Pediatric Orthopaedic Venous Thromboembolism: A Systematic Review Investigating Incidence, Risk Factors, and Outcome.

Background: There is growing evidence of increased venous thromboembolism (VTE) incidence in children with trauma or infection. The purpose of this study was to conduct a systematic review of existing literature related to VTE in the pediatric orthopaedic population, to estimate the overall incidence of VTE and identify risk factors associated with this condition. Methods: A systematic review of the available literature was performed to identify articles that described VTE in pediatric orthopaedic surgery or admission. Literature queries were performed to identify articles published from 1980 to 2021 that included patients ≤21 years of age. A stepwise search strategy of 5 electronic databases yielded 1,426 articles, which were filtered by 2 reviewers to identify 30 articles for full-text review. The primary aim was to determine the rate of VTE, and the secondary aim was to identify risk factors for VTE. The pooled incidence of VTE was estimated and reported in cases per 10,000. Studies were stratified by study size, by trauma versus elective surgery, and by orthopaedic subspecialty. Results: The 30 articles reported 3,113 VTE events in 2,467,764 pediatric patients (including those with non-orthopaedic conditions), for a pooled VTE incidence of 20 events (95% confidence interval [CI] = 10.8 to 37.2) per 10,000. Four of the studies were excluded for incomplete data or high heterogeneity. The remaining 26 studies had 850,268 orthopaedic patients with 1,108 cases of VTE, for a pooled VTE incidence of 16.6 events (95% CI = 9.1 to 30.5) per 10,000. Studies with <10,000 patients and those involving a diagnosis of trauma had the highest VTE incidence when stratification was performed. The most frequently analyzed risk factors in 15 available studies included age, sex, obesity/body mass index, type of surgery, and use of a central venous catheter. Conclusions: This systematic review indicated that the risk of VTE associated with pediatric orthopaedic surgery or admission remains low, at <17 events per 10,000 cases. However, orthopaedic surgeons should be aware of the most common risk factors associated with pediatric orthopaedic VTE and should pay special attention to traumatic etiologies, as these yielded the highest incidence. Levels of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Hemoglobin Wayne Variant and Association With Falsely Elevated HbA1c.

The objective of this work is to explain the effect of the clinically silent hemoglobinopathy hemoglobin Wayne (Hb Wayne) variant on glycated hemoglobin A1c (HbA1c) assay. This variant can result in falsely high HbA1c values among euglycemic individuals without diabetes mellitus (DM). We discuss 3 patients who were diagnosed with type 2 DM based on spuriously high HbA1c values due to the presence of Hb Wayne. All 3 patients were found to have elevated HbA1c values that did not correlate with other glycemic parameters such as capillary blood sugar, 2-hour oral glucose tolerance test, and fructosamine levels. Hemoglobin electrophoresis revealed that each patient had a rare hemoglobinopathy called Hb Wayne variant. These patients were reassured that they did not have DM and were able to avoid unnecessary treatment. These cases emphasize the importance of clinical judgment in recognizing the limitations and caveats of the HbA1c test. It is always necessary to investigate further any discordance between HbA1c values and the clinical picture or other glycemic parameters.

Internal Carotid Artery Aneurysm Disguised as Pituitary Macroadenoma.

Hypopituitarism due to an internal carotid artery (ICA) aneurysm is rare. We present a case of hypopituitarism and hyperprolactinemia due to a giant right ICA aneurysm. A 56-year-old woman with a history of primary hypothyroidism presented with fatigue, right-sided headache, and blurred vision. Magnetic resonance (MR) of the brain revealed a sellar mass measuring 3.5 × 2.2 cm involving the right cavernous sinus. Initial neurologic examination was unremarkable, and her biochemical evaluation revealed secondary adrenal insufficiency, central hypogonadism, low serum free thyroxine, and mildly elevated serum prolactin, consistent with stalk effect. Hydrocortisone therapy was started for secondary adrenal insufficiency and her levothyroxine dose was adjusted. The patient was referred to neurosurgery for surgical management of her sellar lesion. Preoperative computed tomography angiography (CTA) of the brain revealed a right ICA aneurysm that contacted the optic chiasm and displaced the pituitary gland. The aneurysm was embolized and diverting stents were placed. Repeat laboratory tests showed resolution of the patient's secondary adrenal insufficiency, normalization of serum prolactin, and an increase in serum gonadotropin concentrations to the postmenopausal range. This case highlights that not all sellar lesions are pituitary adenomas, and CTA should be performed in the evaluation of large cavernous sinus lesions to exclude ICA aneurysm.

The Impact of COVID-19 on Multidisciplinary Care Delivery to Children with Cerebral Palsy and Other Neuromuscular Complex Chronic Conditions.

The COVID-19 pandemic has caused unprecedented challenges in the care of children with cerebral palsy (CP) and other neuromuscular complex chronic conditions (NCCCs). The purpose of this study is to explore the direct impact of the COVID-19 pandemic on healthcare delivery. From May to August 2020, medical professionals caring for CP and NCCC patients across multiple countries and disciplines completed a self-administered cross-sectional survey comparing practices before and during the COVID-19 pandemic. Of the 79 healthcare workers from eight countries who participated-predominantly pediatric orthopedic surgeons (32%), pediatricians (30%), and pediatric physiatrists (23%)-most of them felt that caring for NCCC patients during the pandemic presented unique difficulties, and they reported a significant decrease in the in-person NCCC clinic volume (p < 0.001), multidisciplinary appointments (p < 0.001), surgical cases (p = 0.008), and botulinum toxin/phenol injections. Most providers affirmed that institutional guidelines for perioperative emergent/urgent and elective procedures, workplace settings, and technology were modified to accommodate the ongoing public health crisis. The usage of telemedicine significantly increased for NCCC patient visits (p < 0.001). During the COVID-19 pandemic, many children with NCCCs lost access to routine, multidisciplinary care. Telemedicine became an integral part of communication and management. In the setting of the COVID-19 pandemic and with the threat of future healthcare disruptions, these data lay the foundation for trending the evolution of healthcare delivery and accelerating best practice guidelines for children with CP and NCCCs.

Clinical Outcomes of Coccygectomy for Coccydynia: A Single Institution Series With Mean 5-Year Follow-Up.

BACKGROUND: Prior studies of coccygectomy consist of small patient groups, heterogeneous techniques, and high wound complication rates (up to 22%). This study investigates our institution's experience with coccygectomy using a novel "off-center" wound closure technique and analyzes prognostic factors for long-term successful clinical outcomes. METHODS: Retrospective review of all patients who underwent coccygectomy from 2006 to 2019 at a single center. Demographics, mechanism of injury, conservative management, morphology (Postacchini and Massobrio), and postoperative complications were collected. Preoperative and postoperative Oswestry Disability Index (ODI), visual analog scale (VAS), Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and EuroQol-5D (EQ-5D) were compared. Risk factors for failing to meet minimum clinically importance difference for ODI and PROMIS-physical function/pain interference were identified. Risk factors for remaining disabled after surgery (ODI <20) and factors associated with VAS and EQ-5D improvement were investigated using stepwise logistic regression. RESULTS: A total of 173 patients (77% women, mean age = 46.56 years, mean follow-up 5.58 ± 3.95 years). The most common etiologies of coccydynia were spontaneous/unknown (42.2%) and trauma/accident (41%). ODI, VAS, and several PROMIS-29 domains improved postoperatively. Older age predicted continued postoperative disability (ODI >20) and history of prior spine surgery, trauma etiology, and women had inferior outcomes. No history of spine surgery (cervical, thoracic, or lumbar) prior to coccygectomy was found to predict improved postoperative VAS back scores. No outcome differences were demonstrated among the coccyx morphologies. Sixteen patients (9.25%) were noted to have postoperative infections of the incision site with no difference in long-term outcomes (all P <0.05). CONCLUSIONS: This is the largest series of coccygectomy patients demonstrating improvement in long-term outcomes. Compared to previous studies, our cohort had a lower wound infection rate, which we attribute to an "off-center" closure. CLINICAL RELEVANCE: Patients should be counseled that their surgical history, along with age, gender, and etiology of pain can influence success following coccygectomy. These data can help surgeons set realistic expectations following surgery.

Coccygectomy for refractory coccygodynia: a systematic review and meta-analysis.

PURPOSE: We sought to systematically assess and summarize the available literature on outcomes following coccygectomy for refractory coccygodynia. METHODS: PubMed, Scopus, and Cochrane Library databases were systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data concerning patient demographics, validated patient reported outcome measures (PROMs) for pain relief, disability outcomes, complications, and reoperation rates were extracted and analyzed. RESULTS: A total of 21 studies (18 retrospective and 3 prospective) were included in the quantitative analysis. A total of 826 patients (females = 75%) received coccygectomy (720 total and 106 partial) for refractory coccygodynia. Trauma was reported as the most common etiology of coccygodynia (56%; n = 375), followed by idiopathic causes (33%; n = 221). The pooled mean difference (MD) in pain scores from baseline on a 0-10 scale was 5.03 (95% confidence interval [CI]: 4.35 to 6.86) at a 6-12 month follow-up (FU); 5.02 (95% CI: 3.47 to 6.57) at > 12-36 months FU; and 5.41 (95% CI: 4.33 to 6.48) at > 36 months FU. The MCID threshold for pain relief was surpassed at each follow-up. Oswestry Disability Index scores significantly improved postoperatively, with a pooled MD from baseline of - 23.49 (95% CI: - 31.51 to - 15.46), surpassing the MCID threshold. The pooled incidence of complications following coccygectomy was 8% (95% CI: 5% to 12%), the most frequent of which were surgical site infections and wound dehiscence. The pooled incidence of reoperations was 3% (95% CI: 1% to 5%). CONCLUSION: Coccygectomy represents a viable treatment option in patients with refractory coccygodynia.

Mental health factors associated with progression to adolescent metabolic and bariatric surgery.

BACKGROUND: While bariatric surgery has demonstrated significant weight loss for adolescents with severe obesity, only a limited number of adolescents referred to surgery successfully complete the surgical program. Better identification of pre-surgical factors, especially mental health factors, associated with completing bariatric surgery may determine successful referrals to surgical programs versus alternative behavioral health interventions. OBJECTIVES: The primary objective of this article was to investigate the relationship between presurgical mental health factors and whether or not a patient received bariatric surgery within the first six months of entering the program. SETTING: Pediatric Children's Hospital, Bariatric Surgery Program within Pediatric Surgery Department. METHODS: A retrospective medical record review of all patients referred from 2016 to 2019 to an adolescent surgical weight loss program was conducted. Patients were determined as completers if they received a laparoscopic sleeve gastrectomy within 6 months of entering the program. Demographic and preoperative mental health factors among completers (n = 30) were compared with surgery noncompleters (n = 44) using enter method logistic regression. RESULTS: Regression analyses revealed that younger patients, White patients, patients with lower internalizing symptoms on a standardized measure, and patients with greater self-reported motivation for surgery at their initial surgery visit were more likely to obtain surgery within 6 months of starting the program. CONCLUSION: The findings underscore the importance of assessing patients' motivation early in the bariatric surgery referral process. This study highlights potential treatment implications in how best to mitigate patient barriers, such as internalizing symptoms and low motivation, to pursue bariatric surgery and remain committed to weight loss goals through techniques such as motivational interviewing.

Membrane insertion exacerbates the α-Synuclein-Cu(II) dopamine oxidase activity: Metallothionein-3 targets and silences all α-synuclein-Cu(II) complexes.

Copper binding to α-synuclein (α-Syn), the major component of intracellular Lewy body inclusions in substantia nigra dopaminergic neurons, potentiate its toxic redox-reactivity and plays a detrimental role in the etiology of Parkinson disease (PD). Soluble α-synuclein-Cu(II) complexes possess dopamine oxidase activity and catalyze ROS production in the presence of biological reducing agents via Cu(II)/Cu(I) redox cycling. These metal-centered redox reactivities harmfully promote the oxidation and oligomerization of α-Syn. While this chemistry has been investigated on recombinantly expressed soluble α-Syn, in vivo, α-Syn is acetylated at its N-terminus and is present in equilibrium between soluble and membrane-bound forms. This post-translational modification and membrane-binding alter the Cu(II) coordination environment and binding modes and are expected to affect the α-Syn-Cu(II) reactivity. In this work, we first investigated the reactivity of acetylated and membrane-bound complexes, and subsequently addressed whether the brain metalloprotein Zn7-metallothionein-3 (Zn7MT-3) possesses a multifaceted-role in targeting these aberrant copper interactions and consequent reactivity. Through biochemical characterization of the reactivity of the non-acetylated/N-terminally acetylated soluble or membrane-bound α-Syn-Cu(II) complexes towards dopamine, oxygen, and ascorbate, we reveal that membrane insertion dramatically exacerbates the catechol oxidase-like reactivity of α-Syn-Cu(II) as a result of a change in the Cu(II) coordination environment, thereby potentiating its toxicity. Moreover, we show that Zn7MT-3 can efficiently target all α-Syn-Cu(II) complexes through Cu(II) removal, preventing their deleterious redox activities. We demonstrate that the Cu(II) reduction by the thiolate ligands of Zn7MT-3 and the formation of Cu(I)4Zn4MT-3 featuring an unusual redox-inert Cu(I)4-thiolate cluster is the molecular mechanism responsible for the protective effect exerted by MT-3 towards α-Syn-Cu(II). This work provides the molecular basis for new therapeutic interventions to control the deleterious bioinorganic chemistry of α-Syn-Cu(II).