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1.
Ann Am Thorac Soc ; 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38335160

RESUMEN

Rationale Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. Molecular mechanisms underlying these changes are poorly understood in patients due, in part, to the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMC) interact with the pulmonary endothelium. Objective To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with 10 or more pack-years. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume (PMBV), and mean transit time were assessed on contrast-enhanced MRI, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with PMBV measures on contrast-enhanced, dual-energy CT. Differential expression analyses were adjusted for age, gender, race-ethnicity, educational attainment, height, weight, smoking status, and pack-years. Results The 79 participants in the discovery sample had mean age of 69±6 years, 44% were female, 25% were non-white, 34% were current smokers and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with MRI (n=47) or dual-energy CT scan (n=157) measures. Many of the identified genes are involved in inflammatory processes, including NF-κB and chemokine signaling pathways. Conclusions PBMC gene expression in NF-κB, inflammatory and chemokine signaling pathways was associated pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.

2.
Neurourol Urodyn ; 43(3): 595-603, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38318969

RESUMEN

OBJECTIVES: Fluoroscopy has significantly improved lead placement and decreased surgical time for implantable sacral neuromodulation (SNM). There is a paucity of data regarding radiation and safety of fluoroscopy during SNM procedures. Our study aims to characterize fluoroscopy time and dose used during SNM surgery across multiple institutions and assess for predictors of increased fluoroscopy time and radiation dose. METHODS: Electronic medical records were queried for SNM procedures (Stage 1 and full implant) from 2016 to 2021 at four academic institutions. Demographic, clinical, and intraoperative data were collected, including fluoroscopy time and radiation dose in milligray (mGy). The data were entered into a centralized REDCap database. Univariate and multivariate analysis were performed to assess for predictive factors using STATA/BE 17.0. RESULTS: A total of 664 procedures were performed across four institutions. Of these, 363 (54.6%) procedures had complete fluoroscopy details recorded. Mean surgical time was 58.8 min. Of all procedures, 79.6% were performed by Female Pelvic Medicine and Reconstructive Surgery specialists. There was significant variability in fluoroscopy time and dose based on surgical specialty and institution. Most surgeons (76.4%) were considered "low volume" implanters. In a multivariate analysis, bilateral finder needle testing, surgical indication, surgeon volume, and institution significantly predicted increased fluoroscopy time and radiation dose (p < 0.05). CONCLUSIONS: There is significant variability in fluoroscopy time and radiation dose utilized during SNM procedures, with differences across institutions, surgeons, and subspecialties. Increased radiation exposure can have harmful impacts on the surgical team and patient. These findings demonstrate the need for standardized fluoroscopy use during SNM procedures.


Asunto(s)
Terapia por Estimulación Eléctrica , Exposición a la Radiación , Cirujanos , Vejiga Urinaria Hiperactiva , Humanos , Femenino , Vejiga Urinaria Hiperactiva/terapia , Terapia por Estimulación Eléctrica/métodos , Sacro , Exposición a la Radiación/efectos adversos
3.
Gene ; 907: 148260, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38342252

RESUMEN

Pokkah Boeng disease (PBD), caused by Fusarium sacchari, severely affects sugarcane yield and quality. Necrosis-inducing secreted protein 1 (Nis1) is a fungal secreted effector that induces necrotic lesions in plants. It interacts with host receptor-like kinases and inhibits their kinase activity. FsNis1 contains the Nis1 structure and triggered a pathogen-associated molecular pattern-triggered immune response in Nicotiana benthamiana, as reflected by causing reactive oxygen species production, callose accumulation, and the upregulated expression of defense response genes. Knockout of this gene in F. sacchari revealed a significant reduction in its pathogenicity, whereas the pathogenicity of the complementary mutant recovered to the wild-type levels, making this gene an important virulence factor for F. sacchari. In addition, the signal peptide of FsNis1 was required for the induction of cell death and PTI response in N. benthamiana. Thus, FsNis1 may not only be a key virulence factor for F. sacchari but may also induce defense responses in plants. These findings provide new insights into the function of Nis1 in host-pathogen interactions.


Asunto(s)
Fusarium , Fusarium/genética , Inmunidad de la Planta/genética , Virulencia/genética , Factores de Virulencia/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología
4.
Clin Transl Med ; 14(2): e1573, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38318637

RESUMEN

BACKGROUND: Patients who possess various histological subtypes of early-stage lung adenocarcinoma (LUAD) have considerably diverse prognoses. The simultaneous existence of several histological subtypes reduces the clinical accuracy of the diagnosis and prognosis of early-stage LUAD due to intratumour intricacy. METHODS: We included 11 postoperative LUAD patients pathologically confirmed to be stage IA. Single-cell RNA sequencing (scRNA-seq) was carried out on matched tumour and normal tissue. Three formalin-fixed and paraffin-embedded cases were randomly selected for 10× Genomics Visium analysis, one of which was analysed by digital spatial profiler (DSP). RESULTS: Using DSP and 10× Genomics Visium analysis, signature gene profiles for lepidic and acinar histological subtypes were acquired. The percentage of histological subtypes predicted for the patients from samples of 11 LUAD fresh tissues by scRNA-seq showed a degree of concordance with the clinicopathologic findings assessed by visual examination. DSP proteomics and 10× Genomics Visium transcriptomics analyses revealed that a negative correlation (Spearman correlation analysis: r = -.886; p = .033) between the expression levels of CD8 and the expression trend of programmed cell death 1(PD-L1) on tumour endothelial cells. The percentage of CD8+ T cells in the acinar region was lower than in the lepidic region. CONCLUSIONS: These findings illustrate that assessing patient histological subtypes at the single-cell level is feasible. Additionally, tumour endothelial cells that express PD-L1 in stage IA LUAD suppress immune-responsive CD8+ T cells.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/genética , Neoplasias Pulmonares/metabolismo , Células Endoteliales/metabolismo , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Perfilación de la Expresión Génica
5.
Radiology ; 310(2): e233241, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38411522
6.
Mol Plant Pathol ; 25(1): e13414, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38279852

RESUMEN

Fusarium sacchari is one of the primary pathogens causing pokkah boeng disease, which impairs the yield and quality of sugarcane around the world. Understanding the molecular mechanisms of the F. sacchari effectors that regulate plant immunity is of great importance for the development of novel strategies for the persistent control of pokkah boeng disease. In a previous study, Fs00367 was identified to inhibit BAX-induced cell death. In this study, Fs00367nsp (without signal peptide) was found to suppress BAX-induced cell death, reactive oxygen species bursts and callose accumulation. The amino acid region 113-142 of Fs00367nsp is the functional region. Gene mutagenesis indicated that Fs00367 is important for the full virulence of F. sacchari. A yeast two-hybrid assay revealed an interaction between Fs00367nsp and sugarcane ScPi21 in yeast that was further confirmed using bimolecular fluorescence complementation, pull-down assay and co-immunoprecipitation. ScPi21 can induce plant immunity, but this effect could be blunted by Fs00367nsp. These results suggest that Fs00367 is a core pathogenicity factor that suppresses plant immunity through inhibiting ScPi21-induced cell death. The findings of this study provide new insights into the molecular mechanisms of effectors in regulating plant immunity.


Asunto(s)
Fusarium , Saccharum , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/farmacología , Inmunidad de la Planta/genética , Saccharum/genética , Saccharum/metabolismo , Muerte Celular , Enfermedades de las Plantas
7.
J Periodontol ; 95(1): 9-16, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37287337

RESUMEN

BACKGROUND: The purpose of this randomized, controlled split-mouth study was to evaluate a videoscope as a visual adjunct to scaling and root planing when utilized in combination with minimally invasive surgery. METHODS: Twenty-five pairs (89 interproximal surfaces) of periodontally hopeless teeth planned for extraction were scaled and root planed with minimal surgical access using surgical loupes (control) or adjunctive use of a videoscope (test). Teeth were extracted with minimal trauma, stained with methylene blue, and photographed with a digital microscope for analysis. The primary outcome of residual calculus was calculated as a percentage of the total interproximal area of interest. Secondary outcomes included treatment time, as well as residual calculus according to probing depth, tooth location, and treatment date. Data were analyzed using Student's paired t-tests, two-way analyses of variance, and Spearman's correlation tests. RESULTS: Residual calculus area was 2.61% on control and 2.71% on test surfaces with no significant difference between groups. Subgroup analysis showed no difference in residual calculus between groups at moderate or deep sites. Treatment time per surface was significantly longer in the test group compared to the control group. Treatment order, tooth location, and operator experience did not significantly affect the primary outcome. CONCLUSIONS: Though the videoscope provided excellent visual access, it did not improve the efficacy of root planing for flat interproximal surfaces during minimally invasive periodontal surgery. Small amounts of calculus remain after instrumentation even with minimal surgical access and when root surfaces appear visually clean and tactilely smooth.


Asunto(s)
Cálculos Dentales , Diente , Humanos , Aplanamiento de la Raíz , Cálculos Dentales/terapia , Raspado Dental , Raíz del Diente/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos
8.
JCO Precis Oncol ; 7: e2300391, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38061008

RESUMEN

PURPOSE: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate approved for the treatment of several advanced cancers; however, severe or fatal interstitial lung disease/pneumonitis can occur. We characterized the computed tomography (CT) patterns of T-DXd‒related pneumonitis as a marker for its clinical severity. MATERIALS AND METHODS: Ninety patients with advanced cancers who developed T-DXd‒related pneumonitis in two completed single-arm clinical trials were included. Three radiologists independently characterized the CT patterns of pneumonitis at diagnosis, for analyses of those patterns' relationships with clinical severity and pneumonitis outcome. RESULTS: T-DXd‒related pneumonitis most commonly presented with cryptogenic organizing pneumonia (COP) pattern, observed in 65 patients (72%), followed by a newly identified COP/hypersensitivity pneumonitis (HP) pattern (13%), acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) pattern (11%), and HP pattern (3%). A subset of cases with COP pattern demonstrated an atypical distribution with upper and peripheral lung involvement (6/65; 9%). CT patterns were associated with Common Terminology Criteria for Adverse Events severity grades of pneumonitis, with the AIP/ARDS pattern having higher grades compared with others (P < .0001). Fatal pneumonitis was more common in the AIP/ARDS pattern than in others (P = .005). The onset of pneumonitis was earlier in the AIP/ARDS pattern compared with others (median time to onset: at 17.9 v 32.7 weeks of therapy; P = .019). Pneumonitis was treated by withholding T-DXd with or without corticosteroids in most patients (78/90; 87%). CONCLUSION: T-DXd‒related pneumonitis most commonly demonstrated a COP pattern, with a subset having an atypical distribution. The AIP/ARDS pattern was indicative of severe, potentially fatal pneumonitis, and requires immediate clinical attention to mitigate serious adverse events.


Asunto(s)
Inmunoconjugados , Enfermedades Pulmonares Intersticiales , Neoplasias , Neumonía , Síndrome de Dificultad Respiratoria , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Tomografía Computarizada por Rayos X
9.
Microbiol Spectr ; 11(6): e0145223, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37962343

RESUMEN

IMPORTANCE: Common fungal extracellular membrane (CFEM) domain-containing protein has long been considered an essential effector, playing a crucial role in the interaction of pathogens and plant. Strategies aimed at understanding the pathogenicity mechanism of F. sacchari are eagerly anticipated to ultimately end the spread of pokkah boeng disease. Twenty FsCFEM proteins in the genome of F. sacchari have been identified, and four FsCFEM effector proteins have been found to suppress BCL2-associated X protein-triggered programmed cell death in N. benthamiana. These four effector proteins have the ability to enter plant cells and inhibit plant immunity. Furthermore, the expression of these four FsCFEM effector proteins significantly increases during the infection stage, with the three of them playing an essential role in achieving full virulence. These study findings provide a direction toward further exploration of the immune response in sugarcane. By applying these discoveries, we can potentially control the spread of disease through techniques such as host-induced gene silencing.


Asunto(s)
Proteínas Fúngicas , Proteínas de la Membrana , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Virulencia , Inmunidad de la Planta , Enfermedades de las Plantas/microbiología
10.
PLoS One ; 18(9): e0291678, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37729332

RESUMEN

BACKGROUND: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. METHODS: Weekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. RESULTS: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older. CONCLUSIONS: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future.


Asunto(s)
COVID-19 , Vacunas , Niño , Humanos , Anciano , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Tablas de Vida , SARS-CoV-2
11.
Clin Transl Med ; 13(9): e1401, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37700496

RESUMEN

Peripheral immune cells play important roles in the maintenance of systemic and microenvironmental hemostasis. Measurements of circulating blood cells by single-cell RNA sequencing (scRNA-seq) were proposed as one of the routine measures in clinical biochemistry of hematology. Out of translational challenges, defining precise identities of cell subsets and states is more difficult, due to the complexity of immune cell development, location, regulation, function, and metabolism. It is also a challenge to precisely interpret clinical significance and impact of each cell identity marker gene panel (ciMGPs). ciMGPs have potential to advance the understanding of systemic responses of the disease, identify disease-specific biomarkers, and to define cell heterogeneity. Recently, a large number of peripheral cell subsets and expending/activating states have been identified and validated for use in the fast developments in clinical single cell biomedicine. Defining specificity, measurability, and repeatability of cell subsets/states is important for translation of peripheral scRNA-seq in clinical hematology and biochemistry. The development of standard operating procedure and performance of clinical trials in large populations at various ages, diseases, and therapies will promote the clinical translation of ciMGPs to measures. Thus, defining cell subset/state identities will provide the multi-dimensional and comprehensive readouts of systemic immune cells, the precision monitoring of immune dynamics, and deeper-understanding of the disease and response to therapy.


Asunto(s)
Relevancia Clínica , Hematología , Diferenciación Celular
12.
Int J Mol Sci ; 24(13)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37446015

RESUMEN

Nitrogen availability might play an essential role in plant diseases by enhancing fungal cell growth and influencing the expression of genes required for successful pathogenesis. Nitrogen availability could modulate secondary metabolic pathways as evidenced by the significant differential expression of several core genes involved in mycotoxin biosynthesis and genes encoding polyketide synthase/nonribosomal peptide synthetases, cytochrome P450 and carbohydrate-active enzymes in Fusarium sacchari, grown on different nitrogen sources. A combined analysis was carried out on the transcript and metabolite profiles of regulatory metabolic processes and the virulence of Fusarium sacchari grown on various nitrogen sources. The nitrogen regulation of the gibberellin gene cluster included the metabolic flux and multiple steps of gibberellin synthesis. UHPLC-MS/MS-based metabolome analysis revealed the coordination of these related transcripts and the accumulation of gibberellin metabolites. This integrated analysis allowed us to uncover additional information for a more comprehensive understanding of biological events relevant to fungal secondary metabolic regulation in response to nitrogen availability.


Asunto(s)
Fusarium , Transcriptoma , Metabolismo Secundario/genética , Nitrógeno/metabolismo , Espectrometría de Masas en Tándem , Giberelinas/metabolismo , Regulación Fúngica de la Expresión Génica
13.
J Orthop Case Rep ; 13(1): 54-58, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37143565

RESUMEN

Introduction: Tibial-sided anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) avulsion fractures compose a rare subset of cruciate ligament injuries. Fixation strategies are mixed in the literature, particularly regarding the PCL, which has traditionally been addressed using an open approach. Case Report: A 41-year-old male sustained avulsion fractures of the tibial eminence involving the ACL, PCL, and posterior medial meniscal root through an unknown mechanism while sleepwalking. Surgical treatment comprised of entirely arthroscopic reduction and transtibial suture fixation. Only seven cases of combined ACL/PCL avulsion fracture have been reported and all but one utilized open fixation for at least the PCL and restricted weight-bearing postoperatively. Conclusion: This previously unreported triad of injury was successfully managed arthroscopically, negating a posterior approach to the knee. Early post-operative weight-bearing and aggressive range of motion aided in swift recovery and a favorable outcome.

14.
Microbiol Spectr ; 11(3): e0016523, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37140457

RESUMEN

Fusarium sacchari is one of the primary pathogens causing Pokkah Boeng disease (PBD) in sugarcane in China. Pectate lyases (PL), which play a critical role in pectin degradation and fungal virulence, have been extensively studied in major bacterial and fungal pathogens of a wide range of plant species. However, only a few PLs have been functionally investigated. In this study, we analyzed the function of the pectate lyase gene, FsPL, from F. sacchari. FsPL is a key virulence factor of F. sacchari and can induce plant cell death. FsPL also triggers the pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) response in Nicotiana benthamiana, as reflected by increases in reactive oxygen species (ROS) production, electrolyte leakage, and callose accumulation, as well as the upregulation of defense response genes. In addition, our study also found that the signal peptide of FsPL was necessary for induced cell death and PTI responses. Virus-induced gene silencing showed that FsPL-induced cell death in Nicotiana benthamiana was mediated by leucine-rich repeat (LRR) receptor-like kinases BAK1 and SOBIR1. Thus, FsPL may not only be a critical virulence factor for F. sacchari but may also induce plant defense responses. These findings provide new insights into the functions of pectate lyase in host-pathogen interactions. IMPORTANCE Pokkah Boeng disease (PBD) is one of the main diseases affecting sugarcane in China, seriously damaging sugarcane production and economic development. Therefore, it is important to clarify the pathogenic mechanisms of this disease and to provide a theoretical basis for the breeding of PBD-resistant sugarcane strains. The present study aimed to analyze the function of FsPL, a recently identified pectate lyase gene from F. sacchari. FsPL is a key virulence factor of F. sacchari that induces plant cell death. Our results provide new insights into the function of pectate lyase in host-pathogen interactions.


Asunto(s)
Nicotiana , Inmunidad de la Planta , Virulencia , Factores de Virulencia/genética , Enfermedades de las Plantas/microbiología
15.
Hortic Res ; 10(4): uhad020, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37035858

RESUMEN

The lemon (Citrus limon; family Rutaceae) is one of the most important and popular fruits worldwide. Lemon also tolerates huanglongbing (HLB) disease, which is a devastating citrus disease. Here we produced a gap-free and haplotype-resolved chromosome-scale genome assembly of the lemon by combining Pacific Biosciences circular consensus sequencing, Oxford Nanopore 50-kb ultra-long, and high-throughput chromatin conformation capture technologies. The assembly contained nine-pair chromosomes with a contig N50 of 35.6 Mb and zero gaps, while a total of 633.0 Mb genomic sequences were generated. The origination analysis identified 338.5 Mb genomic sequences originating from citron (53.5%), 147.4 Mb from mandarin (23.3%), and 147.1 Mb from pummelo (23.2%). The genome included 30 528 protein-coding genes, and most of the assembled sequences were found to be repetitive sequences. Several significantly expanded gene families were associated with plant-pathogen interactions, plant hormone signal transduction, and the biosynthesis of major active components, such as terpenoids and flavor compounds. Most HLB-tolerant genes were expanded in the lemon genome, such as 2-oxoglutarate (2OG)/Fe(II)-dependent oxygenase and constitutive disease resistance 1, cell wall-related genes, and lignin synthesis genes. Comparative transcriptomic analysis showed that phloem regeneration and lower levels of phloem plugging are the elements that contribute to HLB tolerance in lemon. Our results provide insight into lemon genome evolution, active component biosynthesis, and genes associated with HLB tolerance.

16.
Lancet Respir Med ; 11(12): 1051-1063, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36958364

RESUMEN

BACKGROUND: The complement pathway is a potential target for the treatment of severe COVID-19. We evaluated the safety and efficacy of ravulizumab, a terminal complement C5 inhibitor, in patients hospitalised with severe COVID-19 requiring invasive or non-invasive mechanical ventilation. METHODS: This phase 3, multicentre, open-label, randomised controlled trial (ALXN1210-COV-305) enrolled adult patients (aged ≥18 years) from 31 hospitals in France, Japan, Spain, the UK, and the USA. Eligible patients had a confirmed diagnosis of SARS-CoV-2 that required hospitalisation and either invasive or non-invasive mechanical ventilation, with severe pneumonia, acute lung injury, or acute respiratory distress syndrome confirmed by CT scan or x-ray. We randomly assigned participants (2:1) to receive intravenous ravulizumab plus best supportive care (BSC) or BSC alone using a web-based interactive response system. Randomisation was in permuted blocks of six with stratification by intubation status. Bodyweight-based intravenous doses of ravulizumab were administered on days 1, 5, 10, and 15. The primary efficacy endpoint was survival based on all-cause mortality at day 29 in the intention-to-treat (ITT) population. Safety endpoints were analysed in all randomly assigned patients in the ravulizumab plus BSC group who received at least one dose of ravulizumab, and in all randomly assigned patients in the BSC group. The trial is registered with ClinicalTrials.gov, NCT04369469, and was terminated at interim analysis due to futility. FINDINGS: Between May 10, 2020, and Jan 13, 2021, 202 patients were enrolled in the study and randomly assigned to ravulizumab plus BSC or BSC. 201 patients were included in the ITT population (135 in the ravulizumab plus BSC group and 66 in the BSC group). The ravulizumab plus BSC group comprised 96 (71%) men and 39 (29%) women with a mean age of 63·2 years (SD 13·23); the BSC group comprised 43 (65%) men and 23 (35%) women with a mean age of 63·5 years (12·40). Most patients (113 [84%] of 135 in the ravulizumab plus BSC group and 53 [80%] of 66 in the BSC group) were on invasive mechanical ventilation at baseline. Overall survival estimates based on multiple imputation were 58% for patients receiving ravulizumab plus BSC and 60% for patients receiving BSC (Mantel-Haenszel analysis: risk difference -0·0205; 95% CI -0·1703 to 0·1293; one-sided p=0·61). In the safety population, 113 (89%) of 127 patients in the ravulizumab plus BSC group and 56 (84%) of 67 in the BSC group had a treatment-emergent adverse event. Of these events, infections and infestations (73 [57%] vs 24 [36%] patients) and vascular disorders (39 [31%] vs 12 [18%]) were observed more frequently in the ravulizumab plus BSC group than in the BSC group. Five patients had serious adverse events considered to be related to ravulizumab. These events were bacteraemia, thrombocytopenia, oesophageal haemorrhage, cryptococcal pneumonia, and pyrexia (in one patient each). INTERPRETATION: Addition of ravulizumab to BSC did not improve survival or other secondary outcomes. Safety findings were consistent with the known safety profile of ravulizumab in its approved indications. Despite the lack of efficacy, the study adds value for future research into complement therapeutics in critical illnesses by showing that C5 inhibition can be accomplished in severely ill patients. FUNDING: Alexion, AstraZeneca Rare Disease.


Asunto(s)
COVID-19 , Neumonía , Masculino , Adulto , Humanos , Femenino , Adolescente , Persona de Mediana Edad , SARS-CoV-2 , Respiración Artificial , Resultado del Tratamiento
17.
Clin Transl Med ; 13(1): e1173, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36629041

RESUMEN

With rapid developments of single-cell sequencing and multi/trans-omics, clinical single-cell biomedicine is a new and emergent discipline to integrate single-cell molecular and clinical phenomes and uncover new disease-specific diagnoses and therapy. The journal of Clinical and Translational Medicine (CTM) launches the first CTM initiative of clinical single-cell biomedicine (cscBioMed) to promote the discovery and development of single-cell-based biology and medicine, speed the translation from single-cell biology into clinical application, and improve early diagnosis and therapy for human diseases. The cscBioMed initiative is speeding translational processes from circulating single-cell RNA sequencing into routine measures in clinical biochemistry of haematology, from spatial transcriptomics into single-cell pathology, and from single-cell-based biomarkers and targets into clinical diagnostics and target drugs. With a clear goal, we expect that cscBioMed will benefit human health by establishing a clinical single-cell dynamic monitoring and early predicting system and by improving diagnosis and treatment.


Asunto(s)
Ciencia Traslacional Biomédica , Humanos , Biomarcadores , Análisis de Secuencia
18.
Plant Dis ; 107(5): 1299-1309, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36410020

RESUMEN

Pokkah boeng disease (PBD), a sugarcane foliar disease, is caused by various Fusarium spp. within the Fusarium fujikuroi species complex (FFSC). In the current study, we investigated the diversity of Fusarium spp. associated with PBD in China. In total, 320 leaf samples displaying PBD symptoms were collected over 10 consecutive years (2012 to 2021), during winter and summer, from six various sugarcane-growing regions (Guangxi, Yunnan, Guangdong, Zhejiang, Hainan, and Fujian) in China. Phylogenetic analysis of Fusarium spp. was reconstructed using translation elongation factor 1-α, and DNA-directed RNA polymerase II largest subunit and second-largest subunit multigene sequences. Evolutionary studies of these regions categorized the isolates into four FFSC species (F. sacchari, F. proliferatum, F. verticillioides, and F. andiyazi). The identified isolates, which developed irregular necrotic patches and rotting symptoms on the sugarcane plant after approximately 30 days were tested for their pathogenicity. Symptoms that appeared during pathogenicity testing were consistent with those observed under field conditions. Each strain of the pathogenic Fusarium spp. belonged to different vegetative compatibility groups (VCGs), and there was no affinity between VCGs. Our results contribute to understanding FFSC and accurately identifying Fusarium spp. associated with the sugarcane crop.


Asunto(s)
Fusarium , Saccharum , Filogenia , Virulencia/genética , China , Grano Comestible , Variación Genética
19.
Spine Deform ; 11(2): 373-381, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36152234

RESUMEN

PURPOSE: To assess effectiveness of a rapid recovery pathway (RRP) without epidural catheter analgesia (ECA) or intravenous patient controlled analgesia (PCA) in accelerating recovery and decreasing opioid consumption in patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF). METHODS: A retrospective cohort study included collection of demographics, ECA use, IV PCA, postoperative opioid consumption, postoperative pain scores, and reoperation rate. Opioid consumption was calculated using morphine milligram equivalents (MME). Hospital length of stay (HLOS) and first reported ambulation with physical therapy (PT) were also recorded. RESULTS: 53 patients were included, with 18 in the RRP group. Patient characteristics were comparable between the groups, except in ECA use and BMI. The RRP group consumed less total MME from postoperative day (POD) 0 to 2 (mean difference 61.6 MME; 95% CI 37.1-86.1 MME; p < 0.001). In addition, the RRP group had significantly shorter HLOS (2.5 vs 4.0 days; p < 0.001). There were no differences in VAS scores between the two groups. A subset analysis comparing patients who did and did not receive ECA showed that ECA resulted in overall higher inpatient MME and HLOS. A prediction model was developed using multiple regression based on the different medications used for multimodal analgesia (MMA) in the RRP. CONCLUSIONS: An RRP without the use of ECA or IV PCA can provide adequate analgesia in patients with AIS undergoing PSF while lowering inpatient narcotic consumption and accelerating immediate postoperative recovery.


Asunto(s)
Analgesia Epidural , Escoliosis , Humanos , Adolescente , Analgésicos Opioides , Estudios Retrospectivos , Escoliosis/etiología , Analgesia Epidural/métodos , Catéteres
20.
Microbiol Spectr ; 10(6): e0262222, 2022 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-36409071

RESUMEN

Huanglongbing (HLB; greening disease), caused by Candidatus Liberibacter asiaticus (CLas), is the most damaging citrus disease worldwide. The disease has spread throughout the citrus-producing regions of Guangxi, Guangdong, Fujian, and others in China. A total of 1,788 HLB-like symptomatic or asymptomatic samples were collected from the Guangxi and Fujian provinces of China to decipher the genetic diversity of CLas and its correlation with geographic region and host plant. The disease was the most severe in orange and the least in pomelo. CLas bacteria associated with the specific geographical and citrus variety infected more than 50% of the HLB-like symptomatic samples. We identified 6,286 minor variations by comparing 35 published CLas genomes and observed a highly heterogeneous variation distribution across the genome, including four highly diverse nonprophages and three prophage segments. Four hypervariable genomic regions (HGRs) were identified to determine the genetic diversity among the CLas isolates collected from Guangxi and Fujian, China. A phylogenetic tree constructed from four HGRs showed that 100 CLas strains could be separated into four distinct clades. Ten new strains with high variations of prophage regions were identified in the mandarin and tangerine grown in new plantation areas of Guangxi. Characterizing these HGR variations in the CLas bacteria may provide insight into their evolution and adaptation to host plants and insects. IMPORTANCE The hypervariable genomic regions derived from 35 published CLas genomes were used to decipher the genetic diversity of CLas strains and identify 10 new strains with high variations in prophage regions. Characterizing these variations in the CLas bacteria might provide insight into their evolution and adaptation to host plants and insects in China.


Asunto(s)
Liberibacter , Rhizobiaceae , Animales , Filogenia , Rhizobiaceae/genética , China , Insectos , Genómica , Variación Genética , Enfermedades de las Plantas/microbiología
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