteen patients had two independently made preparations on different treatment days that qualified for analysis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Complete blood count (absolute counts and calculated fold enrichment from baseline of platelets, white blood cells, red blood cells, granulocytes, lymphocytes, monocytes; and hematocrit levels). Confounding variables included age, gender, and preparation yield volume. RESULTS: During routine clinical use, the cellular content of both Protocols A and B met or exceeded the manufacturer's expectations of platelet enrichment and granulocyte inclusion or exclusion. Hematocrit values were slightly higher than anticipated from Protocol A preparations. The modification of yield volume from 7 to 4 mL led to a significant difference in platelet enrichment without affecting absolute cell counts (2.88; 95% confidence interval [CI] 1, 4.76; P = .003). Both gender and age moderately affected the level of platelet enrichment from baseline but did not significantly affect absolute platelet counts. CONCLUSION: In the absence of widespread characterization, confirming the variation in commercial PRP kits during clinical use is crucial.

Prevalence of Lumbosacral Transitional Vertebrae in Patients With Symptomatic Femoroacetabular Impingement Requiring Hip Arthroscopy.

PURPOSE: The primary aim of this study was to determine the prevalence of lumbosacral transitional vertebrae (LSTVs) in patients with symptomatic femoroacetabular impingement (FAI) requiring hip arthroscopy. The secondary aim was to determine whether there is an association between LSTV anatomy and patient-reported outcomes. METHODS: This retrospective study included patients aged 18 to 45 years with symptomatic FAI who underwent arthroscopy between March 2010 and March 2016 and had anteroposterior pelvic radiographs. The exclusion criteria included lack of an FAI diagnosis, hip osteoarthritis (Tönnis grade ≥ 2), prior spinal fusion surgery, prior total hip arthroplasty, indications for total hip arthroplasty, and revision surgery on the affected hip. All radiographs were assessed by an interventional spine and sports fellow. The primary outcome was the prevalence of LSTVs, classified using the criteria of Castellvi et al. Secondary outcomes included the modified Harris Hip Score, Hip Outcome Score, and International Hip Outcome Tool 33 score. RESULTS: A total of 1,880 patients were included. Review of the patients' radiographs yielded 262 LSTVs, for an overall prevalence of 13.9% (type IA in 104 [5.5%], type IB in 53 [2.8%], type IIA in 60 [3.2%], type IIB in 25 [1.3%], type IIIA in 8 [0.4%], type IIIB in 0 [0%], and type IV in 12 [0.64%]). The prevalence of type II, III, and IV LSTVs was 5.6% (n = 105). Unilateral LSTV sidedness did not correlate with symptom laterality (κ = 0.07). There were no differences in patient-reported outcomes between patients with LSTV anatomy and those without it. CONCLUSIONS: In this large cohort of 1,880 patients with symptomatic FAI, the prevalence of LSTVs was 13.9%. There was no correlation between sidedness of unilateral LSTVs and the symptomatic hip. Furthermore, there was no association between LSTV anatomy and patient-reported outcomes. The prevalence of LSTVs in this cohort was similar to the prevalence rates previously reported in patients with low-back pain. LEVEL OF EVIDENCE: Level IV, case series.

Cellular and Clinical Analyses of Autologous Bone Marrow Aspirate Injectate for Knee Osteoarthritis: A Pilot Study.

INTRODUCTION: Knee osteoarthritis (OA) is characterized by pain and functional deficits. Common conservative strategies include medications, physical therapy, and intra-articular injections. Recently, treatment using autologous cell injections has increased. OBJECTIVE: To characterize the cellular content of bone marrow aspirate (BMA) and to evaluate the effect of intra-articular autologous BMA injections in patients with mild knee OA. DESIGN: Prospective pilot observational study. SETTING: Academic institution. PATIENTS: Eleven patients with unilateral or bilateral mild knee OA (15 knees) were included in the cellular analysis. Ten patients (13 knees) were included in the overall (cellular and clinical) analysis. INTERVENTIONS: BMA was aspirated from patients' iliac crests and then injected intra-articularly under fluoroscopic and/or ultrasound guidance. BMA samples were analyzed using flow cytometry, colony forming unit (CFU) assays, and enzyme-linked immunosorbent assays. Questionnaires assessing pain and function were administered preinjection and at 1, 3, 6, and 12 months postinjection. Side effects and satisfaction were assessed. MAIN OUTCOME MEASURES: Total nucleated cell (TNC) concentration, mesenchymal stem cell (MSC) concentration, CFU count, and interleukin-1 receptor antagonist (IL-1Ra) concentration. RESULTS: BMA sample analyses revealed wide ranges in TNC concentration (173300-4 491 050 cells/mL), MSC concentration (0-500 cells/mL), CFUs (0-19), and IL-1Ra concentration (2806-29 394 pg/mL). Improvements in Knee Injury and Osteoarthritis Outcomes Score for Joint Replacement were observed throughout the 12-month follow-up period (F[4,12] = 12.29, P < .001). Additionally, current, usual, best, and worst numerical rating scale pain scores significantly decreased over time (P < .001). Patient satisfaction was high (range: 8.1 ± 2.1-8.8 ± 1.9), and side effects were uncommon. CONCLUSIONS: The cellular content of BMA samples varied widely between patients and was lower than the anticipated yield reported by the device's manufacturer. However, intra-articular BMA injections for knee OA in a small pilot cohort appeared to be safe with potential therapeutic value. Larger, prospective, double-blinded studies are warranted.

Propylthiouracil-Induced Anti-Neutrophil Cytoplasmic Antibody Vasculitis Presenting with Red Eye Followed by Pulmonary Hemorrhage: Diagnostic and Management Considerations.

BACKGROUND Drug-induced anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) should be suspected in patients on certain medications who present with inflammatory ocular, constitutional, pulmonary, and/or renal manifestations. Here, we present a case of propylthiouracil (PTU)-induced AAV presenting initially with red eye, and review important diagnostic and management considerations for this uncommon disorder. CASE REPORT A 34-year-old woman with hyperthyroidism taking PTU presented with red eye, later followed by fevers and hemoptysis. She was found to have episcleritis, diffuse alveolar hemorrhage, and microhematuria. The infectious diseases workup was unrevealing. Laboratory evaluations were notable for a high-titer perinuclear ANCA and elevated anti-myeloperoxidase antibodies. Renal function was normal. She was ultimately diagnosed with PTU-induced AAV. PTU was promptly discontinued and she was treated with pulse-dose methylprednisolone for 3 days, followed by prednisone 60 mg daily. A kidney biopsy revealed pauci-immune focal segmental necrotizing and crescentic glomerulonephritis. Given an allergy to methimazole, she underwent thyroidectomy and was ultimately treated with rituximab. Her steroid doses are progressively being tapered and she has complete resolution of symptoms. CONCLUSIONS PTU-induced AAV is a rare and serious condition. Our patient presented with ocular symptoms prior to more commonly recognized pulmonary and renal manifestations. Patients may have favorable outcomes if PTU is discontinued promptly, but patients with vital-organ involvement may require treatment with steroids and may need additional immunosuppression.

Clinical outcomes of globus pallidus deep brain stimulation for Parkinson disease: a comparison of intraoperative MRI- and MER-guided lead placement.

OBJECTIVE: Deep brain stimulation (DBS) lead placement is increasingly performed with the patient under general anesthesia by surgeons using intraoperative MRI (iMRI) guidance without microelectrode recording (MER) or macrostimulation. The authors assessed the accuracy of lead placement, safety, and motor outcomes in patients with Parkinson disease (PD) undergoing DBS lead placement into the globus pallidus internus (GPi) using iMRI or MER guidance. METHODS: The authors identified all patients with PD who underwent either MER- or iMRI-guided GPi-DBS lead placement at Emory University between July 2007 and August 2016. Lead placement accuracy and adverse events were determined for all patients. Clinical outcomes were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor scores for patients completing 12 months of follow-up. The authors also assessed the levodopa-equivalent daily dose (LEDD) and stimulation parameters. RESULTS: Seventy-seven patients were identified (MER, n = 28; iMRI, n = 49), in whom 131 leads were placed. The stereotactic accuracy of the surgical procedure with respect to the planned lead location was 1.94 ± 0.21 mm (mean ± SEM) (95% CI 1.54-2.34) with frame-based MER and 0.84 ± 0.007 mm (95% CI 0.69-0.98) with iMRI. The rate of serious complications was similar, at 6.9% for MER-guided DBS lead placement and 9.4% for iMRI-guided DBS lead placement (RR 0.71 [95% CI 0.13%-3.9%]; p = 0.695). Fifty-seven patients were included in clinical outcome analyses (MER, n = 16; iMRI, n = 41). Both groups had similar characteristics at baseline, although patients undergoing MER-guided DBS had a lower response on their baseline levodopa challenge (44.8% ± 5.4% [95% CI 33.2%-56.4%] vs 61.6% ± 2.1% [95% CI 57.4%-65.8%]; t = 3.558, p = 0.001). Greater improvement was seen following iMRI-guided lead placement (43.2% ± 3.5% [95% CI 36.2%-50.3%]) versus MER-guided lead placement (25.5% ± 6.7% [95% CI 11.1%-39.8%]; F = 5.835, p = 0.019). When UPDRS III motor scores were assessed only in the contralateral hemibody (per-lead analyses), the improvements remained significantly different (37.1% ± 7.2% [95% CI 22.2%-51.9%] and 50.0% ± 3.5% [95% CI 43.1%-56.9%] for MER- and iMRI-guided DBS lead placement, respectively). Both groups exhibited similar reductions in LEDDs (21.2% and 20.9%, respectively; F = 0.221, p = 0.640). The locations of all active contacts and the 2D radial distance from these to consensus coordinates for GPi-DBS lead placement (x, ±20; y, +2; and z, -4) did not differ statistically by type of surgery. CONCLUSIONS: iMRI-guided GPi-DBS lead placement in PD patients was associated with significant improvement in clinical outcomes, comparable to those observed following MER-guided DBS lead placement. Furthermore, iMRI-guided DBS implantation produced a similar safety profile to that of the MER-guided procedure. As such, iMRI guidance is an alternative to MER guidance for patients undergoing GPi-DBS implantation for PD.

Repurposing Protein Degradation for Optogenetic Modulation of Protein Activities.

Non-neuronal optogenetic approaches empower precise regulation of protein dynamics in live cells but often require target-specific protein engineering. To address this challenge, we developed a generalizable light-modulated protein stabilization system (GLIMPSe) to control the intracellular protein level independent of its functionality. We applied GLIMPSe to control two distinct classes of proteins: mitogen-activated protein kinase phosphatase 3 (MKP3), a negative regulator of the extracellular signal-regulated kinase (ERK) pathway, and a constitutively active form of MEK (CA MEK), a positive regulator of the same pathway. Kinetics study showed that light-induced protein stabilization could be achieved within 30 min of blue light stimulation. GLIMPSe enables target-independent optogenetic control of protein activities and therefore minimizes the systematic variation embedded within different photoactivatable proteins. Overall, GLIMPSe promises to achieve light-mediated post-translational stabilization of a wide array of target proteins in live cells.

Treatment of symptomatic degenerative intervertebral discs with autologous platelet-rich plasma: follow-up at 5-9 years.

Aim: This study assessed pain and function at 5-9 years postinjection in a subset of patients who received intradiscal platelet-rich plasma (PRP) injections for moderate-to-severe lumbar discogenic pain. Patients & methods: All patients received injections of intradiscal PRP in a previous randomized controlled trial. Data on pain, function, satisfaction, and need for surgery were collected at one time point of 5-9 years postinjection and compiled with existing data. Results: In comparison to baseline, there were statistically significant improvements in pain and function (p < 0.001). All improvements were clinically significant. Six patients had undergone surgery during the follow-up period. Conclusion: This subset of patients demonstrated statistically and clinically significant improvements in pain and function at 5-9 years postinjection.