Surgical Excision of a Thrombosed Persistent Median Artery in a Professional Hockey Player.

A persistent median artery is a rare anatomical variant found in approximately 10% of the population. Carpal tunnel syndrome due to a thrombosed persistent median artery is exceptionally rare. A 29-year-old professional hockey player presented with a 2 months history of hand pain and intermittent paresthesias without vascular symptoms. Magnetic resonance imaging and angiography demonstrated a 2-cm thrombosis in a persistent median artery at the level of the carpal tunnel, with otherwise normal vascular anatomy. He was treated with surgical excision of the thrombus and carpal tunnel decompression. The patient's symptoms resolved rapidly and he was able to return to sport without restrictions. Incidental imaging performed several months after surgery demonstrated a normal vascular pattern in the treated hand.

AUTOSTERE: Systematic Search for Scaffold Replacement Opportunities within Structural Databases.

Medicinal chemists often bias toward working with scaffolds with which previously they have had direct experience and successes. In this way, it is often the case that scaffolds which have proven tractable within a research group are "reused" across multiple and sometimes unrelated drug targets. With this concept in mind, we designed a new computer algorithm AUTOSTERE which could systematically assess the opportunities to replace any part of any molecule within an entire database of known ligand structures with a target scaffold and automatically evaluate the potential designs in the context of the original ligand's protein environment. As such, it performs scaffold replacement on an unprecedented scale and suggests new target opportunities for preferred chemistries rather than the conventional reverse situation. The results of this approach for one scaffold, a substituted triazolinone, applied to a set of 10 426 ligand conformations extracted from the PDB are described. This led to the identification of ∼600 novel ligands incorporating the triazolinone scaffolds in complex with their predicted drug targets. From these, design examples are provided for HSP-90, cathepsin K, and TIE-2 kinase. A further study involved the searching for possible drug targets for unusual pyridopyrimidine cores. This process resulted in the identification of potential novel HIV reverse transcriptase inhibitors which were synthesized and shown to exhibit similar in vitro potencies to marketed compounds. Overall, the methodology described provides a powerful new approach to identify new target opportunities for scaffolds of provenance.

Hook of Hamate Fractures in Major and Minor League Baseball Players.

PURPOSE: The purpose of this study was to describe an approach to surgical management of the hook of hamate fractures in professional baseball players. METHODS: A retrospective chart review was performed on Major and Minor League Baseball players who underwent surgical excision for the hook of hamate fracture between the years 2003 and 2019 by a single surgeon. Patient demographics, the mechanism and timing of the injury, diagnostic and operative details, postoperative complications, and timeline to return to baseball activities were recorded. RESULTS: A total of 145 professional baseball players affiliated with 17 Major League Baseball organizations were studied, with the majority of athletes playing at the Minor League Baseball level (91.7%). Subacute or chronic patterns of injury (81.7%) were found to be more common than acute patterns based on radiographic and intraoperative findings. Two patients reported transient numbness in the fourth and fifth digits after surgery, 6 patients reported pisotriquetral pain when returning to a hitting program, and 1 patient developed heterotopic ossification after surgery. All complications resolved during a strength and conditioning program. On average, players in our cohort began a hitting program at 4.6 weeks after surgery and were released into full baseball activities at 7.1 weeks after surgery. CONCLUSIONS: Surgical excision remains an effective method of management, with a low risk of minor complications for both acute and chronic hook of hamate fractures in professional baseball players. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic Level IV.

Triceps Rupture After Olecranon Fixation with Proximal Ulna Plate and Suture Augmentation: A Case Report.

CASE: Olecranon fractures treated with proximal ulna plate fixation and repairing the triceps with suture augmentation to the plate decrease the risk of "olecranon escape," but may lead to failure through triceps rupture. In this case report, a rare complication of triceps rupture occurred, and the patient underwent triceps repair. CONCLUSION: When fixing olecranon fractures, surgeons should minimize triceps dissection for hardware placement. If subjected to significant force, a surgical insult to the tendon footprint for a better plate contact on the bone and the presence of suture augmentation may change the construct failure mechanism and result in triceps rupture as opposed to fracture redisplacement.

Synthesis of novel PPARα/γ dual agonists as potential drugs for the treatment of the metabolic syndrome and diabetes type II designed using a new de novo design program PROTOBUILD.

Peroxisome proliferator activated receptors (PPARs) have been shown to have critical roles in fatty acid oxidation, triglyceride synthesis, and lipid metabolism - making them an important target in drug discovery. Here we describe the in silico design, synthesis and in vitro characterisation of a novel series of 2,5-disubstituted indoles as PPARα/γ dual agonists. PPAR activation assays are performed with known agonists diazabenzene (WY14.643), aminopyridine (BRL49653) and bisaryl (L165.041), as positive controls. All the indole compounds synthesized are found to be active PPARα and PPARγ agonists, with particular efficacy from those with 2-naphthylmethyl substitution. This is a useful demonstration of a new de novo design methodology implemented by the protobuild program and its ability to rapidly produce novel modulators for a well characterized drug target.

Hospital outcomes of scoliosis surgery in children with Prader-Willi Syndrome: comparison with adolescent idiopathic scoliosis.

PURPOSE: The purpose of this study was to evaluate the peri-operative outcomes of patients with Prader-Willi Syndrome (PWS) undergoing spinal deformity correction and compare the outcomes to patients with adolescent idiopathic scoliosis (AIS). METHODS: A retrospective review of the Kid's Inpatient Database was performed from 2000 to 2012 to identify all pediatric patients with scoliosis undergoing spinal fusion. Cohorts were created on the basis of PWS diagnosis and adolescent idiopathic scoliosis. Statistical analysis was performed for differences in post-operative outcomes between these two patient cohorts. RESULTS: Between 2000 and 2012, the number of spinal fusions performed increased by 24.6 and 32.2% in the PWS and adolescent idiopathic scoliosis populations, respectively. There was no difference between the incidence of major complications in PWS patients when compared to AIS (1.7% vs. 1.0% in idiopathic scoliosis; p = 0.362). Although there was no significant difference in the rate of overall minor complications, PWS patients were demonstrated to be more likely to experience post-operative pneumonia (p < 0.0001) and implant complications (p < 0.001). CONCLUSION: Patients with scoliosis associated with PWS do not have any increased risk of major complications following spinal deformity correction when compared to patients with adolescent idiopathic scoliosis. Two important minor complications to keep in mind when surgically treating scoliosis in PWS patients include pulmonary and implant-related complications. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

When Do Patients Improve After Hip Arthroscopy for Femoroacetabular Impingement? A Prospective Cohort Analysis.

BACKGROUND: Hip arthroscopy for femoroacetabular impingement (FAI) has been shown to improve patient outcomes, especially for returning to sport. Although previous studies often evaluated outcomes 2 years after hip arthroscopy, there has been no analysis of the progression of patient improvement over time or with respect to achieving the minimal clinically important difference (MCID). HYPOTHESIS/PURPOSE: The purpose was to prospectively evaluate changes in patient-reported outcome (PRO) scores during the first 2 years after hip arthroscopy for FAI and to analyze when the MCID is achieved. It was hypothesized that clinically significant changes will be reached by 1 year after surgery. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients undergoing hip arthroscopy for FAI were prospectively enrolled, and they completed the 12-Item Short Form Health survey (SF-12), modified Harris Hip Score, and Hip disability and Osteoarthritis Outcome Score (HOOS) at preoperative baseline and 3 months, 6 months, 1 year, and 2 years after surgery. Mean scores and the percentage of patients reaching the MCID at each time point were analyzed via analysis of variance and Cochrane-Armitage trend tests. RESULTS: A total of 129 hips from 122 patients were evaluated, revealing significant improvements after hip arthroscopy for FAI (PRO scores increased 19 to 45 points) with 95.8%, 93.6%, and 84.8% of patients achieving the MCID for HOOS-Sports, HOOS-Quality of Life (QoL), and HOOS-Pain, respectively, at 2-year follow-up. Analysis of PRO change showed that for all scores, the greatest improvement occurred from presurgery to postoperative 3 months, with lesser improvements at subsequent 6-month, 1-year, and 2-year time points ( P < .001). The SF-12 physical component score, HOOS-Sports, and HOOS-QoL continued to show statistically significant improvements through 2 years, while other scores plateaued after 3 months. The percentage of patients achieving the MCID for HOOS-Sports, HOOS-QoL, and HOOS-Pain continued to increase over 2 years, but the percentage achieving the MCID did not increase after 3 months for all other scores. CONCLUSION: Hip arthroscopy for FAI yields significant improvements in patient outcomes within 2 years of surgery. The majority of improvement occurs within 3 months after surgery, but certain outcomes, such as returning to sport, QoL, and pain, can continue to improve through 2 years.

Immune or Genetic-Mediated Disruption of CASPR2 Causes Pain Hypersensitivity Due to Enhanced Primary Afferent Excitability.

Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2-/-) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmission within the dorsal horn were increased in Cntnap2-/- mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion (DRG) neuron excitability.

Surface runoff water quality in a managed three zone riparian buffer.

Managed riparian forest buffers are an important conservation practice but there are little data on the water quality effects of buffer management. We measured surface runoff volumes and nutrient concentrations and loads in a riparian buffer system consisting of (moving down slope from the field) a grass strip, a managed forest, and an unmanaged forest. The managed forest consisted of sections of clear-cut, thinned, and mature forest. The mature forest had significantly lower flow-weighted concentrations of nitrate, ammonium, total Kjeldahl N (TKN), sediment TKN, total N (nitrate + TKN), dissolved molybdate reactive P (DMRP), total P, and chloride. The average buffer represented the conditions along a stream reach with a buffer system in different stages of growth. Compared with the field output, flow-weighted concentrations of nitrate, ammonium, DMRP, and total P decreased significantly within the buffer and flow-weighted concentrations of TKN, total N, and chloride increased significantly within the buffer. All loads decreased significantly from the field to the middle of the buffer, but most loads increased from the middle of the buffer to the sampling point nearest the stream because surface runoff volume increased near the stream. The largest percentage reduction of the incoming nutrient load (at least 65% for all nutrient forms) took place in the grass buffer zone because of the large decrease (68%) in flow. The average buffer reduced loadings for all nutrient species, from 27% for TKN to 63% for sediment P. The managed forest and grass buffer combined was an effective buffer system.

An inhibitor of FtsZ with potent and selective anti-staphylococcal activity.

FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian beta-tubulin that polymerizes and assembles into a ring to initiate cell division. We have created a class of small synthetic antibacterials, exemplified by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent and selective in vitro bactericidal activity against staphylococci, including methicillin- and multi-drug-resistant Staphylococcus aureus. The putative inhibitor-binding site of PC190723 was mapped to a region of FtsZ that is analogous to the Taxol-binding site of tubulin. PC190723 was efficacious in an in vivo model of infection, curing mice infected with a lethal dose of S. aureus. The data validate FtsZ as a target for antibacterial intervention and identify PC190723 as suitable for optimization into a new anti-staphylococcal therapy.