Anterior internal versus external fixation of unstable pelvis fractures was not associated with discharge destination, critical care, length of stay, or hospital charges.

PURPOSE: Determine if anterior internal versus supra-acetabular external fixation of unstable pelvic fractures is associated with care needs or discharge. METHODS: A retrospective cohort study was performed at two tertiary trauma referral centers. Adults with unstable pelvis fractures (AO/OTA 61B/61C) who received operative fixation of the anterior and posterior pelvic ring by two orthopedic trauma surgeons from October 2020 to November 2022 were included. The primary outcome was discharge destination. Secondary outcomes included intensive care unit (ICU) or ventilator days, length of stay, and hospital charges. RESULTS: Eighty-three eligible patients were 38.6% female, with a mean age of 47.2 ± 20.3 years and BMI 28.1 ± 6.4 kg/m2. Fifty-nine patients (71.1%) received anterior pelvis internal fixation and 24 (28.9%) received external fixation. External fixation was associated with weight-bearing restrictions (91.7% versus 49.2%, p = 0.01). No differences in demographic, functional status, insurance type, fracture classification, or injury severity measures were observed by treatment. Internal versus external anterior pelvic fixation was not associated with discharge to home (49.2% versus 29.2%, p = 0.10), median ICU days (3.0 [interquartile range (IQR) 7.8 versus 5.5 [IQR 4.3], p = 0.14, ventilator days (0 [IQR 6.0] versus 0 [IQR 2.8], p = 0.51), length of stay (13.0 [IQR 13.0] versus 17.5 (IQR 20.5), p = 0.38), or total hospital charges (US dollars 180,311 [IQR 219,061.75] versus 243,622 [IQR 187,111], p = 0.14). CONCLUSIONS: Anterior internal versus supra-acetabular external fixation of unstable pelvis fractures was not significantly associated with discharge destination, critical care, hospital length of stay, or hospital charges. This sample may be underpowered to detect differences between groups. LEVEL OF EVIDENCE: Therapeutic Level IV.

Subchondral rafting wires reduce tibial plateau fracture subsidence.

PURPOSE: To determine if subchondral rafting wires retained as adjunctive tibial plateau fracture fixation affect postoperative articular subsidence. METHODS: A retrospective cohort study was conducted at one Level 1 trauma center and one academic university hospital. Consecutive adults with closed, displaced OTA/AO 41B/C tibial plateau fractures treated between 2018 and 2023 with open reduction internal fixation were included. Patients who were not ambulatory, with contralateral injuries limiting weight bearing, and without follow-up radiographs of the injured extremity were excluded. The intervention was retention of subchondral rafting wires as definitive fixation. The primary outcome was linear articular surface subsidence between postoperative and follow-up AP knee radiographs. Linear subsidence was compared between groups using Welch's two sample t test. Associations of linear subsidence with patient, injury, and treatment characteristics were assessed by multivariable linear regression. RESULTS: We identified 179 patients of a mean age of 44 ± 14 years, of whom 15 (8.4%) received subchondral rafting wires. Median follow-up was 121 days. No patients who received rafting wires as definitive implants experienced linear subsidence ≥ 2 mm, while 22 patients (13.4%) who did not receive rafting wires experienced linear subsidence ≥ 2 mm (p = 0.130). Subchondral rafting wires were associated with less linear subsidence (0.3 mm [95% confidence interval - 0.3-0.9 mm] vsersus 1.0 mm [- 0.9-2.9 mm], p < 0.001). The depth of linear subsidence was significantly associated on multivariable regression with male sex, depressed plateau area, active smoking, and retained rafting wires. CONCLUSION: Subchondral rafting wires were associated with a small reduction in articular subsidence after internal fixation of tibial plateau fractures. Routine rafting wires may be useful for patients and fractures at high risk of articular subsidence.

Alpha-synuclein inclusion responsive microglia are resistant to CSF1R inhibition.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by the presence of proteinaceous alpha-synuclein (α-syn) inclusions (Lewy bodies), markers of neuroinflammation and the progressive loss of nigrostriatal dopamine (DA) neurons. These pathological features can be recapitulated in vivo using the α-syn preformed fibril (PFF) model of synucleinopathy. We have previously determined that microglia proximal to PFF-induced nigral α-syn inclusions increase in soma size, upregulate major-histocompatibility complex-II (MHC-II) expression, and increase expression of a suite of inflammation-associated transcripts. This microglial response is observed months prior to degeneration, suggesting that microglia reacting to α-syn inclusion may contribute to neurodegeneration and could represent a potential target for novel therapeutics. The goal of this study was to determine whether colony stimulating factor-1 receptor (CSF1R)-mediated microglial depletion impacts the magnitude of α-syn aggregation, nigrostriatal degeneration, or the response of microglial in the context of the α-syn PFF model. METHODS: Male Fischer 344 rats were injected intrastriatally with either α-syn PFFs or saline. Rats were continuously administered Pexidartinib (PLX3397B, 600 mg/kg), a CSF1R inhibitor, to deplete microglia for a period of either 2 or 6 months. RESULTS: CSF1R inhibition resulted in significant depletion (~ 43%) of ionized calcium-binding adapter molecule 1 immunoreactive (Iba-1ir) microglia within the SNpc. However, CSF1R inhibition did not impact the increase in microglial number, soma size, number of MHC-II immunoreactive microglia or microglial expression of Cd74, Cxcl10, Rt-1a2, Grn, Csf1r, Tyrobp, and Fcer1g associated with phosphorylated α-syn (pSyn) nigral inclusions. Further, accumulation of pSyn and degeneration of nigral neurons was not impacted by CSF1R inhibition. Paradoxically, long term CSF1R inhibition resulted in increased soma size of remaining Iba-1ir microglia in both control and PFF rats, as well as expression of MHC-II in extranigral regions. CONCLUSIONS: Collectively, our results suggest that CSF1R inhibition does not impact the microglial response to nigral pSyn inclusions and that CSF1R inhibition is not a viable disease-modifying strategy for PD.

Observing the Dynamics of an Electrochemically Driven Active Material with Liquid Electron Microscopy.

Electrochemical liquid electron microscopy has revolutionized our understanding of nanomaterial dynamics by allowing for direct observation of their electrochemical production. This technique, primarily applied to inorganic materials, is now being used to explore the self-assembly dynamics of active molecular materials. Our study examines these dynamics across various scales, from the nanoscale behavior of individual fibers to the micrometer-scale hierarchical evolution of fiber clusters. To isolate the influences of the electron beam and electrical potential on material behavior, we conducted thorough beam-sample interaction analyses. Our findings reveal that the dynamics of these active materials at the nanoscale are shaped by their proximity to the electrode and the applied electrical current. By integrating electron microscopy observations with reaction-diffusion simulations, we uncover that local structures and their formation history play a crucial role in determining assembly rates. This suggests that the emergence of nonequilibrium structures can locally accelerate further structural development, offering insights into the behavior of active materials under electrochemical conditions.

Titanium versus stainless steel alloy bridge plates for distal femur fractures: Does callus form earlier with titanium?

INTRODUCTION: Distal femur fractures account for 3-6% of all femur fractures. Internal fixation of most distal femur fractures with an anatomic lateral locking plate should permit some motion at the metaphyseal portion of the fracture when secondary bone healing is planned by the operating surgeon. While several studies have been performed evaluating union rates for distal femur fractures with stainless steel and titanium plates, the timing of callus formation between stainless steel and titanium implants used as bridge plates for distal femur fractures (AO/OTA 33-A and -C) has been investigated to a lesser extent. We hypothesize that callus will be visualized earlier with post-operative radiographs with titanium versus stainless steel bridge plates. METHODS: We retrospectively reviewed a consecutive cohort of patients over 18 years of age with acute AO/OTA 33-A and 33-C fracture patterns treated with an isolated stainless steel or titanium lateral bridge plate within 4 weeks of injury by a single fellowship-trained orthopedic trauma surgeon from 2011 to 2020 at one academic Level 1 trauma center. An independent, fellowship-trained orthopedic trauma attending surgeon reviewed anterior-posterior (AP) and lateral radiographs from every available post-operative clinic visit and graded them using the Modified Radiographic Score for Tibia (mRUST). RESULTS: Twenty-five subjects were included in the study with 10 with stainless steel and 15 with titanium plates. There were no significant differences in demographics between both groups, including age, sex, BMI, injury classification, open versus closed, mechanism, and laterality. Statistically significant increased mRUST scores, indicating increased callus formation, were seen on 12-week radiographs (8.4 vs. 11.9, p = 0.02) when titanium bridge plates were used. There were no statistically significant differences in mRUST scores at 6 or 24-weeks, but scores in the titanium group were higher in at every timepoint. DISCUSSION: In conclusion, we observed greater callus formation at 12 weeks after internal fixation of 33-A and 33-C distal femur fractures treated with titanium locked lateral distal femoral bridge plates compared to stainless steel plates. Our data suggest that titanium metallurgy may have quicker callus formation compared to stainless steel if an isolated, lateral locked bridge plate is chosen for distal femur fracture fixation.

Patient Preferences for Operative Versus Nonoperative Treatment of LC1 Pelvis Fracture: A Discrete Choice Experiment.

OBJECTIVES: To quantify how patients with lateral compression type 1 (LC1) pelvis fracture value attributes of operative versus nonoperative treatment. DESIGN: Discrete choice experiment. SETTING: Three US Level 1 trauma centers. PATIENT SELECTION CRITERIA: Adult survivors of an LC1 pelvis treated between June 2016 and March 2023 were identified from institutional registries. The choice experiment was administered as a survey from March through August 2023. OUTCOME MEASURES AND COMPARISONS: Participants chose between 12 hypothetical comparisons of treatment attributes including operative or nonoperative care, risk of death, severity of pain, risk of secondary surgery, shorter hospital stay, discharge destination, and independence in ambulation within 1 month of injury. The marginal utility of each treatment attribute, for example, the strength of participants' aggregate preference for an attribute as indicated by their survey choices, was estimated by multinomial logit modeling with and without stratification by treatment received. RESULTS: Four hundred forty-nine eligible patients were identified. The survey was distributed to 182 patients and collected from 72 patients (39%) at a median 2.3 years after injury. Respondents were 66% female with a median age of 59 years (IQR, 34-69 years). Before injury, 94% ambulated independently and 75% were working; 41% received operative treatment. Independence with ambulation provided the highest relative marginal utility (21%, P < 0.001), followed by discharge to home versus skilled nursing (20%, P < 0.001), moderate versus severe postdischarge pain (17%, P < 0.001), shorter hospital stay (16%, P < 0.001), secondary surgery (15%, P < 0.001), and mortality (10%, P = 0.02). Overall, no relative utility for operative versus nonoperative treatment was observed (2%, P = 0.54). However, respondents strongly preferred the treatment they received: operative patients valued operative treatment (utility, 0.37 vs. -0.37, P < 0.001); nonoperative patients valued nonoperative treatment (utility, 0.19 vs. -0.19, P < 0.001). CONCLUSIONS: LC1 pelvis fracture patients valued independence with ambulation, shorter hospital stay, and avoiding secondary surgery and mortality in the month after their injury. Patients preferred the treatment they received rather than operative versus nonoperative care.

Incidence of Suboptimal Fluoroscopic Outlet Imaging of the Sacrum and Pelvic Retroversion Necessary for Optimal Views.

OBJECTIVES: To estimate the prevalence of suboptimal fluoroscopy of sacral outlet images due to anatomic and equipment dimensions. Pelvic retroversion is hypothesized to mitigate this issue. DESIGN: In silico simulations using retrospectively collected computed tomography (CT) data from human patients. SETTING: Level I trauma center. PATIENT SELECTION CRITERIA: Adults with OTA/AO 61 pelvic ring disruptions treated with posterior pelvic fixation between July and December 2021. OUTCOME MEASURES AND COMPARISONS: C-arm tilt angles required to obtain 3 optimal fluoroscopic sacral outlet images, defined as vectors from pubic symphysis to S2 and parallel to the first and second sacral neural foramina, were calculated from sagittal CT images. A suboptimal view was defined as collision of the C-arm radiation source or image intensifier with the patient/operating table at the required tilt angle simulated using the dimensions of 5 commercial C-arm models and trigonometric calculations. Incidence of suboptimal outlet views and pelvic retroversion necessary to obtain optimal views without collision, which may be obtained by placement of a sacral bump, was determined for each view for all patients and C-arm models. RESULTS: CT data from 72 adults were used. Collision between patient and C-arm would occur at the optimal tilt angle for 17% of simulations and at least 1 view in 68% of patients. Greater body mass index was associated with greater odds of suboptimal imaging (standard outlet: odds ratio [OR] 0.84, confidence interval [CI] 0.79-0.89, P < 0.001; S1: OR 0.91, CI 0.87-0.97, P = 0.002; S2: OR 0.85, CI 0.80-0.91, P < 0.001). S1 anterior sacral slope was associated with suboptimal S1 outlet views (OR 1.12, Cl 1.07-1.17, P < 0.001). S2 anterior sacral slope was associated with suboptimal standard outlet (OR 1.07, Cl 1.02-1.13, P = 0.004) and S2 outlet (OR 1.16, Cl 1.09-1.23, P < 0.001) views. Retroversion of the pelvis 15-20 degrees made optimal outlet views possible without collision in 95%-99% of all simulations, respectively. CONCLUSIONS: Suboptimal outlet imaging of the sacrum is associated with greater body mass index and sacral slope at S1 and S2. Retroversion of the pelvis by 15-20 degrees with a bump under the distal sacrum may offer a low-tech solution to ensure optimal fluoroscopic imaging for percutaneous fixation of the posterior pelvic ring. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Hybrid Photoiniferter and Ring-Opening Polymerization Yields One-Pot Anisotropic Nanorods.

Polymerization-induced self-assembly (PISA) has emerged as a scalable one-pot technique to prepare block copolymer (BCP) nanoparticles. Recently, a PISA process, that results in poly(l-lactide)-b-poly(ethylene glycol) BCP nanoparticles coined ring-opening polymerization (ROP)-induced crystallization-driven self-assembly (ROPI-CDSA), was developed. The resulting nanorods demonstrate a strong propensity for aggregation, resulting in the formation of 2D sheets and 3D networks. This article reports the synthesis of poly(N,N-dimethyl acrylamide)-b-poly(l)-lactide BCP nanoparticles by ROPI-CDSA, utilizing a two-step, one-pot approach. A dual-functionalized photoiniferter is first used for controlled radical polymerization of the acrylamido-based monomer, and the resulting polymer serves as a macroinitiator for organocatalyzed ROP to form the solvophobic polyester block. The resulting nanorods are highly stable and display anisotropy at higher molecular weights (>12k Da) and concentrations (>20% solids) than the previous report. This development expands the chemical scope of ROPI-CDSA BCPs and provides readily accessible nanorods made with biocompatible materials.

Deficits in basal and evoked striatal dopamine release following alpha-synuclein preformed fibril injection: An in vivo microdialysis study.

Parkinson's disease (PD) is characterized by the accumulation of misfolded alpha-synuclein (α-syn) protein, forming intraneuronal Lewy body (LB) inclusions. The α-syn preformed fibril (PFF) model of PD recapitulates α-syn aggregation, progressive nigrostriatal degeneration and motor dysfunction; however, little is known about the time course of PFF-induced alterations in basal and evoked dopamine (DA). In vivo microdialysis is well suited for identifying small changes in neurotransmitter levels over extended periods. In the present study, adult male Fischer 344 rats received unilateral, intrastriatal injections of either α-syn PFFs or phosphate-buffered saline (PBS). At 4 or 8 months post-injection (p.i.), animals underwent in vivo microdialysis to evaluate basal extracellular striatal DA and metabolite levels, local KCl-evoked striatal DA release and the effects of systemic levodopa (l-DOPA). Post-mortem analysis demonstrated equivalent PFF-induced reductions in tyrosine hydroxylase (TH) immunoreactive nigral neurons (~50%) and striatal TH (~20%) at both time points. Compared with reduction in striatal TH, reduction in striatal dopamine transporter (DAT) was more pronounced and progressed between the 4- and 8-month p.i. intervals (36% âž” 46%). Significant PFF-induced deficits in basal and evoked striatal DA, as well as deficits in motor performance, were not observed until 8 months p.i. Responses to l-DOPA did not differ regardless of PBS or PFF treatment. These results suggest that basal and evoked striatal DA are maintained for several months following PFF injection, with loss of both associated with motor dysfunction. Our studies provide insight into the time course and magnitude of PFF-induced extracellular dopaminergic deficits in the striatum.

Liquid-liquid phase separation induced auto-confinement.

Confinement allows macromolecules and biomacromolecules to attain arrangements typically unachievable through conventional self-assembly processes. In the field of block copolymers, confinement has been achieved by preparing thin films and controlled solvent evaporation through the use of emulsions. A significant advantage of the confinement-driven self-assembly process is its ability to enable block copolymers to form particles with complex internal morphologies, which would otherwise be inaccessible. Here, we show that liquid-liquid phase separation (LLPS) can induce confinement during the self-assembly of a model block copolymer system. Since this confinement is driven by the block copolymers' tendency to undergo LLPS, we define this confinement type as auto-confinement. This study adds to the growing understanding of how LLPS influences block copolymer self-assembly and provides a new method to achieve confinement driven self-assembly.

Neuroinflammatory gene expression profiles of reactive glia in the substantia nigra suggest a multidimensional immune response to alpha synuclein inclusions.

Parkinson's disease (PD) pathology is characterized by alpha-synuclein (α-syn) aggregates, degeneration of dopamine neurons in the substantia nigra pars compacta (SNpc), and neuroinflammation. The presence of reactive glia correlates with deposition of pathological α-syn in early-stage PD. Thus, understanding the neuroinflammatory response of microglia and astrocytes to synucleinopathy may identify therapeutic targets. Here we characterized the neuroinflammatory gene expression profile of reactive microglia and astrocytes in the SNpc during early synucleinopathy in the rat α-syn pre-formed fibril (PFF) model. Rats received intrastriatal injection of α-syn PFFs and expression of immune genes was quantified with droplet digital PCR (ddPCR), after which fluorescent in situ hybridization (FISH) was used to localize gene expression to microglia or astrocytes in the SNpc. Genes previously associated with reactive microglia (Cd74, C1qa, Stat1, Axl, Casp1, Il18, Lyz2) and reactive astrocytes (C3, Gbp2, Serping1) were significantly upregulated in the SN of PFF injected rats. Localization of gene expression to SNpc microglia near α-syn aggregates identified a unique α-syn aggregate microglial gene expression profile characterized by upregulation of Cd74, Cxcl10, Rt-1a2, Grn, Csf1r, Tyrobp, C3, C1qa, Serping1 and Fcer1g. Importantly, significant microglial upregulation of Cd74 and C3 were only observed following injection of α-syn PFFs, not α-syn monomer, confirming specificity to α-syn aggregation. Serping1 expression also localized to astrocytes in the SNpc. Interestingly, C3 expression in the SNpc localized to microglia at 2- and 4-months post-PFF, but to astrocytes at 6-months post-PFF. We also observed expression of Rt1-a2 and Cxcl10 in SNpc dopamine neurons. Cumulatively our results identify a dynamic, yet reproducible gene expression profile of reactive microglia and astrocytes associated with early synucleinopathy in the rat SNpc.

CryoEM reveals the complex self-assembly of a chemically driven disulfide hydrogel.

Inspired by the adaptability of biological materials, a variety of synthetic, chemically driven self-assembly processes have been developed that result in the transient formation of supramolecular structures. These structures form through two simultaneous reactions, forward and backward, which generate and consume a molecule that undergoes self-assembly. The dynamics of these assembly processes have been shown to differ from conventional thermodynamically stable molecular assemblies. However, the evolution of nanoscale morphologies in chemically driven self-assembly and how they compare to conventional assemblies has not been resolved. Here, we use a chemically driven redox system to separately carry out the forward and backward reactions. We analyze the forward and backward reactions both sequentially and synchronously with time-resolved cryogenic transmission electron microscopy (cryoEM). Quantitative image analysis shows that the synchronous process is more complex and heterogeneous than the sequential process. Our key finding is that a thermodynamically unstable stacked nanorod phase, briefly observed in the backward reaction, is sustained for ∼6 hours in the synchronous process. Kinetic Monte Carlo modeling show that the synchronous process is driven by multiple cycles of assembly and disassembly. The collective data suggest that chemically driven self-assembly can create sustained morphologies not seen in thermodynamically stable assemblies by kinetically stabilizing transient intermediates. This finding provides plausible design principles to develop and optimize supramolecular materials with novel properties.

Does Topical Vancomycin Powder Use in Fracture Surgery Change Bacteriology and Antibiotic Susceptibilities? An Analysis of the VANCO Trial.

OBJECTIVE: To determine whether intrawound vancomycin changes the bacteriology of surgical site infection pathogens and investigate the emergence of antibiotic-resistant pathogens. DESIGN: Secondary analysis of phase III, prospective, randomized clinical trial. SETTING: Thirty-six US trauma centers. PATIENT SELECTION CRITERIA: Patients who became infected after fixation of tibial plateau or pilon fracture. OUTCOME MEASURES AND COMPARISONS: Pathogen types and bacterial susceptibilities as determined from routine clinical culture in the operating room. RESULTS: Seventy-four patients were studied who were 67.5% male with a mean age of 48.6 years. A lower proportion of gram-positive cocci was observed in the vancomycin powder compared with the standard-of-care group (3.7% vs. 8.0%, P = 0.01). Methicillin-resistant Staphylococcus aureus infection incidence was comparable in both the vancomycin powder and the standard-of-care groups, but rates of methicillin-susceptible S. aureus infections were lower in the treatment group (1.4% vs. 4.8%, P = 0.01). The incidence of coagulase-negative Staphylococci and gram-negative rod infections were similar in both groups. There was no significant difference in susceptibilities between groups in rates of vancomycin-resistant enterococcus. CONCLUSIONS: Topical vancomycin powder decreases the likelihood of gram-positive infections consistent with the biologic activity of vancomycin. Fewer methicillin-susceptible S. aureus and coagulase-negative Staphylococci infections were observed in the group treated with vancomycin powder. An effect of vancomycin powder on methicillin-resistant S. aureus infection risk was not detected given the low incidence in both the intrawound vancomycin and the standard-of-care groups. There was no emergence of gram-negative rod infections or increased resistance patterns observed. Use of topical vancomycin powder does not seem to produce infections in these patients with greater antibiotic resistance than would have occurred without its use. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Transcriptomic profiling of early synucleinopathy in rats induced with preformed fibrils.

Examination of early phases of synucleinopathy when inclusions are present, but long before neurodegeneration occurs, is critical to both understanding disease progression and the development of disease modifying therapies. The rat alpha-synuclein (α-syn) preformed fibril (PFF) model induces synchronized synucleinopathy that recapitulates the pathological features of Parkinson's disease (PD) and can be used to study synucleinopathy progression. In this model, phosphorylated α-syn (pSyn) inclusion-containing neurons and reactive microglia (major histocompatibility complex-II immunoreactive) peak in the substantia nigra pars compacta (SNpc) months before appreciable neurodegeneration. However, it remains unclear which specific genes are driving these phenotypic changes. To identify transcriptional changes associated with early synucleinopathy, we used laser capture microdissection of the SNpc paired with RNA sequencing (RNASeq). Precision collection of the SNpc allowed for the assessment of differential transcript expression in the nigral dopamine neurons and proximal glia. Transcripts upregulated in early synucleinopathy were mainly associated with an immune response, whereas transcripts downregulated were associated with neurotransmission and the dopamine pathway. A subset of 29 transcripts associated with neurotransmission/vesicular release and the dopamine pathway were verified in a separate cohort of males and females to confirm reproducibility. Within this subset, fluorescent in situ hybridization (FISH) was used to localize decreases in the Syt1 and Slc6a3 transcripts to pSyn inclusion-containing neurons. Identification of transcriptional changes in early synucleinopathy provides insight into the molecular mechanisms driving neurodegeneration.

Correlating electrochemical stimulus to structural change in liquid electron microscopy videos using the structural dissimilarity metric.

In-situ liquid cell transmission electron microscopy (LCTEM) with electrical biasing capabilities has emerged as an invaluable tool for directly imaging electrode processes with high temporal and spatial resolution. However, accurately quantifying structural changes that occur on the electrode and subsequently correlating them to the applied stimulus remains challenging. Here, we present structural dissimilarity (DSSIM) analysis as segmentation-free video processing algorithm for locally detecting and quantifying structural change occurring in LCTEM videos. In this study, DSSIM analysis is applied to two in-situ LCTEM videos to demonstrate how to implement this algorithm and interpret the results. We show DSSIM analysis can be used as a visualization tool for qualitative data analysis by highlighting structural changes which are easily missed when viewing the raw data. Furthermore, we demonstrate how DSSIM analysis can serve as a quantitative metric and efficiently convert 3-dimensional microscopy videos to 1-dimenional plots which makes it easy to interpret and compare events occurring at different timepoints in a video. In the analyses presented here, DSSIM is used to directly correlate the magnitude and temporal scale of structural change to the features of the applied electrical bias. ImageJ, Python, and MATLAB programs, including a user-friendly interface and accompanying documentation, are published alongside this manuscript to make DSSIM analysis easily accessible to the scientific community.

The VANCO Trial Findings Are Generalizable to a North American Trauma Registry.

OBJECTIVES: To estimate the generalizability of treatment effects observed in the VANCO trial to a broader population of patients with tibial plateau or pilon fractures. METHODS: Design and Setting: Clinical trial data from 36 United States trauma centers and Trauma Quality Programs registry data from more than 875 Level I-III trauma centers in the United States and Canada.Patient Selection Criteria: Patients enrolled in the VANCO trial treated with intrawound vancomycin powder from January 2015 to June 2017 and 31,924 VANCO-eligible TQP patients admitted in 2019 with tibial plateau and pilon fractures.Outcome Measure and Comparisons: Deep surgical site infection and gram-positive deep surgical site infection estimated in the TQP sample weighed by the inverse probability of trial participation. RESULTS: The 980 patients in the VANCO trial were highly representative of 31,924 TQP VANCO-eligible patients (Tipton generalizability index 0.96). It was estimated that intrawound vancomycin powder reduced the odds of deep surgical infection by odds ratio (OR) = 0.46 (95% confidence interval [CI] 0.25-0.86) and gram-positive deep surgical infection by OR = 0.39 (95% CI, 0.18-0.84) within the TQP sample of VANCO-eligible patients. For reference, the trial average treatment effects for deep surgical infection and gram-positive deep surgical infection were OR = 0.60 (95% CI, 0.37-0.98) and OR = 0.44 (95% CI, 0.23-0.80), respectively. CONCLUSIONS: This generalizability analysis found that the inferences of the VANCO trial generalize and might even underestimate the effects of intrawound vancomycin powder when observed in a wider population of patients with tibial plateau and pilon fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Management of Femoral Neck Fractures in Patients Age ≥50 Years by American Board of Orthopaedic Surgery Part II Examination Candidates.

OBJECTIVE: Assess associations between fellowship training, procedure, and performance in femoral neck fracture (FNF) surgery on adults by American Board of Orthopaedic Surgery (ABOS) Part II Examination candidates. SETTING: ABOS SCRIBE database exam years 2007-2020. PARTICIPANTS: 6,777 candidates performing 39,283 FNF surgeries on adults age ≥ 50 years. INTERVENTION: Fellowship training. MAIN OUTCOME MEASUREMENTS: Case volume; procedure performed: internal fixation (IF), hemiarthroplasty (HA), or total hip arthroplasty (THA); complications; readmission; reoperation. RESULTS: Over the observation period, fewer candidates reported FNF surgery (68% overall, -0.6%/year, R2=0.80) while more candidates reported fellowship training (87% overall, +1.4%/year, R2=0.81). The rate of any complication was significantly associated with fellowship training (32% overall, p<0.001). Readmission (12%, p=0.080) and reoperation (5%, p=0.531) were not significantly associated with fellowship training. The odds of any complication (odds ratio [OR]=-0.03 [95% CI -0.07 to -0.001] per 10 cases) and surgical complication (OR=-0.12 [95% CI -0.17 to -0.07] per 10 cases) were negatively associated with candidate FNF case volume. 3,396 THA for FNF were performed (8% of cases). THA use increased 25 cases/year (R2=0.83) and was associated with adult reconstruction (p<0.001) and oncology (p<0.001) fellowship training. Any complication of THA for FNF (32%, p=0.261), readmission (9% overall, p=0.321), and reoperation (5%, p=0.200) were not significantly associated with fellowship training. CONCLUSIONS: Between 2007-2020, femoral neck fracture surgery was performed by fewer ABOS Part II Examination candidates and there was greater use of THA. Over this time period there was a greater prevalence of fellowship training but complications were not associated with fellowship training. Complications were associated with FNF case volume. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Understanding and controlling the nucleation and growth of metal-organic frameworks.

Metal-organic frameworks offer a diverse landscape of building blocks to design high performance materials for implications in almost every major industry. With this diversity stems complex crystallization mechanisms with various pathways and intermediates. Crystallization studies have been key to the advancement of countless biological and synthetic systems, with MOFs being no exception. This review provides an overview of the current theories and fundamental chemistry used to decipher MOF crystallization. We then discuss how intrinsic and extrinsic synthetic parameters can be used as tools to modulate the crystallization pathway to produce MOF crystals with finely tuned physical and chemical properties. Experimental and computational methods are provided to guide the probing of MOF crystal formation on the molecular and bulk scale. Lastly, we summarize the recent major advances in the field and our outlook on the exciting future of MOF crystallization.

Characterizing the Ligand Shell Morphology of PEG-Coated ZnO Nanocrystals Using FRET Spectroscopy.

Poly(ethylene glycol) (PEG) ligands can inhibit proteins and other biomolecules from adhering to underlying surfaces, making them excellent surface ligands for nanocrystal (NC)-based drug carriers. Quantifying the PEG ligand shell morphology is important because its structure determines the permeability of biomolecules through the shell to the NC surface. However, few in situ analytical tools can reveal whether the PEG ligands form either an impenetrable barrier or a porous coating surrounding the NC. Here, we present a Förster resonance energy transfer (FRET) spectroscopy-based approach that can assess the permeability of molecules through PEG-coated ZnO NCs. In this approach, ZnO NCs serve as FRET donors, and freely diffusing molecules in the bulk solution are FRET acceptors. We synthesized a series of variable chain length PEG-silane-coated ZnO NCs such that the longest chain length ligands far exceed the Förster radius (R0), where the energy transfer (EnT) efficiency is 50%. We quantified the EnT efficiency as a function of the ligand chain length using time-resolved photoluminescence lifetime (TRPL) spectroscopy within the framework of FRET theory. Unexpectedly, the longest PEG-silane ligand showed equivalent EnT efficiency as that of bare, hydroxyl-passivated ZnO NCs. These results indicate that the "rigid shell" model fails and the PEG ligand shell morphology is more likely porous or in a patchy "mushroom state", consistent with transmission electron microscopy data. While the spectroscopic measurements and data analysis procedures discussed herein cannot directly visualize the ligand shell morphology in real space, the in situ spectroscopy approach can provide researchers with valuable information regarding the permeability of species through the ligand shell under practical biological conditions.

Underweight patients experience higher inpatient complication and mortality rates following acetabular fracture.

PURPOSE: Underweight patients experience poor outcomes after elective orthopaedic procedures. The effect of underweight body mass index (BMI) on complications after acetabular fracture is not well-described. We evaluate if underweight status is associated with inpatient complications after acetabular fractures. METHODS: Adult patients (≥ 18 years) presenting with acetabular fracture between 2015 and 2019 were identified from Trauma Quality Program data. Adjusted odds (aOR) of any inpatient complication or mortality were compared between patients with underweight BMI (< 18.5 kg/m2) and normal BMI (18.5-25 kg/m2) using multivariable logistic regression and stratifying by age ≥ 65 years. RESULTS: The 1299 underweight patients aged ≥ 65 years compared to 11,629 normal weight patients experienced a 1.2-times and 2.7-times greater aOR of any complication (38.6% vs. 36.6%, p = 0.010) and inpatient mortality (7.9% vs. 4.2%, p < 0.001), respectively. The 1688 underweight patients aged 18-64 years compared to 24,762 normal weight patients experienced a 1.2-times and 1.5-times greater aOR of any inpatient complication (38.9% vs. 34.8%, aOR p = 0.006) and inpatient mortality (4.1% vs. 2.5%, p < 0.001), respectively. CONCLUSION: Underweight adult patients with acetabular fracture are at increased risk for inpatient complications and mortality, particularly those ≥ 65 years old. LEVEL OF EVIDENCE: Prognostic Level III.