Incidence and Risk Factors of Heterotopic Ossification in the Knee After Reamed Tibial Nailing.

INTRODUCTION: Heterotopic ossification (HO) in the knee after tibial intramedullary nailing (IMN) has yet to be thoroughly investigated. Our aim was to assess frequency and associated factors for HO in the knee after tibial IMN. METHODS: This is a retrospective review at a single level 1 urban trauma center of 213 patients who underwent reamed tibial IMN. Plain radiographs were reviewed postoperatively and on final follow-up (≥6 weeks). Chart review was performed for surgical approach (suprapatellar versus infrapatellar), demographics, injury characteristics, and clinical follow-up. The primary outcome was frequency of HO. RESULTS: HO on final follow-up (mean: 41.43 weeks) was recorded in 15% cases. Postsurgical retroinfrapatellar reaming debris (odds ratio [OR], 4.73), Injury Severity Score (OR, 1.05), intensive care unit admission (OR, 2.89), chest injury (OR, 3.4), and ipsilateral retrograde femoral IMN (OR, 5.08) showed a notable association with HO development. No association was observed in HO formation between surgical approach, knee pain, or range-of-motion deficits. DISCUSSION: Radiographic evidence of HO in the knee after reamed tibial IMN is not uncommon and is associated with retained reaming debris, Injury Severity Score, chest injury, intensive care unit admission, and ipsilateral retrograde femoral nailing. No differences were noted in HO formation between approaches. HO was not associated with knee pain or range-of-motion deficits.

Periprosthetic Joint Infection Risk After Primary Total Knee Arthroplasty: Are All Preoperative Corticosteroid Injections the Same?

BACKGROUND: Previous evidence has demonstrated an increased risk of periprosthetic joint infection (PJI) following primary total knee arthroplasty (TKA) in patients receiving corticosteroid injection (CSI) within 3 months of surgery. The study aimed to determine if PJI risk after TKA varied among different corticosteroid agents. METHODS: A total of 85,073 patients undergoing primary TKA from 2009 to 2019 were identified from a large national database. Of these, 1,092 (1.3%) received an ipsilateral, intra-articular CSI within 90 days of TKA. These patients were compared to those not receiving CSI using multivariate logistic regressions following 1:4 propensity score matching, with PJI development as the primary outcome. RESULTS: Patients given an injection of any corticosteroid within 90 days of TKA had significantly higher PJI rates compared to controls (1.6 versus 0.41%; P < .001). This finding was driven by patients receiving methylprednisolone acetate (n = 543) or betamethasone (n = 153), with prevalence rates of 1.7 and 2.6%, respectively (P = .003 and P = .01, respectively). No significant increase in the rate of PJI was observed for patients receiving triamcinolone (1.2%; P = .08; n = 342) or dexamethasone (0.0%; P = 1; n = 54) within 90 days preceding TKA. PJI risk for all agents, administered more than 90 days preoperatively normalized to control levels (0.51 versus 0.34%). CONCLUSIONS: These results suggest that PJI risk varies with CSI type. In this large database study, only patients given methylprednisolone acetate or betamethasone injections within 90 days of surgery had significantly higher PJI rates compared to controls.

Recent updates and future perspectives in aziridine synthesis and reactivity.

In this review, selected recent advances in the preparation and reactivity of aziridines using modern synthetic approaches are highlighted, while comparing these new strategies with more classical approaches. This critical analysis is designed to help identify current gaps in the field and is showcasing new and exciting opportunities to move the chemistry of aziridines forward in the future.

Yarning about pain: Evaluating communication training for health professionals at persistent pain services in Queensland, Australia.

Background: Providing cultural education to health professionals is essential in improving the quality of care and outcomes for Aboriginal and Torres Strait Islander patients. This study reports the evaluation of a novel training workshop used as an intervention to improve communication with Aboriginal and Torres Strait Islander patients of persistent pain services. Methods: In this single-arm intervention study, health professionals undertook a one-day workshop, which included cultural capability and communication skills training based on a clinical yarning framework. The workshop was delivered across three adult persistent pain clinics in Queensland. At the end of the training, participants completed a retrospective pre/post evaluation questionnaire (5 points Likert scale, 1 = very low to 5 = very high), to rate their perceived importance of communication training, their knowledge, ability and confidence to communicate effectively. Participants also rated their satisfaction with the training and suggested improvements for future trainings. Results: Fifty-seven health professionals were trained (N = 57/111; 51% participation rate), 51 completed an evaluation questionnaire (n = 51/57; 90% response rate). Significant improvements in the perceived importance of communication training, knowledge, ability and confidence to effectively communicate with Aboriginal and Torres Strait Islander patients were identified (p < 0.001). The greatest increase was in the perceived confidence pre-training mean of 2.96 (SE = 0.11) to the post-training mean of 4.02 (SE = 0.09). Conclusion: This patient-centred communication training, delivered through a novel model that combines cultural capability and the clinical yarning framework applied to the pain management setting, was highly acceptable and significantly improved participants' perceived competence. This method is transferrable to other health system sectors seeking to train their clinical workforce with culturally sensitive communication skills.

Communication and access to healthcare: Experiences of Aboriginal and Torres Strait Islander people managing pain in Queensland, Australia.

Background: Pain management requires a multidisciplinary approach and a collaborative relationship between patient-provider in which communication is crucial. This study examines the communication experiences of Aboriginal and Torres Strait Islander patients and Aboriginal and Torres Strait Islander Hospital Liaison Officers (ATSIHLOs), to improve understanding of how pain is managed in and through patient-health professional communication. Methods: This qualitative study involved a purposive sample of patients attending three persistent pain clinics and ATSIHLOs working in two hospitals in Queensland, Australia. Focus groups and in-depth interviews explored the communication experiences of patients managing pain and ATSIHLOs supporting patients with pain. This study adopted a descriptive phenomenological methodology, as described by Colaizzi (1978). Relevant statements (patient and ATSIHLOs quotes) about the phenomenon were extracted from the transcripts to formulate meanings. The formulated meanings were subsequently sorted into thematic clusters and then integrated into themes. The themes were then incorporated into a concise description of the phenomenon of communication within pain management. Findings were validated by participants. Results: A total of 21 Aboriginal and Torres Strait Islander participants were involved in this study. Exploration of the communication experiences of patients and ATSIHLOs revealed overlapping themes of important barriers to and enablers of communication that affected access to care while managing pain. Acknowledging historical and cultural factors were particularly important to build trust between patients and health professionals. Some patients reported feeling stigmatized for identifying as Aboriginal and Torres Strait Islander, while others were reluctant to disclose their background for fear of not having the same opportunity for treatment. Differences in the expression of pain and the difficulty to use standard pain measurement scales were identified. Communication was described as more than the content delivered, it is visual and emotional expressed through body language, voice intonation, language and the speed of the conversation. Conclusion: Communication can significantly affect access to pain management services. Aboriginal and Torres Strait Islander patients highlighted the burden of emotional pain caused by historical factors, negative stereotypes and the fear of discrimination. Pain management services and their health professionals need to acknowledge how these factors impact patients trust and care.

High Altitude as a Risk Factor for Venous Thromboembolism in Tibial Plateau Fractures.

Background: Tibial plateau fractures are often significant injuries that can require complex surgical interventions with prolonged perioperative immobilization, thereby increasing the risk of developing venous thromboembolic (VTE) events, specifically, deep vein thrombosis (DVT) and pulmonary embolism (PE). Risk stratification is paramount for guiding VTE prophylaxis. Although high altitude has been suggested to create a prothrombotic state, virtually no studies have explored its clinical effects in lower extremity trauma. The purpose of this study was to compare surgical fixation of tibial plateau fractures at high and low altitudes and its effects on post-operative VTE development. Methods: The Truven MarketScan claims database was used to retrospectively identify patients who underwent surgical fixation of isolated and closed tibial plateau fractures using Current Procedural Terminology (CPT) codes over a 10-year period. Extraneous injuries were excluded using the International Classification of Diseases, 10th edition (ICD-10), and CPT codes. Patient demographics, comorbidities, and DVT chemoprophylaxis prescriptions were obtained. Patients were partitioned into high altitude (>4000 feet) or low altitude (<100 feet) cohorts based on the zip codes of their surgery locations. One-to-one matching and univariate analysis were used to assess and control any baseline discrepancies between cohorts; multivariate regression was then performed between cohorts to determine the odds ratios (OR) for developing VTEs post-operatively. Results: There were 7,832 patients included for analysis. There was no statistical difference between high and low altitude cohorts in developing VTEs within 30 days post-operatively. Higher altitudes were associated with increased odds of developing DVT (OR 1.21, p = 0.043) and PE (OR 1.27, p = 0.037) within 90 days post-operatively. Conclusions: Surgical fixation of tibial plateau fractures is associated with an increased risk of developing VTEs at high altitudes within 90 days post-operatively. Understanding such risk factors in specific orthopaedic patient populations is essential for optimizing DVT prophylaxis protocols. Further studies should investigate this relationship and the role of DVT prophylaxis regimens in this population.

Design, Synthesis, and Biological Evaluation of Potent 20S Proteasome Activators for the Potential Treatment of α-Synucleinopathies.

While neurodegenerative diseases affect millions of patients worldwide, there are insufficient available therapeutics to halt or slow down the progression of these diseases. A key pathological feature of several neurodegenerative diseases is the oligomerization and aggregation of specific intrinsically disordered proteins (IDPs) creating neuronal deposits, such as Lewy bodies in Parkinson's disease. Clearance of these pathogenic, aggregation-prone IDPs is mediated by the 20S isoform of the human proteasome. Thus, enhancing the 20S proteasome-mediated proteolysis could be a very useful therapeutic pathway to prevent neurotoxicity. Here, we report the successful development of sub-microM 20S proteasome activators based on a phenothiazine scaffold. This class of compounds prevented the accumulation of pathologically relevant IDPs, such as the pathogenic A53T mutated α-synuclein, in vitro and in mammalian cell lines.

Fixation vs Arthroplasty for Femoral Neck Fracture in Patients Aged 40-59 Years: A Propensity-Score-Matched Analysis.

Background: Internal fixation (IF) has historically been favored for the treatment of femoral neck fractures (FNFs) in young, nongeriatric patients. However, recent literature reporting high reoperation rates among those receiving IF, taken in conjunction with favorable survivorship of modern bearing surfaces in total hip arthroplasty (THA), has begun to question this paradigm. Our study sought to compare outcomes between IF and THA for FNFs in patients aged 40-59 years. Methods: Using the Truven MarketScan Database, we performed a retrospective propensity-score-matched cohort study on patients aged 40-59 years who underwent surgical management of an isolated FNF (THA or IF). Patients with pathologic fracture were not included. Analysis was conducted on patients aged 40-49 and 50-59 years separately. A subgroup analysis was performed on those patients with 1 year and 3 years of follow-up. Multivariate analysis, controlling for baseline patient information, was then performed. Results: Seven hundred sevety-eight 40- to 49-year-old patients and 3470 50- to 59-year-old matched patients (IF and THA) were included in this study. A multivariate analysis found that patients aged 40-49 years who underwent IF were at higher odds of both 1-year (odds ratio 2.35, 95% confidence interval 1.22-4.54, P = .011) and 3-year (odds ratio 5.68, 95% confidence interval 2.21-14.60, P < .001) reoperation. Similar results were found in those aged 50-59 years. While complication rates were similar, postoperative anemia and 90-day visits to the emergency room were more common after THA in both age cohorts. Conclusions: While THA is associated with increased postoperative anemia and resource utilization compared with IF, patients aged 40-59 years who undergo IF for FNF are at increased risk of reoperation in the first 3 postoperative years. This information should be used to assist in shared decision-making with patients in this age group.

Quantification of Kuramoto Coupling Between Intrinsic Brain Networks Applied to fMRI Data in Major Depressive Disorder.

Organized patterns of system-wide neural activity adapt fluently within the brain to adjust behavioral performance to environmental demands. In major depressive disorder (MD), markedly different co-activation patterns across the brain emerge from a rather similar structural substrate. Despite the application of advanced methods to describe the functional architecture, e.g., between intrinsic brain networks (IBNs), the underlying mechanisms mediating these differences remain elusive. Here we propose a novel complementary approach for quantifying the functional relations between IBNs based on the Kuramoto model. We directly estimate the Kuramoto coupling parameters (K) from IBN time courses derived from empirical fMRI data in 24 MD patients and 24 healthy controls. We find a large pattern with a significant number of Ks depending on the disease severity score Hamilton D, as assessed by permutation testing. We successfully reproduced the dependency in an independent test data set of 44 MD patients and 37 healthy controls. Comparing the results to functional connectivity from partial correlations (FC), to phase synchrony (PS) as well as to first order auto-regressive measures (AR) between the same IBNs did not show similar correlations. In subsequent validation experiments with artificial data we find that a ground truth of parametric dependencies on artificial regressors can be recovered. The results indicate that the calculation of Ks can be a useful addition to standard methods of quantifying the brain's functional architecture.

Acylated and alkylated benzo(crown-ethers) form ion-dependent ion channels in biological membranes.

Synthetic ion channels based on benzo(crown-ether) compounds have been previously reported to function as ion-selective channels in planar lipid bilayers, with hydrogen bonding networks implicated in the formation of self-aggregated complexes. Herein, we report the synthesis and characterization of two new families of benzo(crown-ether) compounds, termed monoacylated and monoalkylated benzo(crown-ethers) (MABCE), both of which lack hydrogen bond donors. Depending on the length of alkyl chain substituent and the size of macrocycle, MABCE compounds inhibit bacterial growth and transport ions across biological membranes. Single-channel recordings show that the activity is higher in the presence of K+ as compared with Na+; however, under bionic conditions, open channels do not exhibit any preference between the two ions. These findings reveal that the ionic preference of benzo(crown-ether) compounds is either due to the regulation of assembly of ion-conducting supramolecular complexes or its membrane insertion by cations, as opposed to ion-selective transport through these scaffolds. Furthermore, our data show that the H-bonding network is not needed to form these assemblies in the membrane.

Clinician Perspectives of Communication with Aboriginal and Torres Strait Islanders Managing Pain: Needs and Preferences.

Poor communication is an important factor contributing to health disparity. This study sought to investigate clinicians' perspectives about communicating with Aboriginal and Torres Strait Islander patients with pain. This multi-site and mixed-methods study involved clinicians from three pain management services in Queensland, Australia. Clinicians completed a survey and participated in focus groups. Clinicians rated the importance of communication training, their knowledge, ability, and confidence in communicating with Aboriginal and Torres Strait Islander patients using a 5-point Likert scale. Rating scores were combined into low (scores 1-2); moderate (score 3) and high (scores 4-5). Informed by an interpretive description methodology, thematic analysis of focus group data was used to identify the communication needs and training preferences of clinicians. Overall (N = 64), 88% of clinicians rated the importance of communication training when supporting Aboriginal and Torres Strait Islander patients as "high". In contrast, far fewer clinicians rated as "high" their knowledge (28%), ability (25%) and confidence (28%) in effectively communicating with Aboriginal and Torres Strait Islander patients. Thematic analysis identified three areas of need: knowledge of Aboriginal and Torres Strait Islander cultures, health beliefs, and understanding cross-cultural cues. Communication skills can be learned and training, in the form of a tailored intervention to support quality engagement with Aboriginal and Torres Strait Islander patients, should combine cultural and communication aspects with biomedical knowledge.

Behavioral and Socioemotional Outcomes of the Legacy for Children™ Randomized Control Trial to Promote Healthy Development of Children Living in Poverty, 4 to 6 Years Postintervention.

OBJECTIVE: The objective of this article was to assess the impact on behavioral and socioemotional development, 4 to 6 years postintervention (depending on the curriculum), of Legacy for Children™, a public health approach to improve child developmental outcomes among families living in poverty. METHODS: Mothers who were recruited prenatally or at the time of childbirth participated in a set of Legacy parallel design randomized control trials between 2001 and 2009 in Miami, Florida, or Los Angeles, California. Of the initial 574 mother-child dyads, 364 completed at least 1 behavioral or socioemotional outcome measure at the third-grade follow-up. Intention-to-treat analyses compared Legacy and comparison groups on behavioral and socioemotional outcomes. RESULTS: Children of Legacy mothers in Los Angeles were at lower risk for externalizing behaviors and poor adaptive skills than children whose mothers did not participate in the intervention. No significant outcome differences by group assignment were found in Miami. CONCLUSION: Group-based positive parenting interventions such as Legacy may have a sustained impact on children's behavioral and socioemotional development several years after intervention completion.

Impact of Frailty and Malnutrition on Outcomes After Surgical Fixation of Lower Extremity Fractures in Young Patients.

OBJECTIVES: Evaluate the relationship of nutrition parameters and the modified frailty index (mFI) on postsurgical complications within a young patient population sustaining lower extremity orthopaedic trauma. DESIGN: Retrospective observational cohort study. SETTING: Urban, American College of Surgeons-Verified, Level-1, Trauma Center. PATIENTS/PARTICIPANTS: Seventeen-thousand one hundred nine adult patients under the age of 65 sustaining lower extremity fractures undergoing operative intervention from 2006 to 2018. MAIN OUTCOME MEASURES: On admission, mFI and albumin levels were obtained, as well as complication data. Statistical analysis was used to analyze the association between frailty, malnutrition, and postoperative complications. Patients were stratified, healthy (mFI ≤1, albumin ≥3.5 g/dL), malnourished (mFI ≤1, albumin <3.5 g/dL), frail (mFI ≥2, albumin ≥3.5 g/dL), and frail and malnourished (mFI ≥2, albumin <3.5 g/dL). RESULTS: 60.4% of patients were healthy, 18.8% were malnourished, 11.7% were frail, and 9.0% were frail and malnourished. Frailty and/or malnourishment on admission predicted significantly higher odds of postoperative complications and mortality when compared with healthy patients. Frailty and malnourishment in conjunction predicted a significantly higher odds ratio of 1.46 (1.22-1.75) for developing postoperative complications when compared with the only malnourished. This was also observed when compared with the only frail (odd ratio: 1.61, P < 0.001); however, there was also a 2.72 (P < 0.001) increased odds of mortality. CONCLUSIONS: Frailty and malnutrition in conjunction predicts a subset of patients with a higher risk of postoperative complications beyond that of frailty or malnutrition in isolation. Identification of these physiological states on admission allows for interventional opportunities during hospitalization. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Transport losses in market weight pigs: II. U.S. incidence and economic impact.

An industry survey representing approximately 310 million (M) market weight pigs was conducted with 20 U.S. slaughter facilities over the calendars years of 2012 to 2015 to determine the incidence, seasonal patterns, and estimated economic impact of dead and non-ambulatory pigs. Each plant entered daily totals in a secure online database for the following variables: 1) pigs slaughtered, 2) dead on arrival (DOA; dead on the truck), 3) euthanized on arrival (EOA; non-ambulatory pig with an injury that required euthanasia), 4) dead in pen (DIP; died after unloading), and 5) non-ambulatory (pig unable to move or keep up with the rest of the group from unloading to stunning). Total dead pigs were calculated as DOA + EOA + DIP, and total losses were calculated as non-ambulatory + total dead. The economic impact was estimated based on the 4-yr weighted averages from USDA annual reports for market swine slaughtered (108,470,550 pigs), live market weight (126.9 kg), and live market price ($1.44/kg). The 4-yr weighted averages for total dead, non-ambulatory, and total losses were 0.26%, 0.63%, and 0.88%, respectively. Total dead consisted of 0.15% DOA, 0.05% EOA, and 0.05% DIP. The months with the highest rates of total dead were July (0.29%), August (0.32%), and September (0.30%), while the lowest incidence rates occurred in February (0.22%), March (0.22%), and April (0.22%). The months with the highest rates of non-ambulatory pigs were observed during the months of October (0.70%), November (0.71%), and December (0.70%), whereas the lowest rates of non-ambulatory pigs were observed during the months of April (0.57%), May (0.53%), and June (0.54%). The following assumptions were used in the economic analysis: 1) dead pigs received no value and 2) non-ambulatory pigs were discounted 30%. Based on these assumptions, the annual cost to the industry for dead and non-ambulatory pigs was estimated to be $52 M ($0.48 per pig marketed) and $37 M ($0.35 per pig marketed), respectively. Therefore, total losses represent approximately $89 M in economic losses or $0.83 per pig marketed. This is the first industry-wide survey on the incidence of transport losses in market weight pigs at U.S. slaughter facilities, and this information is important for establishing an industry baseline and benchmark for transport losses that can be used for measuring industry improvements.

Exploiting in situ NMR to monitor the formation of a metal-organic framework.

The formation processes of metal-organic frameworks are becoming more widely researched using in situ techniques, although there remains a scarcity of NMR studies in this field. In this work, the synthesis of framework MFM-500(Ni) has been investigated using an in situ NMR strategy that provides information on the time-evolution of the reaction and crystallization process. In our in situ NMR study of MFM-500(Ni) formation, liquid-phase 1H NMR data recorded as a function of time at fixed temperatures (between 60 and 100 °C) afford qualitative information on the solution-phase processes and quantitative information on the kinetics of crystallization, allowing the activation energies for nucleation (61.4 ± 9.7 kJ mol-1) and growth (72.9 ± 8.6 kJ mol-1) to be determined. Ex situ small-angle X-ray scattering studies (at 80 °C) provide complementary nanoscale information on the rapid self-assembly prior to MOF crystallization and in situ powder X-ray diffraction confirms that the only crystalline phase present during the reaction (at 90 °C) is phase-pure MFM-500(Ni). This work demonstrates that in situ NMR experiments can shed new light on MOF synthesis, opening up the technique to provide better understanding of how MOFs are formed.

Re-evaluation of the mechanism of cytotoxicity of dialkylated lariat ether compounds.

The cytotoxicity of dialkylated lariat ethers has been previously attributed to their ionophoric properties. Herein, we provide evidence that these effects are due to loss of membrane integrity rather than ion transport, a finding with important implications for the future design of synthetic ionophores.

Proteasome Activation to Combat Proteotoxicity.

Loss of proteome fidelity leads to the accumulation of non-native protein aggregates and oxidatively damaged species: hallmarks of an aged cell. These misfolded and aggregated species are often found, and suggested to be the culpable party, in numerous neurodegenerative diseases including Huntington's, Parkinson's, Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's Diseases (AD). Many strategies for therapeutic intervention in proteotoxic pathologies have been put forth; one of the most promising is bolstering the efficacy of the proteasome to restore normal proteostasis. This strategy is ideal as monomeric precursors and oxidatively damaged proteins, so called "intrinsically disordered proteins" (IDPs), are targeted by the proteasome. This review will provide an overview of disorders in proteins, both intrinsic and acquired, with a focus on susceptibility to proteasomal degradation. We will then examine the proteasome with emphasis on newly published structural data and summarize current known small molecule proteasome activators.

Pipecolic esters as minimized templates for proteasome inhibition.

Allosteric regulators of clinically important enzymes are gaining popularity as alternatives to competitive inhibitors. This is also the case for the proteasome, a major intracellular protease and a target of anti-cancer drugs. All clinically used proteasome inhibitors bind to the active sites in catalytic chamber and display a competitive mechanism. Unfortunately, inevitable resistance associated with this type of inhibition drives the search for non-competitive agents. The multisubunit and multicatalytic "proteolytic machine" such as the proteasome is occasionally found to be affected by agents with other primary targets. For example the immunosuppressive agent rapamycin has been shown to allosterically inhibit the proteasome albeit at levels far higher than its mTOR related efficacy. As part of an ongoing program to search for novel proteasome-targeting pharmacophores, we identified the binding domain of rapamycin as required for proteasome inhibition even without the macrocyclic context of the parent compound. By subsequent structure-activity relationship studies, we generated a pipecolic ester derivative compound 3 representing a new class of proteasome inhibitors. Compound 3 affects the core proteasome activities and proliferation of cancer cells with low micromolar/high nanomolar efficacy. Molecular modeling, atomic force microscopy imaging and biochemical data suggest that compound 3 binds into one of intersubunit pockets in the proteasomal α ring and destabilizes the α face and the gate. The α face is used as a docking area for proteasome-regulating protein modules and the gate is critical for controlling access to the catalytic chamber. Thus, the pipecolic ester template elicits a new and attractive mechanism for proteasome inhibition distinct from classical competitive drugs.

Outcomes of Revisions for Failed Trapeziometacarpal Joint Arthritis Surgery.

PURPOSE: We compare outcomes of revision surgery for trapeziometacarpal (TM) arthritis with outcomes for both primary and revision surgery for TM arthritis reported in the literature. We hypothesized that patients undergoing revision surgery for TM arthritis would demonstrate pain and functional outcome scores that were worse than those of patients undergoing primary TM surgery. METHODS: A retrospective analysis of all patients undergoing revision TM surgery at a single institution from 1995 to 2015 was performed. Eighty-three patients (86 hands) met the inclusion criteria. Of these, 25 patients (27 hands) were available for follow-up via phone survey or clinical examination; 58 patients (59 hands) were available for chart review only. Patients available for phone survey or clinical examination were evaluated with the visual analog scale, Disabilities of the Arm, Shoulder, and Hand score, and the Conolly-Rath evaluation method. Patients available for clinical examination were also evaluated with grip strength, pinch strength, and radiographs. RESULTS: Median follow-up was 8.5 years (range, 2.0-21.2 years). Twenty percent of patients experienced postoperative complications, most commonly pin problems (7%). Of the 27 hands available for interview or clinical examination, 15 were dominant and 12 were nondominant. The average visual analog scale was 28.2 (SD, 29.7). Disabilities of the Arm, Shoulder, and Hand scores averaged 32.0 (SD, 20.8). According to the Conolly and Rath criteria, 10 patients had a good outcome, 7 were fair, and 10 were poor. For the group of 13 patients who underwent physical examination, average adduction was 42° in the affected side versus 51° in the nonaffected side. Radial abduction was 58° in the affected side versus 65° in the nonaffected side. Palmar abduction was 53° versus 85° in each group, respectively. Tip finger pinch was 3.4 kg for the affected hand versus 4.0 kg for the nonaffected side. Key pinch was 4.7 and 5.5 kg, respectively. Grip strength was measured as 22.1 kg in the affected side versus 27.6 kg in the contralateral side when adjusted for dominance. CONCLUSIONS: In our study group, revision surgery for unsuccessful primary TM surgery demonstrated results inferior to those previously reported for primary surgery for TM arthritis but similar to prior studies of revision TM surgery. Revision surgery, however, can result in satisfactory long-term outcomes particularly when metacarpophalangeal joint pathology is addressed and complications are avoided. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Small Molecule Modulation of Proteasome Assembly.

The 20S proteasome is the main protease that directly targets intrinsically disordered proteins (IDPs) for proteolytic degradation. Mutations, oxidative stress, or aging can induce the buildup of IDPs resulting in incorrect signaling or aggregation, associated with the pathogenesis of many cancers and neurodegenerative diseases. Drugs that facilitate 20S-mediated proteolysis therefore have many potential therapeutic applications. We report herein the modulation of proteasome assembly by the small molecule TCH-165, resulting in an increase in 20S levels. The increase in the level of free 20S corresponds to enhanced proteolysis of IDPs, including α-synuclein, tau, ornithine decarboxylase, and c-Fos, but not structured proteins. Clearance of ubiquitinated protein was largely maintained by single capped proteasome complexes (19S-20S), but accumulation occurs when all 19S capped proteasome complexes are depleted. This study illustrates the first example of a small molecule capable of targeting disordered proteins for degradation by regulating the dynamic equilibrium between different proteasome complexes.