GABAergic/Glycinergic and Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes of STXBP1 Encephalopathy.

An increasing number of pathogenic variants in presynaptic proteins involved in the synaptic vesicle cycle are being discovered in neurodevelopmental disorders. The clinical features of these synaptic vesicle cycle disorders are diverse, but the most prevalent phenotypes include intellectual disability, epilepsy, movement disorders, cerebral visual impairment, and psychiatric symptoms ( Verhage and Sørensen, 2020; Bonnycastle et al., 2021; John et al., 2021; Melland et al., 2021). Among this growing list of synaptic vesicle cycle disorders, the most frequent is STXBP1 encephalopathy caused by de novo heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1, also known as MUNC18-1; Verhage and Sørensen, 2020; John et al., 2021). STXBP1 is an essential protein for presynaptic neurotransmitter release. Its haploinsufficiency is the main disease mechanism and impairs both excitatory and inhibitory neurotransmitter release. However, the disease pathogenesis and cellular origins of the broad spectrum of neurological phenotypes are poorly understood. Here we generate cell type-specific Stxbp1 haploinsufficient male and female mice and show that Stxbp1 haploinsufficiency in GABAergic/glycinergic neurons causes developmental delay, epilepsy, and motor, cognitive, and psychiatric deficits, recapitulating majority of the phenotypes observed in the constitutive Stxbp1 haploinsufficient mice and STXBP1 encephalopathy. In contrast, Stxbp1 haploinsufficiency in glutamatergic neurons results in a small subset of cognitive and seizure phenotypes distinct from those caused by Stxbp1 haploinsufficiency in GABAergic/glycinergic neurons. Thus, the contrasting roles of excitatory and inhibitory signaling reveal GABAergic/glycinergic dysfunction as a key disease mechanism of STXBP1 encephalopathy and suggest the possibility to selectively modulate disease phenotypes by targeting specific neurotransmitter systems.

Analysis of Return to Play After Modified Broström Lateral Ankle Ligament Reconstruction.

BACKGROUND: Despite marked improvements in stability after lateral ankle ligament repair, many patients do not return to their preinjury activity level. There are few studies addressing athletes' assessment of their ability to return to play after lateral ankle ligament reconstruction for recurrent instability. PURPOSE: To determine the rate of return to the preinjury activity level among physically active patients after the modified Broström procedure (MBP) for recurrent lateral ankle instability. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Included were patients who had undergone a primary MBP by a single surgeon over a 6-year period and had a minimum 24 months of follow-up. A telephone questionnaire was conducted to ascertain the patient's ability to return to sport and/or work activity at final follow-up. Activity levels were evaluated utilizing the Tegner activity score. Outcome scores and other measured variables were compared between patients who returned to their preinjury level and those who did not. The reasons for failing to return were also documented. RESULTS: Of the 59 patients who met the inclusion criteria, 41 (69%; 20 men and 21 women) participated in the telephone interview. Results indicated that 22 (54%) returned to their prior level of activity (returners). The mean age of returners was 27.2 years; for nonreturners, the mean age was 27.1 years. Most patients (36/41; 88%) were satisfied with surgery and the overall outcome. Of the 19 nonreturners, 7 (37%) noted ankle-related reasons for not returning (pain: 57%; residual instability: 29%; decreased range of motion: 14%), and 12 (63%) cited non-ankle-related reasons. The mean preinjury and postoperative Tegner score for returners was 6.8. Moreover, 7 of 14 (50%) high-level athletes with preinjury Tegner scores ≥8 returned to their preinjury activity level. For high-level athletes who did not return to their previous level, the mean postoperative Tegner score was 6.6, and only 1 (7%) cited an ankle-related reason for not returning. CONCLUSION: A high patient satisfaction rate was reported after the MBP for recurrent lateral ankle instability. The majority of patients who did not return to their preinjury level cited a non-ankle-related factor as the reason for not returning to sport. This was especially true for the higher level athletes.

Chronic Lateral Ankle Instability: Surgical Management.

Surgical management for chronic lateral ankle ligament instability is useful when patients have failed nonoperative modalities. Open anatomic reconstruction is an effective method of stabilization. Ankle arthroscopy is a recommended to address intra-articular disorder before stabilization. An anatomic approach provides full range of motion, stability, and return to sport and activity. Allograft or suture tape augmentation can be useful for patients with generalized ligamentous laxity, patients with high body mass index, and elite athletes. Allograft reconstruction may be especially useful in revision procedures. Arthroscopic approach to lateral ankle ligament stabilization may provide good outcomes, with long-term data still limited.

Meniscal Repairs in the Adolescent Knee: Can the Number of Fixation Sites Improve Outcomes?

BACKGROUND: Meniscal pathology in children and adolescents is now a common occurrence because of their ever-increasing participation in youth sports. PURPOSE: To investigate the outcomes of arthroscopic meniscal repair in an adolescent cohort and analyze the variables that may affect outcomes, specifically the number of fixation sites utilized during repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective review of all children and adolescents younger than 18 years who underwent arthroscopic meniscal repair at a single institution was performed. Patient characteristics, operative details (eg, tear pattern, tear location, method of repair, and number of fixation sites [determined based on the number of sutures used for repair]), and concomitant procedures were recorded. RESULTS: A total of 175 primary meniscal repairs met inclusion criteria and were analyzed. Of this cohort, 115 were able to be contacted and were included in the final study cohort. The mean follow-up was 41 months. The mean age of the children was 14.9 years, and 91 (79%) had concomitant anterior cruciate ligament reconstructions with their meniscal repair. The mean Pediatric International Knee Documentation Committee functional outcome score was 91 (range, 43-100), and the mean Lysholm functional outcome score was 91 (range, 47-100). Of the 115 meniscal repairs, there were a total of 19 reoperations (17%); 15 (13%) were because of meniscal repair failures. The only variable that statistically increased the risk of meniscal repair failure was low number of fixation sites, with the failure group having a mean of 1.79 sutures and the nonfailure group having a mean of 2.97 sutures (P = .03). CONCLUSION: Successful meniscal repairs and a lower failure rate may be achieved with a greater number of fixation sites with promising results at a minimum 2-year follow-up. Validated functional outcome scores were good, with a 13% failure rate. Larger cohort, longer term, multicenter multisurgeon data are still needed to further elucidate the number of fixation sites needed when performing a meniscal repair in the pediatric and adolescent knee.

Utility of Bioabsorbable Fixation of Osteochondral Lesions in the Adolescent Knee: Outcomes Analysis With Minimum 2-Year Follow-up.

BACKGROUND: Osteochondral lesions (OCLs) of the knee, whether occurring secondary to osteochondritis dissecans or a traumatic osteochondral fracture, are commonly encountered in the pediatric and adolescent population. Given the potential for healing in this population, coupled with adequate surgical reduction and stability of OCL fixation, an opportunity exists to avoid a major restorative procedure and the associated substantial costs and potential morbidity. PURPOSE: To analyze the outcomes of bioabsorbable fixation of OCLs in the adolescent knee at a minimum of 2 years. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: An institutional review board-approved retrospective review was performed of patients younger than 18 years who underwent bioabsorbable fixation of an OCL of the knee with a minimum 2-year follow-up. Patient demographics, operative details, and postoperative clinical findings were detailed and recorded. All cases were performed by a single surgeon. RESULTS: There were 38 patients treated surgically for an OCL between 2009 and 2016. Of these, 38 patients (mean age, 14.7 years) were evaluated at a mean of 59 months. OCL fixation consisted of a mean of 1.4 bioabsorbable screws and 1.5 darts. At final follow-up, mean pre- and postoperative Tegner scores were 6.6 and 6.4, respectively, while Lysholm and Pediatric International Knee Documentation Committee scores were 89.8 and 88.1, respectively. A total of 6 patients underwent secondary procedures postoperatively. One patient required a secondary procedure related to OCL fixation, which was secondary to a proud implant. The other secondary procedures included second-look arthroscopic surgery for pain after an injury postoperatively, planned anterior cruciate ligament reconstruction, staged medial patellofemoral ligament reconstruction, and manipulation under anesthesia for arthrofibrosis (n = 2). None of the 32 patients required a revision cartilage procedure at the time of final follow-up. CONCLUSION: The use of bioabsorbable implants in the adolescent knee appears to be a safe and efficacious treatment with good functional outcomes at long-term follow-up and a low revision rate. Additional long-term multisurgeon and multicenter trials with a larger cohort are needed to further elucidate the role of bioabsorbable fixation of an OCL in the adolescent knee.

Proximal femur prosthetic interposition arthroplasty for painful dislocated hips in children with cerebral palsy.

PURPOSE: Children with cerebral palsy often have musculoskeletal disorders involving the hip. There are several procedures that are commonly used to treat these disorders. Proximal femur prosthetic interposition arthroplasty (PFIA) is an option for non-ambulatory children with cerebral palsy who have a painful, spastic dislocated hip. The purpose of our study was to evaluate the results of PFIA by examining treatment outcomes, complications, and overall effects on the child and their caregiver. METHODS: Charts were reviewed over a 5-year period at our institution. The focus of the data collection was pain, range of motion (ROM), and overall clinical outcome. Clinical outcome was graded as excellent, good, fair, and poor. Length of follow-up, presence of heterotopic ossification, femoral prosthesis migration, and information provided by competed caregiver questionnaires were analyzed. RESULTS: A total of 16 hips in 12 patients met the inclusion criteria. Average age at time of surgery was 12 years 1.2 months. Average follow-up was 40.4 months. Three hips required revision surgery. Average time before revision surgery was 16 months. Overall outcomes were excellent/good for seven hips and fair/poor for nine. Pain outcomes were excellent/good for nine hips and fair/good for seven. ROM outcomes were excellent/good for nine hips and fair/poor for seven. The majority of caregivers surveyed would recommend this procedure. CONCLUSION: Clinical evaluation of the effectiveness of PFIA yielded variable results with this cohort of children with regards to pain and range of motion. Despite these varied results, the majority of caregivers were satisfied with the outcome and would recommend PFIA. PFIA is a salvage option for the painful, spastic dislocated hip, but significant evidence to prove its effectiveness over other salvage procedures is lacking. Based on our results, we conclude that PFIA has the ability to benefit children with cerebral palsy with an acceptable risk profile similar to that reported in recent publications. Level of evidence IV; retrospective case-series.

Casting: Pearls and pitfalls learned while caring for children's fractures.

Casting is a routine procedure used for fracture care in the pediatric population. The purpose of this review is to provide pearls and pitfalls that our institution has learned from previous literature. When applying the cast, we recommend using cotton padding for the liner and fiberglass or plaster depending on how much swelling is expected. A well-molded cast must be applied in order to prevent further fracture displacement. Cast valving is a valuable technique that allows a decrease in pressure which prevents discomfort and complications like compartment syndrome. Preventing thermal injuries, skin complications, and a wet cast are other important considerations when caring for casts. Appropriate use of a cast saw, avoiding pressure spots, and properly covering the cast are ways to respectively prevent those complications. Lastly, patient education remains one of the most valuable tools in ensuring proper cast maintenance.

Monitoring and Surveillance of Hemodialysis Vascular Access Using StenTec and Physical Exam.

Hemodialysis vascular access surveillance for hemodynamically significant stenosis can be a challenge because no universal gold standard exists. The StenTec Gauge measures static intra-access peak pressure and graphically displays the ratio of this pressure to systemic systolic (peak) arterial pressure (PIA ratio). In combination with careful physical exam (PE), the StenTec Gauge is an acceptable and cost-effective way of detecting hemodynamically significant stenosis in arteriovenous fistulas (AVF) or grafts (AVG). In a selected population of 21 hemodialysis patients with mature arteriovenous access, a StenTec reading and physical examination was measured on a weekly basis. Interventional procedures for suspected access dysfunction were performed if there was a greater than 25% increase of the PIA ratio from baseline in two consecutive readings, along with correlating clinical suspicion from physical examination findings. StenTec independently had a sensitivity of 56% and a specificity of 99% in detecting clinically significant stenosis. PE alone had a sensitivity of 89% and a specificity of 100%. StenTec combined with PE had a sensitivity of 100% and a specificity of 99% for predicting hemodynamically significant stenosis. StenTec detected 4 of 10 patients who had a PIA ratio value of ≥0.5, which correlates with current National Kidney Foundation Disease Outcomes Quality Initiative (KDOQI) criteria for mean intra-access pressure ratios indicating a clinically significant outflow stenosis. PE predicted 9 of 10 patients with stenosis, and the combination of StenTec and PE predicted all 10 patients with clinically significant stenosis using the KDOQI criteria for PIA ratio. Hemodynamically significant access stenosis can be detected with excellent accuracy using both StenTec and PE measurements combined for monitoring and surveillance methods.

A Comparison of Various Contemporary Methods to Prevent a Wet Cast.

BACKGROUND: Many traditional methods and commercially available products are available to prevent a wet cast, although there is a paucity of literature regarding the optimal strategy. METHODS: Using a synthetic leg model, a short leg cast was applied and six different methods were tested. Group A (Glad Press'n Seal wrap), Group B (plastic bag with rubber band), Group C (plastic bag with duct tape), Group D (double plastic bags with duct tape), Group E (CVS Pharmacy Reusable Cast & Wound Protector), and Group F (Dry Corp Dry Pro Large Half Leg Waterproof Cast Cover). Casts were submerged in water for two minutes and were weighed. Each group had ten individual trials. Effectiveness was measured by calculating the amount of water absorption using cast weights before and after submersion. RESULTS: The percentage of water absorption prevention ranged from 62% to 100%, with Groups A and B being the least effective and Groups D, E, and F being the most effective. There was considerable variation in the simplicity of use. Groups C, D, and E were found to be simple to use, with increasing difficulty in Groups A, B, and F. CONCLUSIONS: Our findings conclude that the six methods tested are effective in preventing the majority of water saturation. Although abstaining from contact with water is the most prudent approach, if a cast cover is to be used, double plastic bags with duct tape (100% prevention, $10) and the CVS cast protector (100% prevention, $13) are the preferred contemporary methods to prevent a wet cast.

Carbon dioxide gas arthrography for the evaluation of pediatric hip conditions: what is the risk and reliability?

BACKGROUND: Various pediatric conditions often necessitate a morphologic examination of the hip joint in infancy or childhood, and multiple imaging options have been employed to achieve this goal. Arthrography is one such modality. Different types of contrast media have been utilized and include pharmacologic contrast agents, air, and carbon dioxide. There are scattered reports of complications related to the typical various media used during arthrography. Some of the most concerning are related to gas emboli following the use of air or carbon dioxide. This study assesses the potential complications of carbon dioxide hip arthrography in a series of children over a 12-year period. METHODS: A retrospective review of the medical records of children between the ages of 0 and 3 years who underwent hip arthrography using carbon dioxide gas as the contrast medium was conducted. Outcome measures analyzed included volume of CO2 injected, vital signs, and perioperative and postoperative end-tidal CO2. RESULTS: Our study population was comprised of 118 hips in 90 children. We found no correlation between the volume of CO2 injected and the patient's vital signs or end-tidal CO2 at any point during the perioperative or postoperative period. None of the children exhibited any evidence for cardiopulmonary compromise or clinical signs of embolism. DISCUSSION: To our knowledge, there have been no large studies reporting on carbon dioxide arthrography and its potential complications. There were no gas embolisms and/or cardiopulmonary complications in our patients in the perioperative, postoperative, or 1-year follow-up period. Utilizing carbon dioxide gas as the contrast media for hip arthrography in children is safe and can help aid in the treatment of pediatric hip conditions. LEVEL OF EVIDENCE: Therapeutic Level IV.

Trends and demographics in hip arthroscopy in the United States.

PURPOSE: The purpose of this study was to evaluate the trends and report on the demographics of patients undergoing hip arthroscopy in the United States. METHODS: Patients who underwent hip arthroscopy from 2004 to 2009 were identified by searching Current Procedural Terminology codes in the PearlDiver Patient Records Database (PearlDiver Technologies, Fort Wayne, IN), a national database of orthopaedic insurance records. The year of procedure, age, gender, and region of the United States were recorded for each patient. Results were reported for each variable as the incidence of procedures identified per 10,000 patients searched in the database. RESULTS: In total, 3,447 cases of hip arthroscopy were identified between 2004 and 2009. The incidence of procedures increased significantly over the study period, from 1.20 cases per 10,000 patients in 2004 to 5.58 in 2009 (P < .001). Hip arthroscopy was performed most commonly in patients aged 20 to 39 years (P < .05), with an incidence of 4.45 cases in each age group. In contrast to other common arthroscopic procedures searched, no gender differences were observed, with a male-to-female ratio of 0.89 (P = .18). The greatest incidence of hip arthroscopy was observed in the Western region with an incidence of 5.24 cases identified compared with 2.94, 2.70, and 2.56 in the Northeast, Midwest, and South, respectively (P < .001). CONCLUSIONS: A 365% increase in the rate of hip arthroscopy was observed in the examined cohort of patients between 2004 and 2009. The majority of cases were performed in patients aged 20 to 39 years, with no difference in gender. The Western region of the United States was found to have a higher incidence of hip arthroscopy compared with the Midwest, South, and Northeast. LEVEL OF EVIDENCE: Level IV, cross-sectional study.

Increased prevalence of val(66)met BDNF genotype among subjects with cervical dystonia.

Abnormalities of cortical representational maps and their plasticity have been described in dystonia. A common polymorphism for BDNF has been associated with abnormal cortical plasticity, and thus might contribute to pathogenesis of dystonia in some subjects. As a first step towards this suggestion, the current study examined the prevalence of this polymorphism. BDNF genotype was examined in 34 subjects with cervical dystonia, 54 age-matched healthy controls, and 53 subjects with a different movement disorder, Parkinson's disease. ApoE genotype, known to influence neurological outcome in some conditions, was also examined as a control. In subjects with cervical dystonia, the val(66)met polymorphism was approximately twice as prevalent when compared to either control group. This was not true of ApoE genotype, which was similarly distributed across subject groups. The current findings suggest that the BDNF val(66)met polymorphism might play a role in the pathogenesis of cervical dystonia in some subjects.

Prevalence of patch test results from 1970 to 2002 in a multi-centre population in North America (NACDG).

BACKGROUND: The North American Contact Dermatitis Group (NACDG) has members who assess subjects with suspected allergic contact dermatitis (ACD) and patch tests them with the same screening allergens using a standardized procedure permitting analysis of long-term trends in patch test reactions. OBJECTIVE: This study reports the trends in prevalence patch test positivity of allergens by pooling data collected by the NACDG between 1970 and 2002. PATIENTS/METHODS: Patients were tested with the screening series of allergens, using a standardized technique. Data from these patients were recorded on a standard computer entry form and analysed. More than 100 allergens were tested on over 34,000 patients during several patch studies between the period. The Cochran-Armitage test of trend is used to evaluate changes in prevalence over time. RESULTS: 4 trends are noticed: (1) The incidence of presumed allergic nickel (P < 0.0001) and quaternium-15 (P < 0.0001) reactions rose with consistency over the years. (2) While that of cinnamic aldehyde (P = 0.21) and p-phenylenediamine (P < 0.0001) decreased. (3) The prevalence of positive reactions for potassium dichromate (P < 0.0001) shows an initial steady decrease but then a sharp increase starting from the 1996 period. (4) In contrast, thiuram (P = 0.0008) and neomycin (P < 0.0001) show an initial general increase, with a sharp decrease between 1998 and 2002. CONCLUSION: Implications for opportunities to prevent ACD by utilizing less-allergenic alternatives appear robust; however, we do not wish to over generalize interpretations because of important limitations.

Comedogenicity in rabbit: some cosmetic ingredients/vehicles.

The rabbit external ear canal was used to define which chemicals caused comedone formation on topical application. Some of the tested ingredients are currently used in topically applied formulations. Certain raw materials have been shown to produce follicular hyperkeratosis in the rabbit ear assay. This study quantifies comedogenic potential of cosmetic materials, including: isopropyl palmitate, isopropyl myristate, butyl stearate, isopropyl isostearate, decyl oleate, isostearyl neopentanoate, isocetyl stearate, myristle myristate, cocoa butter, cetyl alcohol, paraffin, stearyl alcohol sodium lauryl sulfate (SLS), and petrolatum. The first nine were deemed positive. Factors aiding clinical relevance are listed.