Transcranial Motor-evoked Potentials for Intraoperative Nerve Root Monitoring During Adult Spinal Deformity Surgery: A Prospective Multicenter Study.

STUDY DESIGN: A prospective, multicenter study. OBJECTIVE: This study clarified the uses and limitations of transcranial motor-evoked potentials (Tc-MEPs) for nerve root monitoring during adult spinal deformity (ASD) surgeries. SUMMARY OF BACKGROUND DATA: Whether Tc-MEPs can detect nerve root injuries (NRIs) in ASD surgeries remains controversial. MATERIALS AND METHODS: We prospectively analyzed neuromonitoring data from 14 institutions between 2017 and 2020. The subjects were ASD patients surgically treated with posterior corrective fusion using multichannel Tc-MEPs. An alert was defined as a decrease of ≥70% in the Tc-MEP's waveform amplitude from baseline, and NRI was considered as meeting the focal Tc-MEP alerts shortly following surgical procedures with postoperative nerve root symptoms in the selected muscles. RESULTS: A total of 311 patients with ASD (262 women and 49 men) and a mean age of 65.5 years were analyzed. Tc-MEP results revealed 47 cases (15.1%) of alerts, including 25 alerts after 10 deformity corrections, six three-column osteotomies, four interbody fusions, three pedicle screw placements or two decompressions, and 22 alerts regardless of surgical maneuvers. Postoperatively, 14 patients (4.5%) had neurological deterioration considered to be all NRI, 11 true positives, and three false negatives (FN). Two FN did not reach a 70% loss of baseline (46% and 65% loss of baseline) and one was not monitored at target muscles. Multivariate logistic regression analysis revealed that risk factors of NRI were preexisting motor weakness ( P <0.001, odds ratio=10.41) and three-column osteotomies ( P =0.008, odds ratio=7.397). CONCLUSIONS: Nerve root injuries in our ASD cohort were partially predictable using multichannel Tc-MEPs with a 70% decrease in amplitude as an alarm threshold. We propose that future research should evaluate the efficacy of an idealized warning threshold (e.g., 50%) and a more detailed evoked muscle selection, in reducing false negatives.

Silicone breast implants and connective tissue diseases: How does current evidence add to the no-association consensus? Systematic review and meta-analysis.

To evaluate the current state of the evidence regarding the association of silicone breast implantation with the onset of connective tissue diseases, constitutional symptoms, and rheumatic serological profile in adult women. A comprehensive search was carried out using MEDLINE, Embase, Web of Science and Scopus, from inception to September 2, 2020. Cohort studies assessing the clinical and serological profile of women with cosmetic breast implants were included. Meta-analyses were conducted using risk ratios. A total of 10 cohorts with overall moderate quality of evidence were included in this systematic review. Exposure to silicone breast implants was slightly associated with the development of rheumatoid arthritis [RR: 1.35; (95% CI 1.08 to 1.68); P = .008; I2 = 0%]. However, no significant differences were exhibited between the breast implant-exposed population and controls regarding the rest of the outcomes. In adult women, exposure to silicone breast implantation is not associated with the onset of constitutional symptoms and most connective tissue diseases. A marginal association with rheumatoid arthritis was exhibited, but the certainty of this result is jeopardized by the significant amount of self-reported data for this outcome. Further research is required to adequately explore the clinical significance of these results.

The Clinical Impact of Failing to Achieve Ideal Proportional Realignment in Adult Spinal Deformity Patients.

SUMMARY OF BACKGROUND DATA: The impact of not achieving ideal realignment in the global alignment and proportion (GAP) score in adult spinal deformity (ASD) correction on clinical outcomes is understudied at present. OBJECTIVE: To identify the clinical impact of failing to achieve GAP proportionality in ASD surgery. STUDY DESIGN: Retrospective cohort. METHODS: Operative ASD patients with fusion to S1/pelvis and with pre-(BL) and 2-year (2Y) data were included. Patients were assessed for matching their 6-week (6W) age-adjusted alignment goals. 1 Patients were stratified by age-adjusted match at 6W postoperatively (Matched) and 6W GAP proportionality (proportioned: GAP-P; moderately disproportioned: GAP-MD; severely disproportioned: GAP-SD). Groups were assessed for differences in demographics, surgical factors, radiographic parameters, and complications occurring by 2Y. Multivariable logistic regression was used to assess independent effects of not achieving GAP proportionality on postoperative outcomes for Matched and Unmatched patients. RESULTS: Included: One hundred twenty three ASD patients. At baseline, 39.8% were GAP-SD, and 12.2% GAP-SD at 6W. Of 123 patients, 51.2% (n =63) had more than or equal to one match at 6W. GAP-SD rates did not differ by being Matched or Unmatched ( P = 0.945). GAP-SD/Unmatched patients had higher rates of reoperation, implant failure, and PJF by 2Y postop (all P <0.05). Regressions controlling for age at BL, levels fused, and CCI, revealed 6W GAP-SD/Unmatched patients had higher odds of reoperation (OR: 54 [3.2-899.9]; P =0.005), implant failure (OR: 6.9 [1.1-46.1]; P =0.045), and PJF (OR: 30.1 [1.4-662.6]; P =0.031). Compared to GAP-P or GAP-MD patients, GAP-SD/ Matched patients did not have higher rates of reoperation, implant failure, or junctional failure (all P >0.05). The regression results for both Matched and Unmatched cohorts were consistent when proportionality was substituted by the continuous GAP score. CONCLUSION: In ASD patients who meet age-adjusted realignment goals, GAP proportionality does not significantly alter complication rates. However, GAP proportionality remains an important consideration in patients with sub-optimal age- adjusted alignment. In these cases, severe global disproportion is associated with higher rates of reoperation, implant failure, rod fracture, and junctional failure.

Predictors for progressive fibrosis in patients with connective tissue disease associated interstitial lung diseases.

BACKGROUND: Connective tissue disease associated interstitial lung disease (CTD-ILD) is associated with decreased quality of life and high mortality risk. Outcome and treatment response is unpredictable. This study aimed to identify clinical predictors for CTD-ILD with poor outcome. METHODS: We performed a retrospective single centre cohort study in outpatients with CTD-ILD seen between 2004 and 2018. Clinical and biochemical data, pulmonary function tests (PFT) and high-resolution computed tomography (HRCT) results were analysed. Overall survival and progressive fibrosing ILD (PF-ILD, defined as a significant deterioration of PFT or HRCT) after two years of follow-up were assessed. RESULTS: In total, 150 patients with CTD-ILD were included. Thirty (20%) deaths occurred during a median follow-up of 40 months (IQR 27.3-60.8), which were attributed to pulmonary infection in six (4%), respiratory failure due to PF-ILD in ten (7%) and due to other causes in fourteen patients. PF-ILD occurred in 76 (50.7%) patients and was associated with poor overall survival (adjusted HR 5.73, 95%CI 1.17-28.11). Age, smoking, C-reactive protein, and steroid-use were independently associated with increased mortality risk as well. Furthermore, patients with diabetes mellitus (adjusted OR 4.52, 95%CI 1.10-18.51), steroid-use (adjusted OR 2.26, 95%CI 1.04-4.93), and a fibrotic HRCT pattern at baseline (adjusted OR 3.11, 95%CI 1.15-8.38) had a higher risk of PF-ILD. CONCLUSION: PF-ILD is associated with increased mortality in patients with CTD-ILD. Patients with a fibrotic HRCT pattern at baseline, diabetes mellitus and steroid-use have a higher risk of developing PF-ILD.

Bi-allelic variants in IPO8 cause a connective tissue disorder associated with cardiovascular defects, skeletal abnormalities, and immune dysregulation.

Dysregulated transforming growth factor TGF-ß signaling underlies the pathogenesis of genetic disorders affecting the connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented with a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree of dysmorphic features and developmental delay as well as immune dysregulation; the individuals were from nine unrelated families. Importin 8 belongs to the karyopherin family of nuclear transport receptors and was previously shown to mediate TGF-ß-dependent SMADs trafficking to the nucleus in vitro. The important in vivo role of IPO8 in pSMAD nuclear translocation was demonstrated by CRISPR/Cas9-mediated inactivation in zebrafish. Consistent with IPO8's role in BMP/TGF-ß signaling, ipo8-/- zebrafish presented mild to severe dorso-ventral patterning defects during early embryonic development. Moreover, ipo8-/- zebrafish displayed severe cardiovascular and skeletal defects that mirrored the human phenotype. Our work thus provides evidence that IPO8 plays a critical and non-redundant role in TGF-ß signaling during development and reinforces the existing link between TGF-ß signaling and connective tissue defects.

Adverse pregnancy outcomes and subsequent development of connective tissue disease in the UK: an epidemiological study.

OBJECTIVE: This study assessed prevalence of connective tissue disease (CTDs), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPL) in women with previous adverse pregnancy outcome compared with uncomplicated livebirths. DESIGN: Retrospective case-control study. SETTING: UK Primary Care. POPULATION OR SAMPLE: Records of women, 18 years and older, within the Clinical Practice Research Datalink (CPRD) (1 January 2000-31 December 2013). METHODS: Clinical Practice Research Datalink was searched for pregnancy terms to identify adverse pregnancy outcome. Each identified case was matched to five livebirths. MAIN OUTCOME MEASURES: Diagnosis of SLE, CTD, APS or autoimmune antibodies. Poisson regression was performed to calculate relative risk ratios (RR), comparing adverse pregnancy outcome with livebirth cohorts. RESULTS: Clinical Practice Research Datalink identified 20 123 adverse pregnancy outcomes matched to 97 323 livebirths, with a total of 875 590 person-years follow up. Median follow up from study entry was 7.29 years (SD 4.39). Compared with women with an uncomplicated livebirth, women with adverse pregnancy outcome had an increased risk of developing CTD or autoimmune antibodies (RR 3.20, 95% CI 2.90-3.51). Risk was greatest following a stillbirth (RR 5.82, 95% CI 4.97-6.81). For CTD and SLE, the risk was greatest within the first 5 years of adverse pregnancy outcome. Risk for aPL and APS diagnosis was highest ≥5 years from adverse pregnancy outcome. CONCLUSIONS: Adverse pregnancy outcome is associated with increased risk of developing maternal CTD, including SLE. Either immunological factors predispose women to adverse pregnancy outcome and subsequent CTD diagnosis or, alternatively, adverse pregnancy outcome initiates autoimmune events which culminate in CTD in later life. TWEETABLE ABSTRACT: Stillbirth is associated with increased maternal risk of developing systemic lupus erythematosus (SLE).

JAK Inhibitors: Prospects in Connective Tissue Diseases.

The dysregulation of the JAK-STAT pathway is associated with various immune disorders. Four JAK inhibitors have been approved for rheumatoid arthritis (RA), and numerous JAK inhibitors are currently being tested in phase II and III trials for the treatment of various autoimmune inflammatory diseases. In this narrative review, we elucidate the involvement of the JAK-STAT signaling pathway in the pathogenesis of connective tissue diseases (CTDs). We also discuss the efficacy of the first- and second-generation JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib, filgotinib, upadacitinib, solcitinib, itacitinib, decernotinib, R333, and pf-06651600) for CTDs including RA, systemic lupus erythematosus, dermatomyositis, systemic sclerosis, Sjögren's syndrome, and vasculitis, based on laboratory and clinical research findings. JAK inhibitors have great potential for the treatment of various CTDs by reducing multiple cytokine production and suppressing inflammation, with the advantages of rapid onset in an oral formulation and decreased corticosteroid dependence and the associated adverse events, especially in refractory cases. We also highlight the safety of novel JAK inhibitors, which can cause opportunistic infections, especially viral infections. Being a very recent therapeutic option, information regarding the safety of JAK inhibitors during pregnancy and for pediatric use is limited. However, it is recommended that JAK inhibitors should be avoided in pregnant and breastfeeding women. More clinical data, especially on highly selective inhibitors, are required to judge the efficacy and safety of JAK inhibition in CTDs.

Compartment Syndrome of the Hand after Laparoscopic Gynecologic Surgery.

Acute compartment syndrome of the hand is a potentially devastating and infrequent condition observed after trauma, arterial injury, or prolonged compression of the upper limb. We present the case of a patient diagnosed with compartment syndrome of the hand after laparoscopic surgery for epithelial ovarian cancer. The patient is a 42-year-old woman with incidental finding of high-grade ovarian serous carcinoma after an emergency surgery. On imaging evaluation, the patient was found to have evidence of residual retroperitoneal adenopathy and was taken to the operating room for a staging procedure by laparoscopy. In the immediate postoperative period, she developed compartment syndrome of the right hand that required multiple fasciotomies and multidisciplinary management by plastic surgery, orthopedics, and rehabilitation medicine. The patient was discharged from the hospital 7 days after laparoscopic surgery to undergo rehabilitation. Three months after surgery, she is continuing to recover, with near complete recovery of hand function. The patient has completed a total of 3 cycles of chemotherapy with carboplatin/paclitaxel. Compartment syndrome of the hand is an uncommon event, but it can generate major functional deficits and even death if it is not diagnosed and treated in a timely manner. Strict criteria for patient positioning in laparoscopy surgery may avoid or reduce this complication. To date, this is the first case reporting such complications associated with laparoscopic gynecologic surgery.

Shared and distinct mechanisms of fibrosis.

Fibrosis is defined as an excessive deposition of connective tissue components and can affect virtually every organ system, including the skin, lungs, liver and kidney. Fibrotic tissue remodelling often leads to organ malfunction and is commonly associated with high morbidity and mortality. The medical need for effective antifibrotic therapies is thus very high. However, the extraordinarily high costs of drug development and the rare incidence of many fibrotic disorders hinder the development of targeted therapies for individual fibrotic diseases. A potential strategy to overcome this challenge is to target common mechanisms and core pathways that are of central pathophysiological relevance across different fibrotic diseases. The factors influencing susceptibility to and initiation of these diseases are often distinct, with disease-specific and organ-specific risk factors, triggers and sites of first injury. Fibrotic remodelling programmes with shared fibrotic signalling responses such as transforming growth factor-ß (TGFß), platelet-derived growth factor (PDGF), WNT and hedgehog signalling drive disease progression in later stages of fibrotic diseases. The convergence towards shared responses has consequences for drug development as it might enable the development of general antifibrotic compounds that are effective across different disease entities and organs. Technological advances, including new models, single-cell technologies and gene editing, could provide new insights into the pathogenesis of fibrotic diseases and the development of drugs for their treatment.

Silicone Implant Illness: Science versus Myth?

The purpose of this Special Topic article is to present the current state of scientific evidence related to the safety of silicone breast implants. There is presently overwhelming evidence to support the safety of silicone breast implants. Ultimately, the decision to obtain, keep, or remove breast implants is the choice of the patient. If a patient chooses to have her breast implants removed, it is important to find a board-certified plastic surgeon with expertise in breast surgery. Ongoing studies are strongly encouraged in all areas, from cancer detection to autoimmune disease, as we strive for improved patient safety, patient awareness, and patient education. To the best of our body of scientific knowledge to date, there have not been any concrete or evidence-based studies or peer-reviewed data concerning the formation of a new syndrome: "silicone implant illness." Silicone breast implants are used in nearly 300,000 breast augmentation and 100,000 breast reconstruction operations annually in the United States. Silicone gel-filled implants were first approved by the U.S. Food and Drug Administration in 1962. Since that time, few medical devices have been studied as closely for their safety and associated adverse outcomes. Despite multiple generations of implant shells and gel fillers, the basic components remain as originally designed.

Soft Tissue and Bony Injuries Attributed to the Practice of Yoga: A Biomechanical Analysis and Implications for Management.

OBJECTIVE: To analyze injuries that were directly associated with yoga practice and identify specific poses that should be avoided in patients with osteopenia or osteoporosis. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients with injuries that were primarily caused by yoga. Patients were seen from January 1, 2006, through December 31, 2018. Injuries were categorized into 3 groups: (1) soft tissue injury, (2) axial nonbony injury, and (3) bony injury. Patients underwent evaluation and were counseled to modify exercise activity. RESULTS: We identified 89 patients for inclusion in the study. Within the soft tissue group, 66 patients (74.2%) had mechanical myofascial pain due to overuse. Rotator cuff injury was seen in 6 (6.7%), and trochanteric bursopathy was observed in 1 (1.1%). In the axial group, exacerbation of pain in degenerative joint disease (46 patients [51.7%]) and facet arthropathy (n=34 [38.2%]) were observed. Radiculopathy was seen in 5 patients (5.6%). Within the bony injury category, kyphoscoliosis was seen on imaging in 15 patients (16.9%). Spondylolisthesis was present in 15 patients (16.9%). Anterior wedging was seen in 16 (18.0%), and compression fractures were present in 13 (14.6%). The poses that were most commonly identified as causing the injuries involved hyperflexion and hyperextension of the spine. We correlated the kinesiologic effect of such exercises on specific musculoskeletal structures. CONCLUSION: Yoga potentially has many benefits, but care must be taken when performing positions with extreme spinal flexion and extension. Patients with osteopenia or osteoporosis may have higher risk of compression fractures or deformities and would benefit from avoiding extreme spinal flexion. Physicians should consider this risk when discussing yoga as exercise.

"Semenly" Harmless Back Pain: An Unusual Presentation of a Subcutaneous Abscess

Aims We report, with review of the literature, the case of a patient who developed a subcutaneous abscess after intravenously injecting his own semen in an attempt to treat longstanding back pain. He had devised this "cure" independent of medical advice. Methods A review of EMBASE, PubMed, google scholar and the wider internet was conducted with an emphasis on parenteral semen for the treatment of back pain and for other medical and non-medical uses. Results There were no other reported cases of intravenous semen injection found across the medical literature. A broader search of internet sites and forums found no documentation of semen injection for back pain treatment or otherwise. Conclusion While suicide attempt by intravenous injection of harmful substances is well described, this unique case demonstrates risks involved with innovative treatments prior to clinical research in the form of phased trials inclusive of safety and efficacy assessments.

Recent Advances in Research Regarding Autoantibodies in Connective Tissue Diseases and Related Disorders.

Connective tissue diseases (CTDs), also known as systemic autoimmune diseases, involve a variety of autoantibodies against cellular components. An important factor regarding these autoantibodies is that each antibody is exclusively related to a certain clinical feature of the disease type, which may prove useful in clinical practice. Thus far, more than 100 types of autoantibodies have been found in CTDs, and most of their target antigens have been identified. Many of these autoantigens are enzymes or regulators involved in important cellular functions, such as gene replication, transcription, repair/recombination, RNA processing, and protein synthesis, as well as proteins that form complexes with RNA and DNA. This article reviews the autoantibodies for each CTD, along with an assessment of their clinical significance, and provides suggestions regarding their utilization for clinical practice.

A Comparative Study of the Reverse Sural Fascio-Cutaneous Flap Outcomes in the Management of Foot and Ankle Soft Tissue Defects in Diabetic and Trauma Patients.

Introduction. Soft tissue defects in the distal leg and foot are challenging conditions for reconstruction. The widely used reverse sural fascio-cutaneous flap (RSFCF) has been reported with large variation in complication frequency. Some authors reported higher complications in the diabetic population when compared with trauma patients. We compared the reliability of the RSFCF in treating such defects among both populations. Methods. This is a retrospective series with a prospective data collection of 24 patients (11 with type 2 diabetes and 13 in trauma settings) treated with an ipsilateral RSFCF for soft tissue defects of the distal leg and the rear foot. Healing events and complications were recorded and compared for both groups. The mean follow-up was 32 months. Results. Diabetic group versus trauma group showed the following results; mean flap healing time of 24 versus 22 days, donor site healing time of 14 versus 16 days, 1 total flap necrosis in both groups, 3 versus 2 cases of skin edge necrosis, 2 cases of temporary venous congestion in both groups, and 8 versus 10 cases of transient hypoesthesia of the lateral border of the foot. No infection was encountered in both groups and no recurrence of infection in the primary infected diabetic patients. Conclusions. We found the RSFCF to be useful, reproducible, and reliable in treating soft tissue defects with a very low frequency of serious complications. Diabetic patients were found to have similar outcomes when compared with trauma patients. Therefore, diabetes might not be a major factor of flap failure. Levels of Evidence: Level III: Therapeutic.