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1.
J Biopharm Stat ; : 1-18, 2024 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-39306755

RESUMEN

Single and multiple random change points (RCPs) in survival analysis have arisen naturally in oncology trials, where the time to hazard rate change differs from one subject to another. Recently, Xu formulated and discovered important properties of these survival models using a frequentist approach, allowing us to estimate the hazard rates, rate parameters of the exponential distributions for the RCPs, expected survival and hazard functions. However, these methods did not provide an estimation of the uncertainty or the confidence intervals for the parameters and their differences or ratios. Therefore, statistical inferences were not able to be drawn on the parameters and their comparisons. To solve this issue, this article implements a Gibbs sampler method to estimate the above parameters and the differences or ratios alongside the 100(1 - α)% highest posterior density (HPD) intervals calculated from Chen-Shao's algorithm. The estimated rate parameters from the methods in Xu serve as empirical values in the Gibbs sampler method. Thus, formal statistical inferences can now be readily drawn. Simulation studies demonstrate that the proposed methods yield robust estimates, with the samples from the marginal posterior distributions converging rapidly and exhibiting favorable behavior. The 95% HPD intervals also demonstrate excellent coverage probabilities. This proposed method has a multitude of applications in clinical trials such as efficient clinical trial design and sample size adjustment based on the estimated parameter values at interim analyses.

2.
Artículo en Chino | MEDLINE | ID: mdl-39223044

RESUMEN

Objective: To measure and compare the difference of personal attenuation rating (PAR) of the workers wearing foam earplugs before and after the training, and to evaluate the effect of ear protector wearing training on the noise protection. Methods: In February 2023, 94 workers exposed to noise in a machinery manufacturing factory were selected as subjects. The production noise in the workplace was measured and subjects were trained to wear earplugs. The PAR values of wearing 3M 1110 foam test earplugs were measured and recorded before and after the training by using the fit testing of hearing protection device. The differences between the actual PAR values with nominal values and the noise attenuation values in related standards were compared, and the protective effect of hearing protection device before and after training was evaluated. Results: The average age of the subjects was (36.76±11.48) years old, the average length of service was (16.34±11.64) years, and the average exposure time to noise was (15.67±11.64) years. The noise detection results of the subjects' posts were ranged from 80.1 to 94.3 dB (A). The results of subjects wore 3M 1110 foam test earplugs for fit testing showed that the binaural PAR value after training was (19.3±6.4) dB (A), which was significantly higher than that before training (11.1±7.4) dB (A) (t=13.31, P<0.001). After training, 11 people (11.70%) could reach the corrected noise reduction value (NRR value), 26 people (27.66%) could reach the standard of single noise reduction value (SNR value) ×0.6, and 84 people (89.36%) could reach the standard of (NRR-7) /2. The under protection rate of hearing protectors after training (7.45%) was significantly lower than that before training (45.74%), and the difference of different protection levels before and after training was statistically significant (χ(2)=40.83, P<0.001) . Conclusion: It is suggested that enterprises should use the fit testing instead of nominal value estimation to evaluate the noise reduction effect of hearing protection device. Special training on the selection and use of hearing protection device should be strengthened, so as to ensure that workers wear them correctly and improve the protective effect of hearing protection device.


Asunto(s)
Dispositivos de Protección de los Oídos , Pérdida Auditiva Provocada por Ruido , Ruido en el Ambiente de Trabajo , Exposición Profesional , Humanos , Ruido en el Ambiente de Trabajo/prevención & control , Ruido en el Ambiente de Trabajo/efectos adversos , Adulto , Exposición Profesional/prevención & control , Pérdida Auditiva Provocada por Ruido/prevención & control , Masculino , Persona de Mediana Edad , Femenino , Lugar de Trabajo
3.
Ann Cardiol Angeiol (Paris) ; 73(6): 101758, 2024 Aug 09.
Artículo en Francés | MEDLINE | ID: mdl-39126897

RESUMEN

OBJECTIVES: The aim of the study was to determine the prevalence of AF in the cardiology department of the Hospital Principal of Dakar, then to evaluate the clinical, paraclinical, etiological and evolutionary profiles of AF and finally to identify the limits of its management in our context. PATIENTS AND METHODS: This was a retrospective, descriptive, analytical, mono-centric study carried out at Hospital Principal of Dakar from January 2019 to August 2021. Were included, all patients admitted for atrial fibrillation, or patients who presented an atrial fibrillation during hospitalization, confirmed by electrocardiogram or long-term electrocardiographic recording during the study period. RESULTS: The prevalence of atrial fibrillation during the period of our study compared to the hospital population was 7.71%, with a sex ratio of 1.03. The mean age was 67.88 ± 14.09 years. We noted that 83.64% of patients had at least one cardiovascular risk factor, with 56.36% suffering from hypertension, 50.91% of sedentary person and 23.64% of diabetics. Clinically, 92.72% of the patients were symptomatic, with dyspnea predominating (70.91%). Cardiac arrhythmia was present in 85.45% of patients, and congestive heart failure in 47.27%. Long-term electrocardiographic recording was performed in 10 patients, showing 50% of paroxysmal atrial fibrillation. Sixty-three patients (57.27%) had permanent AF, twenty-three patients (20.91%) had persistent AF, fourteen patients (12.73%) had long-term persistent AF and ten patients (9.09%) had paroxysmal AF. Transthoracic echocardiography showed 57.27% of left atrial dilatation and 72.3% of reduced left ventricular ejection fraction. Etiologies for cardiac causes were dominated by dilated cardiomyopathy (21.82%), followed by ischemic heart disease (17.27%). In terms of treatment, the most commonly used molecule was bisoprolol (38.18%), followed by digoxin (21.81%). Anticoagulants were used in 85.46% of cases. Acenocoumarol alone was used in 69.09% of patients. Drug-induced cardioversion was attempted in 2 patients without success, and 4 patients benefited from external electric shock with 3 successes. Most patients had a favorable outcome, but 34.54% suffered hemodynamic complications (18.18%) and thromboembolic ones as well (16.36%). In-hospital mortality in our series was 20%. It was significantly related to heart failure, with a left ventricular ejection fraction < 35% (p < 0.001). CONCLUSION: Atrial fibrillation is serious because of its hemodynamic, thromboembolic and rhythmic complications. The high mortality is explained by the underlying condition, but also by the delay in management with late diagnosis and, above all, the unavailability of ablation procedures in our context.

4.
BMC Public Health ; 24(1): 1044, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622576

RESUMEN

BACKGROUND: There are numerous complex barriers and facilitators to continuously wearing hearing protection devices (HPDs) for noise-exposed workers. Therefore, the present study aimed to investigate the relationship between HPD wearing behavior and hearing protection knowledge and attitude, HPD wearing comfort, and work-related factors. METHOD: A cross-sectional study was conducted with 524 noise-exposed workers in manufacturing enterprises in Guangdong Province, China. Data were collected on hearing protection knowledge and attitudes, HPD wearing comfort and behavior, and work-related factors through a questionnaire. Using structural equation modeling (SEM), we tested the association among the study variables. RESULTS: Among the total workers, 69.47% wore HPD continuously, and the attitudes of hearing protection (26.17 ± 2.958) and total HPD wearing comfort (60.13 ± 8.924) were satisfactory, while hearing protection knowledge (3.54 ± 1.552) was not enough. SEM revealed that hearing protection knowledge had direct effects on attitudes (ß = 0.333, p < 0.01) and HPD wearing behavior (ß = 0.239, p < 0.01), and the direct effect of total HPD wearing comfort on behavior was ß = 0.157 (p < 0.01). The direct effect also existed between work shifts and behavior (ß=-0.107, p < 0.05). Indirect relationships mainly existed between other work-related factors, hearing protection attitudes, and HPD wearing behavior through knowledge. Meanwhile, work operation had a direct and negative effect on attitudes (ß=-0.146, p < 0.05), and it can also indirectly and positively affect attitudes through knowledge (ß = 0.08, p < 0.05). CONCLUSION: The behavior of wearing HPD was influenced by hearing protection knowledge, comfort in wearing HPD, and work-related factors. The results showed that to improve the compliance of noise-exposed workers wearing HPD continuously when exposed to noise, the HPD wearing comfort and work-related factors must be taken into consideration. In addition, we evaluated HPD wearing comfort in physical and functional dimensions, and this study initially verified the availability of the questionnaire scale of HPD wearing comfort.


Asunto(s)
Pérdida Auditiva Provocada por Ruido , Ruido en el Ambiente de Trabajo , Humanos , Pérdida Auditiva Provocada por Ruido/prevención & control , Estudios Transversales , Análisis de Clases Latentes , Ruido en el Ambiente de Trabajo/efectos adversos , Ruido en el Ambiente de Trabajo/prevención & control , Dispositivos de Protección de los Oídos , Audición , Encuestas y Cuestionarios , China
5.
Ultrasound Obstet Gynecol ; 64(2): 214-221, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38456522

RESUMEN

OBJECTIVES: Well-established clinical practice for assessing progress in labor involves routine abdominal palpation and vaginal examination (VE). However, VE is subjective, poorly reproducible and painful for most women. In this study, our aim was to evaluate the feasibility of systematically integrating transabdominal and transperineal ultrasound assessment of fetal position, parasagittal angle of progression (psAOP), head-perineum distance (HPD) and sonographic cervical dilatation (SCD) to monitor the progress of labor in women undergoing induction of labor (IOL). We also aimed to determine if ultrasound can reduce women's pain during such examinations. METHODS: Women were recruited as they presented for IOL in three maternity units. Ultrasound assessments were performed in 100 women between 37 + 0 and 41 + 6 weeks' gestation. A baseline combined transabdominal and transperineal scan was performed, including assessment of fetal biometry, umbilical artery and fetal middle cerebral artery Doppler, amniotic fluid index, fetal spine and occiput positions, psAOP, HPD, SCD and cervical length. Intrapartum scans were performed instead of VE, unless there was a clinical indication to perform a VE, according to protocol. Participants were asked to indicate their level of pain by verbally giving a pain score between 0 and 10 (with 0 representing no pain) during assessment. Repeated measures data were analyzed using mixed-effect models to identify significant factors that affected the relationship between psAOP, HPD, SCD and mode of delivery. RESULTS: A total of 100 women were included in the study. Of these, 20% delivered by Cesarean section, 65% vaginally and 15% by instrumental delivery. There were no adverse fetal or maternal outcomes. A total of 223 intrapartum ultrasound scans were performed in 87 participants (13 women delivered before intrapartum ultrasound was performed), with a median of two scans per participant (interquartile range (IQR), 1-3). Of these, 76 women underwent a total of 151 VEs with a median of one VE per participant (IQR, 0-2), with no significant difference between vaginal- or Cesarean-delivery groups. After excluding those with epidural anesthesia during examination, the median pain score for intrapartum scans was 0 (IQR, 0-1) and for VE it was 3 (IQR, 0-6). Cesarean delivery was significantly associated with a slower rate of change in psAOP, HPD and SCD. CONCLUSIONS: Comprehensive transabdominal and transperineal ultrasound assessment can be used to assess progress in labor and can reduce the level of pain experienced during examination. Ultrasound assessment may be able to replace some transabdominal and vaginal examinations during labor. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Asunto(s)
Estudios de Factibilidad , Presentación en Trabajo de Parto , Ultrasonografía Prenatal , Humanos , Femenino , Embarazo , Ultrasonografía Prenatal/métodos , Adulto , Trabajo de Parto Inducido/métodos , Trabajo de Parto Inducido/estadística & datos numéricos , Primer Periodo del Trabajo de Parto , Perineo/diagnóstico por imagen , Trabajo de Parto/fisiología
6.
JMIR Hum Factors ; 11: e54854, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38502170

RESUMEN

BACKGROUND: Falls represent a large percentage of hospitalized patients with trauma as they may result in head injuries. Brain injury from ground-level falls (GLFs) in patients is common and has substantial mortality. As fall prevention initiatives have been inconclusive, we changed our strategy to injury prevention. We identified a head protection device (HPD) with impact-resistant technology, which meets head impact criteria sustained in a GLF. HPDs such as helmets are ubiquitous in preventing head injuries in sports and industrial activities; yet, they have not been studied for daily activities. OBJECTIVE: We investigated the usability of a novel HPD on patients with head injury in acute care and home contexts to predict future compliance. METHODS: A total of 26 individuals who sustained head injuries, wore an HPD in the hospital, while ambulatory and were evaluated at baseline and 2 months post discharge. Clinical and demographic data were collected; a usability survey captured HPD domains. This user experience design revealed patient perceptions, satisfaction, and compliance. Nonparametric tests were used for intragroup comparisons (Wilcoxon signed rank test). Differences between categorical variables including sex, race, and age (age group 1: 55-77 years; age group 2: 78+ years) and compliance were tested using the chi-square test. RESULTS: Of the 26 patients enrolled, 12 (46%) were female, 18 (69%) were on anticoagulants, and 25 (96%) were admitted with a head injury due to a GLF. The median age was 77 (IQR 55-92) years. After 2 months, 22 (85%) wore the device with 0 falls and no GLF hospital readmissions. Usability assessment with 26 patients revealed positive scores for the HPD post discharge regarding satisfaction (mean 4.8, SD 0.89), usability (mean 4.23, SD 0.86), effectiveness (mean 4.69, SD 0.54), and relevance (mean 4.12, SD 1.10). Nonparametric tests showed positive results with no significant differences between 2 observations. One issue emerged in the domain of aesthetics; post discharge, 8 (30%) patients had a concern about device weight. Analysis showed differences in patient compliance regarding age (χ12=4.27; P=.04) but not sex (χ12=1.58; P=.23) or race (χ12=0.75; P=.60). Age group 1 was more likely to wear the device for normal daily activities. Patients most often wore the device ambulating, and protection was identified as the primary benefit. CONCLUSIONS: The HPD intervention is likely to have reasonably high compliance in a population at risk for GLFs as it was considered usable, protective, and relevant. The feasibility and wearability of the device in patients who are at risk for GLFs will inform future directions, which includes a multicenter study to evaluate device compliance and effectiveness. Our work will guide other institutions in pursuing technologies and interventions that are effective in mitigating injury in the event of a fall in this high-risk population.


Asunto(s)
Cuidados Posteriores , Traumatismos Craneocerebrales , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Traumatismos Craneocerebrales/epidemiología , Dispositivos de Protección de la Cabeza , Alta del Paciente , Centros Traumatológicos , Interfaz Usuario-Computador , Anciano de 80 o más Años
7.
Planta ; 259(5): 93, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509429

RESUMEN

MAIN CONCLUSION: dnal7, a novel allelic variant of the OsHSP40, affects rice plant architecture and grain yield by coordinating auxins, cytokinins, and gibberellic acids. Plant height and leaf morphology are the most important traits of the ideal plant architecture (IPA), and discovering related genes is critical for breeding high-yield rice. Here, a dwarf and narrow leaf 7 (dnal7) mutant was identified from a γ-ray treated mutant population, which exhibits pleiotropic effects, including dwarfing, narrow leaves, small seeds, and low grain yield per plant compared to the wild type (WT). Histological analysis showed that the number of veins and the distance between adjacent small veins (SVs) were significantly reduced compared to the WT, indicating that DNAL7 controls leaf size by regulating the formation of veins. Map-based cloning and transgenic complementation revealed that DNAL7 is allelic to NAL11, which encodes OsHSP40, and the deletion of 2 codons in dnal7 destroyed the His-Pro-Asp (HPD) motif of OsHSP40. In addition, expression of DNAL7 in both WT and dnal7 gradually increased with the increase of temperature in the range of 27-31 °C. Heat stress significantly affected the seedling height and leaf width of the dnal7 mutant. A comparative transcriptome analysis of WT and dnal7 revealed that DNAL7 influenced multiple metabolic pathways, including plant hormone signal transduction, carbon metabolism, and biosynthesis of amino acids. Furthermore, the contents of the cytokinins in leaf blades were much higher in dnal7 than in the WT, whereas the contents of auxins were lower in dnal7. The contents of bioactive gibberellic acids (GAs) including GA1, GA3, and GA4 in shoots were decreased in dnal7. Thus, DNAL7 regulates rice plant architecture by coordinating the balance of auxins, cytokinins, and GAs. These results indicate that OsHSP40 is a pleiotropic gene, which plays an important role in improving rice yield and plant architecture.


Asunto(s)
Giberelinas , Oryza , Oryza/metabolismo , Alelos , Fitomejoramiento , Citocininas/metabolismo , Grano Comestible/genética , Ácidos Indolacéticos/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Hojas de la Planta/metabolismo
8.
Artículo en Chino | MEDLINE | ID: mdl-38311944

RESUMEN

Objective: To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing. Methods: From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed. Results: The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [M (Q(1), Q(3)) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant (P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups (P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion: The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.


Asunto(s)
Pérdida Auditiva Provocada por Ruido , Ruido en el Ambiente de Trabajo , Enfermedades Profesionales , Exposición Profesional , Humanos , Masculino , Pérdida Auditiva Provocada por Ruido/epidemiología , Pérdida Auditiva Provocada por Ruido/prevención & control , Dispositivos de Protección de los Oídos , Enfermedades Profesionales/prevención & control , Audición , Ruido en el Ambiente de Trabajo/efectos adversos , Ruido en el Ambiente de Trabajo/prevención & control , Exposición Profesional/prevención & control
9.
Hum Vaccin Immunother ; 20(1): 2313281, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38348622

RESUMEN

Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic option for large cell neuroendocrine carcinoma (LCNEC). However, various studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving ICI, which might be associated with gene alterations. Here, this is the first report on an unknown primary LCNEC patient who had achieved a long-term response from ICI treatment (atezolizumab), but developed HPD after tumor progression due to receiving another ICI agent (serplulimab). The mutation region of FAT4, SMARCA4, CYLD, CTNNB1, and KIT was altered prior to serplulimab treatment compared to before atezolizumab treatment. This case suggested a potential association between these mutated genes and HPD. Patients with the aforementioned genes should caution when selecting ICI treatment. These findings required further confirmation in a larger study cohort.


Asunto(s)
Carcinoma Neuroendocrino , Inhibidores de Puntos de Control Inmunológico , Humanos , Inmunoterapia/efectos adversos , Anticuerpos Monoclonales , Retratamiento , Progresión de la Enfermedad , ADN Helicasas , Proteínas Nucleares , Factores de Transcripción
10.
Am J Transplant ; 24(1): 20-29, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37659605

RESUMEN

Strong xenorejection limits the clinical application of porcine islet transplantation in type 1 diabetes. Targeting T cell-mediated rejection is one of the main approaches to improve long-term graft survival. Here we study engraftment and survival of porcine islet cells expressing human programmed cell death ligand-1 (hPD-L1) in a humanized mouse model. Neonatal islet-like clusters (NPICCs) from transgenic hPD-L1 (hPD-L1-Tg) and wild-type (Wt) pigs were transplanted into nonobese diabetic-scid IL2rγnull mice stably reconstituted with human immune cells (hPD-L1 n = 10; Wt n = 6). Primary endpoint was development of normoglycemia during a 16-week observation period after transplantation. Secondary endpoints were porcine C-peptide levels and immune cell infiltration. Animals transplanted with hPD-L1-Tg neonatal islet-like clusters achieved a superior normoglycemic rate (50% versus 0%) and significantly higher plasma C-peptide levels as compared to the Wt group, indicating long-term beta cell function. Intracytoplasmic fluorescence-activated cell sorting analysis and immunohistochemistry revealed significantly decreased frequencies of interferonγ-expressing splenic hCD8-positive T cells and reduced intragraft-infiltrating immune cells. We here demonstrate that expression of hPD-L1 provides strong islet xenograft protection without administration of immunosuppressive drugs. These findings support the hypothesis that hPD-L1 has the capacity to control cellular rejection and therefore represents a very promising transgene candidate for clinical porcine islet xenotransplantation.


Asunto(s)
Diabetes Mellitus , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Ratones , Animales , Humanos , Porcinos , Antígeno B7-H1/metabolismo , Péptido C/metabolismo , Islotes Pancreáticos/metabolismo , Ratones Noqueados , Trasplante Heterólogo , Ratones SCID , Rechazo de Injerto/etiología
11.
Mol Genet Genomic Med ; 12(1): e2298, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37817461

RESUMEN

BACKGROUND: Hereditary tyrosinemia type III (HT III) is an extremely rare form of tyrosinemia, characterized by autosomal recessive inheritance and biallelic mutations in the HPD gene. The clinical presentation of HT III is variable and poorly understood, with symptoms ranging from developmental delay and intellectual impairment to seizures and intermittent ataxia. This study aimed to provide further insights into the clinical and genetic characteristics of HT III. METHODS: A 3-year-old girl, identified through newborn screening, was diagnosed with HT III using targeted next-generation sequencing. A comprehensive literature review was conducted, and the clinical, biochemical, and genetic findings of previously reported HT III patients were summarized and analyzed. RESULTS: The genetic analysis of the proband revealed compound heterozygous mutations in the HPD gene such as c.731C>T (p.A244V) and c.656C>T (p.T219M). Notably, the HPD p.A244V mutation had not been previously documented in public databases or the scientific literature. Bioinformatics analysis classified both variants as pathogenic variants. The patient exhibited persistent tyrosinemia, elevated levels of related metabolite derivatives, confirming the diagnosis of HT III. The review of previously published cases contributed to a better understanding of the clinical and genetic characteristics associated with HT III. CONCLUSION: Early diagnosis and prompt treatment in infancy are crucial for managing HT III effectively. Dietary therapy, particularly during childhood, plays a significant role in disease management. The findings from this study enhance our understanding of the genotype-phenotype associations in HT III and emphasize the importance of early intervention for improved patient outcomes.


Asunto(s)
Tirosinemias , Recién Nacido , Femenino , Humanos , Preescolar , Tirosinemias/genética , Mutación , Genotipo , Fenotipo , China
12.
Front Oncol ; 13: 1283194, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38090479

RESUMEN

Chimeric antigen receptor T-cell therapy (CAR-T) has been widely applied in the clinical practice of relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) due to its promising effects. Hyperprogressive disease (HPD) has gained attention for rapid tumor progression and has become a therapeutic and prognostic challenge. Here, we present a patient who had suffered from several recurrences previously and controlled well with a very small tumor lesion left was infused with CD19/CD22 bispecific CAR-T, with no immune effector cell-associated neurotoxicity syndrome, or cytokine release syndrome observed. However, rapid deterioration, subsequent imaging examination, circulating tumor DNA, and serum biomarkers detection identified HPD. The patient did not respond to salvage treatment and died 40 days after infusion. To our knowledge, only one case of HPD in DLBCL after CAR-T therapy has been reported. This fatal case alarmed the risk of HPD and the ctDNA profile monitoring we used was performed as a non-invasive method to diagnose HPD, providing far-reaching practical instruction for CAR-T therapy.

13.
Front Med (Lausanne) ; 10: 1051034, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37215717

RESUMEN

Approximately 5% of advanced colorectal carcinomas (CRCs) and 12-15% of early CRCs are microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors. Nowadays, PD-L1 inhibitors or combined CTLA4 inhibitors are the major strategies for advanced or metastatic MSI-H colorectal cancer, but some people still show drug resistance or progression. Combined immunotherapy has been shown to expand the benefit population in non-small-cell lung carcinoma (NSCLC), hepatocellular carcinoma (HCC), and other tumors while reducing the incidence of hyper-progression disease (HPD). Nevertheless, advanced CRC with MSI-H remains rare. In this article, we describe a case of an elder patient with MSI-H advanced CRC carrying MDM4 amplification and DNMT3A co-mutation who responded to sintilimab plus bevacizumab and chemotherapy as the first-line treatment without obvious immune-related toxicity. Our case provides a new treatment option for MSI-H CRC with multiple risk factors of HPD and highlights the importance of predictive biomarkers in personalized immunotherapy.

14.
Immunotherapy ; 15(9): 631-639, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37020412

RESUMEN

Immune checkpoint inhibitors are important therapeutic agents for advanced non-small-cell lung cancer. Nevertheless, these new therapies can lead to unexpected serious complications, such as hyperprogressive disease (HPD). Once HPD occurs, most patients die within 1-3 months due to the lack of effective treatments. This paper reports a patient with advanced lung cancer who experienced HPD after two cycles of third-line sintilimab treatment. Sintilimab was stopped, and rescue anlotinib treatment was started. A partial response was achieved, and the clinical signs and symptoms were relieved. The patient died 7 months later from a lung infection. Although the mechanisms are unknown, anlotinib might be effective in managing non-small-cell lung cancer with HPD after sintilimab.


Immune checkpoint inhibitors (ICIs) are important drugs against advanced lung cancer, but these new drugs can lead to some unexpected serious complications, such as an uncontrolled progression of the disease (termed hyperprogressive disease [HPD]). Once HPD occurs, most patients die within 1­3 months because of the lack of effective treatments for HPD. This article presents a patient with advanced lung cancer who experienced HPD during treatment with an ICI. The ICI treatment was stopped, and anlotinib, another drug against cancer, was started. A partial response was achieved, and the symptoms were relieved. The patient died 7 months later from a lung infection but not of his lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Indoles/efectos adversos , Progresión de la Enfermedad
15.
Front Nutr ; 10: 1139098, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36819691

RESUMEN

[This corrects the article DOI: 10.3389/fnut.2022.1073576.].

16.
Integr Cancer Ther ; 22: 15347354221144310, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36624619

RESUMEN

Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber, and previous studies have shown many unique bioactivities of hGAG, including antitumor, anti-angiogenesis, anti coagulation, anti thrombosis, anti-inflammation, antidiabetic effect, antivirus, and immune regulation. The effects of 3W and 5W molecular weights hGAG with hematoporphyrin derivative-photodynamic therapy (HPD-PDT) on lung cancer were investigated. Human lung adenocarcinoma A549 cells were divided into 6 groups: control group, 3W molecular weight hGAG group, 5W molecular weight hGAG group, HPD-PDT group, 3W molecular weight hGAG + HPD-PDT group, and 5W molecular weight hGAG + HPD-PDT group. Cell morphology was observed under inverted phase contrast microscope. Cell proliferative activity was detected by CCK8 and cell apoptosis was assayed by Hoechst33258 staining and flow cytometry. The results showed that two different molecular weights hGAG could inhibit proliferation, promote apoptosis rates of A549 cells, and enhance the sensitivity of A549 cells to HPD-PDT. The combined use of hGAG and HPD-PDT has synergistic inhibitory effects on A549 cells, and the effects of 3W molecular weight hGAG are better than that of 5W molecular weight hGAG.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Peso Molecular , Adenocarcinoma del Pulmón/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Apoptosis , Glicosaminoglicanos , Derivado de la Hematoporfirina , Proliferación Celular
17.
Front Nutr ; 9: 1073576, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36570146

RESUMEN

Introduction: Obesity has become a major health problem worldwide. Diet management is an important means of weight loss. The aim of this study was to explore the improvement effect of a calorie-restricted diet (CRD), 5 + 2 intermittent fasting (5 + 2 IF), and high protein diet (HPD) on weight composition and serum lipid level of overweight and obese people in a short period (3 months). Methods: Fifty-three participants aged 18-60 years and with body mass index (BMI) ranging from 24 to 35 kg/m2 were screened for inclusion and exclusion criteria and were randomly divided into three groups, i.e., CRD, 5 + 2 IF, and HPD. Basic information, body composition, and venous blood samples were collected at baseline and after 3 months of intervention. Body composition was measured using a body composition analyzer (SK-V9), and serum lipids were assayed using the Roche Cobas e702 automatic biochemistry analysis system. The generalized estimating equation (GEE) was used to analyze and compare the repeated measurements of body composition and levels of serum lipids. Results: The results showed that total weight, BMI, body fat mass, muscle mass, visceral fat index, and waist and hip circumferences had significantly decreased in all three groups after 3 months of intervention, and the average weight loss was 3.3 ± 1.14, 4.12 ± 0.05, and 2.62 ± 0.13 kg in CRD, 5 + 2 IF, and HPD groups, respectively. The results of the GEE model indicated that compared with the CRD group, the 5 + 2 IF group showed a more significant decrease in weight (ß = -0.272, P < 0.001), BMI (ß = -0.091, P < 0.001), body fat mass (ß = -0.172, P < 0.001), muscle (ß = -0.043, P < 0.001), and visceral fat index (ß = -0.019, P < 0.001), however, HPD has more advantages in visceral fat index loss (ß = -0.011, P < 0.001) and lean body mass preserve (ß = 0.229, P < 0.001). Conclusion: Our findings showed that the 5 + 2 IF may be more effective in reducing total weight and body fat, and HPD may be more helpful in preventing lean body mass loss during a short-term weight loss intervention.

18.
Rev. méd. Maule ; 37(2): 76-80, dic. 2022.
Artículo en Español | LILACS | ID: biblio-1428590

RESUMEN

The evaluation of labor is the clinical process by which variables are analyzed in order to determine whether the patient is in labor, which by definition includes regular uterine contractions that increase in frequency and intensity, associated with dilation cervical. This is done through the anamnesis and physical examination, specifically through the evaluation of contractions and vaginal examination, the latter is intended to specify the degree of dilation, cervical effacement that the patient presents and also allows to a certain degree, establish the presentation, attitude and variety of position in which the fetus is located. From this premise, it is proposed that vaginal examination, since it is operator dependent, is not an objective evaluation, therefore, there is a need to reach consensus on the evaluation, and in order to carry it out, evaluation with ultrasound is proposed, which has as a purpose to objectify the variety of position and presentation of the fetus. Due to the above, this article aims to capture the knowledge that is currently possessed about the uses and methodology that intrapartum ultrasound presents.


Asunto(s)
Humanos , Femenino , Embarazo , Arterias Umbilicales/diagnóstico por imagen , Cesárea , Placenta/diagnóstico por imagen , Resultado del Embarazo , Ultrasonografía Prenatal , Ultrasonografía Doppler , Arteria Cerebral Media/diagnóstico por imagen
19.
Psychol Res Behav Manag ; 15: 3097-3116, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36304736

RESUMEN

Purpose: Pay for employee characteristic human capital inputs, which results in part of horizontal pay dispersion (HPD) and is well acknowledged by organizations and employees, has been greatly ignored by scholars. This study proposes "the characteristic-human-capital-inputs-based HPD" and explores what impact it tends to exert on team member work role performance (TMWRP), why, and when. Drawing on social comparison theory, goal-setting theory, and self-regulatory depletion theory, we develop a dual-mediation model elaborating the detrimental effect of this type of HPD on TMWRP from the perspective of employee benign and malicious envy and test it using objective and subjective data of 364 members coming from 65 Chinese ordinary employee teams. Methods: We on-site collected objective data including each member's pay level, outcome performance, and characteristic human capital inputs. Using five-point Likert rating method, team supervisors were requested to evaluate each member's TMWRP and members were asked to self-rate benign and malicious envy. Hierarchical regression analysis, simple slope analysis, and bootstrapping approach were employed to verify the model. Results: The characteristic-human-capital-inputs-based HPD adversely affects TMWRP by reducing employee benign envy (the mediating effect=-0.053, 95% CI=[-0.111, -0.002], excluding 0) and enhancing employee malicious envy (the mediating effect=-0.025, 95% CI=[-0.059, -0.004], excluding 0). The positive linkage between employee benign envy and TMWRP is only observed in lower-paid employees (the simple slope=0.145, p<0.05). Employee pay level does not moderate the relationship between malicious envy and TMWRP (ß=-0.033, p>0.10). Conclusion: The characteristic-human-capital-inputs-based HPD, which involves the HPD part mainly resulting from employee differences in characteristic human capital inputs, tends to impair TMWRP through inhibiting employee benign envy and promoting employee malicious envy. Employee pay level is an important boundary condition constraining the positive effect of benign envy on TMWRP.

20.
J Clin Med ; 11(17)2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-36079101

RESUMEN

Purpose: With the widespread use of immunotherapy agents, we encounter treatment responses such as hyperprogression disease (HPD) that we have not seen with previous standard chemotherapy and targeted therapies. It is known that survival in patients with HPD is shorter than in patients without HPD. Therefore, it is important to know the factors that will predict HPD. We aimed to identify HPD-related factors in patients treated with immunotherapy. Methods: A total of 121 adult metastatic cancer patients treated with immunotherapy for any cancer were included. Baseline demographics, the ECOG performance status, type of tumors and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. Results: The median age was 62.28 (interquartile range (IQR) 54.02−67.63) years, and the median follow-up was 12.26 (IQR 5.6−24.36) months. Renal cell carcinoma (33%) and melanoma (33.8%) were the most common diagnoses. Twenty patients (16.5%) had HPD. A high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007) were found to be associated with hyperprogression. Sex (female vs. male, p: 0.114), age (>65 vs. <65, p: 0.772), ECOG (0 vs. 1−4, p: 0.480) and the line of treatment (1−5, p: 0.112) were not found to be associated with hyperprogression. Conclusions: In this study, we observed HPD in 16.5% of immunotherapy-treated patients and increased HPD risk in patients with a high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007).

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