Does Anesthesiologist Experience Influence Early Postoperative Outcomes Following Orthognathic Surgery?

BACKGROUND: Anesthesia provider experience impacts nausea and vomiting in other surgical specialties but its influence within orthognathic surgery remains unclear. PURPOSE: The study purpose was to evaluate whether anesthesiologist experience with orthognathic surgery impacts postoperative outcomes, including nausea, emesis, narcotic use, and perioperative adverse events, for patients undergoing orthognathic surgery. STUDY DESIGN, SETTING, SAMPLE: This is a retrospective cohort study of subjects aged 12 to 35 years old who underwent orthognathic surgery, including Le Fort 1 osteotomy ± bilateral sagittal split osteotomy, at Boston Children's Hospital from August 2018 to January 2022. Subjects were excluded if they had incomplete medical records, a syndromic diagnosis, or a hospital stay of greater than 2 days. PREDICTOR VARIABLE: The predictor variable was attending anesthesia provider experience with orthognathic surgery. Providers were classified as experienced or inexperienced, with experienced providers defined as having anesthetized ≥10 orthognathic operations during the study period. MAIN OUTCOME VARIABLES: The primary outcome variable was postoperative nausea. Secondary outcome variables were emesis, narcotic use in the hospital, and perioperative adverse events within 30 days of their operation. COVARIATES: Study covariates included age, sex, race, comorbidities (body mass index, history of psychiatric illness, cleft lip and/or palate, chronic pain, postoperative nausea/vomiting, gastrointestinal conditions), enhanced recovery after surgery protocol enrollment, and intraoperative factors (operation performed, anesthesia/procedure times, estimated blood loss, intravenous fluid and narcotic administration, and anesthesiologist's years in practice). ANALYSES: χ2 and unpaired t-tests were used to compare primary predictor and covariates against outcome variables. A P-value <.05 was considered significant. RESULTS: There were 118 subjects included in the study after 4 were excluded (51.7% female, mean age 19.1 ± 3.30 years). There were 71 operations performed by 5 experienced anesthesiologists (mean cases/provider 15.4 ± 5.95) and 47 cases by 22 different inexperienced providers (mean cases/provider 1.91 ± 1.16). The nausea rate was 52.1% for experienced providers and 53.2% for inexperienced providers (P = .909). There were no statistically significant associations between anesthesiologist experience and any outcome variable (P > .341). CONCLUSIONS AND RELEVANCE: Anesthesia providers' experience with orthognathic surgery did not significantly influence postoperative nausea, emesis, narcotic use, or perioperative adverse events.

An Enhanced Recovery After Surgery (ERAS) Protocol for Orthognathic Surgery Reduces Rates of Postoperative Nausea.

For many surgical procedures, enhanced recovery after surgery (ERAS) protocols have improved patient outcomes, particularly postoperative nausea and vomiting. The purpose of this study was to evaluate postoperative nausea following orthognathic surgery after the implementation of an ERAS protocol. This retrospective cohort study included patients between 12 and 35 years old who underwent orthognathic surgery at Boston Children's Hospital from April 2018 to December 2022. Patients with syndromes or a hospital stay greater than 48 hours were excluded from the study. The primary predictor was enrollment in our institutional ERAS protocol. The main outcome variable was postoperative nausea. Intraoperative and postoperative covariates were compared between groups using unpaired t tests and chi squared analysis. Univariate and multivariate regression models with 95% confidence intervals were performed to identify predictors for nausea. A P value<0.05 was considered significant. There were 128 patients (68 non-ERAS, 60 ERAS) included in this study (51.6% female, mean age 19.02±3.25 years). The ERAS group received less intraoperative fluid (937.0±462.3 versus 1583.6±847.6 mL, P ≤0.001) and experienced less postoperative nausea (38.3% versus 63.2%, P =0.005). Enhanced recovery after surgery status ( P =0.005) was a predictor for less postoperative nausea, whereas bilateral sagittal split osteotomy ( P =0.045) and length of stay ( P =0.007) were positive predictors for postoperative nausea in multivariate logistic regression analysis. Implementing an ERAS protocol for orthognathic surgery reduces postoperative nausea. Level of Evidence: Level III-therapeutic.

Immunoproteasome inhibition prevents chronic antibody-mediated allograft rejection in renal transplantation.

Chronic antibody-mediated rejection is the major cause of fading allograft function and loss after renal transplantation. Currently, pharmacological agents for the suppression of chronic antibody-mediated rejection are lacking. Non-selective proteasome inhibitors suppress antibody-mediated allograft rejection. However, extensive adverse side effects of these inhibitors severely limit their application. In contrast, immunoproteasome inhibition is effective in preclinical models of autoimmune diseases and was applied over weeks without obvious adverse side effects. ONX 0914, an immunoproteasome subunit LMP7 (ß5i)-selective inhibitor, impeded the chronic rejection of kidneys transplanted from Fischer to allogeneic Lewis rats. ONX 0914 inhibited immunoproteasome induction both in immune organs and renal allografts. Selective immunoproteasome inhibition reduced the numbers of B and plasma cells, and suppressed donor-specific alloantibody production. The infiltration of T cells, B cells and macrophages as well as interferon-γ, interleukin-17, IgG and complement deposition were reduced in renal allografts of ONX 0914-treated recipients. Chronic nephropathy was ameliorated and renal allograft function preserved, enabling long-term survival of recipients. Thus, our studies define a critical role of the immunoproteasome in chronic kidney allograft rejection and suggest immunoproteasome inhibition as a promising therapeutic approach to suppress chronic antibody-mediated rejection.

Recent advances in the application of capillary electromigration methods for food analysis and Foodomics.

This review work presents and discusses the main applications of capillary electromigration methods in food analysis and Foodomics. Papers that were published during the period February 2015-February 2017 are included following the previous review by Acunha et al. (Electrophoresis 2016, 37, 111-141). The paper shows the large variety of food related molecules that have been analyzed by CE including amino acids, biogenic amines, carbohydrates, chiral compounds, contaminants, DNAs, food additives, heterocyclic amines, lipids, peptides, pesticides, phenols, pigments, polyphenols, proteins, residues, toxins, vitamins, small organic and inorganic compounds, as well as other minor compounds. This work describes the last results on food quality and safety, nutritional value, storage, bioactivity, as well as uses of CE for monitoring food interactions and food processing including recent microchips developments and new applications of CE in Foodomics.

An artificial PAP gene breaks self-tolerance and promotes tumor regression in the TRAMP model for prostate carcinoma.

Prostate cancer (PCa) is the most commonly diagnosed type of cancer in men in western industrialized countries. As a public health burden, the need for the invention of new cost-saving PCa immunotherapies is apparent. In this study, we present a DNA vaccine encoding for the prostate-specific antigen prostatic acid phosphatase (PAP) linked to the J-domain and the SV40 enhancer sequence. The PAP DNA vaccine induced a strong PAP-specific cellular immune response after electroporation (EP)-based delivery in C57BL/6 mice. Splenocytes from mice immunized with PAP recognized the naturally processed PAP epitopes, indicating that vaccination with the PAP-J gene broke its self-tolerance against PAP. Remarkably, DNA vaccination with PAP-J inhibited tumor growth in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse model that closely resembled human PCa. Therefore, this study highlights a novel cancer immunotherapy approach with the potential to control PCa in clinical settings.

A comparative review of epinephrine and phenylephrine as vasoconstrictors in dental anesthesia: exploring the factors behind epinephrine's prevalence in the US.

This review paper delves into the comparative study of epinephrine and phenylephrine as vasoconstrictors in dental anesthesia, exploring their histories, pharmacological properties, and clinical applications. The study involved a comprehensive literature search, focusing on articles that directly compared the two agents in terms of efficacy, safety, and prevalence in dental anesthesia. Epinephrine, with its broad receptor profile, has been a predominant choice, slightly outperforming in the context of prolonging dental anesthesia and providing superior hemostasis, which is crucial for various dental procedures. However, the stimulation of beta-adrenergic receptors caused by epinephrine poses risks, especially to patients with cardiovascular conditions. Phenylephrine, a selective alpha-1 adrenergic agonist, emerges as a safer alternative for such patients, avoiding the cardiovascular risks associated with epinephrine. Moreover, its vasoconstrictive effect may not be as deleterious as that of epinephrine, due to its selective action. This review reveals that despite the potential benefits of phenylephrine, epinephrine continues to dominate in clinical settings, due to its historical familiarity, availability, and cost-effectiveness. The lack of commercially available pre-made phenylephrine dental carpules in most countries, except Brazil, and a knowledge gap within dental academia regarding phenylephrine, contribute to its limited use. This review concludes that while both agents are effective, the choice between them should be based on individual patient conditions, availability, and the practitioner's knowledge and familiarity with the agents. The underuse of other vasoconstrictors like levonordefrin and the unavailability of phenylephrine in pre-mixed dental cartridges in many countries highlights the need for further exploration and research in this field. Furthermore, we also delve into the role of levonordefrin and examine the rationale behind the exclusion of phenylephrine from commercially available pre-mixed local anesthetic carpules, suggesting a need for a responsive approach from pharmaceutical manufacturers to the distinct needs of the dental community.

The global reach of social media in oral and maxillofacial surgery.

PURPOSE: Social media use among oral and maxillofacial surgeons (OMSs) has grown in recent years, serving as an important resource for the dissemination of medical/surgical knowledge, research, education, diplomacy, and advocacy. However, no studies have attempted to characterize the global reach of social media in OMS. METHODS: This study examined the profile activity, content performance, and demographic characteristics of followers from a single OMS-related Instagram account. Variables assessed include the total number of followers since the account's inception, profile views over the selected time period, and unique media content posts, as well as likes, comments, saves, impressions, and reach for all media content posts. The top 45 countries, cities, and languages based on each follower's geolocation and user settings were also included. RESULTS: There were 9569 followers of which 6208 (64.9%) were listed as public accounts. Of the 6208 followers with public accounts, 2496 (40.2%) were female. The countries with the most followers included the United States (31.7%), India (12.5%), Malaysia (5.3%), Mexico (4.0%), and Pakistan (3.6%). The cities with the most followers included New York, New York (8.9%), Boston, Massachusetts (5.2%), Cairo, Egypt (4.3%), Santiago, Chile (3.7%), and Karachi, Pakistan (3.5%). CONCLUSION: OMS-related social media is uniquely positioned to facilitate global collaboration and augment the dissemination of surgical knowledge and expertise. This information is critical in understanding the distribution and demographics of the OMS workforce, trainees, and affiliates around the world.

Differences in Longevity and Temperature-Driven Extrinsic Incubation Period Correlate with Varying Dengue Risk in the Arizona-Sonora Desert Region.

Dengue transmission is determined by a complex set of interactions between the environment, Aedes aegypti mosquitoes, dengue viruses, and humans. Emergence in new geographic areas can be unpredictable, with some regions having established mosquito populations for decades without locally acquired transmission. Key factors such as mosquito longevity, temperature-driven extrinsic incubation period (EIP), and vector-human contact can strongly influence the potential for disease transmission. To assess how these factors interact at the edge of the geographical range of dengue virus transmission, we conducted mosquito sampling in multiple urban areas located throughout the Arizona-Sonora desert region during the summer rainy seasons from 2013 to 2015. Mosquito population age structure, reflecting mosquito survivorship, was measured using a combination of parity analysis and relative gene expression of an age-related gene, SCP-1. Bloodmeal analysis was conducted on field collected blood-fed mosquitoes. Site-specific temperature was used to estimate the EIP, and this predicted EIP combined with mosquito age were combined to estimate the abundance of "potential" vectors (i.e., mosquitoes old enough to survive the EIP). Comparisons were made across cities by month and year. The dengue endemic cities Hermosillo and Ciudad Obregon, both in the state of Sonora, Mexico, had higher abundance of potential vectors than non-endemic Nogales, Sonora, Mexico. Interestingly, Tucson, Arizona consistently had a higher estimated abundance of potential vectors than dengue endemic regions of Sonora, Mexico. There were no observed city-level differences in species composition of blood meals. Combined, these data offer insights into the critical factors required for dengue transmission at the ecological edge of the mosquito's range. However, further research is needed to integrate an understanding of how social and additional environmental factors constrain and enhance dengue transmission in emerging regions.

The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA.

Therapeutic DNA vaccination is an attractive adjuvant option to conventional methods in the fight against cancer, like surgery radiotherapy and chemotherapy. Despite strong antitumor effects that were observed in small animals with different antigens, DNA-based vaccines remain weakly immunogenic in large animals and primates compared to protein-based vaccines. Here, we sought to enhance the immunogenicity of a therapeutic nontransforming cervical cancer DNA vaccine (HPV-16 E7SH) by introduction of a highly optimized CpG cassette into the plasmid backbone as well as by an optimized DNA delivery using an advanced electroporation (EP) technology. By integrating the means for agent administration and EP into a single device, this technology enables a simple, one-step procedure that facilitates reproducibility. We found that highly optimized CpG motifs alone triggers an enhanced IFN-γ and granzyme B response in Elispot assays as well as stronger tumor regression. Furthermore, these effects could be dramatically enhanced when the CpG cassette containing plasmid was administered via the newly developed EP technology. These data suggest that an optimized application of CpG-enriched DNA vaccines may be an attractive strategy for the treatment of cancer. Collectively, these results provide a basis for the transfer of preclinical therapeutic DNA-based immunization studies into successful clinical cancer trials.

Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants.

Treatment of patients with cervical cancer by conventional methods (mainly surgery, but also radiotherapy and chemotherapy) results in a significant loss in quality of life. A therapeutic DNA vaccine directed to tumor-specific antigens of the human papilloma virus (HPV) could be an attractive treatment option. We have developed a nontransforming HPV-16 E7-based DNA vaccine containing all putative T cell epitopes (HPV-16 E7SH). DNA vaccines, however, are less immunogenic than protein- or peptide-based vaccines in larger animals and humans. In this study, we have investigated an adjuvant gene support of the HPV-16 E7SH therapeutic cervical cancer vaccine. DNA encoded cytokines (IL-2, IL-12, GM-CSF, IFN-gamma) and the chemokine MIP1-alpha were co-applied either simultaneously or at different time points pre- or post-E7SH vaccination. In addition, sequence-optimized adjuvant genes were compared to wild type genes. Three combinations investigated lead to an enhanced IFN-gamma response of the induced T cells in mice. Interestingly, IFN-gamma secretion of splenocytes did not strictly correlate with tumor response in tumor regression experiments. Gene-encoded MIP-1alpha applied 5 days prior to E7SH-immunization combined with IFN-gamma or IL-12 (3 days) or IL-2 (5 days) postimmunization lead to a significantly enhanced tumor response that was clearly associated with granzyme B secretion and target cells lysis. Our results suggest that a conditioning application and combination with adjuvant genes may be a promising strategy to enhance synergistically immune responses by DNA immunization for the treatment of cervical cancer.

The 20S immunoproteasome and constitutive proteasome bind with the same affinity to PA28αß and equally degrade FAT10.

The 20S immunoproteasome (IP) is an interferon(IFN)-γ - and tumor necrosis factor (TNF) -inducible variant of the 20S constitutive proteasome (CP) in which all its peptidolytically active subunits ß1, ß2, and ß5 are replaced by their cytokine inducible homologues ß1i (LMP2), ß2i (MECL-1), and ß5i (LMP7). These subunit replacements alter the cleavage specificity of the proteasome and the spectrum of proteasome-generated peptide ligands of MHC class I molecules. In addition to antigen processing, the IP has recently been shown to serve unique functions in the generation of pro-inflammatory T helper cell subtypes and cytokines as well as in the pathogenesis of autoimmune diseases, but the mechanistic involvement of the IP in these processes has remained elusive. In this study we investigated whether the IP differs from the CP in the interaction with two IFN-γ/TNF inducible factors: the 11S proteasome regulator PA28αß and the ubiquitin-like modifier FAT10 (ubiquitin D). Using thermophoresis, we determined the affinity of PA28αß for the CP and IP to be 12.2nM +/- 2.8nM and 15.3nM +/- 2.7nM, respectively, which is virtually identical. Also the activation of the peptidolytic activities of the IP and CP by PA28αß did not differ. For FAT10 we determined the degradation kinetics in cycloheximide chase experiments in cells expressing almost exclusively IP or CP as well as in IFN-γ stimulated and unstimulated cells and found no differences between the degradation rates. Taken together, we conclude that neither differences in the binding strength to, nor activation by PA28αß, nor a difference in the rate of FAT10-mediated degradation can account for distinct functional capabilities of the IP as compared to the CP.

Diagnóstico diferencial: ¿Qué es, cómo se hace, dónde lo enseñan? / Differential diagnosis: what is it, how is it done and where is it taught?

El diagnóstico es la piedra angular de la medicina individual, por tanto, dominarlo y conocerlo es esencial para todo médico al indagar en el estado de salud y patológico de los pacientes. Los profesionales de la salud deben dedicar todos sus esfuerzos a su realización, siempre que disponga de los elementos y medios necesarios, tanto teóricos como prácticos, para la correcta utilización del método clínico, elemento esencial del diagnóstico diferencial. En este artículo se abordan los aspectos más relevantes que intervienen en la realización del diagnóstico de los pacientes; se enfatiza en los pasos necesarios para efectuar un verdadero diagnóstico diferencial que posibilite la decantación de las posibilidades etiológicas del cuadro clínico del enfermo. A través de la correcta aplicación del método clínico es posible la aproximación al diagnóstico clínico definitivo del paciente.

Diagnosis is the cornerstone of individual medicine, therefore, mastering it and knowing it is essential for every doctor when inquiring into the health and pathological status of patients. Health professionals must dedicate all their efforts to its realization as long as they have the necessary elements and means, both theoretical and practical, for the correct use of the clinical method, which is an essential element of differential diagnosis. This article addresses the most relevant aspects involved in carrying out patient's diagnosis; emphasis is placed on the necessary steps to carry out a true differential diagnosis that makes it possible to decant the etiological possibilities of the patient's clinical manifestations. It is possible to approach the definitive clinical diagnosis of the patient through the correct application of the clinical method.

Enfermedades asintomáticas o diagnósticos incipientes / Asymptomatic diseases or early diagnoses

RESUMEN Introducción: Constituye hecho relevante en el ejercicio de la medicina, individual o poblacional, conocer precozmente la instauración de las enfermedades, y por ello se tratan de realizar los diagnósticos clínicos precozmente. Sin embargo, un grupo de enfermedades, infecciosas o no infecciosas, agudas o crónicas, se caracterizan por escasas manifestaciones clínicas, por lo que el conocimiento de su existencia es de vital importancia, por ejemplo, la hipertensión arterial o la diabetes mellitus, cuyas expresiones sintomáticas pueden aparecer tardíamente. En igual medida, la actual pandemia por SARS-CoV-2, ha proliferado rápidamente debido al gran número de personas infectadas que no expresan síntomas. Objetivo: Caracterizar aspectos clínicos relevantes sobre las enfermedades asintomáticas y la importancia de los diagnósticos clínicos o biotecnológicos incipientes, individuales y poblacionales. Métodos: Se realizaron búsquedas bibliográficas de los últimos cinco años en libros clásicos de Medicina Interna, se analizaron artículos publicados en revistas nacionales e internacionales, específicamente en revistas de alto impacto como Lancet y The New England Journal of Medicine. Se consideraron bases de datos de la Organización Mundial de la Salud, así como lo expuesto en Infomed; además se utilizó Google Académico, con los descriptores de interés al respecto. Conclusiones: Por el momento siempre serán parciales, pues se enfatiza en las recomendaciones de la Organización Mundial de la Salud sobre la actual pandemia, para la identificación y control del SARS-CoV-2; se acentúa en la importancia de los métodos clínicos y epidemiológicos, así como en el desarrollo de la biotecnología para el conocimiento de las enfermedades.

ABSTRACT Introduction: early detection of the onset of diseases constitutes a relevant fact in the practice of individual or population medicine that is why early clinical diagnoses are tried to be made. However, a group of infectious or non-infectious, acute or chronic clinical diseases are characterized by few clinical manifestations, for which knowledge of their existence is of vital importance, for example, arterial hypertension or diabetes mellitus, whose symptomatic expressions may appear late. To the same extent, the current SARS-CoV-2 pandemic has proliferated rapidly due to the large number of infected people who do not express symptoms. Objective: to characterize relevant clinical aspects of asymptomatic diseases and the importance of incipient, individual and population clinical or biotechnological diagnoses. Methods: bibliographic searches of the last five years were carried out in classic books on Internal Medicine, articles published in national and international journals were analyzed, specifically in high-impact journals such as the Lancet and The New England Journal of Medicine. Databases of the World Health Organization were considered, as well as what was exposed in Infomed; in addition, Google Scholar was used, with the descriptors of interest in this regard. Conclusions: conclusions will always be partial for the moment, since the recommendations of the World Health Organization for the identification and control of SARS-CoV-2 are emphasized; the importance of clinical and epidemiological methods is highlighted, as well as the development of biotechnology for the knowledge of diseases.

El error en medicina / Error in medicine

RESUMEN En la Medicina, como en todas las actividades humanas, ocurren errores involuntarios con frecuencia. Este tema debe ser tratado con profundidad y sinceridad en la comunidad científica, como paso inicial para su futura prevención. Se realizó una revisión actualizada sobre el error en Medicina. Se discutieron diferentes aristas de este tópico y la utilidad que tiene su reconocimiento para mejorar el trabajo médico asistencial; a partir de ahí se trazaron diferentes estrategias y pautas para su correcta interpretación. Se insistió en su utilización para alejar a los pacientes de esa infeliz probabilidad y obtener beneficios. Este cambio realmente debe comenzar desde la propia profesión médica; la primera tarea sería su divulgación en prestigiosas revistas médicas del mundo para su análisis y conocimiento.

ABSTRACT In Medicine, as in all human activities, involuntary errors occur frequently. This topic must be treated with depth and sincerity in the scientific community, as an initial step for its future prevention. An updated review on the error in Medicine was made, and different aspects of this topic were discussed, as well as, the usefulness of its recognition to improve medical practice; from thereon, different strategies and guidelines were drawn up for its correct interpretation. It was insisted on its use to keep patients away from that unfortunate probability and obtain benefits. This change must really start from the medical profession itself; the first task would be its dissemination in prestigious medical journals of the world for its analysis and knowledge.

Estimation of Insulin Resistance in Mexican Adults by the [(13)C]Glucose Breath Test Corrected for Endogenous Total CO(2) Production.

Objective. To evaluate the efficacy of the [(13)C]glucose breath test for measuring insulin resistance in Mexican adults with different glycemic states. Research Design and Methods. Fifty-eight adults underwent a [(13)C]glucose breath test with simultaneous measurement of total CO(2) production by indirect calorimetry, at baseline and 90 minutes after the ingestion of 15 g of dextrose and 25 mg of [(13)C]glucose. HOMA was used as a marker of insulin resistance. Results. We found an inverse correlation between HOMA and the breath test δ(13)CO(2) (‰), r = -0.41 (P = 0.001). After adjusting for total CO(2) production, correlations between HOMA and fasting glucose were less strong but remained significant. An ROC curve was constructed using δ(13)CO(2) (‰) and HOMA values; the cut-off point was 9.99‰ δ(13)CO(2), corresponding to a sensitivity of 80.0 (95% CI: 51.9, 95.7) and a specificity of 67.4 (95% CI: 51.5, 80.9). Conclusions. The [(13)C]glucose breath test is a simple noninvasive procedure but was not sufficiently robust for an accurate diagnosis of insulin resistance. Our findings suggest that the test might be helpful in identifying individuals who are not IR, which in turn may contribute to improved diabetes prevention.