Influenza A virus during pregnancy disrupts maternal intestinal immunity and fetal cortical development in a dose- and time-dependent manner.

Epidemiological studies link exposure to viral infection during pregnancy, including influenza A virus (IAV) infection, with increased incidence of neurodevelopmental disorders (NDDs) in offspring. Models of maternal immune activation (MIA) using viral mimetics demonstrate that activation of maternal intestinal T helper 17 (TH17) cells, which produce effector cytokine interleukin (IL)-17, leads to aberrant fetal brain development, such as neocortical malformations. Fetal microglia and border-associated macrophages (BAMs) also serve as potential cellular mediators of MIA-induced cortical abnormalities. However, neither the inflammation-induced TH17 cell pathway nor fetal brain-resident macrophages have been thoroughly examined in models of live viral infection during pregnancy. Here, we inoculated pregnant mice with two infectious doses of IAV and evaluated peak innate and adaptive immune responses in the dam and fetus. While respiratory IAV infection led to dose-dependent maternal colonic shortening and microbial dysregulation, there was no elevation in intestinal TH17 cells nor IL-17. Systemically, IAV resulted in consistent dose- and time-dependent increases in IL-6 and IFN-γ. Fetal cortical abnormalities and global changes in fetal brain transcripts were observable in the high-but not the moderate-dose IAV group. Profiling of fetal microglia and BAMs revealed dose- and time-dependent differences in the numbers of meningeal but not choroid plexus BAMs, while microglial numbers and proliferative capacity of Iba1+ cells remained constant. Fetal brain-resident macrophages increased phagocytic CD68 expression, also in a dose- and time-dependent fashion. Taken together, our findings indicate that certain features of MIA are conserved between mimetic and live virus models, while others are not. Overall, we provide consistent evidence of an infection severity threshold for downstream maternal inflammation and fetal cortical abnormalities, which recapitulates a key feature of the epidemiological data and further underscores the importance of using live pathogens in NDD modeling to better evaluate the complete immune response and to improve translation to the clinic.

No Revisions Attributable To Wear of Highly Cross-Linked Polyethylene Liners: A Long Term Follow-up Study.

INTRODUCTION: There is a paucity of data beyond 15 years on the survivorship of total hip arthroplasty since the introduction of highly cross-linked polyethylene (HXLPE) liners. Our aim was to evaluate implant survivorship, liner wear rates, and clinical outcomes after primary THA using HXLPE liners implanted between 1999 and 2002. METHODS: Between 1999 and 2002, 690 primary THAs utilizing 28-mm femoral heads and HXLPE liners of a single design were identified using our institutional total joint registry. Femoral heads were made of metal in 96% of cases and ceramic in 4%. The mean age was 56 years, 48% were women, and the mean BMI was 30. Survivorship analyses were performed for the outcomes of implant revision, reoperation, and complications for the entire cohort. Linear HXLPE liner wear rates were determined on 197 hips with radiographs with more than 18.5 years of follow-up. RESULTS: At 20 years, survivorship free of revision was 94%, free of reoperation was 92%, and free of any complication was 81%. There were no documented wear-related revisions. The linear wear rate at a mean of 20.3 years postoperatively was 0.02 mm/year. There was no statistically significant difference in measured wear observed between the first available postoperative radiographs and those taken at the final follow-up. The use of elevated liners, patient BMI, age, preoperative diagnosis, acetabular component inclination, and anteversion angles were not associated with increased wear rates. Mean Harris Hip Scores improved from 52 preoperatively to 90 at greater than 18.5 years. CONCLUSIONS: Primary THAs using a single first generation HXLPE liner demonstrated excellent survivorship and clinical outcomes at long-term follow-up with no wear-related revisions. Wear rates of HXLPE liners at 20 years are exceedingly low and are not significantly impacted by acetabular component position or patient-dependent variables such as BMI. LEVEL OF EVIDENCE: IV.

Identifying Critical Evidence Gaps in Wound Closure and Incision Management After Total Knee Arthroplasty: Delphi Panel Insights.

INTRODUCTION: In orthopaedic surgery, particularly total knee arthroplasty (TKA), the management of surgical wounds is critical for optimal wound healing and successful patient outcomes. Despite advances in surgical techniques, challenges persist in effectively managing surgical wounds to prevent complications and infections. This study aimed to identify and address the critical evidence gaps in wound management in TKA, including preoperative optimization, intraoperative options, and for the avoidance of postoperative complications. These are important issues surrounding wound management, which is essential for improving patient recovery and the overall success of the surgery. METHODS: Utilizing the Delphi method, this study brought together 20 experienced orthopaedic surgeons from Europe and North America. Conducted from April to September 2023, the process involved three stages: an initial electronic survey, a virtual meeting, and a concluding electronic survey. The panel reviewed and reached a consensus on 26 specific statements about wound management in TKA based on a comprehensive literature review. During these three stages and after further panel review, an alternative goal of the Delphi panel was to also identify critical evidence gaps in the current understanding of wound management practices for TKA. RESULTS: While the panel reached consensus on various wound management practices, they highlighted several major evidence gaps. Also, there was general consensus on issues such as wound closure methods including the use of mesh-adhesive dressings, skin glue, staples, sutures (including barbed sutures),and negative-pressure wound therapy (NPWT). However, it was deemed necessary that further evidence needs to be generated to address the cost-effectiveness of each and develop best practices for promoting patient outcomes. The identification of these gaps points to areas requiring more in-depth research and improvements to enhance wound care in TKA. DISCUSSION: The identification of these major evidence gaps underscores the need for targeted research in wound management surrounding TKA. Addressing these evidence gaps is crucial for the future development of more effective, efficient, and patient-friendly wound care strategies. Future research should prioritize these areas, focusing on comparative effectiveness studies and further developing clear guidelines for the use of emerging technologies. Bridging these gaps has the potential to improve patient outcomes, reduce complications, and elevate the overall success rate of TKA surgeries.

Concepts for the development of person-centred, digitally-enabled, Artificial Intelligence-assisted ARIA care pathways (ARIA 2024).

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own life based on their lived experiences. Improving healthcare safety, quality and coordination, as well as quality of life, are important aims in the care of patients with chronic conditions. Person-centred care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (i) digital care pathways for rhinitis and asthma multimorbidity and (ii) digitally-enabled person-centred care (1). It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally-enabled, patient-centred care. The paper includes (i) Allergic Rhinitis and its Impact on Asthma (ARIA), a two-decade journey, (ii) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (iii) mHealth impact on airway diseases, (iv) from guidelines to digital care pathways, (v) embedding Planetary Health, (vi) novel classification of rhinitis and asthma, (vi) embedding real-life data with population-based studies, (vii) the ARIA-EAACI strategy for the management of airway diseases using digital biomarkers, (viii) Artificial Intelligence, (ix) the development of digitally-enabled ARIA Person-Centred Care and (x) the political agenda. The ultimate goal is to propose ARIA 2024 guidelines centred around the patient in order to make them more applicable and sustainable.

TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication.

SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. We identified the host E3-ubiquitin ligase TRIM7 as an inhibitor of apoptosis and SARS-CoV-2 replication via ubiquitination of the viral membrane (M) protein. Trim7 -/- mice exhibited increased pathology and virus titers associated with epithelial apoptosis and dysregulated immune responses. Mechanistically, TRIM7 ubiquitinates M on K14, which protects cells from cell death. Longitudinal SARS-CoV-2 sequence analysis from infected patients revealed that mutations on M-K14 appeared in circulating variants during the pandemic. The relevance of these mutations was tested in a mouse model. A recombinant M-K14/K15R virus showed reduced viral replication, consistent with the role of K15 in virus assembly, and increased levels of apoptosis associated with the loss of ubiquitination on K14. TRIM7 antiviral activity requires caspase-6 inhibition, linking apoptosis with viral replication and pathology.

Dependence on mitochondrial respiration of malignant T cells reveals a new therapeutic target for angioimmunoblastic T-cell lymphoma.

Cancer metabolic reprogramming has been recognized as one of the cancer hallmarks that promote cell proliferation, survival, as well as therapeutic resistance. Up-to-date regulation of metabolism in T-cell lymphoma is poorly understood. In particular, for human angioimmunoblastic T-cell lymphoma (AITL) the metabolic profile is not known. Metabolic intervention could help identify new treatment options for this cancer with very poor outcomes and no effective medication. Transcriptomic analysis of AITL tumor cells, identified that these cells use preferentially mitochondrial metabolism. By using our preclinical AITL mouse model, mimicking closely human AITL features, we confirmed that T follicular helper (Tfh) tumor cells exhibit a strong enrichment of mitochondrial metabolic signatures. Consistent with these results, disruption of mitochondrial metabolism using metformin or a mitochondrial complex I inhibitor such as IACS improved the survival of AITL lymphoma-bearing mice. Additionally, we confirmed a selective elimination of the malignant human AITL T cells in patient biopsies upon mitochondrial respiration inhibition. Moreover, we confirmed that diabetic patients suffering from T-cell lymphoma, treated with metformin survived longer as compared to patients receiving alternative treatments. Taking together, our findings suggest that targeting the mitochondrial metabolic pathway could be a clinically efficient approach to inhibit aggressive cancers such as peripheral T-cell lymphoma.

Total knee replacement with an accelerometer-based, hand-held navigation system improves knee alignment: reliable in all patients.

BACKGROUND: Achieving adequate alignment has traditionally been an important goal in total knee arthroplasty to achieve long-term implant survival. While accelerometer-based hand-held navigation systems (ABN) has been introduced as a way to achieve alignment, there is a limited body of evidence on its accuracy, especially in patients under 65 years with differing etiologies for knee arthritis. This study aimed to assess the precision of a specific ABN system in restoring the mechanical axis and report surgical variables and complications, with particular attention to younger patients. METHODS: We conducted a retrospective review of 310 primary TKA performed with ABN from May 2016 to February 2021. The mean patient age was 67.4 (SD 8.9) years, with 43% under 65 years and mean body mass index of 33.2 (SD 6.8). The average surgical time was 96.8 min (57-171) and the average follow-up was 3.3 years (1.9-6.7). Data regarding length of stay, pain, range of motion (ROM), complications, and reinterventions were collected from the institutional joint arthroplasty registry and the medical records. Preoperative mechanical axis measurements and postoperative radiological data, including mechanical axis, component alignment and mechanical alignment outliers were analyzed. RESULTS: The mean preoperative mechanical axis was 175.4° (SD 7.6), with 248 knees (80%) in preoperative varus. The mean postoperative mechanical axis was 179.5° (SD 1.96) with 98% of knees falling within ± 3° of the neutral mechanical axis. Only 6 knees (2 varus, 4 valgus) fell outside the ± 3° range. And 3 knees (1 varus, 2 valgus) fell outside the ± 5° range. In the sagittal plane, 296 knees (95.5%) knees were within ± 3° of goal of 3 degrees of femoral flexion and 302 (97.4%) knees were within ± 2° of goal 1° of slope for tibial component. Far outliers (alignment outside ± 5° of targeted position) were found in 3 knees. Factors such as posttraumatic arthrosis, previous surgery, presence of retained hardware, and age below 65 years were not associated with increase in alignment outliers and far outliers. No complications related to the navigation system were observed. There were 22 complications and 20 reoperations, including 2 revisions for periprosthetic joint infection and 1 revision for flexion instability. Patients that required knee manipulation achieved an ultimate flexion of 110° (SD 14.1). CONCLUSIONS: The ABN system proved to be user-friendly and accurate in reducing alignment outliers in both coronal and sagittal planes in all patient populations. It offers a straightforward navigation solution while preserving surgeon autonomy and the use of traditional surgical tools. These findings advocate for the integration of this navigation system as a valuable tool to enhance the precision of TKA surgery in all patient groups.

Metabolically active neutrophils represent a permissive niche for Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb)-infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection. Using single-cell metabolic and transcriptional analyses, we found that neutrophils in the Mtb-infected lung displayed elevated mitochondrial metabolism, which was largely attributed to the induction of activated neutrophils with enhanced metabolic activities. The activated neutrophil subpopulation was also identified in the lung granulomas from Mtb-infected non-human primates. Functionally, activated neutrophils harbored more viable bacteria and displayed enhanced lipid uptake and accumulation. Surprisingly, we found that interferon-γ promoted the activation of lung neutrophils during Mtb infection. Lastly, perturbation of lipid uptake pathways selectively compromised Mtb survival in activated neutrophils. These findings suggest that neutrophil heterogeneity and metabolic diversity are key to their permissiveness for Mtb and that metabolic pathways in neutrophils represent potential host-directed therapeutics in TB.

Peri-Operative Management of Periacetabular Osteotomy: A Report of Current Practices from the Anchor Group, Supporting Literature, and Areas for Future Investigation.

Background: Periacetabular osteotomy (PAO) is a well-established surgical treatment for hip dysplasia, but very few studies report the impact of peri-operative management strategies on early pain and function. The purpose of this study is to describe peri-operative management variability among a group of experienced surgeons and review the literature supporting these practice patterns. Methods: We surveyed 16 surgeons that perform PAO to document various aspects of peri-operative management at four stages: pre-operative, intra-operative, post-operative in the hospital, and at discharge. Our goal was to report current surgical pain management strategies, adjunct medications, type of anesthesia, deep venous thrombosis and heterotopic ossification prophylaxis strategies, initiation of physical therapy, and use of continuous passive motion (CPM). We reviewed current literature to identify studies supporting these perioperative strategies and identify knowledge gaps that would benefit from further investigation. Results: Of the 16 surgeons surveyed, 75% had been in practice greater than 10 years and most had not altered their post-operative protocol for more than 3 years. 15/16 surgeons felt that length of stay could be reduced at their institution with improved peri-operative pain management. 6/16 were considering or had already implemented outpatient PAO as a part of their practice. We found significant variability in the pain medications provided at all peri-operative stages. 14/16 utilized general anesthesia, and many utilized epidural or peripheral nerve blocks. 6/16 surgeons utilized surgical field block (also referred to as periarticular block). These surgeons advocated that surgical field block was an effective intervention with no/minimal complication risk. There is very little literature critically evaluating efficacy of these perioperative management strategies for PAO. Conclusion: There is significant practice variability in peri-operative management of PAO surgery. We report various strategies utilized by a group of experienced surgeons and review supporting literature. There are significant knowledge gaps in best surgical pain management strategies, adjunct medications, surgical field blocks, and use of CPM that need further investigation. Level of Evidence: IV.

Elevated glycolytic metabolism of monocytes limits the generation of HIF1A-driven migratory dendritic cells in tuberculosis.

During tuberculosis (TB), migration of dendritic cells (DCs) from the site of infection to the draining lymph nodes is known to be impaired, hindering the rapid development of protective T-cell-mediated immunity. However, the mechanisms involved in the delayed migration of DCs during TB are still poorly defined. Here, we found that infection of DCs with Mycobacterium tuberculosis (Mtb) triggers HIF1A-mediated aerobic glycolysis in a TLR2-dependent manner, and that this metabolic profile is essential for DC migration. In particular, the lactate dehydrogenase inhibitor oxamate and the HIF1A inhibitor PX-478 abrogated Mtb-induced DC migration in vitro to the lymphoid tissue-specific chemokine CCL21, and in vivo to lymph nodes in mice. Strikingly, we found that although monocytes from TB patients are inherently biased toward glycolysis metabolism, they differentiate into poorly glycolytic and poorly migratory DCs compared with healthy subjects. Taken together, these data suggest that because of their preexisting glycolytic state, circulating monocytes from TB patients are refractory to differentiation into migratory DCs, which may explain the delayed migration of these cells during the disease and opens avenues for host-directed therapies for TB.

Mathematical modeling for estimating influenza vaccine efficacy: A case study of the Valencian Community, Spain.

Vaccine efficacy and its quantification is a crucial concept for the proper design of public health vaccination policies. In this work we proposed a mathematical model to estimate the efficacy of the influenza vaccine in a real-word scenario. In particular, our model is a SEIR-type epidemiological model, which distinguishes vaccinated and unvaccinated populations. Mathematically, its dynamics is governed by a nonlinear system of ordinary differential equations, where the non-linearity arises from the effective contacts between susceptible and infected individuals. Two key aspects of this study is that we use a vaccine distribution over time that is based on real data specific to the elderly people in the Valencian Community and the calibration process takes into account that over one influenza season a specific proportion of the population becomes infected with influenza. To consider the effectiveness of the vaccine, the model incorporates a parameter, the vaccine attenuation factor, which is related with the vaccine efficacy against the influenza virus. With this framework, in order to calibrate the model parameters and to obtain an influenza vaccine efficacy estimation, we considered the 2016-2017 influenza season in the Valencian Community, Spain, using the influenza reported cases of vaccinated and unvaccinated. In order to ensure the model identifiability, we choose to deterministically calibrate the parameters for different scenarios and we find the one with the minimum error in order to determine the vaccine efficacy. The calibration results suggest that the influenza vaccine developed for 2016-2017 influenza season has an efficacy of approximately 76.7%, and that the risk of becoming infected is five times higher for an unvaccinated individual in comparison with a vaccinated one. This estimation partially agrees with some previous studies related to the influenza vaccine. This study presents a new integrated mathematical approach to study the influenza vaccine efficacy and gives further insight into this important public health topic.

Potentiation of the Antimicrobial Effect of Oxytetracycline Combined with Cinnamon, Clove, Oregano, and Red Thyme Essential Oils against MDR Salmonella enterica Strains.

Tetracyclines have a high resistance percentage in Salmonella spp. of both human and animal origin. Essential oils, such as cinnamon (Cinnamomum zeylanicum), clove (Eugenia caryophyllata), oregano (Origanum vulgare), and red thyme (Thymus zygis), have shown bactericidal activity against this bacterium. However, in many cases, the minimum inhibitory concentration (MIC) exceeds the cytotoxicity limits. The objective of this study was to assess the in vitro efficacy of combining oxytetracycline with essential these oils against field multidrug-resistant (MDR) Salmonella enterica strains. The MIC of each product was determined using the broth microdilution method. The interaction was evaluated using the checkerboard method, by means of the fractional inhibitory concentration index (FICindex) determination. The results showed a positive interaction (synergy and additivity) between oxytetracycline and the four oils tested, resulting in a reduction in both products' MICs by 2 to 4 times their initial value, in the case of oils, and by 2 to 1024 times in the case of the antibiotic. The combination of oxytetracycline and cinnamon achieved the best results (FICindex 0.5), with a decrease in the antibiotic effective concentration to below the sensitivity threshold (MIC of the combined oxytetracycline 0.5 µg/mL). There was no antagonistic effect in any case, although differences in response were observed depending on the bacterial strain. The results of this study suggest that combining oxytetracycline with cinnamon oil could be an effective alternative for controlling tetracycline-resistant strains of Salmonella. However, its individual use should be further evaluated through in vitro susceptibility tests.

Osteochondral Allograft Transplantation for the Treatment of an Acetabular Defect: A Case Report.

CASE: A 20-year-old woman presented with a unipolar, 1.8 × 1.8-cm osteochondral defect of the left acetabulum. Osteochondral allograft transplantation was performed using a medial tibial plateau allograft resulting in excellent clinical outcomes across 4 different outcome scores and maintenance of the joint space at 4.3 years postoperatively. CONCLUSION: Although previous literature has demonstrated long-term clinical success of osteochondral allograft transplantation in knee, excellent clinical outcomes can also be obtained in the hip. Thus, osteochondral allograft transplantation may be a viable treatment option for adolescents and young adults with concomitant cartilage and subchondral bone hip defects.

A Randomized Clinical Trial of Direct Anterior Versus Mini-Posterior Total Hip Arthroplasty: Small, Early Functional Differences Did Not Lead to Meaningful Clinical Differences at 7.5 Years.

BACKGROUND: Our previously reported randomized clinical trial of direct anterior approach (DAA) versus mini-posterior approach (MPA) total hip arthroplasty showed slightly faster initial recovery for patients who had a DAA and no differences in complications or clinical or radiographic outcomes beyond 8 weeks. The aims of the current study were to determine if early advantages of DAA led to meaningful clinical differences beyond 5 years and to identify differences in midterm complications. METHODS: Of the 101 original patients, 93 were eligible for follow-up at a mean of 7.5 years (range, 2.1 to 10). Clinical outcomes were compared with Harris Hip, 12-Item Short Form Health Survey, and Hip Disability and Osteoarthritis Outcomes Scores (HOOS) scores and subscores, complications, reoperations, and revisions. RESULTS: Harris Hip scores were similar (95.3 ± 6.0 versus 93.5 ± 10.3 for DAA and MPA, respectively, P = .79). The 12-Item Short Form Health Survey physical and mental scores were similar (46.2 ± 9.3 versus 46.2 ± 10.6, P = .79, and 52.3 ± 7.1 versus 55.2 ± 4.5, P = .07 in the DAA and MPA groups, respectively). The HOOS scores were similar (97.4 ± 7.9 versus 96.3 ± 6.7 for DAA and MPA, respectively, P = .07). The HOOS quality of life subscores were 96.9 ± 10.8 versus 92.3 ± 16.0 for DAA and MPA, respectively (P = .046). No clinical outcome met the minimally clinically important difference. There were 4 surgical complications in the DAA group (1 femoral loosening requiring revision, 1 dislocation treated closed, and 2 wound dehiscences requiring debridement), and 6 surgical complications in the MPA group (3 dislocations, 2 treated closed, and 1 revised to dual mobility; 2 intraoperative fractures treated with a cable; and 1 wound dehiscence treated nonoperatively). CONCLUSIONS: At a mean of 7.5 years, this randomized clinical trial demonstrated no clinically meaningful differences in outcomes, complications, reoperations, or revisions between DAA and MPA total hip arthroplasty. LEVEL OF EVIDENCE: IV.

Diaphyseal Impaction Grafting Combined with Metaphyseal Cones: Outcomes in 88 Revision Total Knee Arthroplasties.

BACKGROUND: Metaphyseal cones with cemented stems can be successfully utilized in most revision total knee arthroplasties (TKAs). However, if the diaphysis has been previously violated, fixation of the cemented stem, which is important for cone ingrowth and construct survival, can be compromised. The initial results of our novel technique combining diaphyseal impaction bone-grafting with a metaphyseal cone were promising but required additional study. The purpose of the present study was to assess results of this technique in a larger cohort. METHODS: A metaphyseal cone combined with diaphyseal impaction grafting and a cemented stem was utilized in 88 revision TKAs at our institution, including 35 from our prior study. The mean age at the time of revision was 67 years, and 67% of patients were male. Patients had had a mean of 4 prior knee arthroplasty procedures. The 2 most common reasons for revision were aseptic loosening (78%) and 2-stage reimplantation for periprosthetic joint infection (PJI) (19%). The mean follow-up was 4 years. RESULTS: At the time of the latest follow-up, no cone-impaction grafting constructs required re-revision for aseptic loosening. Five-year survivorship free from any revision of the cone-impaction grafting construct and free from any reoperation was 95% and 65%, respectively. A total of 25 knees (28%) underwent reoperation, with the 2 most common indications being PJI and periprosthetic fracture. All cones were osseointegrated, and all bone graft appeared stable or incorporated. One patient had radiographic evidence of tibial component loosening despite a well-fixed cone; however, this patient was asymptomatic and had not undergone revision at 9 years. CONCLUSIONS: When presented with a sclerotic, polished diaphyseal canal with deficient cancellous bone and concomitant metaphyseal bone loss, our technique of combining diaphyseal impaction grafting with a metaphyseal cone proved extremely durable in this larger series of patients. No cone-impaction grafting constructs required re-revision for aseptic loosening. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Relevance of individual bronchial symptoms for asthma diagnosis and control in patients with rhinitis: A MASK-air study.

RATIONALE: It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. OBJECTIVES: To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. METHODS: In this cross-sectional study, we assessed real-world data using the MASK-air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e-DASTHMA score). Results were validated in a sample of patients with a physician-established diagnosis of asthma. MEASUREMENT AND MAIN RESULTS: We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e-DASTHMA. Consistent results were observed when assessing patients with a physician-made diagnosis of asthma. CONCLUSIONS: Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.

Assessing the negative impact of chlorantraniliprole, isoxaflutole, and simazine pesticides on phospholipid membrane models and tilapia gill tissues.

The indiscriminate and, very often, incorrect use of pesticides in Brazil, as well as in other countries, results in severe levels of environmental pollution and intoxication of human life. Herein, we studied plasma membrane models (monolayer and bilayer) of the phospholipid Dioleoyl-sn-glycerol-3-phosphocholine (DOPC) using Langmuir films, and large (LUVs) and giant (GUVs) unilamellar vesicles, to determine the effect of the pesticides chlorantraniliprole (CLTP), isoxaflutole (ISF), and simazine (SMZ), used in sugarcane. CLTP affects the lipid organization of the bioinspired models of DOPC π-A isotherms, while ISF and SMZ pesticides significantly affect the LUVs and GUVs. Furthermore, the in vivo study of the gill tissue in fish in the presence of pesticides (2.0 × 10-10 mol/L for CLTP, 8.3 × 10-9 mol/L for ISF, and SMZ at 9.9 × 10-9 mol/L) was performed using optical and fluorescence images. This investigation was motivated by the gill lipid membranes, which are vital for regulating transporter activity through transmembrane proteins, crucial for maintaining ionic balance in fish gills. In this way, the presence of phospholipids in gills offers a model for understanding their effects on fish health. Histological results show that exposure to CLTP, ISF, and SMZ may interfere with vital gill functions, leading to respiratory disorders and osmoregulation dysfunction. The results indicate that exposure to pesticides caused severe morphological alterations in fish, which could be correlated with their impact on the bioinspired membrane models. Moreover, the effect does not depend on the exposure period (24h and 96h), showing that animals exposed to pesticides for a short period suffer irreparable damage to gill tissue. In summary, we can conclude that the harm caused by pesticides, both in membrane models and in fish gills, occurs due to contamination of the aquatic system with pesticides. Therefore, water quality is vital for the preservation of ecosystems.

Novel portable hypothermic machine perfusion preservation device enhances cardiac viability of donated human hearts.

Introduction: Heart transplant remains the gold standard treatment for patients with advanced heart failure. However, the list of patients waiting for a heart transplant continues to increase. We have developed a portable hypothermic oxygenated machine perfusion device, the VP.S ENCORE®, to extend the allowable preservation time. The purpose of this study was to test the efficacy of the VP.S. ENCORE® using deceased donors derived hearts. Methods: Hearts from brain-dead donors not utilized for transplant (n = 11) were offered for research from the Texas Organ Sharing Alliance (TOSA), South and Central Texas' Organ Procurement Organization (OPO) and were preserved in the VP.S ENCORE® for 4 (n = 2), 6 (n = 3), and 8 (n = 3) hours or were kept in static cold storage (SCS) (n = 3). After preservation, the hearts were placed in an isolated heart Langendorff model for reperfusion and evaluated for cardiac function. Results: The mean donor age was 37.82 ± 12.67 with the youngest donor being 19 and the oldest donor being 58 years old. SCS hearts mean weight gain (%) was -1.4 ± 2.77, while perfused at 4 h was 5.6 ± 6.04, perfused at 6 h 2.1 ± 6.04, and 8 h was 7.2 ± 10.76. Venous and arterial lactate concentrations were less than 2.0 mmol/L across all perfused hearts. Left ventricular contractility (+dPdT, mmHg/s) for 4 h (1,214 ± 1,064), 6 (1,565 ± 141.3), and 8 h (1,331 ± 403.6) were within the range of healthy human heart function. Thus, not significant as compared to the SCS group (1,597 ± 342.2). However, the left ventricular relaxation (mmHg/s) was significant in 6-hour perfused heart (p < 0.05) as compared to SCS. Gene expression analysis of inflammation markers (IL-6, IL-1ß) showed no significant differences between SCS and perfused hearts, but a 6-hour perfusion led to a downregulated expression of these markers. Discussion: The results demonstrate that the VP.S ENCORE® device enhances cardiac viability and exhibits comparable cardiac function to a healthy heart. The implications of these findings suggest that the VP.S ENCORE® could introduce a new paradigm in the field of organ preservation, especially for marginal hearts.

Hemoglobin Drop is Associated with Early Post-operative Stroke Following Revascularization Surgery for Moyamoya Disease.

BACKGROUND: Postoperative stroke is a potentially devastating neurological complication following surgical revascularization for Moyamoya disease. We sought to evaluate whether peri-operative hemoglobin levels were associated with the risk of early post-operative stroke following revascularization surgery in adult Moyamoya patients. METHODS: Adult patients having revascularization surgeries for Moyamoya disease between 1999-2022 were identified through single institutional retrospective review. Logistic regression analysis was used to test for the association between hemoglobin drop and early postoperative stroke. RESULTS: In all, 106 revascularization surgeries were included in the study. A stroke occurred within 7 days after surgery in 9.4% of cases. There were no significant associations between the occurrence of an early postoperative stroke and patient age, gender, or race. Mean postoperative hemoglobin drop was greater in patients who suffered an early postoperative stroke compared with patients who did not (2.3±1.1 g/dL vs. 1.3±1.1 g/dL, respectively; P=0.034). Patients who experienced a hemoglobin drop post-operatively had 2.03 times greater odds (95% confidence interval, 1.06-4.23; P=0.040) of having a stroke than those whose hemoglobin levels were stable. Early postoperative stroke was also associated with an increase in length of hospital stay (P<0.001), discharge to a rehabilitation facility (P=0.014), and worse modified Rankin scale at 1 month (P=0.001). CONCLUSION: This study found a significant association between hemoglobin drop and early postoperative stroke following revascularization surgery in adult patients with Moyamoya disease. Based on our findings, it may be prudent to avoid hemoglobin drops in Moyamoya patients undergoing surgical revascularization.

Modular fluted tapered stems in two-stage reimplantation of previously infected total hip arthroplasties.

Aims: Uncemented implants are now commonly used at reimplantation of a two-stage revision total hip arthoplasty (THA) following periprosthetic joint infection (PJI). However, there is a paucity of data on the performance of the most commonly used uncemented femoral implants - modular fluted tapered (MFT) femoral components - in this setting. This study evaluated implant survival, radiological results, and clinical outcomes in a large cohort of reimplantation THAs using MFT components. Methods: We identified 236 reimplantation THAs from a single tertiary care academic institution from September 2000 to September 2020. Two designs of MFT femoral components were used as part of an established two-stage exchange protocol for the treatment of PJI. Mean age at reimplantation was 65 years (SD 11), mean BMI was 32 kg/m2 (SD 7), and 46% (n = 109) were female. Mean follow-up was seven years (SD 4). A competing risk model accounting for death was used. Results: The 15-year cumulative incidence of any revision was 24%. There were 48 revisions, with the most common reasons being dislocation (n = 25) and infection (n = 16). The 15-year cumulative incidence of any reoperation was 28%. Only 13 revisions involved the fluted tapered component (FTC), for a 15-year cumulative incidence of any FTC revision of 8%. Only two FTCs were revised for aseptic loosening, resulting in a 15-year cumulative incidence of FTC revision for aseptic loosening of 1%. Stem subsidence ≥ 5 mm occurred in 2% of unrevised cases. All stems were radiologically stable at most recent follow-up. Mean Harris Hip Score was 69 (SD 20) at most recent follow-up. Conclusion: This series demonstrated that MFT components were durable and reliable in the setting of two-stage reimplantation THA for infection. While the incidence of aseptic loosening was very low, the incidence of any revision was 24% at 15 years, primarily due to dislocation and recurrent PJI.