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Inflammatory markers and mediators that affect the development of car-diovascular diseases have been the focus of recent scientific work. Thus, the purpose of this editorial is to promote a critical debate about the article titled "Nε-carboxymethyl-lysine and inflammatory cytokines, markers, and mediators of coronary artery disease progression in diabetes", published in the World Journal of Diabetes in 2024. This work directs us to reflect on the role of advanced glycation end products, which are pro-inflammatory products arising from the metabolism of fatty acids and sugars whose main marker in tissues is Nε-carboxymethyl-lysine (NML). Recent studies have linked high levels of pro-inflammatory agents with the development of coronary artery disease (CAD), especially tumor necrosis factor alpha, interleukins, and C-reactive protein. These inflammatory agents increase the production of reactive oxygen species (ROS), of which people with diabetes are known to have an increased production. The increase in ROS promotes lipid peroxidation, which causes damage to myocytes, promoting myocardial damage. Furthermore, oxidative stress induces the binding of NML to its receptor RAGE, which in turn activates the nuclear factor-kB, and conse-quently, inflammatory cytokines. These inflammatory cytokines induce endo-thelial dysfunction, with increased expression of adhesion molecules, changes in endothelial permeability and changes in the expression of nitric oxide. In this sense, the therapeutic use of monoclonal antibodies (inflammatory reducers such as statins and sodium-glucose transport inhibitors) has demonstrated positive results in the regression of atherogenic plaques and consequently CAD. On the other hand, many studies have demonstrated a relationship between mito-chondrial dynamics, diabetes, and cardiovascular diseases. This link occurs since ROS have their origin in the imbalance in glucose metabolism that occurs in the mitochondrial matrix, and this imbalance can have its origin in inadequate diet as well as some pathologies. Photobiomodulation (PBM) has recently been considered a possible therapeutic agent for cardiovascular diseases due to its effects on mitochondrial dynamics and oxidative stress. In this sense, therapies such as PBM that act on pro-inflammatory mediators and mitochondrial modulation could benefit those with cardiovascular diseases.
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BACKGROUND: The wearing-off phenomenon is a key driver of medication change for patients with Parkinson's disease (PD) treated with levodopa. Common first-line options include increasing the levodopa dose or adding a catechol-O-methyltransferase (COMT) inhibitor, but there are no trials comparing the efficacy of these approaches. We evaluated the effectiveness of adjunct opicapone versus an additional 100 mg levodopa dose in PD patients with early wearing-off using pooled data from 2 randomized studies. METHODS: The ADOPTION study program included two similarly designed 4-week, open-label studies conducted in South Korea (NCT04821687) and Europe (NCT04990284). Patients with PD, treated with 3-4 daily doses of levodopa therapy and with signs of early wearing-off were randomized (1:1) to adjunct opicapone 50 mg or an additional dose of levodopa 100 mg. Patient-level data from the two studies were pooled. RESULTS: The adjusted mean [SE] change from baseline to week 4 in absolute OFF time (key endpoint) was - 62.8 min [8.8] in the opicapone group and - 33.8 min [9.0] in the levodopa 100 mg group, the difference significantly favoring opicapone (- 29.0 [- 53.8, - 4.2] min, p = 0.02). Significant differences in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III subscore (- 4.1 with opicapone vs - 2.5 with levodopa 100 mg), also favored opicapone (- 1.7 [- 3.3, - 0.04], p < 0.05). Dyskinesia was the most frequently reported adverse event (opicapone 7.2% vs. levodopa 100 mg 4.2%). CONCLUSIONS: In these short-term trials, introducing adjunct opicapone was more effective at reducing OFF time than adding another 100 mg levodopa dose in PD patients with early signs of wearing-off.
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Introduction: Breast cancer (BC) is the most common cancer among women globally. Vitamin D has been considered a protective factor; however, its relationship with any aspect of the disease remains controversial. Methods: A cross-sectional, single-center clinical study was conducted between 2015 and 2018, including 141 women diagnosed with BC and 239 women in the control group, with mean ages of 43.1 and 41.7 years, respectively (p = 0.103). Serum levels of vitamin D and lipid profile were measured. Clinical and nutritional data were obtained through interviews and medical records. Results: The vitamin D dosage presented an average value of 25.5 ng/mL and 31.0 ng/mL in the case and control groups, respectively (p < 0.001). The vitamin D cut-off point for discriminating the presence of BC was 27.45 ng/mL. Additionally, low-density lipoprotein cholesterol levels were higher in the case group (121.4 mg/dL) compared to the control group (110.7 mg/dL) (p = 0.002), whereas high-density lipoprotein cholesterol levels were lower in the case group (47.6 mg/dL) compared to the control group (53.3 mg/dL) (p = 0.001). Alcohol consumption was significantly higher in the case group than in the control group (2.7 vs. 5.3 doses/day; p < 0.001). Conclusion: The results indicate a significant association between lower vitamin D levels and BC, persisting after multivariate analysis (p < 0.001). These findings could inform prevention strategies, highlighting the importance of maintaining adequate vitamin D levels and potentially identifying a risk group.
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Thyroid nodules in pediatric patients are less common than in adults but show a higher malignancy rate. Accordingly, the management of thyroid nodules in pediatric patients is more complex the younger the patient is, needing careful evaluation by physicians. In adult patients, specific ultrasound (US) features have been associated with an increased risk of malignancy (ROM) in thyroid nodules. Moreover, several US risk stratification systems (RSSs) combining the US features of the nodule were built to define the ROM. RSSs are developed for the adult population and their use has not been fully validated in pediatric patients. This study aimed to evaluate the available data about US features of thyroid nodules in pediatric patients and to provide a summary of the evidence regarding the performance of RSS in predicting malignancy. Moreover, insights into the management of thyroid nodules in pediatric patients will be provided.
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Tumor hypoxia may compromise the results of chemotherapy for treating colorectal cancer because it stimulates angiogenesis and the release of tumor growth factors. Hyperbaric oxygen (HBO) supplementation may potentiate the effects of chemotherapy in such cases. This study aimed to assess the effect of HBO therapy combined with chemotherapy on the treatment of colorectal cancer in mice. C57BL6 mice were submitted to the intrarectal instillation of N-methyl-N-nitrosoguanidine (MNNG) and treated with 5-fluorouracil (5FU) and/or HBO therapy. The MNNG group presented the highest dysplastic crypt rate. The 5FU + HBO group presented the highest rate of apoptotic cells per dysplastic crypt. The 5FU group presented the highest expression of hypoxia-inducible factor-1 alpha and CD44. HBO therapy increased the effect of 5FU on the treatment of the experimental colorectal neoplasia in mice.
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Neoplasias Colorrectales , Fluorouracilo , Oxigenoterapia Hiperbárica , Ratones Endogámicos C57BL , Animales , Fluorouracilo/farmacología , Ratones , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/tratamiento farmacológico , Masculino , Antimetabolitos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Receptores de Hialuranos/metabolismo , Terapia Combinada , Metilnitronitrosoguanidina/farmacologíaRESUMEN
BACKGROUND: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes. METHODS: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation). RESULTS: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65-0.87]; P<0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82-0.97]; P<0.001). The score's predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71-0.92]; P<0.001). CONCLUSIONS: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS.
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Biomarcadores , Accidente Cerebrovascular Isquémico , Proteínas tau , Humanos , Femenino , Masculino , Anciano , Proteínas tau/sangre , Pronóstico , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/terapia , Persona de Mediana Edad , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios Prospectivos , Procedimientos Endovasculares/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/irrigación sanguínea , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/sangre , Isquemia Encefálica/terapia , Estudios de Cohortes , Proteína Ácida Fibrilar de la Glía/sangreRESUMEN
Background: Hematological cancer patients are prone to the development of sarcopenia and impaired nutritional and functional status. SARC-CalF is a screening tool for the risk of sarcopenia that has shown good results in this population. This study aimed to identify the risk of sarcopenia by SARC-CalF and to verify its association with nutritional status and Hand Grip Strength (HGS) in patients with hematological cancer. Materials and Methods: Adult patients, of both sexes, with hematological cancer, and in outpatient care participated in the study. We measured the Hand Grip Strength of the Dominant Hand (HGSD) and the Adductor Pollicis Muscle Thickness of the Dominant Hand (APMTD). Moreover, we applied the Patient-Generated Subjective Global Assessment (PG-SGA) and SARC-CalF. Data were analyzed with SPSS® software, 22.0, with a significance level of 5.0%. Results: Fifty-one patients aged an average of 60.4 ± 15.1 years were evaluated. Of those, 58.8% were elderly, 51% female, and 80.4% declared themselves non-white. The predominant diagnosis was Mature B Lymphoid Cell Neoplasia (37.7%), and 60.8% of the patients had a diagnosis time of ≤ 3 years. PG-SGA revealed that 35.3% of the patients were malnourished; APMTD and HGSD revealed that 60.8% and 25.5% had reduced muscle strength, respectively. SARC-CalF exposed that 39.2% of the patients were at risk for sarcopenia. Significant associations were found between SARC-CalF and diagnosis time ≤ 3 years (p = 0.039), PG-SGA (p = 0.020), APMTD (p = 0.039) and HGSD (p = 0.002). After binary logistic regression adjusted for age and sex, the reduced HGSD remained associated with the risk of sarcopenia. Conclusion: SARC-CalF identified a risk of sarcopenia in 39.2% of patients. The reduced HGSD was associated with the risk of sarcopenia.
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OBJECTIVES: Rumination is a maladaptive emotion regulation strategy. It has been associated with several psychological disorders and physical problems. This cross-sectional study aimed to evaluate whether cognitive rumination is associated with periodontal disease (PD), tooth loss (TL), and oral health-related quality of life (OHRQoL). MATERIALS AND METHODS: A population-based sample from a rural area in southern Brazil was evaluated. Calibrated examiners carried out a complete periodontal examination at six sites-per-tooth. Rumination and Reflection (RRQ) and Oral Health Impact Profile (OHIP-14) questionnaires were administered. Regression modeling was used to assess the prevalence ratio (PR) between rumination and PD and to estimate the rate ratio (RR) between rumination and TL and rumination and OHIP. RESULTS: Severe periodontitis prevalence of 33% was observed in the sample. In the Poisson-adjusted model (n = 587), individuals who ruminate more have 27% more periodontal disease (PR: 1.27, 95%CI:1.02 - 1.60). Regarding TL and OHIP, negative binomial regression (n = 672) showed an association with rumination, but it was not significant (RR 1.14, 95%CI 0.99 - 1.31) and (RR 1.20, 95%CI 0.98 - 1.48), respectively. CONCLUSIONS: Cognitive rumination was independently associated with periodontal disease in individuals living in a rural area. Borderline non-significant estimates were observed regarding TL and OHRQoL. More research using different populations and focusing on individual's responses to psychological stress may confirm these results. CLINICAL RELEVANCE: Emotional regulation is crucial to deal with stress, anxiety, and depression. Since psychopathologies are among the most prevalent diseases in the world, it is critical to understand the role of these issues in dental outcomes.
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Salud Bucal , Enfermedades Periodontales , Calidad de Vida , Rumiación Cognitiva , Población Rural , Pérdida de Diente , Humanos , Femenino , Masculino , Brasil/epidemiología , Estudios Transversales , Pérdida de Diente/epidemiología , Pérdida de Diente/psicología , Enfermedades Periodontales/psicología , Enfermedades Periodontales/epidemiología , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto , Prevalencia , AncianoRESUMEN
The objective of the article was to investigate the possible inducing factors that contributed to determine the frequency of social conflicts at the subnational level in Peru between 2016 and 2021, including income inequality, social exclusion, fiscal centralism, corruption and revocation of authorities, for which four regression models were built. Disaggregated official data from the 24 departments and the provinces of Lima and Callao were analyzed. Economic inequality was associated with the Gini coefficient. To establish the association between social conflict and the inducers, it was estimated using Spearman's Rho correlation coefficient. Statistical calculation was also employed to appreciate the collinearity between the inducers. The results showed that the revocation of subnational authorities determines 42.5% of social conflict. On the other hand, corruption and fiscal centralism determine 28.5% of the perception of suffering social exclusion. Inequality and social conflict determined 21.8% of the relevance of the execution and quality of public spending by the national government in the regions. Sixty percent of social conflicts in Peru are of an environmental nature. The population that has declared the greatest discrimination corresponds to Puno (28%). 55.6% of those surveyed consider corruption to be one of the country's main problems. Corruption and social exclusion have a negative impact on the effectiveness of economic results and promote social conflicts. Inefficient use of fiscal resources translates into low quality of services and diminished credibility of the national and subnational governments. This situation highlights the need to design public policies that reduce conflicts and promote adequate governance.
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Objetivo:identificar fatores clínicos associados à sobrevida de pacientes com COVID-19 internados em Unidade de Terapia Intensiva. Método:estudo de coorte retrospectivo, por meiode análise documental de 100 prontuários de pacientes com COVID-19 internados em uma Unidade de Terapia Intensiva, no período marçoa maio de 2021. Resultados:os fatores sociodemográficos, comorbidades e fatores de risco indicaram mudança no perfil do paciente, em comparação aestudos realizados na primeira onda pandêmica. Dentre os fatores associados à sobrevida dos pacientes com COVID-19 internados em Unidade de Terapia Intensiva destacam-se a oxigenoterapia de baixo fluxo via nasal, a posição autoprona, a sedação com midazolam e o tempo de internação. Já a hemodiálise e o uso de rocurônio aumentaram o risco de óbito dos pacientes. Conclusão:os resultados podem contribuir para a tomada de decisões e melhorar o atendimento ao paciente crítico com COVID-19.
Objective:to identify clinical factors associated with the survival of patients with COVID-19 admitted to the Intensive Care Unit. Method:retrospective cohort study, through documentary analysis of 100 medical records of patients with COVID-19 admitted to an Intensive Care Unit, in the period from Marchto May 2021. Results:sociodemographic factors, comorbidities,and risk factors indicated a change in the patient's profile, compared to studies carried out in the first pandemic wave. Among the factors associated with the survival of patients with COVID-19 admitted to the Intensive Care Unit, low-flow nasal oxygen therapy, prone position, sedation with midazolam and length of stay stand out. Hemodialysis and the use of rocuronium increased the risk of death for patients. Conclusion:the results can contribute to decision-making and improve care for critical patients with COVID-19
Objetivo:identificar factores clínicos asociados a la supervivencia de pacientes con COVID-19 ingresados en la Unidad de Cuidados Intensivos. Método:estudio de cohorte retrospectivo, mediante análisis documental de 100 historias clínicas de pacientes con COVID-19 ingresados en una Unidad de Cuidados Intensivos, en el período de marzoa mayo de 2021. Resultados:factores sociodemográficos, comorbilidades y factores de riesgo indicaron un cambio en el perfil del paciente, en comparación con estudios realizados en laprimera ola pandémica. Entre los factores asociados a la supervivencia de los pacientes con COVID-19 ingresados en la Unidad de Cuidados Intensivos destacan la oxigenoterapia nasal de bajo flujo, la posición prona, la sedación con midazolam y el tiempo deestancia hospitalaria. La hemodiálisis y el uso de rocuronio aumentaron el riesgo de muerte de los pacientes. Conclusión:los resultados pueden contribuir a la toma de decisiones y mejorar la atención al paciente crítico con COVID-19
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COVID-19 , Mortalidad , Enfermería , Cuidados Críticos , Unidades de Cuidados IntensivosRESUMEN
Objective: To analyze the amount of muscle and the presence of sarcopenia in postmenopausal women using different methods, verifying the agreement between them as to skeletal muscle mass (SMM). Methods: This cross-sectional observational study was conducted with postmenopausal women aged ≥ 50 years. SMM was obtained from a predictive equation, Bioelectrical Impedance (BIA), and Dual Energy X-Ray Absorptiometry (DXA). The skeletal muscle mass index (SMI) and the appendicular skeletal muscle mass index (ASMI) were calculated. The cut-off point of SMI was determined for the population itself. The agreement between the SMI obtained using the different methods was verified. Sarcopenia was diagnosed according to the criteria proposed by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). The significance level adopted for all tests was 5.0%. Results: A total of 112 women were evaluated, with an average age of 66.1 ± 5.65 years. Among them, 51.8% were sufficiently active and 43.8% were overweight and obese. The SMI cut-offs were 6.46 kg/m2 for the predictive equation and 7.66 kg/m2 for BIA, with high sensitivity and specificity. There was an excellent agreement in the identification of SMM by the predictive equation (0.89 [0.824-0.917], p < 0.001) and BIA (0.92 [0.883-0.945], p < 0.001), in reference to DXA. The prevalence of sarcopenia was 0.9%, 1.8%, and 2.7% according to BIA, DXA, and the predictive equation, respectively. Conclusion: The predictive equation showed the expected agreement in estimating skeletal muscle mass in postmenopausal women, offering a viable and accurate alternative.
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Absorciometría de Fotón , Músculo Esquelético , Posmenopausia , Sarcopenia , Humanos , Femenino , Sarcopenia/epidemiología , Sarcopenia/diagnóstico por imagen , Sarcopenia/diagnóstico , Estudios Transversales , Posmenopausia/fisiología , Anciano , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/anatomía & histología , Persona de Mediana Edad , Impedancia Eléctrica , AntropometríaRESUMEN
Stanhopea tigrina Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as "Calavera" or "calaverita", in the Huasteca Potosina (central region of Mexico). This plant species is used for the folk treatment of mental disorders and urological kidney disorders, according to the ethnomedicinal information obtained in this study. Ethanolic extracts of leaves (HE) and pseudobulb (PE) were obtained by microwave-assisted extraction (MAE). Gas Chromatography coupled with Mass Spectrometry (GC-MS) was used to carry out the chemical characterization of HE and PE. The pharmacological effects (antioxidant, diuretic, anxiolytic, locomotor, hypnotic, and sedative) of HE and PE were evaluated. The possible mechanism of action of the anxiolytic-like activity induced by HE was assessed using inhibitors of the GABAergic, adrenergic, and serotonergic systems. The possible mechanism of the diuretic action of HE was assessed using prostaglandin inhibitory antagonists and nitric oxide synthase (NOS) blockers. HE at 50 and 100 mg/kg exerted anxiolytic-like activity without inducing hypnosis or sedation. Flumazenil, prazosin, and ketanserin inhibited the anxiolytic-like activity shown by HE, which suggests the participation of GABA, α1-adrenergic receptors, and 5-HT2 receptors, respectively. The diuretic effect was reversed by the non-selective NOS inhibitor L-NAME, which caused the reduction in nitric oxide (NO). These results demonstrate that the ethanolic extract of S. tigrina leaves exhibited anxiolytic-like activity and diuretic effects without inducing hypnosis or sedation. This work validates the medicinal uses of this orchid species.
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Introduction: Tolvaptan has been shown to reduce renal volume and delay disease progression in autosomal-dominant polycystic kidney disease (ADPKD). However, no biomarkers are currently available to guide dose adjustment. We aimed to explore the possibility of individualized tolvaptan dose adjustments based on cut-off values for urinary osmolality (OsmU). Methods: This prospective cohort study included patients with ADPKD, with rapid disease progression. Tolvaptan treatment was initiated at a dose of 45/15 mg and increased based on OsmU, with a limit set at 200 mOsm/kg. Primary renal events (25% decrease in estimated glomerular filtration rate [eGFR] during treatment), within-patient eGFR slope, and side effects were monitored during the 3-year follow-up. Results: Forty patients participated in the study. OsmU remained below 200 mOsm/kg throughout the study period, and most patients required the minimum tolvaptan dose (mean dose, 64 [±10] mg), with a low discontinuation rate (5%). The mean annual decline in eGFR was -3.05 (±2.41) ml/min per 1.73 m2 during tolvaptan treatment, compared to the period preceding treatment, corresponding to a reduction in eGFR decline of more than 50%. Primary renal events occurred in 20% of patients (mean time to onset, 31 months; 95% confidence interval [CI] = 28-34). Conclusion: Individualized tolvaptan dose adjustment based on OsmU in patients with ADPKD and rapid disease progression provided benefits in terms of reducing eGFR decline, compared with reference studies, and displayed lower dropout rates and fewer side effects. Further studies are required to confirm optimal strategies for the use of OsmU for tolvaptan dose adjustment in patients with ADPKD.
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BACKGROUND: Choristoma is a well-defined benign lesion formed by histologically normal tissue in an unusual location. Diagnosis is confirmed after surgical removal of the mass. To our knowledge, to date there has been only one case of thyroid choristoma described in the literature. PATIENT FINDINGS: A 70-year-old man with a history of non-Hodgkin lymphoma presented with sudden cervical enlargement. Cervical CT scan showed a 47mm hypodense nodule on the right thyroid lobe. Fine-needle aspiration revealed follicular lesion of undetermined significance. During the following weeks there was noticeable thyroid enlargement. Reassessment with thyroid ultrasound showed a 73mm nodule. The patient underwent total thyroidectomy. Histopathological examination revealed a choristoma composed of squamous epithelium lined cysts, smooth muscle, adipose tissue, connective tissue, foci of ossification and extramedullary hematopoiesis. No cytological atypia or tumoral necrosis were found. Thyroid choristomas are an exceedingly rare cause of a thyroid nodule.
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BACKGROUND: Increasing levodopa (L-dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing-off symptoms in Parkinson's disease (PD) patients. OBJECTIVES: To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing-off in PD patients. METHODS: ADOPTION was a randomized, parallel-group, open-label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L-dopa 100 mg (n = 81) (added to current L-dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society-Unified Parkinson's Disease Rating Scale and 8-item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change. RESULTS: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L-dopa 100 mg (-62.1 vs. -16.7 minutes; P = 0.0015). Opicapone-treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L-dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied. CONCLUSIONS: Opicapone 50 mg was more effective than an additional 100 mg L-dopa dose at decreasing off time in patients with PD and early wearing-off.
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Antiparkinsonianos , Levodopa , Oxadiazoles , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Levodopa/uso terapéutico , Levodopa/administración & dosificación , Antiparkinsonianos/uso terapéutico , Antiparkinsonianos/administración & dosificación , Oxadiazoles/uso terapéutico , Oxadiazoles/administración & dosificación , Inhibidores de Catecol O-Metiltransferasa/uso terapéutico , Inhibidores de Catecol O-Metiltransferasa/farmacología , Inhibidores de Catecol O-Metiltransferasa/administración & dosificación , República de Corea , Resultado del TratamientoRESUMEN
INTRODUCTION: In BIPARK-1 and BIPARK-2, addition of once-daily opicapone to levodopa/carbidopa significantly reduced daily "OFF"-time relative to placebo in adults with Parkinson's disease (PD) and motor fluctuations. Diary data from these studies were pooled and analyzed post hoc to characterize "OFF"-times around nighttime sleep and to explore the effects of opicapone 50 mg. METHODS: "OFF" before sleep (OBS), "OFF during the nighttime sleep period" (ODNSP), early morning "OFF" (EMO), and duration of nighttime sleep and awake periods were analyzed descriptively at baseline. Mean changes from baseline to Week 14/15 (end of double-blind treatment) were analyzed using two-sided t-tests in participants with data for both visits. RESULTS: At baseline, 88.3 % (454/514) of participants reported having OBS (34.0 %), ODNSP (17.1 %), or EMO (79.6 %). Those with ODNSP had substantially shorter mean duration of uninterrupted sleep (4.4 h) than the overall pooled population (7.1 h). At Week 14/15, mean decrease from baseline in ODNSP duration was significantly greater with opicapone than with placebo (-0.9 vs. -0.4 h, P < 0.05). In participants with ODNSP at baseline, the decrease in total time spent awake during the night-time sleep period was significantly greater with opicapone than with placebo (-1.0 vs. -0.4 h, P < 0.05), as was the reduction in percent time spent awake during the night-time sleep period (-12.8 % vs. -4.5 %, P < 0.05). CONCLUSION: "OFF"-times around nighttime sleep were common in BIPARK-1 and BIPARK-2. Opicapone may improve sleep by decreasing the amount of time spent awake during the night in patients with PD who have night-time sleep period "OFF" episodes.
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Antiparkinsonianos , Levodopa , Oxadiazoles , Enfermedad de Parkinson , Sueño , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/complicaciones , Masculino , Femenino , Método Doble Ciego , Persona de Mediana Edad , Anciano , Sueño/efectos de los fármacos , Sueño/fisiología , Antiparkinsonianos/uso terapéutico , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/farmacología , Levodopa/farmacología , Levodopa/administración & dosificación , Oxadiazoles/farmacología , Oxadiazoles/administración & dosificación , Oxadiazoles/uso terapéutico , Carbidopa/farmacología , Carbidopa/administración & dosificación , Combinación de Medicamentos , Vigilia/efectos de los fármacos , Vigilia/fisiologíaRESUMEN
PURPOSE: To evaluate patient characteristics and factors associated with surgical resection in patients with Crohn's disease (CD). METHODS: An analysis was performed on data from 295 patients with CD in follow-up from 2001 to 2018. Medical record data comprised age, gender, location, behavior and duration of the CD, smoking, and extraintestinal manifestation. Patients were divided into two groups according to the presence or absence of surgical resection. RESULTS: Out of the 295 patients with CD, 155 underwent surgical resection (53.2% male, mean age: 43.88 ± 14.35 years). The main indications for surgery were stenosis (44.5%), clinical intractability (15.5%), and intra-abdominal fistulas (15.5%). Smoking (p < 0.001), longer CD duration (p < 0.0001), ileo-colonic location (p = 0.003), stenosing behavior (p < 0.0001), and fistulizing behavior (p < 0.0001) were significantly associated with surgical resection. Initial use of biological was significantly more frequent in the group of patients without surgical resection (p < 0.001). CONCLUSIONS: Patients with CD still frequently need surgical treatment. Smoking (current or past), longer disease time, stenosing and fistulizing behavior, and ileo-colonic localization in CD patients were associated with a higher risk of surgery. Awareness about factors associated with unfavorable outcome allows such patients to be treated more appropriately.
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Enfermedad de Crohn , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/cirugía , Íleon , Estudios RetrospectivosRESUMEN
Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present a history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for the detection of plasma cytokines and lipopolysaccharides (LPS). Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies. Our results show that CD patients had augmented plasma interleukin (IL)-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with a history of PCD produced higher IL-6, IL-8, and interferon-γ, along with decreased tumor necrosis factor alpha (TNF). CD patients had augmented FoxP3 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4 as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact on the disease management.
Asunto(s)
Antígeno CTLA-4 , Enfermedad de Crohn , Humanos , Antígeno CTLA-4/metabolismo , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/sangre , Masculino , Femenino , Adulto , Estudios Transversales , Persona de Mediana Edad , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Interleucina-6/sangre , Lipopolisacáridos/inmunología , Citocinas/sangre , Citocinas/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Factores de Transcripción Forkhead/metabolismoRESUMEN
Seafood product labels with accurate allergen contents can avoid and/or minimize allergic reactions. Therefore, an electrochemical immunosensor for the analysis of ß-parvalbumin (ß-PV, a major fish allergen) was developed. Screen-printed carbon electrodes were nanostructured with reduced graphene oxide and gold nanoparticles. The platform was characterized by scanning electron microscopy and elemental analysis. In a sandwich-type assay (â¼75 min), the antigen-antibody interaction was detected by chronoamperometry using horseradish peroxidase and TMB-H2O2. A linear range of 25-3000 ng/mL, a sensitivity of 2.99 µA.mL/ng, and a limit of detection of 9.9 ng/mL (corresponding to 0.40 ng in the analysed aliquot) were obtained. The selectivity and possible interferences were assessed by analysing several other food allergens and a marine toxin. The sensor was applied to the analysis of 17 commercial foods and the effect of culinary processing (e.g., grilled, canned, smoked) on the ß-PV concentration was assessed. Traces of ß-PV were successfully quantified and ELISA was used to assess the results.
Asunto(s)
Técnicas Biosensibles , Grafito , Nanopartículas del Metal , Animales , Grafito/química , Oro/química , Alérgenos/análisis , Técnicas Biosensibles/métodos , Peróxido de Hidrógeno/química , Técnicas Electroquímicas/métodos , Inmunoensayo/métodos , Nanopartículas del Metal/química , Alimentos Marinos/análisis , Límite de DetecciónRESUMEN
BACKGROUND: The eTEP Rives-Stoppa (RS) procedure, increasingly used for ventral hernia repair, has raised concerns about postoperative upper abdominal bulging. This study aims to objectively evaluate changes in the abdominal contour after eTEP RS and explore potential causes using a novel analytical tool, the Ellipse 9. METHODS: Thirty patients undergoing eTEP RS without posterior rectus sheath closure were assessed before and 3 months after surgery using CT scan images. Key measurements analyzed included the distance between linea semilunaris (X2), eccentricity over the Cord (c/a Cord), superior eccentricity (c/a Sup), Y2, and the superior perimeter of the abdomen. The Ellipse 9 tool, which provides graphical images and numerical representations, was utilized alongside patient-reported outcomes to assess perceived abdominal changes. RESULTS: The study group exhibited a trend toward a flatter abdomen with reduced distance between linea semilunaris(X2). However, 17% of patients developed upper abdominal bulging (5). Significant differences in c/a Cord, c/a Sup, Y2, and the superior perimeter of the abdomen, confirmed with Bonferroni corrections, were noted between bulging (5 patients) and non-bulging groups (25 patients). There was a notable disparity between patient perceptions and objective outcomes. CONCLUSION: The eTEP RS procedure improved abdominal contour in most patients from a selected cohort. The Ellipse 9 tool was valuable for the objective analysis of these changes. The cause of bulging post-eTEP RS is probably multifactorial. Notably, there was often a discrepancy between patient perceptions of bulging and objective clinical findings.