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Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in children, adolescents, and young adults. Debate and controversy remain in the management of relapsed/refractory ES (RR-ES). The authors leveraged the expertise assembled by the National Ewing Sarcoma Tumor Board, a multidisciplinary virtual tumor board that meets monthly to discuss challenging cases of ES. In this review, they focus on select topics that apply to the management of patients with RR-ES. The specific topics covered include the initial approach of such patients and discussion of the goals of care, the role of molecular testing, chemotherapy regimens and novel agents to consider, the role of maintenance therapy, and the use of high-dose chemotherapy with autologous stem cell rescue. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, these guidelines are intended to support clinicians and provide some clarity and recommendations for the management of patients with RR-ES. PLAIN LANGUAGE SUMMARY: Ewing sarcoma (ES) is a bone and soft tissue cancer that most often occurs in teenagers and young adults. This article uses the experience of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss challenging cases of ES and to address questions related to the treatment of patients with relapsed ES. Although not intended to replace the clinical judgement of treating physicians and limited by available data, these consensus recommendations will support clinicians who treat patients with this challenging malignancy, made even more difficult when it recurs.
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INTRODUCTION: To evaluate the antimicrobial activity of Triton irrigation versus 4% sodium hypochlorite (NaOCl) utilizing a direct contact test and an extracted tooth model. METHODS: In the first experiment, a direct contact test was conducted to compare bacterial DNA removal and microbial diversity changes following irrigation with 4% NaOCl or Triton. Hydroxyapatite and dentin discs were inoculated with subgingival human-derived dental plaque for 2 weeks utilizing the Center for Disease Control biofilm reactor and subsequently challenged with the root canal irrigants for 5 minutes. In the second experiment, teeth contaminated with a multispecies biofilm (n = 24) were assigned into two treatment groups, NaOCl or Triton irrigation. Samples were obtained for quantitative real-time polymerase chain reaction and next-generation sequencing analysis before and after instrumentation. The Shannon and Chao1 indices were used to measure alpha diversity. The Bray-Curtis dissimilarity and ANOSIM was used to measure beta diversity. Differences in abundances of genera were evaluated using Kruskal-Wallis test with Bonferroni corrections. RESULTS: The direct contact test revealed no significant differences in the bacterial load based on 16S rRNA gene molecules/µL, reads, or differences in the Shannon index among groups. In the extracted tooth model, a bacterial load reduction of log10 3.08 ± 0.69 and 2.76 ± 0.91 were found for NaOCl and Triton, respectively (P = .348). Next-generation sequencing showed fewer reads, lower Chao1, and beta diversity values when pretreatment and post-treatment samples were assessed in both experimental groups (P < .0001). The Kruskal-Wallis analysis found that 17 genera of bacteria were over-represented in minimal values in the Triton post-treatment group, 14 of these genera represented less than 1% of the microbial community. CONCLUSIONS: Both irrigants had limited antimicrobial activity in the direct contact test. When used in conjunction with mechanical instrumentation both irrigants were able to reduce the bacterial DNA load and diversity in comparison with pretreatment communities. The NaOCl irrigation, followed by ethylenediaminetetraacetic acid flush, was more effective in decreasing DNA counts from low-abundance organisms.
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Over 50% of patients with systemic LCH are not cured with front-line therapies, and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with clofarabine. Clofarabine monotherapy was active against LCH in this cohort, including heavily pretreated patients with a systemic objective response rate of 92.6%, higher in children (93.8%) than adults (83.3%). BRAFV600E+ variant allele frequency in peripheral blood is correlated with clinical responses. Prospective multicentre trials are warranted to determine optimal dosing, long-term efficacy, late toxicities, relative cost and patient-reported outcomes of clofarabine compared to alternative LCH salvage therapy strategies.
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Clofarabina , Histiocitosis de Células de Langerhans , Humanos , Clofarabina/uso terapéutico , Clofarabina/administración & dosificación , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Masculino , Femenino , Adulto , Adolescente , Niño , Persona de Mediana Edad , Preescolar , Adulto Joven , Anciano , Recurrencia , Proteínas Proto-Oncogénicas B-raf/genética , Lactante , Resultado del Tratamiento , Terapia Recuperativa , Nucleótidos de Adenina/uso terapéutico , Nucleótidos de Adenina/administración & dosificación , Nucleótidos de Adenina/efectos adversos , Arabinonucleósidos/uso terapéutico , Arabinonucleósidos/administración & dosificación , Arabinonucleósidos/efectos adversosRESUMEN
BACKGROUND: There are increased efforts to maximize medical optimization to improve the outcomes of total joint arthroplasty (TJA). However, there is a paucity of literature demonstrating that optimized parameters are maintained throughout the perioperative period. METHODS: A retrospective review of 877 elective TJA patients from 2015 to 2019 was conducted. Patients who underwent medical optimization for body mass index (BMI), hemoglobin A1c (HbA1c), hemoglobin, albumin, and smoking status were reviewed at the initial visit, preoperatively, time of surgery, and one year postoperatively. For each of these variables at each time point, patients were stratified into 3 optimization groups. Analyses were performed to identify mean time to optimization, loss of optimization, and maintenance of optimization. RESULTS: Patients considered not optimized due to specific parameters at the initial visit were as follows: BMI (19%), HbA1c (13.5%), hemoglobin (16%), albumin (19%), and smoking status (9.5%). The mean time to optimization was 187.7 days [longest being BMI (220.1 days), and the shortest being HbA1c (60.9 days) (P = .0003)]. Patients who had intermediate optimization of BMI at the preoperative visit were at higher risk [odds ratio: 2.1 (0.97 to 4.6)] of worsening BMI by time of surgery (P < .0001). Between the preoperative and surgery time points, over 93.5% of patients maintained or improved optimization. CONCLUSIONS: Surgeon led medical optimization efforts alongside a TJA program provide maintenance of, or improvement in optimization in more than half of TJA patients up to one year postoperatively. Patients who had a BMI between 40 and 45 at the preoperative visit are at significant risk of increasing their BMI by the day of surgery.
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Índice de Masa Corporal , Hemoglobina Glucada , Humanos , Estudios Retrospectivos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Artroplastia de Reemplazo de Cadera , Fumar , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Artroplastia de Reemplazo de Rodilla , Artroplastia de ReemplazoRESUMEN
Prosthetic joint infections (PJI) are associated with orthopaedic morbidity and mortality. Mitochondria, the "cell's powerhouses," are thought to play crucial roles in infection response and in increased risk of sepsis mortality. No current research discusses PJI's effect on mitochondrial function and a lack of understanding of immune-infection interactions potentially hinders patient care. The purpose of this pilot study was to evaluate the impact of simulated PJI on local tissue mitochondrial function. Using an established prosthetic implant-associated in vivo model, tissues were harvested from the surgical limb of a methicillin-sensitive Staphylococcus aureus implant-associated infection group (n = 6) and compared to a noninfected group (n = 6) at postoperative day (POD) 21. Using mitochondrial coupling assays, oxygen consumption rate and extracellular acidification rate were assessed in each group. Electron flow through mitochondrial complexes reflected group activity. Electron Paramagnetic Resonance (EPR) spectrometry measured the oxidizing potential of serum samples from infected versus noninfected groups. On POD21, colony-forming units per gram of tissue showed 5 × 109 in the infected group and 101 in the noninfected group (p < 0.0001). Maximal respiration and oxygen consumption due to adenosine triphosphate synthesis were significantly lower in isolated mitochondria from infected limbs (p = 0.04). Both groups had similar complex I, III, IV, and V activity (p > 0.1). Infected group EPR signal intensity reflecting reactive oxygen species levels was 1.31 ± 0.30 compared to 1.16 ± 0.28 (p = 0.73) in the noninfected group. This study highlights PJI's role in mammalian cell mitochondrial dysfunction and oxidative tissue damage, which can help develop interventions to combat PJI.
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Artritis Infecciosa , Infecciones Relacionadas con Prótesis , Infecciones Estafilocócicas , Animales , Artritis Infecciosa/etiología , Mamíferos , Ortopedia , Proyectos Piloto , Prótesis e Implantes/efectos adversos , Infecciones Relacionadas con Prótesis/etiología , Estudios Retrospectivos , Infecciones Estafilocócicas/etiología , Staphylococcus aureusRESUMEN
Extended oral antibiotic prophylaxis (EOAP) has been suggested to reduce rates of periprosthetic joint infection (PJI) postoperatively after total joint arthroplasty (TJA). The purpose of this multicenter study is to define how many TJA patients are considered high risk for developing PJI based on published EOAP criteria and determine whether this status is associated with socioeconomic or demographic factors. All primary and aseptic revision TJAs performed in 2019 at three academic medical centers were reviewed. High-risk status was defined based on prior published EOAP criteria. Area deprivation index (ADI) was calculated as a measure of socioeconomic status. Data were reported as means with standard deviation. Both overall and institutional differences were compared. Of the 2,511 patients (2,042 primary and 469 revision) in this cohort, 73.3% met criteria for high risk (primary: 72.9% [1,490] and revision: 74.6% [350]). Patient's race or age did not have a significant impact on risk designation; however, a larger proportion of high-risk patients were women (p = 0.002) and had higher Elixhauser scores (p < 0.001). The mean ADI for high-risk patients was higher (more disadvantaged) than for standard-risk patients (64.0 [20.8] vs. 59.4 [59.4]) (p < 0.001). Over 72% of primary and revision TJA patients at three medical centers met published criteria for EOAP. These patients were more often women, had more comorbidities, and lived in more disadvantaged areas. Our findings suggest that most patients qualify for EOAP, which may call for more stringent criteria on who would benefit extended antibiotic prophylaxis.
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Profilaxis Antibiótica , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Infecciones Relacionadas con Prótesis , Reoperación , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Femenino , Masculino , Artroplastia de Reemplazo de Cadera/efectos adversos , Infecciones Relacionadas con Prótesis/prevención & control , Infecciones Relacionadas con Prótesis/etiología , Anciano , Persona de Mediana Edad , Administración Oral , Estudios Retrospectivos , Antibacterianos/administración & dosificaciónRESUMEN
Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.
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Microbioma Gastrointestinal , Ratones , Humanos , Animales , Modelos Animales de Enfermedad , Colon/cirugía , Colon/microbiología , Anastomosis Quirúrgica/efectos adversos , Trasplante de Microbiota Fecal/métodos , Fuga Anastomótica/microbiología , Dieta Occidental/efectos adversosRESUMEN
Background: Current nasal decolonization strategies utilize pre-operative agents without consideration for short-term re-colonization or de novo colonization. Many strategies utilize an antibiotic-based agent, raising concerns of limited gram-negative antimicrobial coverage and the emergence of resistant bacterial strains. This study evaluated the clinical utility of a non-antibiotic, alcohol-based nasal decolonization agent in decreasing surgical site infection (SSI) rates after total joint arthroplasty. Patients and Methods: We retrospectively compared an 18-month cohort of elective primary total joint arthroplasty patients treated peri-operatively with an alcohol-based sanitizer to historical controls. The alcohol-based agent was administered pre-operatively the day of surgery and for two weeks after surgery. Patients were followed for 90 days and assessed for signs or symptoms of SSI. Patient and caregiver compliance was recorded. There were 779 patients included in the experimental group and 647 included in the historical control group. Results: Patients receiving alcohol-based nasal decolonization had a lower rate of SSI compared with controls not receiving nasal decolonization (0.64% [5/779] vs. 1.55% [10/647]; p = 0.048; odds ratio, 2.43). Utilization of an alcohol-based nasal sanitizer in the pre-operative and prolonged post-operative setting decreased infection rates by 41.3% in our elective total joint arthroplasty setting. Conclusions: When used pre- and post-operatively, alcohol-based nasal decolonization of bacteria in patients undergoing total joint arthroplasty led to a substantial decrease in SSIs.
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Antiinfecciosos Locales , Humanos , Antiinfecciosos Locales/uso terapéutico , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Estudios Retrospectivos , Etanol , Antibacterianos , ArtroplastiaRESUMEN
BACKGROUND: The risk of postoperative complications in patients who had a positive COVID-19 test prior to a total joint arthroplasty (TJA) is unknown. The purpose of this investigation was to study the complications and mortality associated with a recent COVID-19 diagnosis prior to TJA. METHODS: Patients undergoing primary and revision total hip arthroplasties (THAs) or total knee arthroplasties (TKAs) were identified using the National COVID Cohort Collaborative (N3C) Data Enclave. Patients were divided into a COVID-19-positive group (positive polymerase chain reaction [PCR] test, clinical diagnosis, or positive antibody test) and a COVID-19-negative group, and the time from diagnosis was noted. There was no differentiation between severity or acuity of illness available. The postoperative complications reviewed included venous thromboembolism, pneumonia, acute myocardial infarction, readmission rates, and 30-day mortality rates. RESULTS: A total of 85,047 patients who underwent elective TJA were included in this study, and 3,516 patients (4.13%) had had a recent positive COVID-19 diagnosis. Patients diagnosed with COVID-19 at 2 weeks prior to TJA were at increased risk of pneumonia (odds ratio [OR], 2.46), acute myocardial infarction (OR, 2.90), sepsis within 90 days (OR, 2.63), and 30-day mortality (OR, 10.61). CONCLUSIONS: Patients with a recent COVID-19 diagnosis prior to TJA are at greater risk of postoperative complications including 30-day mortality. Our analysis presents critical data that should be considered prior to TJA in patients recently diagnosed with COVID-19. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , COVID-19 , Infarto del Miocardio , Humanos , Estudios Retrospectivos , Prueba de COVID-19 , Factores de Riesgo , COVID-19/complicaciones , COVID-19/diagnóstico , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Cadera/efectos adversos , Complicaciones Posoperatorias/etiología , Infarto del Miocardio/etiologíaRESUMEN
Outcomes in those with advanced cutaneous squamous cell carcinoma (cSCC) are poor. Upon incidence of metastasis, the mortality rate has been shown to be >70% with median overall survival (OS) of less than 2 years. While there is no standardized combination and multimodal therapy recommendation for advanced cases, there is a significant necessity to include surgical intervention for improved locoregional control of disease and improved OS. Currently, Cisplatin as monotherapy or combination with Fluorouracil (5-FU), and radiotherapy followed by surgical intervention are the most likely regimens used in the treatment of advanced cSCC. Secondary chemotherapy options include carboplatin and paclitaxel. Here, we report the effectiveness of neoadjuvant chemoradiotherapy (CRT) using carboplatin and paclitaxel agents with intensity modulated radiation therapy (IMRT) followed by radical surgical resection, and later, muscle flap reconstruction with split-thickness skin grafting to treat a very high-risk Stage IV cSCC of the left chest wall.
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Neoplasias de la Mama , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Pared Torácica , Humanos , Femenino , Carboplatino/uso terapéutico , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/radioterapia , Pared Torácica/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/tratamiento farmacológico , Cisplatino/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Músculos , QuimioradioterapiaRESUMEN
AIM: To evaluate the root canal microbiome composition and bacterial functional capability in cases of primary and secondary apical periodontitis utilizing whole-metagenome shotgun sequencing. METHODOLOGY: Twenty-two samples from patients with primary root canal infections, and 18 samples obtained from previously treated teeth currently diagnosed with apical periodontitis were analysed with whole-metagenome shotgun sequencing at a depth of 20 M reads. Taxonomic and functional gene annotations were made using MetaPhlAn3 and HUMAnN3 software. The Shannon and Chao1 indices were utilized to measure alpha diversity. Differences in community composition were evaluated utilizing analysis of similarity (ANOSIM) using Bray-Curtis dissimilarities. The Wilcoxon rank sum test was used to compare differences in taxa and functional genes. RESULTS: Microbial community variations within a community were significantly lower in secondary relative to primary infections (alpha diversity p = .001). Community composition was significantly different in primary versus secondary infection (R = .11, p = .005). The predominant taxa observed among samples (>2.5%) were Pseudopropionibacterium propionicum, Prevotella oris, Eubacterium infirmum, Tannerella forsythia, Atopobium rimae, Peptostreptococcus stomatis, Bacteroidetes bacterium oral taxon 272, Parvimonas micra, Olsenella profusa, Streptococcus anginosus, Lactobacillus rhamnosus, Porphyromonas endodontalis, Pseudoramibacter alactolyticus, Fusobacterium nucleatum, Eubacterium brachy and Solobacterium moorei. The Wilcoxon rank test revealed no significant differences in relative abundances of functional genes in both groups. Genes with greater relative abundances (top 25) were associated with genetic, signalling and cellular processes including the iron and peptide/nickel transport system. Numerous genes encoding toxins were identified: exfoliative toxin, haemolysins, thiol-activated cytolysin, phospholipase C, cAMP factor, sialidase, and hyaluronic glucosaminidase. CONCLUSIONS: Despite taxonomic differences between primary and secondary apical periodontitis, the functional capability of the microbiomes was similar.
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BACKGROUND: Therapeutic interventions that optimize angiogenic activities may reduce rates of end-stage kidney disease, critical limb ischemia, and lower extremity amputations in individuals with diabetic kidney disease (DKD). Infusion of autologous mesenchymal stromal cells (MSC) is a promising novel therapy to rejuvenate vascular integrity. However, DKD-related factors, including hyperglycemia and uremia, might alter MSC angiogenic repair capacity in an autologous treatment approach. METHODS: To explore the angiogenic activity of MSC in DKD, the transcriptome of adipose tissue-derived MSC obtained from DKD subjects was compared to age-matched controls without diabetes or kidney impairment. Next-generation RNA sequencing (RNA-seq) was performed on MSC (DKD n = 29; Controls n = 9) to identify differentially expressed (DE; adjusted p < 0.05, |log2fold change|> 1) messenger RNA (mRNA) and microRNA (miRNA) involved in angiogenesis (GeneCards). Paracrine-mediated angiogenic repair capacity of MSC conditioned medium (MSCcm) was assessed in vitro using human umbilical vein endothelial cells incubated in high glucose and indoxyl sulfate for a hyperglycemic, uremic state. RESULTS: RNA-seq analyses revealed 133 DE mRNAs (77 upregulated and 56 down-regulated) and 208 DE miRNAs (119 up- and 89 down-regulated) in DKD-MSC versus Control-MSC. Interestingly, miRNA let-7a-5p, which regulates angiogenesis and participates in DKD pathogenesis, interacted with 5 angiogenesis-associated mRNAs (transgelin/TAGLN, thrombospondin 1/THBS1, lysyl oxidase-like 4/LOXL4, collagen 4A1/COL4A1 and collagen 8A1/COL8A1). DKD-MSCcm incubation with injured endothelial cells improved tube formation capacity, enhanced migration, reduced adhesion molecules E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 mRNA expression in endothelial cells. Moreover, angiogenic repair effects did not differ between treatment groups (DKD-MSCcm vs. Control-MSCcm). CONCLUSIONS: MSC from individuals with DKD show angiogenic transcriptome alterations compared to age-matched controls. However, angiogenic repair potential may be preserved, supporting autologous MSC interventions to treat conditions requiring enhanced angiogenic activities such as DKD, diabetic foot ulcers, and critical limb ischemia.
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Diabetes Mellitus , Nefropatías Diabéticas , Células Madre Mesenquimatosas , MicroARNs , Humanos , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/metabolismo , Isquemia Crónica que Amenaza las Extremidades , Transcriptoma , Neovascularización Fisiológica/genética , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , ARN Mensajero/metabolismo , Diabetes Mellitus/metabolismo , Proteína-Lisina 6-Oxidasa/genética , Proteína-Lisina 6-Oxidasa/metabolismoRESUMEN
Advances in our understanding of the complex, multifaceted interactions between tumor epithelia, immune infiltrate, and tumor microenvironmental cells have been driven by highly multiplexed imaging technologies. These techniques are capable of labeling many more biomarkers than conventional immunostaining methods. However, multiplexed imaging techniques suffer from low detection sensitivity, cell loss-particularly in fragile samples-, and challenges with antibody labeling. Herein, we developed and optimized an oligonucleotide antibody barcoding strategy for cyclic immunofluorescence (cyCIF) that can be amplified to increase the detection efficiency of low-abundance antigens. Stained fluorescence signals can be readily removed using ultraviolet light treatment, preserving tissue and fragile cell sample integrity. We also extended the oligonucleotide barcoding strategy to secondary antibodies to enable the inclusion of difficult-to-label primary antibodies in a cyCIF panel. Using both the amplification oligonucleotides to label DNA barcoded antibodies and in situ hybridization of multiple fluorescently labeled oligonucleotides resulted in signal amplification and increased signal-to-background ratios. This procedure was optimized through the examination of staining parameters including staining oligonucleotide concentration, staining temperature, and oligonucleotide sequence design, resulting in a robust amplification technique. As a proof-of-concept, we demonstrate the flexibility of our cyCIF strategy by simultaneously imaging with the original oligonucleotide conjugated antibody (Ab-oligo) cyCIF strategy, the novel Ab-oligo cyCIF amplification strategy, as well as direct and indirect immunofluorescence to generate highly multiplexed images.
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AIM: To evaluate the root canal microbiome composition in cases of primary and secondary apical periodontitis. METHODOLOGY: Thirty-nine samples from patients with primary root canal infections obtained before root canal treatment, and 40 samples obtained during root-end resection procedures from previously filled cases with apical periodontitis were evaluated using 16S rRNA next-generation sequencing analysis (NGS). Demographic and clinical factors included age, sex, infection type, percussion sensitivity, and presence of pain. Differences in abundances of genera were evaluated using Kruskal-Wallis test. Alpha and beta diversity indices were calculated using mothur. The Shannon and Chao1 indices were used to measure alpha diversity. The Bray-Curtis dissimilarity was used to measure beta diversity. Differences in community composition were evaluated using analysis of similarity (ANOSIM) with Bonferroni correction for multiple comparisons. RESULTS: Significantly fewer operational taxonomic units values were observed from samples from secondary infections (p < .0001). While no significant differences were observed in the Chao 1 index between primary and secondary infections, the Shannon alpha diversity was significantly lower in secondary relative to primary infections (p = .008). Among samples, sex, age (adult vs. older adult), percussion sensitivity, and presence of pain all showed no significant effects on community composition via an analysis of similarity (ANOSIM). However, community composition was significantly different depending on whether the sample was from a primary or secondary infection (R = .051, p = .03). Nine microbial genera comprised the predominant taxa observed among samples (>3.3%) and included Parvimonas, Fusobacterium, Campylobacter, Arachnia, Eubacterium, Prevotella, Peptostreptococcus, Fretibacterirum, and Pseudoramibacter. Significantly greater relative abundances of Prevotella, Peptostreptococcus, Veillonella, Lactucaseibacillus, and Dialister were observed in primary infections. CONCLUSIONS: Primary endodontic infections are more diverse than secondary infections. The microbial composition is not associated with the clinical manifestations of apical periodontitis.
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Coinfección , Cavidad Pulpar , Periodontitis Periapical , Anciano , Humanos , Bacterias , Cavidad Pulpar/microbiología , Dolor , Periodontitis Periapical/microbiología , ARN Ribosómico 16S/genéticaRESUMEN
Background: Combined Orthopaedic Infectious Disease Clinics facilitate care for prosthetic joint infection (PJI) patients similar to multidisciplinary care in cancer centers. The National Comprehensive Cancer Network developed a standardized distress thermometer (DT) to measure distress in cancer patients. We propose using this tool to assess distress in PJI patients. Methods: In this pilot study, a retrospective review of patients treated in our combined clinic over 2 years was conducted. In addition to providing information surrounding their treatment, patients completed a questionnaire and DT, adapted with permission from the National Comprehensive Cancer Network. DT scores were compared to a chronologically collected matched aseptic control group. Results: There were 122 patients in the septic group and 40 patients in the aseptic group. On a scale of 0-10 (10, the highest level of distress), the septic group reported a mean DT score of 6.18 (±3.2), which was significantly higher than the aseptic mean score of 3.33 (±2.06) [P < .0001]. Over 75% of patients in the septic group reported a DT score ≥4, the cutoff used in most cancer centers to warrant additional support. Twenty-one percent of the septic group (26/122) reported extreme distress (defined as a score ≥10) compared to 0/40 of aseptic patients. Conclusions: Patients treated for PJI experience significantly higher levels of distress compared to aseptic revision patients. More attention is needed to measure and clinically address distress. Improved screening for distress would allow us to provide more comprehensive care and possibly improve compliance, outcomes, and resources available for the treatment of PJI patients.
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The viscosity measurements are of clinical significance for evaluation of the potential pathological conditions of biological lubricants such as synovial fluids of joints, and for formulation and characterization of peptide- and protein-based biotherapeutics. Due to inherent potential therapeutic activity, protein drugs have proven to be one of the most efficient therapeutic agents in treatment of several life-threatening disorders, such as diabetes and autoimmune diseases. However, home-use applications for treating chronic inflammatory diseases, such as diabetes and rheumatoid arthritis, necessitate the development of high-concentration insulin and monoclonal antibodies formulations for patient self-administration. High protein concentrations can affect viscosity of the corresponding drug solutions complicating their manufacture and administration. The measurements of the viscosity of new insulin analogs and monoclonal antibodies solutions under development is of practical importance to avoid unwanted highly viscous, and therefore, painful for injection drug formulations. Recently, we have demonstrated capability of the electron paramagnetic resonance (EPR) viscometry using viscosity-sensitive 13C-labeled trityl spin probe (13C1-dFT) to report the viscosity of human blood, and interstitial fluids measured in various organs in mice ex-vivo and in anesthetized mice, in vivo. In the present work, we demonstrate utility of the EPR viscometry using 13C1-dFT to measure microviscosity of commercial insulin samples, antibodies solution, and human synovial fluids using small microliter volume samples (5-50 µL). This viscometry analysis approach provides useful tool to control formulations and administration of new biopharmaceuticals, and for evaluation of the state of synovial fluids of importance for clinical applications.
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Introduction: Long antibiotic courses, including intravenous (IV) and oral administrations, are utilized in prosthetic joint infection (PJI) treatment. This meta-analysis examines the non-inferiority of short courses ( < â¯4 weeks) of IV antibiotics compared to long courses in treating PJI. Critical review of IV treatment is necessary due to the clinical, physical, and financial burden associated with it and its continued prolonged use in the US without much evidence to support the practice. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), databases were searched using predefined medical subject headings (MeSH). Results: The nine included studies reported 521 total hip arthroplasties (THAs) and 530 total knee arthroplasties (TKAs). There was no significant difference in the overall success rate in short- vs. long-duration IV antibiotics for PJI treatment: odds ratio (OR) of 1.65, 95â¯% confidence interval (CI) of 0.78-3.46, and p = 0 .18. However, due to the moderate to high heterogeneity ( I 2 = 68 â¯%, p ⯠< â¯0.01) amongst studies, an adjusted success rate was calculated after the exclusion of two studies. This showed a statistically significant difference between both groups (OR of 2.45, 95â¯% CI of 1.21-4.96, p ⯠< â¯0.001) favoring a short course of antibiotics and reflecting a more homogenous population ( I 2 = 51 â¯%, p = 0 .06). Conclusion: This study highlights the limited data available for evaluating IV antibiotic duration in the setting of PJI. We found that a shorter duration of IV antibiotics was non-inferior to a longer duration, with an improved OR of 2.45 for treatment success, likely shortening inpatient stay as well as lessening side effects and antimicrobial resistance with a lower cost to patients and overall healthcare.
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BACKGROUND: Aspirin, as a routine venous thromboembolism (VTE) prophylaxis, is approved along with pneumatic compression pumps by the American College of Chest Physicians. We assessed compliance of aspirin and pump use after total joint arthroplasty. METHODS: A randomized trial of aspirin alone or aspirin/mobile compression pumps after total joint arthroplasty was performed. Aspirin and pump compliance, VTE events, and satisfaction with pump use were collected. Compliance was assessed through an internal device monitor and drug log book. Patients were also contacted 90 days postoperatively for reported symptomatic VTEs. RESULTS: Each group had 40 patients and greater than 94% compliance with aspirin use, with no difference between groups (P = 0.55). Overall pump compliance during the first 14 days after hospital discharge was 51% (SD ± 33), which was significantly worse than aspirin compliance at 99% (SD ± 4.1) (P < 0.0001). Only 10 patients were compliant (>20 hr/d) with recommended pump use throughout the entire recommended period. There was no notable association between aspirin compliance and VTE within 90 days. There was no notable association between pump compliance and VTE at 90 days. However, average pump use compliance was 20% in patients with VTE and 54% in patients without VTE within 90 days. With the numbers available in this compliance study, there was no significant difference (P = 0.11). DISCUSSION: Aspirin compliance was notably greater than pump compliance. In this study, we found that pump compliance was not associated with lower VTE risk. In fact, no increased risk was recognized in patients with an average pump usage of >50%. Further study is warranted to define the duration of pump use required for clinical significance. The recommended use of compression pumps should continue to be examined.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Tromboembolia Venosa , Anticoagulantes/uso terapéutico , Artroplastia de Reemplazo de Cadera/efectos adversos , Aspirina/uso terapéutico , Humanos , Periodo Posoperatorio , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & controlRESUMEN
The treatment and prognosis of non-operable high-risk head and neck squamous cell carcinoma (SCC) are poor. There is no definitive model for therapy in these cases to date, but strategies that have been utilized include radiation therapy (RT) with or without chemotherapy. Here, we report the effectiveness of arterial embolization with subsequent chemoradiation with cisplatin in a case of advanced oropharyngeal SCC. These interventions resulted in a remarkable tumor burden reduction of a stage IV SCC of the head and neck that had been deemed nonresectable.
RESUMEN
AIM: The aim of the study was to assess biofilm removal efficacy of GentleWave System and passive ultrasonic irrigation (PUI). METHODOLOGY: Twenty-two human mandibular molars with Vertucci's type II configuration in the mesial root were selected. Teeth were autoclaved, inoculated with dental plaque and incubated in a CDC biofilm reactor for two weeks. The mesial roots were instrumented up to 20.06 file (V-Taper) for the GentleWave group and up to 35.04 file (Vortex Blue) for PUI group. Irrigation was performed using GentleWave and PUI irrigation protocols (n = 11). Dentine debris on paper points samples were obtained for quantitative real-time polymerase chain reaction (qPCR) and 16S ribosomal RNA gene sequencing (next-generation aequencing-NGS). For qPCR, a non-parametric test (α = 0.05) was used. Next-generation sequencing data were analysed using mothur, with alpha diversity calculated as the Shannon and Chao1 indices and Bray-Curtis dissimilarities were used for beta diversity. Differences in alpha diversity and abundances of genera were evaluated using Kruskal-Wallis test. Differences in community composition were evaluated using analysis of similarity with Bonferroni correction for multiple comparisons. RESULTS: Quantitative real-time polymerase chain reaction results showed that the reduction estimated in percentages for both groups was equivalent (p > .05). NGS analysis showed that both techniques promoted a significant reduction in reads and OTUs number (p < .05). Shannon alpha diversity and Chao1 index showed no differences between pre- or post-treatment samples for both groups (p > .05). Additionally, pre-treatment communities differed from post-treatment samples in both groups regarding bacterial taxa reduction (ANOSIM R = 0.50 and 0.55, p < .001). CONCLUSIONS: Bacterial reduction in mesial roots of mandibular molars prepared to 35.04 with PUI was similar to those prepared to 20.06 with a multisonic irrigant activation system.