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1.
J Gen Virol ; 105(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38767609

RESUMO

Hepeviruses have been identified in a broad range of animal hosts, including mammals, birds, and fish. In this study, rodents (n=91) from seven different species and ten pikas (Ochotona curzoniae) were collected in Qinghai Province, China. Using transcriptomic sequencing and confirmatory molecular testing, hepeviruses were detected in 27 of 45 (60 %) long-tailed dwarf hamsters (Cricetulus longicaudatus) and were undetected in other rodents and pika. The complete genome sequences from 14 representative strains were subsequently obtained, and phylogenetic analyses suggested that they represent a novel species within the genus Rocahepevirus, which we tentatively designated as Cl-2018QH. The virus was successfully isolated in human hepatoma (Huh-7) and murine fibroblast (17 Cl-1) cell lines, though both exhibited limited replication as assayed by detection of negative-sense RNA intermediates. A129 immunodeficient mice were inoculated with Cl-2018QH and the virus was consistently detected in multiple organs, despite relatively low viral loads. In summary, this study has described a novel rodent hepevirus, which enhances our knowledge of the genetic diversity of rodent hepeviruses and highlights its potential for cross-species transmission.


Assuntos
Genoma Viral , Hepevirus , Filogenia , Animais , China , Cricetinae , Camundongos , Hepevirus/genética , Hepevirus/isolamento & purificação , Hepevirus/classificação , Humanos , Linhagem Celular , RNA Viral/genética
2.
Virus Res ; 345: 199388, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38714218

RESUMO

Human enteroviruses (EVs) represent a global public health concern due to their association with a range of serious pediatric illnesses. Despite the high morbidity and mortality exerted by EVs, no broad-spectrum antivirals are currently available. Herein, we presented evidence that doxycycline can inhibit in vitro replication of various neurotropic EVs, including enterovirus A71 (EV-A71), enterovirus D68 (EV-D68), and coxsackievirus (CV)-A6, in a dose-dependent manner. Further investigations indicated that the drug primarily acted at the post-entry stage of virus infection in vitro, with inhibitory effects reaching up to 89 % for EV-A71 when administered two hours post-infection. These findings provide valuable insights for the development of antiviral drugs against EV infections.

3.
Euro Surveill ; 29(16)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639093

RESUMO

BackgroundMpox, caused by monkeypox virus (MPXV), was considered a rare zoonotic disease before May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Cases of mpox in Ireland, a country without previous mpox reports, could reflect extended local transmission or multiple epidemiological introductions.AimTo elucidate the origins and molecular characteristics of MPXV circulating in Ireland between May 2022 and October 2023.MethodsWhole genome sequencing of MPXV from 75% of all Irish mpox cases (182/242) was performed and compared to sequences retrieved from public databases (n = 3,362). Bayesian approaches were used to infer divergence time between sequences from different subclades and evaluate putative importation events from other countries.ResultsOf 242 detected mpox cases, 99% were males (median age: 35 years; range: 15-60). All 182 analysed genomes were assigned to Clade IIb and, presence of 12 distinguishable subclades suggests multiple introductions into Ireland. Estimation of time to divergence of subclades further supports the hypothesis for multiple importation events from numerous countries, indicative of extended and sustained international spread of mpox. Further analysis of sequences revealed that 92% of nucleotide mutations were from cytosine to thymine (or from guanine to adenine), leading to a high number of non-synonymous mutations across subclades; mutations associated with tecovirimat resistance were not observed.ConclusionWe provide insights into the international transmission dynamics supporting multiple introductions of MPXV into Ireland. Such information supported the implementation of evidence-informed public health control measures.


Assuntos
Monkeypox virus , Mpox , Masculino , Humanos , Adulto , Feminino , Irlanda/epidemiologia , Monkeypox virus/genética , Teorema de Bayes , Mpox/diagnóstico , Mpox/epidemiologia , Surtos de Doenças
4.
Resusc Plus ; 18: 100624, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38666254

RESUMO

Background: The Cardiac Arrest Registry to Enhance Survival (CARES) was created in 2004 in collaboration with the Centers for Disease Control and Prevention (CDC) and Emory University School of Medicine's Department of Emergency Medicine. The registry allows local communities to benchmark their performance, enhance the quality of care, and increase survival rates for out-of-hospital cardiac arrest (OHCA). Methods/design: CARES enrolls patients who experience a non-traumatic, EMS-treated OHCA. For each case, data is collected from three sources: 911 call center data, EMS data, and hospital data. CARES data is de-identified and stored in a secured web-based cloud platform and maintains confidentiality throughout the process. CARES data is subjected to an internal auditing system that oversees both local and regional levels. The variables in CARES adhere with the Utstein style reporting system and the National EMS Information System (NEMSIS) standard. Discussion: As of 2023, CARES captures data from a population base of over 178 million people which accounts for 53% of the total U.S. population. Over the past two decades, CARES has consistently been a part of public health surveillance for OHCA and serves as a quality improvement tool to improve cardiac arrest outcomes. Moreover, CARES commits to facilitate observational research on OHCA, continues to modernize its software platform, and comprehensively expands its coverage for the entire U.S.

6.
Metabolism ; 154: 155818, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38369056

RESUMO

BACKGROUND: Cardiac glucose oxidation is decreased in heart failure with reduced ejection fraction (HFrEF), contributing to a decrease in myocardial ATP production. In contrast, circulating ketones and cardiac ketone oxidation are increased in HFrEF. Since ketones compete with glucose as a fuel source, we aimed to determine whether increasing ketone concentration both chronically with the SGLT2 inhibitor, dapagliflozin, or acutely in the perfusate has detrimental effects on cardiac glucose oxidation in HFrEF, and what effect this has on cardiac ATP production. METHODS: 8-week-old male C57BL6/N mice underwent sham or transverse aortic constriction (TAC) surgery to induce HFrEF over 3 weeks, after which TAC mice were randomized to treatment with either vehicle or the SGLT2 inhibitor, dapagliflozin (DAPA), for 4 weeks (raises blood ketones). Cardiac function was assessed by echocardiography. Cardiac energy metabolism was measured in isolated working hearts perfused with 5 mM glucose, 0.8 mM palmitate, and either 0.2 mM or 0.6 mM ß-hydroxybutyrate (ßOHB). RESULTS: TAC hearts had significantly decreased %EF compared to sham hearts, with no effect of DAPA. Glucose oxidation was significantly decreased in TAC hearts compared to sham hearts and did not decrease further in TAC hearts treated with high ßOHB or in TAC DAPA hearts, despite ßOHB oxidation rates increasing in both TAC vehicle and TAC DAPA hearts at high ßOHB concentrations. Rather, increasing ßOHB supply to the heart selectively decreased fatty acid oxidation rates. DAPA significantly increased ATP production at both ßOHB concentrations by increasing the contribution of glucose oxidation to ATP production. CONCLUSION: Therefore, increasing ketone concentration increases energy supply and ATP production in HFrEF without further impairing glucose oxidation.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Masculino , Camundongos , Animais , Insuficiência Cardíaca/metabolismo , Glucose/metabolismo , Volume Sistólico , Miocárdio/metabolismo , Oxirredução , Trifosfato de Adenosina/metabolismo , Cetonas/farmacologia , Cetonas/metabolismo
7.
Am J Cardiol ; 212: 41-47, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38042265

RESUMO

Pediatric patients are often referred to cardiopulmonary exercise testing (CPET) laboratories for assessment of exercise-related symptoms. For clinicians to understand results in the context of performance relative to peers, adequate fitness-based prediction equations must be available. However, reference equations for prediction of peak oxygen uptake (VO2peak) in pediatrics are largely developed from field-based testing, and equations derived from CPET are primarily developed using adult data. Our objective was to develop a pediatric reference equation for VO2peak. Clinical CPET data from a validation cohort of 1,383 pediatric patients aged 6 to 18 years who achieved a peak respiratory exchange ratio ≥1.00 were analyzed to identify clinical and exercise testing factors that contributed to the prediction of VO2peak from tests performed using the Bruce protocol. The resultant prediction equation was applied to a cross-validation cohort of 1,367 pediatric patients. Exercise duration, gender, weight, and age contributed to the prediction of VO2peak, generating the following prediction equation: (R2 = 0.645, p <0.001, standard error of the estimate = 6.19 ml/kg/min): VO2peak (ml/kg/min) =16.411+ 3.423 (exercise duration [minutes]) - 5.145 (gender [0 = male, 1 = female]) - 0.121 (weight [kg]) + 0.179 (age [years]). This equation was stable across the age range included in the present study, with differences ≤0.5 ml/kg/min between mean measured and predicted VO2peak in all age groups. In conclusion, this study represents what we believe is the largest pediatric CPET-derived VO2peak prediction effort to date, and this VO2peak prediction equation provides clinicians who perform and interpret exercise tests in pediatric patients with a resource with which to better quantify fitness when CPET is not available.


Assuntos
Teste de Esforço , Exercício Físico , Adulto , Humanos , Masculino , Feminino , Criança , Teste de Esforço/métodos , Testes de Função Respiratória , Consumo de Oxigênio , Oxigênio
8.
Pediatr Cardiol ; 45(2): 446-451, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37955720

RESUMO

Absent pulmonary valve with tricuspid atresia or tricuspid stenosis (APV-TA/TS) is an extremely rare congenital heart defect associated with significant morbidity and mortality. Compared to Tetralogy of Fallot with Absent Pulmonary Valve Syndrome, branch pulmonary arteries are not typically significantly dilated. We present the case of a newborn male prenatally diagnosed APV-TA with intact ventricular septum (IVS) and nearly discontinuous branch pulmonary arteries, the surgical strategy employed, and the salient hemodynamic factors considered in the medical decision-making.


Assuntos
Cardiopatias Congênitas , Atresia Pulmonar , Valva Pulmonar , Atresia Tricúspide , Septo Interventricular , Recém-Nascido , Masculino , Humanos , Atresia Tricúspide/diagnóstico por imagem , Atresia Tricúspide/cirurgia , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/anormalidades , Artéria Pulmonar/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Atresia Pulmonar/diagnóstico por imagem , Atresia Pulmonar/cirurgia
9.
J Pediatr ; 264: 113770, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37802386

RESUMO

OBJECTIVE: To develop reference values for cardiorespiratory fitness, as quantified by peak oxygen uptake (VO2peak) and treadmill time, in patients aged 6 through 18 years referred for cardiopulmonary exercise testing (CPET). STUDY DESIGN: We reviewed a clinical pediatric CPET database for fitness data in children aged 6-18 years with no underlying heart disease. CPET was obtained via the Bruce protocol utilizing objectively confirmed maximal effort via respiratory exchange ratio. Fitness data (VO2peak and treadmill test duration) were analyzed to determine age- and sex-specific reference values for this pediatric cohort. RESULTS: Data from 2025 pediatric CPETs (53.2% female) were included in the analyses. VO2peak increased with age in males, but not females. Treadmill test duration increased with age in both males and females. Fitness was generally higher in males when compared with females in the same age groups. CONCLUSIONS: Our study provides extensive reference values for both VO2peak and total treadmill test time via the Bruce protocol for a pediatric population without known cardiac disease. Furthermore, the inclusion of objectively confirmed maximal exercise effort increases confidence in these findings compared with prior studies in this area. Clinicians performing CPET in pediatric populations can utilize these reference values to characterize test results according to representative peer data.


Assuntos
Aptidão Cardiorrespiratória , Cardiopatias , Masculino , Humanos , Feminino , Criança , Valores de Referência , Teste de Esforço/métodos , Exercício Físico , Consumo de Oxigênio
10.
Cancer Control ; 30: 10732748231206957, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37876208

RESUMO

BACKGROUND AND OBJECTIVES: Primary cutaneous leiomyosarcoma (cLMS), a rare, typically intradermal tumor, has previously been reported to exhibit an indolent course of disease with zero-to-low risk of local recurrence or distant metastasis. This study seeks to evaluate recurrence and survival of cLMS patients through study of its clinicopathologic and treatment characteristics. METHODS: All patients included underwent resection of primary cLMS at this institution between 2006 and 2019. A retrospective cohort study analysis of clinicopathologic characteristics, treatment, recurrence, and overall survival was performed. Data was assessed through descriptive statistics and outcome measures assessed by Cox proportional models and log-rank tests. RESULTS: Eighty-eight patients with cLMS were evaluated. The majority were men (n = 68, 77%) and Caucasian (n = 85, 97%), with median age at diagnosis of 66 years (range 20-96). 65% of tumors were located on the extremities, with a median size of 1.3 cm (range .3-15). Assessment revealed low (n = 41, 47%), intermediate (n = 29, 33%), and high (n = 18, 20%) grade tumors, demonstrating extension into subcutaneous tissue in 38/60 (60%), with 3 patients exhibiting extension into muscle (3%). All underwent resection as primary treatment with median 1 cm margins (range .5-2). With median follow-up of 27.5 months (IQR 8-51; range 1-131), no low-grade cases had recurrence or death while there was a recurrence rate of 19.1% (9/47) and death rate of 8.5% (4/47) in intermediate- to high-grade cases. CONCLUSIONS: Primary tumor resection of cLMS provides excellent local control for low-grade tumors as no low-grade cases experienced recurrence. For patients with intermediate- to high-grade tumors, there is potential for local recurrence, distant metastasis, and death, and therefore surveillance following treatment is encouraged.


Assuntos
Leiomiossarcoma , Neoplasias Cutâneas , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Leiomiossarcoma/cirurgia , Leiomiossarcoma/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Modelos de Riscos Proporcionais , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Prognóstico
12.
Indian J Thorac Cardiovasc Surg ; 39(Suppl 1): 101-113, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37525709

RESUMO

Since the time of their invention, implantable continuous flow left ventricular assist devices (LVADs) have improved the quality of life and extended survival for patients with advanced heart failure. The decision surgeons and their physician colleagues make with these patients to undergo implantation must come with full understanding of the immediate, short-term, and long-term implications of such a life-changing procedure. The presence of pathology regarding the aortic, mitral, and tricuspid valves introduces particularly complex problems for the surgical treatment strategy. Concomitant valve repair or replacement increases cardiopulmonary bypass and cross clamp times, and could potentially lead to worse outcomes in the perioperative setting. Following perioperative recovery, valvular pathology may worsen or arise de novo given the often drastic immediate physiologic changes in blood flow, septal function, and, over time, ventricular remodeling. Over the past two decades, there has been vast improvement in the device manufacturing, surgical techniques, and medical management surrounding LVAD implantation. Yet, addressing concomitant valvular pathology remains a complex question with no perfect solutions. This review aims to briefly describe the evolution of approach to valvular pathology in the LVAD patient and offer our opinion and treatment rationale.

13.
Virology ; 587: 109855, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37536021

RESUMO

Influenza C virus (ICV) was identified in five pediatric acute respiratory cases in Shandong. Co-infection with other respiratory viruses was detected in four of these cases. Two ICV genomes were obtained and clustered in the S1-sublineage of C/Sao Paulo/378/82, indicating that genetically diverse ICV strains have been circulating in mainland China.

14.
Front Immunol ; 14: 1166574, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37261339

RESUMO

Background: Dysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are thought to underlie the progression of coronavirus disease 2019 (COVID-19) to severe disease. We sought to determine whether early host immune-related gene expression could predict clinical progression to severe disease. Methods: We analysed the expression of 579 immunological genes in peripheral blood mononuclear cells taken early after symptom onset using the NanoString nCounter and compared SARS-CoV-2 negative controls with SARS-CoV-2 positive subjects with mild (SARS+ Mild) and Moderate/Severe disease to evaluate disease outcomes. Biobanked plasma samples were also assessed for type I (IFN-α2a and IFN-ß), type II (IFN-γ) and type III (IFN-λ1) interferons (IFNs) as well as 10 additional cytokines using multiplex immunoassays. Results: We identified 19 significantly deregulated genes in 62 SARS-CoV-2 positive subject samples within 5 days of symptom onset and 58 SARS-CoV-2 negative controls and found that type I interferon (IFN) signalling (MX1, IRF7, IFITM1, IFI35, STAT2, IRF4, PML, BST2, STAT1) and genes encoding proinflammatory cytokines (TNF, TNFSF4, PTGS2 and IL1B) were upregulated in both SARS+ groups. Moreover, we found that FCER1, involved in mast cell activation, was upregulated in the SARS+ Mild group but significantly downregulated in the SARS+ Moderate/Severe group. In both SARS+ groups we discovered elevated interferon type I IFN-α2a, type II IFN and type III IFN λ1 plasma levels together with higher IL-10 and IL-6. These results indicate that those with moderate or severe disease are characterised by deficiencies in a mast cell response together with IFN hyper-responsiveness, suggesting that early host antiviral immune responses could be a cause and not a consequence of severe COVID-19. Conclusions: This study suggests that early host immune responses linking defects in mast cell activation with host interferon responses correlates with more severe outcomes in COVID-19. Further characterisation of this pathway could help inform better treatment for vulnerable individuals.


Assuntos
COVID-19 , Interferon Tipo I , Humanos , SARS-CoV-2 , Leucócitos Mononucleares , Mastócitos , Linhagem Celular , Citocinas , Ligante OX40
15.
Ann Surg Oncol ; 30(11): 6401-6410, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37380911

RESUMO

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela/métodos , Terapia Neoadjuvante/métodos , Axila/patologia , Estudos Prospectivos , Metástase Linfática/patologia , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Excisão de Linfonodo
16.
Ann Surg ; 278(3): 320-327, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37325931

RESUMO

Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8-4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.


Assuntos
Neoplasias da Mama , Mastectomia , Humanos , Feminino , Mastectomia/métodos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Mastectomia Segmentar , Quimioterapia Adjuvante/métodos , Estudos Retrospectivos
17.
Pediatr Cardiol ; 44(7): 1605-1612, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37344558

RESUMO

Myocarditis is common in Multisystem Inflammatory Syndrome in Children (MIS-C), and the mechanism may differ from idiopathic/viral myocarditis as MIS-C involves a hyper-inflammatory state weeks after COVID-19. We sought to evaluate exercise stress testing (EST) in these patients as EST may help guide return-to-play recommendations. Retrospective cohort study evaluating ESTs (standard Bruce treadmill protocol) from MIS-C patients from 2020 to 2022, compared to myocarditis patients and age, sex, and weight matched controls from 2005 to 2019. ESTs included 22 MIS-C patients (mean age 11.9 years) with 14 cardiopulmonary and 8 cardiovascular tests, 33 myocarditis (15.5 years), and 44 controls (12.0 years). Percent-predicted peak VO2 was abnormal (< 80% predicted) in 11/14 (79%) MIS-C patients, 13/33 (39%) myocarditis, and 17/44 (39%) controls (p = 0.04). Exercise duration was shorter in MIS-C than myocarditis or control cohorts (p = 0.01). Isolated atrial or ventricular ectopy was seen in 8/22 (36%) MIS-C, 9/33 (27%) myocarditis, and 5/44 (11%) controls (p = 0.049). No arrhythmias/complex ectopy or evidence of ischemia were noted, though non-specific ST/T wave abnormalities occurred in 4/22 (18%) MIS-C, 5/33 (15%) myocarditis, and 3/44 (7%) controls. Exercise duration and percent-predicted peak VO2 were significantly reduced in MIS-C at mean 6-month follow-up compared to pre-COVID era idiopathic/viral myocarditis and control cohorts. This may be secondary to deconditioning during the pandemic and/or chronic cardiopulmonary or autonomic effects of COVID/MIS-C. Although there were no exercise-induced arrhythmias in our MIS-C patients, larger cohort studies are warranted. EST in MIS-C follow-up may help evaluate safety and timing of return to play and potentially mitigate further deconditioning.


Assuntos
COVID-19 , Miocardite , Criança , Humanos , Seguimentos , Estudos Retrospectivos , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
18.
J Drugs Dermatol ; 22(5): 457-464, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37133478

RESUMO

BACKGROUND: The standard of care when treating melanoma in situ (MMIS) is an excision with at least 5 mm surgical margins.1 Some studies have suggested up to 9 mm margins to maximize local recurrence-free survival.2 This retrospective review aims to assess the efficacy of imiquimod as a topical treatment for persistently positive MMIS at the margins of prior excisions or where surgery is not an option. METHODS: Retrospective study conducted at Moffitt Cancer Center between 2019 and 2021 with patients aged > 18 years with MMIS at the margins of excision of an invasive melanoma or MMIS. Included patients were not ideal candidates for primary or additional surgical resection due to non-feasibility of surgery because of comorbidity or cosmetically sensitive location and/or the need for repeated skin grafting, or due to patient's refusal. Patients received imiquimod on protocol for 16 weeks and were monitored for treatment response and side effects. Following completion of the treatment, scouting biopsies were performed to assess histological response, and dermoscopy was used to determine the clinical disease status. RESULTS: Ten patients completed 16 weeks of imiquimod. Seven (75%) had a median of 2 surgical resections, and 3 refused surgery despite discussion that surgery was standard of care. Seven were deemed free of disease on post-imiquimod treatment scouting biopsies, while 2 were found to be clinically free of disease following confocal microscopy, indicating a tumor clearance rate of 90% with imiquimod treatment. One patient was found to have persistent residual disease following 2 rounds of imiquimod and was taken for an additional surgical excision after which they were deemed free of disease. Median follow-up duration from the onset of imiquimod therapy to the last clinic visit was 18 months, without any recurrences to date. CONCLUSION: Imiquimod appears to demonstrate an encouraging tumor clearance among patients with persistent MMIS after surgery where further surgical resection may not be feasible. Although long-term durability has not been demonstrated in this study, a 90% tumor clearance rate is promising. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.6987.


Assuntos
Antineoplásicos , Melanoma , Neoplasias Cutâneas , Humanos , Imiquimode/efeitos adversos , Antineoplásicos/efeitos adversos , Estudos Retrospectivos , Melanoma/tratamento farmacológico , Melanoma/cirurgia , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Aminoquinolinas/efeitos adversos , Resultado do Tratamento , Melanoma Maligno Cutâneo
19.
iScience ; 26(6): 106799, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37250798

RESUMO

The impairment of antibody-mediated immunity is a major factor associated with fatal cases of severe fever with thrombocytopenia syndrome (SFTS). By collating the clinical diagnosis reports of 30 SFTS cases, we discovered the overproliferation of monoclonal plasma cells (MCP cells, CD38+cLambda+cKappa-) in bone marrow, which has only been reported previously in multiple myeloma. The ratio of CD38+cLambda+ versus CD38+cKappa+ in SFTS cases with MCP cells was significantly higher than that in normal cases. MCP cells presented transient expression in the bone marrow, which was distinctly different from multiple myeloma. Moreover, the SFTS patients with MCP cells had higher clinical severity. Further, the overproliferation of MCP cells was also observed in SFTS virus (SFTSV)-infected mice with lethal infectious doses. Together, SFTSV infection induces transient overproliferation of monoclonal lambda-type plasma cells, which have important implications for the study of SFTSV pathogenesis, prognosis, and the rational development of therapeutics.

20.
Infect Genet Evol ; 112: 105439, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37105345

RESUMO

Polyomaviruses (PyVs) are known to infect a diverse range of vertebrate host species. We report the discovery of PyVs in vesper bats (family Vespertilionidae) from sampling in Central Europe. Seven partial VP1 sequences from different PyVs were detected in samples originating from six distinct vesper bat species. Using a methodology based on conserved segments within the major capsid virus protein 1 (VP1) among known PyVs, the complete genomes of two different novel bat PyVs were determined. The genetic distances of the large T antigen coding sequences from these PyVs compared to previously-described bat PyVs exceeded 15% meriting classification as representatives of two novel PyV species: Alphapolyomavirus epserotinus and Alphapolyomavirus myodaubentonii. Phylogenetic analysis revealed that both belong to the genus Alphapolyomavirus and clustered together with high confidence in clades including other bat alphapolyomaviruses reported from China, South America and Africa. In silico protein modeling of the VP1 subunits and capsid pentamers, and electrostatic surface potential comparison of the pentamers showed significant differences between the reference template (murine polyomavirus) and the novel bat PyVs. An electrostatic potential difference pattern between the two bat VP1 pentamers was also revealed. Disaccharide molecular docking studies showed that the reference template and both bat PyVs possess the typical shallow sialic acid-binding site located between two VP1 subunits, with relevant oligosaccharide-binding affinities. The characterisation of these novel bat PyVs and the reported properties of their capsid proteins will potentially contribute in the elucidation of the conditions creating the host-pathogen restrictions associated with these viruses.


Assuntos
Quirópteros , Polyomavirus , Animais , Camundongos , Filogenia , Simulação de Acoplamento Molecular , Genoma Viral , Polyomavirus/genética , Polyomaviridae/genética
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