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Giant exoplanets orbiting close to their host stars are unlikely to have formed in their present configurations1. These 'hot Jupiter' planets are instead thought to have migrated inward from beyond the ice line and several viable migration channels have been proposed, including eccentricity excitation through angular-momentum exchange with a third body followed by tidally driven orbital circularization2,3. The discovery of the extremely eccentric (e = 0.93) giant exoplanet HD 80606 b (ref. 4) provided observational evidence that hot Jupiters may have formed through this high-eccentricity tidal-migration pathway5. However, no similar hot-Jupiter progenitors have been found and simulations predict that one factor affecting the efficacy of this mechanism is exoplanet mass, as low-mass planets are more likely to be tidally disrupted during periastron passage6-8. Here we present spectroscopic and photometric observations of TIC 241249530 b, a high-mass, transiting warm Jupiter with an extreme orbital eccentricity of e = 0.94. The orbit of TIC 241249530 b is consistent with a history of eccentricity oscillations and a future tidal circularization trajectory. Our analysis of the mass and eccentricity distributions of the transiting-warm-Jupiter population further reveals a correlation between high mass and high eccentricity.
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INTRODUCTION: A paucity of literature exists regarding current opioid prescribing and use following bariatric surgery. We aimed to characterize opioid prescribing practices and use following bariatric surgery to inform future studies and optimized prescribing practices. METHODS AND PROCEDURE: We performed a systematic review of Ovid MEDLINE, Ovid Embase, Scopus, Web of Science Core Collection, and Cochrane Library (via WILEY) on August 20, 2021. Two reviewers reviewed and extracted data independently. Studies evaluating adult patients undergoing bariatric surgery that reported opioid prescriptions at discharge were included. Abstracts, non-English studies, and those with n < 5 were excluded. Primary outcomes assessed the amount of morphine milligram equivalents (MMEs) prescribed at discharge. Secondary outcomes evaluated opioids used following discharge, proportion of patients with unused opioid, and if unused opioids were properly discarded. RESULTS: We evaluated 2113 studies, with 18 undergoing full-text review, and 5 meeting inclusion criteria. Overall, 847 patients were included, with 450 (53%) undergoing sleeve gastrectomy and 393 (46%) receiving Roux-en-Y gastric bypass. Most patients were female (n = 484/589, 82.2%), and the average age and BMI were 44.6 (± 11.8) years and 48.1 kg/m2 (± 8.4 kg/m2), respectively. On average, 348.4 MMEs were prescribed to patients undergoing bariatric surgery. Patients used only 84.7 MMEs, with 87.0% (95% CI 66.0-99.0%) having unused opioid, and 41/120 (34.2%) retaining these excess opioids. CONCLUSION: Nearly 90% of all bariatric patients evaluated in our systematic review are prescribed excessive opioids at discharge. Further work characterizing current opioid prescribing practices and use may help guide development of standardized post-bariatric surgery prescription guidelines.
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Cirugía Bariátrica , Derivación Gástrica , Adulto , Femenino , Humanos , Masculino , Analgésicos Opioides/uso terapéutico , Derivación Gástrica/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Persona de Mediana EdadRESUMEN
BACKGROUND: Patient comfort during invasive and therapeutic procedures is important. The use of virtual reality (VR) devices during flexible bronchoscopy (FB) as a method of distraction to increase patient tolerability and improve satisfaction has not been investigated. We aim to assess the satisfaction and tolerability of participants undergoing FB with or without VR. METHODS: This was a single-center, open-label study on patients undergoing bronchoscopy, randomized into the control and interventional (VR) groups. The control group received standard care during FB. The interventional group was given a VR device during FB showing nature videos with soothing instrumental music. Pain, breathlessness, and cough were evaluated using a 10 cm visual analogue scale administered before and after FB. Anxiety was assessed using the State-Trait Anxiety Inventory. Satisfaction questionnaire (5-point Likert scale) was given to participants post FB. RESULTS: Eighty participants enrolled, 40 in each arm. Median (IQR) satisfaction score in the VR group was 5.0 (3.0-5.0), and in the control group was 4.0 (3.0-5.0); (p < 0.001). Breathlessness, cough, and anxiety post FB were significantly less severe in the interventional group (p = 0.042, p = 0.001, p < 0.001), but the pain was not significantly different (p = 0.290). CONCLUSION: VR used during FB led to better participants' satisfaction and tolerability (breathlessness and cough). There was a significantly lower anxiety score in the VR group.
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Tos , Realidad Virtual , Humanos , Broncoscopía/efectos adversos , Satisfacción del Paciente , Ansiedad , DolorRESUMEN
INTRODUCTION: Wound care is a substantial industry costing nearly $19 billion USD, and dedicated wound care centers play a critical role via a multidisciplinary team-based approach. At the same time, plastic surgeons are often considered experts in evaluation and management of wounds, particularly chronic and complex wounds. However, the extent of direct involvement of plastic surgeons in wound care centers is unclear. In this study, we sought to evaluate the presence of plastic surgeons and other specialties in wound care centers across all Northeastern states Connecticut, Delaware, District of Columbia, Maine, Maryland, Massachusetts, New Jersey, New York, New Hampshire, Pennsylvania, Rhode Island, Virginia, West Virginia, and Vermont. METHODS: A comprehensive list of wound care clinics in northeastern United States was obtained from the Healogics website. For each site, information was gathered via website listings, including number of providers and the professional certification/specialization for each provider. Providers were those with qualifications including Doctor of Medicine (MD), Doctor of Osteopathic Medicine (DO), Doctor of Physical Therapy (DPT), Doctor of Podiatric Medicine (DPM), Certified Registered Nurse Anesthetist (CRNA), Certified Registered Nurse Practitioner (CRNP), Physician Associate (PA), and Physical Therapist (PT). RESULTS: A total of 118 Healogics wound care clinics and 492 providers were located across 14 northeastern states including District of Columbia. After researching each location, updated in November 2022, plastic surgeons were only 3.7% (18 of 492) providers employed. Specialties such as internal medicine (90 of 492 [18%]), general surgery (76 of 492 [15%]), podiatry (68 of 292 [13.8% ]), and other midlevel providers such as nurse practitioners (35 of 492 [7.1%]) were more frequently employed over plastic surgery. All plastic surgeons were board certified the American Board of Plastic Surgery. CONCLUSIONS: Wound care requires collaboration between specialties, with significant repercussions on health care costs and patient outcomes. Plastic surgery provides unique surgical services for the healing of wounds, and the natural expectation would be that plastic surgery should be heavily involved at wound care centers. However, the data do not reflect significant involvement at an official level. Further studies will investigate causes and the societal, financial, and patient impacts of this lack of direct engagement. Although many plastic surgeons may not desire the majority of their practice to be wound care management, it stands to reason that some affiliation, at least for patient awareness and referral, may be warranted.
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Cirugía Plástica , Humanos , Costos de la Atención en Salud , New England , New York , Pennsylvania , Estados UnidosRESUMEN
NK cells can recognize target cells such as virus-infected and tumor cells through integration of activation and inhibitory receptors. Recognition by NK cells can lead to direct lysis of the target cell and production of the signature cytokine IFN-γ. However, it is unclear whether stimulation through activation receptors alone is sufficient for IFN-γ production. In this study, we show that NK activation receptor engagement requires additional signals for optimal IFN-γ production, which could be provided by IFN-ß or IL-12. Stimulation of murine NK cells with soluble Abs directed against NK1.1, Ly49H, Ly49D, or NKp46 required additional stimulation with cytokines, indicating that a range of activation receptors with distinct adaptor molecules require additional stimulation for IFN-γ production. The requirement for multiple signals extends to stimulation with primary m157-transgenic target cells, which triggers the activation receptor Ly49H, suggesting that NK cells do require multiple signals for IFN-γ production in the context of target cell recognition. Using quantitative PCR and RNA flow cytometry, we found that cytokines, not activating ligands, act on NK cells to express Ifng transcripts. Ly49H engagement is required for IFN-γ translational initiation. Results using inhibitors suggest that the proteasome-ubiquitin-IKK-TPL2-MNK1 axis was required during activation receptor engagement. Thus, this study indicates that activation receptor-dependent IFN-γ production is regulated on the transcriptional and translational levels.
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Interferón gamma/inmunología , Células Asesinas Naturales/inmunología , Complejo de la Endopetidasa Proteasomal/inmunología , Biosíntesis de Proteínas/inmunología , Transducción de Señal/inmunología , Transcripción Genética/inmunología , Animales , Antígenos Ly/genética , Antígenos Ly/inmunología , Interferón gamma/genética , Células Asesinas Naturales/citología , Ratones , Ratones Noqueados , Subfamilia A de Receptores Similares a Lectina de Células NK/genética , Subfamilia A de Receptores Similares a Lectina de Células NK/inmunología , Subfamilia B de Receptores Similares a Lectina de Células NK/genética , Subfamilia B de Receptores Similares a Lectina de Células NK/inmunología , Receptor 1 Gatillante de la Citotoxidad Natural/genética , Receptor 1 Gatillante de la Citotoxidad Natural/inmunología , Complejo de la Endopetidasa Proteasomal/genética , Transducción de Señal/genéticaRESUMEN
The rapid increase in the number of worldwide human infections caused by the extremely antibiotic resistant bacterial pathogen Stenotrophomonas maltophilia is cause for concern. An alternative treatment solution in the post-antibiotic era is phage therapy, the use of bacteriophages to selectively kill bacterial pathogens. In this study, the novel bacteriophage AXL3 (vB_SmaS-AXL_3) was isolated from soil and characterized. Host range analysis using a panel of 29 clinical S. maltophilia isolates shows successful infection of five isolates and electron microscopy indicates that AXL3 is a member of the Siphoviridae family. Complete genome sequencing and analysis reveals a 47.5 kb genome predicted to encode 65 proteins. Functionality testing suggests AXL3 is a virulent phage and results show that AXL3 uses the type IV pilus, a virulence factor on the cell surface, as its receptor across its host range. This research identifies a novel virulent phage and characterization suggests that AXL3 is a promising phage therapy candidate, with future research examining modification through genetic engineering to broaden its host range.
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Bacteriófagos/crecimiento & desarrollo , Bacteriófagos/aislamiento & purificación , Genoma Viral , Especificidad del Huésped , Receptores Virales/metabolismo , Stenotrophomonas maltophilia/virología , Virión/crecimiento & desarrollo , Bacteriófagos/genética , Bacteriófagos/ultraestructura , HumanosRESUMEN
BACKGROUND AND OBJECTIVE: The Southeast Asia (SEA) haze is an annual problem and at its worst could produce respirable particles of concentrations up to 500 µg/m3 which is five times the level considered as 'unhealthy'. However, there are limited reports examining the direct clinical impact of the annual haze. This study examines the effects of the SEA haze on respiratory admissions. METHODS: Data from all respiratory admissions in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from 1st January 2014 to 31st December 2015 were collected retrospectively from chart and electronic database. A total of 16 weeks of haze period had been formally dated by the Department of Environment using the definition of weather phenomenon leading to atmospheric visibility of less than 10 km. Multivariable regression analyses were performed to estimate rate ratios and 95% CI. RESULTS: There were 1968 subjects admitted for respiratory admissions in UKMMC during the study period. Incidence rates per week were significantly different between the two groups with 27.6 ± 9.2 cases per week during the haze versus 15.7 ± 6.7 cases per week during the non-haze period (P < 0.01). A total of 4% versus 2% was admitted to the intensive care unit in the haze and the non-haze groups, respectively (P = 0.02). The mean ± SD lengths of stay was 12.1 ± 5.2 days; the haze group had a longer stay (18.2 ± 9.7 days) compared to the non-haze groups (9.7 ± 3.9) (P < 0.001). CONCLUSION: The annual SEA haze is associated with increased respiratory admissions.
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Contaminación del Aire , Material Particulado , Admisión del Paciente/estadística & datos numéricos , Enfermedades Respiratorias/epidemiología , Centros Médicos Académicos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Tiempo de Internación , Malasia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estaciones del AñoRESUMEN
Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types, such as neurons, and mesodermal cell types, such as smooth muscle. The mechanisms controlling this cell fate choice are not known. The basic Helix-loop-Helix (bHLH) transcription factor Twist1 is expressed throughout the migratory and post-migratory cardiac neural crest. Twist1 ablation or mutation of the Twist-box causes differentiation of ectopic neuronal cells, which molecularly resemble sympathetic ganglia, in the cardiac outflow tract. Twist1 interacts with the pro-neural factor Sox10 via its Twist-box domain and binds to the Phox2b promoter to repress transcriptional activity. Mesodermal cardiac neural crest trans-differentiation into ectodermal sympathetic ganglia-like neurons is dependent upon Phox2b function. Ectopic Twist1 expression in neural crest precursors disrupts sympathetic neurogenesis. These data demonstrate that Twist1 functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages.
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Músculo Liso , Miocardio , Cresta Neural , Neuronas , Proteínas Nucleares , Proteína 1 Relacionada con Twist , Animales , Diferenciación Celular , Linaje de la Célula , Ectodermo/metabolismo , Regulación del Desarrollo de la Expresión Génica , Células HeLa , Proteínas de Homeodominio/metabolismo , Humanos , Mesodermo/metabolismo , Ratones , Ratones Transgénicos , Músculo Liso/citología , Músculo Liso/metabolismo , Miocardio/citología , Miocardio/metabolismo , Cresta Neural/citología , Cresta Neural/metabolismo , Neuronas/citología , Neuronas/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Organogénesis/genética , Factores de Transcripción SOXE/metabolismo , Factores de Transcripción/metabolismo , Proteína 1 Relacionada con Twist/genética , Proteína 1 Relacionada con Twist/metabolismoRESUMEN
Introduction: Interruptions that occur during sign-out in the emergency department (ED) may affect workflow, quality of care, patient safety, errors in documentation, and resident education. Our objective in this study was to determine the frequency and classification (emergent vs non-emergent, in-person vs phone call) of interruptions that occur during emergency medicine (EM) resident sign-out before and after the institution of a group sign-out process involving residents and attending physicians. Methods: A convenience sample of sign-out observations between EM residents were observed and coded between April-December 2021. We excluded sign-out observations of pediatric patients (<18 years of age) and observations not conducted in the main ED. Collected data included number of patients signed out during each observation; total duration in minutes for each observation; total number of interruptions during each observation; and type of interruption (emergent vs non-emergent, in-person vs phone call). We further stratified data before and after the institution of a group sign-out process (July 2021). Results: We performed data analysis on 58 individual and 65 group sign-out observations, respectively. Although the total number of patients signed out, the total duration of sign-outs observed, mean number of patients signed out per minute, and mean duration of sign-out per observation were more for the group sign-out aggregate compared with the individual sign-out aggregate, the total number of interruptions (44 vs 73, P = 0.007), number of interruptions per minute (0.05 vs 0.16, P < 0.001), total number of non-emergent interruptions (38 vs. 67, P = 0.005), and total number of in-person interruptions (14 vs 44, P < 0.001) was less in the group sign-out compared with the individual sign-out totals. Conclusion: Based on our sample, although the total duration of group sign-out with both residents and an attending was longer than individual resident-to-resident sign-out, the total number of interruptions, number of interruptions per minute, total number of non-emergent interruptions, and total number of in-person interruptions was less in the group sign-out. Group sign-out may be an option to limit the negative effects of interruptions in the ED.
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Documentación , Medicina de Emergencia , Humanos , Niño , Recolección de Datos , Escolaridad , Servicio de Urgencia en HospitalRESUMEN
At the onset of the COVID-19 pandemic, the US Department of Health and Human Services implemented a range of flexibilities to expedite the adoption of telehealth. As our specialty moved past the height of the pandemic and the use of telehealth transitioned from a necessity to a convenience, numerous health care providers (physicians, advanced practice providers, speech-language pathologists, and audiologists) recognized its benefits and continued to offer these services. In May 2023, the current administration terminated the COVID-19 public health emergency declaration, with some telehealth guidelines in effect until December 31, 2023, and others extended through December 31, 2024. Amidst the changing telehealth landscape, the objective of this commentary is to explain policy implications on Otolaryngology-Head and Neck Surgery and provide insight into how to best implement telehealth under these new guidelines.
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COVID-19 , Otolaringología , Telemedicina , Humanos , SARS-CoV-2 , Pandemias , Salud PúblicaRESUMEN
Introduction: The chronic failure to significantly increase the number of underrepresented minorities (URM) in medicine requires that we look for new mechanisms for channelling URM students through pre-medical education and into medical school. One potential mechanism is medical scribing, which involves a person helping a physician engage in real-time documentation in the electronic medical record. Methods: As a precursor to evaluating this mechanism, this survey pilot study explored individuals' experiences working as a medical scribe to look for any differences related to URM status. Of 248 scribes, 159 (64% response rate) completed an online survey. The survey was comprised of 11 items: demographics (4 items), role and length of time spent as a scribe (2 items), and experience working as a scribe (5 items). Results: The vast majority (>80%) of participants reported that working as a medical scribe gave them useful insight into being a clinician, provided valuable mentoring, and reinforced their commitment to pursue a career in medicine. The experiences reported by scribes who identified as URM did not differ from those reported by their majority counterparts. Discussion: It remains to be seen whether medical scribing can serve as an effective pipeline for URM individuals to matriculate into medical school. But the present findings suggest that the experience of working as a medical scribe is a positive one for URM.
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Pelvic tumours are a rare cause of pleural effusion. We describe an approach to a case of Meigs syndrome with recurrent unilateral pleural effusion. A woman in her 60s' presented with recurrent right-sided pleural effusion, leading to cough and shortness of breath. Thoracentesis yielded exudative pleural fluid with cytology negative for malignancy. Pleuroscopy revealed inflamed pleura, and pleural biopsy was consistent with inflammatory changes. The patient's cancer antigen 125 level was elevated at 256 U/mL. Given the high suspicion of malignancy, a computed tomography scan of the chest, abdomen, and pelvis was performed and revealed ascites and a large left ovarian and uterine mass. The patient underwent a total abdominal hysterectomy and bilateral salphingo oophorectomy after experiencing three additional episodes of pleural effusion. Histological examination revealed the left ovarian mass to be a cellular fibroma and the uterine masses to be leiomyomata. Following the operation, there was no recurrence of pleural effusion.
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A 37-year-old woman, 25 weeks pregnant, experienced sudden massive hemoptysis. She had a background history of systemic lupus erythematosus (SLE) and past pulmonary tuberculosis (PTB). Emergency intubation was necessary, and bronchoscopy revealed blood pooling in both main bronchi, with active bleeding from the right upper lobe bronchus. Urgent computed tomography (CT) angiography of the bronchial artery identified a bleeding source and was successfully embolized. Antifungal and anti-tuberculous therapy was initiated based on bronchoalveolar lavage results. Despite initial improvement, hemoptysis recurred after the third week, leading to repeat embolization, followed by a caesarean section and right upper lobectomy. Both mother and baby survived, remaining well at a 6-week follow-up, emphasizing the complexities of managing recurrent hemoptysis during pregnancy and potential drug interactions.
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INTRODUCTION: Asthma management is strongly dependent on physician and patient beliefs and perceptions about the disease and its long-term treatment. The APPaRENT 3 study was conducted to explore factors influencing treatment choice and to understand patients' and physicians' attitudes and perspectives on the use of controller inhalers in regular versus flexible dosing for asthma management. METHODS: This cross-sectional survey of patients with asthma and treating physicians was conducted in seven countries: Indonesia, Malaysia, Philippines, Thailand, Vietnam (patient survey only), Saudi Arabia, and the United Arab Emirates. Assessment was carried out through an online/face-to-face questionnaire, where patients' viewpoints were focused on their attitudes and beliefs about asthma and treatment adherence, whereas physicians' viewpoints were gathered on their attitudes and beliefs about asthma management, knowledge of and adherence to asthma treatment guidelines, and asthma treatment regimens. RESULTS: Overall, 1400 patients (mean age, 34 years) and 599 physicians (mean age, 43 years) were included in the survey. Physicians similarly prioritised symptom control (39%) and exacerbation reduction (40%) in moderate asthma, whereas patients prioritised symptom control (41%) over exacerbation reduction (22%). Although both groups (physicians, 86%; patients, 84%) perceived asthma as well-controlled, poor management was evident based on Asthma Control Test (ACT) scores (mean, 15.7; standard deviation, 4.14; 82% had an ACT score < 20) and high symptom burden (39% reported nighttime awakenings or early mornings ≥ 2 nights/week). Most patients (76%) with moderate asthma were prescribed regular dosing, with the most common treatment being inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA) with as-needed inhaled short-acting ß2-agonist (SABA; 20%). Among patients on maintenance and reliever therapy, 93% of patients received a separate inhaled reliever. CONCLUSIONS: Despite high symptom burden, patients overestimated their level of asthma control. Physicians prioritised controlling symptoms and reducing exacerbations as treatment goals for moderate asthma, often prescribing regular dosing with ICS/LABA with as-needed inhaled SABA.
Managing asthma depends a lot on what doctors and patients think about the illness and its long-term treatment. This study looked into what influences treatment decisions and what patients and doctors think about using inhalers regularly or on an as-needed basis to manage asthma across seven countries (Indonesia, Malaysia, Philippines, Thailand, Vietnam [patient survey only], Saudi Arabia, and the United Arab Emirates). In this study, patients with asthma and doctors managing asthma completed an online/face-to-face questionnaire. The study aimed to understand what patients think about asthma and their treatment plan. Meanwhile, the doctors were asked what they think about managing asthma and how much they apply clinical guidelines for treating patients with asthma. Doctors believed it is equally important to control symptoms and prevent worsening of symptoms in patients with moderate asthma, while patients cared more about controlling symptoms than preventing worsening of symptoms. While doctors and patients both regarded asthma as well-controlled, many patients had low Asthma Control Test scores and experienced a lot of symptoms, suggesting that they are poor perceivers of asthma control. Most patients with moderate asthma were given regular treatment, usually with inhaled corticosteroid combined with long-acting ß2-agonist along with as-needed short-acting ß2-agonist as a reliever. Most patients who were prescribed the same inhaler for regular use and as a reliever also had a separate inhaler for quick relief of symptoms. This study shows the need for patients and doctors to have better conversations about asthma, its treatments, and what to expect from them.
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Antiasmáticos , Asma , Humanos , Asma/tratamiento farmacológico , Asma/terapia , Masculino , Adulto , Femenino , Estudios Transversales , Antiasmáticos/uso terapéutico , Antiasmáticos/administración & dosificación , Persona de Mediana Edad , Malasia , Emiratos Árabes Unidos , Vietnam , Arabia Saudita , Indonesia , Actitud del Personal de Salud , Tailandia , Filipinas , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Administración por Inhalación , Nebulizadores y Vaporizadores , Cumplimiento de la Medicación/estadística & datos numéricos , Adulto Joven , Costo de Enfermedad , Médicos/psicologíaRESUMEN
Transplanting a kidney from a hepatitis B surface antigen (HBsAg)-positive donor to an HBsAg-negative recipient who is naturally immune has been successful in countries endemic for hepatitis B virus (HBV). However, in most of these cases, the donors were deceased. We present a report of a successful HBsAg-discordant kidney transplantation in the United States; in this case, a living donor kidney was transplanted to a vaccinated recipient. The wife of a 58-year-old HBsAg-negative man volunteered to donate a kidney to her husband. She had chronic hepatitis B but undetectable HBV DNA. She tested positive for HBsAg and antibody to hepatitis B core antigen, but hepatitis B e antigen was undetectable. The recipient failed to develop an antibody response to 3 doses of intramuscular recombinant HBV vaccine given in consecutive months. Immunity was induced by using biweekly intradermal vaccine. However, antibody titer tapered to <10 mIU/mL over 14 months. An intramuscular booster vaccine resulted in a prolonged anamnestic response, allowing for successful living unrelated donor transplantation. During the 10 years since transplantation, the patient has continued to have normal liver function, with undetectable HBsAg and HBV DNA. Antibody titers to HBsAg slowly decreased to 5.8 mIU/mL during the 10 years. Transplant function has been well preserved. This approach to inducing long-term immunity for transplantation merits further study in the United States.
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Inmunidad Adaptativa , Anticuerpos contra la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Vacunas contra Hepatitis B/administración & dosificación , Trasplante de Riñón/inmunología , Donadores Vivos , Humanos , Inmunización Secundaria , Inyecciones Intradérmicas , Masculino , Persona de Mediana EdadRESUMEN
There is a pressing clinical need for minimally invasive liquid biopsies to supplement imaging in the treatment of glioblastoma. Diagnostic imaging is often difficult to interpret and the medical community is divided on distinguishing among complete response, partial response, stable disease, and progressive disease. A minimally invasive liquid biopsy would supplement imaging and clinical findings and has the capacity to be helpful in several ways: 1) diagnosis, 2) selection of patients for specific treatments, 3) tracking of treatment response, and 4) prognostic value. The liquid biome is the combination of biological fluids including blood, urine, and cerebrospinal fluid that contain small amounts of tumor cells, DNA/RNA coding material, peptides, and metabolites. Within the liquid biome, 2 broad categories of biomarkers can exist: tumor-derived, which can be directly traced to the tumor, and tumor-associated, which can be traced back to the response of the body to disease. Although tumor-associated biomarkers are promising liquid biopsy candidates, recent advances in biomarker enrichment and detection have allowed concentration on a new class of biomarker: tumor-derived biomarkers. This review focuses on making the distinction between the 2 biomarker categories and highlights promising new direction.
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Líquidos Corporales , Glioblastoma , Humanos , Biomarcadores de Tumor , Glioblastoma/diagnóstico , Biopsia Líquida/métodos , ARNRESUMEN
BACKGROUND: Despite optimal neoadjuvant chemotherapy only 40% of gastric cancer tumours achieve complete or partial treatment response. In the absence of treatment response, neoadjuvant chemotherapy in gastric cancer contributes to adverse events without additional survival benefit compared to adjuvant treatment or surgery alone. Additional strategies and methods are required to optimize the allocation of existing treatment regimens such as FLOT chemotherapy (5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel). Predictive biomarkers detected using immunohistochemistry (IHC) methods may provide useful data regarding treatment response. AIM: To investigate the utility of CD4, CD8, Galectin-3 and E-cadherin in predicting neoadjuvant FLOT chemotherapy tumour response in gastric adenocarcinoma. METHODS: Forty-three adult patients with gastric adenocarcinoma, of which 18 underwent neoadjuvant chemotherapy, were included in a prospective clinical cohort. Endoscopic biopsies were obtained from gastric cancer and normal adjacent gastric mucosa. Differences in expression of Galectin-3, E-cadherin, CD4+ and CD8+ molecules between tumours with and without treatment response to neoadjuvant chemotherapy were assessed with IHC. Treatment response was graded by clinical pathologists using the Tumour Regression Score according to the College of American Pathologists criteria. Treatment response was defined as complete or near complete tumour response, whereas partial or poor/no response was defined as incomplete. Digital IHC images were annotated and quantitatively assessed using QuPath 0.3.1. Biomarker expression between responsive and incomplete response tumours was assessed using a two-sided Wilcoxon test. Biomarker expression was also compared between normal and cancer tissue and between 15 paired tumour samples before and after chemotherapy. We performed a preliminary multivariate analysis and power analysis to guide future study. Statistical analyses were completed using R 4.1.2. RESULTS: The ratio between CD4+ and CD8+ lymphocytes was significantly greater in treatment responsive tumours (Wilcoxon, P = 0.03). In univariate models, CD4+/CD8+ ratio was the only biomarker that significantly predicted favourable treatment response (Accuracy 86%, P < 0.001). Using a glmnet multivariate model, high CD4+/CD8+ ratio and low Galectin-3 expression were the most influential variables in predicting a favourable treatment response. Analyses of paired samples found that FLOT chemotherapy also results in increased expression of CD4+ and CD8+ tumour infiltrating lymphocytes (Paired Wilcoxon, P = 0.002 and P = 0.008, respectively). Our power analysis suggests future study requires at least 35 patients in each treatment response group for CD8 and Galectin-3 molecules, whereas 80 patients in each treatment response group are required to assess CD4 and E-cadherin biomarkers. CONCLUSION: We demonstrate that an elevated CD4+/CD8+ Ratio is a promising IHC-based biomarker to predict favourable treatment response to FLOT neoadjuvant chemotherapy in locally advanced gastric cancer.
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BACKGROUND AND OBJECTIVE: People with epilepsy frequently encounter sleep disruptions that can stem from a variety of complex factors. Epilepsy-related sleep disturbance can lead to reduced quality of life and excessive daytime hypersomnolence. Identification of sleep disturbances may help in the overall management of epilepsy patients. This study was conducted to determine the prevalence and predictors of poor sleep quality and daytime sleepiness in epilepsy. METHODS: A cross-sectional study on 284 epilepsy patients was performed in a local tertiary centre. The demographic and clinical epilepsy data were collected. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires were utilised to determine the quality of life and daytime hypersomnolence of epilepsy patients, respectively. RESULTS: Poor sleep quality was reported in 78 (27.5%) patients while daytime hypersomnolence was present in 17 (6%) patients. The predictors of poor sleep quality include structural causes (OR = 2.749; 95% CI: 1.436, 5.264, p = 0.002), generalised seizures (OR = 1.959, 95% CI: 1.04, 3.689, p = 0.037), and antiseizure medications such as Carbamazepine (OR = 2.34; 95% CI: 1.095, 5.001, p = 0.028) and Topiramate (OR 2.487; 95% CI: 1.028, 6.014, p = 0.043). Females are 3.797 times more likely score higher in ESS assessment (OR 3.797; 95% CI: 1.064, 13.555 p = 0.04). DISCUSSION: Sleep disturbances frequently coexist with epilepsy. Patients should be actively evaluated using the PSQI and ESS questionnaires. It is imperative to identify the key factors that lead to reduced sleep quality and heightened daytime sleepiness in patients with epilepsy, as this is essential to properly manage their condition.
Asunto(s)
Trastornos de Somnolencia Excesiva , Epilepsia , Narcolepsia , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Femenino , Humanos , Calidad del Sueño , Estudios Transversales , Calidad de Vida , Malasia/epidemiología , Prevalencia , Epilepsia/complicaciones , Epilepsia/epidemiología , Epilepsia/tratamiento farmacológico , Trastornos de Somnolencia Excesiva/epidemiología , Trastornos de Somnolencia Excesiva/etiología , Sueño , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/etiología , Encuestas y CuestionariosRESUMEN
We report a 35-year-old woman who presented with dyspnoea and chest pain for 1 week. High-resolution computed tomography (HRCT) thorax revealed bilateral pneumothoraces with diffuse lung cysts. Bilateral intercostal chest tubes were inserted, and there was a persistent air leak (PAL) bilaterally. We performed an autologous blood patch pleurodesis (ABPP) for the left PAL. For the right PAL, she underwent a successful right video-assisted thoracic (VATS) surgery, wedge biopsy, and surgical pleurodesis. Histopathology examination confirmed the diagnosis of lymphangioleiomyomatosis (LAM). The left pneumothorax recurred. An indwelling pleural catheter (Rocket® IPC™; Rocket Medical plc; WASHINGTON) was inserted and the patient was discharged after 1 day with an atrium pneumostat (Pneumostat™; Atrium Medical Corporation, Hudson, NH, USA) chest drain valve. The patient was initiated on Sirolimus 2 mg daily. The left PAL resolved at 6 weeks. This case highlights the benefit of IPC with an ambulatory pneumothorax device in a patient with LAM with PAL.
RESUMEN
Background: The extent of short-acting Beta-2-agonist (ß2-agonist) (SABA) use across Asian countries is not well documented. As part of the SABA use IN Asthma (SABINA) III study, we assessed SABA prescriptions and clinical outcomes in patients with asthma from Asia. Methods: This cross-sectional study recruited patients (aged ≥12 years) with asthma from 8 Asian countries. Data on disease characteristics and asthma treatments were collected using electronic case report forms. Patients were classified by practice type (primary or specialist care) and investigator-defined asthma severity (per Global Initiative for Asthma [GINA] 2017 recommendations). The association of SABA prescriptions with clinical outcomes was analyzed using multivariable regression models. Results: Overall, 3066 patients were analyzed, with a mean (standard deviation) age of 51.8 (16.7) years; of these patients, 2116 (69%) were female, 2517 (82.1%) had moderate-to-severe asthma and 2498 (81.5%) and 559 (18.2%) were treated in specialist and primary care, respectively. In total, 1423 (46.4%) patients had partly controlled/uncontrolled asthma, with 1149 (37.5%) patients experiencing ≥1 severe asthma exacerbation in the previous year. Overall, 800 (26.7%) patients were prescribed ≥3 SABA canisters in the previous year, which is regarded as overprescription and was associated with a significantly decreased odds of at least partly controlled asthma and increased incidence rates of severe exacerbations (P < 0.01 for both associations). Conclusion: The findings from this cohort of predominantly specialist-treated patients with asthma indicate SABA overprescription in at least 1 in every 4 patients, and this overprescription is associated with poor clinical outcomes. These data highlight the need for adherence to recently updated asthma treatment recommendations in Asia.