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1.
Am Surg ; : 31348241256062, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38756087

RESUMO

Introduction: Epiploic appendagitis (EA) is an essential cause of abdominal pain that can be confused with more typical causes such as acute diverticulitis and appendicitis. Epiploic appendagitis accounts for 1% of all cases of abdominal pain in adults. The scarcity of information has limited its recognition as an essential nonsurgical cause of acute abdominal pain.Methods: We performed a systematic review of all EA cases published. We searched Scopus, Medline, Web of Science, and Google Scholar to retrieve all available studies from January 2000 to November 2023.Results: 196 case reports and case series were analyzed, with 371 patients with EA included. The mean age at the time of diagnosis was 39 years. Most patients were male (59%). The primary presenting symptoms were pain (100%), tenderness (59.5%), and rebound tenderness (27.4%). The left abdomen was the most common localization of pain (53%). The most frequently identified differential diagnoses were acute appendicitis (26.4%) and acute diverticulitis (16.1%). Most patients (53%) were treated conservatively, and 98 (26.4%) underwent surgical treatment. A significant difference in the choice of treatment was found for signs and symptoms such as rebound tenderness, nausea, anorexia, and diarrhea.Conclusions: Acute EA is an essential clinical condition of rare occurrence that might present a diagnostic challenge, as it can masquerade as another acute abdominal pain etiology. The optimal management of EA is conservative, so a higher recognition by surgeons and emergency physicians is essential to avoid unnecessary surgical interventions and their associated consequences.

2.
JACC Heart Fail ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38752934

RESUMO

BACKGROUND: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease. OBJECTIVES: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes. METHODS: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection fraction were assessed using adjusted Cox models. RESULTS: Among 16,925 participants (53.5% women; 21.8% Black), there were 612 incident HF events (3.6%) (HF with reduced ejection fraction, 309 [50.5%]; HF preserved ejection fraction, 303 [49.5%]) over median follow-up of 11.4 years. In adjusted models, higher HDL-P was significantly associated with lower HF risk (HR of highest vs lowest tertile of HDL-P: 0.76 [95% CI: 0.62-0.93]). Larger HDL-size was significantly associated with higher overall HF risk (HR of largest vs smallest tertile of HDL-size: 1.27 [95% CI: 1.03-1.58]). HF risk associated with HDL-P and HDL-size was similar for HF subtypes. In adjusted analyses, there was no significant association between HDL-C and HF risk. Higher HDL-C/HDL-P was significantly associated with higher overall HF risk (HR of highest vs lowest tertile of HDL-C/HDL-P: 1.29 [95% CI: 1.04-1.60]). CONCLUSIONS: Higher HDL-P was associated with a lower risk of HF. In contrast, larger HDL-size was associated with higher risk of HF and there was no significant association observed between HDL-C and HF risk after accounting for cardiovascular risk factors.

3.
Pathogens ; 13(5)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38787210

RESUMO

This study demonstrates the capability of Raman microscopy for detecting structural differences in Giardia cells exposed to different drugs and incubation times. While metronidazole (MTZ) visibly affects the cells by inducing extracellular vesicle releases of toxic iron intermediates and modified triple-bond moieties, oseltamivir (OSM) alters the phenylalanine and lipid structures. Modifications in the heme protein environment and the transformation of iron from ferric to ferrous observed for both drug treatments are more notable for MTZ. Different contents and amounts of vesicle excretion are detected for 24 h or 48 h with MTZ incubation. At a shorter drug exposure, releases of altered proteins, glycogen, and phospholipids dominate. Agglomerates of transformed iron complexes from heme proteins and multiple-bond moieties prevail at 48 h of treatment. No such vesicle releases are present in the case of OSM usage. Drug incorporations into the cells and their impact on the plasma membrane and the dynamics of lipid raft confirmed by confocal fluorescence microscopy reveal a more destructive extent by OSM, corroborating the Raman results. Raman microscopy provides a broader understanding of the multifaceted factors and mechanisms responsible for giardiasis treatment or drug resistance by enabling a label-free, simultaneous monitoring of structural changes at the cellular and molecular levels.

4.
World Neurosurg ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38692567

RESUMO

OBJECTIVE: To describe a simple variation of burr hole craniostomy for the management of chronic subdural hematoma (CSDH) that uses a frontal drainage system to facilitate timely decompression in the event of tension pneumocephalus and spares the need for additional surgery. METHODS: We conducted a retrospective analysis of 20 patients with CSDH who underwent burr hole craniostomy and 20 patients who underwent the same procedure alongside the placement of a 5fr neonatal feeding tube as a backup drainage for the anterior craniostomy. Depending on the situation, the secondary drain stayed for a maximum of 72 hours to be opened and used in emergency settings for drainage, aspiration, or as a one-way valve with a water seal. RESULTS: The outcomes of 20 patients who underwent this procedure and 20 controls are described. One patient from each group presented tension pneumocephalus. One was promptly resolved by opening the backup drain under a water seal to evacuate pneumocephalus and the other patient had to undergo a re-opening of the craniostomy. CONCLUSIONS: The described variation of burr hole craniostomy represents a low-cost and easy-to-implement technique that can be used for emergency decompression of tension pneumocephalus. It also has the potential to reduce re-operation rates and CSDH recurrence. Prospective controlled research is needed to validate this approach further.

5.
Heliyon ; 10(7): e28751, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586365

RESUMO

In this work, the utilization of phosphogypsum (PG), a waste coming from the manufacture of phosphate fertilizers, as fertilizer for alfalfa (Medicago sativa L.) crops was investigated using pot experiments. The objective of this study was to evaluate the effects of both phosphogypsum and red mud (RM) in two soils representative of the pasture production area in Southern Spain. The morpho-physiological parameters of biomass, plant height, number of stems and number of leaves, as well as the chemical parameters of soil content, were measured. High doses of PG inhibited seed germination in some treatments. In addition, the treatment substrate (2550 g soil + 50 g kg-1 PG + 100 g kg-1 RM) also affected seed germination, possibly due to the large amount of RM. The application of PG and RM to the soil increased the availability of important nutrients for alfalfa, such as phosphorus (P), calcium (Ca2+) and magnesium (Mg2+). The results demonstrate that the treatment with PG significantly improved the uptake of P in alfalfa.

6.
Ecol Evol ; 14(4): e11255, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628915

RESUMO

Animals that co-occur in a region (sympatry) may share the same environment (syntopy), and niche differentiation is expected among closely related species competing for resources. The masked booby (Sula dactylatra) and smaller congeneric red-footed booby (Sula sula) share breeding grounds. In addition to the inter-specific size difference, females of both species are also larger than the respective males (reversed sexual size dimorphism). Although both boobies consume similar prey, sometimes in mixed-species flocks, each species and sex may specialize in terms of their diet or foraging habitats. We examined inter- and intra-specific differences in isotopic values (δ13C and δ15N) in these pelagically feeding booby species during the incubation period at Clarion Island, Mexico, to quantify the degrees of inter- and intra-specific niche partitioning throughout the annual cycle. During incubation, both species preyed mainly on flyingfish and squid, but masked boobies had heavier food loads than red-footed boobies. There was no overlap in isotopic niches between masked and red-footed boobies during breeding (determined from whole blood), but there was slight overlap during the non-breeding period (determined from body feathers). Female masked boobies had a higher trophic position than conspecific males during breeding; however, no such pattern was detected in red-footed boobies. These results provide evidence of inter- and intra-specific niche partitioning in these tropical seabird species, particularly during the breeding period and in the more-dimorphic species. Our results suggest that these closely related species use different strategies to cope with the same tropical marine environment.

7.
Pain Rep ; 9(3): e1153, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38646658

RESUMO

Objective: This cohort study used Sankey plots and exponential bar plots for visualizing the fluctuating nature and trajectory of post-COVID pain in previously hospitalized COVID-19 survivors. Methods: A cohort of 1266 subjects hospitalised because of COVID-19 during the first wave of the pandemic were scheduled for a telephone interview at 8.4 (T1), 13.2 (T2), and 18.3 (T3) months in average after hospitalization for collecting data about post-COVID pain. Patients were asked for about pain symptomatology that was attributed to the infection. Hospitalization and clinical data were collected from medical records. Results: The prevalence of myalgia as COVID-19-associated symptom was 29.82% (n = 389) at hospitalization (T0). The prevalence of post-COVID pain was 41.07% (n = 520) at T1, 34.29% (n = 434) at T2, and 28.47% (n = 360) at T3. The recovery exponential curve revealed a decrease trend visualizing that post-COVID pain improved over the time span investigated. Pain in the lower extremity and widespread pain were the most prevalent locations. Female sex (OR 1.507, 95% CI 1.047-2.169), pre-existing pain symptoms (OR 1.724, 95% CI 1.237-2.403), headache as onset-symptom (OR 2.374, 95% CI 1.550-3.639), days at hospital (OR 1.012, 95% CI 1.000-1.025), and presence of post-COVID pain at T1 (OR 13.243, 95% CI 9.428-18.601) were associated with post-COVID pain at T2. Only the presence of post-COVID pain at T1 (OR 5.383, 95% CI 3.896-7.439) was associated with post-COVID pain at T3. Conclusion: Current results show a fluctuating evolution with a decreasing tendency of post-COVID pain during the first years after hospitalization. The development of post-COVID pain soon after SARS-CoV-2 infection predispose for long-lasting chronic pain.

8.
Int J Mol Sci ; 25(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38612518

RESUMO

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, with proto-oncogene, receptor tyrosine kinase (c-kit), or PDGFRα mutations detected in around 85% of cases. GISTs without c-kit or platelet-derived growth factor receptor alpha (PDGFRα) mutations are considered wild-type (WT), and their diverse molecular alterations and biological behaviors remain uncertain. They are usually not sensitive to tyrosine kinase inhibitors (TKIs). Recently, some molecular alterations, including neurotrophic tyrosine receptor kinase (NTRK) fusions, have been reported in very few cases of WT GISTs. This novel finding opens the window for the use of tropomyosin receptor kinase (TRK) inhibitor therapy in these subtypes of GIST. Herein, we report a new case of NTRK-fused WT high-risk GIST in a female patient with a large pelvic mass (large dimension of 20 cm). The tumor was removed, and the histopathology displayed spindle-predominant morphology with focal epithelioid areas, myxoid stromal tissue, and notable lymphoid infiltration with tertiary lymphoid structures. Ten mitoses were quantified in 50 high-power fields without nuclear pleomorphism. DOG1 showed strong and diffuse positivity, and CD117 showed moderate positivity. Succinate dehydrogenase subunit B (SDHB) was retained, Pan-TRK was focal positive (nuclear pattern), and the proliferation index Ki-67 was 7%. Next-generation sequencing (NGS) detected an ETV6::NTRK3 fusion, and this finding was confirmed by fluorescence in situ hybridization (FISH), which showed NTRK3 rearrangement. In addition, an RB1 mutation was found by NGS. The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered. After 3 months of follow-up, a new CT scan showed a complete response. Based on our results and the cases from the literature, GISTs with NTRK fusions are very uncommon so far; hence, further screening studies, including more WT GIST cases, may increase the possibility of finding additional cases. The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions. Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.


Assuntos
Tumores do Estroma Gastrointestinal , Estruturas Linfoides Terciárias , Feminino , Humanos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Hibridização in Situ Fluorescente , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Imunoterapia , Proteínas Proto-Oncogênicas c-kit , Receptores Proteína Tirosina Quinases
10.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 42(3): 146-148, Mar. 2024. ilus
Artigo em Espanhol | IBECS | ID: ibc-231153

RESUMO

Introducción: Las enfermedades de transmisión sexual, como la cervicitis, la proctitis y la uretritis, se asocian a altas tasas de infección por VIH. Ante la sospecha de estas patologías, se debería solicitar una serología del VIH. Material y métodos: Estudio retrospectivo realizado durante 2018 en el Hospital Costa del Sol (Marbella, Málaga). Se revisaron las serologías para el VIH solicitadas en pacientes a los que se les pidió una PCR para Chlamydia trachomatis y Neisseria gonorrhoeae. Resultados: Se valoraron 1.818 pacientes, en los que se realizó serología para el VIH al 44,7%, de las cuales 14 (1,7%) resultaron positivas. El 55,3% restante fueron oportunidades perdidas de diagnóstico. Conclusiones: Las infecciones por C.trachomatis y N.gonorrhoeae están asociadas a una elevada tasa de infección oculta por el VIH. El grado de sospecha de VIH en esta población sigue siendo bajo, y resulta esencial que se refuerce ante la posibilidad de infección por estas patologías.(AU)


Introduction: Sexually transmitted diseases such as cervicitis, proctitis and urethritis are associated with high rates of HIV infection. When these pathologies are suspected, HIV serology should be requested. Material and methods: A Retrospective study was performed during 2018 at the Hospital Costa del Sol (Marbella, Málaga, Spain). HIV serologies requested in patients who were asked for PCR for Chlamydia trachomatis and Neisseria gonorrhoeae were reviewed. Results: A total of 1818 patients were evaluated, in which HIV serology was performed in 44.7%, of which 14 (1.7%) were positive. The remaining 55.3% were missed diagnostic opportunities. Conclusions: C.trachomatis and N.gonorrhoeae infections are associated with a high rate of occult HIV infection. The degree of suspicion of HIV in this population remains low and it is essential that it be reinforced in the presence of the possibility of infection by these pathologies.(AU)


Assuntos
Humanos , Masculino , Feminino , Infecções por HIV/diagnóstico , Diagnóstico Precoce , Infecções Sexualmente Transmissíveis , Chlamydia , Gonorreia , Epidemiologia Descritiva , Estudos Retrospectivos , Estudos Transversais , Microbiologia , Técnicas Microbiológicas , Doenças Transmissíveis , Uretrite , Cervicite Uterina , Proctite
11.
Psiquiatr. biol. (Internet) ; 31(1): [100441], ene.-mar 2024. graf
Artigo em Espanhol | IBECS | ID: ibc-231632

RESUMO

Introducción la diabetes mellitus y los trastornos del estado de ánimo son 2 entidades que se entrelazan entre sí con mecanismos fisiopatológicos en común. Los hipoglucemiantes orales son un pilar fundamental para obtener el control glucémico en los individuos diabéticos y, recientemente, la alta prevalencia de estas 2 patologías en un mismo paciente han hecho que los estudios clínicos se enfoquen en analizar el efecto de los hipoglucemiantes orales en los pacientes con diabetes mellitus tipo 2 y trastorno depresivo. Objetivo realizar una revisión de la literatura disponible sobre la medicación hipoglucemiante en el contexto de los pacientes con diabetes mellitus y trastorno depresivo. Conclusiones si bien los antidiabéticos orales han mostrado tener un efecto antidepresivo en ciertos modelos experimentales, en la práctica clínica la evidencia es escasa, pero llama particularmente la atención el menor riesgo de depresión con ciertos antidiabéticos dejando abierta las posibilidades de futuros estudios con la naturaleza adecuada que permita aclarar el efecto de los hipoglucemiantes orales en la población con diabetes mellitus y trastorno depresivo. (AU)


Introduction Diabetes mellitus and mood disorders are two entities that are intertwined with common pathophysiological mechanisms. Oral hypoglycemic agents are a fundamental pillar in obtaining adequate glucose control in diabetic individuals and, recently, the high prevalence of these two pathologies in the same patient have led clinical studies to focus on analyzing the effect of oral hypoglycemic agents in diabetics. patients with type 2 diabetes mellitus and depressive disorder. Objective To carry out a review of the available literature on hypoglycemic medication in the context of patients with diabetes mellitus and depressive disorder. Conclusions Although oral antidiabetics have been shown to have an antidepressant effect in certain experimental models, in clinical practice the evidence is scarce, but the lower risk of depression with certain antidiabetics is particularly noteworthy, leaving open the possibilities of future studies with the adequate nature that allows clarifying the effect of oral hypoglycemic agents in the population with diabetes mellitus and depressive disorder. (AU)


Assuntos
Humanos , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/fisiopatologia , Transtorno Depressivo , Hipoglicemiantes/uso terapêutico
12.
Front Cardiovasc Med ; 11: 1355980, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529333

RESUMO

Cardiac sex differences represent a pertinent focus in pursuit of the long-awaited goal of personalized medicine. Despite evident disparities in the onset and progression of cardiac pathology between sexes, historical oversight has led to the neglect of gender-specific considerations in the treatment of patients. This oversight is attributed to a predominant focus on male samples and a lack of sex-based segregation in patient studies. Recognizing these sex differences is not only relevant to the treatment of cisgender individuals; it also holds paramount importance in addressing the healthcare needs of transgender patients, a demographic that is increasingly prominent in contemporary society. In response to these challenges, various agencies, including the National Institutes of Health, have actively directed their efforts toward advancing our comprehension of this phenomenon. Epigenetics has proven to play a crucial role in understanding sex differences in both healthy and disease states within the heart. This review presents a comprehensive overview of the physiological distinctions between males and females during the development of various cardiac pathologies, specifically focusing on unraveling the genetic and epigenetic mechanisms at play. Current findings related to distinct sex-chromosome compositions, the emergence of gender-biased genetic variations, and variations in hormonal profiles between sexes are highlighted. Additionally, the roles of DNA methylation, histone marks, and chromatin structure in mediating pathological sex differences are explored. To inspire further investigation into this crucial subject, we have conducted global analyses of various epigenetic features, leveraging data previously generated by the ENCODE project.

13.
J Psychosom Res ; 179: 111635, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38432061

RESUMO

OBJECTIVE: To apply Sankey plots and exponential bar plots for visualizing the evolution of anxiety/depressive symptoms and poor sleep in previously hospitalized COVID-19 survivors. METHODS: A sample of 1266 subjects who were hospitalized due to a SARS-CoV-2 from March-May 2020 were assessed at 8.4 (T1), 13.2 (T2) and 18.3 (T3) months after hospitalization. The Hospital Anxiety and Depression Scale was used to determine anxiety (HADS-A) and depressive (HADS-D) symptoms. The Pittsburgh Sleep Quality Index (PSQI) evaluated sleep quality. Clinical features, onset symptoms and hospital data were collected from medical records. RESULTS: Sankey plots revealed that the prevalence of anxiety symptomatology (HADS-A ≥ 8 points) was 22.5% (n = 285) at T1, 17.6% (n = 223) at T2, and 7.9% (n = 100) at T3, whereas the prevalence of depressive symptoms (HADS-D ≥ 8 points) was 14.6% (n = 185) at T1, 10.9% (n = 138) at T2, and 6.1% (n = 78) at T3. Finally, the prevalence of poor sleep (PSQI≥8 points) decreased from 32.8% (n = 415) at T1, to 28.8% (n = 365) at T2, and to 24.8% (n = 314) at T3. The recovery curves show a decrease trend visualizing that these symptoms recovered the following years after discharge. The regression models did not reveal medical records associated with anxiety/depressive symptoms or poor sleep. CONCLUSION: The use of Sankey plots shows a fluctuating evolution of anxiety/depressive symptoms and poor sleep during the first years after the infection. In addition, exponential bar plots revealed a decrease prevalence of these symptoms during the first years after hospital discharge. No risk factors were identified in this cohort.


Assuntos
COVID-19 , Distúrbios do Início e da Manutenção do Sono , Humanos , Depressão/epidemiologia , Depressão/diagnóstico , COVID-19/epidemiologia , Qualidade do Sono , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Ansiedade/epidemiologia , Ansiedade/diagnóstico , Distúrbios do Início e da Manutenção do Sono/epidemiologia
14.
Res Sq ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38496464

RESUMO

Background: Patients with COVID-19 under invasive mechanical ventilation are at higher risk of developing ventilator-associated pneumonia (VAP), associated with increased healthcare costs, and unfavorable prognosis. The underlying mechanisms of this phenomenon have not been thoroughly dissected. Therefore, this study attempted to bridge this gap by performing a lung microbiota analysis and evaluating the host immune responses that could drive the development of VAP. Materials and methods: In this prospective cohort study, mechanically ventilated patients with confirmed SARS-CoV-2 infection were enrolled. Nasal swabs (NS), endotracheal aspirates (ETA), and blood samples were collected initially within 12 hours of intubation and again at 72 hours post-intubation. Plasma samples underwent cytokine and metabolomic analyses, while NS and ETA samples were sequenced for lung microbiome examination. The cohort was categorized based on the development of VAP. Data analysis was conducted using RStudio version 4.3.1. Results: In a study of 36 COVID-19 patients on mechanical ventilation, significant differences were found in the nasal and pulmonary microbiome, notably in Staphylococcus and Enterobacteriaceae, linked to VAP. Patients with VAP showed a higher SARS-CoV-2 viral load, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1ß, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. Metabolomic analysis revealed changes in 22 metabolites in non-VAP patients and 27 in VAP patients, highlighting D-Maltose-Lactose, Histidinyl-Glycine, and various phosphatidylcholines, indicating a metabolic predisposition to VAP. Conclusions: This study reveals a critical link between respiratory microbiome alterations and ventilator-associated pneumonia in COVID-19 patients, with elevated SARS-CoV-2 levels and metabolic changes, providing novel insights into the underlying mechanisms of VAP with potential management and prevention implications.

15.
Life (Basel) ; 14(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38541649

RESUMO

Sucralose is a food additive initially used to mitigate glycemic peaks and calorie intake in patients with diabetes and obesity. Although sucralose has been considered safe for human consumption, the World Health Organization (WHO) issued a global alert in 2023 concerning the potential health implications of this artificial sweetener. This review aims to comprehensively explore the effects of sucralose intake on human health by understanding sucralose absorption, metabolism, and excretion. We also outline the role of the sweet taste 1 receptor 3 (T1R3) in mediating sucralose-dependent signaling pathways that regulate satiety, incretin release, and insulin response. Finally, we discuss the impact of sucralose on microbiome dysbiosis, inflammatory response origin, liver damage, and toxicity. Gaining a deeper understanding of the manifold effects of sucralose on human physiology will help promote further studies to ensure its consumption is deemed safe for a broader population, including children, adolescents, and pregnant women.

16.
Breast Cancer Res Treat ; 205(3): 589-598, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38456970

RESUMO

PURPOSE: The prognostic and predictive role of trophoblast cell-surface antigen-2 (Trop-2) overexpression in human epidermal growth factor receptor 2-positive (HER2-positive) breast cancer is currently unknown. We retrospectively analyzed Trop-2 expression and its correlation with clinicopathologic features and pathological complete response (pCR) in HER2-positive early breast cancer (EBC) patients treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab in the PHERGain study. METHODS: Trop-2 expression at baseline was determined in formalin-fixed, paraffin-embedded primary tumor biopsies by immunohistochemistry and was first classified into expressing (Trop-2-positive) or not-expressing (Trop-2-negative) tumors. Then, it was classified by histochemical score (H-score) according to its intensity into low (0-9), intermediate (10-49), and high (≥ 50). The association between clinicopathologic features, pCR, and Trop-2 expression was performed with Fisher's exact test. RESULTS: Forty-one patients with tissue evaluable for Trop-2 expression were included, with 28 (68.3%) Trop-2-positive tumors. Overall, 17 (41.46%), 14 (34.15%), and 10 (24.40%) tumors were classified as low, intermediate, and high, respectively. Trop-2 expression was significantly associated with decreased pCR rates (50.0% vs. 92.3%; odds ratio [OR] 0.05; 95% CI, 0.002-0.360]; p adjusted = 0.01) but was not correlated with any clinicopathologic features (p ≥ 0.05). Tumors with the highest Trop-2 H-score were less likely to obtain a pCR (OR 0.03; 95% CI, 0.001-0.290, p adjusted < 0.01). This association was confirmed in univariate and multivariate regression analyses. CONCLUSION: These findings suggest a potential role of Trop-2 expression as a biomarker of resistance to neoadjuvant chemotherapy plus dual HER2 blockade and may become a strategic target for future combinations in HER2-positive EBC patients.


Assuntos
Anticorpos Monoclonais Humanizados , Antígenos de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Carboplatina , Moléculas de Adesão Celular , Docetaxel , Terapia Neoadjuvante , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Antígenos de Neoplasias/metabolismo , Receptor ErbB-2/metabolismo , Terapia Neoadjuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/administração & dosagem , Docetaxel/uso terapêutico , Moléculas de Adesão Celular/metabolismo , Pessoa de Meia-Idade , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Adulto , Trastuzumab/uso terapêutico , Trastuzumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Idoso , Resultado do Tratamento , Taxoides/administração & dosagem , Taxoides/uso terapêutico , Estudos Retrospectivos , Biomarcadores Tumorais/metabolismo , Prognóstico , Imuno-Histoquímica
17.
ISA Trans ; 148: 435-448, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38443274

RESUMO

In this research project, a closed-chain robotic active ankle orthosis with six degrees of freedom is designed, constructed, numerically valued, instrumented, and experimentally validated. The mechanical arrangement to implement the orthosis corresponds to a six-legged Stewart platform. An adaptive gain control strategy with state constraints based on a state-dependent gains control (that behaves as a diverging function as the states approach the state restrictions) operates the device's motion. The convergence to an invariant positive set centered at the origin of the tracking error space is validated using the stability analysis based on the second method of Lyapunov, with the implementation of a state barrier Lyapunov-like function. The ultimate boundedness of the tracking error is proven with an endorsed gains adjustment method leading to a reachable minimum size of the ultimate bound. Hence, the impact of the state constraints and the formal reason for applying the controller on the suggested orthosis are all established. The orthosis is also controlled using a conventional state feedback strategy to assess the tracking error for an external disturbance and contrast its performance with the proposed control approach. The technology is tested on a few carefully chosen volunteers, successfully limiting the range of motion within a pre-defined region based on the scope of movement reported by patients with ankle illnesses discovered in the literature. Based on a unique mechatronic device, the created system offers a fresh approach to treating this class of impairments.

18.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474051

RESUMO

Alzheimer's disease (AD), the leading cause of dementia, presents a significant global health challenge with no known cure to date. Central to our understanding of AD pathogenesis is the ß-amyloid cascade hypothesis, which underlies drug research and discovery efforts. Despite extensive studies, no animal models of AD have completely validated this hypothesis. Effective AD models are essential for accurately replicating key pathological features of the disease, notably the formation of ß-amyloid plaques and neurofibrillary tangles. These pathological markers are primarily driven by mutations in the amyloid precursor protein (APP) and presenilin 1 (PS1) genes in familial AD (FAD) and by tau protein mutations for the tangle pathology. Transgenic mice models have been instrumental in AD research, heavily relying on the overexpression of mutated APP genes to simulate disease conditions. However, these models do not entirely replicate the human condition of AD. This review aims to provide a comprehensive evaluation of the historical and ongoing research efforts in AD, particularly through the use of transgenic mice models. It is focused on the benefits gathered from these transgenic mice models in understanding ß-amyloid toxicity and the broader biological underpinnings of AD. Additionally, the review critically assesses the application of these models in the preclinical testing of new therapeutic interventions, highlighting the gap between animal models and human clinical realities. This analysis underscores the need for refinement in AD research methodologies to bridge this gap and enhance the translational value of preclinical studies.


Assuntos
Doença de Alzheimer , Camundongos , Animais , Humanos , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Modelos Animais de Doenças , Proteínas tau/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Presenilina-1/genética , Placa Amiloide/metabolismo
19.
Enferm Infecc Microbiol Clin (Engl Ed) ; 42(3): 146-148, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38302371

RESUMO

INTRODUCTION: Sexually transmitted diseases such as cervicitis, proctitis and urethritis are associated with high rates of HIV infection. When these pathologies are suspected, HIV serology should be requested. MATERIAL AND METHODS: A retrospective study was performed during 2018 at the Hospital Costa del Sol (Marbella, Málaga, Spain). HIV serologies requested in patients who were asked for PCR for Chlamydia trachomatis and Neisseria gonorrhoeae were reviewed. RESULTS: A total of 1818 patients were evaluated, in which HIV serology was performed in 44.7%, of which 14 (1.7%) were positive. The remaining 55.3% were missed diagnostic opportunities. CONCLUSIONS: C. trachomatis and N. gonorrhoeae infections are associated with a high rate of occult HIV infection. The degree of suspicion of HIV in this population remains low and it is essential that it be reinforced in the presence of the possibility of infection by these pathologies.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , Infecções Sexualmente Transmissíveis , Feminino , Humanos , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Estudos Retrospectivos , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/complicações , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Chlamydia trachomatis
20.
World Neurosurg ; 185: 207-215, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38403012

RESUMO

OBJECTIVE: Describe a new, safe, technique that uses titanium mesh to partially cover skull defects immediately after decompressive craniectomy (DC). METHODS: This study is a retrospective review of 8 patients who underwent DC and placement of a titanium mesh. The mesh partially covered the defect and was placed between the temporalis muscle and the dura graft. The muscle was sutured to the mesh. All patients underwent cranioplasty at a later time. The study recorded and analyzed demographic information, time between surgeries, extra-axial fluid collections, postoperative infections, need for reoperation, cortical hemorrhages, and functional and aesthetic outcomes. RESULTS: After craniectomy, all patients underwent cranioplasty within an average of 112.5 days (30-240 days). One patient reported temporalis muscle atrophy, which was the only complication observed. During the cranioplasties, no adhesions were found between temporalis muscle, titanium mesh, and underlying dura. None of the patients showed complications in the follow-up computerized tomography scans. All patients had favorable aesthetic and functional results. CONCLUSIONS: Placing a titanium mesh as an extra step during DC could have antiadhesive and protective properties, facilitating subsequent cranioplasty by preventing adhesions and providing a clear surgical plane between the temporalis muscle and intracranial tissues. This technique also helps preserve the temporalis muscle and enhances functional and aesthetic outcomes postcranioplasty. Therefore, it represents a safe alternative to other synthetic anti-adhesive materials. Further studies are necessary to draw definitive conclusions and elucidate long-term outcomes, however, the results obtained hold great promise for the safety and efficacy of this technique.


Assuntos
Craniectomia Descompressiva , Procedimentos de Cirurgia Plástica , Crânio , Telas Cirúrgicas , Titânio , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Craniectomia Descompressiva/métodos , Estudos Retrospectivos , Adulto , Procedimentos de Cirurgia Plástica/métodos , Crânio/cirurgia , Resultado do Tratamento , Idoso , Estética , Complicações Pós-Operatórias/prevenção & controle , Adulto Jovem
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