Percepção profissional sobre tratamento endodôntico em sessão única e múltiplas sessões / Professional perception of single and multi-session endodontic treatment

Na odontologia a decisão do tratamento é exclusiva dos cirurgiões dentistas e suas percepções, incluindo filosofia de tratamento, fazendo com que a prática de novos conceitos, tratamentos ou técnicas dependam não apenas de sua lógica ou eficácia biológica. Sendo assim, este estudo teve como objetivo avaliar os parâmetros envolvidos na tomada de decisão de cirurgiões dentistas clínicos e especialistas para a realização do tratamento endodôntico em sessão única ou múltiplas sessões. Para tanto, este estudo contou com uma coleta de dados através de um questionário online, aplicado cirurgiões dentistas clínicos gerais e especialistas em endodontia. As respostas foram tabuladas e analisadas por meio de estatística descritiva. Os resultados revelaram que a maioria dos endodontistas e dos clínicos gerais prefere realizar tratamento endodôntico em sessão única, devido ao menor desperdício de material, além do melhor domínio da anatomia e tratamento em um único momento. O motivo mais comum para os endodontistas e clínicos gerais escolherem o tratamento com múltiplas visitas é para dentes com prognóstico duvidoso e os casos em que o profissional aguarda a remissão dos sintomas antes da obturação. Em conclusão, a maioria dos endodontistas e dos clínicos gerais preferiu realizar tratamento endodôntico em sessão única.

In dentistry, treatment decisions are made exclusively by dental surgeons and their perceptions, including treatment philosophy, which means that the practice of new concepts, treatments or techniques depends not only on their logic or biological efficacy. Therefore, the aim of this study was to evaluate the parameters involved in clinical and specialist dental surgeons' decision to carry out endodontic treatment in single or multiple sessions. To this end, data was collected using an online questionnaire administered to general dental surgeons and endodontic specialists. The answers were tabulated and analyzed using descriptive statistics. The results revealed that the majority of endodontists and general practitioners prefer to carry out endodontic treatment in a single session, due to less wastage of material, as well as better mastery of the anatomy and treatment at a single time. The most common reason for endodontists and general practitioners to choose treatment with multiple visits is for teeth with a doubtful prognosis and cases in which the professional is waiting for symptoms to remit before filling. In conclusion, the majority of endodontists and general practitioners preferred to carry out endodontic treatment in a single session.

Advances in meniscus tissue engineering: Towards bridging the gaps from bench to bedside.

Meniscus is vital for maintaining the anatomical and functional integrity of knee. Injuries to meniscus, commonly caused by trauma or degenerative processes, can result in knee joint dysfunction and secondary osteoarthritis, while current conservative and surgical interventions for meniscus injuries bear suboptimal outcomes. In the past decade, there has been a significant focus on advancing meniscus tissue engineering, encompassing isolated scaffold strategies, biological augmentation, physical stimulus, and meniscus organoids, to improve the prognosis of meniscus injuries. Despite noteworthy promising preclinical results, translational gaps and inconsistencies in the therapeutic efficiency between preclinical and clinical studies exist. This review comprehensively outlines the developments in meniscus tissue engineering over the past decade (Scheme 1). Reasons for the discordant results between preclinical and clinical trials, as well as potential strategies to expedite the translation of bench-to-bedside approaches are analyzed and discussed.

Precision pore structure optimization of additive manufacturing porous tantalum scaffolds for bone regeneration: A proof-of-concept study.

Currently, the treatment of bone defects in arthroplasty is a challenge in clinical practice. Nonetheless, commercially available orthopaedic scaffolds have shown limited therapeutic effects for large bone defects, especially for massiveand irregular defects. Additively manufactured porous tantalum, in particular, has emerged as a promising material for such scaffolds and is widely used in orthopaedics for its exceptional biocompatibility, osteoinduction, and mechanical properties. Porous tantalum has also exhibited unique advantages in personalised rapid manufacturing, which allows for the creation of customised scaffolds with complex geometric shapes for clinical applications at a low cost and high efficiency. However, studies on the effect of the pore structure of additively manufactured porous tantalum on bone regeneration have been rare. In this study, our group designed and fabricated a batch of precision porous tantalum scaffolds via laser powder bed fusion (LPBF) with pore sizes of 250 µm (Ta 250), 450 µm (Ta 450), 650 µm (Ta 650), and 850 µm (Ta 850). We then performed a series of in vitro experiments and observed that all four groups showed good biocompatibility. In particular, Ta 450 demonstrated the best osteogenic performance. Afterwards, our team used a rat bone defect model to determine the in vivo osteogenic effects. Based on micro-computed tomography and histology, we identified that Ta 450 exhibited the best bone ingrowth performance. Subsequently, sheep femur and hip defect models were used to further confirm the osteogenic effects of Ta 450 scaffolds. Finally, we verified the aforementioned in vitro and in vivo results via clinical application (seven patients waiting for revision total hip arthroplasty) of the Ta 450 scaffold. The clinical results confirmed that Ta 450 had satisfactory clinical outcomes up to the 12-month follow-up. In summary, our findings indicate that 450 µm is the suitable pore size for porous tantalum scaffolds. This study may provide a new therapeutic strategy for the treatment of massive, irreparable, and protracted bone defects in arthroplasty.

Nanotechnology approaches to drug delivery for the treatment of ischemic stroke.

Ischemic stroke is a major global public health concern that lacks effective treatment options. A significant challenge lies in delivering therapeutic agents to the brain due to the restrictive nature of the blood-brain barrier (BBB). The BBB's selectivity hampers the delivery of therapeutically relevant quantities of agents to the brain, resulting in a lack of FDA-approved pharmacotherapies for stroke. In this article, we review therapeutic agents that have been evaluated in clinical trials or are currently undergoing clinical trials. Subsequently, we survey strategies for synthesizing and engineering nanoparticles (NPs) for drug delivery to the ischemic brain. We then provide insights into the potential clinical translation of nanomedicine, offering a perspective on its transformative role in advancing stroke treatment strategies. In summary, existing literature suggests that drug delivery represents a major barrier for clinical translation of stroke pharmacotherapies. While nanotechnology has shown significant promise in addressing this challenge, further advancements aimed at improving delivery efficiency and simplifying formulations are necessary for successful clinical translation.

(Pre)Clinical Metabolomics Analysis.

Metabolomics is the scientific field with the eager goal to comprehensively analyze the entirety of all small molecules of a biological system, i.e., the metabolome. Over the last few years, metabolomics has matured to become an analytical cornerstone of life science research across diverse fields, from fundamental biochemical applications to preclinical studies, including biomarker discovery and drug development. In this chapter, we provide an introduction to (pre)clinical metabolomics. We define key metabolomics aspects and provide the basis to thoroughly understand the relevance of this field in a biological and clinical context. We present and explain state-of-the-art analytical technologies devoted to metabolomic analysis as well as emerging technologies, discussing both strengths and weaknesses. Given the ever-increasing demand for handling complex datasets, the role of bioinformatics approaches in the context of metabolomic analysis is also illustrated.

Global Metabolomics Using LC-MS for Clinical Applications.

Metabolomics can be used for a multitude of purposes, including monitoring of treatment effects and for increasing the knowledge of the pathophysiology of a wide range of diseases. Global (commonly referred to as "untargeted") metabolomics is hypothesis-generating and provides the opportunity to discover new biomarkers. Being versatile and having a high degree of selectivity and sensitivity, liquid chromatography-mass spectrometry (LC-MS) is the most common technique applied for metabolomics. We here present our global metabolomics LC-electrospray ionization-MS/MS method. The sample preparation procedures for plasma, serum, dried blood spots, urine, and cerebrospinal fluid are simple and nonspecific to reduce the risk of analyte loss. The method is based on reversed-phase chromatography using a diphenyl column. The high-resolution Q Exactive Orbitrap MS with data-dependent acquisition provides MS/MS spectra of a wide range of analytes. Our method covers a large part of the metabolome regarding hydrophobicity and compound class.

Sphingolipid Analysis in Clinical Research.

Sphingolipids are the most diverse class of lipids due to the numerous variations in their structural components. This diversity is also reflected in their extremely different functions. Sphingolipids are not only constituents of cell membranes but have emerged as key signaling molecules involved in a variety of cellular functions, such as cell growth and differentiation, proliferation and apoptotic cell death. Lipidomic analyses in clinical research have identified pathways and products of sphingolipid metabolism that are altered in several human pathologies. In this article, we describe how to properly design a lipidomic experiment in clinical research, how to handle plasma and serum samples for this purpose, and how to measure sphingolipids using liquid chromatography-mass spectrometry.

CE-MS-Based Clinical Metabolomics of Human Plasma.

Capillary electrophoresis coupled to mass spectrometry (CE-MS) has emerged as a powerful analytical technique with significant implications for clinical research and diagnostics. The integration of information from CE and MS strengthens confidence in the identification of compounds present in clinical samples. The ability of CE to separate molecules based on their electrophoretic mobility coupled to MS enables the accurate identification and quantification of analytes, even in complex biological matrices such as human plasma.Here, we present a detailed protocol for an untargeted metabolomics study using CE-MS and its application in a study on human plasma from patients suffering Long COVID syndrome. The protocol ranges from sample preparation to biological interpretation, detailing a workflow enabling the analysis of cationic and anionic compounds, metabolite identification, and data processing.

Association of Lipopolysaccharide-Type Endotoxins with Retinal Neurodegeneration: The Alienor Study.

Purpose: Lipopolysaccharide (LPS)-type endotoxins are naturally found in the gut microbiota and there is emerging evidence linking gut microbiota and neuroinflammation leading to retinal neurodegeneration. Thinning of the retinal nerve fiber layer (RNFL) is a biomarker of retinal neurodegeneration, and a hallmark of glaucoma, the second leading cause of blindness worldwide. We assessed the association of a blood biomarker of LPS with peripapillary RNFL thickness (RNFLT) and its longitudinal evolution up to 11 years. Design: The Alienor study is a single center prospective population-based cohort study. Subjects: The studied sample of this study includes 1062 eyes of 548 participants receiving ≥1 gradable RNFL measurement. Methods: Plasma esterified 3-hydroxy fatty acids (3-OH FAs) were measured as a proxy of LPS burden. Retinal nerve fiber layer thickness was acquired using spectral-domain OCT imaging every 2 years from 2009 to 2020 (up to 5 visits). Main Outcome Measures: Associations of plasma esterified 3-OH FAs with RNFLT were assessed using linear mixed models. Results: Mean age of the included 548 participants was 82.4 ± 4.3 years and 62.6% were women. Higher plasma esterified 3-OH FAs was significantly associated with thinner RNFLT at baseline (coefficient beta = -1.42 microns for 1 standard deviation-increase in 3-OH FAs, 95% confidence interval [-2.56; -0.28], P = 0.02). This association remained stable after multivariate adjustment for potential confounders. No statistically significant association was found between 3-OH FAs and longitudinal RNFLT change. Conclusions: Higher plasma esterified 3-OH FAs were associated with thinner RNFLT at baseline, indicating an involvement of LPS in the early processes of optic nerve neurodegeneration and highlighting the potential importance of the human microbiota in preserving retinal health. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Escala de alerta precoce na identificação de pacientes com risco de deterioração clínica / Early warning scale for identifying patients at risk of clinical deterioration / Escala de alerta temprana en la identificación de pacientes con riesgo de deterioro clínico

Objetivo: avaliar pontuação da National Early Warning Score (NEWS) em relação ao tipo de desfecho e perfil dos pacientes da enfermaria clínica médica de um hospital em Teresina, Piauí, Brasil. Método: estudo quantitativo realizado num hospital público, em Teresina, com 150 prontuários de pacientes internados no setor clínica médica de fevereiro de 2022 a dezembro de 2022, a partir de registros demográficos, clínicos e valores da escala na admissão e desfecho. Resultados: houve associação dos valores da escala com a faixa etária (p=0,029), tempo de internação (p=0,023) e tipo de desfecho (p < 0,001). Alto risco clínico prevaleceu entre pacientes do sexo masculino (13%), na faixa etária de 60 a 94 anos (13%), com permanência de 21 a 57 dias (19,2%) e óbito como desfecho (100%). Conclusão: implementação da referida escala evidenciou ser fundamental para prever agravos clínicos e melhorar qualidade da assistência.

Objective: to evaluate the National Early Warning Score (NEWS) in relation to the type of outcome and profile of patients in the medical clinical ward of a hospital in Teresina, Piauí, Brazil. Method: a quantitative study conducted in a public hospital in Teresina, with 150 medical records of patients admitted to the medical clinic sector from February 2022 to December 2022, based on demographic and clinical records and scale values at admission and outcome. Results: there was an association between the scale values and the age group (p=0.029), length of stay (p=0.023) and type of outcome (p < 0.001). High clinical risk prevailed among male patients (13%), aged between 60 and 94 years (13%), with a stay of 21 to 57 days (19.2%), and death as an outcome (100%). Conclusion: implementation of the aforementioned scale proved to be fundamental for predicting clinical problems and improving care quality.

Objetivo: evaluar el puntaje de la National Early Warning Score (NEWS) con respecto al tipo de desenlace y el perfil de los pacientes de la enfermería clínica médica de un hospital en Teresina, Piauí, Brasil. Método: estudio cuantitativo realizado en un hospital público en Teresina, con 150 historiales médicos de pacientes internados en el sector de clínica médica desde febrero de 2022 hasta diciembre de 2022, a partir de registros demográficos, clínicos y valores de la escala en la admisión y desenlace. Resultados: hubo asociación de los valores de la escala con la edad (p=0,029), tiempo de internación (p=0,023) y tipo de desenlace (p < 0,001). El alto riesgo clínico prevaleció entre los pacientes del sexo masculino (13%), en la franja de edad entre 60 y 94 años (13%), con una estancia de 21 a 57 días (19,2%) y fallecimiento como desenlace (100%). Conclusión: la implementación de dicha escala demostró ser fundamental para prever agravios clínicos y mejorar la calidad de la asistencia.

Mecánica y energética durante la marcha en cinta caminadora en adultos uruguayos saludables: efecto del IMC y la edad / Mechanics and energy during treadmill walking in healthy uruguayan adults: effect of BMI and age / Mecânica e energia durante a caminhada em esteira em adultos uruguaios saudáveis: efeito do IMC e Idade

La evaluación de la marcha en cinta caminadora puede resultar relevante para la toma de decisiones clínicas. No obstante, factores demográficos como la edad y el IMC pueden alterar la interpretación de los resultados. Nuestro objetivo fue obtener variables espacio- temporales, energéticas y costo de transporte durante la velocidad autoseleccionada en cinta caminadora para una muestra representativa de adultos uruguayos (n=28) y evaluar si diferentes rangos de edades e IMC pueden ser factores a tener en cuenta en pruebas clínicas donde se consideren dichas variables. Participaron 17 hombres y 11 mujeres (39,3 ± 14,8 años, 75,9 ± 12,5 kg, 1,74 ± 0,09 m, IMC 25,2 ± 4,06). Se realizó una reconstrucción 3D del movimiento en forma sincronizada con el consumo energético. Se obtuvieron valores de referencia y luego de agrupar los participantes según su IMC y rango de edad se compararon los datos mediante test de t (p≤0.05). Los resultados revelaron discrepancias significativas en las medidas espacio-temporales y energéticas de los adultos uruguayos al caminar en cinta con respecto a la literatura. La marcha difiere entre adultos jóvenes y de mediana edad en su velocidad autoseleccionada (p=0,03), longitud de zancada (p=0,01), trabajo mecánico externo (<0,001) y recuperación de energía mecánica (0,009), destacando la importancia de considerar la edad en evaluaciones clínicas. El IMC no influyó significativamente en estas variables. Estos hallazgos subrayan la necesidad de ajustar las interpretaciones de las pruebas clínicas de la marcha sobre cinta caminadora en adultos uruguayos de mediana edad (45 a 65 años).

Treadmill gait assessment can be relevant for clinical decision-making. However, demographic factors such as age and BMI may alter result interpretation. Our aim was to obtain spatiotemporal, energetic, and cost of transport variables during self-selected treadmill walking speed for a representative sample of Uruguayan adults (n=28) and to assess if different age ranges and BMI could be factors to consider in clinical tests involving these variables. Seventeen men and eleven women participated (39.3 ± 14.8 years, 75.9 ± 12.5 kg, 1.74 ± 0.09 m, BMI 25.2 ± 4.06). A synchronized 3D motion reconstruction was performed with energy consumption. Reference values were obtained and data were compared using t-tests (p≤0.05), after grouping participants by BMI and age range. Results revealed significant discrepancies in spatiotemporal and energetic measures of Uruguayan adults walking on the treadmill, compared to the literature. Gait differed between young and middle-aged adults in their self-selected speed (p=0.03), stride length (p=0.01), external mechanical work (p<0.001), and mechanical energy recovery (0.009), emphasizing the importance of considering age in clinical evaluations. BMI did not significantly influence these variables. These findings underscore the need to adjust interpretations of treadmill gait clinical tests in middle-aged Uruguayan adults (45 to 65 years).

A avaliação da marcha na esteira pode ser relevante para a tomada de decisões clínicas. No entanto, fatores demográficos como idade e IMC podem alterar a interpretação dos resultados. Nosso objetivo foi obter variáveis espaço-temporais, energéticas e custo de transporte durante a velocidade de caminhada autoselecionada na esteira para uma amostra representativa de adultos uruguaios (n = 28) e avaliar se diferentes faixas etárias e IMC podem ser fatores a serem considerados em testes clínicos que envolvam essas variáveis. Dezessete homens e onze mulheres participaram (39,3 ± 14,8 anos, 75,9 ± 12,5 kg, 1,74 ± 0,09 m, IMC 25,2 ± 4,06). Foi realizada uma reconstrução tridimensional do movimento sincronizada com o consumo de energia. Foram obtidos valores de referência e os dados foram comparados usando testes t (p≤0,05), após agrupar os participantes por IMC e faixa etária. Os resultados revelaram discrepâncias significativas nas medidas espaço-temporais e energéticas dos adultos uruguaios ao caminhar na esteira, em comparação com a literatura. A marcha diferiu entre adultos jovens e de meia-idade em sua velocidade autoselecionada (p=0,03), comprimento da passada (p=0,01), trabalho mecânico externo (<0,001) e recuperação de energia mecânica (0,009), destacando a importância de considerar a idade em avaliações clínicas. O IMC não influenciou significativamente essas variáveis. Esses achados destacam a necessidade de ajustar as interpretações dos testes clínicos de marcha na esteira em adultos uruguaios de meia- idade (45 a 65 anos).

Have orthodontists changed their retention and follow-up protocols due to contemporary orthodontics? An online survey.

Background: With advancements in orthodontic technology, treatment durations have shortened, often concluding at earlier ages. This shift prompts scrutiny of contemporary retention and post-treatment protocols. The study aimed to assess current professional preferences, compare them against patient age and treatment duration, and investigate the potential impacts of reduced treatment times on professional protocols, particularly when treatment concludes before pubertal growth. Methods: A questionnaire comprising 12 multiple-choice questions focused on active treatment and retention phases was developed using an online survey platform. It was distributed to licensed orthodontists engaged in patient treatment. Bivariate analysis was conducted using ANOVA and the Kruskal-Wallis test, with pairwise comparisons facilitated by the Dwass-Steel-Critchlow-Fligner method. Results: Of 743 respondents, representing a 32% response rate, approximately 70% reported initiating treatment with fixed appliances in pre-pubertal patients. The most prevalent treatment combination involved commencing treatment during early permanent dentition and lasting between 12 to 24 months, resulting in treatment completion before full growth maturation. No discernible individualization was observed in retention protocols or post-retention follow-ups. Traditional retainer prescription post-orthodontic therapy was unanimous among respondents. Notably, experienced orthodontists tended to prefer regular patient visits for follow-up, while less experienced counterparts discharged patients after 12 months. Conclusion: Contemporary orthodontic treatments are characterized by shorter durations, yet orthodontists have not adopted retention and post-treatment follow-up practices accordingly. There is a pressing need for evidence-based guidelines to develop protocols tailored to the shorter treatment durations and the increasing prevalence of younger patients completing treatment.

Advancing patient-centric care: integrating patient reported outcomes for tolerability assessment in early phase clinical trials - insights from an expert virtual roundtable.

Early phase clinical trials provide an initial evaluation of therapies' risks and benefits to patients, including safety and tolerability, which typically relies on reporting outcomes by investigator and laboratory assessments. Use of patient-reported outcomes (PROs) to inform risks (tolerability) and benefits (improvement in disease symptoms) is more common in later than early phase trials. We convened a two-day expert roundtable covering: (1) the necessity and feasibility of a universal PRO core conceptual model for early phase trials; (2) the practical integration of PROs in early phase trials to inform tolerability assessment, guide dose decisions, or as real-time safety alerts to enhance investigator-reported adverse events. Participants (n = 22) included: patient advocates, regulators, clinicians, statisticians, pharmaceutical representatives, and PRO methodologists working across diverse clinical areas. In this manuscript, we report major recommendations resulting from the roundtable discussions corresponding to each theme. Additionally, we highlight priority areas necessitating further investigation.

Alleviation of Allergic Rhinoconjunctivitis Symptoms in Participants Treated with a 0.005% Tacrolimus Eye-Drop Solution.

Purpose: This randomized, placebo-controlled, crossover, double-blind trial aimed to evaluate the efficacy and safety of Tacrosolv, a novel 0.005% tacrolimus eye-drop solution, in adults with grass pollen-induced allergic conjunctivitis. Methods: A total of 64 adult participants were randomized to receive 2.5 µg or 5 µg tacrolimus/eye/day or placebo treatment for 8 days, with grass pollen exposure on day 1 and day 8. After a 2-week washout period, placebo participants crossed over to Tacrosolv treatment and vice versa, with repeated treatment and exposure. During exposure, participants recorded ocular, nasal, and respiratory allergy symptoms every 15 minutes. The primary endpoint was the mean total ocular symptom score (TOSS) on day 8. Objective ocular safety parameters were assessed before, during, and after exposure. Adverse events were recorded throughout the study. Results: On day 8, high-dose Tacrosolv reduced the TOSS compared to placebo towards the end of exposure (p<0.05 at time points 3 hours, 45 minutes and 4 hours). A 26% reduction in baseline adjusted TOSS from day 1 to day 8 was observed in participants treated with high-dose Tacrosolv, whereas placebo-treated participants showed no difference in TOSS between day 1 and day 8. Nasal symptoms were reduced on both day 1 and day 8 in participants treated with high-dose Tacrosolv (p<0.05). No safety concerns were raised. All adverse events were resolved within the study period. Conclusion: High-dose Tacrosolv is safe and effective for alleviating symptoms of allergic rhinoconjunctivitis. Trial Registration: NCT04532710; EudraCT No. 2019-002847-62.

Automated manufacturing and characterization of clinical grade autologous CD20 CAR T cells for the treatment of patients with stage III/IV melanoma.

Introduction: Point-of-care (POC) manufacturing of chimeric antigen receptor (CAR) modified T cell has expanded rapidly over the last decade. In addition to the use of CD19 CAR T cells for hematological diseases, there is a growing interest in targeting a variety of tumor-associated epitopes. Methods: Here, we report the manufacturing and characterization of autologous anti-CD20 CAR T cells from melanoma patients within phase I clinical trial (NCT03893019). Using a second-generation lentiviral vector for the production of the CD20 CAR T cells on the CliniMACS Prodigy®. Results: We demonstrated consistency in cell composition and functionality of the products manufactured at two different production sites. The T cell purity was >98.5%, a CD4/CD8 ratio between 2.5 and 5.5 and transduction rate between 34% and 61% on day 12 (harvest). Median expansion rate was 53-fold (range, 42-65-fold) with 1.7-3.8×109 CAR T cells at harvest, a sufficient number for the planned dose escalation steps (1×105/kg, 1×106/kg, 1×107/kg BW). Complementary research of some of the products pointed out that the CAR+ cells expressed mainly central memory T-cell phenotype. All tested CAR T cell products were capable to translate into T cell activation upon engagement of CAR target cells, indicated by the increase in pro-inflammatory cytokine release and by the increase in CAR T cell amplification. Notably, there were some interindividual, cell-intrinsic differences at the level of cytokine release and amplification. CAR-mediated T cell activation depended on the level of CAR cognate antigen. Discussion: In conclusion, the CliniMACS Prodigy® platform is well suited for decentralized POC manufacturing of anti-CD20 CAR T cells and may be likewise applicable for the rapid and automated manufacturing of CAR T cells directed against other targets. Clinical trial registration: https://clinicaltrials.gov/study/NCT03893019?cond=Melanoma&term=NCT03893019&rank=1, identifier NCT03893019.

Scalp Rosacea Treated with Topical Ivermectin.

Introduction: Scalp rosacea is often misdiagnosed or overlooked, and few reports deal with this peculiar localization. Furthermore, the pharmacological approach to scalp rosacea remains a therapeutic challenge, as no topical and/or systemic drugs have been approved for this specific area so far. Case Presentation: A series of 5 adult patients affected by inflammatory rosacea and concurrent scalp involvement, confirmed by dermoscopy and histopathology with negative microbiologic swabs, and effectively treated with ivermectin 1% cream once daily for 12 weeks is presented. Conclusion: Our experience, although limited, suggests that evaluation of rosacea subjects should also include the scalp and that the treatment with ivermectin 1% cream may be effective on scalp rosacea.

Unveiling the Molecular Features of SCLC With a Clinical RNA Expression Panel.

Introduction: The translation of gene expression profiles of SCLC to clinical testing remains relatively unexplored. In this study, gene expression variations in SCLC were evaluated to identify potential biomarkers. Methods: RNA expression profiling was performed on 44 tumor samples from 35 patients diagnosed with SCLC using the clinically validated RNA Salah Targeted Expression Panel (RNA STEP). RNA sequencing (RNA-Seq) and immunohistochemistry were performed on two different SCLC cohorts, and correlation analyses were performed for the ASCL1, NEUROD1, POU2F3, and YAP1 genes and their corresponding proteins. RNA STEP and RNA-Seq results were evaluated for gene expression profiles and heterogeneity between SCLC primary and metastatic sites. RNA STEP gene expression profiles of independent SCLC samples (n = 35) were compared with lung adenocarcinoma (n = 160) and squamous cell carcinoma results (n = 25). Results: The RNA STEP results were highly correlated with RNA-Seq and immunohistochemistry results. The dominant transcription regulator by RNA STEP was ASCL1 in 74.2% of the samples, NEUROD1 in 20%, and POU2F3 in 2.9%. The ASCL1, NEUROD1, and POU2F3 gene expression profiles were heterogeneous between primary and metastatic sites. SCLCs displayed markedly high expression for targetable genes DLL3, EZH2, TERT, and RET. SCLCs were found to have relatively colder immune profiles than lung adenocarcinomas and squamous cell carcinomas, characterized by lower expression of HLA genes, immune cell, and immune checkpoint genes, except the LAG3 gene. Conclusions: Clinical-grade SCLC RNA expression profiling has value for SCLC subtyping, design of clinical trials, and identification of patients for trials and potential targeted therapy.

A droplet digital PCR method for the detection of scale drop disease virus in yellowfin seabream (Acanthopagrus latus).

In this study, a ddPCR method for the detection of scale drop disease virus (SDDV) in yellowfin seabream (Acanthopagrus latus) was established based on Real-time fluorescence quantitative PCR detection methods and principles. The reaction conditions were optimized, and the sensitivity, specificity, accuracy, and reproducibility were assessed. The results showed that threshold line position was determined to be 1900 by the ddPCR method; the optimum annealing temperature for SDDV detection by the ddPCR method was 60°C; the limit of detection was 1.4-1.7 copies/µL; the results of specific detection of other common viruses, except for SDDV specific amplification, were all negative; and the relative standard deviation (RSD) for the reproducibility validation was 0.77%. The samples of yellowfin seabream (Acanthopagrus latus) liver, spleen, kidney, heart, intestine, brain, blood, muscle, skin and ascites with three replicates, respectively, were tested using the ddPCR method, and the results were consistent with clinical findings. The ddPCR method established in this study has the advantages of high sensitivity, high specificity, good reproducibility and simple steps for the quantitative detection of SDDV, which could be used for the nucleic acid detection of clinical SDDV samples, and provided a new quantitative method for the diagnosis of yellowfin seabream SDDV in the early stage of pathogenesis.

Clinicopathological features and surgical treatments of intraductal papillary neoplasm of the bile duct: a case report and literature review.

Intraductal papillary neoplasm of bile duct (IPNB), as a precancerous lesion of cholangiocarcinoma, is a rare biliary tract tumor. A 66-year-old female patient was found to have a bile duct mass by routine examination. The liver function tests and tumor markers were normal. Imaging findings revealed a 2.6 cm mass in the common hepatic duct, accompanied by dilatation of both intrahepatic and extrahepatic bile ducts. The patient underwent open extrahepatic bile duct resection, cholecystectomy and Roux-en-Y hepaticojejunostomy. We also conducted a literature review to summarize the clinicopathological features and surgical treatments of IPNB.

Clinical characteristics and risk factors associated with diverse manifestations of COVID-19 in patients aged 85 years and older.

Objective: The goal of this study is to assess the clinical attributes exhibited by patients aged 85 years and older who present different manifestations of COVID-19, and to examine the factors influencing the classification of the disease severity. Method: This retrospective study was conducted at a single center, encompassing an analysis of clinical data obtained from patients with COVID-19 admitted to a general geriatric hospital in Hangzhou, Zhejiang, China, during the period from December 20, 2022, to February 1, 2023. The study focused on 91 eligible patients whose disease severity was compared based on the imaging findings. Results: A total of 91 patients aged 85 years and older, with a median age of 92, including 46 males, 10 exhibiting mild symptoms, 48 moderate cases, and 33 severe cases met the inclusion criteria. Notably, disease severity displayed a significant correlation with age (p < 0.011). All patients presented with complicated chronic underlying conditions and a history of prolonged medication use. Rheumatic immune diseases (p = 0.040) and endocrine medications, primarily hypoglycemic agents (p = 0.034), exhibited statistical significance. Additionally, markers such as lactate dehydrogenase (LDH) (p = 0.030), interleukin 6 (IL-6) (p = 0.014), and D-dimer (p = 0.007) revealed significant associations with disease severity. Chest computed tomography scans predominantly revealed inflammatory features (n = 81, 89.0%). Notably, patients classified as having mild or moderate conditions exhibited eventual improvement, while 13 patients (39.4%) among the severe cases succumbed to the disease. Conclusion: The classification of disease among patients aged 85 years or older old is correlated with advanced age, concurrent rheumatic immune diseases, and prolonged administration of endocrine medications. Furthermore, patients with elevated levels of LDH, IL-6, and D-dimer demonstrated a higher propensity for developing severe diseases.