Functional Outcomes of Congenital Scoliosis at a Mean 35-Year Follow-up Post In Situ Fusion. Revisiting Patients From the 2002 Goldberg et al Study.

BACKGROUND: The management of congenital scoliosis poses a significant challenge for treating surgeons. The aim of our study was to provide insight into the long-term clinical results of spinal fusion in congenital scoliosis. METHODS: We performed a retrospective review of the scoliosis database in our institution for the period 1976 until 2002 identifying 43 patients with congenital scoliosis who underwent spinal fusion. Patient demographics, diagnosis, levels fused, and radiographs were evaluated. Patients were evaluated for unplanned return to the operating room (UPROR) via SRS 22, EQ5D-5L, and Oswestry Disability Index (ODI). RESULTS: Of the 43 patients who fulfilled the inclusion criteria, 22 patients agreed to participate, 3 patients were known to be deceased and 18 patients were lost to follow-up or declined to participate and were excluded. The mean age of the respondents was 40.7 years (range, 30 to 47 y) with a mean follow-up from index surgery of 35 years (range, 20 to 44 y). At most recent follow-up, 12 patients (54%) underwent UPROR. The mean age at diagnosis was 3.4 years (range, birth to 11.5 y), and the mean age for first surgery was 5.8 years (range, 1 to 13 y). As regards radiologic follow-up; the mean number of levels fused was 5.2 (range, 2 to 12). Thoracic fusion was performed in 17 patients (77%). The mean T1 to T12 height at index surgery and maturity was 166 mm (range, 130 to 240 mm) and 202 mm (range, 125 to 270 mm), respectively. The mean functional scores at follow-up were SRS 22: 4.5 (range, 2.4 to 5), cumulative EQ5D-5L score 7.2 (range, 5 to 15), and ODI: 8% (range, 2 to 30%). All respondents completed high school, 10 patients (45%) completed university, and 2 patients were awarded doctorates. Currently, 17 patients (77%) are in paid employment. CONCLUSIONS: This report constitutes the largest series of patients treated by spinal arthrodesis for congenital scoliosis followed into maturity. We demonstrate the thorax continues to grow after index fusion, patient-reported outcomes were satisfactory with superior educational and employment rates and unplanned return to theatre is rare in adult life. LEVEL OF EVIDENCE: Therapeutic Level IV.

Acid-sensing ion channel 3 mediates pain hypersensitivity associated with high-fat diet consumption in mice.

ABSTRACT: Lipid-rich diet is the major cause of obesity, affecting 13% of the worldwide adult population. Obesity is a major risk factor for metabolic syndrome that includes hyperlipidemia and diabetes mellitus. The early phases of metabolic syndrome are often associated with hyperexcitability of peripheral small diameter sensory fibers and painful diabetic neuropathy. Here, we investigated the effect of high-fat diet-induced obesity on the activity of dorsal root ganglion (DRG) sensory neurons and pain perception. We deciphered the underlying cellular mechanisms involving the acid-sensing ion channel 3 (ASIC3). We show that mice made obese through consuming high-fat diet developed the metabolic syndrome and prediabetes that was associated with heat pain hypersensitivity, whereas mechanical sensitivity was not affected. Concurrently, the slow conducting C fibers in the skin of obese mice showed increased activity on heating, whereas their mechanosensitivity was not altered. Although ASIC3 knockout mice fed with high-fat diet became obese, and showed signs of metabolic syndrome and prediabetes, genetic deletion, and in vivo pharmacological inhibition of ASIC3, protected mice from obesity-induced thermal hypersensitivity. We then deciphered the mechanisms involved in the heat hypersensitivity of mice and found that serum from high-fat diet-fed mice was enriched in lysophosphatidylcholine (LPC16:0, LPC18:0, and LPC18:1). These enriched lipid species directly increased the activity of DRG neurons through activating the lipid sensitive ASIC3 channel. Our results identify ASIC3 channel in DRG neurons and circulating lipid species as a mechanism contributing to the hyperexcitability of nociceptive neurons that can cause pain associated with lipid-rich diet consumption and obesity.

The Evaluation of Serum Metal Ion Levels and Metallosis in Graduated Patients With Magnetically Controlled Growing Rods.

BACKGROUND: Magnetically controlled growing rods (MCGR) aim to control curve progression while limiting surgical burden in children with early-onset scoliosis. Systemic and local distribution of metal debris has been documented in children with spinal implants. The aim of the study was to assess serum metal ion levels and local metal debris-related changes at the conclusion of MCGR treatment. METHODS: Between February 2019 and September 2022, all patients who had a conversion to definitive fusion at the completion of MCGR treatment in our institution were invited to participate in this study. Consenting patients had serum metal ion levels drawn (titanium, cobalt, and chromium) and histologic analyses of peri-implant tissue samples. RESULTS: We enrolled 24 children who underwent definitive fusion post-MCGR treatment for early-onset scoliosis. The average age at definitive fusion was 13.3 years (range: 11 to 17 y). The average length of MCGR treatment was 4.8 years (range: 1.5 to 6.8 y). At the end of the MCGR treatment, 23 (96%) patients had elevated serum metal ion levels. Mean serum titanium levels were 165.4 nmol/L (range: 30 to 390 nmol/L), mean serum cobalt levels were 4.6 nmol/L (range: 1.2 to 14 nmol/L), and mean serum chromium levels were 14 nmol/L (range: 2.4 to 30 nmol/L). Peri-implant soft tissue histologic analysis demonstrated local metal debris and foreign body reactions in all patients. CONCLUSIONS: At the completion of MCGR treatment, the majority of patients demonstrate elevated serum metal ion levels and local metal debris-related peri-implant soft tissue changes. Although there is no current literature to suggest these findings are harmful, further research as to the clinical significance is required. LEVEL OF EVIDENCE: Level IV.

Weight Gain and Nutritional Improvement After Magnetically Controlled Growing Rod Surgery in Early-Onset Scoliosis: A Single Centre Analysis of 68 Patients.

BACKGROUND: Early-onset scoliosis (EOS) is frequently associated with complex spine and chest wall deformities that may lead to severe cardiopulmonary impairment and malnutrition. The aim of this study is to evaluate the change in the nutritional status of EOS patients after treatment with magnetically controlled growing rod instrumentation (MCGR) in a single center. METHODS: We prospectively collected data of patients treated with MCGR for EOS in a single center. Exclusion criteria were <2 years' follow-up and incomplete weight-for-age Z-scores (WAZ) data. Preoperative and postoperative WAZ, radiographic parameters, including major coronal curve, kyphosis angle, space available for lung ratios, thoracic height, and unplanned returns to the operating room (UPROR), were analyzed. SD and 95% Confidence intervals (CI) are presented with means. RESULTS: Sixty-eight patients (37 males/31 females) were included. The mean age at surgery was 8.2 years (SD 2.8, range 1.8-14.2), and the mean follow-up time was 3.8 years (SD 1.0, range 2.1-6.8). The study population was categorized by the primary diagnosis as follows: 23 neuromuscular, 18 idiopathic, 15 congenital, and 12 syndromic patients. The major coronal curve improved between the preoperative and latest visits by 40% ( P <0.005, SD 27, CI 33-47), while the space available for lung ratios improved by 8% ( P <0.005, SD 13, CI 5-12). Thoracic height increased by 25% ( P <0.005, SD 13, CI 22-28), and kyphosis angle decreased by 25% ( P <0.005, SD 26, CI 9-39). Eighteen patients (27%) required a total of 53 UPRORs. WAZ improved significantly between the preoperative and the latest follow-up ( P =0.005). Regression analysis showed WAZ improvements were most significant in the underweight patients and the Idiopathic or Syndromic EOS patients. UPROR was not associated with deterioration in WAZ. CONCLUSIONS: Treatment of EOS patients with MCGR resulted in an improvement in nutritional status, as evidenced by the significant increase in WAZ. Underweight, Idiopathic and Syndromic EOS patients, and those who required UPROR all had significant improvement in their WAZ with MCGR treatment. LEVEL OF EVIDENCE: Therapeutic Study-Level II.

Children's Hip Predictive (CHiP) Score: A Triage Tool for Hip Dislocation in Children Referred With Suspected Hip Dysplasia.

BACKGROUND: A fundamental tenent of treating developmental dysplasia of the hip is to identify patients with dislocated hips early so as to avoid the long-term sequelae of late diagnosis. The aim of this study was to develop a readily useable triage tool for patients with suspected hip dislocation, based on the clinical history and examination findings of the referring practitioner. METHODS: All primary care referrals (n=934) over a 3-year period for suspected developmental dysplasia of the hip to a tertiary pediatric center were evaluated. Defined parameters with respect to history and clinical examination were evaluated. Multivariable logistic regression was used to establish predictors of hip dislocation, and from this a predictive model was derived which incorporated significant predictors of dislocation. An illustrative nomogram translated this predictive model into a usable numerical scoring system called the Children's Hip Prediction score, which estimates probability of hip dislocation. RESULTS: There were 97 dislocated hips in 85 patients. The final predictive model included age, sex, family history, breech, gait concerns, decreased abduction, leg length discrepancy, and medical/neurological syndrome. The area under receiver operating curve for the model is 0.761. A Children's Hip Prediction score of≥5 corresponds to a sensitivity of 76.3% and a score of≥15 has a specificity of 97.8%, corresponding to an odds ratio of 27.3 for increased risk of dislocation. CONCLUSION: We found that a novel clinical prediction score, based on readily available history and examination parameters strongly predicted risk of dislocations in hip dysplasia referral. It is hoped that this tool could be utilized to optimize resource allocation and may be of particular benefit in less well-resourced health care systems. LEVEL OF EVIDENCE: Level II.

Vitamin D levels in Irish children with fractures: A prospective case-control study with 5 year follow-up.

INTRODUCTION: Twenty-five-hydroxy-vitamin D3 (25-OH-vit D) is a prohormone that is essential for normal calcium homeostasis and bone metabolism. Understanding its role is an important component of the proper care of the pediatric orthopaedic patient. The aim of this study was to determine whether children in Ireland with fractures have increased prevalence of 25-OH-Vit D deficiency compared with age matched controls and to ascertain the relationship between a low 25-OH-vit D level and the incidence of fractures in Irish children. We hypothesised that children presenting to our centre following a fracture would have significantly lower 25-OH-vit D. METHODS: A prospective case-control study at a large urban tertiary referral academic hospital located in Dublin, Ireland was completed over a 14 month period from June 2014 to August 2015. A total of 116 subjects, distributed as cases (n = 58) and controls (n = 58) were included in this study. Whole blood (10 ml) was taken in two serum bottles from each patient. Serum 25-hydroxy-vitamin D3 levels were measured. An age matched control group was generated from other children attending the hospital, who also had vitamin D levels measured for different clinical reasons. We followed up both the fracture and control group for the next 5 years to assess the repeat fracture rate. RESULTS: Fifty-eight patients with a fracture requiring operative intervention, were included in the study. Statistical analysis was performed comparing to 58 age and sex-matched controls. The mean vitamin D level for the fracture group was 63.2 nmol/L (SD = 27.3), which was higher than the mean of the controls (62.5 nmol/L) (SD = 21.3) (p = 0.86), but this difference was found not to be statistically significant in unadjusted analysis. There was no statistically significant difference in the number of patients classified with low serum Vitamin D levels (<50 nmolL), with the fracture group consisting of 22 (37.9%) patients, and the control group of 17 patients (29.3%) (p = 0.33) with a level below 50 nmol/L. At five-year follow-up, 11 of the 58 patients (18.9%) in the fracture group went on to have a further fracture compared with eight patients (13.7%) from the control group. Out of these 11 from the fracture group five (45.45%) had been found to have a low serum 25-OH-Vit D level five years previously. Out of the eight controls that presented with a fracture within the five-year period, 3 (37.5%) had had a low vitamin D level at the origin of this study. CONCLUSION: The results of this study show that children presenting to our institution with low energy fractures have a prevalence of 38% 25-hydroxy-vitamin D deficiency. This study included children from age 1 to 16 primarily Caucasian encompassing all fracture types resulting from accidental trauma. Our findings suggest that in an Irish pediatric population vitamin D status may impact fracture risk with more than one-third being deficient in this review.

Establishing a Virtual Clinic for Developmental Dysplasia of the Hip: A Prospective Study.

BACKGROUND: The aim was to describe the introduction and operation of a virtual developmental dysplasia of the hip (DDH) clinic. Our secondary objectives were to provide an overview of DDH referral reasons, treatment outcomes, and adverse events associated with it. METHODS: A prospective observational study involving all patients referred to the virtual DDH clinic was conducted. The clinic consultant delivered with 2 DDH clinical nurse specialists (CNS). The outcomes following virtual review include further virtual review, CNS review, consultant review or discharge. Treatment options include surveillance, brace therapy, or surgery. Efficiency and cost analysis were assessed. RESULTS: Over the 3.5-year study period, 1002 patients were reviewed, of which 743 (74.2%) were female. The median age at time of referral was 7 months, (interquartile range of 5 to 11) with a median time to treatment decision of 9 days. Median waiting times from referral to treatment decision was reduced by over 70%. There were 639 virtual reviews, 186 CNS reviews, and 144 consultant reviews. The direct discharge rate was 24%. One hundred one patients (10%) had dislocated or subluxed hips at initial visit while 26.3% had radiographically normal hips. Over the study period 704 face to face (F2F) visits were avoided. Cost reductions of €170 were achieved per patient, with €588,804 achieved in total. Eighteen parents (1.8%) opted for F2F instead of virtual review. There were no unscheduled rereferrals or recorded adverse events. CONCLUSION: We report the outcomes of the first prospective virtual DDH clinic. This clinic has demonstrated efficiency and cost-effectiveness, without reported adverse outcomes to date. It is an option to provide consultant delivered DDH care, while reducing F2F consults. LEVEL OF EVIDENCE: Level III.

TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity.

KEY POINTS: TRESK background K+ channel is expressed in sensory neurons and acts as a brake to reduce neuronal activation. Deletion of the channel enhances the excitability of nociceptors. Skin nociceptive C-fibres show an enhanced activation by cold and mechanical stimulation in TRESK knockout animals. Channel deletion selectively enhances mechanical and cold sensitivity in mice, without altering sensitivity to heat. These results indicate that the channel regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold-sensing. ABSTRACT: Background potassium-permeable ion channels play a critical role in tuning the excitability of nociceptors, yet the precise role played by different subsets of channels is not fully understood. Decreases in TRESK (TWIK-related spinal cord K+ channel) expression/function enhance excitability of sensory neurons, but its role in somatosensory perception and nociception is poorly understood. Here, we used a TRESK knockout (KO) mouse to address these questions. We show that TRESK regulates the sensitivity of sensory neurons in a modality-specific manner, contributing to mechanical and cold sensitivity but without any effect on heat sensitivity. Nociceptive neurons isolated from TRESK KO mice show a decreased threshold for activation and skin nociceptive C-fibres show an enhanced activation by cold and mechanical stimulation that was also observed in behavioural tests in vivo. TRESK is also involved in osmotic pain and in early phases of formalin-induced inflammatory pain, but not in the development of mechanical and heat hyperalgesia during chronic pain. In contrast, mice lacking TRESK present cold allodynia that is not further enhanced by oxaliplatin. In summary, genetic removal of TRESK uncovers enhanced mechanical and cold sensitivity, indicating that the channel regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold-sensing, acting as a brake to prevent activation by innocuous stimuli.

High expression of LC3A, LC3B, and p62/SQSTM1 autophagic proteins in human colonic ganglion cells

@#Introduction: Autophagy is a mechanism that degrades large damaged organelles and misfolded proteins to maintain the homeostasis in all cells. It plays double-faceted roles in tumourigenesis and prevention of various cancers. In our side observation of investigating the prognostic value of autophagy in colorectal cancer (CRC), we found high expression of autophagy proteins (LC3A, LC3B, and p62/SQSTM1) in the colonic ganglion cells. To our best understanding, this is the first paper reporting such finding. Materials and Methods: Formalin-fixed paraffin-embedded (FFPE) CRC tissues blocks were retrieved and confirmed by haematoxylin & eosin (H&E) staining. Immunohistochemistry (IHC) targeting autophagy proteins (LC3A, LC3B, and p62/SQSTM1) was then performed followed by pathological examination. Results: All three autophagy proteins were present in both normal and tumour tissues of CRC patients. Interestingly, high expression of autophagy proteins in colonic ganglion cells was consistently seen regardless of tissue type (normal or cancer) or tumour site (caecum, ascending, transverse, descending, sigmoid colon and rectum). Conclusions: This work highlights the high autophagic activities in human colonic ganglion cells.

Current Update of Laboratory Molecular Diagnostics Advancement in Management of Colorectal Cancer (CRC).

Colorectal cancer (CRC) continues to be one of the most common cancers globally. The incidence has increased in developing countries in the past few decades, this could be partly attributed to aging populations and unhealthy lifestyles. While the treatment of CRC has seen significant improvement since the advent of target-specific therapies and personalized medicine, CRC is oftentimes detected at late or advanced stages, thereby reducing the efficacy of treatment. Hence, screening for early detection is still the key to combat CRC and to increase overall survival (OS). Considering that the field of medical diagnostics is moving towards molecular diagnostics, CRC can now be effectively screened and diagnosed with high accuracy and sensitivity. Depending on the tumor genotype and genetic profile of the individual, personalized treatments including tyrosine kinase inhibitor therapy and immunotherapy can be administered. Notably, there can be no one single treatment that is effective for all CRC patients due to the variation in tumor genetics, which highlights the importance of molecular diagnostics. This review provides insights on therapeutic modalities, molecular biomarkers, advancement of diagnostic technologies, and current challenges in managing CRC.

Antibody-Mediated Therapy against HIV/AIDS: Where Are We Standing Now?

Acquired immunodeficiency syndrome (AIDS) cases are on the rise globally. To date, there is still no effective measure to eradicate the causative agent, human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is being used in HIV/AIDS management, but it results in long-term medication and has major drawbacks such as multiple side effects, high cost, and increasing the generation rate of escape mutants. In addition, HAART does not control HIV-related complications, and hence more medications and further management are required. With this, other alternatives are urgently needed. In the past, small-molecule inhibitors have shown potent antiviral effects, and some of them are now being evaluated in clinical trials. The challenges in developing these small molecules for clinical use include the off-target effect, poor stability, and low bioavailability. On the other hand, antibody-mediated therapy has emerged as an important therapeutic modality for anti-HIV therapeutics development. Many antiviral antibodies, namely, broad neutralizing antibodies (bnAbs) against multiple strains of HIV, have shown promising effects in vitro and in animal studies; further studies are ongoing in clinical trials to evaluate their uses in clinical applications. This short review aims to discuss the current development of therapeutic antibodies against HIV and the challenges in adopting them for clinical use.

An ex vivo Perifusion Method for Quantitative Determination of Neuropeptide Release from Mouse Hypothalamic Explants.

The hypothalamus is a primary brain area which, in mammals, regulates several physiological functions that are all related to maintaining general homeostasis, by linking the central nervous system (CNS) and the periphery. The hypothalamus itself can be considered an endocrine brain region of some sort as it hosts in its different nuclei several kinds of neuropeptide-producing and -secreting neurons. These neuropeptides have specific roles and participate in the regulation of homeostasis in general, which includes the regulation of energy metabolism, feeding behavior, water intake and body core temperature for example. As previously mentioned, in order to exert their effects, these peptides have to be produced but also, and mostly, to be secreted. In this context, it is of great importance to be able to assess how certain conditions, diseases, or treatments can actually influence the secretion of neuropeptides, thus the function of the different neuropeptidergic circuits. One method to assess this is the perifusion of hypothalamic explants followed by quantification of peptides within the collected fractions. Here, we explain step-by-step how to collect fractions during ex vivo perifusion of hypothalamic explants in which one can determine quantitatively neuropeptide/neurohormone release from these viable isolated tissues. Hypothalami perifusion has two great advantages over other existing assays: (1) it allows pharmacological manipulation to dissect out signaling mechanisms underlying release of different neuropeptides/neurohormones in the hypothalamic explants and, (2) it allows simultaneous experiments with different conditions on multiple hypothalami preparations, (3) it is, to our knowledge, the only method that permits the study of neuropeptide secretion in basal conditions and under repeated stimulations with the same hypothalami explants.

New Insight in Cold Pain: Role of Ion Channels, Modulation, and Clinical Perspectives.

Cold temperature detection involves the process of sensory transduction in cutaneous primary sensory nerve terminals, which converts thermal stimuli into depolarizations of the membrane. This transformation into electrical signals is followed by the subsequent propagation of action potentials in cold-sensitive afferent nerve fibers. A large array of ion channels shapes this process; however, the precise contribution of specific ion channel subtypes to cold perception and cold pain remains elusive. This review aims at giving an update on our current understanding of the role played by TRPs, leak K+ and voltage-gated Na+ and K+ channels in the transduction of cold by nociceptors and in cold-induced pain.

The efficacy of an extended scope physiotherapy clinic in paediatric orthopaedics.

BACKGROUND: The demand for paediatric orthopaedic care is growing, and providing the service required is an increasingly challenging task. Physiotherapist-led triage clinics are utilised in adult orthopaedics to enable the provision of care to patients who may not require a surgical consult. The Physiotherapy Orthopaedic Triage Clinic (POTC) was established in Our Lady's Children's Hospital Crumlin in response to increasing demands on the paediatric orthopaedic service. The clinic is run by physiotherapists working in an advanced practice role (APP), and is the first paediatric clinic of its type and scale in the Republic of Ireland. PURPOSE: To evaluate the efficacy of the service over the 3-year period from January 2011 to December 2013. METHODS: A review of the prospectively gathered database was performed in order to establish the demographic profile of patients, investigate clinic outcomes, and evaluate the reduction in patient waiting times. RESULTS: 2650 patients were managed by the clinic over the 3-year period. A total of 77 % of patients were managed without consultant intervention. Fifty-three percent of patients were diagnosed as having a normal presentation. The mean waiting time reduced from 101.9 weeks pre-2010 to 15.4 weeks in 2013 for those patients managed by the POTC. CONCLUSION: Since its inception, the clinic has significantly reduced waiting times for routine elective paediatric orthopaedic patients while managing the majority of patients independent of surgical opinion. This study shows that the APP can deliver high-quality care in the paediatric orthopaedic setting, benefitting both patients and service.

Non-acidic activation of pain-related Acid-Sensing Ion Channel 3 by lipids.

Extracellular pH variations are seen as the principal endogenous signal that triggers activation of Acid-Sensing Ion Channels (ASICs), which are basically considered as proton sensors, and are involved in various processes associated with tissue acidification. Here, we show that human painful inflammatory exudates, displaying non-acidic pH, induce a slow constitutive activation of human ASIC3 channels. This effect is largely driven by lipids, and we identify lysophosphatidylcholine (LPC) and arachidonic acid (AA) as endogenous activators of ASIC3 in the absence of any extracellular acidification. The combination of LPC and AA evokes robust depolarizing current in DRG neurons at physiological pH 7.4, increases nociceptive C-fiber firing, and induces pain behavior in rats, effects that are all prevented by ASIC3 blockers. Lipid-induced pain is also significantly reduced in ASIC3 knockout mice. These findings open new perspectives on the roles of ASIC3 in the absence of tissue pH variation, as well as on the contribution of those channels to lipid-mediated signaling.

A Long-term Retrospective Evaluation of Functional and Radiographic Outcomes of Pediatric Hip Surgery in Hurler Syndrome.

BACKGROUND: After successful hematopoietic stem cell transplantation, maintaining function and mobility have become key goals in the management of patients with Hurler syndrome, (mucopolysaccharoidosis type 1H). The aim of this study was to establish the functional and radiologic outcomes after hip surgery in patients with this condition who had reached skeletal maturity. METHODS: We prospectively followed 13 mucopolysaccharoidosis type 1H patients with closed triradiate cartilages who had undergone hip surgery in a single institution (Our Lady's Children's Hospital, Crumlin) in early childhood, after successful hematopoietic stem cell transplantation. Functional assessment was performed using the Harris Hip Score. Acetabular and femoral head morphology were defined using a pelvic radiograph. RESULTS: The average age at follow-up was 18.6 years (range, 13.2 to 23.8 y). The average length of follow-up from surgical intervention was 14.6 years (range, 10.3 to 21.6 y). The average Harris Hip Score at follow-up was 61.0 (range, 19 to 91). At follow-up, 4 patients were either wheelchair bound or required a walking frame to mobilize in the community. At follow-up, all hips were in-joint with an average center edge angle of 37.7 degrees (range, 0 to 63 degrees). All hips displayed characteristic medial flattening of the femoral head. Ten hips (of 26 hips) showed radiologic degenerative changes with loss of joint space <2 mm. CONCLUSIONS: Despite the surgical provision of stable well-covered hips, active intervention did not prevent the development of radiologic deterioration and clinically significant hip arthritis. We recommend that pediatric hip surgery in Hurler syndrome be designed with the possibility of early hip replacement in mind. LEVEL OF EVIDENCE: Level III.

The Nav1.9 channel is a key determinant of cold pain sensation and cold allodynia.

Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in response to noxious cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory neurons responding to cooling, which allows the channel to amplify subthreshold depolarizations generated by the activation of cold transducers. Consequently, cold-triggered firing is impaired in Nav1.9(-/-) neurons, and Nav1.9 null mice and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9 expression in rodents also alleviates cold pain hypersensitivity induced by the antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons and is required for the perception of cold pain under normal and pathological conditions.

The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function.

The T-type calcium channel Cav3.2 emerges as a key regulator of sensory functions, but its expression pattern within primary afferent neurons and its contribution to modality-specific signaling remain obscure. Here, we elucidate this issue using a unique knockin/flox mouse strain wherein Cav3.2 is replaced by a functional Cav3.2-surface-ecliptic GFP fusion. We demonstrate that Cav3.2 is a selective marker of two major low-threshold mechanoreceptors (LTMRs), Aδ- and C-LTMRs, innervating the most abundant skin hair follicles. The presence of Cav3.2 along LTMR-fiber trajectories is consistent with critical roles at multiple sites, setting their strong excitability. Strikingly, the C-LTMR-specific knockout uncovers that Cav3.2 regulates light-touch perception and noxious mechanical cold and chemical sensations and is essential to build up that debilitates allodynic symptoms of neuropathic pain, a mechanism thought to be entirely A-LTMR specific. Collectively, our findings support a fundamental role for Cav3.2 in touch/pain pathophysiology, validating their critic pharmacological relevance to relieve mechanical and cold allodynia.

Discectomy-related information on the internet: does the quality follow the surge?

STUDY DESIGN: A quality-control Internet-based study using recognized quality-scoring systems. OBJECTIVE: To evaluate the quality of information available on the Internet. SUMMARY OF BACKGROUND DATA: Quality of health information on the Internet is of much concern and the emphasis for appraisal of Internet Web sites is needed. This study is to determine if it has improved with the surge in Internet usage. METHODS: The 3 most commonly used search engines were identified and a search for "Discectomy" was performed on each. Two reviewers categorized the Web sites according to their types and the quality of each was assessed using recognized scoring systems including the Journal of the American Medical Association (JAMA) benchmark, DISCERN score, and discectomy-specific content score. The quality of the information was also assessed according to the presence and absence of the Health on the Net code. RESULTS: Fifty-three Web sites were identified, and analyzed. Commercial Web sites were predominant, 24 of them were identified, 7 were governmental, 6 were produced by physicians, none were produced by allied health professionals, 3 were academic, 4 were public health information Web sites, 4 were attached to social media and discussion groups, 3 were related to media, and 2 were unspecified. Internet sites with a Health on the Net code demonstrated significantly higher quality than those without the code (P < 0.0001). Public health information Web sites attained the highest overall DISCERN and discectomy-specific scores followed by Web sites of the government and nonprofit organizations. CONCLUSION: The overall quality of information regarding discectomy remains poor and variable despite an exponential increase in the number of users and Web sites, with a slight trend toward improvement, only 20% to 30% are of good quality, compared with that 10 years ago (<10%). Presence of Health on the Net code is a very reliable marker for health information quality.

The prevalence of abnormal preoperative coagulation tests in pediatric patients undergoing spinal surgery for scoliosis.

BACKGROUND CONTEXT: Multilevel spinal fusion surgery for deformity correcting spinal surgery in pediatric patients with scoliosis has typically been associated with significant blood loss. The mechanism of bleeding in such patients is not fully understood. Coagulation abnormalities, which may be associated with scoliosis, are thought to play a role. PURPOSE: To document and compare the prevalence of preoperative coagulation abnormalities among patients with scoliosis attending a pediatric orthopedic department for spinal fusion surgery with patients attending for minor surgery. STUDY DESIGN: An observational study. All patients were recruited from a pediatric tertiary referral center in Dublin, Ireland. PATIENT SAMPLE: Coagulation profile results were prospectively collected over a 2-year period from 165 spinal surgery patients. In total, 175 patients were included in the non-scoliosis group. These patients attended the day ward for minor procedures and were recruited over a 4-month period. OUTCOME MEASURES: The primary outcome measure was the coagulation profiles, which included prothrombin time, activated partial thromboplastin time (APTT), and thrombin time (TT). Levels of Coagulation Factors II, V, VII, and X were also recorded. METHODS: All blood samples were sent to the haematology laboratory to establish the coagulation profile. The primary outcome was the presence of an abnormal coagulation screening test (if any of PT, APTT, or TT were abnormal). Prothrombin time, APTT, and TT were also analyzed as individual continuous variables, as well as Coagulation Factors II, V, VII, and X. Regression analysis was used to compare the coagulation profile of scoliosis patients with that of non-scoliosis patients. There were no outside funding sources or any potential conflict of interest associated with this study. RESULTS: The scoliosis patients were more likely to have an abnormal preoperative screening test compared with non-scoliosis patients, with an odds ratio of 2.6. Further analysis showed statistically significant longer clotting times for patients with scoliosis compared with those without; PT (t=3.37, p=.001), APTT (t=4.26, p<.001), TT (t=4.52, p<.001). Of the coagulation factors analyzed, only factor X was significantly different in scoliosis patients compared with non-scoliosis controls (t=-4.41, p<.001). CONCLUSIONS: Children with scoliosis have a higher prevalence of preoperative coagulation abnormalities compared with normal healthy patients.