Polyoxometalate-Ionic Liquids for Mitigating the Effects of Iron Gall Ink Corrosion on Cellulosic Supports.

Iron gall ink (IGI), renowned for its indelibility, was the most important writing ink in the Western world from the 15th to the late 19th century. However, it is now known that IGIs induce acid-catalyzed hydrolysis and iron-catalyzed oxidation of the cellulose in historical paper documents. These mechanisms of deterioration cause significant damage to the writing support materials, including color alteration and burn-through appearance, and in the worst scenarios, physical disintegration of the supports. Minimally invasive, long-term effective conservation treatments that tackle the underlying mechanisms of IGI degradation and their corrosion effects are yet to be developed. This study introduces the deployment of hydrophobic and anticorrosive polyoxometalate-ionic liquids (POM-ILs) as colorless coatings to counteract IGI-corrosion of cellulosic supports. Model IGI-containing papers (mockups) were prepared, coated with POM-ILs, and artificially aged to assess the compatibility of POM-ILs with IGI-containing documents. Comprehensive monitoring using colorimetric and scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM/EDS) analyses showed minimal interference with the aesthetic properties and morphology of the IGI mockups. In addition, polyoxometalates (POMs) with vacant metal atom sites in the cluster shell can be used to coordinate free transition metal ions. The ability of a monolacunary Keggin-type polyoxotungstate to coordinate free Fe(II) from IGI solution was demonstrated using UV-vis analysis. This led to the formation of a dimeric species, [(SiW11O39Fe)2O]K12·28H2O, which was characterized by single-crystal X-ray diffraction. Altogether, this study points to POM-ILs as promising protective coatings for effectively preserving historical IGI-written heritage.

Management of gunshot wounds near the elbow: experiences at a high-volume level I trauma center.

BACKGROUND: Gunshot-related fractures near the elbow are challenging, and available data to guide the practitioner are lacking. This report analyzes injury patterns and treatment strategies in a case series from a high-volume urban trauma center. METHODS: All periarticular gunshot fractures near the elbow treated at a level 1 trauma center from 2014 to 2018 were retrospectively reviewed. Fracture location, patient demographics, concomitant injuries, treatment modalities, and complications were analyzed. RESULTS: Twenty-four patients were identified. All patients received prophylactic antibiotics upon admission and underwent urgent surgical debridement. Open reduction and internal fixation (ORIF) was performed with initial debridement in 22 of 24 patients. Seven patients sustained distal humerus fractures, 10 patients sustained isolated proximal ulna or proximal radius fractures, and seven had combined fracture patterns. Eleven patients presented with nerve palsy, and two had transected nerves. Two patients had vascular injury requiring repair. One patient required a temporary elbow-spanning external fixator and underwent staged debridement followed by ORIF. One patient with a grade IIIC fracture developed a deep infection that precluded ORIF. One patient required revision ORIF due to fracture displacement. CONCLUSIONS: This investigation reports on management of ballistic fractures near the elbow at a busy urban level I trauma center. Our management centered on rapid debridement, early definitive fixation, and intravenous antibiotic administration. We report on associated neurovascular injury, bone loss, and other challenges in this patient population. Level of evidence: IV.

Use of Questionnaire-Based Research in Hand Surgery.

INTRODUCTION: Questionnaire-based research is ubiquitous, and careful survey design is paramount to obtaining meaningful results. This study characterizes the use of questionnaire-based studies in the current hand surgery literature. METHODS: We conducted a systematic review of questionnaire-based studies published between 2010 and 2020 in 4 major American journals. We included studies in which questionnaire results represented a primary outcome. Validation status of the survey instruments was assessed, and topics of study were categorized. Nonvalidated instruments were assessed for reporting of parameters to limit bias. RESULTS: Three hundred fifty-four studies were identified, including 186 (52.5%) using validated instruments, 98 (27.7%) using nonvalidated instruments, 64 (18.1%) using a combination, and 6 (1.7%) that sought to validate an instrument. Of the studies that used validated instruments, 84.9% focused on patient-reported outcomes and 15.1% focused on other patient-centered topics. In contrast, of studies that used nonvalidated instruments, 44.9% focused on physician practice, 30.6% were patient centered, and 13.3% focused on education. Among nonvalidated questionnaires, 74.5% did not report predistribution testing, 49.0% did not publish full survey questions, and 33.3% did not report response rates. CONCLUSIONS: Survey research is common in the hand surgery literature. Forty-six percent of examined studies included at least some nonvalidated elements. Techniques to limit bias in the design and reporting of studies based on nonvalidated surveys were not uniformly disclosed. Identified areas for improvement include (1) pilot testing to assess for question clarity; (2) publication of full texts to improve transparency; and (3) better reporting on sample selection, respondents, and nonrespondents.

Mimicking hypomethylation of FUS requires liquid-liquid phase separation to induce synaptic dysfunctions.

The hypomethylation of fused in sarcoma (FUS) in frontotemporal lobar degeneration promotes the formation of irreversible condensates of FUS. However, the mechanisms by which these hypomethylated FUS condensates cause neuronal dysfunction are unknown. Here we report that expression of FUS constructs mimicking hypomethylated FUS causes aberrant dendritic FUS condensates in CA1 neurons. These hypomethylated FUS condensates exhibit spontaneous, and activity induced movement within the dendrite. They impair excitatory synaptic transmission, postsynaptic density-95 expression, and dendritic spine plasticity. These neurophysiological defects are dependent upon both the dendritic localisation of the condensates, and their ability to undergo liquid-liquid phase separation. These results indicate that the irreversible liquid-liquid phase separation is a key component of hypomethylated FUS pathophysiology in sporadic FTLD, and this can cause synapse dysfunction in sporadic FTLD.

Antibacterial properties of phosphine gold(I) complexes with 5-fluorouracil.

New gold(I) complexes with coordination to 5-fluorouracil (5-FU), an anticancer drug with antibacterial properties, have been synthesised and characterised, and are the first reported examples of 5-FU-Au compounds. These new complexes show high solution stability, even in the presence of a cysteine derivative, and so were evaluated as antibacterial compounds against model Gram-positive and Gram-negative bacteria. All the complexes show excellent antibacterial activity against Gram-positive B. subtilis, most of them improving the activity of 5-FU alone. Furthermore, these new complexes are also active against Gram-negative E. coli, where [Au(5-FU)(PTA)], the complex with the smallest phosphane, is the most bactericidal, 32 times more active than 5-FU on its own.

Prevalence, Perceptions, and Patterns of Cannabis Use Among Cardiac Inpatients at a Tertiary-Care Hospital: A Cross-Sectional Survey.

Background: Cannabis use may adversely affect cardiovascular health. Patterns of use by cardiac patients are unknown. We evaluated the prevalence, perceptions, and patterns of cannabis use among cardiac inpatients. Methods: A consecutive cross-section of cardiac inpatients, hospitalized between November 2019 and May 2020, were surveyed in-person or via telephone. Descriptive statistics and logistic regression were used to examine the characteristics of cannabis use. Results: The prevalence of past-12-month cannabis use was 13.8% (95% confidence interval [CI]: 11.8%-16.0%). Characteristics independently associated with cannabis use were as follows: age < 64 years (< 44 years, odds ratio [OR] = 3.96 [95% CI: 1.65-9.53]; age 45-64 years, OR = 2.72 [95% CI: 1.65-4.47]); tobacco use in the previous 6 months (OR = 1.91 [95% CI: 1.18-3.07]); having a cannabis smoker in one's primary social group (OR = 4.17 [95% CI: 2.73-6.38]); and a history of a mental health diagnosis (OR = 1.82 [95% CI: 1.19-2.79]). Among those using cannabis, 70.5% reported smoking or vaping it; 47.2% reported daily use. Most did not know the tetrahydrocannabinol (THC; 71.6%) or cannabidiol (CBD; 83.3%) content of their cannabis, or the dose of cannabis in their edibles (66.7%). As defined by Canada's Lower Risk Cannabis Use Guidelines, 96.7% of cannabis users reported ≥ 1 higher-risk use behaviour (mean = 2.3, standard deviation = 1.2). Over 60% of patients expressed no intention to quit or reduce cannabis use in the next 6 months. Conclusions: Cannabis use appears prevalent among cardiac patients. Most users demonstrated higher-risk use behaviours and low intentions to quit. Further work is needed to understand the impacts of cannabis use on the cardiovascular system and to develop guidelines and educational tools relating to lower-risk use, for cardiac patients and providers.

Contexte: L'utilisation du cannabis peut nuire à la santé cardiovasculaire, mais les habitudes d'utilisation des patients atteints de troubles cardiaques ne sont pas connues. Nous avons évalué la prévalence, les perceptions et les habitudes d'utilisation du cannabis chez des patients hospitalisés présentant des troubles cardiaques. Méthodologie: Une analyse transversale a été réalisée en interrogeant en personne ou au téléphone des patients hospitalisés consécutivement entre novembre 2019 et mai 2020 et présentant des troubles cardiaques. Des statistiques descriptives et une régression logistique ont été utilisées pour examiner les caractéristiques liées à l'utilisation du cannabis. Résultats: La prévalence de l'utilisation du cannabis au cours des 12 mois précédents était de 13,8 % (intervalle de confiance [IC] à 95 % : 11,8 % à 16,0 %). Les caractéristiques indépendamment associées à l'utilisation du cannabis étaient les suivantes : âge < 64 ans (< 44 ans, rapport de cotes [RC] = 3,96 [IC à 95 % : 1,65 à 9,53]; âge de 45 à 64 ans, RC = 2,72 [IC à 95 % : 1,65 à 4,47]); tabagisme dans les six mois précédents (RC = 1,91 [IC à 95 % : 1,18 à 3,07]); présence d'un consommateur de cannabis au sein du cercle social principal (RC = 4,17 [IC à 95 % : 2,73 à 6,38]); et diagnostic antérieur lié à la santé mentale (RC = 1,82 [IC à 95 % : 1,19 à 2,79]). Parmi les utilisateurs de cannabis, 70,5 % d'entre eux ont rapporté qu'ils fumaient ou vapotaient et 47,2 % ont déclaré en consommer quotidiennement. La plupart ne connaissaient pas le contenu en tétrahydrocannabinol (THC; 71,6 %) ou en cannabidiol (CBD; 83,3 %) du cannabis consommé, ou la dose contenue dans les aliments à base de cannabis consommés (66,7 %). Au total, 96,7 % des utilisateurs de cannabis ont rapporté ≥ 1 comportement(s) à risque élevé (moyenne = 2,3, écart-type = 1,2) selon les Recommandations canadiennes pour l'usage du cannabis à moindre risque. Par ailleurs, plus de 60 % des patients n'ont exprimé aucune intention d'interrompre ou de diminuer leur consommation de cannabis au cours des six prochains mois. Conclusions: L'utilisation du cannabis semble courante chez les patients qui présentent des troubles cardiaques. La plupart des utilisateurs ont démontré des comportements à risque élevé, et une faible intention de mettre fin à leur consommation. D'autres études sont requises pour caractériser les répercussions de l'utilisation du cannabis sur l'appareil cardiovasculaire et élaborer des lignes directrices et des outils éducatifs à l'intention des patients atteints de troubles cardiaques et des professionnels de la santé en vue de favoriser un usage à moindre risque.

A holistic approach to understanding the iron-gall inks in the historical documents of the Portuguese Inquisition (1570-1790).

A substantial part of our written heritage is threatened by the fact that much of it has been written using iron-gall ink (IGI). One such example is the documents of the Portuguese Inquisition Tribunals, held by the Arquivo Nacional da Torre do Tombo. Here we present the first systematic analytical approach, using SEM/EDS, µ-FT-IR-ATR and µ-Raman techniques, to characterise fragments from historical records of the Inquisition Tribunals of Évora, Lisboa and Coimbra from the 16th to 18th centuries. The writing ink was identified as IGI, providing complementary compositional data and establishing differences between various formulations of the ink. Additionally, the deleterious effects of the inks-associated degradation phenomena were highlighted. This work allowed understand the writing inks used by this Portuguese institution.

Accuracy and Safety of Non-Image Guided Trigger Finger Injections: A Cadaveric Study.

BACKGROUND: Stenosing flexor tenosynovitis is commonly treated by injection of corticosteroids into the flexor tendon sheath. However, there is no consensus in the literature regarding the optimal technique, specifically when not utilizing ultrasound guidance. Here, we present a cadaver study in which 3 common techniques of flexor sheath injection were compared with regard to their accuracy and safety profiles. METHODS: Fifteen fresh-frozen cadaver hands (60 digits) were evenly divided into 3 groups (20 digits per group). Digits in each group were injected with methylene blue dye using 1 of the 3 techniques (palmar-to-bone, palmar supra-tendinous, and mid-axial). The fingers were then dissected and were inspected for location of dye, as well as injury to tendon or digital nerves. RESULTS: The mid-axial technique demonstrated the greatest accuracy with the highest rate of all intra-sheath injection, 15 of 20 digits (75%), while the palmar-to-bone technique produced the most combined intra- and extra-sheath injections, 13 of 20 digits, (65%) and the palmar supra-tendinous technique resulted in the most all extra-sheath injections, 9 of 20 digits (45%). The difference in rates of all intra-sheath injection was significant (P = .01). The mid-axial technique also produced the fewest intra-tendinous injections 0 of 20, although this result did not reach statistical significance (P = .15). CONCLUSIONS: Compared to other common non-image guided flexor tendon sheath injection techniques, the mid-axial injection technique was found to be the most accurate in producing all intra-sheath injection and least likely to result in intra-tendinous injection.

Polyoxometalate-polypeptide nanoassemblies as peroxidase surrogates with antibiofilm properties.

Developing artificial metalloenzymes that possess a superior performance to their natural counterparts is an attractive concept. Polyoxometalates (POMs) are a class of anionic molecular metal-oxides with excellent redox properties and bioactivity. We have recently introduced "POMlymers" - covalently conjugated POM-peptide hybrid materials - where the polypeptide chain is obtained through a ring-opening polymerisation (ROP) of α-amino acid N-carboxyanhydrides (NCA) on an inorganic POM scaffold. Attracted by the idea of preparing artificial metalloenzymes, here we report the supramolecular self-assembly of POMlymer hybrids into nanoparticles where an optimal environment for catalysis is created. Our results demonstrate that the self-assembly of covalent POMlymers, enhances the peroxidase-like activity of the parent POM anion whereas, in contrast, the catalytic activity for nanoparticles obtained by ionic self-assembly of the same peptide and POM components practically disappears. Furthermore, POMlymer nanoparticles also present antimicrobial and antibiofilm activity against the skin bacterium Staphylococcus epidermidis; whereas, ionic POM-peptide hybrids significantly increase biofilm production and endogenous production of reactive oxygen species. In summary, we present the self-assembly of POMlymer hybrids into nanoparticles and a combination of peroxidase activity and microbiology assays that show that the POM-peptide covalent bond is essential for the stability of the self-assembled nanoparticles and therefore for their catalytic and biological activity.

Sacral Insufficiency Fracture Following Short-Segment Lumbosacral Fusion: Case Series and Review of the Literature.

STUDY DESIGN: Retrospective case series. OBJECTIVE: Sacral insufficiency fracture is a rare and serious complication following lumbar spine instrumented fusion. The purpose of this study was to describe the patient characteristics, presentation, evaluation, treatment options, and outcomes for patients with sacral insufficiency fracture after short-segment lumbosacral fusion. METHODS: Six patients from our institutional database and 16 patients from literature review were identified with a sacral insufficiency fracture after short-segment (L4-S1 or L5-S1) lumbar fusion within 1 year of surgery. RESULTS: Patients were 55% female with a mean age of 58 years and body mass index of 30 kg/m2. Osteoporosis or osteopenia was the most common comorbidity (85%). Half of patients sustained a sacral fracture after surgery from a posterior approach, while the others had anterior or anterior-posterior surgery. Mean time to fracture was 42 days with patients clinically presenting with new sacral pain (86%), radiculopathy (60%), or neurologic deficit (5%). Ultimately, 73% of patients underwent operative fixation often involving extension of the construct (75%) and fusion to the pelvis (69%). Men (P = .02) and patients with new radicular pain or neurologic deficit (P = .01) were more likely to undergo revision surgical treatment while women over 50 years of age were more likely to be treated conservatively (P = .003). CONCLUSIONS: Spine surgeons should monitor for sacral insufficiency fracture as a source of new-onset pain in the postoperative period in patients with a short segment fusion to the sacrum. The recognition of this complication should prompt an assessment of bone health and management of underlying bone fragility.

Selective quantitation of B2Pin2 and B2(OH)4 in active pharmaceutical ingredients by gas chromatography- mass spectrometry.

This paper describes a sensitive and selective method for the simultaneous determination of bispinacolato diboron (B2Pin2) and tetrahydroxy diboron (B2(OH)4) in a small molecule Active Pharmaceutical Ingredient (API) by gas chromatography - mass spectrometry (GC-MS). These reagents are commonly used in the Suzuki-Miyaura coupling reaction and analytical methods are typically required to monitor these reagents at the Threshold of Toxicological Concern (TTC) level since they are Class II impurities based on ICH M7 guideline. In this study, hexylene glycol was added to derivatize B2(OH)4 before direct injection to the GC-MS, and B2Pin2 is analyzed in the same analysis without derivatization. Under the optimal conditions, the limit of detection (LOD) and the limit of quantitation (LOQ) were 65 ng/mL and 130 ng/mL respectively. Average recoveries of the analytes spiked in the drug substance at the 13 ppm (LOQ) and 104 ppm (TTC) levels were in the range of 77.9 %-85.3 % with relative standard deviations (RSDs) of 2.8 %-6.8 %. The linearity for both analytes was established in the range of 0.130-2.080 µg/mL with a correlation coefficient (r) of 0.9998 and the derivatization reaction is very rapid and complete within 15 minutes.

On-POM Ring-Opening Polymerisation of N-Carboxyanhydrides.

The ring-opening polymerisation of α-amino acid N-carboxyanhydrides (NCAs) offers a simple and scalable route to polypeptides with predicted and narrow molecular weight distributions. Here we show how polyoxometalates (POMs)-redox-active molecular metal-oxide anions-can serve as inorganic scaffold initiators for such NCA polymerisations. This "On-POM polymerisation" strategy serves as an innovative platform to design hybrid materials with additive or synergistic properties stemming from the inorganic and polypeptide component parts. We have used this synthetic approach to synthesise a library of bactericidal poly(lysine)-POM hybrid derivatives that can be used to prevent biofilm formation. This versatile "On-POM polymerisation" method provides a flexible synthetic approach for combining inorganic scaffolds with amino acids, and the potential to tailor and improve the specificity and performance of hybrid antimicrobial materials.

Discovery of Lanraplenib (GS-9876): A Once-Daily Spleen Tyrosine Kinase Inhibitor for Autoimmune Diseases.

Spleen tyrosine kinase (SYK) is a critical regulator of signaling in a variety of immune cell types such as B-cells, monocytes, and macrophages. Accordingly, there have been numerous efforts to identify compounds that selectively inhibit SYK as a means to treat autoimmune and inflammatory diseases. We previously disclosed GS-9973 (entospletinib) as a selective SYK inhibitor that is under clinical evaluation in hematological malignancies. However, a BID dosing regimen and drug interaction with proton pump inhibitors (PPI) prevented development of entospletinib in inflammatory diseases. Herein, we report the discovery of a second-generation SYK inhibitor, GS-9876 (lanraplenib), which has human pharmacokinetic properties suitable for once-daily administration and is devoid of any interactions with PPI. Lanraplenib is currently under clinical evaluation in multiple autoimmune indications.

Culturally safe and sustainable solution for Closing the Gap-registered patients discharging from a tertiary public hospital.

This case study describes the development, implementation and review of a sustainable and culturally sensitive procedure for a hospital-funded discharge medicine subsidy for Aboriginal and Torres Strait Islander patients registered with the Closing the Gap (CTG) program discharging from a public hospital. A 7-day fully subsidised medication supply was approved to be offered to Aboriginal and Torres Strait Islander patients admitted under cardiac care teams, including cardiology and cardiothoracic surgery patients. Patients were offered the option of a 7-day supply free of cost to them or a full Pharmaceutical Benefits Scheme (PBS) supply if preferred. A general practitioner (GP) appointment was organised within 7 days of discharge to ensure patients received ongoing supply of their medications as well as timely clinical review after discharge. Over a 34-month period from September 2015 to June 2018, 535 Aboriginal and Torres Strait Islander patients were admitted to the hospital under cardiac care teams. Of these patients, 296 received a subsidised discharge medication supply with a total cost of A$6314.56 to the hospital over the trial period, with a mean cost of A$21.26 per discharge. The provision of subsidised medications through the CTG program has improved the continuity of care for Aboriginal and Torres Strait Islander patients. The culturally sensitive approach is well received and has allowed smooth transition back to the community. This site-specific and state-based funding model was found to be financially sustainable at a public hospital.

Reliability of the Dorsal Tangential View in Assessment of Distal Radioulnar Joint Reduction in the Neutral, Pronated, and Supinated Positions in a Cadaver Model.

PURPOSE: Intraoperative assessment of distal radioulnar joint (DRUJ) alignment is often based on lateral radiographs whose interpretation is dependent upon positioning the forearm in neutral rotation. The dorsal tangential view (DTV) is a near-axial view of the dorsal wrist used in assessing dorsal screw penetration during radius fixation. The purpose of this study was to determine whether the DTV can also reliably assess DRUJ alignment in multiple forearm positions. METHODS: Four transhumeral cadaveric specimens were used to simulate an unstable DRUJ. The stabilizing soft tissue structures of the DRUJ were sectioned. Fluoroscopic DTV images were obtained with the DRUJ of each specimen held in 5 positions: dorsally dislocated, dorsally subluxated, reduced, volarly subluxated, and volarly dislocated. In each position, images were taken with the forearm in neutral rotation, full pronation, and full supination. Three observers independently assessed DRUJ position on DTV images. Intra- and interobserver reliability were assessed in each forearm position. RESULTS: Observers correctly identified DRUJ position as reduced, volarly malreduced, or dorsally malreduced on 94% of the DTV images (97%, 95%, and 92% in the neutral, supinated, and pronated forearm positions, respectively). Weighted kappa values for intraobserver reliability were 0.965, 0.964, and 0.965 for the 3 observers. The mean kappas for intraobserver reliability were 1.000, 0.967, and 0.930 with the forearm in neutral, supinated, and pronated positions, respectively. Weighted kappa values for interobserver reliability between paired observers were 0.948, 0.912, and 0.929. The mean kappa for interobserver reliability was 0.926, 0.931, and 0.930 for the forearm in neutral, supinated, and pronated positions, respectively. CONCLUSIONS: The DTV reliably demonstrated the position of the DRUJ independent of forearm rotation in a cadaveric model. CLINICAL RELEVANCE: Surgeons may consider the DTV as another tool for fluoroscopic verification of the DRUJ reduction in the operating room or clinic.

Radiographic Outcomes of Dorsal Spanning Plate for Treatment of Comminuted Distal Radius Fractures in Non-Elderly Patients.

Purpose: Multifragmentary fractures of the distal radius with articular and metaphyseal comminution (AO 23-C3) represent challenging injuries to manage. Distal fracture lines, articular comminution, and limited distal bone stock may preclude stable fixation with a volar locking plate. The use of a dorsal spanning plate (DSP) offers an alternative treatment option in this setting. We examined the radiographic outcomes of a consecutive series of patients with comminuted intra-articular distal radius fractures not amenable to volar locked plating, who were treated with a DSP. Methods: We reviewed all distal radius fractures treated with a dorsal spanning plate at our institution between October, 2014 and March, 2018. Patients with AO 23-C3 fractures treated with dorsal spanning plate fixation were included in this study. Demographic data, time from plate placement to removal, and postoperative radiographic outcomes were examined. Results: We identified 24 patients, mean age 41 years (range, 19-62 years). Mean follow-up was 19.5 weeks (range, 12-35 weeks) from the time of plate placement. Plates were removed at a mean of 87 days (range, 40-215 days) after surgery. All patients achieved radiographic union. Mean radial height at the time of union was 11.1 mm (SD, ±3.7 mm; range, 6-18 mm), radial inclination was 19.7° (SD, ±5.4°; range, 9° to 30°), ulnar variance was 1.0 mm (SD, ±2.4 mm; range, -3 to 6 mm), and volar tilt was 1.4° (SD, ±5.2°; range, -10° to 14°). Mean articular displacement was 1.7 mm (SD, ±1.7 mm; range, 0-6 mm). Malalignment of at least one of these radiographic parameters was identified in 16 of 24 patients at the time of union. Conclusions: Dorsal spanning plate fixation offers an alternative treatment option for comminuted intra-articular distal radius fractures (AO 23-C3). Although this technique presents a straightforward means for fixation of complex distal radius fractures, radiographic outcomes may be inferior relative to less complex fractures treated with standard volar plating techniques. Type of study/level of evidence: Therapeutic IV.

Effect of initial emergency room imaging choice on time to hip reduction and repeat imaging.

OBJECTIVES: Hip dislocations are highly morbid injuries necessitating prompt reduction and post-reduction assessment for fracture and incarcerated fragments. Recent literature has questioned the need for initial pelvic radiographs for acute trauma patients, resulting in computed tomography (CT) scans as the initial evaluation. This study investigates the relationship between choice of pre-reduction imaging and treatment of acute hip dislocations. DESIGN: Retrospective Case-Control. SETTING: Single Academic Level I Trauma Center. METHODS: All acute hip dislocations from 2011 to 2016 were reviewed. Exclusion criteria were diagnosis of dislocation at another facility, death prior to reduction, emergent surgical or ICU intervention, and periprosthetic dislocation. Patients were grouped by those with only a radiograph prior to reduction, Group I, versus those with a pre-reduction CT scan, Group II. The primary outcomes were time to reduction and the acquisition of a second CT scan. RESULTS: Of the 123 hip dislocations identified, 35 patients were excluded, mostly for transfer with a known dislocation. Group I included 29 patients and Group II included 59 patients. The mean time to reduction was 74 min in Group I and 129 min in Group II for a difference of 55 min (p < 0.001). The rate of repeat CT scan was 0 in Group I versus 48 (81%) in Group II (p < 0.001). CONCLUSION: Initial trauma pelvic radiography prior to CT is still important in the setting of suspected hip pathology to decrease time to hip reduction and unnecessary radiation exposure. LEVEL OF EVIDENCE: Prognostic Level III.

Masquelet Reconstruction for Posttraumatic Segmental Bone Defects in the Forearm.

PURPOSE: The Masquelet technique is a procedure increasingly utilized for addressing segmental bone defects. The technique involves staged procedures consisting of bone debridement and temporary spacer placement to induce membrane formation, followed by delayed bone grafting. This report summarizes our center's experience with the Masquelet technique to reconstruct bone loss exclusively in the forearm. METHODS: We reviewed all cases in which the Masquelet technique was used to reconstruct segmental bone defects in the forearm resulting from acute trauma or nonunion, with or without infection, between 2014 and 2017 at a level-1 trauma center. Injury mechanism, prior surgeries, extent of bone defect, and demographic data were collected. Union was assessed along with treatment-related complications or reoperations. RESULTS: We identified 9 patients with segmental bony defects in the forearm treated with the Masquelet technique. Among this cohort, 5 patients had bone defects associated with acute open fractures and 4 patients presented with nonunion (1 atrophic and 3 infected nonunions). The median bony defect was 4.7 cm (range, 1.7-5.4 cm) at the time of grafting. Second stage grafting was performed with Reamer Irrigator Aspirator autograft from the femur in 8 patients and iliac crest bone cancellous graft in 1 patient. Union was achieved in all 9 patients. Six patients achieved union by 3-month follow-up, 2 patients by 6 months, and 1 patient by 12 months. One patient required a reoperation for plate fracture prior to union treated with revision internal fixation and grafting. CONCLUSIONS: The Masquelet technique effectively reconstructed traumatic and posttraumatic segmental defects in the forearm with a low incidence of complication. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Current status and future perspectives of gold nanoparticle vectors for siRNA delivery.

Discovering the vast therapeutic potential of siRNA opened up new clinical research areas focussing on a number of diseases and applications; however significant problems with siRNA stability and delivery have hindered its clinical applicability. As a result, interest in the development of practical siRNA delivery systems has grown in recent years. Of the numerous siRNA delivery strategies currently on offer, gold nanoparticles (AuNPs) stand out thanks to their biocompatibility and capacity to protect siRNA against degradation; not to mention the versatility offered by their tuneable shape, size and optical properties. Herein this review provides a complete summary of the methodologies for functionalizing AuNPs with siRNA, paying singular attention to the AuNP shape, size and surface coating, since these key factors heavily influence cellular interaction, internalization and, ultimately, the efficacy of the hybrid particle. The most noteworthy hybridization strategies have been highlighted along with the most innovative and outstanding in vivo studies with a view to increasing clinical interest in the use of AuNPs as siRNA nanocarriers.

Homogeneous BTK Occupancy Assay for Pharmacodynamic Assessment of Tirabrutinib (GS-4059/ONO-4059) Target Engagement.

Bruton's tyrosine kinase (BTK) is a clinically validated target for B-cell leukemias and lymphomas with FDA-approved small-molecule inhibitors ibrutinib and acalabrutinib. Tirabrutinib (GS-4059/ONO-4059, Gilead Sciences, Inc., Foster City, CA) is a second-generation, potent, selective, irreversible BTK inhibitor in clinical development for lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL). An accurate pharmacodynamic assay to assess tirabrutinib target coverage in phase 1/2 clinical studies will inform dose and schedule selection for advanced clinical evaluation. We developed a novel duplex homogeneous BTK occupancy assay based on time-resolved fluorescence resonance energy transfer (TR-FRET) to measure free and total BTK levels in a multiplexed format. The dual-wavelength emission property of terbium-conjugated anti-BTK antibody served as the energy donor for two fluorescent energy acceptors with distinct excitation and emission spectra. The assay was characterized and qualified using full-length purified recombinant human BTK protein and peripheral blood mononuclear cells derived from healthy volunteers and patients with CLL. We demonstrated assay utility using cells derived from lymph node and bone marrow samples from patients with CLL and DLBCL. Our TR-FRET-based BTK occupancy assay provides accurate, quantitative assessment of BTK occupancy in the clinical trial program for tirabrutinib and is in use in ongoing clinical studies.