Predicting Septic Arthritis in the Setting of Crystalline Arthropathy in the Native Joint Using Laboratory Data.

Background: Septic arthritis is an orthopedic emergency. Diagnosis is difficult in patients with concomitant crystalline arthropathy (gout or pseudogout). The symptomatology of crystal arthritis mimics septic arthritis, clouding clinical diagnosis. Arthrocentesis and synovial fluid analysis are the standard diagnostic tests for both pathologies. Crystals on microscopy are diagnostic of crystal arthritis, however their presence does not rule out septic arthritis. Septic arthritis is diagnosed by positive microbiology culture. Though septic arthritis is associated with elevated synovial total nucleated count (TNC), TNC elevations can also occur with gout. The literature suggests that a TNC count of > 50,000 cells in a crystal-positive joint should raise suspicion for concurrent septic arthritis, however data is limited. Further diagnostic indicators are needed to help clinicians promptly identify crystal positive septic arthritis as the treatments and prognoses are different. Methods: Patients were retrospectively identified who had arthrocentesis of a native joint positive for monosodium urate (MSU) and/or (CPPD) crystals. Laboratory data was collected including synovial fluid cultures, total nucleated cell count (TNC), percent polymorphic neutrophils (%PMN), and crystal analysis; and serum CRP, ESR, and white blood cell count (WBC). Statistical analysis performed using Spearman correlation, Univariate-Fischer's exact and Wilcoxon tests, and multivariate analysis. Results: 442 joints identified with positive CPPD and/or MSU crystals, 31% female, 69% male. Of 442 aspirates, 58 had positive cultures. Patients were more likely to have positive cultures if synovial TNC > 50,000 (odds ratio 7.7), CRP > 10 mg/dL (OR 3.2), PMN > 90% (OR 2.17), and if the patient was female (OR 1.9), all were statistically significant with p < 0.05. There were 55 patients who underwent irrigation and debridement based on clinical suspicion or a positive gram stain, 37 of these ultimately had a positive culture (67%), the remaining 18 had negative cultures. Conclusion: Results are consistent with the literature, a TNC > 50,000 warrants a high suspicion for concurrent septic arthritis and should prompt providers to critically evaluate other patient laboratory data. Results further suggests that a patient with positive crystals, synovial TNC > 50,000 cells, PMN > 90%, and serum CRP > 10mg/dL is at high risk for having a concurrent septic arthritis and may warrant urgent irrigation and debridement and antibiotic therapy. This data serves as a supporting to develop an infection risk calculator for crystal positive septic arthritis. Level of Evidence: III.

Deciphering "Immaturity-Stemness" in Human Epidermal Stem Cells at the Levels of Protein-Coding and Non-Coding Genomes: A Prospective Computational Approach.

The epidermis hosts populations of epithelial stem cells endowed with well-documented renewal and regenerative functions. This tissue thus constitutes a model for exploring the molecular characteristics of stem cells, which remain to date partially characterized at the molecular level in human skin. Our group has investigated the regulatory functions of the KLF4/TGFB1 and the MAD4/MAX/MYC signaling pathways in the control of the immaturity-stemness versus differentiation fate of keratinocyte stem and precursor cells from human interfollicular epidermis. We described that down-modulation of either KLF4 or MXD4/MAD4 using RNA interference tools promoted an augmented stemness cellular status; an effect which was associated with significant transcriptional changes, as assessed by RNA-sequencing. Here, we have implemented a computational approach aimed at integrating the level of the coding genome, comprising the transcripts encoding conventional proteins, and the non-coding genome, with a focus on long non-coding RNAs (lncRNAs). In addition, datasets of micro-RNAs (miRNAs) with validated functions were interrogated in view of identifying miRNAs that could make the link between protein-coding and non-coding transcripts. Putative regulons comprising both coding and long non-coding transcripts were built, which are expected to contain original pro-stemness candidate effectors available for functional validation approaches. In summary, interpretation of our basic functional data together with in silico biomodeling gave rise to a prospective picture of the complex constellation of transcripts regulating the keratinocyte stemness status.

Comprehensive phylogeny of Pieridae butterflies reveals strong correlation between diversification and temperature.

Temperature is thought to be a key factor influencing global species richness patterns. We investigate the link between temperature and diversification in the butterfly family Pieridae by combining next generation DNA sequences and published molecular data with fine-grained distribution data. We sampled nearly 600 pierid butterfly species to infer the most comprehensive molecular phylogeny of the family and curated a distribution dataset of more than 800,000 occurrences. We found strong evidence that species in environments with more stable daily temperatures or cooler maximum temperatures in the warm seasons have higher speciation rates. Furthermore, speciation and extinction rates decreased in tandem with global temperatures through geological time, resulting in a constant net diversification.

A sweet tooth makes a fly a pest.

The major insect pest of soft and stone fruits, the spotted-wing drosophila, Drosophila suzukii, has evolved a greater preference for laying eggs on ripe fruits over fermented ones. In a recent study, Cavey et al. found that higher responsiveness to low sugar concentrations has had an important role in this evolutionary shift in egg-laying behavior.

A fast and reliable larval sampling method for improving the monitoring of fruit flies in soft and stone fruits.

The spotted-wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), threatens both the soft-skinned and stone fruit industry in Asia, Europe, and America. Integrated pest management requires monitoring for infestation rates in real time. Although baited traps for adult D. suzukii are widely used for field monitoring, trap captures are weakly correlated to larval infestation rates. Thus, monitoring for larvae instead of adult flies represents the most reliable monitoring technique. Current methods for larval monitoring (e.g., sugar or salt floatation) are time-consuming and labor-intensive. In this study, we develop a new "sleeve method" for detecting larvae in strawberries through the inspection of individual fruits crushed within transparent plastic sleeves. Samples can be optionally frozen until further processing. Based on count data from non-expert observers, the estimation of larval infestation with the sleeve method is fast, precise, and highly repeatable within and among observers. Mean processing time is half the time compared to previous methods (33-80 s per sample depending on infestation levels). As the accuracy of the sleeve method decreases with infestation levels, we suggest ways to improve its accuracy by incubating fruits for 48 h and calibrating data using fruits with a known number of larvae. The method could also be used in other fruits, as it is easier to use, faster, and requires less equipment than previous monitoring methods. Finally, the method represents a promising tool for growers or researchers to effectively monitor and manage D. suzukii and other insect pests of soft and stone fruits.

Outcomes After Successful Debridement, Antibiotic, and Implant Retention Therapy for Periprosthetic Joint Infection in Total Knee Arthroplasty.

BACKGROUND: Controversy surrounds debridement, antibiotic and implant retention (DAIR) for treatment of acute periprosthetic joint infection (PJI). Data regarding DAIR's rate of infection resolution is variable with little investigation of functional outcomes. METHODS: We identified 191 DAIR cases at a single institution from 2008 to 2020. Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) and Patient Reported Outcome Measurement Information System-10 (PROMIS) scores were collected. Patient Reported Outcome Scores were obtained from 60 cases. Median follow-up (IQR) was 4.5 (2.1 to 7.6) versus 3.0 (1.2 to 5.3) years for the control group. Mean scores were compared to a cohort of uncomplicated total knee arthroplasties matched by age, body mass index, and sex using generalized linear models adjusted for follow-up duration. Kaplan-Meier survivorship curves for PJI were constructed. RESULTS: Mean Patient Reported Outcome Scores for the DAIR cohort were 57.2 ± 19.7 for KOOS-JR, 41.6 ± 7.1 for PROMIS physical health (PH), and 46.6 ± 8.7 for PROMIS mental health (MH). Mean control group values were 65.8 ± 21.0 for KOOS-JR, 44.6 ± 8.4 for PROMIS PH, and 49.2 ± 9.2 for PROMIS MH. No difference was observed in KOOS-JR (P = .83) or PROMIS MH (P = .11). PROMIS PH was lower in the DAIR cohort compared to the control group (P = .048). Median follow-up (years) for all 191 cases was 5.9 (range, 0.5 to 13.1). Survivorship (years) without subsequent operation for infection was 84% at 1, 82% at 2, and 79% at 5. CONCLUSION: Knee and MH outcomes in successful DAIR procedures were similar to uncomplicated total knee arthroplasty. DAIR's success rate was 79% in treating acute PJI at 5 years. LEVEL OF EVIDENCE: Level III.

Unusual Combination of Lateral Condyle Mass Fracture and Olecranon Fracture in a Child: A Case Report.

Fractures of the lateral condyle and olecranon are two of the most common elbow injuries in the pediatric age group. However, their simultaneous occurrence is rare. Proper understanding and management of these injuries are essential to prevent long-term complications. This case report presents a patient who suffered both fractures, with surgical intervention for the condyle and non-surgical management for the olecranon. A two-year-old female child was brought to the emergency department following a fall from monkey bars, landing on her outstretched left arm. Clinical examination showed a markedly swollen and tender elbow with a restricted range of motion. No neurovascular deficit was noted. Plain radiographs revealed a displaced fracture of the lateral condyle and an associated non-displaced olecranon fracture. Given the displacement of the lateral condyle fracture, surgical intervention was deemed necessary. The patient underwent open reduction and internal fixation (ORIF) of the lateral condyle using Kirschner wires. The olecranon fracture, being non-displaced, was managed conservatively with a posterior splint. The patient's postoperative recovery was uneventful. The Kirschner wires were removed at six weeks of follow-up, and active mobilization was started. The patient achieved full range of motion at three months post-injury. At a one-year follow-up, she had no pain, restriction, or any deformity, and radiographs confirmed the complete union of both fractures. Simultaneous fractures of the lateral condyle and olecranon in children are rare. The mechanism of injury is complex and warrants a high index of suspicion for associated injuries. Surgical fixation of the lateral condyle and conservative management of the olecranon fracture can yield excellent outcomes.

Minimum Free Energy Pathways of Reactive Processes with Nudged Elastic Bands.

The determination of minimum free energy pathways (MFEP) is one of the most widely used strategies to study reactive processes. For chemical reactions in complex environments, the combination of quantum mechanics (QM) with a molecular mechanics (MM) representation is usually necessary in a hybrid QM/MM framework. However, even within the QM/MM approximation, the affordable sampling of the phase space is, in general, quite restricted. To reduce drastically the computational cost of the simulations, several methods such as umbrella sampling require performing a priori a selection of a reaction coordinate. The quality of the computed results, in an affordable computational time, is intimately related to the reaction coordinate election which is, in general, a nontrivial task. In this work, we provide an approach to model reactive processes in complex environments that does not require the a priori selection of a reaction coordinate. The proposed methodology combines QM/MM simulations with an extrapolation of the nudged elastic bands (NEB) method to the free energy surface (FENEB). We present and apply our own FENEB scheme to optimize MFEP in different reactive processes, using QM/MM frameworks at semiempirical and density functional theory levels. Our implementation is based on performing the FENEB optimization by uncoupling the optimization of the band in a perpendicular and tangential direction. In each step, a full optimization with the spring force is performed, which guarantees that the images remain evenly distributed. The robustness of the method and the influence of sampling on the quality of the optimized MFEP and its associated free energy barrier are studied. We show that the FENEB method provides a good estimation of the reaction barrier even with relatively short simulation times, supporting that its combination with QM/MM frameworks provides an adequate tool to study chemical processes in complex environments.

AMPKγ3 Controls Muscle Glucose Uptake in Recovery From Exercise to Recapture Energy Stores.

Exercise increases muscle glucose uptake independently of insulin signaling and represents a cornerstone for the prevention of metabolic disorders. Pharmacological activation of the exercise-responsive AMPK in skeletal muscle has been proven successful as a therapeutic approach to treat metabolic disorders by improving glucose homeostasis through the regulation of muscle glucose uptake. However, conflicting observations cloud the proposed role of AMPK as a necessary regulator of muscle glucose uptake during exercise. We show that glucose uptake increases in human skeletal muscle in the absence of AMPK activation during exercise and that exercise-stimulated AMPKγ3 activity strongly correlates to muscle glucose uptake in the postexercise period. In AMPKγ3-deficient mice, muscle glucose uptake is normally regulated during exercise and contractions but impaired in the recovery period from these stimuli. Impaired glucose uptake in recovery from exercise and contractions is associated with a lower glucose extraction, which can be explained by a diminished permeability to glucose and abundance of GLUT4 at the muscle plasma membrane. As a result, AMPKγ3 deficiency impairs muscle glycogen resynthesis following exercise. These results identify a physiological function of the AMPKγ3 complex in human and rodent skeletal muscle that regulates glucose uptake in recovery from exercise to recapture muscle energy stores. ARTICLE HIGHLIGHTS: Exercise-induced activation of AMPK in skeletal muscle has been proposed to regulate muscle glucose uptake in recovery from exercise. This study investigated whether the muscle-specific AMPKγ3-associated heterotrimeric complex was involved in regulating muscle glucose metabolism in recovery from exercise. The findings support that exercise-induced activation of the AMPKγ3 complex in human and mouse skeletal muscle enhances glucose uptake in recovery from exercise via increased translocation of GLUT4 to the plasma membrane. This work uncovers the physiological role of the AMPKγ3 complex in regulating muscle glucose uptake that favors replenishment of the muscle cellular energy stores.

NSAIDs use history: impact on the genome-wide DNA methylation profile and possible mechanisms of action.

BACKGROUND AND OBJECTIVE: NSAIDs inhibit cyclooxygenase, but their role in aging and other diseases is not well understood. Our group previously showed the potential benefit of NSAIDs in decreasing the risk of delirium and mortality. Concurrently, epigenetics signals have also been associated with delirium. Therefore, we sought to find differentially methylated genes and biological pathways related to exposure with NSAIDs by comparing the genome-wide DNA methylation profiles of patients with and without a history of NSAIDs use. METHODS: Whole blood samples were collected from 171 patients at the University of Iowa Hospital and Clinics from November 2017 to March 2020. History of NSAIDs use was assessed through a word-search function in the subjects' electronic medical records. DNA was extracted from the blood samples, processed with bisulfite conversion, and analyzed using Illumina's EPIC array. The analysis of top differentially methylated CpG sites and subsequent enrichment analysis were conducted using an established pipeline using R statistical software. RESULTS: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) showed several biological pathways relevant to NSAIDs' function. The identified GO terms included "arachidonic acid metabolic process," while KEGG results included "linoleic acid metabolism," "cellular senescence," and "circadian rhythm." Nonetheless, none of the top GO and KEGG pathways and the top differentially methylated CpG sites reached statistical significance. CONCLUSION: Our results suggest a potential role of epigenetics in the mechanisms of the action of NSAIDs. However, the results should be viewed with caution as exploratory and hypothesis-generating given the lack of statistically significant findings.

Macrophage phagocytosis of SARS-CoV-2-infected cells mediates potent plasmacytoid dendritic cell activation.

Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent or unregulated proinflammatory cytokine responses are associated with severe disease outcomes. Previous work suggested that monocyte-derived macrophages (MDMs) are resistant and unresponsive to SARS-CoV-2 infection. Here, we demonstrate that upon phagocytosis of SARS-CoV-2-infected cells, MDMs are activated and secrete IL-6 and TNF. Importantly, activated MDMs in turn mediate strong activation of plasmacytoid dendritic cells (pDCs), leading to the secretion of high levels of IFN-α and TNF. Furthermore, pDC activation promoted IL-6 production by MDMs. This kind of pDC activation was dependent on direct integrin-mediated cell‒cell contacts and involved stimulation of the TLR7 and STING signaling pathways. Overall, the present study describes a novel and potent pathway of pDC activation that is linked to the macrophage-mediated clearance of infected cells. These findings suggest that a high infection rate by SARS-CoV-2 may lead to exaggerated cytokine responses, which may contribute to tissue damage and severe disease.

A New Bioassay for the Detection of Paralytic and Amnesic Biotoxins Based on Motor Behavior Impairments of Zebrafish Larvae.

The global concern about the increase of harmful algal bloom events and the possible impacts on food safety and aquatic ecosystems presents the necessity for the development of more accessible techniques for biotoxin detection for screening purposes. Considering the numerous advantages that zebrafish present as a biological model and particularly as a toxicants sentinel, we designed a sensitive and accessible test to determine the activity of paralytic and amnesic biotoxins using zebrafish larvae immersion. The ZebraBioTox bioassay is based on the automated recording of larval locomotor activity using an IR microbeam locomotion detector, and manual assessment of four complementary responses under a simple stereoscope: survival, periocular edema, body balance, and touch response. This 24 h acute static bioassay was set up in 96-well microplates using 5 dpf zebrafish larvae. For paralytic toxins, a significant decrease in locomotor activity and touch response of the larvae was detected, allowing a detection threshold of 0.1-0.2 µg/mL STXeq. In the case of the amnesic toxin the effect was reversed, detecting hyperactivity with a detection threshold of 10 µg/mL domoic acid. We propose that this assay might be used as a complementary tool for environmental safety monitoring.

A computational framework for testing hypotheses of the minimal mechanical requirements for cell aggregation using early annual killifish embryogenesis as a model.

Introduction: Deciphering the biological and physical requirements for the outset of multicellularity is limited to few experimental models. The early embryonic development of annual killifish represents an almost unique opportunity to investigate de novo cellular aggregation in a vertebrate model. As an adaptation to seasonal drought, annual killifish employs a unique developmental pattern in which embryogenesis occurs only after undifferentiated embryonic cells have completed epiboly and dispersed in low density on the egg surface. Therefore, the first stage of embryogenesis requires the congregation of embryonic cells at one pole of the egg to form a single aggregate that later gives rise to the embryo proper. This unique process presents an opportunity to dissect the self-organizing principles involved in early organization of embryonic stem cells. Indeed, the physical and biological processes required to form the aggregate of embryonic cells are currently unknown. Methods: Here, we developed an in silico, agent-based biophysical model that allows testing how cell-specific and environmental properties could determine the aggregation dynamics of early Killifish embryogenesis. In a forward engineering approach, we then proceeded to test two hypotheses for cell aggregation (cell-autonomous and a simple taxis model) as a proof of concept of modeling feasibility. In a first approach (cell autonomous system), we considered how intrinsic biophysical properties of the cells such as motility, polarity, density, and the interplay between cell adhesion and contact inhibition of locomotion drive cell aggregation into self-organized clusters. Second, we included guidance of cell migration through a simple taxis mechanism to resemble the activity of an organizing center found in several developmental models. Results: Our numerical simulations showed that random migration combined with low cell-cell adhesion is sufficient to maintain cells in dispersion and that aggregation can indeed arise spontaneously under a limited set of conditions, but, without environmental guidance, the dynamics and resulting structures do not recapitulate in vivo observations. Discussion: Thus, an environmental guidance cue seems to be required for correct execution of early aggregation in early killifish development. However, the nature of this cue (e.g., chemical or mechanical) can only be determined experimentally. Our model provides a predictive tool that could be used to better characterize the process and, importantly, to design informed experimental strategies.

TBC1D4-S711 Controls Skeletal Muscle Insulin Sensitization After Exercise and Contraction.

The ability of insulin to stimulate glucose uptake in skeletal muscle is important for whole-body glycemic control. Insulin-stimulated skeletal muscle glucose uptake is improved in the period after a single bout of exercise, and accumulating evidence suggests that phosphorylation of TBC1D4 by the protein kinase AMPK is the primary mechanism responsible for this phenomenon. To investigate this, we generated a TBC1D4 knock-in mouse model with a serine-to-alanine point mutation at residue 711 that is phosphorylated in response to both insulin and AMPK activation. Female TBC1D4-S711A mice exhibited normal growth and eating behavior as well as intact whole-body glycemic control on chow and high-fat diets. Moreover, muscle contraction increased glucose uptake, glycogen utilization, and AMPK activity similarly in wild-type and TBC1D4-S711A mice. In contrast, improvements in whole-body and muscle insulin sensitivity after exercise and contractions were only evident in wild-type mice and occurred concomitantly with enhanced phosphorylation of TBC1D4-S711. These results provide genetic evidence to support that TBC1D4-S711 serves as a major point of convergence for AMPK- and insulin-induced signaling that mediates the insulin-sensitizing effect of exercise and contractions on skeletal muscle glucose uptake.

Venetoclax resistance induced by activated T cells can be counteracted by sphingosine kinase inhibitors in chronic lymphocytic leukemia.

The treatment of chronic lymphocytic leukemia (CLL) patients with venetoclax-based regimens has demonstrated efficacy and a safety profile, but the emergence of resistant cells and disease progression is a current complication. Therapeutic target of sphingosine kinases (SPHK) 1 and 2 has opened new opportunities in the treatment combinations of cancer patients. We previously reported that the dual SPHK1/2 inhibitor, SKI-II enhanced the in vitro cell death triggered by fludarabine, bendamustine or ibrutinib and reduced the activation and proliferation of chronic lymphocytic leukemia (CLL) cells. Since we previously showed that autologous activated T cells from CLL patients favor the activation of CLL cells and the generation of venetoclax resistance due to the upregulation of BCL-XL and MCL-1, we here aim to determine whether SPHK inhibitors affect this process. To this aim we employed the dual SPHK1/2 inhibitor SKI-II and opaganib, a SPHK2 inhibitor that is being studied in clinical trials. We found that SPHK inhibitors reduce the activation of CLL cells and the generation of venetoclax resistance induced by activated T cells mainly due to a reduced upregulation of BCL-XL. We also found that SPHK2 expression was enhanced in CLL cells by activated T cells of the same patient and the presence of venetoclax selects resistant cells with high levels of SPHK2. Of note, SPHK inhibitors were able to re-sensitize already resistant CLL cells to a second venetoclax treatment. Our results highlight the therapeutic potential of SPHK inhibitors in combination with venetoclax as a promising treatment option for the patients.

Mechanistic Modelling of Biomass Growth, Glucose Consumption and Ethanol Production by Kluyveromyces marxianus in Batch Fermentation.

This paper presents results concerning mechanistic modeling to describe the dynamics and interactions between biomass growth, glucose consumption and ethanol production in batch culture fermentation by Kluyveromyces marxianus (K. marxianus). The mathematical model was formulated based on the biological assumptions underlying each variable and is given by a set of three coupled nonlinear first-order Ordinary Differential Equations. The model has ten parameters, and their values were fitted from the experimental data of 17 K. marxianus strains by means of a computational algorithm design in Matlab. The latter allowed us to determine that seven of these parameters share the same value among all the strains, while three parameters concerning biomass maximum growth rate, and ethanol production due to biomass and glucose had specific values for each strain. These values are presented with their corresponding standard error and 95% confidence interval. The goodness of fit of our system was evaluated both qualitatively by in silico experimentation and quantitative by means of the coefficient of determination and the Akaike Information Criterion. Results regarding the fitting capabilities were compared with the classic model given by the logistic, Pirt, and Luedeking-Piret Equations. Further, nonlinear theories were applied to investigate local and global dynamics of the system, the Localization of Compact Invariant Sets Method was applied to determine the so-called localizing domain, i.e., lower and upper bounds for each variable; whilst Lyapunov's stability theories allowed to establish sufficient conditions to ensure asymptotic stability in the nonnegative octant, i.e., R+,03. Finally, the predictive ability of our mechanistic model was explored through several numerical simulations with expected results according to microbiology literature on batch fermentation.

Anti-inflammatory medication use associated with reduced delirium risk and all-cause mortality: A retrospective cohort study.

OBJECTIVE: To investigate the relationship between history of anti-inflammatory medication use and delirium risk, as well as long-term mortality. METHODS: In this retrospective cohort study, subjects recruited between January 2016 and March 2020 were analyzed. Information about anti-inflammatory medication use history including aspirin, NSAIDs, glucosamine, and other anti-inflammatory drugs, was collected. Logistic regression analysis investigated the relationship between anti-inflammatory medications and delirium. Log-rank analysis and cox proportional hazards model investigated the relationship between anti-inflammatory medications and one-year mortality. RESULTS: The data from 1274 subjects were analyzed. The prevalence of delirium was significantly lower in subjects with NSAIDs usage (23.0%) than in those without NSAIDs usage (35.0%) (p < 0.001). Logistic regression analysis controlling for age, sex, dementia status, and hospitalization department showed that the risk of delirium tended to be reduced by a history of NSAIDs use (OR, 0.76 [95% CI, 0.55 to 1.03]). The one-year mortality in the subjects with NSAIDs (survival rate, 0.879 [95% CI, 0.845 to 0.906]) was significantly lower than in the subjects without NSAIDs (survival rate, 0.776 [95% CI, 0.746 to 0.803]) (p < 0.001). A history of NSAIDs use associated with the decreased risk of one-year mortality even after adjustment for age, sex, Charlson Comorbidity Index, delirium status, and hospitalization department (HR, 0.70 [95% CI, 0.51 to 0.96]). CONCLUSION: This study suggested that NSAIDs usage was associated with decreased delirium prevalence and lower one-year mortality. The potential benefit of NSAIDs on delirium risk and mortality were shown.

Gradually supply of isoamyl alcohol increases the isoamyl acetate production in solid-state fermentation.

Nowadays, isoamyl acetate production is carried out by chemical synthesis with a recent interest in developing biological producing processes, mainly based on microorganisms in submerged fermentation. This work assayed producing isoamyl acetate through solid-state fermentation (SSF), feeding the precursor in the gas phase. Polyurethane foam functioned as the inert support to contain 20 ml of a solution of molasses (10% w/v, pH 5.0). The yeast Pichia fermentans was inoculated at 3 × 107 cells per gram of initial dry weight. The airstream to supply oxygen also served to supply the precursor. Slow supply was obtained using an isoamyl alcohol solution of 5 g l-1 in the bubbling columns and an air stream of 50 ml min-1. For fast supply, fermentations were aerated using 10 g l-1 and 100 ml min-1 for isoamyl alcohol solution and air stream, respectively. It demonstrated the feasibility of isoamyl acetate production in SSF. Moreover, the slow supply of the precursor increased isoamyl acetate production up to 390 mg l-1, which is 12.5 times higher than that obtained without precursor (32 mg l-1). On the other hand, fast supply caused an evident inhibition of the growth and production capacity of the yeast.

What Is the Fate of Total Joint Arthroplasty Patients Who Are Asked to Quit Smoking Prior to Surgery?

Background: Smoking is a known risk factor for complications following primary total joint arthroplasty (TJA). Little is known regarding the fate of patients who are asked to quit smoking before surgery. The purpose of this study was to evaluate the success of smoking cessation prior to primary TJA and the impact of smoking cessation on perioperative outcomes. Methods: This is a retrospective review of patients who presented between 2008 and 2020 to a single academic medical center with a documented smoking history and were asked to quit smoking prior to receiving a date for primary TJA. The cohort was surveyed about smoking cessation, smoking history, use of quit aids, seeking surgery elsewhere due to the cessation policy, and postoperative complications. Descriptive statistics evaluated the relationship between demographics, smoking cessation, and postoperative complications. Results: A total of 101 patients completed the survey with an overall response rate of 48%. Sixty-two percent of patients quit smoking before surgery, and 51% of these patients reported remaining smoke-free at 6 months postoperatively. The average time to quit before TJA was 45 days (range: 1-365 days), and 62% quit without quit aids. The wound complication/infection rate was significantly higher for patients who did not stop smoking prior to TJA (4 of 16; 27%) than for those who did quit prior to surgery (3 of 63; 5%; P = .02). Conclusions: This study demonstrates that most patients (62%) will stop smoking, if required, prior to primary TJA. Furthermore, 51% of patients reported abstinence from smoking at 6 months following TJA. TJA appears to be an effective motivator for smoking cessation. Level of Evidence: III (retrospective cohort study).

Satisfactory clinical outcomes with autologous matrix-induced chondrogenesis in the treatment of grade IV chondral injuries of the knee.

OBJECTIVE: The research aims to evaluate short- and medium-term outcomes of patients treated using autologous matrix-induced chondrogenesis (AMIC) with a hyaluronic acid scaffold (Hyalofast, Anika Therapeutics, MA, USA) in grade IV chondral lesions according to the Outerbridge classification in the knee. METHODS: This is a multicentre, non-randomized, retrospective study conducted between 2017 and 2022. To determine the clinical outcome of the patients, the follow-up was done with the subjective International Knee Documentation Committee (IKDC) score, pre-surgery, and with a follow-up at 12, 24, and 32 months. RESULTS: Fifty patients (28 female) with a mean age of 45.9 ± 12.7 years were recruited. The mean size of the lesion was 3.5 cm2, and the injuries located in the patella (30%) and trochlear groove (24%) were the most frequent. The total IKDC clinical score significantly increased from baseline to the 32 months of follow-up with a mean difference of 36.4 (95% CI, 29.1-43.7, p < 0.001). Besides, there was a statistically significant improvement in all categories of the IKDC (symptoms, sports activities, function, and activity of daily living) compared between pre-surgery and 24 and 32 months of follow-up. The patients younger than 45 years presented better clinical outcomes than older ones with a difference between medians of 10.40 (95% CI, 1.10-11.50, p = 0.0247), and a negative correlation was found between the 32-month IKDC score and the age. In addition, no statistically significant difference was found when comparing the last results of the IKDC between patients with and without associated surgical procedures or between patients with single and several lesions, neither nor between men and women. The level of satisfaction with the procedure of all the patients, on a score of 1-10, was on average 8 ± 1.5. CONCLUSION: Results of this study indicate that patients who underwent the AMIC procedure with hyaluronic acid scaffold for the treatment of grade IV chondral lesions in the knee presented satisfactory results throughout the follow-up. LEVEL OF EVIDENCE: Level IV.