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1.
Sci Transl Med ; 16(754): eadl3848, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959329

RESUMO

Autoantibodies to nuclear antigens are hallmarks of systemic lupus erythematosus (SLE) where they contribute to pathogenesis. However, there remains a gap in our knowledge regarding how different isotypes of autoantibodies contribute to this autoimmune disease, including the production of the critical type I interferon (IFN) cytokines by plasmacytoid dendritic cells (pDCs) in response to immune complexes (ICs). We focused on IgA, which is the second-most prevalent isotype in serum and, along with IgG, is deposited in glomeruli in individuals with lupus nephritis. We show that individuals with SLE have serum IgA autoantibodies against most nuclear antigens, correlating with IgG against the same antigen. We investigated whether IgA autoantibodies against a major SLE autoantigen, Smith ribonucleoprotein (Sm/RNP), played a role in IC activation of pDCs. We found that pDCs expressed the IgA-specific Fc receptor, FcαR, and IgA1 autoantibodies synergized with IgG in RNA-containing ICs to generate robust primary blood pDC IFN-α responses in vitro. pDC responses to these ICs required both FcαR and FcγRIIa, showing synergy between these Fc receptors. Sm/RNP IC binding to and internalization by pDCs were greater when ICs contained both IgA1 and IgG. Circulating pDCs from individuals with SLE had higher binding of IgA1-containing ICs and higher expression of FcαR than pDCs from healthy control individuals. Although pDC FcαR expression correlated with the blood IFN-stimulated gene signature in SLE, Toll-like receptor 7 agonists, but not IFN-α, up-regulated pDC FcαR expression in vitro. Together, we show a mechanism by which IgA1 autoantibodies contribute to SLE pathogenesis.


Assuntos
Complexo Antígeno-Anticorpo , Autoanticorpos , Células Dendríticas , Imunoglobulina A , Imunoglobulina G , Lúpus Eritematoso Sistêmico , Humanos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Imunoglobulina A/sangue , Autoanticorpos/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Complexo Antígeno-Anticorpo/imunologia , Complexo Antígeno-Anticorpo/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/sangue , RNA/metabolismo , Feminino , Interferon-alfa/metabolismo , Adulto , Receptores Fc/metabolismo , Receptores Fc/imunologia , Receptor 7 Toll-Like/metabolismo , Masculino , Receptores de IgG/metabolismo
2.
AIDS Educ Prev ; 36(1): 48-59, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38349354

RESUMO

Prescription rates of pre-exposure prophylaxis (PrEP) have remained low among noninfectious disease providers in the United States despite almost a decade since their introduction. For future primary care doctors, residency is the optimal time to build practice patterns around HIV prevention. We assessed baseline knowledge of PrEP in specific pre- and post-exposure prophylaxis content areas among internal medicine trainees who completed the Physician Education and Assessment Center HIV learning module between 2013 to 2020 (N = 12,060). Resident baseline PrEP knowledge was universally low; despite rising awareness of antiretroviral therapy for PrEP in successive years following the nadir of 41% in 2014, still only 56% of residents affirmed this means of HIV prevention by 2020. Knowledge remained limited regardless of academic year, local HIV prevalence, or training program type. Online module completion increased competence across all content areas. There is still a deficit in HIV prevention knowledge across U.S. internal medicine residents, suggesting insufficient education and exposure to HIV-related care.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Infecções por HIV/prevenção & controle , Profilaxia Pós-Exposição , Escolaridade
3.
J Laryngol Otol ; : 1-6, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38250823

RESUMO

OBJECTIVE: This study investigates the impact of primary care utilisation of a symptom-based head and neck cancer risk calculator (Head and Neck Cancer Risk Calculator version 2) in the post-coronavirus disease 2019 period on the number of primary care referrals and cancer diagnoses. METHODS: The number of referrals from April 2019 to August 2019 and from April 2020 to July 2020 (pre-calculator) was compared with the number from the period January 2021 to August 2022 (post-calculator) using the chi-square test. The patients' characteristics, referral urgency, triage outcome, Head and Neck Cancer Risk Calculator version 2 score and cancer diagnosis were recorded. RESULTS: In total, 1110 referrals from the pre-calculator period were compared with 1559 from the post-calculator period. Patient characteristics were comparable for both cohorts. More patients were referred on the cancer pathway in the post-calculator cohort (pre-calculator patients 51.1 per cent vs post-calculator 64.0 per cent). The cancer diagnosis rate increased from 2.7 per cent in the pre-calculator cohort to 3.3 per cent in the post-calculator cohort. A lower rate of cancer diagnosis in the non-cancer pathway occurred in the cohort managed using the Head and Neck Cancer Risk Calculator version 2 (10 per cent vs 23 per cent, p = 0.10). CONCLUSION: Head and Neck Cancer Risk Calculator version 2 demonstrated high sensitivity in cancer diagnosis. Further studies are required to improve the predictive strength of the calculator.

4.
J Emerg Med ; 66(2): 192-196, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38278678

RESUMO

BACKGROUND: Eye-related symptoms are a common presentation in the emergency department (ED). The cases range from simple viral conjunctivitis to trauma-related eye injuries. One pathological condition that could lead to vision loss is retinal artery occlusion (RAO). Evaluating a patient with an eye symptom requires thorough eye examination and advanced imaging in certain instances. Consultation with an ophthalmologist is also necessary for cases that require treatment recommendations and further testing. In the ED, point-of-care ultrasound (POCUS) is a commonly used diagnostic tool that can be used for ocular examination. CASE REPORT: We reported a case of a 60-year-old man who presented with painless partial right-eye vision loss. POCUS showed decreased flow in the right central retinal artery with an area of the pale retina seen on the image from the retinal camera, suggesting a possible branch RAO. Further examination with POCUS showed plaque formation at the carotid bifurcation, a potential cause of the patient's symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians and other providers should be encouraged to use POCUS to diagnose eye symptoms accurately and promptly. Abnormal findings will prompt immediate specialty consult and early appropriate management. Our case and other reported cases highlight POCUS's reliability and rapid diagnostic ability.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Masculino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Ultrassonografia/métodos , Cegueira/etiologia , Serviço Hospitalar de Emergência
5.
J Laryngol Otol ; 138(4): 466-471, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38073419

RESUMO

BACKGROUND: Following limited clinical exposure during the coronavirus disease 2019 pandemic, a simulation-based platform aimed at providing a unique and safe learning tool was established. The aim was to improve the skills, knowledge and confidence of new ENT doctors. METHOD: The course was developed through 5 iterations over 28 months, moving from a half-day session to 2 full-day courses with more scenarios. Participant, faculty and local simulation team feedback drove course development. High-fidelity scenarios were provided, ranging from epistaxis to stridor, using technology including SimMan3 G mannequin, mask-Ed™ and nasendoscopy simulators. RESULTS: Participant feedback consistently demonstrated that the knowledge and skills acquired enhanced preparedness for working in ENT, with impact being sustained in clinical practice. CONCLUSION: Preparing healthcare professionals adequately is essential to enhancing patient safety. This simulation course has been effective in supporting new doctors in ENT and has subsequently been rolled out at a national level.


Assuntos
COVID-19 , Internato e Residência , Treinamento por Simulação , Humanos , Emergências , Epistaxe , Competência Clínica
6.
J Pediatr Adolesc Gynecol ; 37(2): 198-204, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38070700

RESUMO

STUDY OBJECTIVE: Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) includes uterine didelphys, unilateral obstructed hemivagina, and ipsilateral renal anomaly. Surgical management of this condition relies on accurate diagnosis to excise the obstructed longitudinal vaginal septum (OLVS). Vital considerations involve identifying the side affected, ipsilateral renal anomaly (IRA), thickness of the septum (TS), septal axis (SA), and distance of the septum to perineum (DSP). The study aimed to evaluate the preoperative characteristics, imaging findings, and surgical outcomes of OHVIRA. METHODS: Institutional review board approval was obtained for this retrospective chart review. ICD-10 codes identified OHVIRA cases between 2012 and 2019 at a single children's hospital. Patient demographic characteristics, magnetic resonance imaging findings, surgical management, outcomes, and complications were reviewed. Descriptive statistics were utilized. RESULTS: Twenty-six patients met inclusion criteria. Most were diagnosed at puberty (92%). Abdominal pain (50%) was the most common presenting complaint. The mean age of diagnosis was 13.2 years overall and 11.2 years for those with regular cycles vs 13.4 years for those with irregular cycles. Preoperative imaging showed predominant right-sided OLVS (50%), IRA (77%), and oblique SA (65%). All patients underwent vaginoscopy, septum resection, and vaginoplasty, except 1 who was managed with an abdominal drain as a neonate. Four required postoperative vaginal stent or Foley, with DSP greater than 5 cm in all cases. One intraabdominal abscess complication occurred. No instances of hematocolpos re-accumulation or reoperation were observed during the 3-year follow-up period. CONCLUSION: This study demonstrates that detailed preoperative planning and a systematic surgical approach lead to favorable outcomes in OHVIRA irrespective of the OLVS laterality, TS, SA, or DSP.


Assuntos
Anormalidades Múltiplas , Nefropatias , Doenças Vaginais , Criança , Feminino , Recém-Nascido , Humanos , Adolescente , Rim/anormalidades , Anormalidades Múltiplas/cirurgia , Estudos Retrospectivos , Nefropatias/diagnóstico , Útero/anormalidades , Vagina/cirurgia , Vagina/anormalidades , Imageamento por Ressonância Magnética/métodos
8.
bioRxiv ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37745328

RESUMO

Autoantibodies to nuclear antigens are hallmarks of the autoimmune disease systemic lupus erythematosus (SLE) where they contribute to pathogenesis. However, there remains a gap in our knowledge regarding how different isotypes of autoantibodies contribute to disease, including the production of the critical type I interferon (IFN) cytokines by plasmacytoid dendritic cells (pDCs) in response to immune complexes (ICs). We focused on IgA, which is the second most prevalent isotype in serum, and along with IgG is deposited in glomeruli in lupus nephritis. Here, we show that individuals with SLE have IgA autoantibodies against most nuclear antigens, correlating with IgG against the same antigen. We investigated whether IgA autoantibodies against a major SLE autoantigen, Smith ribonucleoproteins (Sm/RNPs), play a role in IC activation of pDCs. We found that pDCs express the IgA-specific Fc receptor, FcαR, and there was a striking ability of IgA1 autoantibodies to synergize with IgG in RNA-containing ICs to generate robust pDC IFNα responses. pDC responses to these ICs required both FcαR and FcγRIIa, showing a potent synergy between these Fc receptors. Sm/RNP IC binding to and internalization by pDCs were greater when ICs contained both IgA1 and IgG. pDCs from individuals with SLE had higher binding of IgA1-containing ICs and higher expression of FcαR than pDCs from healthy control individuals. Whereas pDC FcαR expression correlated with blood ISG signature in SLE, TLR7 agonists, but not IFNα, upregulated pDC FcαR expression in vitro. Together, we show a new mechanism by which IgA1 autoantibodies contribute to SLE pathogenesis.

9.
Med Mycol ; 61(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37950559

RESUMO

Histoplasmosis, the most common endemic mycosis in North America, presents in a myriad of ways, spanning the spectrum from self-limiting pneumonia to progressive disseminated histoplasmosis (PDH). Toward better describing contemporary histoplasmosis syndromes, risks, and outcomes, this single-center retrospective cohort study was performed (2009-2019). The population who developed PDH was similar to that with other forms of histoplasmosis (OFH) except for higher rates of preexisting immunocompromising conditions (91.3% vs. 40%, P < .001) and a trend toward receiving more chronic immunosuppression (65.2% vs. 33.3%, P = .054) compared to those with OFH. Diagnosis was most frequently achieved by urinary or serum antigen positivity. People with PDH more frequently tested positive compared to those with OFH, but negative tests did not rule out histoplasmosis. Median time to diagnosis was prolonged among people with both PDH and OFH (32 vs. 31 days, respectively). Following diagnosis, people with PDH received more liposomal amphotericin (78.3% vs. 20%, P < .001). Subsequent survival at 90 and 365 days and treatment response were similar in both groups. Patients with PDH were more often hospitalized (95.7% vs. 60%, P = .006); however, once admitted, there were no differences in hospital length of stay or intensive care unit admission rate. The challenges of diagnosing histoplasmosis based on clinical presentation alone highlight the need for heightened awareness of these entities especially given the recent reports on expanded endemicity and delays in diagnosis.


Histoplasmosis is the most common endemic mycosis in North America. This article summarizes the clinical features, risk factors, and outcomes in patients who developed disseminated disease compared to more localized forms of histoplasmosis.


Assuntos
Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Histoplasmose/epidemiologia , Histoplasmose/veterinária , Estudos Retrospectivos , Hospedeiro Imunocomprometido , Terapia de Imunossupressão/veterinária , Hospitais
10.
Microbiol Spectr ; 11(6): e0219123, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37843271

RESUMO

IMPORTANCE: Acinetobacter baumannii is a multidrug-resistant nosocomial pathogen that colonizes and infects debilitated patients in the ICU. There is very little information on the genomic characteristics of colonizing strains. This information is important to understand the evolution of lineages of A. baumannii that develop resistance while patients receive antibiotic treatment in the ICU. Our study demonstrated different patterns of colonization of the rectum of ICU patients with different STs of A. baumannii while one ST colonized all patients. Some STs carried more antibiotic resistance genes compared to others. However, there was a correlation between ST and a particular resistance gene profile. Our results further elucidate the dynamics of enteric colonization of this opportunistic pathogen.


Assuntos
Acinetobacter baumannii , Infecção Hospitalar , Adulto , Humanos , Centros de Atenção Terciária , Epidemiologia Molecular , Reto , Farmacorresistência Bacteriana Múltipla/genética , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana
11.
BJS Open ; 7(5)2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37875126

RESUMO

BACKGROUND: Groin hernias commonly present acutely in high-risk populations and can be challenging to manage. This retrospective, observational study aimed to report on patient demographics and outcomes, following acute admissions with a groin hernia, in relation to contemporary investigative and management practices. METHODS: Adult (≥18 years old) patients who presented acutely with a groin hernia to nine National Health Service trusts in the north of England between 2002 and 2016 were included. Data were collected regarding patient demographics, radiological investigations, and operative intervention. The primary outcome of interest was 30-day inpatient mortality rate. RESULTS: Overall, 6165 patients with acute groin hernia were included (4698 inguinal and 1467 femoral hernias). There was a male preponderance (72.5 per cent) with median age of 73 years (interquartile range (i.q.r.) 58-82). The burden of patient co-morbidity increased over the study period (P < 0.001). Operative repair was performed in 2258 (55.1 per cent) of patients with an inguinal and 1321 (90.1 per cent) of patients with a femoral hernia. Bowel resection was more commonly required for femoral hernias (14.7 per cent) than inguinal hernias (3.5 per cent, P < 0.001) and in obstructed (14.6 versus 0.2 per cent, P < 0.001) or strangulated (58.4 versus 4.5 per cent, P < 0.001) hernias. The 30-day mortality rate was 3.1 per cent for the overall cohort and 3.9 per cent for those who underwent surgery. Bowel resection was associated with increased duration of hospital stay (P < 0.001) and 30-day inpatient mortality rate (P < 0.001). Following adjustment for confounding variables, advanced age, co-morbidity, obstruction, and strangulation were all associated with an increased 30-day mortality rate (all P < 0.001). CONCLUSION: Emergency hernia repair has high mortality rates. Advanced age and co-morbidity increase both duration of hospital stay and 30-day mortality rate.


Assuntos
Hérnia Femoral , Hérnia Inguinal , Idoso , Humanos , Masculino , Demografia , Virilha , Hérnia Femoral/epidemiologia , Hérnia Femoral/cirurgia , Hérnia Inguinal/diagnóstico , Hérnia Inguinal/epidemiologia , Hérnia Inguinal/cirurgia , Estudos Retrospectivos , Medicina Estatal , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais
12.
Clin Infect Dis ; 77(9): 1247-1256, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37348870

RESUMO

BACKGROUND: Death within a specified time window following a positive SARS-CoV-2 test is used by some agencies for attributing death to COVID-19. With Omicron variants, widespread immunity, and asymptomatic screening, there is cause to re-evaluate COVID-19 death attribution methods and develop tools to improve case ascertainment. METHODS: All patients who died following microbiologically confirmed SARS-CoV-2 in the Veterans Health Administration (VA) and at Tufts Medical Center (TMC) were identified. Records of selected vaccinated VA patients with positive tests in 2022, and of all TMC patients with positive tests in 2021-2022, were manually reviewed to classify deaths as COVID-19-related (either directly caused by or contributed to), focused on deaths within 30 days. Logistic regression was used to develop and validate a surveillance model for identifying deaths in which COVID-19 was causal or contributory. RESULTS: Among vaccinated VA patients who died ≤30 days after a positive test in January-February 2022, death was COVID-19-related in 103/150 cases (69%) (55% causal, 14% contributory). In June-August 2022, death was COVID-19-related in 70/150 cases (47%) (22% causal, 25% contributory). Similar results were seen among the 71 patients who died at TMC. A model including hypoxemia, remdesivir, and anti-inflammatory drugs had positive and negative predictive values of 0.82-0.95 and 0.64-0.83, respectively. CONCLUSIONS: By mid-2022, "death within 30 days" did not provide an accurate estimate of COVID-19-related death in 2 US healthcare systems with routine admission screening. Hypoxemia and use of antiviral and anti-inflammatory drugs-variables feasible for reporting to public health agencies-would improve classification of death as COVID-19-related.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Pandemias , Anti-Inflamatórios , Hipóxia
13.
J Laryngol Otol ; 137(12): 1312-1325, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37078528

RESUMO

OBJECTIVE: Digital health tools are increasingly being recognised as effective interventions in monitoring chronic health conditions. This systematic review addressed how digital health is currently utilised in patients with head and neck cancer as an adjunct to care. METHOD: Studies of the development or evaluation of an eHealth, telemedicine or telemonitoring tool were eligible. A narrative synthesis was performed as per Preferred Reporting Items for Systematic Review and Meta-Analyses reporting guidelines. RESULTS: Twenty-nine studies of digital health tools in head and neck cancer were identified. Nine were randomised, controlled trials but most had concern of bias. Fourteen (48 per cent) of the interventions used multiple modes of delivery. The primary digital tool functions are symptom tracking and self-care, prehabilitation and rehabilitation, psychological support, and education, including decision aids. Most tools aimed to support patients during active cancer treatment. CONCLUSION: There are a small number of digital health tools for head and neck cancer patients; however, there is a lack of well-designed randomised, controlled trials to demonstrate effectiveness.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/terapia , Autocuidado
15.
Infect Control Hosp Epidemiol ; 44(1): 40-46, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35311638

RESUMO

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in neonatal intensive care units (NICU) that confers significant morbidity and mortality. OBJECTIVE: Improving our understanding of MRSA transmission dynamics, especially among high-risk patients, is an infection prevention priority. METHODS: We investigated a cluster of clinical MRSA cases in the NICU using a combination of epidemiologic review and whole-genome sequencing (WGS) of isolates from clinical and surveillance cultures obtained from patients and healthcare personnel (HCP). RESULTS: Phylogenetic analysis identified 2 genetically distinct phylogenetic clades and revealed multiple silent-transmission events between HCP and infants. The predominant outbreak strain harbored multiple virulence factors. Epidemiologic investigation and genomic analysis identified a HCP colonized with the dominant MRSA outbreak strain who cared for most NICU patients who were infected or colonized with the same strain, including 1 NICU patient with severe infection 7 months before the described outbreak. These results guided implementation of infection prevention interventions that prevented further transmission events. CONCLUSIONS: Silent transmission of MRSA between HCP and NICU patients likely contributed to a NICU outbreak involving a virulent MRSA strain. WGS enabled data-driven decision making to inform implementation of infection control policies that mitigated the outbreak. Prospective WGS coupled with epidemiologic analysis can be used to detect transmission events and prompt early implementation of control strategies.


Assuntos
Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Recém-Nascido , Lactente , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Unidades de Terapia Intensiva Neonatal , Infecção Hospitalar/epidemiologia , Infecções Estafilocócicas/prevenção & controle , Virulência/genética , Estudos Prospectivos , Filogenia , Surtos de Doenças/prevenção & controle , Controle de Infecções/métodos , Genômica
16.
Eur J Surg Oncol ; 49(1): 55-59, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36244845

RESUMO

INTRODUCTION: This study aimed to determine if post-treatment HPV cell-free DNA (cfDNA) can assist in the decision-making process for salvage neck dissection in patients following non-surgical treatment of oropharyngeal squamous cell carcinoma (OPSCC) with a partial response in the neck on imaging at 12 weeks post-treatment. METHODS: 86 patients who completed treatment were prospectively recruited through the regional multidisciplinary team (MDT). Treatment response was categorised as complete response (CR), partial response (PR) or progressive disease on 12-week post-treatment imaging. Pre- and post-treatment blood samples were assessed for HPV cfDNA through droplet digital PCR (ddPCR). RESULTS: Eight patients had an isolated partial response in the neck. One (12.5%) had detectable HPV cfDNA (22.96 copies/ml) at ∼12 weeks post-treatment with positive disease on subsequent neck dissection (positive predictive value; PPV = 100%). Of the seven patients with undetectable HPV cfDNA, two patients had evidence of regional disease recurrence at 23.9 and 27.4 months respectively (negative predictive value; NPV = 71%). CONCLUSION: The detection of HPV cfDNA may help target salvage therapy in patients with a partial response in the neck. Follow-up studies in larger cohorts would be required to further validate the use of post-treatment HPV cfDNA in the management of OPSCC.


Assuntos
Carcinoma de Células Escamosas , Ácidos Nucleicos Livres , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Biópsia Líquida , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia
17.
Clin Otolaryngol ; 48(1): 88-93, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183341

RESUMO

BACKGROUND: The incidence of thyroid cancer is increasing globally due to the increase in detection of subclinical, low volume papillary thyroid microcarcinomas (PTMC) (<1 cm). Several international groups have recommended an active surveillance approach for this low-risk disease. In contrast to many other countries, the United Kingdom's (UK's) approach to thyroid nodules is to avoid detection of incidental lesions where appropriate. OBJECTIVE: This study aims to establish the proportion of patients with thyroid cancer in the UK that would benefit from active surveillance. DESIGN, PARTICIPANTS, AND OUTCOME MEASURES: Individuals with PTMC in NHS Lothian from 2009-2020 were reviewed from a local thyroid cancer database. The mode of detection of PTMC and proportion of patients who might benefit from active surveillance were established. RESULTS: From 651 individuals with differentiated thyroid cancer managed over 12-year period, 185 individuals with PTMC were identified (28.4%). The majority of PTMC 151/185 (81.6%) were either diagnosed post-operatively following thyroidectomy for benign disease or with nodal disease. Only 24 individuals with PTMC were identified following palpable thyroid nodule, incidental finding on imaging, and surveillance screening. Therefore, when the indication for surgery was considered, only 24/651 (3.7%) patients were identified pre-operatively and would, therefore, be realistic candidates for active surveillance. CONCLUSION: Less than 4% of patients with thyroid cancer in the UK would be appropriate for active surveillance. Rather than developing programmes to deal with this minority of patients, focus should be maintained on minimising detection of these low-risk cases.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Conduta Expectante , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Nódulo da Glândula Tireoide/cirurgia , Reino Unido/epidemiologia , Estudos Retrospectivos
18.
Nat Commun ; 13(1): 3937, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35803954

RESUMO

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults whereas disease burden in children is lower. To investigate whether differences in the upper airway immune response may contribute to this disparity, we compare nasopharyngeal gene expression in 83 children (<19-years-old; 38 with SARS-CoV-2, 11 with other respiratory viruses, 34 with no virus) and 154 older adults (>40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes is robustly activated in both children and adults with SARS-CoV-2 infection compared to the respective non-viral groups, with only subtle distinctions. Children, however, demonstrate markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including response to TNF and production of IFNγ, IL-2 and IL-4. Cell type deconvolution confirms greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibit a decrease in proportions of ciliated cells, among the primary targets of SARS-CoV-2, upon infection. These findings demonstrate that children elicit a more robust innate and especially adaptive immune response to SARS-CoV-2 in the upper airway that likely contributes to their protection from severe disease in the lower airway.


Assuntos
COVID-19 , SARS-CoV-2 , Imunidade Adaptativa/genética , Adulto , Idoso , COVID-19/genética , Criança , Expressão Gênica , Humanos , Nasofaringe , Adulto Jovem
19.
Int J Behav Nutr Phys Act ; 19(1): 66, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35701784

RESUMO

BACKGROUND: A recent dialogue in the field of play, learn, and teach outdoors (referred to as "PLaTO" hereafter) demonstrated the need for developing harmonized and consensus-based terminology, taxonomy, and ontology for PLaTO. This is important as the field evolves and diversifies in its approaches, contents, and contexts over time and in different countries, cultures, and settings. Within this paper, we report the systematic and iterative processes undertaken to achieve this objective, which has built on the creation of the global PLaTO-Network (PLaTO-Net). METHODS: This project comprised of four major methodological phases. First, a systematic scoping review was conducted to identify common terms and definitions used pertaining to PLaTO. Second, based on the results of the scoping review, a draft set of key terms, taxonomy, and ontology were developed, and shared with PLaTO members, who provided feedback via four rounds of consultation. Third, PLaTO terminology, taxonomy, and ontology were then finalized based on the feedback received from 50 international PLaTO member participants who responded to ≥ 3 rounds of the consultation survey and dialogue. Finally, efforts to share and disseminate project outcomes were made through different online platforms. RESULTS: This paper presents the final definitions and taxonomy of 31 PLaTO terms along with the PLaTO-Net ontology model. The model incorporates other relevant concepts in recognition that all the aspects of the model are interrelated and interconnected. The final terminology, taxonomy, and ontology are intended to be applicable to, and relevant for, all people encompassing various identities (e.g., age, gender, culture, ethnicity, ability). CONCLUSIONS: This project contributes to advancing PLaTO-based research and facilitating intersectoral and interdisciplinary collaboration, with the long-term goal of fostering and strengthening PLaTO's synergistic linkages with healthy living, environmental stewardship, climate action, and planetary health agendas. Notably, PLaTO terminology, taxonomy and ontology will continue to evolve, and PLaTO-Net is committed to advancing and periodically updating harmonized knowledge and understanding in the vast and interrelated areas of PLaTO.


Assuntos
Aprendizagem , Consenso , Humanos , Inquéritos e Questionários
20.
Glob Health Action ; 15(1): 2062175, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-35730550

RESUMO

Science education and research have the potential to drive profound change in low- and middle-income countries (LMICs) through encouraging innovation, attracting industry, and creating job opportunities. However, in LMICs, research capacity is often limited, and acquisition of funding and access to state-of-the-art technologies is challenging. The Alliance for Global Health and Science (the Alliance) was founded as a partnership between the University of California, Berkeley (USA) and Makerere University (Uganda), with the goal of strengthening Makerere University's capacity for bioscience research. The flagship program of the Alliance partnership is the MU/UCB Biosciences Training Program, an in-country, hands-on workshop model that trains a large number of students from Makerere University in infectious disease and molecular biology research. This approach nucleates training of larger and more diverse groups of students, development of mentoring and bi-directional research partnerships, and support of the local economy. Here, we describe the project, its conception, implementation, challenges, and outcomes of bioscience research workshops. We aim to provide a blueprint for workshop implementation, and create a valuable resource for bioscience research capacity strengthening in LMICs.


Assuntos
Países em Desenvolvimento , Saúde Global , Fortalecimento Institucional , Humanos , Pobreza , Estudantes , Universidades
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