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Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S, and Novavax NVX-CoV2373 were examined longitudinally for 6 months 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though only detectable in 60-67% of subjects at 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in antibodies, while memory T and B cells were comparatively stable. These results may also be relevant for insights against other pathogens.
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Vacunas contra la COVID-19 , COVID-19 , Ad26COVS1 , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Humanos , Inmunidad Humoral , Memoria Inmunológica , SARS-CoV-2RESUMEN
Extraintestinal pathogenic Escherichia coli (ExPEC) is the leading cause of adult life-threatening sepsis and urinary tract infections (UTI). The emergence and spread of multidrug-resistant (MDR) ExPEC strains result in a considerable amount of treatment failure and hospitalization costs, and contribute to the spread of drug resistance amongst the human microbiome. Thus, an effective vaccine against ExPEC would reduce morbidity and mortality and possibly decrease carriage in healthy or diseased populations. A comparative genomic analysis demonstrated a gene encoding an invasin-like protein, termed sinH, annotated as an autotransporter protein, shows high prevalence in various invasive ExPEC phylogroups, especially those associated with systemic bacteremia and UTI. Here, we evaluated the protective efficacy and immunogenicity of a recombinant SinH-based vaccine consisting of either domain-3 or domains-1,2, and 3 of the putative extracellular region of surface-localized SinH. Immunization of a murine host with SinH-based antigens elicited significant protection against various strains of the pandemic ExPEC sequence type 131 (ST131) as well as multiple sequence types in two distinct models of infection (colonization and bacteremia). SinH immunization also provided significant protection against ExPEC colonization in the bladder in an acute UTI model. Immunized cohorts produced significantly higher levels of vaccine-specific serum IgG and urinary IgG and IgA, findings consistent with mucosal protection. Collectively, these results demonstrate that autotransporter antigens such as SinH may constitute promising ExPEC phylogroup-specific and sequence-type effective vaccine targets that reduce E. coli colonization and virulence.
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Bacteriemia , Infecciones por Escherichia coli , Escherichia coli Patógena Extraintestinal , Infecciones Urinarias , Animales , Humanos , Ratones , Escherichia coli , Sistemas de Secreción Tipo V/genética , Infecciones por Escherichia coli/prevención & control , Escherichia coli Patógena Extraintestinal/genética , Vacunación , Factores de Virulencia/genética , Vacunas Sintéticas , Infecciones Urinarias/prevención & control , Bacteriemia/prevención & control , Inmunoglobulina G/farmacologíaRESUMEN
Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of worldwide morbidity and mortality, the top cause of antimicrobial-resistant (AMR) infections, and the most frequent cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The development of an effective and universal vaccine is complicated by this pathogen's pan-genome, its ability to mix and match virulence factors and AMR genes via horizontal gene transfer, an inability to decipher commensal from pathogens, and its intimate association and co-evolution with mammals. Using a pan virulome analysis of >20,000 sequenced E. coli strains, we identified the secreted cytolysin α-hemolysin (HlyA) as a high priority target for vaccine exploration studies. We demonstrate that a catalytically inactive pure form of HlyA, expressed in an autologous host using its own secretion system, is highly immunogenic in a murine host, protects against several forms of ExPEC infection (including lethal bacteremia), and significantly lowers bacterial burdens in multiple organ systems. Interestingly, the combination of a previously reported autotransporter (SinH) with HlyA was notably effective, inducing near complete protection against lethal challenge, including commonly used infection strains ST73 (CFT073) and ST95 (UTI89), as well as a mixture of 10 of the most highly virulent sequence types and strains from our clinical collection. Both HlyA and HlyA-SinH combinations also afforded some protection against UTI89 colonization in a murine UTI model. These findings suggest recombinant, inactive hemolysin and/or its combination with SinH warrant investigation in the development of an E. coli vaccine against invasive disease.
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Infecciones por Escherichia coli , Proteínas de Escherichia coli , Vacunas contra Escherichia coli , Escherichia coli Patógena Extraintestinal , Proteínas Hemolisinas , Animales , Escherichia coli Patógena Extraintestinal/genética , Escherichia coli Patógena Extraintestinal/inmunología , Infecciones por Escherichia coli/prevención & control , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/inmunología , Ratones , Proteínas Hemolisinas/inmunología , Proteínas Hemolisinas/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/inmunología , Vacunas contra Escherichia coli/inmunología , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/genética , Femenino , Factores de Virulencia/genética , Factores de Virulencia/inmunología , Sistemas de Secreción Tipo V/inmunología , Sistemas de Secreción Tipo V/genética , Modelos Animales de Enfermedad , HumanosRESUMEN
Diabetes mellitus and obesity are growing health concerns. New pharmacologic interventions have recently begun to play a more notable role in the treatment pathway of these separate but related conditions. In particular, glucagon-like peptide-1 receptor agonists, such as semaglutides (Ozempic, Wegovy) and tirzepatide (Mounjaro), and sodium glucose co-transporter 2 inhibitors, such as dapagliflozin (Farxiga) and empagliflozin (Jardiance), have emerged as treatment options. Multiple clinical trials have demonstrated their efficacy in regulating metabolism, improving glycemic control, and managing long-term weight reduction. However, glucagon-like peptide-1 receptor agonists have also been associated with gastrointestinal side effects, including delayed gastric emptying as well as regurgitation and aspiration during general anesthesia or deep sedation, and sodium glucose co-transporter 2 inhibitors have been associated with severe diabetic ketoacidosis. Therefore, discontinuation of these medications before surgery is imperative. Given the popularity of these medications among the general public, it is essential for hand surgeons, to understand how to appropriately manage them perioperatively. The objective of this article was to review these new diabetes mellitus and weight loss medications, including their mechanisms of action, indications for use, and perioperative management guidelines. Additionally, we will take this opportunity to review perioperative guidelines for other common medications relevant to patients undergoing procedures involving the hand and upper extremity such as antithrombotic medications and rheumatoid arthritis-related immunosuppressive medications. Finally, we will describe how the electronic medical record system can be used to optimize perioperative medication management in this population.
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OBJECTIVE: To understand whether reduced lengths of stay after kidney transplantation were associated with excess health care utilization in the first 90 days or long-term graft and patient survival outcomes. BACKGROUND: Reducing length of stay after kidney transplant has an unknown effect on post-transplant health care utilization. We studied this association in a cohort of 1001 consecutive kidney transplants. METHODS: We retrospectively reviewed 2011-2015 data from a prospectively-maintained kidney transplant database from a single center. RESULTS: A total of 1001 patients underwent kidney transplant, and were dismissed from the hospital in 3 groups: Early [≤2 days] (19.8%), Normal [3-7 days] (79.4%) and Late [>7 days] (3.8%). 34.8% of patients had living donor transplants (Early 51%, Normal 31.4%, Late 18.4%, P < 0.001). Early patients had lower delayed graft function rates (Early 19.2%, Normal 32%, Late73.7%, P = 0.001). By the hospital dismissal group, there were no differences in readmissions or emergency room visits at 30 or 90 days. Glomerular filtration rate at 12 months and rates of biopsy-proven acute rejection were also similar between groups. The timing of hospital dismissal was not associated with the risk-adjusted likelihood of readmission. Early and Normal patients had similar graft and patient survival. Late dismissal patients, who had higher rates of cardiovascular complications, had significantly higher late mortality versus Normal dismissal patients in unadjusted and risk-adjusted models. CONCLUSION: Dismissing patients from the hospital 2 days after kidney transplant is safe, feasible, and improves value. It is not associated with excess health care utilization or worse short or long-term transplant outcomes.
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Trasplante de Riñón , Tiempo de Internación/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Alta del Paciente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Pesticide management is a crucial issue for sustainable agriculture and food safety. The high-resolution mass spectrometry (HRMS)-based screening method has become a popular choice to monitor pesticide residues in foods and the environment. Data-independent acquisition (DIA) was the first option allowing for this type of analysis due to the wide compound coverage compared to traditional targeted analysis using triple-quadrupole tandem mass spectrometry (QqQ). However, a higher false-positive detection rate is a critical shortcoming in DIA. To overcome this concern, a rigorous method is needed to determine the reliable information acquired from DIA screening. A systematic strategy, traceable and integrated pesticide screening (TIPS), was proposed in this study to comprehensively monitor pesticides and metabolites in a complex tea matrix, avoiding false-positive detection. A total of 900 pesticides were added to an in-house database and evaluated through precision tests, which showed good repeatability and reproducibility. One hundred pesticides and metabolites were detected and confirmed by TIPS in 98 commercial tea samples. In addition to the authorized pesticides that could be detected in TIPS, chlorfluazuron, diafenthiuron, and tolfenpyrad, which are pesticides not allowed to be used in tea farming, were frequently found in this study. In addition, dinotefuran DN and fenbuconazole metabolites RH-9129 and/or RH-9130 were tentatively identified in the archived data using retrospective analysis. The HRMS-based data in TIPS could be a record platform for tracing novel or emerging contaminants not initially targeted in samples. TIPS, a novel strategy, has great potential for rapidly conducting a risk assessment of unexpected pesticides in food.
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Residuos de Plaguicidas , Plaguicidas , Plaguicidas/análisis , Estudios Retrospectivos , Reproducibilidad de los Resultados , Residuos de Plaguicidas/análisis , Espectrometría de Masas en Tándem/métodos , Té/químicaRESUMEN
BACKGROUND: Centers discard high kidney donor profile index (KDPI) allografts, potentially related to delayed graft function and prolonged hospital use by kidney transplant recipients (KTR). We sought to determine whether high KDPI KTRs have excess health care utilization. METHODS: We conducted a retrospective cohort study from a high-volume center analyzing KTRs from January 3, 2011 to April 12, 2015 (n = 652). We measured differences in hospital use, emergency visits, and outpatient visits within the first 90 days between low (≤85%) versus high KDPI (>85%) KTRs, as well as long-term graft function and patient survival. RESULTS: High (n = 107) and low KDPI (n = 545) KTRs had similar length of stay (median = 3 days, P = .66), and readmission rates at 7, 30, and 90 days after surgery (all, P > .05). High KDPI kidneys were not associated with excess utilization of the hospital, emergency services, outpatient transplant clinics, or ambulatory infusion visits on univariate or multivariate analysis (all, P > .05). Low KDPI KTRs had significantly better eGFR at 2 years (Low vs. High KDPI: 60.35 vs. 41.54 ml/min, P < .001), but similar 3-year patient and graft survival (both, P > .09). CONCLUSIONS: High and low KDPI KTRs demonstrated similar 90-day risk-adjusted health care utilization, which should encourage use of high KDPI kidneys.
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Trasplante de Riñón , Obtención de Tejidos y Órganos , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Aceptación de la Atención de Salud , Estudios Retrospectivos , Donantes de TejidosRESUMEN
PURPOSE: Partial rotator cuff tears can cause shoulder pain and dysfunction and are more common than complete tears. However, few studies examine partial injuries in small animals and, therefore a robust, clinically relevant model may be lacking. This study aimed to fully characterize the established rat model of partial rotator cuff injury over time and determine if it models human partial rotator cuff tears. METHODS: We created a full-thickness, partial-width injury at the supraspinatus tendon-bone interface bilaterally in 31 Sprague-Dawley rats. Rats were euthanized immediately, and at 2-, 3-, 4-, and 8-weeks after surgery. Fourteen intact shoulders were used as controls. Samples were assessed biomechanically, histologically, and morphologically. RESULTS: Biomechanically, load to failure in controls and 8 weeks after injury was significantly greater than immediately and 3 weeks after injury. Load to failure at 8 weeks was comparable to control. However, the locations of failure were different between intact shoulders and partially injured samples. Bone mineral density at 8 weeks was significantly greater than that at 2 and 3 weeks. Although no animals demonstrated propagation to complete tear and the injury site remodeled histologically, the appearance at 8 weeks was not identical to that in the controls. CONCLUSIONS: The biomechanical properties and bone quality decreased after the injury and was restored gradually over time with full restoration by 8 weeks after injury. However, the findings were not equivalent to the intact shoulder. This study demonstrated the limitations of the current model in its application to long-term outcome studies, and the need for better models that can be used to assess chronic partial rotator cuff injuries. CLINICAL RELEVANCE: There is no small animal model that mimics human chronic partial rotator cuff tears, which limits our ability to improve care for this common condition.
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Airborne spread of coronavirus disease 2019 (COVID-19) by infectious aerosol is all but certain. However, easily implemented approaches to assess the actual environmental threat are currently unavailable. We present a simple approach with the potential to rapidly provide information about the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the atmosphere at any location. We used a portable dehumidifier as a readily available and affordable tool to collect airborne virus in the condensate. The dehumidifiers were deployed in selected locations of a hospital ward with patients reporting flu-like symptoms which could possibly be due to COVID-19 over three separate periods of one week. Samples were analyzed frequently for both virus envelope protein and SARS-CoV-2 RNA. In several samples across separate deployments, condensate from dehumidifiers tested positive for the presence of SARS-CoV-2 antigens as confirmed using two independent assays. RNA was detected, but not attributable to SARS-CoV-2. We verified the ability of the dehumidifier to rapidly collect aerosolized sodium chloride. Our results point to a facile pool testing method to sample air in any location in the world and assess the presence and concentration of an infectious agent to obtain quantitative risk assessment of exposure, designate zones as "hot spots" and minimize the need for individual testing which may often be time consuming, expensive, and laborious.
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COVID-19/genética , ARN Viral , SARS-CoV-2 , Manejo de Especímenes , COVID-19/epidemiología , COVID-19/transmisión , Humanos , ARN Viral/química , ARN Viral/genética , SARS-CoV-2/química , SARS-CoV-2/genéticaRESUMEN
Background: Epinephrine is the first-line therapy for patients with anaphylaxis, and intramuscular (IM) delivery is shown to be superior to subcutaneous (SC) delivery. There currently is no consensus on the ideal body position for epinephrine autoinjector (EAI) administration. Objective: We designed this study to investigate whether SC tissue depth (SCTD) is affected by body position (e.g., standing, sitting, supine), which can potentially impact delivery of EAI into the IM space. Methods: Volunteer adults (ages ≥ 18 years) from a military medical treatment facility in the United States were recruited to participate in this study. SCTD of the vastus lateralis was measured via ultrasound at standing, sitting, and supine body positions. Subjects' age, sex, and body mass index (BMI) were collected. Statistical analysis was performed to compare average SCTD between body positions, sex, and BMI. Results: An analysis of variance of 51 participants (33 men and 18 women) did not reveal statistically significant difference in SCTD among standing, sitting, and supine body positions. It did show a significantly greater SCTD in women than in men (2.72 ± 1.36 cm versus 1.10 ± 0.38 cm; p < 0.001). There was no significant association observed between BMI and SCTD in this study. Conclusion: Body position did not seem to significantly change the distance between skin and thigh muscle in adults. This would suggest that there might not be an ideal body position for EAI administration. Therefore, in case of anaphylaxis, prompt administration of epinephrine is recommended at any position.
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Anafilaxia/tratamiento farmacológico , Epinefrina/administración & dosificación , Postura , Vasoconstrictores/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Epinefrina/uso terapéutico , Femenino , Voluntarios Sanos , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Autoadministración , Muslo , Vasoconstrictores/uso terapéuticoRESUMEN
BACKGROUND: ReSurge International is a nongovernmental organization that organizes surgical team trips to low- and middle-income countries. Cleft palate repair is commonly performed on these trips. A comprehensive cleft care program was implemented to help reduce postoperative palatal fistula rates. METHODS: A retrospective review of all patients undergoing cleft palate repair surgery with ReSurge International in Vietnam from 2013 through 2019 was performed. The cleft care program was implemented in 2018. This intervention involved preoperative education of patients and close postoperative monitoring. Critically, this program also provided closer access to providers. Subsequent follow-up was performed by a ReSurge physician. Parent-reported outcomes were assessed preoperatively and postoperatively using 5-point Likert-like survey questions. RESULTS: Two hundred three patients underwent cleft palate repair. The patients were older and of higher Veau classification than is usually seen in the United States. The palatal fistula rate in the preintervention group was 37.5% and 14.3% in the intervention group (P = 0.014). Patients without fistulas demonstrated improvements on parent-reported outcomes compared with those with fistulas, with food less likely to go up their nose (P < 0.001), less difficulty eating (P < 0.001), and more understandable speech (P = 0.015). CONCLUSIONS: Implementation of a comprehensive cleft palate program reduced postoperative fistula rates by more than 50%. Improvements in parent-reported outcomes were observed after surgery among patients without fistulas. The blueprint for improved outcomes in these more complex patients includes enhanced perioperative patient counseling, close follow-up, and maintenance of communication with patients.
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Fisura del Paladar , Fístula , Procedimientos de Cirugía Plástica , Fisura del Paladar/cirugía , Humanos , Lactante , Fístula Oral/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , VietnamRESUMEN
Chronic wounds are a prominent concern, accounting for $25 billion of health care costs annually. Biofilms have been implicated in delayed wound closure, but they are susceptible to developing antibiotic resistance and treatment options continue to be limited. A novel collagen-rich hydrogel derived from human extracellular matrix presents an avenue for treating chronic wounds by providing appropriate extracellular proteins for healing and promoting neovascularization. Using the hydrogel as a delivery system for localized secretion of a therapeutic dosage of antibiotics presents an attractive means of maximizing delivery while minimizing systemic side effects. We hypothesize that the hydrogel can provide controlled elution of antibiotics leading to inhibition of bacterial growth and disruption of biofilm formation. The rate of antibiotic elution from the collagen-rich hydrogel and the efficacy of biofilm disruption was assessed with Pseudomonas aeruginosa Bacterial growth inhibition, biofilm disruption, and mammalian cell cytotoxicity were quantified using in vitro models. The antibiotic-loaded hydrogel showed sustained release of antibiotics for up to 24 h at therapeutic levels. The treatment inhibited bacterial growth and disrupted biofilm formation at multiple time points. The hydrogel was capable of accommodating various classes of antibiotics and did not result in cytotoxicity in mammalian fibroblasts or adipose stem cells. The antibiotic-loaded collagen-rich hydrogel is capable of controlled antibiotic release effective for bacteria cell death without native cell death. A human-derived hydrogel that is capable of eluting therapeutic levels of antibiotic is an exciting prospect in the field of chronic wound healing.
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Antibacterianos , Hidrogeles , Animales , Antibacterianos/farmacología , Biopelículas , Colágeno , Humanos , Pseudomonas aeruginosaRESUMEN
BACKGROUND: As global rates of mortality decrease, rates of non-fatal injury have increased, particularly in low Socio-demographic Index (SDI) nations. We hypothesised this global pattern of non-fatal injury would be demonstrated in regard to bony hand and wrist trauma over the 27-year study period. METHODS: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 was used to estimate prevalence, age-standardised incidence and years lived with disability for hand trauma in 195 countries from 1990 to 2017. Individual injuries included hand and wrist fractures, thumb amputations and non-thumb digit amputations. RESULTS: The global incidence of hand trauma has only modestly decreased since 1990. In 2017, the age-standardised incidence of hand and wrist fractures was 179 per 100 000 (95% uncertainty interval (UI) 146 to 217), whereas the less common injuries of thumb and non-thumb digit amputation were 24 (95% UI 17 to 34) and 56 (95% UI 43 to 74) per 100 000, respectively. Rates of injury vary greatly by region, and improvements have not been equally distributed. The highest burden of hand trauma is currently reported in high SDI countries. However, low-middle and middle SDI countries have increasing rates of hand trauma by as much at 25%. CONCLUSIONS: Certain regions are noted to have high rates of hand trauma over the study period. Low-middle and middle SDI countries, however, have demonstrated increasing rates of fracture and amputation over the last 27 years. This trend is concerning as access to quality and subspecialised surgical hand care is often limiting in these resource-limited regions.
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Carga Global de Enfermedades , Traumatismos de la Mano , Traumatismos de la Muñeca , Muñeca , Amputación Quirúrgica , Femenino , Salud Global , Traumatismos de la Mano/cirugía , Humanos , Incidencia , Masculino , Prevalencia , Años de Vida Ajustados por Calidad de Vida , Traumatismos de la Muñeca/cirugíaRESUMEN
BACKGROUND: Epinephrine is the first-line therapy for patients with anaphylaxis, and intramuscular (IM) delivery is shownto be superior to subcutaneous (SC) delivery. There currently is no consensus on the ideal body position for epinephrine autoinjector (EAI) administration. OBJECTIVE: We designed this study to investigate whether SC tissue depth (SCTD) is affected by body position (e.g., standing, sitting, supine), which can potentially impact delivery of EAI into the IM space. METHODS: Volunteer adults (ages >/= 18 years) from a military medical treatment facility in the United States were recruitedto participate in this study. SCTD of the vastus lateralis was measured via ultrasound at standing, sitting, and supine bodypositions. Subjects' age, sex, and body mass index (BMI) were collected. Statistical analysis was performed to compare averageSCTD between body positions, sex, and BMI. RESULTS: An analysis of variance of 51 participants (33 men and 18 women) did not reveal statistically significant differencein SCTD among standing, sitting, and supine body positions. It did show a significantly greater SCTD in women than in men (2.72 +/- 1.36 cm versus 1.10 +/- 0.38 cm; p < 0.001). There was no significant association observed between BMI and SCTD in this study. CONCLUSION: Body position did not seem to significantly change the distance between skin and thigh muscle in adults. Thiswould suggest that there might not be an ideal body position for EAI administration. Therefore, in case of anaphylaxis, promptadministration of epinephrine is recommended at any position.
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BACKGROUND: Application of collagen products to wounds has been shown to improve wound healing. Using a collagen-based hydrogel (cHG) capable of cellular support previously developed by our laboratory, we hypothesize that our hydrogel will increase the speed of wound healing by providing a 3-dimensional framework for cellular support, increasing angiogenesis and cell-proliferation at the wound bed. METHODS: Two, 10-mm excisional wounds were created over the dorsum of 12 male, genetically modified Zucker diabetic rats. Wounds were splinted open to limit healing by wound contracture. One wound was treated with an occlusive dressing (OD), whereas the adjacent wound was treated with an OD plus cHG. Occlusive dressings were changed every other day. Hydrogel was applied on day 2 and every 4 days after until complete wound closure. Rate of wound closure was monitored with digital photography every other day. Wounds were harvested at days 10 and 16 for histological and immunohistochemical analysis. RESULTS: Wound closure was significantly faster in cHG-treated wounds compared with OD-treated wounds. By day 10, cHG-treated wounds achieved 63% wound closure, compared with 55% wound closure in OD-treated wounds (P < 0.05). By day 16, cHG-treated wounds achieved 84% wound closure, compared with 68% wound closure in OD-treated wounds (P < 0.05).Histologically, wound depth was not different between the cHG and OD groups on days 10 and 16. However, wound length was significantly less in the cHG group compared with the OD group (P < 0.05) consistent with digital photographic analysis. Immunohistochemical analysis for RECA-1 demonstrated that blood vessel density in the wound bed was 2.3 times higher in the cHG group compared with the OD group (P = 0.01) on day 16. Cell proliferation was 3.8 times higher in the cHG group versus the OD group (P < 0.05) on day 10. CONCLUSIONS: Collagen-based hydrogel-treated wounds demonstrated significantly improved healing compared with control. The thermoresponsive feature of collagen hydrogel and its structural stability at body temperature demonstrate promising clinical potential as a vehicle for the delivery of therapeutic cells to the wound bed.
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Diabetes Mellitus Experimental , Hidrogeles , Animales , Colágeno , Humanos , Masculino , Ratas , Ratas Zucker , Cicatrización de HeridasRESUMEN
PURPOSE: Tendons are difficult to heal owing to their hypocellularity and hypovascularity. Our laboratory has developed a tendon-derived hydrogel (tHG) that significantly improves tendon healing in an animal model. We hypothesized that a potential mechanism for improved healing with tHG is through the attraction of systemic stem cells. METHODS: Homing of systemic adipose-derived stem cells (ADSCs) to tendon injuries was assessed with acute and chronic injury models. Injury sites were treated with saline or tHG, and animals given a tail vein injection (TVI) of labeled ADSCs 1 week after treatment. One week following TVI, rats were harvested for histology. To further evaluate a potential difference in homing to tHG, a subcutaneous injection (SQI) model was used. Rats were treated with an SQI of saline, silicone, ADSCs in media, tHG, tHG + fibroblasts (FBs), or tHG + ADSCs on day 0. One week after SQI, rats underwent TVI with labeled ADSCs. Samples were harvested 2 or 3 weeks after SQI for analysis. Flow cytometry confirmed homing in the SQI model. RESULTS: Systemically delivered ADSCs homed to both acute tendon and chronic tendon-bone interface (TBI) injury sites. Despite their presence at the injury site, there was no difference in the number of macrophages, amount of cell proliferation, or angiogenesis 1 week after stem cell delivery. In an SQI model, ADSCs homed to tHG. There was no difference in the number of ADSCs homing to tHG alone versus tHG + ADSCs. However, there was an increase in the number of living cells, general immune cells, and T-cells present at tHG + ADSC versus tHG alone. CONCLUSIONS: The ADSCs home to tendon injury sites and tHG. We believe the attraction of additional systemic ADSCs is one mechanism for improved tendon and TBI healing with tHG. CLINICAL RELEVANCE: Treatment of tendon and TBI injuries with tHG can augment healing via homing of systemic stem cells.
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Tejido Adiposo , Hidrogeles , Animales , Ratas , Células Madre , Tendones , Cicatrización de HeridasRESUMEN
PURPOSE: Physician burnout affects approximately half of US physicians, significantly higher than the general working population. The aims of this study were to determine the prevalence of burnout specifically among hand surgeons and to identify factors unique to the practice of hand surgery that may contribute to burnout. METHODS: A Web-based survey, developed in conjunction with the American Medical Association, was administered to all active and lifetime members of the American Society for Surgery of the Hand using the Mini Z Burnout assessment tool. Additional data were collected regarding physician demographics and practice characteristics. RESULTS: The final cohort included 595 US hand surgeons (American Society for Surgery of the Hand [ASSH] members) and demonstrated that 77% of respondents were satisfied with their job, although 49% regarded themselves as having burnout. Lower burnout rates were correlated with physicians aged older than 65, those who practice in an outpatient setting, practice hand surgery only, visit one facility per week, having a lower commute time, those who performed 10 or fewer surgeries per month, and being considered grandfathered for Maintenance of Certification. It was shown that sex, the use of physician extenders, compensation level, and travel club involvement had no impact on burnout rates. CONCLUSIONS: The survey demonstrated that nearly half of US hand surgeons experience burnout even though most are satisfied with their jobs. There is a need to increase awareness and promote targeted interventions to reduce burnout, such as creating a strong team culture, improving resiliency, and enhancing leadership. CLINICAL RELEVANCE: Burnout has been shown to affect physicians, their families, patient care, and the health care system as a whole negatively. The findings should promote awareness among hand surgeons and inform future quality improvement efforts targeted at reducing burnout for hand surgeons.
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Agotamiento Profesional , Cirujanos , Anciano , Agotamiento Profesional/epidemiología , Humanos , Satisfacción en el Trabajo , Prevalencia , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Accurate monitoring of free flap perfusion after complex reconstruction is critical for early recognition of flap compromise. Surgeons use a variety of subjective and objective measures to evaluate flap perfusion postoperatively. However, these measures have some limitations. We have developed a wireless, biodegradable, and flexible sensor that can be applied to real-time postoperative free flap monitoring. Here we assess the biocompatibility and function of our novel sensor. METHODS: Seven Sprague-Dawley (SD) rats were used for biocompatibility studies. The sensor was implanted around the femoral artery near the inguinal ligament on one leg (implant side) and sham surgery was performed on the contralateral leg (control side). At 6 and 12 weeks, samples were harvested to assess the inflammation within and around the implant and artery. Two animals were used to assess sensor function. Sensor function was evaluated at implantation and 7 days after the implantation. Signal changes after venous occlusion were also assessed in an epigastric artery island flap model. RESULTS: In biocompatibility studies, the diameter of the arterial lumen and intima thickness in the implant group were not significantly different than the control group at the 12-week time point. The number of CD-68 positive cells that infiltrated into the soft tissue, surrounding the femoral artery, was also not significantly different between groups at the 12-week time point. For sensor function, accurate signaling could be recorded at implantation and 7 days later. A change in arterial signal was noted immediately after venous occlusion in a flap model. CONCLUSION: The novel wireless, biodegradable sensor presented here is biocompatible and capable of detecting arterial blood flow and venous occlusion with high sensitivity. This promising new technology could combat the complications of wired sensors, while improving the survival rate of flaps with vessel compromise due to its responsive nature.
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Colgajos Tisulares Libres/irrigación sanguínea , Miembro Posterior/irrigación sanguínea , Monitoreo Fisiológico/instrumentación , Tecnología Inalámbrica , Animales , Materiales Biocompatibles , Microcirugia/métodos , Proyectos Piloto , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo RegionalRESUMEN
A non-target data acquisition for target analysis (nDATA) workflow based on accurate mass measurements using UHPLC/ESI Q-Orbitrap full MS-data-independent acquisition and a compound database was developed to screen pesticide residues in fruit and vegetable samples. The compound database of 845 pesticides was built from dd-MS2 (data-dependent acquisition) product ion spectral data and LC retention times of individual pesticide standards. MS2 spectra of samples were acquired using multiplexing data-independent acquisition (mDIA) and variable data-independent acquisition (vDIA). Screening of pesticides in samples was based on either the retention time (± 0.5 min) and the mass accuracy (± 5 ppm) of a precursor (RTP by full MS) or the retention time (± 0.5 min) and the mass accuracy (± 5 ppm) of a precursor and its fragment ion (RTFI by full MS/DIA). In validation studies involving mDIA and vDIA analysis of 10 fruits and vegetables spiked with pesticides prior to QuEChERS sample preparation, RTP correctly found up to 765 and 796 pesticides at 10 and 100 µg/kg, respectively, whereas RTFI correctly identified up to 729 and 764 pesticides at the same respective concentrations. UHPLC/ESI Q-Orbitrap full MS/mDIA or vDIA proved to be a comprehensive detection technique and has potential for pesticide residue screening in fruits and vegetables. Graphical Abstract.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Contaminación de Alimentos/análisis , Frutas/química , Plaguicidas/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos , Verduras/química , Análisis de los Alimentos/métodos , Límite de Detección , Residuos de Plaguicidas/análisisRESUMEN
Maffucci syndrome is a rare genetic disease due to somatic mutation of IDH1 gene. Currently there is no medical treatment available for spindle cell hemangioma associated with this disorder. Here we report successful management of these hemangiomas using sirolimus in combination with surgery.