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The remarkable ability of a single genome sequence to encode a diverse collection of distinct cell types, including the thousands of cell types found in the mammalian brain, is a key characteristic of multicellular life. While it has been observed that some cell types are far more evolutionarily conserved than others, the factors driving these differences in evolutionary rate remain unknown. Here, we hypothesized that highly abundant neuronal cell types may be under greater selective constraint than rarer neuronal types, leading to variation in their rates of evolution. To test this, we leveraged recently published cross-species single-nucleus RNA-sequencing datasets from three distinct regions of the mammalian neocortex. We found a strikingly consistent relationship where more abundant neuronal subtypes show greater gene expression conservation between species, which replicated across three independent datasets covering >106 neurons from six species. Based on this principle, we discovered that the most abundant type of neocortical neurons-layer 2/3 intratelencephalic excitatory neurons-has evolved exceptionally quickly in the human lineage compared to other apes. Surprisingly, this accelerated evolution was accompanied by the dramatic down-regulation of autism-associated genes, which was likely driven by polygenic positive selection specific to the human lineage. In sum, we introduce a general principle governing neuronal evolution and suggest that the exceptionally high prevalence of autism in humans may be a direct result of natural selection for lower expression of a suite of genes that conferred a fitness benefit to our ancestors while also rendering an abundant class of neurons more sensitive to perturbation.
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INTRODUCTION: The immune receptor triggering receptor expressed on myeloid cells 2 (TREM2) is among the strongest genetic risk factors for Alzheimer's disease (AD) and is a therapeutic target. TREM2 multimers have been identified in crystallography and implicated in the efficacy of antibody therapeutics; however, the molecular basis for TREM2 multimerization remains poorly understood. METHODS: We used molecular dynamics simulations and binding energy analysis to determine the effects of AD-associated variants on TREM2 multimerization and validated with experimental results. RESULTS: TREM2 trimers remained stably bound, driven primarily by salt bridge between residues D87 and R76 at the interface of TREM2 units. This salt bridge was disrupted by the AD-associated variants R47H and R98W and nearly ablated by the D87N variant. This decreased binding among TREM2 multimers was validated with co-immunoprecipitation assays. DISCUSSION: This study uncovers a molecular basis for TREM2 forming stable trimers and unveils a novel mechanism by which TREM2 variants may increase AD risk by disrupting TREM2 oligomerization to impair TREM2 normal function. HIGHLIGHTS: Triggering receptor expressed on myeloid cells 2 (TREM2) multimerization could regulate TREM2 activation and function. D87-R76 salt bridges at the interface of TREM2 units drive the formation of stable TREM2 dimers and trimers. Alzheimer's disease (AD)-associated R47H and R98W variants disrupt the D87-R76 salt bridge. The AD-associated D87N variant leads to complete loss of the D87-R76 salt bridge.
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Objectives: Reverse total shoulder arthroplasty (RTSA) continues to increase in popularity as a surgical operation in the United States. As indications for this procedure expand, more attention is needed to evaluate perioperative risk factors and patient characteristics. Postoperative anemia requiring blood transfusion (BT) is a well-documented risk factor for increased in-house mortality although little has been studied on the relationship between RTSA and postoperative BT. The purpose of this study was to identify comorbidities and patient characteristics as risk factors for BT in patient's undergoing RTSA. Methods: Using the Nationwide Inpatient Sample (NIS) database, 59,925 RTSA patients (2016-2019) were analyzed, with 1.96% requiring postoperative BT. Demographics, comorbidities, and preoperative factors were compared between BT and non-BT groups via univariate and multivariate analyses. Results: Overall prevalence of blood transfusion in all patients was 1.96%. Male sex (OR 1.75, p < 0.001), Asian ethnicity (OR 1.96, p = 0.012), age >80 (OR 1.51, p < 0.001), age >90 (OR 2.26, p < 0.001), CKD (OR 1.94, p < 0.001), and Parkinson's disease (OR 2.08, p < 0.001) were associated with increased BT odds. Cirrhosis exhibited the highest impact (OR 5.7, p < 0.001). Conversely, Caucasian ethnicity (OR 0.76, p = 0.023), uncomplicated DM (OR 0.73, p = 0.002), tobacco-related disorders (OR 0.43, p < 0.001), BMI >30 (OR 0.8, p = 0.011), and elective procedures (OR 0.16, p < 0.001) decreased BT odds. Conclusion: These results were useful with identifying several risk factors that predispose to a higher risk of postoperative BT in patients undergoing RTSA including male sex, people of Asian descent, age > 80, CKD, Parkinson's disease, and cirrhosis. These findings provide clinicians with information that may be helpful with preoperative planning and perioperative management of complex patient populations.
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BACKGROUND: It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016-2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis. METHODS: Retrospective chart review was performed. Statistical analysis was conducted using STATA. Receiver operating characteristic(ROC) curves identified the performance of angle for predicting recurrence&survival. Unadjusted and adjusted cox regression models were used to identify significant predictors of these outcomes. RESULTS: 47 patients were included with median follow-up of 29.6 months. ROC curves for angle predicting recurrence and survival identified a cutoff of 44.5°. KM curves demonstrated that patients above the cutoff were more likely to recur(90%vs46 â%,p â= â0.001) and less likely to survive(16%vs56 â%,p â= â0.001). Angle remained significant on multivariate analyses (HR recurrence:3.64[1.32-10.25],HR survival:3.80[1.38-10.46]). CONCLUSIONS: TEG angle is independently associated with disease recurrence and overall survival in pancreas cancer. This may be identifying virulent tumor biology, but further studies are required. A prospective study is underway.
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BACKGROUND: Direct peritoneal resuscitation (DPR) is associated with improved outcomes in trauma. Animal models suggest DPR has favorable effects on the liver. We sought to evaluate its safety and assess for improved outcomes in liver transplantation (LT). METHODS: LT patients with renal dysfunction and/or obesity were enrolled in a phase-I clinical trial. DPR lasted 8-24 âh depending on postoperative disposition. Primary outcome was percent of patients completing DPR. Secondary outcomes evaluated complications. Controls with either obesity (control-1) or both risk factors (obesity â+ ârenal dysfunction, control-2) were analyzed. RESULTS: Fifteen patients were enrolled (seven with both criteria and eight with obesity alone). DPR was completed in 87 â% of patients, with one meeting stopping criteria. Controls included 45 (control-1) and 24 (control-2) patients. Return to operating room, graft loss, and late infections were lower with DPR. CONCLUSION: DPR appears to be safe in closed abdomens following LT, warranting a follow-up phase-II trial to assess efficacy.
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The densities of eutectic (LiF)2-BeF2 and mixtures of this salt (FLiBe) with LaF3 were measured by dilatometry and by neutron attenuation from 673 K to 1,073 K. Because LaF3 has a limited solubility in FLiBe, it was necessary to determine the amount of LaF3 in solution before the density could be determined. The FLiBe density determination was favorably benchmarked against the literature data. A simple comparison was not available for the LaF3-FLiBe mixtures, so extrapolation of published data was necessary based on analysis using the Molten Salt Thermal Properties Database-Thermochemistry, or MSTDB-TC, developed by the US Department of Energy. Solubilities for LaF3 in FLiBe ranged from 1 to 4 mol % over 673 to 1,073 K. The salt system was heated and cooled over 24 h to evaluate potential changes in composition and hysteresis during the measurement. Changes in the meniscus were observed, and these were included in the correction for density determinations. Salt surface tension may have led to supersaturation of LaF3 in the salt because the solubility curve was nonlinear with respect to the inverse temperature, as would be expected for an ideal system. Surface tension measurements are currently underway to test this hypothesis.
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INTRODUCTION: Discrepant data exists regarding the outcomes following total knee arthroplasty (TKA) with a prior anterior cruciate reconstruction (ACLR). The purpose of our study was to compare surgical and medical outcomes in the patients with prior ACLR undergoing TKAs compared to a matched control group of the patients who had undergone TKAs without prior ACLR. We hypothesized that the patients with prior ACLR would have inferior clinical outcomes. MATERIAL/METHODS: We retrospectively queried the PearlDiver-database for patients who underwent TKA following ACLR from 2011 to 2020. We used propensity-score matching to create two cohorts. The two-sided independent t-test and Chi-Squared test were used. RESULTS: We identified 2,174 patients who had prior ACLR before the TKAs. There were another 1,348,870 patients who did not have ACLR before the TKAs. After matching, each group had 2,171 patients. The ACLR-TKA group had significantly lower rates of aseptic revision at 2 years (1.2% vs. 4.0%, OR 0.3, p < 0.01), PJI requiring antibiotic spacer at 2 years (0.3% vs. 0.8%, OR 0.35, p = 0.02), and MUA at 90 days (0.4% vs. 7.5%, OR 0.05, p < 0.01). The rate of wound disruption was lower for the ACLR-TKA group at 90 days (p = 0.03) as were several medical complications including AKI at 90 days (p < 0.01), DVT at 90 days (p < 0.01), pneumonia at 90 days (0.04), and required blood transfusion at 90 days (p < 0.01). CONCLUSION: These results differed from our expectations. Within the limitations of the study, we are unable to determine the factors for the lower complications in the ACLR-TKA group. The data from this study are different from what had been reported in the previous studies.
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Reconstrucción del Ligamento Cruzado Anterior , Artroplastia de Reemplazo de Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Estudios Retrospectivos , Masculino , Femenino , Reconstrucción del Ligamento Cruzado Anterior/métodos , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/epidemiología , Reoperación/estadística & datos numéricos , Resultado del Tratamiento , Puntaje de Propensión , AdultoRESUMEN
Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field. In these illustrated SOA capsules, you will find an exploration of novel models of thrombosis and bleeding and biomaterial discoveries that can trigger or block coagulation. Thromboinflammation is now understood to drive many disease states, and the SOA speakers cover cellular and coagulation responses to COVID-19 and other infections. The theme of crosstalk between coagulation and inflammation expands with capsules on protein S signaling, complement, and fibrinolytic inhibitors. Novel agents for hemophilia and thrombosis prevention are introduced. Challenging clinical conditions are also covered, such as inherited platelet disorders and antiphospholipid antibody syndrome. The scientific program in Bangkok will also showcase the work of clinicians and scientists from all parts of the world and chronicle real-world challenges. For example, 2 SOA capsules address the diagnosis and management of von Willebrand disease in low-income settings. Take some time to browse through these short illustrated reviews; we're sure that you'll be entertained, educated, and inspired to further explore the world of thrombosis and hemostasis.
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Integration of physiological sensing modalities within tissue and organ perfusion systems is becoming a steadily expanding field of research, aimed at achieving technological breakthrough innovations that will expand the sites and clinical settings at which such systems can be used. This is becoming possible in part due to the advancement of user-friendly optical sensors in recent years, which rely both on synthetic, luminescent sensor molecules and inexpensive, low-power electronic components for device engineering. In this article we report a novel approach towards enabling automated, continuous monitoring of oxygenation during ex vivo organ perfusion, by combining versatile flow cell components and low-power, programmable electronic readout devices. The sensing element comprises a 3D printed, miniature flow cell with tubing connectors and an affixed oxygen-sensing thin film material containing in-house developed, brightly-emitting metalloporphyrin phosphor molecules embedded within a polymer matrix. Proof-of-concept validation of this technology is demonstrated through integration within the tubing circuit of a transportable medical device for hypothermic oxygenated machine perfusion of extracted kidneys as a model for organs to be preserved as transplants.
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Background: Early dislocation following primary total hip arthroplasty (THA) is a rare but devastating complication and represents a source of patient morbidity and financial burden to the healthcare system. The objective of this study was to identify patient characteristics and comorbidities that are associated with increased early in-hospital dislocation rates following primary THA. Methods: A retrospective cohort study was conducted using patient data from the Nationwide Inpatient Sample (NIS) database; we identified patients who had undergone THA from 2016 to 2019 and compared those with an early periprosthetic dislocation prior to discharge to those without. The patient characteristics and comorbidities were compared using univariate analysis with a subsequent investigation of statistically significant variables using multivariate analysis. The variables were compared using chi square, Fisher's exact test, and independent sample t-tests with data assessed using odds ratio with 95% confidence intervals. Results: A total of 5151 patients sustained an early dislocation compared to 362,743 who did not. Those who sustained an in-hospital dislocation were more likely to share the following characteristics: female sex (OR 1.21, p < 0.01), age > 70 (OR 1.45, p < 0.01), Caucasian ethnicity (OR 1.22, p < 0.01), SLE (OR 1.87, p < 0.01), and Parkinson's disease (OR 1.93, p < 0.01). Certain characteristics were also associated with decreased odds of having an in-hospital dislocation including elective surgery (OR 0.14, p < 0.01), tobacco use (OR 0.8, p < 0.01), diabetes without complications (OR 0.87, p < 0.01), and a history of heart valve replacement (OR 0.81, p < 0.01). The length of stay was significantly longer (4.7 days vs. 2.3 days) as was the total hospital charges (USD $101,517 vs. USD $66,388) for the early in-hospital dislocation group. Conclusions: Several patient characteristics and comorbidities are associated with early in-hospital dislocation episodes following total hip arthroplasty including female sex, age > 70, non-elective surgery, SLE, and Parkinson's. This information may be useful to help guide intraoperative implant selection and/or postoperative protocol in select patient populations to limit early instability as well as decrease the financial burden associated with this postoperative complication.
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BACKGROUND: Complex pleural space infections often require treatment with multiple doses of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease, with treatment failure frequently necessitating surgery. Pleural infections are rich in neutrophils, and neutrophil elastase degrades plasminogen, the target substrate of tPA, that is required to generate fibrinolysis. We hypothesized that pleural fluid from patients with pleural space infection would show high elastase activity, evidence of inflammatory plasminogen degradation, and low fibrinolytic potential in response to tPA that could be rescued with plasminogen supplementation. RESEARCH QUESTION: Does neutrophil elastase degradation of plasminogen contribute to intrapleural fibrinolytic failure? STUDY DESIGN AND METHODS: We obtained infected pleural fluid and circulating plasma from hospitalized adults (n = 10) with institutional review board approval from a randomized trial evaluating intrapleural fibrinolytics vs surgery for initial management of pleural space infection. Samples were collected before the intervention and on days 1, 2, and 3 after the intervention. Activity assays, enzyme-linked immunosorbent assays, and Western blot analysis were performed, and turbidimetric measurements of fibrinolysis were obtained from pleural fluid with and without exogenous plasminogen supplementation. Results are reported as median (interquartile range) or number (percentage) as appropriate, with an α value of .05. RESULTS: Pleural fluid elastase activity was more than fourfold higher (P = .02) and plasminogen antigen levels were more than threefold lower (P = .04) than their corresponding plasma values. Pleural fluid Western blot analysis demonstrated abundant plasminogen degradation fragments consistent with elastase degradation patterns. We found that plasminogen activator inhibitor 1 (PAI-1), the native tPA inhibitor, showed high antigen levels before the intervention, but the overwhelming majority of this PAI-1 (82%) was not active (P = .003), and all PAI-1 activity was lost by day 2 after the intervention in patients receiving intrapleural tPA and deoxyribonuclease. Finally, using turbidity clot lysis assays, we found that the pleural fluid of 9 of 10 patients was unable to generate a significant fibrinolytic response when challenged with tPA and that plasminogen supplementation rescued fibrinolysis in all patients. INTERPRETATION: Our findings suggest that inflammatory plasminogen deficiency, not high PAI-1 activity, is a significant contributor to intrapleural fibrinolytic failure. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03583931; URL: www. CLINICALTRIALS: gov.
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A key goal of developmental biology is to determine the extent to which cells and organs develop autonomously, as opposed to requiring interactions with other cells or environmental factors. Chimeras have played a foundational role in this by enabling qualitative classification of cell-intrinsically vs. extrinsically driven processes. Here, we extend this framework to precisely decompose evolutionary divergence in any quantitative trait into cell-intrinsic, extrinsic, and intrinsic-extrinsic interaction components. Applying this framework to thousands of gene expression levels in reciprocal rat-mouse chimeras, we found that the majority of their divergence is attributable to cell-intrinsic factors, though extrinsic factors also play an integral role. For example, a rat-like extracellular environment extrinsically up-regulates the expression of a key transcriptional regulator of the endoplasmic reticulum (ER) stress response in some but not all cell types, which in turn strongly predicts extrinsic up-regulation of its target genes and of the ER stress response pathway as a whole. This effect is also seen at the protein level, suggesting propagation through multiple regulatory levels. Applying our framework to a cellular trait, neuronal differentiation, revealed a complex interaction of intrinsic and extrinsic factors. Finally, we show that imprinted genes are dramatically mis-expressed in species-mismatched environments, suggesting that mismatch between rapidly evolving intrinsic and extrinsic mechanisms controlling gene imprinting may contribute to barriers to interspecies chimerism. Overall, our conceptual framework opens new avenues to investigate the mechanistic basis of developmental processes and evolutionary divergence across myriad quantitative traits in any multicellular organism.
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Raman spectroscopy is an emerging technique for rapid and nondestructive analysis of nuclear materials for forensic and nonproliferation applications as it is a powerful tool for distinguishing multiple chemical forms of materials with similar stoichiometries. Recent developments in spectroscopic software have enabled rapid data collection with high-speed Raman spectroscopic mapping capabilities. However, some uranium-rich materials are susceptible to degradation in humid air and/or laser-induced phase transformations. To mitigate environmental or measurement-related sample degradation of potential samples of interest, we have taken a systematic approach to define optimized data collection parameters for high-throughput measurements of uranyl fluoride (UO2F2), which is an important intermediate material in the nuclear fuel cycle. First, we systematically describe the influence of optical magnification (5× to 100×), laser power, and exposure time on obtained signal for identical particles of UO2F2 and find that at low laser power and exposure times, comparable signal is obtained regardless of optical magnification. Second, we ensure sample integrity during data collection, and third, collect spectroscopic maps that employ optimized parameters to reduce the time required to obtain spatially resolved spectroscopic information. Reductions of 90% and 99% in measurement times are discussed as they relate to differences in resolving spectroscopic features of particles in identical mapping areas. During this work, we found that additional data processing options were needed and thus developed a customized Python script for importing, processing, analyzing, and visualizing Raman spectroscopic map data.
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Uranyl fluoride (UO2F2) particles (<20 µm) were subjected to first-of-its-kind analysis via simultaneous laser-induced breakdown spectroscopy (LIBS) and laser ablation multi-collector inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS). Briefly, a nanosecond pulsed high-energy laser was focused onto the sample (particle) surface. In a single laser pulse, the UO2F2 particle was excited/ionized within the microplasma volume, and the emission of light was collected via fiber optics such that emission spectroscopy could be employed for the detection of uranium (U) and fluorine (F). The ablated particle was simultaneously transported into the MC-ICP-MS for high precision isotopic (i.e., 234U, 235U, and 238U) analysis. This method, LIBS/LA-MC-ICP-MS was optimized and employed to rapidly measure 80+ UO2F2 particles, which were subjected to different calcination processes, which results in varying degrees of F loss from the individual particles. In measuring the particles, the average F/U ratios for the populations treated at 100 and 500 °C were 2.78 ± 1.28 and 1.01 ± 0.50, respectively, confirming loss of F through the calcination process. The average 235U/238U on the particle populations for the 100 and 500 °C were 0.007262 (22) and 0.007231 (23), which was determined to be <0.2% from the expected value. The 234U/238U ratios on the same particles were 0.000053 (11) and 0.000050 (10) for the 100 and 500 °C, respectively, <10% from the expected value. Notably, each population was analyzed in under 5 min, demonstrating the truly rapid analysis technique presented here.
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Índice de Masa Corporal , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Factores Sexuales , Pronóstico , Factores de Riesgo , Adulto , Resultado del Tratamiento , Obesidad/complicaciones , Obesidad/cirugía , Obesidad/diagnósticoRESUMEN
Cerium oxide is a low-value byproduct of rare-earth mining yet constitutes the largest fraction of the rare earth elements. The reduction of cerium oxide by liquid aluminum is proposed as an energy- and cost-efficient route to produce high-strength Al-Ce alloys. This work investigated the mechanism of a multi-step reduction reaction to facilitate the industrial adaptation of the process. Differential scanning calorimetry in combination with time-resolved synchrotron diffraction data uncovered the rate-limiting reaction step as the origin of the reported temperature dependence of reduction efficiency. This is the first in situ study of a metallothermic reaction mechanism and will serve as guidance for cost- and energy efficient industrial process control.
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Vertical and horizontal rhythms are crucial aspects of a dynamic golf swing, and the two-step swing drills (TSSD) were specifically designed to promote rhythmic unloading and loading of the legs. The purpose of this study was to evaluate the effects of a TSSD training session on the swing rhythm and clubhead speed (CHS) among competitive junior golfers (3.1 ± 4.4 hcp). The driver swings (7 swings each) of 10 competitive junior golfers (aged 15-18) were captured before and after a TSSD session consisting of four stages (lasting less than 45 minutes). Post-TSSD training, there were significant increases in CHS (p < .001), maximum unweighting (p = .006), the trail-side push (p = .009), the horizontal motion ranges of the body and pelvis (p = .005-.031), the upward/downward motion range of the body in the backswing (p = .042/.024), and the backswing/downswing angular velocity peaks of the axle-chain system (p < .033). The stepping-like leg actions primarily facilitated horizontal motion rhythm over vertical motion and unweighting over push in terms of ground interaction. These findings suggest that TSSD can serve as an effective method for developing a rhythmic and dynamic motion pattern while increasing CHS.
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We measure the thermal conductivity of solid and molten tungsten using steady state temperature differential radiometry. We demonstrate that the thermal conductivity can be well described by application of Wiedemann-Franz law to electrical resistivity data, thus suggesting the validity of Wiedemann-Franz law to capture the electronic thermal conductivity of metals in their molten phase. We further support this conclusion using ab initio molecular dynamics simulations with a machine-learned potential. Our results show that at these high temperatures, the vibrational contribution to thermal conductivity is negligible compared to the electronic component.
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BACKGROUND: Complex surgical back wounds represent significant morbidity in patients who have undergone spinal procedures requiring closure or revision by plastic surgeons. This study aimed to assess the utility of bacterial wound culture data for predicting surgical outcomes of wound management. METHODS: This study is a single-institution retrospective review of consecutive patients who required plastic surgery intervention for wound infection following spinal procedures between the years 2010 and 2021 (n = 70). Statistical analysis was performed for demographics, comorbidities, perioperative laboratory studies, and treatment methods. The primary outcomes of interest were rate of postoperative complications after soft tissue reconstruction and reconstructive failure. The secondary outcome of interest was time to healing in number of days. RESULTS: The overall complication rate after wound closure was 31.4%, with wound infection in 12.9%, seroma in 10%, dehiscence in 12.9%, and hematoma in 1.4%. Increasing number of debridements before wound closure increased the likelihood of a surgical complication of any kind (odds ratio [OR], 1.772; 95% confidence interval [CI], 1.045-3.002). Positive wound cultures before reconstruction were associated with development of seroma only (OR, 0.265; 95% CI, 0.078-0.893). Use of incisional vacuum-assisted closure devices significantly decreased the odds of postoperative wound dehiscence (OR, 0.179; 95% CI, 0.034-0.904) and increased odds of healing (hazard ratio, 3.638; 95% CI, 1.547-8.613). CONCLUSIONS: Positive wound cultures were not significantly associated with negative outcomes after complex closure or reconstruction of infected spinal surgical wounds. This finding emphasizes the importance of clinical judgment with a multidisciplinary approach to complex surgical back wounds over culture data for wound closure timing.
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Infección de la Herida Quirúrgica , Humanos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/etiología , Anciano , Adulto , Cicatrización de Heridas , Procedimientos de Cirugía Plástica/métodos , Procedimientos de Cirugía Plástica/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/microbiología , Técnicas de Cierre de Heridas , Resultado del Tratamiento , Valor Predictivo de las PruebasRESUMEN
This work describes an analytical procedure, single particle-inductively coupled plasma-time-of-flight-mass spectrometry (SP-ICP-TOF-MS), that was developed to determine the platinum binding efficiency of protein-coated magnetic microparticles. SP-ICP-TOF-MS is advantageous due to its ability to quasi-simultaneously detect all nuclides (7Li-242Pu), allowing for both platinum and iron (composition of magnetic microparticles) to be measured concurrently. This method subsequently allows for the differentiation between bound and unbound platinum. The 1 µm magnetic microparticles were fully characterized for their iron concentration, particle concentration, and trace element composition by bulk digestion-ICP-MS and SP-ICP-TOF-MS. The results of both approaches agreed with the certificate values. Using the single particle methodology the platinum loading was quantified to be to 0.18 ± 0.02 fg per particle and 0.32 ± 0.02 fg per particle, for the streptavidin-coated and azurin-coated microparticles, respectively. Both streptavidin-coated and the azurin-coated microparticles had a particle-platinum association of >65%. Platinum bound samples were also analyzed via bulk digestion-based ICP-MS. The bulk ICP-MS results overestimated platinum loading due to free platinum in the samples. This highlights the importance of single particle analysis for a closer inspection of platinum binding performance. The SP-ICP-TOF-MS approach offers advantages over typical bulk digestion methods by eliminating laborious sample preparation, enabling differentiation between bound/unbound platinum in a solution, and quantification of platinum on a particle-by-particle basis. The procedure presented here enables quantification of metal content per particle, which could be broadly implemented for other single particle applications.