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2.
J Pain Symptom Manage ; 67(4): 306-316.e6, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38218414

RESUMEN

CONTEXT: Early palliative care is recommended within eight-week of diagnosing advanced cancer. Although guidelines suggest routine screening to identify cancer patients who could benefit from palliative care, implementing screening can be challenging due to understaffing and time constraints. OBJECTIVES: To develop and evaluate machine learning models for predicting specialist palliative care needs in advanced cancer patients undergoing chemotherapy, and to investigate if predictive models could substitute screening tools. METHODS: We conducted a retrospective cohort study using supervised machine learning. The study included patients aged 18 or older, diagnosed with metastatic or stage IV cancer, who underwent chemotherapy and distress screening at a designated cancer hospital in Japan from April 1, 2018, to March 31, 2023. Specialist palliative care needs were assessed based on distress screening scores and expert evaluations. Data sources were hospital's cancer registry, health claims database, and nursing admission records. The predictive model was developed using XGBoost, a machine learning algorithm. RESULTS: Out of the 1878 included patients, 561 were analyzed. Among them, 114 (20.3%) exhibited needs for specialist palliative care. After under-sampling to address data imbalance, the models achieved an Area Under the Curve (AUC) of 0.89 with 95.8% sensitivity and a specificity of 71.9%. After feature selection, the model retained five variables, including the patient-reported pain score, and showcased an 0.82 AUC. CONCLUSION: Our models could forecast specialist palliative care needs for advanced cancer patients on chemotherapy. Using five variables as predictors could replace screening tools and has the potential to contribute to earlier palliative care.


Asunto(s)
Neoplasias , Cuidados Paliativos , Humanos , Estudios Retrospectivos , Neoplasias/tratamiento farmacológico , Pacientes , Aprendizaje Automático
3.
Antimicrob Agents Chemother ; 63(12)2019 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-31570396

RESUMEN

Staphylococcus aureus is responsible for numerous community outbreaks and is one of the most frequent causes of nosocomial infections with significant morbidity and mortality. While the function of lytic transglycosylases (LTs) in relation to cell division, biofilm formation, and antibiotic resistance has been determined for several bacteria, their role in S. aureus remains largely unknown. The only known LTs in S. aureus are immunodominant staphylococcal antigen A (IsaA) and Staphylococcus epidermidis D protein (SceD). Our study demonstrates that, in a strain of methicillin-resistant S. aureus (MRSA), IsaA and SceD contribute differently to biofilm formation and ß-lactam resistance. Deletion of isaA, but not sceD, led to decreased biofilm formation. Additionally, in isaA-deleted strains, ß-lactam resistance was significantly decreased compared to that of wild-type strains. Plasmid-based expression of mecA, a major determinant of ß-lactam resistance in MRSA, in an isaA-deleted strain did not restore ß-lactam resistance, demonstrating that the ß-lactam susceptibility phenotype is exhibited by isaA mutant regardless of the production level of PBP2a. Overall, our results suggest that IsaA is a potential therapeutic target for MRSA infections.

4.
Ann Clin Microbiol Antimicrob ; 17(1): 44, 2018 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-30577829

RESUMEN

BACKGROUND: Catheter-related infection (CRI) is one of the serious challenges in clinical practice. This preliminary clinical study aimed to examine whether next-generation sequencing (NGS) targeting 16S rDNA, which was PCR-amplified directly from the tip of a central venous catheter (CVC), can be used to identify causative pathogens in CRI, compared to the culture method. METHODS: Hospitalized patients, from whom a CVC had just been removed, were prospectively enrolled and divided into the CRI-suspected and routine removal groups. DNA was extracted from the sonication fluid of CVC specimens derived from patients. For analysis of bacterial composition by NGS, the V3-V4 fragments of bacterial 16S rDNA were PCR-amplified, followed by index PCR and paired-end sequencing on an Illumina MiSeq device. Conventional culture methods were also performed in the CRI-suspected group. RESULTS: Of CVCs collected from the 156 enrolled patients (114 men; mean age 65.6 years), a total of 14 specimens [nine out of 31 patients suspected with CRI and five out of 125 patients without infection symptoms (routine removal group)] were PCR-positive. In five patients with definite CRI, Staphylococcus was the most frequently detected genus by NGS (4/5 specimens), although no pathogens were detected by NGS in the one remaining specimen. The genera identified by NGS were consistent with those from conventional culture tests. There was high agreement between NGS and the culture method in the CRI-suspected group, with sensitivity and specificity values of 80.0% and 76.9%, respectively; meanwhile, the false-positive rate of NGS was as low as 4.0% in the routine removal group. Moreover, several genera, besides the genus identified by culture test, were detected in each patient with definite CRI and surgical site infection (SSI). Additionally, in one patient with SSI, Enterococcaceae were detected not only by NGS but also by abdominal abscess drainage culture. CONCLUSIONS: NGS targeting 16S rDNA was able to analyze the bacterial composition of CVC specimens and detect causative pathogens in patients with CRI and was therefore suggested as a promising diagnostic tool for CRI.


Asunto(s)
Infecciones Relacionadas con Catéteres/microbiología , Catéteres Venosos Centrales/microbiología , ADN Bacteriano/genética , Adulto , Anciano , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad
5.
Front Microbiol ; 9: 182, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29491850

RESUMEN

The present study aimed to understand the biofilm formation mechanism of Propionibacterium acnes by analyzing the components and structure of the biofilms. P. acnes strains were isolated from the surface of explanted cardiac pacemaker devices that exhibited no clinical signs of infection. Culture tests using a simple stamp culture method (pressing pacemakers against the surface of agar plates) revealed frequent P. acnes colonization on the surface of cardiac pacemaker devices. P. acnes was isolated from 7/31 devices, and the isolates were categorized by multilocus sequence typing into five different sequence types (STs): ST4 (JK18.2), ST53 (JK17.1), ST69 (JK12.2 and JK13.1), ST124 (JK5.3), ST125 (JK6.2), and unknown ST (JK19.3). An in vitro biofilm formation assay using microtiter plates demonstrated that 5/7 isolates formed biofilms. Inhibitory effects of DNase I and proteinase K on biofilm formation varied among isolates. In contrast, dispersin B showed no inhibitory activity against all isolates. Three-dimensional live/dead imaging of P. acnes biofilms with different biochemical properties using confocal laser microscopy demonstrated different distributions and proportions of living and dead cells. Additionally, it was suggested that extracellular DNA (eDNA) plays a role in the formation of biofilms containing living cells. Ultrastructural analysis of P. acnes biofilms using a transmission electron microscope and atmospheric scanning electron microscope revealed leakage of cytoplasmic components along with cell lysis and fibrous structures of eDNA connecting cells. In conclusion, the biochemical properties and structures of the biofilms differed among P. acnes isolates. These findings may provide clues for establishing countermeasures against biofilm-associated infection by P. acnes.

7.
Artículo en Inglés | MEDLINE | ID: mdl-28758016

RESUMEN

Formation of bacterial biofilms on medical devices can cause severe or fatal infectious diseases. In particular, biofilm-associated infections caused by methicillin-resistant Staphylococcus aureus are difficult to eradicate because the biofilm is strongly resistant to antibiotics and the host immune response. There is no effective treatment for biofilm-associated infectionss, except for surgical removal of contaminated medical devices followed by antibiotic therapy. Here we show that norgestimate, an acetylated progestin, effectively inhibits biofilm formation by staphylococcal strains, including methicillin-resistant S. aureus, without inhibiting their growth, decreasing the selective pressure for emergence of resistance. 17-Deacetyl norgestimate, a metabolite of norgestimate, shows much weaker inhibitory activity against staphylococcal biofilm formation, indicating that the acetyl group of norgestimate is important for its activity. Norgestimate inhibits staphylococcal biofilm formation by inhibiting production of polysaccharide intercellular adhesin and proteins in the extracellular matrix. Proteome analysis of S. aureus indicated that norgestimate represses the expression of the cell wall-anchored protein SasG, which promotes intercellular adhesion, and of the glycolytic enzyme enolase, which plays a secondary role in biofilm formation. Notably, norgestimate induces remarkable changes in cell wall morphology, characterized by increased thickness and abnormal rippled septa. Furthermore, norgestimate increases the expression level of penicillin binding protein 2 and resensitizes methicillin-resistant S. aureus to ß-lactam antibiotics. These results suggest that norgestimate is a promising lead compound for the development of drugs to treat biofilm-associated infections, as well as for its ability to resensitize methicillin-resistant S. aureus to ß-lactam antibiotics.

8.
Int J Biochem Mol Biol ; 5(1): 21-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24955285

RESUMEN

We have shown that the receptor tyrosine kinase ErbB4 signals neuregulin1-stimulated proliferation of human cells. Some isoforms of ErbB4 are cleaved to release the soluble intracellular domain p80; however, the function of p80 in cell proliferation remained unclear. Here we propose the possibility for p80 as a negative feedback modulator of ErbB4-mediated cell proliferation. Cells exposed to lower doses of neuregulin1 displayed a stimulated proliferation and contained ErbB4 but barely p80. By contrast, cells exposed to its higher doses displayed a suppressed proliferation and contained p80 but barely ErbB4. Analyses with cells overexpressing the p80 wild type and mutants indicated that nuclear p80 inhibits cell proliferation independently of the tyrosine kinase activity. A screen for a novel protein that interacts with p80 identified α-enolase, which is reported as a transcriptional inhibitor for the proliferation-associated c-myc gene. The c-myc mRNA expression was induced by lower doses of neuregulin1 but was suppressed by its higher doses. Subcellular fractionation demonstrated the localization of not only p80 and α-enolase but also the decrease of the functional c-myc amount in the nuclei of cells exposed to higher doses of neuregulin1. These results suggested that p80, which is generated from ErbB4 and translocates to the nuclei, interacts with α-enolase and inhibits neuregulin1-dependent ErbB4-mediated cell proliferation by impairing the c-myc gene transcription.

10.
Antimicrob Agents Chemother ; 57(11): 5572-9, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23979748

RESUMEN

Control of biofilms formed by microbial pathogens is an important subject for medical researchers, since the development of biofilms on foreign-body surfaces often causes biofilm-associated infections in patients with indwelling medical devices. The present study examined the effects of different kinds of bacteriocins, which are ribosomally synthesized antimicrobial peptides produced by certain bacteria, on biofilms formed by a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA). The activities and modes of action of three bacteriocins with different structures (nisin A, lacticin Q, and nukacin ISK-1) were evaluated. Vancomycin, a glycopeptide antibiotic used in the treatment of MRSA infections, showed bactericidal activity against planktonic cells but not against biofilm cells. Among the tested bacteriocins, nisin A showed the highest bactericidal activity against both planktonic cells and biofilm cells. Lacticin Q also showed bactericidal activity against both planktonic cells and biofilm cells, but its activity against biofilm cells was significantly lower than that of nisin A. Nukacin ISK-1 showed bacteriostatic activity against planktonic cells and did not show bactericidal activity against biofilm cells. Mode-of-action studies indicated that pore formation leading to ATP efflux is important for the bactericidal activity against biofilm cells. Our results suggest that bacteriocins that form stable pores on biofilm cells are highly potent for the treatment of MRSA biofilm infections.


Asunto(s)
Antibacterianos/farmacología , Bacteriocinas/farmacología , Biopelículas/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Nisina/farmacología , Proteínas Citotóxicas Formadoras de Poros/farmacología , Adenosina Trifosfato/metabolismo , Secuencia de Aminoácidos , Antibacterianos/química , Bacteriocinas/química , Biopelículas/crecimiento & desarrollo , Humanos , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Nisina/química , Plancton/efectos de los fármacos , Plancton/crecimiento & desarrollo , Proteínas Citotóxicas Formadoras de Poros/química , Relación Estructura-Actividad , Vancomicina/farmacología
11.
Intern Med ; 50(15): 1559-63, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21804281

RESUMEN

OBJECTIVE: Several reports have indicated that cilostazol is effective in the prevention of recurrence after cerebral infarction. However, cilostazol is inferior in tolerability for the adverse events than other anti-platelet agents. The goal of this study was to determine whether cilostazol escalation oral administration affects its tolerability. METHODS: One hundred sixty-eight patients hospitalized for brain infarction with cilostazol treatment in our stroke center from 2006 to 2008 were enrolled in this study. During this term, we had two teams in our center and used different regimens. One of which used 100 mg b.i.d. regimen of cilostazol (Standard group) and the other used 50 mg b.i.d. for the initial 4 days, followed by a dose of 100 mg b.i.d. of it (Escalation group). Patient's information such as baseline characteristics, adverse events, were collected and statistically analyzed retrospectively. RESULTS: Seventy-nine patients were enrolled in Standard group and 87 patients in Escalation group. Comparison between these groups demonstrated that Escalation group had fewer patients who discontinued treatment (p=0.001) and a lower incidence of headache (p=0.004). CONCLUSION: This type of dose escalation regimen of cilostazol may be superior to the standard regimen in tolerability.


Asunto(s)
Infarto Encefálico/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 3/administración & dosificación , Tetrazoles/administración & dosificación , Anciano , Circulación Cerebrovascular/efectos de los fármacos , Cilostazol , Esquema de Medicación , Femenino , Cefalea/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa 3/efectos adversos , Estudios Retrospectivos , Tetrazoles/efectos adversos , Vasodilatación/efectos de los fármacos
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