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1.
Ann Hematol ; 103(4): 1389-1396, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38393657

RESUMEN

Transfusion reactions induced by platelet transfusions may be reduced and alleviated by leukocyte reduction of platelets. Although leukoreduction of apheresis platelets can be performed either pre-storage or post-storage, seldom studies directly compare the incidence of transfusion reaction in these two different blood products. We conducted a retrospective study to compare the transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets. We reviewed the general characteristics and the transfusion reactions, symptoms, and categories for inpatients who received pre-storage or post-storage leukoreduced apheresis platelets. Propensity-score matching was performed to adjust for baseline differences between groups. A total of 40,837 leukoreduction apheresis platelet orders were reviewed. 116 (0.53%) transfusion reactions were reported in 21,884 transfusions with pre-storage leukoreduction, and 174 (0.91%) reactions were reported in 18,953 transfusions with post-storage leukoreduction. Before propensity-score matching, the odds ratio for transfusion reactions in the pre-storage group relative to the post-storage group was 0.57 (95% confidence interval [CI] 0.45-0.72, P < 0.01); the odds ratio after matching was 0.63 (95% CI 0.49-0.80, P < 0.01). A two-proportion z-test revealed pre-storage leukoreduction significantly decreases the symptoms of chills, fever, itching, urticaria, dyspnea, and hypertension as compared with those in post-storage leukoreduction. Pre-storage leukoreduced apheresis platelet significantly decreased febrile non-hemolytic transfusion reaction as compared with post-storage groups. This study suggests pre-storage leukoreduction apheresis platelet significantly decreases the transfusion reaction as compared with those in post-storage leukoreduction.


Asunto(s)
Eliminación de Componentes Sanguíneos , Reacción a la Transfusión , Humanos , Estudios Retrospectivos , Puntaje de Propensión , Plaquetas , Eliminación de Componentes Sanguíneos/efectos adversos , Transfusión de Plaquetas/efectos adversos
2.
Clin Lab ; 70(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38868872

RESUMEN

BACKGROUND: Gastrointestinal infections present a significant public health concern as they lead to diverse clinical presentations and healthcare challenges. The rapid and accurate identification of causative pathogens is imperative for effective patient management. This study aimed to assess the clinical utility of the FilmArrayTM Gastrointestinal (GI) Panel for detecting gastrointestinal pathogens. METHODS: Between November 1, 2022, and December 31, 2023, we analysed gastrointestinal specimens collected from a cohort of patients aged 21 to 91 at Asia University Hospital. These specimens were analyzed using the FilmArrayTM GI Panel. RESULTS: The study included 76 patients for whom the FilmArrayTM GI assay was conducted, with 40 (52.6%) showing positive results. Among the positive specimens, 23 (57.5%) had a single pathogen, while the remaining 17 (42.5%) had multiple pathogens. The remaining 36 (47.4%) specimens showed no pathogens. The overall positivity rate of the specimens was 52.6%. The most frequently detected pathogens included Salmonella, Clostridium difficile (toxin A/B), and Enteropathogenic Escherichia coli (EPEC). CONCLUSIONS: This study underscores the clinical value of the FilmArrayTM GI assay as a rapid and reliable tool for diagnosing gastrointestinal infections. Its capacity to detect multiple pathogens simultaneously enhances diagnostic accuracy and gives information to use in clinical decision-making. We strongly recommend its integration into clinical practice to expedite the diagnosis and management of gastrointestinal infections, ultimately leading to improved patient care and healthcare efficiency.


Asunto(s)
Enfermedades Gastrointestinales , Humanos , Persona de Mediana Edad , Anciano , Adulto , Femenino , Masculino , Anciano de 80 o más Años , Adulto Joven , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/microbiología , Técnicas de Diagnóstico Molecular/métodos
3.
J Nanobiotechnology ; 22(1): 5, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38169397

RESUMEN

We have successfully generated oligonucleotide aptamers (Apts) and monoclonal antibodies (mAbs) targeting the recombinant nucleocapsid (N) protein of SARS-CoV-2. Apts were obtained through seven rounds of systematic evolution of ligands by exponential enrichment (SELEX), while mAbs were derived from the 6F6E11 hybridoma cell line. Leveraging these Apts and mAbs, we have successfully devised two innovative and remarkably sensitive detection techniques for the rapid identification of SARS-CoV-2 N protein in nasopharyngeal samples: the enzyme-linked aptamer-antibody sandwich assay (ELAAA) and the hybrid lateral flow strip (hybrid-LFS). ELAAA exhibited an impressive detection limit of 0.1 ng/mL, while hybrid-LFS offered a detection range of 0.1 - 0.5 ng/mL. In the evaluation using ten nasopharyngeal samples spiked with known N protein concentrations, ELAAA demonstrated an average recovery rate of 92%. Additionally, during the assessment of five nasopharyngeal samples from infected individuals and ten samples from healthy volunteers, hybrid-LFS displayed excellent sensitivity and specificity. Our study introduces a novel and efficient on-site approach for SARS-CoV-2 detection in nasopharyngeal samples. The reliable hybrid Apt-mAb strategy not only advances virus diagnostic methods but also holds promise in combating the spread of related diseases.


Asunto(s)
Aptámeros de Nucleótidos , COVID-19 , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , Anticuerpos Monoclonales , Sensibilidad y Especificidad
4.
Pestic Biochem Physiol ; 201: 105854, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38685234

RESUMEN

Pyridine alkylsulfone derivatives typified by oxazosulfyl (Sumitomo Chemical Company Ltd.) and compound A2 (Syngenta) represent a new class of insecticides, with potent activity against several insect orders. Whilst the MOA of this class has been attributed to interaction with the voltage-gated sodium channel (VGSC), here we present strong evidence that their toxicity to insects is mediated primarily through inhibition of the vesicular acetylcholine transporter (VAChT). Alkylsulfone intoxication in insects is characterised by (i) a reduction in cholinergic synaptic transmission efficiency demonstrated by a depression of cercal afferent activity in giant-interneurone preparations of American cockroach (Periplaneta americana), (ii) selective block of cholinergic-transmission dependent post-synaptic potentials in the Drosophila giant-fibre pathway and (iii) abolition of miniature excitatory post-synaptic currents (mEPSCs) in an identified synapse in Drosophila larvae. Ligand-binding studies using a tritiated example compound ([3H]-A1) revealed a single saturable binding-site, with low nanomolar Kd value, in membrane fractions of green bottle fly (Lucilia sericata). Binding is inhibited by vesamicol and by several examples of a previously identified class of insecticidal compounds known to target VAChT, the spiroindolines. Displacement of this binding by analogues of the radioligand reveals a strong correlation with insecticidal potency. No specific binding was detected in untransformed PC12 cells but a PC12 line stably expressing Drosophila VAChT showed similar affinity for [3H]-A1 as that seen in fly head membrane preparations. Previously identified VAChT point mutations confer resistance to the spiroindoline class of insecticides in Drosophila by Gal-4/UAS directed expression in cholinergic neurones and by CRISPR gene-editing of VAChT, but none of these flies show detectable cross-resistance to this new chemical class. Oxazosulfyl was previously shown to stabilise voltage-gated sodium channels in their slow-inactivated conformation with an IC50 value of 12.3µM but inhibits binding of [3H]-A1 with approximately 5000 times greater potency. We believe this chemistry class represents a novel mode-of-action with high potential for invertebrate selectivity.


Asunto(s)
Insecticidas , Sulfonas , Animales , Insecticidas/farmacología , Insecticidas/química , Sulfonas/farmacología , Sulfonas/química , Drosophila , Periplaneta/efectos de los fármacos , Periplaneta/metabolismo , Transmisión Sináptica/efectos de los fármacos , Acetilcolina/metabolismo
5.
Opt Express ; 31(12): 19897-19908, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37381395

RESUMEN

Quantitative differential phase contrast (QDPC) microscope plays an important role in biomedical research since it can provide high-resolution images and quantitative phase information for thin transparent objects without staining. With weak phase assumption, the retrieval of phase information in QDPC can be treated as a linearly inverse problem which can be solved by Tikhonov regularization. However, the weak phase assumption is limited to thin objects, and tuning the regularization parameter manually is inconvenient. A self-supervised learning method based on deep image prior (DIP) is proposed to retrieve phase information from intensity measurements. The DIP model that takes intensity measurements as input is trained to output phase image. To achieve this goal, a physical layer that synthesizes the intensity measurements from the predicted phase is used. By minimizing the difference between the measured and predicted intensities, the trained DIP model is expected to reconstruct the phase image from its intensity measurements. To evaluate the performance of the proposed method, we conducted two phantom studies and reconstructed the micro-lens array and standard phase targets with different phase values. In the experimental results, the deviation of the reconstructed phase values obtained from the proposed method was less than 10% of the theoretical values. Our results show the feasibility of the proposed methods to predict quantitative phase with high accuracy, and no use of ground truth phase.

6.
J Neurooncol ; 162(1): 179-189, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36894719

RESUMEN

PURPOSE: Microsurgery is the mainstay of treatment for large vestibular schwannomas (VS), but the benefits of radiosurgery remain incompletely defined. Here, we aim to use automated volumetric analysis software to quantify the degree of brain stem deformity to predict long-term outcomes of patients with large VS following GKRS. METHODS: Between 2003 and 2020, 39 patients with large VS (volume > 8 cc) undergoing GKRS with a margin dose of 10-12 Gy were analyzed. The reconstruction 3D MRI was used to evaluate the extent of deformity for predicting the long-term outcome of patients. RESULTS: Their mean tumor volume was 13.7 ± 6.3 cc, and their mean follow-up after GKRS was 86.7 ± 65.3 months. Favorable clinical outcome was observed in 26 (66.7%) patients, while 13 (33.3%) patients had treatment failure. Patients with small tumor volumes, low vital structure deformity indice [(TV/(BSV + CerV) and (TV + EV)/(BSV + CerV)], and long distance of tumor to the central line were more likely to have favorable clinical outcome after GKRS. Significant prognostic value was with tumor shrinkage ratio (< 50%) were CV, CV/TV, TV/CerV, (TV + EV)/(BSV + CerV), and the distance of tumor to the central line. In cox regression, favorable clinical outcome was correlated with the Charlson comorbidity index and cochlear dosage (both p < 0.05). In multivariant analysis, tumor regression was highly correlated with the CV/TV ratio (p < 0.001). CONCLUSIONS: The brainstem deformity ratio is likely a useful index to assess the clinical and tumor regression outcomes. Clinical outcomes are multifactorial and the tumor regression was highly correlated with the ratio of cystic components.


Asunto(s)
Neuroma Acústico , Radiocirugia , Humanos , Neuroma Acústico/diagnóstico por imagen , Neuroma Acústico/radioterapia , Neuroma Acústico/cirugía , Radiocirugia/efectos adversos , Resultado del Tratamiento , Pronóstico , Insuficiencia del Tratamiento , Estudios Retrospectivos , Estudios de Seguimiento
7.
Clin Lab ; 69(7)2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37436371

RESUMEN

BACKGROUND: Lower respiratory tract infections (LRIs) are an important public health concern and a leading cause of death from infection worldwide. The current study aims to evaluate the distribution of viral and bacterial pathogens in lower respiratory tract specimens. METHODS: Between April 2022 and December 2022, specimens from lower respiratory tract from patients aged between 37 and 85 years in an intensive care unit (ICU) of Asia University Hospital were analysed by the FilmArrayTM pneumonia panel (PP) assay. RESULTS: There were 54 patients for whom the FilmArrayTM PP assay was analysed, and 25 (46.3%) of them showed positive results. Among the 54 specimens, 12 (22.2%, 12/54) had a single pathogen, 13 (24.1%, 13/54) had multiple pathogens, and 29 (53.7%, 29/54) had no pathogens. The overall positive rate of the specimens was 46.3% (25/54). CONCLUSIONS: The FilmArrayTM PP assay may act as a feasible diagnostic tool for LRIs in ICUs.


Asunto(s)
Neumonía , Infecciones del Sistema Respiratorio , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Bacterias , Unidades de Cuidados Intensivos , Neumonía/diagnóstico , Neumonía/microbiología
8.
J Formos Med Assoc ; 122(10): 1069-1076, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37120338

RESUMEN

BACKGROUND/PURPOSE: A prehospital bypass strategy was suggested for large vessel occlusion. This study aimed to evaluate the effect of a bypass strategy using the gaze-face-arm-speech-time test (G-FAST) implemented in a metropolitan community. METHODS: Pre-notified patients with positive Cincinnati Prehospital Stroke Scale and symptom onset <3 h from July 2016 to December 2017 (pre-intervention period) and those with positive G-FAST and symptom onset <6 h from July 2019 to December 2020 (intervention period) were included. Patients aged <20 years and those with missing in-hospital data were excluded. The primary outcomes were the rates of receiving endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT). The secondary outcomes were total prehospital time, door-to-computed tomography (CT) time, door-to-needle (DTN) time, and door-to-puncture (DTP) time. RESULTS: We included 802 and 695 pre-notified patients from the pre-intervention and intervention periods, respectively. The characteristics of the patients in the two periods were similar. In the primary outcomes, pre-notified patients during the intervention period showed higher rates of receiving EVT (4.49% vs. 15.25%, p < 0.001) and IVT (15.34% vs. 21.58%, p = 0.002). In the secondary outcomes, pre-notified patients during intervention period had longer total prehospital time (mean 23.38 vs 25.23 min, p < 0.001), longer door-to-CT time (median 10 vs 11 min, p < 0.001), longer DTN time (median 53 vs 54.5 min, p < 0.001) but shorter DTP time (median 141 vs 139.5 min, p < 0.001). CONCLUSION: The prehospital bypass strategy with G-FAST showed benefits for stroke patients.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Administración Intravenosa , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/etiología , Trombectomía/métodos , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Tiempo de Tratamiento , Resultado del Tratamiento
9.
Int J Mol Sci ; 24(10)2023 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-37240094

RESUMEN

Numerous pathogenic CALR exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion; CALRDEL) and type 2 (5bp insertion; CALRINS) being the most prevalent. Despite the universal pathobiology of MPN driven by various CALR mutants, it is unclear why different CALR mutations result in diverse clinical phenotypes. Through RNA sequencing followed by validation at the protein and mRNA levels, we found that S100A8 was specifically enriched in CALRDEL but not in CALRINS MPN-model cells. The expression of S100a8 could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment. Pyrosequencing demonstrated relative hypomethylation in two CpG sites within the potential pSTAT3-targeting S100a8 promoter region in CALRDEL cells as compared to CALRINS cells, suggesting that distinct epigenetic alteration could factor into the divergent S100A8 levels in these cells. The functional analysis confirmed that S100A8 non-redundantly contributed to accelerated cellular proliferation and reduced apoptosis in CALRDEL cells. Clinical validation showed significantly enhanced S100A8 expression in CALRDEL-mutated MPN patients compared to CALRINS-mutated cases, and thrombocytosis was less prominent in those with S100A8 upregulation. This study provides indispensable insights into how different CALR mutations discrepantly drive the expression of specific genes that contributes to unique phenotypes in MPN.


Asunto(s)
Trastornos Mieloproliferativos , Humanos , Trastornos Mieloproliferativos/genética , Mutación , Calgranulina A/genética , Secuencia de Bases , Fenotipo , Calreticulina/genética , Janus Quinasa 2/genética
11.
J Biomed Sci ; 29(1): 88, 2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36303164

RESUMEN

BACKGROUND: Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. METHODS: Microbiota composition was determined through 16S rRNA V3-V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as "tri-part samples") in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. RESULTS: Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. CONCLUSION: This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.


Asunto(s)
Adenocarcinoma , Adenoma , Pólipos Adenomatosos , Neoplasias Colorrectales , Humanos , Fusobacterium nucleatum/genética , Prevotella intermedia/genética , ARN Ribosómico 16S/genética , Medios de Cultivo Condicionados , Adenoma/genética , Adenoma/microbiología , Adenoma/patología , Neoplasias Colorrectales/patología , Transformación Celular Neoplásica/genética , Bacterias/genética , Adenocarcinoma/genética , Pólipos Adenomatosos/genética
12.
Dement Geriatr Cogn Disord ; 51(4): 310-321, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35995033

RESUMEN

INTRODUCTION: Cognitive impairment (COIM) is a major challenge for healthcare systems and is associated with an increased risk of adverse outcomes in older people visiting emergency departments (EDs). Owing to global aging, both cognitive screening and comprehensive geriatric assessment (CGA) application in ED settings are developing areas of geriatric emergency medicine. Meanwhile, the association between clinical outcomes of COIM; cognitive impairment, no dementia (CIND); and dementia in the ED could be better investigated. Our study aims to identify individuals with COIM from older patients in the ED via CGA and to describe the association of CIND and dementia with prognosis in ED visits. METHODS: A prospective cross-sectional study was conducted in the ED of the Taipei Veterans General Hospital, a medical center located in Taipei, Taiwan, from August 2018 to November 2020. Patients aged ≥75 years with and without COIM were compared using data obtained from the CGAs conducted by trained nurses. RESULTS: A total of 823 older patients were enrolled in the study and underwent CGA. Of these, 463 (56.3%) were diagnosed with COIM, of which 292 (35.5%) were diagnosed with dementia; and 171 (20.8%), CIND. Between the no-COIM and COIM groups, the COIM group had a higher rate of hospital admission (p = 0.002) and mortality at 3 months (p < 0.05). Among the no-COIM, CIND, and dementia groups, ED disposition (p = 0.001) and the rate of revisit/readmission (p < 0.05) showed significant differences. In particular, the dementia group had a significantly higher rate of revisit/readmission as compared to the CIND group among the three groups. DISCUSSION/CONCLUSION: Older patients with COIM had a higher rate of hospital admission and mortality at the 3-month follow-up than older patients without COIM. Among the no-COIM, CIND, and dementia groups, patients with dementia had significantly increased risks of hospital admission and revisit/readmission. The early detection of COIM, and even dementia, could help ED physicians formulate strategies with geriatric specialists to improve mortality outcomes and revisit/readmission.


Asunto(s)
Evaluación Geriátrica , Readmisión del Paciente , Anciano , Humanos , Estudios Prospectivos , Estudios de Seguimiento , Estudios Transversales , Servicio de Urgencia en Hospital , Factores de Riesgo , Hospitales , Cognición
13.
Biomed Eng Online ; 21(1): 6, 2022 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-35090461

RESUMEN

BACKGROUND: Menopause-induced decline in estrogen levels in women is a main factor leading to osteoporosis. The objective of this study was to investigate the effect of intermittent parathyroid hormone (PTH) on bone structural parameters of the femoral neck in ovariectomized rats, in addition to correlations of maximum fracture force. METHODS: Fifteen female Wister rats were divided into three groups: (1) control group; (2) ovariectomized (OVX) group; and (3) OVX + PTH group. All rats were then killed and the femurs extracted for microcomputed tomography scanning to measure volumetric bone mineral density (vBMD) and bone structural parameters of the femoral neck. Furthermore, the fracture forces of femoral neck were measured using a material testing system. RESULTS: Compared with the control and OVX + PTH groups, the OVX group had significantly lower aBMD, bone parameter, and mechanical strength values. A comparison between OVX and OVX + PTH groups indicated that PTH treatment increased several bone parameters. However, the OVX + PTH groups did not significantly differ with the control group with respect to the bone structural parameters, except for trabecular bone thickness of cancellous bone, which was greater. In addition, among the bone structural parameters, the CSA and BSI of cortical bone were significantly correlated with the maximum fracture force of the femoral neck, with correlations of, respectively, 0.682 (p = 0.005) and 0.700 (p = 0.004). CONCLUSION: Intermittent PTH helped treat ovariectomy-induced osteoporosis of cancellous bone and cortical bone in the femoral necks of rats. The ability of the femoral neck to resist fracture was highly correlated with the two parameters, namely cross-sectional area (CSA) and bone strength index (= vBMD × CSA), of cortical bone in the femoral neck and was less correlated with aBMD or other bone structural parameters.


Asunto(s)
Cuello Femoral , Osteoporosis , Animales , Femenino , Cuello Femoral/diagnóstico por imagen , Humanos , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Ovariectomía , Hormona Paratiroidea , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Microtomografía por Rayos X
14.
J Formos Med Assoc ; 120(2): 863-873, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32873465

RESUMEN

BACKGROUND/PURPOSE: Ropeginterferon alpha-2b (Ropeg) is a novel pegylated interferon-alpha recently approved for the treatment of polycythemia vera (PV) in Europe. However, other than data from clinical trials, little is known about this agent in real world practice. METHODS: A compassionate use program employing Ropeg for treating patients with unmet medical need was initiated in Taiwan in 2017. Herein, we collected clinical data and assessed the safety as well as efficacy of Ropeg in nine patients treated in this program. RESULTS: Collectively, among evaluable patients, both the molecular response and complete blood count remission rates were 62.5%. Most therapy-related side effects were mild, and there was no treatment discontinuation attributable to intolerable adverse events. The agent also showed efficacy in symptom amelioration and spleen size reduction. Although no specific patterns of cytokine level alteration could be identified, significantly attenuated plasma levels of inflammation markers were observed in one particular patient who happened to have normalized spleen size and most remarkable reduction in JAK2 mutant allele burden, indicating all-around improvement in every aspect of this case. Furthermore, plasma hepcidin levels increased in two-thirds of PV patients, illustrating the potential of Ropeg to restore normal regulation of erythropoiesis. Using RNA sequencing on pre- and post-treatment samples from one patient, we demonstrated altered expression of genes participating in IFN response, inflammation, apoptosis, and cellular differentiation. CONCLUSION: Conclusively, observed signs of efficacy and safety in our real-world experience prove Ropeg as a promising option for the treatment of MPN.


Asunto(s)
Leucemia Mieloide Crónica Atípica BCR-ABL Negativa , Policitemia Vera , Alelos , Europa (Continente) , Humanos , Policitemia Vera/tratamiento farmacológico , Policitemia Vera/genética , Polietilenglicoles , Taiwán
15.
Br J Haematol ; 188(5): 707-722, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31610612

RESUMEN

Significant phenotypic heterogeneity exists in patients with all subtypes of myeloproliferative neoplasms (MPN), including essential thrombocythaemia (ET). Single-cell RNA sequencing (scRNA-Seq) holds the promise of unravelling the biology of MPN at an unprecedented level of resolution. Herein we employed this approach to dissect the transcriptomes in the CD34+ cells from the peripheral blood of seven previously untreated ET patients and one healthy adult. The mutational profiles in these patients were as follows: JAK2 V617F in two, CALR in three (one type I and two type II) and triple-negative (TN) in two. Our results reveal substantial heterogeneity within this enrolled cohort of patients. Activation of JAK/STAT signalling was recognized in discrepant progenitor lineages among different samples. Significantly disparate molecular profiling was identified in the comparison between ET patients and the control, between patients with different driver mutations (JAK2 V617F and CALR exon 9 indel), and even between patients harbouring the same driver. Intra-individual clonal diversity was also found in the CD34+ progenitor population of a patient, possibly indicating the presence of multiple clones in this case. Estimation of subpopulation size based on cellular immunophenotyping suggested differentiation bias in all analysed samples. Furthermore, combining the transcriptomic information with data from targeted sequencing enabled us to unravel key somatic mutations that are molecularly relevant. To conclude, we demonstrated that scRNA-Seq extended our knowledge of clonal diversity and inter-individual heterogeneity in patients with ET. The obtained information could potentially leapfrog our efforts in the elucidation of the pathogenesis of the disease.


Asunto(s)
Calreticulina , Janus Quinasa 2 , RNA-Seq , Análisis de la Célula Individual , Trombocitemia Esencial , Transcriptoma , Adulto , Sustitución de Aminoácidos , Calreticulina/genética , Calreticulina/metabolismo , Femenino , Humanos , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo , Masculino , Persona de Mediana Edad , Mutación Missense , Trombocitemia Esencial/sangre , Trombocitemia Esencial/genética
16.
Hematol Oncol ; 38(3): 390-398, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32011024

RESUMEN

BCR-ABL mutations are associated with resistance to tyrosine kinase inhibitors (TKIs) in Philadelphia chromosome-positive leukaemia. The emergence of these mutations in the era of second-generation TKIs, such as dasatinib and nilotinib, remains an evolving field. We conducted a retrospective study to quantitatively characterize the BCR-ABL transcript and mutation status during treatment with first-generation and second-generation TKI therapies. BCR-ABL mutations were detected by direct sequencing for patients with Philadelphia chromosome-positive leukaemia receiving TKI therapies. The efficacy of TKI therapy was quantitatively assessed by calculating the log reduction of BCR-ABL transcripts, which was measured using real-time quantitative polymerase chain reaction. Fisher's exact test was performed to analyse the associations of log reduction <3 and mutation status. We found 35 patients harbouring 55 mutations of 43 different types, of which 30% occurred in patients receiving imatinib, 27% in nilotinib, and 43% in dasatinib. We found a novel germline mutation, N336 N (AAC➔AAT), and two novel frameshift mutations, Asn358Thr fs*14 and Gly251Ala fs*16. T315I was the most common missense mutation, followed by V299L and F317L. Intron 8 35-bp insertion was the most frequent frameshift mutation. Both missense and multiple BCR-ABL mutations were significantly associated with worse molecular response compared with the molecular response of patients without mutation. Missense mutations, rather than frameshift, were associated with less log reduction, while the T315I, F317L, and T315A mutations were significantly correlated with poor log reduction. Collectively, amino acid substitutions at T315I, F317L, and T315A accounted for the majority of missense mutations and the loss of major molecular response. Mutation analysis is essential for patients receiving TKI therapy who exhibit an unfavourable response. The present study provided a landscape of BCR-ABL mutations in the era of second-generation TKIs.


Asunto(s)
Biomarcadores de Tumor/antagonistas & inhibidores , Proteínas de Fusión bcr-abl/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Mutación , Cromosoma Filadelfia , Inhibidores de Proteínas Quinasas/uso terapéutico , Biomarcadores de Tumor/genética , Resistencia a Antineoplásicos/genética , Femenino , Estudios de Seguimiento , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
17.
Aging Clin Exp Res ; 32(1): 149-155, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30877643

RESUMEN

BACKGROUND: Pneumonia is a leading cause of hospitalization and death worldwide. However, studies focusing on risk factors of community-acquired pneumonia (CAP) in the home health care (HHC) population remain scarce. AIMS: This study aimed to evaluate risk factors associated with hospitalization for CAP among HHC patients in Taiwan. METHODS: This retrospective cross-sectional study extracted data from patients' electronic medical records between 1 January 2017 and 31 December 2017. Multiple logistic regression analyses were performed to explore factors associated with hospitalization for CAP. RESULTS: In total, 598 patients (men/women: 236/362) were included. One hundred ninety-nine patients (33.28%) were hospitalized for pneumonia. Inpatients showed a higher proportion of the following: male sex, functional impairment, hypoalbuminemia, anemia, nasogastric tube use, excessive polypharmacy, stroke, dementia, heart failure, chronic respiratory disease, and chronic liver disease. Furthermore, nasogastric tube use (odds ratio [OR] 3.01, 95% confidence interval [CI] 1.88-4.82), anemia (OR 2.37, 95% CI 1.48-3.80), male sex (OR 2.14, 95% CI 1.43-3.20), chronic respiratory disease (OR 2.09, 95% CI 1.33-3.30), dementia (OR 1.94, 95% CI 1.27-2.97), heart failure (OR 1.69, 95% CI 1.11-2.56), and hypoalbuminemia (OR 1.57, 95% CI 1.03-2.40) significantly increased the risk of hospitalization for CAP. CONCLUSIONS: Our results revealed risk factors associated with hospitalization for CAP in HHC patients. In addition to chronic diseases, malnutrition is an important risk factor. Caregivers should make prompt assessments and take preventive measures for such patients.


Asunto(s)
Infecciones Comunitarias Adquiridas/etiología , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Neumonía/etiología , Anciano , Anciano de 80 o más Años , Enfermedad Crónica/epidemiología , Infecciones Comunitarias Adquiridas/epidemiología , Comorbilidad , Estudios Transversales , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Intubación Gastrointestinal/efectos adversos , Masculino , Oportunidad Relativa , Neumonía/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología
18.
Hu Li Za Zhi ; 67(2): 45-57, 2020 Apr.
Artículo en Zh | MEDLINE | ID: mdl-32281082

RESUMEN

BACKGROUND: Relocating from home to a long-term facility is frequently a stressful event for older persons with diabetes. Therefore, it is important that nurses have available an intervention program that effectively reduces relocation anxiety and promotes adaptation in this population. PURPOSE: To evaluate the effectiveness of a mindfulness-based intervention in reducing relocation anxiety and promoting adaptation in older persons with diabetes. METHODS: Four long-term care facilities in Kaohsiung City were selected as the study sites. Residents of these facilities who had diabetes and who had moved in within the previous year were recruited as participants using a simple random-sampling method. The experimental group (n = 34) received a 9-week mindfulness-based intervention and the control group (n = 32) received routine diabetes care and maintained their normal daily routine. Outcome measurements included a demographic datasheet, the Taiwanese version of the State Anxiety Inventory, and the individual mental factors subscale of the elderly adaptation problem scale. These measures were administered at baseline and upon completion of the intervention. RESULTS: Thirty participants in each group completed the study. The mean differences between the baseline and post-test scores in the experimental group for relocation anxiety (t = 5.15, p < .01) and adaptation (t = -5.57, p < .01) were both significant. Among the participants who tested positive for relocation anxiety at pretest (a mean score > 30.13; 83.3% of the participants), those in the experimental group reported a more significant decrease (p < .05) in relocation anxiety at posttest than their control group peers. Among the participants who tested as having poor adaptation pretest (a mean scores < 45.62; 71.7% of the participants), those in the experimental group reported a more significant improvement (p < .05) in adaptation at posttest than their control group peers. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results indicate that the 9-week intervention has the potential to help older people with diabetes improve their relocation anxiety and adaptation. This study may be used as a reference to improve emotional distress among residents of long-term care facilities.


Asunto(s)
Adaptación Psicológica , Ansiedad/psicología , Diabetes Mellitus/psicología , Atención Plena , Características de la Residencia , Anciano , Diabetes Mellitus/epidemiología , Humanos , Evaluación de Programas y Proyectos de Salud , Instituciones Residenciales , Taiwán/epidemiología
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