Targeting the muscarinic M1 receptor with a selective, brain-penetrant antagonist to promote remyelination in multiple sclerosis.

Multiple sclerosis (MS) is a chronic and debilitating neurological disease that results in inflammatory demyelination. While endogenous remyelination helps to recover function, this restorative process tends to become less efficient over time. Currently, intense efforts aimed at the mechanisms that promote remyelination are being considered promising therapeutic approaches. The M1 muscarinic acetylcholine receptor (M1R) was previously identified as a negative regulator of oligodendrocyte differentiation and myelination. Here, we validate M1R as a target for remyelination by characterizing expression in human and rodent oligodendroglial cells (including those in human MS tissue) using a highly selective M1R probe. As a breakthrough to conventional methodology, we conjugated a fluorophore to a highly M1R selective peptide (MT7) which targets the M1R in the subnanomolar range. This allows for exceptional detection of M1R protein expression in the human CNS. More importantly, we introduce PIPE-307, a brain-penetrant, small-molecule antagonist with favorable drug-like properties that selectively targets M1R. We evaluate PIPE-307 in a series of in vitro and in vivo studies to characterize potency and selectivity for M1R over M2-5R and confirm the sufficiency of blocking this receptor to promote differentiation and remyelination. Further, PIPE-307 displays significant efficacy in the mouse experimental autoimmune encephalomyelitis model of MS as evaluated by quantifying disability, histology, electron microscopy, and visual evoked potentials. Together, these findings support targeting M1R for remyelination and support further development of PIPE-307 for clinical studies.

Immune Checkpoint Inhibitors-Associated Generalized Lipodystrophy: Reconstructive Challenges of an Emerging and Distinct Form of Lipodystrophy.

Total and permanent loss of facial and nonfacial fat is a rare side effect of immune checkpoint inhibitors (ICIs). Consequently, effective treatment modalities for patients remain undefined. Here, we discuss the surgical treatment of a patient with both ICI-related acquired generalized lipodystrophy (AGL). We additionally performed a comprehensive literature review (Cochrane, Embase, and MEDLINE) to summarize what is known about ICI-related lipodystrophy and available treatments for this rare complication. A 66-year-old female diagnosed with metastatic lung adenocarcinoma started ICI (pembrolizumab) treatment. She developed generalized lipodystrophy 13 months after her first cycle. Her primary concern was the loss of facial fat volume, which significantly aged her appearance. The patient underwent a 2-staged restoration of her facial fat compartments using dermal grafts from the lower abdomen and medial thighs. The patient recovered uneventfully and was satisfied with the aesthetic improvement at 18 months of follow-up. The authors identified 8 case reports with patients with ICI-AGL. The mean age was 53.63 years, and the mean BMI was 36.72 kg/m2. The average onset of symptoms was 7.44 months after ICI initiation. None of the studies described any sort of surgical or nonsurgical options to restore the volume of the facial fat compartments. The management of combined facial and nonfacial lipodystrophy remains challenging due to the lack of suitable autologous fat donor sites. In this report, the authors demonstrate that staged volume restoration can be achieved using autologous dermal grafts from the thigh, making it a viable reconstructive option in this subset of patients.

Development of a novel radiofluorinated riboflavin probe for riboflavin receptor-targeting PET imaging.

Riboflavin receptor 3 (RFVT3) is a key protein in energetic metabolism reprogramming and is overexpressed in multiple cancers involved in malignant proliferation, angiogenesis, chemotherapy resistance, and immunosuppression. To enable non-invasive real-time quantification of RFVT3 in tumors, we sought to develop a suitable PET probe that would allow specific and selective RFVT3 imaging in vivo. A novel radiofluorinated riboflavin probe (18F-RFTA) based on riboflavin was synthesized and characterized in terms of radiochemical purity, hydrophilicity, binding affinity, and stability. Positron emission tomography (PET) imaging of 18F-RFTA was performed in U87MG tumor-bearing mice. Immunohistochemistry staining was carried out to determine the expression of RFVT3 in U87MG tumors. 18F-RFTA was characterized by high radiochemical purity and RFVT3 binding affinity, and remarkable stability in vitro and in vivo. Small-animal PET imaging with 18F-RFTA revealed significantly higher uptake in RFVT3-expressing U87MG tumors than in muscle. In conclusion, we have developed the first radiofluorinated riboflavin-based PET probe that is suitable for imaging RFVT3-positive tumors. The new target/probe system can be leveraged for extensive use in the diagnosis and treatment of RFVT3 overexpressing diseases, such as oncologic, cardiovascular, and neurodegenerative diseases.

Atrophy and cognitive profiles in older adults with temporal lobe epilepsy are similar to mild cognitive impairment.

Epilepsy incidence and prevalence peaks in older adults yet systematic studies of brain ageing and cognition in older adults with epilepsy remain limited. Here, we characterize patterns of cortical atrophy and cognitive impairment in 73 older adults with temporal lobe epilepsy (>55 years) and compare these patterns to those observed in 70 healthy controls and 79 patients with amnestic mild cognitive impairment, the prodromal stage of Alzheimer's disease. Patients with temporal lobe epilepsy were recruited from four tertiary epilepsy surgical centres; amnestic mild cognitive impairment and control subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Whole brain and region of interest analyses were conducted between patient groups and controls, as well as between temporal lobe epilepsy patients with early-onset (age of onset <50 years) and late-onset (>50 years) seizures. Older adults with temporal lobe epilepsy demonstrated a similar pattern and magnitude of medial temporal lobe atrophy to amnestic mild cognitive impairment. Region of interest analyses revealed pronounced medial temporal lobe thinning in both patient groups in bilateral entorhinal, temporal pole, and fusiform regions (all P < 0.05). Patients with temporal lobe epilepsy demonstrated thinner left entorhinal cortex compared to amnestic mild cognitive impairment (P = 0.02). Patients with late-onset temporal lobe epilepsy had a more consistent pattern of cortical thinning than patients with early-onset epilepsy, demonstrating decreased cortical thickness extending into the bilateral fusiform (both P < 0.01). Both temporal lobe epilepsy and amnestic mild cognitive impairment groups showed significant memory and language impairment relative to healthy control subjects. However, despite similar performances in language and memory encoding, patients with amnestic mild cognitive impairment demonstrated poorer delayed memory performances relative to both early and late-onset temporal lobe epilepsy. Medial temporal lobe atrophy and cognitive impairment overlap between older adults with temporal lobe epilepsy and amnestic mild cognitive impairment highlights the risks of growing old with epilepsy. Concerns regarding accelerated ageing and Alzheimer's disease co-morbidity in older adults with temporal lobe epilepsy suggests an urgent need for translational research aimed at identifying common mechanisms and/or targeting symptoms shared across a broad neurological disease spectrum.

Decline in Rehab Transfers Among Rehab-Eligible Stroke Patients During the COVID-19 Pandemic.

OBJECTIVE: To characterize differences in disposition arrangement among rehab-eligible stroke patients at a Comprehensive Stroke Center before and during the COVID-19 pandemic. MATERIALS AND METHODS: We retrospectively analyzed a prospective registry for demographics, hospital course, and discharge dispositions of rehab-eligible acute stroke survivors admitted 6 months prior to (10/2019-03/2020) and during (04/2020-09/2020) the COVID-19 pandemic. The primary outcome was discharge to an inpatient rehabilitation facility (IRF) as opposed to other facilities using descriptive statistics, and IRF versus home using unadjusted and adjusted backward stepwise logistic regression. RESULTS: Of the 507 rehab-eligible stroke survivors, there was no difference in age, premorbid disability, or stroke severity between study periods (p>0.05). There was a 9% absolute decrease in discharges to an IRF during the pandemic (32.1% vs. 41.1%, p=0.04), which translated to 38% lower odds of being discharged to IRF versus home in unadjusted regression (OR 0.62, 95%CI 0.42-0.92, p=0.016). The lower odds of discharge to IRF persisted in the multivariable model (aOR 0.16, 95%CI 0.09-0.31, p<0.001) despite a significant increase in discharge disability (median discharge mRS 4 [IQR 2-4] vs. 2 [IQR 1-3], p<0.001) during the pandemic. CONCLUSIONS: Admission for stroke during the COVID-19 pandemic was associated with a significantly lower probability of being discharged to an IRF. This effect persisted despite adjustment for predictors of IRF disposition, including functional disability at discharge. Potential reasons for this disparity are explored.

Plastic Surgery in the Time of COVID-19.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has swept the world in the last several months, causing massive disruption to existing social, economic, and health care systems. As with all medical fields, plastic and reconstructive surgery has been profoundly impacted across the entire spectrum of practice from academic medical centers to solo private practice. The decision to preserve vital life-saving equipment and cancel elective procedures to protect patients and medical staff has been extremely challenging on multiple levels. Frequent and inconsistent messaging disseminated by many voices on the national stage often conflicts and serves only to exacerbate an already difficult decision-making process. METHODS: A survey of relevant COVID-19 literature is presented, and bioethical principles are utilized to generate guidelines for plastic surgeons in patient care through this pandemic. RESULTS: A cohesive framework based upon core bioethical values is presented here to assist plastic surgeons in navigating this rapidly evolving global pandemic. CONCLUSION: Plastic surgeons around the world have been affected by COVID-19 and will adapt to continue serving their patients. The lessons learned in this present pandemic will undoubtedly prove useful in future challenges to come.

Beyond the Tip of the Blade: An Investigation of Upper Extremity Machete Injuries in Honduras.

BACKGROUND: Machete injuries constitute a major cause of morbidity in Honduras. In this study, we aimed to determine the incidence, initial management, surgical treatment, and follow-up patterns for machete injuries at the national public hospital in Honduras. Microsurgery in Honduras is currently in transition with limitations at multiple levels. This study aims to provide critical information to better prepare visiting surgeons and establishes a blueprint to improve microsurgical reconstruction. METHODS: A retrospective chart review was performed to identify patients with machete injuries to the upper extremity (UE) who presented to the Hospital Escuela Universitario (HEU) for treatment from 2015 to 2017. Additional microsurgical data was obtained by personal communication with members of the plastic surgery department at the HEU. RESULTS: Complete data was retrieved for 100 patients who presented to the HEU with a UE machete wound. The cohort was male dominated (93%), employed as farmers (47%), and had a mean age of 32.1 years. Violence was the most common mechanism of injury (p < 0.001). The majority of UE machete injuries involved tendon (70%), nerve (28%), and an open fracture (55%). Of the 76% of patients who were scheduled for a follow-up visit, only 25% attended. Within the last calendar year, one replantation, 10 revascularizations at the wrist and forearm level, three microvascular free tissue transfers, and 175 nerve repairs were performed. CONCLUSION: Management of UE machete injuries in Honduras is challenging and requires early recognition of possible injuries to multiple anatomical systems. The majority of injuries required operative intervention. Only a small percentage of patients presented for follow up. A program to streamline care starting at injury recognition up to final follow-up is currently unavailable and needs to be developed to optimize microsurgical care.

Surgical Approaches and 30-Day Complications of Velopharyngeal Insufficiency Repair Using American College of Surgeons National Surgical Quality Improvement Program-Pediatric.

BACKGROUND: This study aims to outline the 30-d complications of different velopharyngeal insufficiency (VPI) correction techniques using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric, VPI cases from 2012 to 2015 were identified. Patients were subdivided into two cohorts: (1) palatal procedures and (2) pharyngeal procedures, with the latter being subdivided into (1) pharyngeal flap and (2) sphincter pharyngoplasty. Patient characteristics and postoperative outcomes were compared using Pearson's chi-squared or Fischer's exact test for categorical variables and independent t-tests, Wilcoxon-Mann-Whitney, or analysis of variance for continuous variables. RESULTS: A total of 767 VPI cases were identified: 191 (24.9%) treated with palatal procedures and 576 (75.1%) with pharyngeal procedures, of which 444 were pharyngeal flap and 132 were sphincter pharyngoplasty. Patients who underwent palatal procedure had longer anesthesia (152.41 min) and operating time (105.72 min), whereas patients who underwent pharyngeal procedure had longer length of stay (1.66 d). There were no significant differences in outcomes between the two groups, nor were there significant differences in outcomes between pharyngeal flap and sphincter pharyngoplasty subgroups. Patients who experienced complications were younger, shorter, inpatient, and having a shorter operation time, longer anesthesia time, or longer length of stay. Plastic surgeons performed the majority of palatal procedures (62.3%), whereas pharyngeal procedures were most often performed by otolaryngologists (48.8%). CONCLUSIONS: As per national data, both palatal and pharyngeal procedures for repair can be performed with comparable 30-d complications. The chosen technique may be based on patient presentation and on the surgeon comfort level.

The impact of cerebrovascular risk factors on postoperative memory decline in patients with left temporal lobe epilepsy.

Cerebrovascular risk factors (CVRFs) and comorbid cardiovascular and metabolic disease have been linked to accelerated cognitive aging and dementia in the general population; however, the contribution of these comorbidities to the risk of post anterior temporal lobectomy (ATL) memory decline has been unexamined. We explored the effects of CVRFs on postoperative verbal memory decline in a cohort of 22 patients with left temporal lobe epilepsy (LTLE) who completed pre- and one-year postsurgical neuropsychological testing. Diagnoses of interest included preoperative cardiovascular and metabolic disorders, as well as CVRFs [pulse pressure proxy, body mass index (BMI), and fasting glucose]. Twenty-three percent of patients had a history of cardiovascular disease, 9% of metabolic disorders, and 38% had a BMI indicating overweight or obese status. Higher preoperative BMI and glucose were associated with greater decline in verbal memory. The association between BMI and memory decline remained significant after controlling for age and left hippocampal volume. These findings suggest that modifiable health-related risk factors, including CVRFs, may impact the risk of postoperative cognitive decline, and that BMI in particular could be an important factor to consider and/or target for intervention early in clinical care to protect cognitive health.

Return to Play in Amateur Soccer Players Undergoing Hip Arthroscopy: Short- to Mid-Term Follow-Up.

PURPOSE: To describe patient-reported outcomes (PROs) and return to play at any level in amateur soccer players undergoing hip arthroscopy for femoroacetabular impingement syndrome at short- to mid-term follow-up. METHODS: Data were prospectively collected and retrospectively reviewed for patients who underwent hip arthroscopy between March 2009 and June 2014. Patients who participated in amateur soccer within 1 year prior to surgery and intended to return to their sport after hip arthroscopy for femoroacetabular impingement syndrome were considered for inclusion in our study. Patients were excluded if they had a preoperative Tönnis osteoarthritis grade of 2 or greater, previous ipsilateral hip conditions or hip surgical procedures, or Workers' Compensation status. The patients from the initial group who had preoperative and minimum 2-year postoperative measures for the modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score-Sports Specific Subscale, and visual analog scale for pain were included in our final group. In addition to PROs, data regarding the patients' return to soccer, surgical complications, and secondary surgical procedures were collected. RESULTS: A total of 41 patients were eligible for inclusion in our study, of whom 34 (82.9%) had a mean follow-up period of 47.4 months. Five patients were not eligible because they did not intend to return to soccer. There were 15 male hips (44.1%) and 19 female hips (55.9%). The mean age at surgery was 20.8 ± 7.4 years. All PROs and the visual analog scale score improved significantly from preoperatively to latest follow-up. Of the 34 patients, 27 (79.4%) returned to soccer. Of the patients who returned to soccer, 19 (70.4%) were competing at the same level or a higher level compared with their highest level within 1 year of surgery. Regardless of competitive level, 21 patients (77.8%) reported that their athletic ability was the same as or higher than it was within 1 year of surgery. CONCLUSIONS: Hip arthroscopy was associated with significant improvements in PROs for amateur soccer players. There was a high level of return to soccer and a high proportion of patients whose competitive level was similar or improved. As such, hip arthroscopy is a good option for soccer players, in the absence of underlying osteoarthritis, presenting with hip pathology. LEVEL OF EVIDENCE: Level IV, case series.

Myotomy In Situ for Essential Blepharospasm Refractory to Botulinum Toxin.

BACKGROUND: Full myectomy is recommended for benign essential blepharospasm (BEB) refractory to botulinum toxin (BT) treatment, but long-term swelling, scar contracture, hollow appearance, and unnatural contour of the eyelids are common postoperative complications. We present myotomy in situ to minimize these adverse outcomes. METHODS: The redundant eyelid skin with its underlying muscle is resected first, and myotomy in situ is performed by completely cutting the residual orbicularis oculi muscles into multiple cubes and down to the subcutaneous layer, and then cutting the procerus and corrugator muscles down to the periosteum. Patient demographics, medical treatment history, BT injection history, blepharoptosis correction techniques, associated surgical procedures, and aesthetic outcomes were analyzed. Preoperative and postoperative BT injection dosage and frequency, as well as modified disability scores, were compared using paired Student t tests. RESULTS: Twenty-five patients underwent this technique. Their average ± SD age was 64.4 ± 8.9 years, with average postoperative follow-up occurring 17.0 ± 8.0 months. Associated diseases included blepharoptosis (88%) and apraxia of lid opening (44%). There were no postoperative hematoma, seroma, scar contracture, and depressed hollow eyelid contours. Preoperative to postoperative assessments revealed improvements in mean BT injection interval (10.4 ± 2.1 to 14.6 ± 2.9 weeks, P < 0.001), BT injection dosage (44.4 ± 13.3 to 28.1 ± 6.7 units, P < 0.001), and modified disability score (15.3 ± 3.0 to 2.8 ± 2.2, P < 0.001). All patients were highly satisfied with functional and aesthetic surgical outcomes (4.5 ± 0.6 on Likert scale). CONCLUSIONS: Myotomy in situ is effective for patients with BEB who are refractory to BT treatment, with therapeutic benefits similar to that of full myectomy with the ability to maintain favorable cosmetic results. Relative high incidence of blepharoptosis and apraxia of lid opening in patients with refractory BEB was reported. Simultaneous correction of the ptosis can further optimize outcomes.

Comparative Effectiveness of Transversus Abdominis Plane Blocks in Abdominally Based Autologous Breast Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: The abdomen is the most common donor site in autologous microvascular free flap breast reconstruction and contributes significantly to postoperative pain, resulting in increased opioid use, length of stay, and hospital costs. Enhanced Recovery After Surgery (ERAS) protocols have demonstrated multiple clinical benefits, but these protocols are widely heterogeneous. Transversus abdominis plane (TAP) blocks have been reported to improve pain control and may be a key driver of the benefits seen with ERAS pathways. METHODS: A systematic review and meta-analysis of studies reporting TAP blocks for abdominally based breast reconstruction were performed. Studies were extracted from 6 public databases before February 2019 and pooled in accordance with the PROSPERO registry. Total opioid use, postoperative pain, length of stay, hospital cost, and complications were analyzed using a random effects model. RESULTS: The initial search yielded 420 studies, ultimately narrowed to 12 studies representing 1107 total patients. Total hospital length of stay (mean difference, -1.00 days; P < 0.00001; I = 81%) and opioid requirement (mean difference, -133.80 mg of oral morphine equivalent; P < 0.00001; I = 97%) were decreased for patients receiving TAP blocks. Transversus abdominis plane blocks were not associated with any significant differences in postoperative complications (P = 0.66), hospital cost (P = 0.22), and postoperative pain (P = 0.86). CONCLUSIONS: Optimizing postoperative pain management after abdominally based microsurgical breast reconstruction is invaluable for patient recovery. Transversus abdominis plane blocks are associated with a reduction in length of stay and opioid use, representing a safe and reasonable strategy for decreasing postoperative pain.

Revisiting the Relationship Between Hospital Case Volume and Outcomes in Abdominally Based Free Flap Breast Reconstruction.

BACKGROUND: Increased operative volume has been associated with benefits in patient outcomes for a variety of surgical procedures. In autologous abdominally based breast reconstruction, however, there are few studies assessing the association between procedure volume and patient outcomes. The objectives of this study are to evaluate the associations between abdominal-based free flap breast reconstruction and patient outcomes. METHODS: The 2013-2014 Healthcare Cost and Utilization Project National Inpatient Sample was queried for all female patients with a diagnosis of breast cancer who underwent mastectomy and immediate abdominally based breast reconstruction (deep inferior epigastric perforator or transverse rectus abdominus muscle free flaps). Outcomes included occurrence of major or surgical site in-hospital complications, hospital cost, and length of stay (LOS). High-volume (HV) hospitals were defined as the 90th percentile of annual case volume or higher (>18 cases/y). Multivariate regressions and generalized linear modeling with gamma log-link function were performed to access the outcomes associated with HV hospitals. RESULTS: Overall, 7145 patients at 473 hospitals were studied; of these, 42.4% of patients were treated at HV hospitals. There were significant differences in unadjusted major complications (2.1% vs 4.3%; P < 0.001) and unadjusted surgical site complications (3.5% vs 6.1%; P < 0.001) between HV and non-HV hospitals. After adjustments for clinical and hospital characteristics, patients treated at HV hospitals were less likely to experience a major complication (odds ratio, 0.488; 95% confidence interval, 0.353-0.675; P < 0.001) or surgical site complication (odds ratio, 0.678; 95% confidence interval, 0.519-0.887; P = 0.005). There was no difference in inpatient cost between HV and non-HV hospitals ($26,822 vs $26,295; marginal cost, $528; P = 0.102); however, HV hospitals had a shorter LOS (4.31 vs 4.40 days; marginal LOS, -0.10 days; P = 0.005). CONCLUSIONS: Hospitals that perform a larger volume of immediate abdominal-based breast reconstructions after mastectomy, when compared with those that perform a lower volume of these procedures, seem to have an associated lower rate of major complications and a shorter LOS. However, these same HV centers demonstrate no decrease in costs. Further research is needed to understand how these HV centers can reduce hospital costs.

Severe Ocular Complications After Blepharoptosis Correction in the Oculopharyngeal Muscular Dystrophy Patient: Literature Review and Case Presentation.

BACKGROUND: Blepharoptosis correction in oculopharyngeal muscular dystrophy (OPMD) patients may result in severe ocular complications owing to lagophthalmos and ophthalmoplegia. Managing the acute episode to prevent further aggravation of the keratopathy or blindness is of paramount importance. METHODS: A review of the literature for severe chemosis, keratopathy, and corneal ulceration in the patient population was performed using the PubMed database, with key words including ptosis surgery, ptosis correction, ptosis repair, and oculopharyngeal muscular dystrophy. A retrospective review of all patients with blepharoptosis from a single surgeon from September 2009 and May 2017 was performed, selecting those with OPMD who underwent blepharoptosis correction. RESULTS: Our literature review revealed a total of 15 articles after excluding repeated articles and selecting those meeting our inclusion criteria. A total of 232 OPMD patients underwent blepharoptosis correction. Severe ocular complications were noted in 7 patients, with treatment unspecified. For 9 years, 2 OPMD patients at our institute underwent blepharoptosis correction, with one developing severe acute keratitis, chemosis, and corneal ulceration due to lagophthalmos and ophthalmoplegia. Use of the temporary drawstring tarsorrhaphy and topical eye drop treatment for 2 weeks led to resolution of corneal ulcerations without necessitating further intervention. CONCLUSIONS: Severe ocular complications may occur after blepharoptosis correction in OPMD patients, potentially owing to lagophthalmos and ophthalmoplegia. Temporary drawstring tarsorrhaphy is an effective option to treat these adverse outcomes.

Hip Arthroscopy Successfully Treats Femoroacetabular Impingement in Adolescent Athletes.

BACKGROUND: There is evidence that femoroacetabular impingement (FAI) is increasingly prevalent among adolescent athletes. Abnormal contact forces across the hip and alterations in bony morphology characteristic of FAI may be especially detrimental in this group, given their young age and active lifestyle. PURPOSE: The purpose of this study was to report the findings, outcomes, and return to sport percentage among adolescent athletes with FAI treated with hip arthroscopy. METHODS: A retrospective review of all patients younger than 18 years who underwent hip arthroscopy for FAI at a single institution was performed. All athletes who were attempting to return to sport and underwent hip arthroscopy were included. Patients with previous hip surgery and/or hip conditions were excluded. Arthroscopic procedures and an assessment of intra-articular findings were recorded. Patient-reported outcome measures were recorded at 3 months, 1 year, and 2 years postoperatively, and included the modified Harris hip score, the nonarthritic hip score, hip outcome score-sports subscale, visual analogue scale for pain, and patient satisfaction. Return to sport percentage and ability levels were also noted. RESULTS: There were 96 eligible cases of adolescent athletes treated with hip arthroscopy; 81 (84.4%) hips in 69 patients had 2-year follow-up. Running/track and field was the most common sport (25), followed by soccer (12), dance (10), baseball/softball (9), and basketball (6). There were 61 females and 20 males, whose average age was 15.9±1.2 y (range: 13.1 to 18.0 y). The most common procedures were labral repair (81.5%), iliopsoas fractional lengthening (72.8%), femoroplasty (69.1%), and acetabuloplasty (66.7%). Capsular repair or plication was performed in most patients (81.5%). Cartilage damage was more common on the acetabulum than the femur, with Outerbridge grade 2 or higher occurring in 23.5% and 4.9% of hips, respectively. Statistically significant improvements were seen in all patient-reported outcomes from preoperative to minimum 2-year follow-up. A total of 84.0% of patients had returned to their sport at latest follow-up. There were 6 (7.4%) patients who underwent revision arthroscopy at a mean of 37.3 months postoperatively. CONCLUSION: Symptomatic FAI in adolescent athletes can be successfully treated with hip arthroscopy, with a higher return to sport rate and low complications and reoperation rate at minimum 2-year follow-up.

Discovery of potent and selective PPARα/δ dual antagonists and initial biological studies.

We previously published on the design and synthesis of novel, potent and selective PPARα antagonists suitable for either i.p. or oral in vivo administration for the potential treatment of cancer. Described herein is SAR for a subsequent program, where we set out to identify selective and potent PPARα/δ dual antagonist molecules. Emerging literature indicates that both PPARα and PPARδ antagonism may be helpful in curbing the proliferation of certain types of cancer. This dual antagonism could also be used to study PPARs in other settings. After testing for selective and dual potency, off-target counter screening, metabolic stability, oral bioavailability and associated toxicity, compound 11, the first reported PPARα/δ dual antagonist was chosen for more advanced preclinical evaluation.

The Effect of Complete Tearing of the Ligamentum Teres in Patients Undergoing Primary Hip Arthroscopy for Femoroacetabular Impingement and Labral Tears: A Match-Controlled Study.

PURPOSE: To compare the patient-reported outcomes scores (PROs) of patients with femoroacetabular impingement (FAI), labral tears, and complete ligamentum teres (LT) tears to a matched-pair control group with intact LTs, as well as to report the relative risk of total hip arthroplasty (THA) conversion. METHODS: Data between February 2008 and April 2015 were retrospectively reviewed. Patients undergoing hip arthroscopy included those who had complete LT tear, labral tears, FAI, and minimum 2-year follow-up with modified Harris Hip Score (mHHS), Non-arthritic Hip Score (NAHS), Hip Outcome Score-Sports Specific Subscale (HOS-SSS), International Hip Outcome Tool-12 (iHOT-12), and visual analog scale (VAS). Patients were excluded for Tönnis osteoarthritis grade >1, previous hip conditions or surgeries, and Worker's Compensation claims. Patients with full LT tears were matched in a 1:3 ratio with patients without LT tears based on age at surgery ± 5 years, sex, body mass index ± 5, capsular treatment, and acetabular Outerbridge grade. Revision surgeries and conversions to THA were documented. Relative risk for conversion to THA was determined (P = .05). RESULTS: Eighteen patients (18 hips) had minimum 2-year follow-up and were eligible for matching; as described, each study group patient was matched to 3 control patients, resulting in a size of 18 to 54 patients. PROs showed significant improvement in the complete LT tear group with the exception of the HOS-SSS measure. In the intact LT control group, all PROs significantly improved, with no exception. Based on relative risk, patients with complete LT tears were 3 times more likely to require THA than a matched control group. CONCLUSIONS: After hip arthroscopy, patients with FAI and complete LT tears reported significant improvement in PROs. Among hips that did not require THA, functional scores were comparable to a matched control group. However, patients with complete LT tears were 3 times more likely to require an eventual THA than the matched control group. We conclude that patients with complete LT tears should be considered an at-risk population, and that indications and treatment may be refined to incorporate the clinical significance of complete LT tears. LEVEL OF EVIDENCE: Level III, comparative trial, case-control.

Return to Basketball After Hip Arthroscopy: Minimum 2-Year Follow-up.

PURPOSE: To present minimum 2-year patient-reported outcomes (PROs) and return to sport (RTS) data for a population of basketball players after hip arthroscopy. METHODS: Data were prospectively collected and retrospectively reviewed for all patients who underwent hip arthroscopy between February 2009 and May 2014. Patients with preoperative and minimum 2-year postoperative PROs, visual analog scale score for pain, and satisfaction, who regularly played basketball within 1 year before surgery, and who attempted to RTS met the inclusion criteria. Exclusion criteria were previous ipsilateral hip surgery or conditions such as fracture, dysplasia, or femoral avascular necrosis. Patients were matched 1:1 to a control group composed of those who did not play any sports before surgery, based on the following matching criteria: age ±5 years, sex, and body mass index ±5. Statistical analysis was performed to determine significant differences in PROs. Conversion to total hip arthroplasty (THA) was considered an endpoint. RESULTS: Thirty-one patients (81.6%) met inclusion criteria with follow-up of 46.8 ± 20.6 months. The mean age was 30.0 ± 12.3, and the mean body mass index was 26.3 ± 6.5. Male patients (64.5%) outnumbered female patients (35.5%). A majority of the players (54.8%) identified themselves as recreational athletes; the remainder competed at the high school, collegiate, amateur, or professional level. There was significant (P < .001) improvement in all PRO measures and visual-analog scale scores from baseline to a minimum 2-year follow-up. At the most recent follow-up, mean patient satisfaction was 8.1 ± 2.1. Twenty-two (78.6%), and 23 patients (82.1%) achieved the patient acceptable symptom state on the modified Harris Hip Score and the Hip Outcomes Score-Sports Specific Subscale. Twenty-one (75.0%) and 17 (60.7%) patients had a minimal clinically important difference on the modified Harris Hip Score and the Hip Outcomes Score-Sports Specific Subscale, respectively. Three patients (9.7%) with an average age of 47.5 (P = .023) converted to THA at a mean of 35.9 ± 7.2 (range 29.66-43.75) months after arthroscopy. At the most recent follow-up, the RTS rate was 83.9%. Subjective ability level was the same or higher in 23 patients (74.2%). CONCLUSION: Hip arthroscopy in basketball athletes demonstrates a significant increase in PROs, a high RTS rate, and a low risk of complications. Hip arthroscopy may be considered in basketball players <40 years old for whom nonoperative treatment fails and who have a significantly limited level of play. Careful patient selection and counseling should be used when considering hip arthroscopy in basketball players >40 years old because there may be a high rate of conversion to THA. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Intra-articular Volume Reduction With Arthroscopic Plication for Capsular Laxity of the Hip: A Cadaveric Comparison of Two Surgical Techniques.

PURPOSE: To compare intracapsular volume reduction between interportal capsular shift and T-capsulotomy plication in a cadaveric model. METHODS: Twelve pair-matched specimens were randomized into T-capsulotomy plication or interportal capsular shift. T-capsulotomy was performed using a 2-cm interportal and 2-cm bisecting, longitudinal limb to the intertrochanteric line. Plication was performed utilizing 5-mm bites on either side of the capsulotomy with arthroscopic knot tying technique standard alternating half hitches. Pair-matched interportal capsular shift specimens underwent 5-cm interportal capsulotomy, and capsular shift was performed utilizing 5 nonabsorbable sutures placed in 45° orientation at 5 mm from the capsulotomy margin. With each specimen in a position of slight flexion and adduction, a spinal needle was used to inject methylene blue-colored saline solution intra-articularly; the volcano method was used to measure capsular volume before and after each respective plication technique. Mean absolute volumes and relative volumetric reduction for each technique were quantified and compared to determine statistical significance. RESULTS: At baseline, there were no statistically significant differences in capsular volume between pair-matched specimens (T-capsulotomy plication, 42.5 ± 5.1 mL; interportal capsular shift, 45.0 ± 88.6 mL; P = .555). After capsulotomy and secondary plication, both the T-capsulotomy (post: mean = 32.5 ± 8.0 mL; P < .001) and interportal capsulotomy groups (post: mean = 29.4 ± 10.0; P < .0001) demonstrated significant decreases in capsular volume, with average reductions of 10.0 ± 3.3 mL and 15.6 ± 3.2 mL, respectively. Although the interportal capsular shift (35.9% ± 11.3%) demonstrated greater volumetric reduction relative to baseline when compared with the T-capsular plication (24.5% ± 10.8%), these results were not significant (P = .104). CONCLUSIONS: Both T-capsular plication and interportal capsular shift produce statistically significant reductions in overall hip capsular volume. Although the interportal capsular shift may generate modestly higher degrees of capsular reduction, the comparative biomechanical repercussions of each technique are not currently known. CLINICAL RELEVANCE: Irrespective of arthroscopic technique, capsular plication with 5-mm bites decreases capsular volume by approximately one-third to one-fourth that of baseline measures.

A Comparison of Outcomes and Resource Utilization Between Plastic Surgeons and General Surgeons in Implant-Based Breast Reconstruction.

BACKGROUND: Because of lack of patient education on the importance of surgeon certification and barriers to access a plastic surgeon (PS), non-PSs are becoming more involved in providing implant-based breast reconstruction procedures. We aim to clarify differences in outcomes and resource utilization by surgical specialty for implant-based breast reconstruction. METHODS: Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2014. Patients undergoing immediate implant-based reconstruction or immediate/delayed tissue expander-based reconstruction were identified (Current Procedural Terminology codes 19340 and 19357, respectively). Outcomes studied were major and wound-based 30-day complications, operation time, unplanned readmission or reoperation, and length of hospital stay. RESULTS: We identified 9264 patients who underwent prosthesis or tissue expander-based breast reconstruction, 8362 (90.3%) by PSs and 902 (9.7%) by general surgeons (GSs). There were significant differences in major complications between specialty (1.2% PS vs 2.8% GS; P < 0.001). There were no significant differences in unplanned reoperation (5.3% PS vs 4.9% GS; P = 0.592), unplanned readmissions (4.3% PS vs 3.8% GS; P = 0.555), wound dehiscence (0.7% PS vs 0.6% GS; P = 0.602), or wound-based infection rates (2.9% PS vs 2.8% GS; P = 0.866). As it pertains to resource utilization, the GS patients had a significantly longer length of stay (1.02 ± 4.41 days PS vs 1.62 ± 4.07 days GS; P < 0.001) and operative time (164.3 ± 97.6 minutes PS vs 185.4 ± 126.5 minutes; P = 0.001) than PS patients. CONCLUSIONS: This current assessment demonstrates that patients who undergo breast implant reconstruction by a GS have significantly more major complications. It is beneficial for the health care system for PSs to be the primary providers of breast reconstruction services. Measures should be taken to ensure that PSs are available and encouraged to provide this service.