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Background and Objective: Adjacent segment disease (ASD) is a late complication of lumbar fusion characterized by persistent symptoms correlating to radiographic changes in the levels immediately above or below the prior fusion. Lateral interbody fusion (LIF) through a direct lateral approach is a minimally invasive and effective surgical treatment for ASD. Biomechanically, LIF for ASD provides significantly decreased motion in multiple planes. While hardware failure and injury to the lumbar plexus are potential complications, these risks may be outweighed by decreased blood loss, shorter operating room (OR) times, and possibly superior patient reported visual analog scale (VAS) scores compared to traditional posterior spinal fusion (PSF) alone. The purpose of this review is to summarize the history, uses, outcomes, and future directions of LIF for ASD. Methods: A review of national databases (PubMed and SCOPUS) was performed using literature from 1900 to 2022. Keywords included terms "LATERAL" and "LUMBAR" and "INTERBODY" and "FUSION" and "ADJACENT" and "SEGMENT" and "DISEASE". Studies that aimed to describe the biomechanical, clinical course and complications, radiological outcomes, biomechanical aspects, need for revision surgery, and/or patient reported outcomes of the XLIF/LIF technique were included. Key Content and Findings: This review includes a brief overview of the natural history of ASD and current approaches to address it. It then summarizes the main indications and utilization of LIF to address ASD, summarizing reported outcomes in regard to biomechanical, clinical, and radiographic outcomes. Conclusions: LIF has emerged as a minimally invasive and effective surgical treatment for ASD. This mini-review suggests that LIF provides a solid foundational biomechanical construct that has been paired with good patient-reported, clinical, and radiographic outcomes. While further research is required, current literature suggests that LIF for ASD results in fewer complications, decreased morbidity, and decreased need for subsequent surgery compared to other commonly utilized techniques.
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Given high patient expectations in the setting of complex surgeries, orthopedic surgeons are at risk of being subject to malpractice claims which can impose significant economic and psychological burden. This study investigates malpractice claims against orthopedic surgeons and podiatrists performing hindfoot arthrodesis and determine factors associated with plaintiff verdicts and settlements using the Westlaw legal database. The database was queried for all cases involving hindfoot arthrodesis using the terms "malpractice" and either "ankle fusion," "arthrodesis," "subtalar fusion," "tibiotalar fusion," "tibiotalocalcaneal fusion," "TTC fusion," or "tibiofibular fusion" from 1987 to 2023. Data regarding patient demographics, causes cited for litigation, case outcomes, and indemnity settlements were collected. Cases were excluded if the defendant was not an orthopedic surgeon or a podiatrist, the procedure involved was not a hindfoot arthrodesis, or if the patient was a minor. Forty-five cases of hindfoot arthrodesis met the inclusion criteria. The mean plaintiff age was 51.5 ± 13.8 years with 51.1% male. Thirty-three cases (73%) were in favor of the defendant, with an average inflation-adjusted payout of $853,863 (±456,179). The most alleged category of negligence was procedural/intraoperative error (75%) followed by postsurgical error (38%) and failure to inform (31%). The most common specific damages included functional/ROM limitation (49%), need for additional surgery (47%), continuing/worsened pain (27%), and nonunion/malunion (29%). Given the frequency of hindfoot arthrodesis performed, this study highlights the importance of effective communication with patients concerning potential postoperative complications, prognosis of their injury, and risks and benefits associated with each treatment modality.
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Tears of the gluteus medius and minimus have emerged as significant contributors to lateral hip pain and functional impairment. Surgical intervention reliably delivers pain alleviation and ability to return to activities. Nevertheless, conventional open procedures entail substantial incisions, extensive tissue damage, and protracted recovery. Endoscopic approaches have provided minimally invasive alternative strategies. This Technical Note details a method for addressing partial gluteus medius tears by recreating the hip abductor tendon insertion footprint and employing a bioinductive patch to promote wound healing.
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INTRODUCTION: Clinicians have limited options outside controlled substances to address sleep disturbance, which left untreated can negatively affect patient outcomes in cardiovascular health, mental health, immunologic function, and more. For some, genetic factors may influence sleep disturbances. L-methylfolate, the active form of folate, plays a critical role in regulation of monoamine neurotransmitters known to have significant impact on sleep regulation: dopamine, serotonin, norepinephrine. Single nucleotide polymorphisms of the enzyme methylene-tetrahydrofolate-reductase are common and can impact monoamine production. The goal of this study was to evaluate effects of L-methylfolate supplementation on sleep in a cohort with reduced methylene tetrahydrofolate reductase (MTHFR) activity. METHODS: A retrospective cohort of patients being treated with L-methylfolate in a concierge medical clinic setting was studied. Patients presenting with sleep complaints were evaluated using the Patient-Reported Outcomes Measurement Information System at baseline. Patients with known MTHFR polymorphisms at either C667T and/or A1298C were recommended 5 mg of L-methylfolate daily and were reevaluated at 2 wks, at 4 wks, and at 8 wks of supplementation. Statistical comparisons were made utilizing ANOVA and T-test comparisons. RESULTS: Ten were included in the final cohort: six male and four female, average age 43 ± 16 years. Beginning at wk 2, average sleep disturbance improved significantly by -6.94 points (p = 0.005) and by 8 wks, all patients had improvement with a -14.34 change in disturbance from baseline (p = 0.001). CONCLUSION: Improvement in sleep disturbance was seen in both low and intermediate function phenotypes. L-methylfolate may be useful for improving sleep in patients with MTHFR polymorphism.
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Suplementos Dietéticos , Metilenotetrahidrofolato Reductasa (NADPH2) , Sueño , Tetrahidrofolatos , Humanos , Masculino , Femenino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Estudios Retrospectivos , Persona de Mediana Edad , Tetrahidrofolatos/administración & dosificación , Adulto , Sueño/efectos de los fármacos , Polimorfismo de Nucleótido Simple , Trastornos del Sueño-Vigilia/tratamiento farmacológicoRESUMEN
BACKGROUND: Smoking cessation therapy, including nicotine replacement therapy (NRT), is used perioperatively to assist patients to reduce their tobacco smoke intake and consequently decrease their risk of smoking-associated complications. There are, however, theoretical concerns that nicotine-induced peripheral vasoconstriction could impair wound healing. This study investigated the effect of NRT on postoperative outcomes in patients undergoing breast surgery. METHODS: A retrospective chart review of patients undergoing breast surgery within the Yale New Haven Health System from the years 2014 to 2020 was performed. Documented smoking status within 6 months before surgery, use or prescription of NRT, type of surgery, and surgical complications of infection, wound dehiscence, tissue necrosis, hematoma, seroma, fat necrosis, and return to operating room within 30 days were recorded. Demographic and complication data were compared between patients with NRT usage and those without using t-tests and chi-square analyses. Multivariable logistic regression models were created to predict the effect of NRT usage on the occurrence of any complication. RESULTS: A total of 613 breast procedures met inclusion criteria, of which 105 (17.2%) had documented NRT use. The NRT cohort and the non-NRT cohort were well balanced with respect to demographics and procedural variables. Upon multivariable modeling for risk of any surgical complication, NRT was not a significant predictor (odds ratio [OR]: 1.199, p = 0.607 and OR: 0.974, p = 0.912, respectively), whereas procedure type, increased body mass index, and increased age were. CONCLUSION: NRT use was not associated with an increased risk of postoperative complications compared with not using NRT as part of smoking cessation therapy prior to operation.
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Neoplasias de la Mama , Cese del Hábito de Fumar , Humanos , Femenino , Cese del Hábito de Fumar/métodos , Agonistas Nicotínicos , Terapia de Reemplazo de Nicotina , Estudios Retrospectivos , Dispositivos para Dejar de Fumar Tabaco , Prevención del Hábito de Fumar , Complicaciones PosoperatoriasRESUMEN
Transplant-associated thrombotic microangiopathy (TA-TMA) is a common and potentially severe complication of hematopoietic cell transplantation. TA-TMA-directed therapy with eculizumab, a complement C5 inhibitor, has resulted in a survival benefit in some studies. However, children with TA-TMA refractory to C5 inhibition with eculizumab (rTA-TMA) have mortality rates exceeding 80%, and there are no other known therapies. Narsoplimab, an inhibitor of the MASP-2 effector enzyme of the lectin pathway, has been studied in adults with TA-TMA as first-line therapy with a response rate of 61%. Although there are limited data on narsoplimab use as a second-line agent in children, we hypothesized, that complement pathways proximal to C5 are activated in rTA-TMA, and that narsoplimab may ameliorate rTA-TMA in children. In this single-center study, children were enrolled on single-patient, Institutional Review Board-approved compassionate use protocols for narsoplimab treatment. Clinical complement lab tests were obtained at the discretion of the treating physician, although all patients were also offered participation in a companion biomarker study. Research blood samples were obtained at the time of TA-TMA diagnosis, prior to eculizumab treatment, at the time of refractory TA-TMA diagnosis prior to the first narsoplimab dose, and 2 weeks after the first narsoplimab dose. Single ELISA kits were used to measure markers of complement activation according to the manufacture's instructions. Five children with rTA-TMA received narsoplimab; 3 were in multiorgan failure and 2 had worsening multiorgan dysfunction at the time of treatment. Additional comorbidities at the time of treatment included sinusoidal obstructive syndrome (SOS; n = 3), viral infection (n = 3), and steroid-refractory stage 4 lower gut grade IV acute graft-versus-host disease (aGVHD, n = 3). Two infants with concurrent SOS and no aGVHD had resolution of organ dysfunction; 1 also developed transfusion-independence (complete response), and the other's hematologic response was not assessable in the setting of leukemia and chemotherapy (partial response). One additional patient achieved transfusion independence but had no improvement in organ manifestations (partial response), and 2 patients treated late in the course of disease had no response. Narsoplimab was well tolerated without any attributed adverse effects. Three patients consented to provide additional research blood samples. One patient with resolution of organ failure demonstrated evidence of proximal pathway activation prior to narsoplimab treatment with subsequent declines in Ba, Bb, C3a, and C5a and increases in C3 in both clinical and research lab tests. Otherwise, there was no clear pattern of other complement markers, including MASP-2 levels, after therapy. In this cohort of ill children with rTA-TMA and multiple comorbidities, 3 patients benefited from narsoplimab. Notably, the 2 patients with resolution of organ involvement did not have steroid-refractory aGVHD, which is thought to be a critical driver of TA-TMA. Additional studies are needed to determine which patients are most likely to benefit from narsoplimab and which markers may be most helpful for monitoring lectin pathway activation and inhibition.
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Anticuerpos Monoclonales Humanizados , Ensayos de Uso Compasivo , Microangiopatías Trombóticas , Adulto , Niño , Lactante , Humanos , Ensayos de Uso Compasivo/efectos adversos , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/uso terapéutico , Microangiopatías Trombóticas/tratamiento farmacológico , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/diagnóstico , Proteínas del Sistema Complemento/uso terapéutico , Inactivadores del Complemento/uso terapéutico , Lectinas/uso terapéutico , Esteroides/uso terapéuticoRESUMEN
PURPOSE: A medical chaperone serves as a witness for a patient and health care practitioner during a medical examination. We sought to better understand the preferences of parents and children toward the use of chaperones during pediatric physical examinations. METHODS: This cross-sectional study surveyed patients aged 8 to 18 years and their parents presenting primarily to the emergency department as well as primary care ambulatory clinic and inpatient units. Participants were asked which individuals (patient alone, parent, or medical chaperone) should be present for each aspect of the child's physical examination. RESULTS: The survey was completed by 121 patients (mean age 14 years, 58.5% girls) and 122 parents (mean age 42 years, 82.8% women) in a variety of clinical settings (17 in inpatient, 17 in outpatient clinic, and 87 emergency department admissions). Significant differences existed between male and female patients regarding preferred presence for every body part being examined ( P ≤ 0.002). Female patients preferred to have a same-sex parent in the room, particularly for examination of the breasts, genitalia, or rectum and when the examination was performed by a male provider. Male patients preferred to be alone or with either parent for any body part being examined, regardless of provider sex. CONCLUSIONS: Adolescents have significant differences in who they prefer to be in the room for the physical examination based on patient and provider sex in settings where they are unfamiliar with the health care examiner. Few patients and parents preferred a medical chaperone; most preferred a parent to be in the room. Patient and parent considerations should be prioritized when creating policies for the use of medical chaperones.
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Introduction Head and neck cancers are heterogeneous malignancies associated with significant morbidity. Oral cancers are related to the use of tobacco products. Smokeless tobacco usage is a health problem worldwide, and its carcinogenic mechanism is largely unknown. Despite advances in conventional treatments, side effects and drug resistance remain unsolved. Therefore, novel therapeutic agents with minimal side effects using plant derivatives should be explored. An active antihyperglycemic and antioxidant compound known as FIIc was isolated from the fruit pulp of Eugenia jambolana (US Patent No.: 2,30,753). Although E. jambolana is reported to have anticancer activity, no study has been reported on its growth kinetics and apoptotic potential in the human head and neck cancer cell line (SCC4). The present study evaluated the effect of an herbal compound isolated from the fruit pulp of E. jambolana and chemically synthesized the same compound, α-hydroxy succinamic acid (α-HSA), on SCC4 proliferation and apoptotic gene expression. Methods The SCC4 cell line was cultured in Dulbecco's Modified Eagle Medium (DMEM). The dosages of smokeless tobacco extract (STE), herbal compound, and synthetic compound were determined by cell viability assay, and their effect on mRNA expression of apoptotic genes was measured by real-time polymerase chain reaction. Results The present study observed significant therapeutic effects of the natural and synthetic compounds from the fruit pulp of E. jambolana at the concentration range of 100-200 µg/mL on the SCC4 cell line. α-HSA had antiproliferative action; upregulated apoptotic genes like p53, p21, and Bax; and downregulated anti-apoptotic genes like survivin in the SCC4 cell line. Conclusion The therapeutic potential of α-HSA and the putative mechanisms involved may be explored to provide the basis for future therapeutic interventions in oral cancer mediated by smokeless tobacco.
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Background: Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. Methods: We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. Results: Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. Conclusions: DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.
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Idarrubicina , Leucemia Mieloide Aguda , Humanos , Idarrubicina/efectos adversos , Citarabina/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Estaurosporina/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Tirosina Quinasa 3 Similar a fms/genética , Mutación , Inducción de RemisiónRESUMEN
RBC alloimmunization remains a significant barrier to ongoing transfusion therapy leading to morbidity, and in extreme cases mortality, due to delayed or insufficient units of compatible RBCs. In addition, the monitoring and characterization of alloantibodies, often with multiple specificities in a single patient, consumes substantial health care resources. Extended phenotypic matching has mitigated, but not eliminated, RBC alloimmunization and is only logistically available for specialized populations. Thus, RBC alloimmunization remains a substantial problem. In recent decades it has become clear that mechanisms of RBC alloimmunization are distinct from other antigens and lack of mechanistic understanding likely contributes to the fact that there are no approved interventions to prevent RBC alloimmunization from transfusion. The combination of human studies and murine modeling have identified several key factors in RBC alloimmunization. In both humans and mice, immunogenicity is a function of alloantigen copy number on RBCs. Murine studies have further shown that copy number not only changes rates of immunization but the mechanisms of antibody formation. This review summarizes the current understanding of quantitative and qualitative effects of alloantigen copy number on RBC alloimmunization.
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Variaciones en el Número de Copia de ADN , Isoantígenos , Humanos , Ratones , Animales , Eritrocitos , Transfusión Sanguínea , IsoanticuerposRESUMEN
The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease-a major complication of allogeneic HCT-to enable the patient and clinician to assess management options in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for HCT, including the incorporation of a newly developed section on the Principles of Conditioning for HCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Humanos , Trasplante Homólogo , Recurrencia Local de Neoplasia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
OBJECTIVE: To understand the effects of nutrition security and social determinants of health (SDOHs) on pressure injury (PI) progression through a scoping review and retrospective review of patients reporting to New England's largest healthcare system. METHODS: Authors performed a scoping review for full-text, original articles reporting outcomes data specific to PIs in patients with socially informed nutrition insecurity. Investigators also performed a retrospective review of all patients from 2012 to 2021 to search for patients with PI documentation and International Classification of Diseases, Tenth Revision Z codes related to the SDOHs. RESULTS: A full-text review of 2,323 articles from 1965 to 2020 failed to locate any eligible studies. Investigators identified 1,044 patients who met the inclusion criteria; 50.7% were men, 74.3% were White, and 13.3% had evidence of detrimental SDOHs. The average PI duration was 12.13 days (interquartile range, 6 days). Multivariate regression analysis revealed that PI duration was longer in men, Black patients, and patients with evidence of detrimental SDOHs compared with their converse counterparts (P < .0001). The presence of detrimental SDOHs independently predicted an increased duration of disease by 13.07 days (95% CI, 8.99-17.15; t = 6.29, P < .0001). CONCLUSIONS: A patient's SDOH history has a significant and considerably stronger correlation with disease progression than predictors that are traditionally studied such as sex, race, or body mass index. These findings are novel, as highlighted by the absence of data uncovered in the literature. These data carry relevance for plastic surgeons wishing to prevent early recurrence following operative closure of PI-related wounds.
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Úlcera por Presión , Determinantes Sociales de la Salud , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Antibodies against red blood cell (RBC) alloantigens can increase morbidity and mortality among transfusion recipients. However, alloimmunization rates can vary dramatically, as some patients never generate alloantibodies after transfusion, whereas others not only become alloimmunized but may also be prone to generating additional alloantibodies after subsequent transfusion. Previous studies suggested that CD4 T-cell responses that drive alloantibody formation recognize the same alloantigen engaged by B cells. However, because RBCs express numerous antigens, both internally and externally, it is possible that CD4 T-cell responses directed against intracellular antigens may facilitate subsequent alloimmunization against a surface RBC antigen. Here, we show that B cells can acquire intracellular antigens from RBCs. Using a mouse model of donor RBCs expressing 2 distinct alloantigens, we demonstrate that immune priming to an intracellular antigen, which would not be detected by any currently used RBC compatibility assays, can directly influence alloantibody formation after exposure to a subsequent distinct surface RBC alloantigen. These findings suggest a previously underappreciated mechanism whereby transfusion recipient responders may exhibit an increased rate of alloimmunization because of prior immune priming toward intracellular antigens.
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Transfusión de Eritrocitos , Isoanticuerpos , Transfusión de Eritrocitos/efectos adversos , Eritrocitos , Antígenos , Isoantígenos , InmunizaciónRESUMEN
INTRODUCTION: The impact of blood storage on red blood cell (RBC) alloimmunization remains controversial, with some studies suggesting enhancement of RBC-induced alloantibody production and others failing to observe any impact of storage on alloantibody formation. Since evaluation of storage on RBC alloimmunization in patients has examined antibody formation against a broad range of alloantigens, it remains possible that different clinical outcomes reflect a variable impact of storage on alloimmunization to specific antigens. METHODS: RBCs expressing two distinct model antigens, HEL-OVA-Duffy (HOD) and KEL, separately or together (HOD × KEL), were stored for 0, 8, or 14 days, followed by detection of antigen levels prior to transfusion. Transfused donor RBC survival was assessed within 24 h of transfusion, while IgM and IgG antibody production were assessed 5 and 14 days after transfusion. RESULTS: Stored HOD or KEL RBCs retained similar HEL or KEL antigen levels, respectively, as fresh RBCs, but did exhibit enhanced RBC clearance with increased storage age. Storage enhanced IgG antibody formation against HOD, while the oppositive outcome occurred following transfusion of stored KEL RBCs. The distinct impact of storage on HOD or KEL alloimmunization did not appear to reflect intrinsic differences between HOD or KEL RBCs, as transfusion of stored HOD × KEL RBCs resulted in increased IgG anti-HOD antibody development and reduced IgG anti-KEL antibody formation. CONCLUSIONS: These data demonstrate a dichotomous impact of storage on immunization to distinct RBC antigens, offering a possible explanation for inconsistent clinical experience and the need for additional studies on the relationship between RBC storage and alloimmunization.
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Antígenos , Transfusión de Eritrocitos , Ratones , Animales , Transfusión de Eritrocitos/efectos adversos , Eritrocitos , Isoantígenos , Isoanticuerpos , Inmunoglobulina GRESUMEN
The COVID-19 pandemic has provided stiff challenges for planning and resourcing in health services in the UK and worldwide. Epidemiological models can provide simulations of how infectious disease might progress in a population given certain parameters. We adapted an agent-based model of COVID-19 to inform planning and decision-making within a healthcare setting, and created a software framework that automates processes for calibrating the model parameters to health data and allows the model to be run at national population scale on National Health Service (NHS) infrastructure. We developed a method for calibrating the model to three daily data streams (hospital admissions, intensive care occupancy, and deaths), and demonstrate that on cross-validation the model fits acceptably to unseen data streams including official estimates of COVID-19 incidence. Once calibrated, we use the model to simulate future scenarios of the spread of COVID-19 in England and show that the simulations provide useful projections of future COVID-19 clinical demand. These simulations were used to support operational planning in the NHS in England, and we present the example of the use of these simulations in projecting future clinical demand during the rollout of the national COVID-19 vaccination programme. Being able to investigate uncertainty and test sensitivities was particularly important to the operational planning team. This epidemiological model operates within an ecosystem of data technologies, drawing on a range of NHS, government and academic data sources, and provides results to strategists, planners and downstream data systems. We discuss the data resources that enabled this work and the data challenges that were faced.
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COVID-19 , Humanos , Medicina Estatal , Pandemias , Vacunas contra la COVID-19 , Calibración , Ecosistema , Atención a la SaludRESUMEN
MPYS/STING (stimulator of IFN genes) senses cyclic dinucleotides (CDNs), generates type I IFNs, and plays a critical role in infection, inflammation, and cancer. In this study, analyzing genotype and haplotype data from the 1000 Genomes Project, we found that the R71H-G230A-R293Q (HAQ) MPYS allele frequency increased 57-fold in East Asians compared with sub-Saharan Africans. Meanwhile, the G230A-R293Q (AQ) allele frequency decreased by 98% in East Asians compared with sub-Saharan Africans. We propose that the HAQ and AQ alleles underwent a natural selection during the out-of-Africa migration. We used mouse models of HAQ and AQ to investigate the underlying mechanism. We found that the mice carrying the AQ allele, which disappeared in East Asians, had normal CDN-type I IFN responses. Adult AQ mice, however, had less fat mass than did HAQ or wild-type mice on a chow diet. AQ epididymal adipose tissue had increased regulatory T cells and M2 macrophages with protein expression associated with enhanced fatty acid oxidation. Conditional knockout mice and adoptive cell transfer indicate a macrophage and regulatory T cell-intrinsic role of MPYS in fatty acid metabolism. Mechanistically, AQ/IFNAR1-/- mice had a similar lean phenotype as for the AQ mice. MPYS intrinsic tryptophan fluorescence revealed that the R71H change increased MPYS hydrophilicity. Lastly, we found that the second transmembrane (TM) and the TM2-TM3 linker region of MPYS interact with activated fatty acid, fatty acyl-CoA. In summary, studying the evolution of the human MPYS gene revealed an MPYS function in modulating fatty acid metabolism that may be critical during the out-of-Africa migration.
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Ácidos Grasos , Tolerancia Inmunológica , Proteínas de la Membrana , Adulto , Animales , Humanos , Ratones , Ácidos Grasos/metabolismo , Homeostasis , Proteínas de la Membrana/metabolismo , Ratones Noqueados , Interferón Tipo IRESUMEN
Responsibilities placed on nurses increased during the COVID-19 pandemic. Hospital-acquired PI monitoring was deferred in favor of more critical patient needs. It was hypothesized that a counterintuitive dip in HAPI reporting would be observed despite maximum hospital capacity across much of the United States. The electronic medical records of patients treated in the YNHH System between December 2017 and February 2021 were retrospectively reviewed to identify patients with HAPIs, defined as PIs not documented upon admission but subsequently present during the patient's hospital stay. Paired t test revealed a significantly lower number of reported incidents mid-pandemic than during the prepandemic baseline months (P <.0001). The data in this report show interdisciplinary clinician-led teams must continue to monitor for HAPIs and congruous conditions to minimize reporting gaps and progression in PI severity despite COVID-19 pandemic-related conditions and additional related responsibilities.
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COVID-19 , Úlcera por Presión , COVID-19/epidemiología , Humanos , Enfermedad Iatrogénica , Pandemias , Úlcera por Presión/epidemiología , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
Small intestinal bacterial overgrowth (SIBO) can exist in common conditions such as irritable bowel syndrome, obesity, cirrhosis, and Parkinson. Using the functional medicine matrix broadens the lens of how to evaluate SIBO. Assessing the predisposing factors, triggers, and contributors of SIBO enables the provider to better understand possible management strategies. Applying the functional medicine 5R program, remove, replenish, repair, reinoculate, and rebalance includes conventional treatment of SIBO and expands the provider's toolbox on different modalities to restore gut function.