Medial Patellofemoral Ligament Augmentation Repair for Primary Patellar Dislocation With Concomitant Chondral or Osteochondral Injury in Children and Adolescents: Outcomes at Minimum 2-Year Follow-up.

Background: Treatment of primary patellar dislocation (PPD) with chondral or osteochondral injury without patellar stabilization in the adolescent population may lead to unsatisfactory outcomes. Surgical treatment, with or without traditional medial patellofemoral ligament (MPFL) reconstruction, is a topic of interest. Purpose: To compare postoperative outcomes and rates of patellar redislocation and return to the operating room (OR) in patients who sustained a PPD with chondral or osteochondral injury and were surgically treated with versus without suture tape augmentation repair of the MPFL. Study Design: Cohort study; Level of evidence, 3. Methods: Adolescents who sustained a PPD with chondral or osteochondral injury confirmed via magnetic resonance imaging (MRI) and who were treated by a single surgeon between January 2009 and November 2020 were retrospectively reviewed. Patients were grouped into those who underwent chondral or osteochondral treatment with suture tape augmentation repair of the MPFL (ST group; n = 20) and those who did not have suture tape augmentation or repair (no-ST group; n = 20; 11 patients within the no-ST group did undergo medial imbrication). Demographic characteristics, postoperative knee range of motion, pre- and postoperative radiographic measurements, and preoperative MRI parameters were recorded, and minimum 2-year patient-reported outcomes were collected. Data were compared between the ST and no-ST groups. Results: The mean patient age was 15.02 years (range, 12.64-17.61 years) in the ST group and 14.18 years (range, 10.56-16.38 years) in the no-ST group, with a mean follow-up of 3.63 years (range, 2.01-6.11 years) in the ST group and 4.98 years (range, 2.23-9.03 years) in the no-ST group. Significantly more patients returned to the OR in the no-ST group compared with the ST group (7 [35%] vs 0 [0%]; P = .008). Further patellar stabilization with an MPFL allograft (n = 5) and manipulation under anesthesia (n = 2) were reasons for returning to the OR. There were no redislocation events in the ST group. Conclusion: Treating PPDs with chondral or osteochondral injury using suture tape to augment and repair the MPFL has promising advantages over not repairing it-including lower rates of postoperative patellar instability and return to the OR.

Chemotherapeutic metabolism presenting as a recalcitrant case of hand-foot syndrome and mucositis.

INTRODUCTION: Mercaptopurine (6MP) and methotrexate (MTX) are commonly used for maintenance chemotherapy for acute lymphoblastic leukemia (ALL). These medications have been associated with various side effects such as myelosuppression, colitis, and thyroiditis in addition to numerous cutaneous adverse events. Cutaneous side-effects most reported include mucositis, alopecia, xerosis, and pruritus. We report an interesting case of hand-foot syndrome to 6MP in a child on maintenance therapy for B-cell ALL from an alteration in medication metabolism. CASE: We report a 10-year-old male on maintenance chemotherapy for pre-Bcell ALL who presented to the hospital with worsening oral lesions and erythematous, fissured plaques on the palms and soles. Maintenance therapy consisted of IV vincristine and 5-day pulse of steroids every 12 weeks, daily 6MP, and weekly MTX, which were increased to ≥ 150% of standard dosing due to persistent absolute neutrophil counts > 1500. Metabolites obtained on admission demonstrated elevated 6MMP metabolites at 35,761 (normal < 5700). TPMT and NUDT15 enzyme activity were normal and no alterations in genotyping were discovered. OUTCOME: Patient's oral chemotherapy, including both 6MP and MTX, were stopped and allopurinol 100 mg daily was initiated, which lead to overall improvement. DISCUSSION: Clinical findings of acute mucositis and worsening of hand-foot syndrome, in the setting of inadequate myelosuppression in a child on maintenance therapy for ALL should raise concerns to consider altered metabolism pathway leading to toxic metabolite buildup. Allopurinol can play in improving cutaneous manifestation and chemotherapeutic dosing in patients with altered metabolism.

Keloid treatments: an evidence-based systematic review of recent advances.

BACKGROUND: Keloids are pathologic scars that pose a significant functional and cosmetic burden. They are challenging to treat, despite the multitude of treatment modalities currently available. OBJECTIVE: The aim of this study was to conduct an evidence-based review of all prospective data regarding keloid treatments published between 2010 and 2020. METHODS: A systematic literature search of PubMed (National Library of Medicine), Embase (Elsevier), and Cochrane Library (Wiley) was performed in November of 2020. Search strategies with the keywords "keloid" and "treatment" were performed by a medical librarian. The search was limited to prospective studies that were peer-reviewed, reported on clinical outcomes of keloid therapies, and were published in the English language between January 1, 2010, and November 24, 2020. RESULTS: A total of 3462 unique citations were identified, of which 108 studies met inclusion criteria. Current literature supports silicone gel or sheeting with corticosteroid injections as first-line therapy for keloids. Adjuvant intralesional 5-fluorouracil (5-FU), bleomycin, or verapamil can be considered, although mixed results have been reported with each. Laser therapy can be used in combination with intralesional corticosteroids or topical steroids with occlusion to improve drug penetration. Excision of keloids with immediate post-excision radiation therapy is an effective option for recalcitrant lesions. Finally, silicone sheeting and pressure therapy have evidence for reducing keloid recurrence. CONCLUSIONS: This review was limited by heterogeneity of subject characteristics and study outcome measures, small sample sizes, and inconsistent study designs. Larger and more robust controlled studies are necessary to further understand the variety of existing and emerging keloid treatments, including corticosteroids, cryotherapy, intralesional injections, lasers, photodynamic therapy, excision and radiation, pressure dressings, and others.

Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials.

Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30-40% means the majority are cured, although two-thirds have life-long disability, linked to accumulated brain injury that is acquired prior to diagnosis, and after surgery or chemo-radiotherapy. Only four drugs have been licensed globally for brain tumors in 40 years and only one for children. Most new cancer drugs in clinical trials do not cross the blood-brain barrier (BBB). Techniques to enhance brain tumor drug delivery are explored in this review, and cover those that augment penetration of the BBB, and those that bypass the BBB. Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. Together, this drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. A literature review of repurposed drugs is reported, and a range of preclinical brain tumor models available for translational development are explored.

How common is acute pelvic fixation failure after adult spine surgery? A single-center study of 358 patients.

OBJECTIVE: There is a paucity of literature on pelvic fixation failure after adult spine surgery in the early postoperative period. The purpose of this study was to determine the incidence of acute pelvic fixation failure in a large single-center study and to describe the lessons learned. METHODS: The authors performed a retrospective review of adult (≥ 18 years old) patients who underwent spinal fusion with pelvic fixation (iliac, S2-alar-iliac [S2AI] screws) at a single academic medical center between 2015 and 2020. All patients had a minimum of 3 instrumented levels. The minimum follow-up was 6 months after the index spine surgery. Patients with prior pelvic fixation were excluded. Acute pelvic fixation failure was defined as revision of the pelvic screws within 6 months of the primary surgery. Patient demographics and operative, radiographic, and rod/screw parameters were collected. All rods were cobalt-chrome. All iliac and S2AI screws were closed-headed screws. RESULTS: In 358 patients, the mean age was 59.5 ± 13.6 years, and 64.0% (n = 229) were female. The mean number of instrumented levels was 11.5 ± 5.5, and 79.1% (n = 283) had ≥ 6 levels fused. Three-column osteotomies were performed in 14.2% (n = 51) of patients, and 74.6% (n = 267) had an L5-S1 interbody fusion. The mean diameter/length of pelvic screws was 8.5/86.6 mm. The mean number of pelvic screws was 2.2 ± 0.5, the mean rod diameter was 6.0 ± 0 mm, and 78.5% (n = 281) had > 2 rods crossing the lumbopelvic junction. Accessory rods extended to S1 (32.7%, n = 117) or S2/ilium (45.8%, n = 164). Acute pelvic fixation failure occurred in 1 patient (0.3%); this individual had a broken S2AI screw near the head-neck junction. This 76-year-old woman with degenerative lumbar scoliosis and chronic lumbosacral zone 1 fracture nonunion had undergone posterior instrumented fusion from T10 to pelvis with bilateral S2AI screws (8.5 × 90 mm); i.e., transforaminal lumbar interbody fusion L4-S1. The patient had persistent left buttock pain postoperatively, with radiographically confirmed breakage of the left S2AI screw 68 days after surgery. Revision included instrumentation removal at L2-pelvis and a total of 4 pelvic screws. CONCLUSIONS: The acute pelvic fixation failure rate was exceedingly low in adult spine surgery. This rate may be the result of multiple factors including the preference for multirod (> 2), closed-headed pelvic screw constructs in which large-diameter long screws are used. Increasing the number of rods and screws at the lumbopelvic junction may be important factors to consider, especially for patients with high risk for nonunion.

Incidence, mechanism, and protective strategies for 2-year pelvic fixation failure after adult spinal deformity surgery with a minimum six-level fusion.

OBJECTIVE: The purpose of this study was to determine the incidence, mechanism, and potential protective strategies for pelvic fixation failure (PFF) within 2 years after adult spinal deformity (ASD) surgery. METHODS: Data for ASD patients (age ≥ 18 years, minimum of six instrumented levels) with pelvic fixation (S2-alar-iliac [S2AI] and/or iliac screws) with a minimum 2-year follow-up were consecutively collected (2015-2019). Patients with prior pelvic fixation were excluded. PFF was defined as any revision to pelvic screws, which may include broken rods across the lumbosacral junction requiring revision to pelvic screws, pseudarthrosis across the lumbosacral junction requiring revision to pelvic screws, a broken or loose pelvic screw, or sacral/iliac fracture. Patient information including demographic data and health history (age, sex, BMI, smoking status, American Society of Anesthesiologists score, osteoporosis), operative (total instrumented levels [TIL], three-column osteotomy [3CO], interbody fusion), screw (iliac, S2AI, length, diameter), rod (diameter, kickstand), rod pattern (number crossing lumbopelvic junction, lowest instrumented vertebra [LIV] of accessory rod[s], lateral connectors, dual-headed screws), and pre- and postradiographic (lumbar lordosis, pelvic incidence, pelvic tilt, major Cobb angle, lumbosacral fractional curve, C7 coronal vertical axis [CVA], T1 pelvic angle, C7 sagittal vertical axis) parameters was collected. All rods across the lumbosacral junction were cobalt-chrome. All iliac and S2AI screws were closed-headed tulips. Both univariate and multivariate analyses were performed to determine risk factors for PFF. RESULTS: Of 253 patients (mean age 58.9 years, mean TIL 13.6, 3CO 15.8%, L5-S1 interbody 74.7%, mean pelvic screw diameter/length 8.6/87 mm), the 2-year failure rate was 4.3% (n = 11). The mechanisms of failure included broken rods across the lumbosacral junction (n = 4), pseudarthrosis across the lumbosacral junction requiring revision to pelvic screws (n = 3), broken pelvic screw (n = 1), loose pelvic screw (n = 1), sacral/iliac fracture (n = 1), and painful/prominent pelvic screw (n = 1). A higher number of rods crossing the lumbopelvic junction (mean 3.8 no failure vs 2.9 failure, p = 0.009) and accessory rod LIV to S2/ilium (no failure 54.2% vs failure 18.2%, p = 0.003) were protective for failure. Multivariate analysis demonstrated that accessory rod LIV to S2/ilium versus S1 (OR 0.2, p = 0.004) and number of rods crossing the lumbar to pelvis (OR 0.15, p = 0.002) were protective, while worse postoperative CVA (OR 1.5, p = 0.028) was an independent risk factor for failure. CONCLUSIONS: The 2-year PFF rate was low relative to what is reported in the literature, despite patients undergoing long fusion constructs for ASD. The number of rods crossing the lumbopelvic junction and accessory rod LIV to S2/ilium relative to S1 alone likely increase construct stiffness. Residual postoperative coronal malalignment should be avoided to reduce PFF.

Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism.

Mutations in many synaptic genes are associated with autism spectrum disorders (ASD), suggesting that synaptic dysfunction is a key driver of ASD pathogenesis. Among these mutations, the R451C substitution in the NLGN3 gene that encodes the postsynaptic adhesion molecule Neuroligin-3 is noteworthy because it was the first specific mutation linked to ASDs. In mice, the corresponding Nlgn3 R451C-knockin mutation recapitulates social interaction deficits of ASD patients and produces synaptic abnormalities, but the impact of the NLGN3 R451C mutation on human neurons has not been investigated. Here, we generated human knockin neurons with the NLGN3 R451C and NLGN3 null mutations. Strikingly, analyses of NLGN3 R451C-mutant neurons revealed that the R451C mutation decreased NLGN3 protein levels but enhanced the strength of excitatory synapses without affecting inhibitory synapses; meanwhile NLGN3 knockout neurons showed reduction in excitatory synaptic strengths. Moreover, overexpression of NLGN3 R451C recapitulated the synaptic enhancement in human neurons. Notably, the augmentation of excitatory transmission was confirmed in vivo with human neurons transplanted into mouse forebrain. Using single-cell RNA-seq experiments with co-cultured excitatory and inhibitory NLGN3 R451C-mutant neurons, we identified differentially expressed genes in relatively mature human neurons corresponding to synaptic gene expression networks. Moreover, gene ontology and enrichment analyses revealed convergent gene networks associated with ASDs and other mental disorders. Our findings suggest that the NLGN3 R451C mutation induces a gain-of-function enhancement in excitatory synaptic transmission that may contribute to the pathophysiology of ASD.

The Intraoperative Pelvic Radiograph During Total Hip Arthroplasty: Is It Reliable to Estimate Leg Length?

Background: Symptomatic leg length discrepancies (LLDs) are a significant complication after total hip arthroplasty. Many surgeons incorporate an intraoperative anteroposterior pelvis radiograph, to help prevent LLD; however, obtaining a high-quality radiograph is often difficult. The purpose of this study is to evaluate the accuracy and reliability of estimating LLD using different radiographic reference landmarks on suboptimal anteroposterior pelvis radiographs. Material and methods: We obtained 2 pelvis Sawbones models with attached femurs and created a true shortening of the left femur of the experimental model by 7 mm. We then obtained a series of radiographs manipulating each model in standardized increments for a total of 66 different permutations of suboptimal radiographs. Each radiograph was evaluated for LLD by 2 separate orthopedic surgeons using reference lines bisecting the following anatomic landmarks: ischial tuberosities, acetabular teardrops, obturator foramina, sacroiliac joints, and the femoral heads, to the lesser trochanters. The accuracy and reliability of each line were then analyzed. Results: The obturator foramina line yielded the most reliable LLD estimates with an intraclass correlation coefficient of 0.939. This reference line was also the most accurate, with an average difference of 1.5 mm from the true LLD (P < .001), with 95% confidence to be within 1.8 mm. Conclusion: The obturator foramen reference line on an intraoperative radiograph is an accurate and reliable tool that should be utilized by joint replacement surgeons to estimate LLD even if the radiograph is suboptimal. This estimate is reliably reproduced among multiple observers and puts the estimate within 1.8 mm of a true LLD.

How does Covid-19 affect global equity markets?

This study applies OLS, panel regression and Granger causality test to investigate the impact of the Coronavirus disease 2019 (Covid-19) outbreak on the global equity markets during the early stage of the pandemic. We find that the Covid-19 outbreak has a significant negative impact on the overall equity index return of the eight economies even at 0.1% significance level. Furthermore, the pandemic has a more significant impact on the European countries than on the East Asian economies. The results have three main implications. Firstly, policy makers should react fast to mitigate the impact of a crisis. Secondly, investors should be aware of an outbreak of disease or other risks and adjust their investments accordingly. Furthermore, the Covid-19 outbreak results in a shift of power from the west to the east.

Magnetic Resonance Imaging Predictive Model Determines Hamstring Autograft Size for Anterior Cruciate Ligament Reconstruction in Patients Under 18 Years Old.

PURPOSE: To evaluate the predictive value of magnetic resonance imaging in determining hamstring autograft size preoperatively for pediatric anterior cruciate ligament reconstruction. METHODS: We conducted an analysis of patients younger than 18 years who underwent quadrupled hamstring autograft anterior cruciate ligament reconstruction. Semitendinosus tendon (ST) and gracilis tendon (GT) cross-sectional areas were measured on preoperative knee magnetic resonance imaging scans. Height, weight, body mass index, and sex were analyzed using ordinal regression analysis. A classification and regression tree (CART) was constructed to identify predictors of the predetermined intraoperative graft size of 8 mm or greater. Sensitivity and specificity were determined based on specified predictors. RESULTS: This study included 102 patients (52 female and 50 male patients). The average age was 15.8 ± 1.4 years. At the time of surgery, 38 patients (37.3%) had open physes, with an average age of 13.4 ± 0.96 years. Of the 102 patients, 55 (53.9%) had 8-mm or larger grafts, 31 (30.4%) had 7.5-mm grafts, and 16 (15.7%) had 7-mm or smaller grafts. In 12 patients (31.6%) with open physes, the graft size was less than 8 mm. Male patients were more likely to have 8-mm or larger grafts (P < .001), as were patients with a greater height (170.1 ± 7.3 cm vs 161.1 ± 12.0 cm, P = .013) and those with a greater weight (79.7 ± 23.4 kg vs 57.1 ± 16.2 kg, P = .005). For all patients, predictive modeling determined that if the cross-sectional areas of the ST and GT were 31.2 mm2 or greater, then 87.5% of patients would have a graft size of 8 mm or greater with an 80% sensitivity and 74% specificity. Similarly, if the cross-sectional areas of the ST and GT were 31.4 mm2 or greater in patients with open physes, then 100% of patients would have a graft size of 8 mm or greater with a 46% sensitivity and 99% specificity. CONCLUSIONS: A preoperative summation of the cross-sectional areas of the ST and GT greater than 31 mm2 in patients younger than 18 years with open or closed physes can help the surgeon preoperatively predict which patients will have an intraoperative graft size of 8 mm or greater. The risk factors for a smaller graft size include female sex, a shorter height, and a lighter weight. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Interdisciplinary treatment of posterior fossa dural arteriovenous fistulas.

BACKGROUND: Posterior fossa dural arteriovenous fistulas (dAVFs) are rare vascular lesions with variable risk of hemorrhage, mostly depending on the pattern of the venous drainage. While endovascular embolization is the mainstay treatment for most dAVFs, some posterior fossa lesions require a multidisciplinary approach including surgery. The goal of our study was to examine the outcome of an interdisciplinary treatment for posterior fossa dAVFs. METHODS: A retrospective review of patients treated for posterior fossa dAVFs was conducted. RESULTS: A total of 28 patients with a mean age of 57.8 years were included. Patients presented with a Cognard grade I in 2 (7%), II a in 5 (18 %), II b in 7 (25%), II a + b in 5 (18%), III in 3 (11%), and IV in 6 (21%) cases. Hemorrhage was the initial presentation in 2 (22%) patients with Cognard grade IV, in 3 with Cognard grade III (33%), in 1 (11%) with Cognard II a + b, and 3 (33%) with Cognard II b. A complete angiographic cure was achieved in 24 (86%) patients-after a single-session embolization in 16 (57%) patients, multiple embolization sessions in 2 (7%), a multimodal treatment with embolization and surgical disconnection in 3 (11%), and with an upfront surgery in 3 (11%). Complete long-term obliteration was demonstrated in 18/22 (82%) at the mean follow-up of 17 months. Fistulas were converted into asymptomatic Cognard I lesion in 4 (14%) patients. CONCLUSION: Posterior fossa dAVFs represent a challenging vascular pathology; however, despite their complexity, an interdisciplinary treatment can achieve high rates of angiographic and symptomatic cure with low morbidity and mortality rates. Long-term surveillance is warranted as late recurrences may occur.

Skin tightening.

There are many undesirable manifestations that arise as one ages. One of the most notable undesired effects is increasing skin laxity. Traditionally, the gold standard of treatment is surgical correction of skin laxity. However, demand for noninvasive aesthetic procedures has grown due to minimal risk and accelerated recovery time. Over the years, many new devices have become available for addressing skin laxity including laser therapy, radiofrequency (RF), ultrasound, and intense pulsed light (IPL). This article discusses these various noninvasive treatment options and seeks to give providers details of the science behind each device.