Clinical Disease Research Articles

Atypical fractures at non-classical sites associated with anti-resorptive therapy: A Systematic Review.

Osteoporosis is common, affecting more than 20% of women and 6% of men globally over the age of 50 (1). Anti-resorptive drugs, bisphosphonates and denosumab, have been effective treatments for osteoporosis for more than 30years. Rare complications of anti-resorptive therapy include medication-related osteonecrosis of the jaw and atypical femur fractures (AFF). The American Society for Bone and Mineral Research (ASBMR) proposed a case definition for these atypical femoral fractures in 2010, which was updated in 2013. However, atypical fractures at non-classical sites have been increasingly described. We aimed to systematically identify atypical fracture cases, excluded from the ASBMR AFF case definition in patients receiving anti-resorptive medication for longer than three years. A structured search of electronic databases, including PubMed, Medline (Ovid), Embase (Ovid), Cochrane and Web of Sciences, and hand-searching of conference abstracts was undertaken. All full-text articles written in English describing an atypical fracture in patients (aged >18years) and receiving anti-resorptive medication for >3years were included, with data extracted and analysed by two independent reviewers. Sixty-six articles were identified, describing 151 cases of atypical fractures in 114 individuals. The most frequent fracture site was the ulna, followed by the tibia. All patients were taking anti-resorptive treatment prior to or at the time of fracture, most frequently alendronate monotherapy (44%). Most commonly, fractures were transverse in nature (95%), following minimal or no trauma (96%), non-comminuted (98%) with cortical thickening of the surrounding bone (69%). Anti-resorptive treatment was ceased following atypical fracture in the majority (89%). Atypical fractures are rare and should not deter physicians from appropriate anti-resorptive therapy for osteoporosis. However, clinicians should be alert to their presence, at additional sites to the femur. An update of the current ASBMR AFF case definition to include other skeletal sites could be timely.

Trends in the Care of Locally Advanced Pancreatic Cancer in the Modern Era of Chemotherapy.

Current guidelines for treatment for locally advanced pancreatic cancer recommend chemotherapy ± radiation, or radiation alone when multimodal therapy is contraindicated. In a subset of patients, guideline-recommended treatment (GRT) achieves sufficient response to qualify for potentially curative resection. This study evaluated trends in treatment utilization and aimed to identify barriers to GRT. Patients with clinical T4M0 disease in the National Cancer Database from 2010 to 2017 were included. Potential predictors were assessed by relative risk regression with Poisson distribution and compared by log-link function. In total, 28 056 patients met the criteria. Among 17 059 (67.67%) patients treated primarily with chemotherapy, 41.19% also had radiation and 8.89% went onto resection. Many received no cancer-directed treatment or failed to receive GRT. Another 710 patients had radiation (±surgery) without chemotherapy despite few contraindications to chemotherapy. Over time, patients were more likely to undergo resection after chemotherapy (aRR = 1.58; p < 0.0001) and less likely to have chemoradiation (aRR = 0.78; p < 0.0001) or go untreated (aRR = 0.90; p < 0.0001). Socioeconomic factors (race, education, income, and insurance status) affected the likelihood of receiving chemotherapy and surgery. Median overall survival (OS) was significantly improved for patients treated with chemotherapy and particularly in those patients who went on to receive RT or undergo surgical resection. OS was also longer for patients treated at high-volume academic centers. Patients insured by Medicaid, Medicare, or those without insurance had worse OS. Despite improvement over time, many patients go untreated. Clinical factors were influential, but the impact of vulnerable social standing suggests persistent inequity in access to care.

Rhesus rotavirus NSP1 mediates extra-intestinal infection and is a contributing factor for biliary obstruction.

We previously demonstrated that in Ifnar1-/-Ifngr1-/- or Stat1-/- suckling mice lacking intact type I and type II interferon (IFN) signaling, rhesus rotavirus (RRV) infection causes a lethal disease with clinical manifestations similar to biliary atresia, including acholic stools, oily fur, growth retardation, and excess mortality. Elevated levels of viral RNA are detected in the bile ducts and liver of diseased pups together with severe inflammatory responses in these tissues. However, the viral determinants and the molecular mechanisms driving this process remain incompletely understood. Using an optimized rotavirus (RV) reverse genetics system, we generated a panel of recombinant RVs that encode non-structural protein 1 (NSP1) derived from different RV strains. We found that compared to the parental simian SA11 strain that is less biliary pathogenic, SA11 containing an RRV-derived NSP1 resulted in severe biliary obstructive disease comparable to that associated with RRV infection, reflected by high levels of viral RNA and inflammation in the biliary tract, liver, and pancreas. In contrast, RRV containing an SA11-originated NSP1 showed only mild biliary obstruction comparable to what was observed during SA11 infection. Infection with a monoreassortant RRV virus carrying NSP1 from the bovine RV UK strain also showed substantially reduced viral replication in extra-intestinal organs and did not develop clinical biliary diseases. Mechanistically, RRV NSP1 seemed to promote active viral replication in hepatocytes and this expanded tropism led to enhanced infiltration of CD4 and CD8 T cells, causing immunopathology and damage in the hepatobiliary system. These results highlight an unexpectedly important role of RV NSP1 in viral replication and disease progression in extra-intestinal tissues.

Applications of cerebrospinal fluid circulating tumor cells and circulating tumor-derived DNA in diagnosis, prognosis, and personalized treatment of CNS metastases.

A common feature of advanced solid tumors is their ability to metastasize and colonize distant organs, including the Central Nervous System (CNS), which encompasses brain and leptomeningeal metastases (LM). While cerebrospinal fluid cytopathological analysis remains a gold standard diagnostic tool, it only provides limited insights into the biology of tumor cells; thus, it is urgent to develop minimally invasive biomarkers that enable a comprehensive quantitative and molecular characterization of disseminated cells, therapy response assessment, and disease monitoring. Liquid biopsy methods have been swiftly developed for some readily accessible bodily fluids such as plasma and urine; circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) from these sources have been rapidly implemented into clinical trial design, disease monitoring, and treatment assignment across different tumor types. However, the filter imposed by the brain blood barrier (BBB) hampers the release of tumor-derived cells and molecules from CNS metastases. Crucially, cerebrospinal fluid (CSF) liquid biopsy methods offer a unique and unparallel source to develop liquid biopsy methodologies in patients with CNS-disseminated disease, including the characterization of CTCs and ctDNA arising specifically from brain and leptomeningeal metastasis. These technologies have enabled a deeper understanding of tumor cell and molecular dynamics, including the reconstruction of clonal evolution in the brain microenvironment through longitudinal sapling. Here, we discuss the current challenges and opportunities that CSF liquid biopsy methods face for the implementation of these approaches into clinical settings.

Artificial Intelligence in Infectious Disease Clinical Practice: An Overview of Gaps, Opportunities, and Limitations.

The integration of artificial intelligence (AI) in clinical medicine marks a revolutionary shift, enhancing diagnostic accuracy, therapeutic efficacy, and overall healthcare delivery. This review explores the current uses, benefits, limitations, and future applications of AI in infectious diseases, highlighting its specific applications in diagnostics, clinical decision making, and personalized medicine. The transformative potential of AI in infectious diseases is emphasized, addressing gaps in rapid and accurate disease diagnosis, surveillance, outbreak detection and management, and treatment optimization. Despite these advancements, significant limitations and challenges exist, including data privacy concerns, potential biases, and ethical dilemmas. The article underscores the need for stringent regulatory frameworks and inclusive databases to ensure equitable, ethical, and effective AI utilization in the field of clinical and laboratory infectious diseases.

Research Progress of Transcatheter Tricuspid Regurgitation Repair Device

The tricuspid valve has been nicknamed the "forgotten valve" and is often neglected by clinicians. However, tricuspid regurgitation is a common clinical heart valve disease. With the continuous development of transcatheter interventional medical device technology, the treatment of tricuspid regurgitation has gradually attracted attention, and more and more companies are developing interventional medical devices for treating this disease. This review will provide an overview of the current research progress on transcatheter therapy for tricuspid regurgitation repair devices at home and abroad, including the design principles, operational steps, clinical outcomes, and the advantages and disadvantages of these devices.

High prevalence of antibodies against feline calicivirus in Australian feral and stray cat (Felis catus) populations.

Feline calicivirus (FCV) commonly causes upper respiratory tract, oral and ocular infections in species of the family Felidae, with high prevalence amongst domestic cat (Felis catus) populations worldwide. Detection of FCV-specific antibodies in serum provides evidence of previous infection with FCV and an indication of whether a cat may be protected against clinical FCV disease. This study describes the most extensive sampling for anti-FCV antibodies in feral and stray cat populations in Australia, and examines variation in prevalence associated with cat age, sex and location. Blood samples were opportunistically collected from 669 feral, stray or Indigenous community cats from the Northern Territory, South Australia, Victoria, south-east Tasmania and south-west New South Wales. The sera were harvested and tested for antibodies capable of neutralising the FCV vaccine strain F9 by serum-virus neutralisation assay. Of the 669 cats tested, 69.7% had detectable FCV-F9-neutralising antibodies (titres ≥5). Maturity was significantly associated with higher seroprevalence and higher antibody titres, with adult cats being more than twice as likely to have detectable FCV-neutralising antibodies than subadults. Male cats had a higher seroprevalence and slightly higher antibody titres than females. Cats living in closer proximity to humans had significantly higher seroprevalences and higher FCV-neutralising antibody titres than feral cats from more remote regions of Australia. Australian feral and stray cats have a high risk of natural exposure to and infection with FCV, with the prevalence and levels of pre-existing immunity to FCV being highest amongst adult cats living in highly modified urban, peri-urban and agricultural environments.

Role of melatonin in rheumatoid arthritis: a narrative review

Melatonin, also known as methoxytryptamine-5-acetyl-N, is the main hormone secreted by the pineal gland. It shows that exogenous melatonin as a supplement can help improve sleep quality and act as an anti-inflammatory factor. Melatonin, in multiple ways, controls the immune system, including regulating inflammatory pathways, apoptosis signaling pathways, and regulating the circadian clock. CD4+ T helper (Th1), Th17, and regulatory T cells, which are the important cells in the immune system, are affected by melatonin. Studies did not demonstrate serious complications following the consumption of melatonin. Rheumatoid Arthritis (RA) is an autoimmune disease that causes a chronic inflammatory situation. RA is a systematic disease that affects multi-organ. The characteristic feature of RA is targeting symmetrically small joints. RA has an unknown etiology, and numerous immune cells, cytokines, interleukins, and inflammatory factors participate in the etiology of RA. In addition, oxidative stress and the relation of oxidative stress with clinical presentation and RA disease activity. Due to the following information, melatonin might be a possible supplementary treatment for RA. Some studies demonstrated that melatonin supplements have advantages in some autoimmune and inflammatory diseases. Studies suggest pro-inflammatory factors reduction and increase in anti-inflammatory agents with melatonin supplementation, while other studies have reported no considerable effects, and the results are controversial. Some clinical studies evaluate the impact of melatonin on RA disease clinical signs and symptoms, but they did not report any clinical improvements. Considering the lack of a definite conclusion due to the limited available evidence, future studies are suggested.

The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies.

Cytomegalovirus (CMV) infection is associated with severe clinical disease and high morbidity in immunocompromised hosts. Letermovir and maribavir, are two recently developed antiviral drugs used in the prevention and treatment of resistant and refractory CMV. Following the publication of landmark randomized trials and increased use, both clinical trial data and real-world experience has reported the development of antiviral drug resistance. The aim of this review was to comprehensively review the published literature on letermovir and maribavir drug resistance and to describe the clinical scenarios in which they may emerge. For letermovir, the most frequently detected resistance mutations occur in the UL56 gene (C325Y/W/F) and confer total resistance. Maribavir resistance mutations most often occur in the UL97 gene and resistance-associated variants (RAVs) T409M, H411Y, C480F have all been detected. The clinical context in which letermovir and maribavir resistance occurs include high viral loads at initiation, intensified immunosuppression, subtherapeutic drug exposure because of poor adherence, drug interactions, and inadequate central nervous system (CNS) penetration. Emergence of resistance mutations generally occurs within the first 3 months of initiation. The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV.

Survival impact of pathologic features after salvage lung resection following definitive chemoradiotherapy or systemic therapy for initially unresectable lung cancer.

Salvage surgery for primary lung cancer is expected to become increasingly common. This study aimed to clarify the survival impact of pathologic characteristics after salvage surgery. Consecutive patients who underwent salvage surgery following definitive chemoradiotherapy or systemic therapy for initially unresectable lung cancer from 2010 to 2020 were enrolled in this study. The tumor slides were reviewed to determine the size of the tumor bed and the proportions of viable tumor, necrosis, and stroma. A total of 23 patients were evaluated, and 18 had clinical stage IIIB-IV disease. Six received chemoradiotherapy and 17 received systemic therapy alone. A major pathologic response (MPR, ≤ 10% of viable tumor) was observed in 6 patients, and 4 patients achieved a pathological complete response. The 3-year overall and recurrence-free survival rates (OS and RFS) were 78.6% and 59.2%, respectively. There was no significant difference in OS between patients with and without MPR, and even non-MPR patients achieved a favorable 3-year OS of 70.2%. Meanwhile, patients with high (≥ 30%) stroma showed significantly better OS than those with low (< 30%) stroma (3-year OS: 100% vs. 23.3%, p < 0.001). This study showed that the proportion of stroma can be useful for predicting long-term survival after salvage surgery. Further large-scale studies are warranted to confirm the current findings.

Analysis of computed tomography venography for the diagnosis and endovascular treatment of iliac venous compression syndrome with venous leg ulcers: a retrospective study

Iliac vein compression syndrome (IVCS) is a clinical condition defined as obstruction of the iliac vein caused by chronic compression imposed by various causes. Currently, the clinical role of computed tomography venography (CTV) in the diagnosis of IVCS is unclear. Accurately diagnosing IVCS using CTV may enhance the understanding of the pathological anatomy of iliac veins, which may lead to better treatment outcomes, especially for recalcitrant venous leg ulcers (VLU). We aimed to investigate diagnostic criteria, contributing clinical factors, and stenting for IVCS with VLU in this study. CTV, digital subtraction angiography (DSV), and Doppler ultrasound (DUS) data were obtained from the medical and imaging records of 62 patients. Additionally, contributing factors and stenting for IVCS were analysed. Patients (100%) had clinical, aetiological, anatomic, or pathological C6 disease. CTV reduced the procedure time and contrast medium dose and provided more information than DSV. Risk factors for IVCS with VLU included female sex (P = 0.036) and advanced age (P = 0.014). The rate of ulcer healing was lower in the IVCS group without stent implantation (P = 0.020). Significant improvements were noted in venous clinical severity scores (P < 0.001) and chronic venous insufficiency questionnaire-20 scores (P < 0.001) after stenting for IVCS with C6 ulcers. CTV provides a more accurate diagnosis than DUS and DSV and allows detection of possible causes of IVCS. Female sex and advanced age were potential contributing factors for IVCS. Satisfactory outcomes were observed with stenting in the treatment of IVCS with C6 ulcers.

Establishment and evaluation of prediction model of recurrence after laparoscopic choledocholithotomy.

Choledocholithiasis is a common clinical bile duct disease, laparoscopic choledocholithotomy is the main clinical treatment method for choledocholithiasis. However, the recurrence of postoperative stones is a big challenge for patients and doctors. To explore the related risk factors of gallstone recurrence after laparoscopic choledocholithotomy, establish and evaluate a clinical prediction model. A total of 254 patients who underwent laparoscopic choledocholithotomy in the First Affiliated Hospital of Ningbo University from December 2017 to December 2020 were selected as the research subjects. Clinical data of the patients were collected, and the recurrence of gallstones was recorded based on the postoperative follow-up. The results were analyzed and a clinical prediction model was established. Postoperative stone recurrence rate was 10.23% (26 patients). Multivariate Logistic regression analysis showed that cholangitis, the diameter of the common bile duct, the diameter of the stone, number of stones, lithotripsy, preoperative total bilirubin, and T tube were risk factors associated with postoperative recurrence (P < 0.05). The clinical prediction model was ln (p/1-p) = -6.853 + 1.347 × cholangitis + 1.535 × choledochal diameter + 2.176 × stone diameter + 1.784 × stone number + 2.242 × lithotripsy + 0.021 × preoperative total bilirubin + 2.185 × T tube. Cholangitis, the diameter of the common bile duct, the diameter of the stone, number of stones, lithotripsy, preoperative total bilirubin, and T tube are the associated risk factors for postoperative recurrence of gallstone. The prediction model in this study has a good prediction effect, which has a certain reference value for recurrence of gallstone after laparoscopic choledocholithotomy.

Neuronal alpha-Synuclein Disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson’s disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively. We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.

Risk factors of diphtheria outbreak in damt district of Al Dhalea Governorate, 2023 -Yemen: a case–control study

BackgroundIn Yemen, diphtheria has become an important health problem since 2017 when diphtheria re-emergence as a consequence of war and the collapse of the health system. In 2023, there has been a 57% increase in diphtheria cases compared to 2021 and 2022. Damt district of Al Dhalea Governorate had the highest reported cases for year 2023. The study aims to determine the risk factors associated with diphtheria outbreak in Damt District.MethodsA retrospective matched case–control (1:2) was used. All confirmed cases based on the WHO case definition reported from Damt district during 2023 were considered cases. Two age-matched (± 5years) neighborhood controls were recruited per case. A pretested questionnaire was used for collecting data during household interviews including demographic and household characteristics, knowledge of diphtheria, vaccination status, contact with a case of diphtheria, and travel history. Frequency and proportion for quantitative and median with interquartile range (IQR) for quantitative variables. Chi-square and Mann–Whitney tests to compare the distribution of categorical and numerical variables between cases and controls. Univariate and multivariate conditional binary logistic regression, and Adjusted Odds ratio (AOR) with a 95% confidence interval at P < 0.05 were used to identify risk factors.ResultsA total of 118 cases and 236 controls were enrolled, 56% were females (63% of cases vs. 53% of controls). The median (IQR) age was 14 (9,22) years for cases vs 12(7,23) of control, it was significantly higher for females than males in the case group: (16(10,29) Vs 10(6,18), P < 0.001) and control group: (15(8,25) vs 12(7,18), p-value = 0.022). Partial vaccination status AOR = 13.7(6.1–31.1), P-value < 0.001), contacts with a case of diphtheria AOR = 8.5(2.3–31.0), P value < 0.001) and Female gender, AOR = 3.3(CI; 1.1–9.5, P value = 0.029), were the main risk factors.ConclusionsPoor vaccination and contact with a case of diphtheria were the main contributors to diphtheria in the Damt district particularly among adult females. Increasing the vaccination coverage with a diphtheria-containing vaccine through routine immunization as well as tetanus-diphtheria vaccine for childbearing age females along with community awareness regarding protection measures during home care of diphtheria cases. Vaccination services as well as gender barriers related to Td vaccination should be investigated.

Comparison of Chikungunya Virus-Induced Disease Progression and Pathogenesis in Type-I Interferon Receptor-Deficient Mice (A129) and Two Wild-Type (129Sv/Ev and C57BL/6) Mouse Strains.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus causing a debilitating febrile illness with rheumatic disease symptoms of arthralgia and arthritis. Since its spread outside of Africa in 2005, it continues to cause outbreaks and disseminates into new territories. Intervention strategies are urgently required, including vaccination and antiviral approaches. To test efficacy, the use of small animal models is required. Two mouse strains, A129, with a deficiency in their type-I interferon (IFN) receptor, and C57BL/6 are widely used. A direct comparison of these strains alongside the wild-type parental strain of the A129 mice, 129Sv/Ev, was undertaken to assess clinical disease progression, viral loads in key tissues, histological changes and levels of sera biomarkers. Our results confirm the severe disease course in A129 mice which was not observed in the parental 129Sv/Ev strain. Of the two wild-type strains, viral loads were higher in 129Sv/Ev mice compared to C57BL/6 counterparts. Our results have established these models and parameters for the future testing of vaccines and antiviral approaches.

Neuropathic pain in spondyloarthritis: Decoding its prevalence, risk factors, and impact on disease activity

ObjectivesThis study aimed to evaluate the prevalence and characteristics of neuropathic pain in patients with various subtypes of spondyloarthritis (SpA), including axial SpA (axSpA), psoriatic arthritis (PsA), and undifferentiated peripheral SpA (p-SpA). Additionally, the study sought to identify potential risk factors associated with the presence or severity of neuropathic pain and to investigate its impact on clinical disease activity assessment. MethodsWe conducted a cross-sectional study at two tertiary rheumatology centers, enrolling patients diagnosed with SpA. Data on demographic and clinical characteristics, comorbidities, and current therapies were collected. Neuropathic pain was assessed using the PainDETECT Questionnaire (PD-Q) and the Neuropathic Pain Symptom Inventory (NPSI). Statistical analyses included descriptive statistics, t-tests, and Pearson's correlations to evaluate the relationships between neuropathic pain scores and clinical disease activity indices. ResultsThe study included 177 patients. Of these, 22.2% had a PD-Q score ≥19, showing a high likelihood of neuropathic pain, while 64.9% scored ≤12, suggesting the absence of significant neuropathic components. The mean PD-Q score was 11.5 ± 10.1. Subgroup analyses showed that females had significantly higher scores for paroxysmal and evoked pain (p < 0.05), and obese patients had significantly higher scores across all NPSI subscores (p < 0.05). Moderate positive correlations were found between neuropathic pain scores and clinical disease activity indices, such as DAPSA (r = 0.46, p < 0.0001) and ASDAS-CRP (r = 0.42, p < 0.01). ConclusionsNeuropathic pain is prevalent among patients with SpA and is significantly associated with disease activity assessments and management. This study highlights the importance of integrating neuropathic pain evaluation into the clinical assessment of SpA to tailor treatment approaches effectively and improve patient outcomes.

Global trends and hotspots in research of paronychia: A bibliometric analysis.

Paronychia is a prevalent clinical disease profoundly affecting patients' quality of life. As ongoing evolution in modern living environments, factors contributing to paronychia are becoming increasingly diverse. Therefore, a further understanding about latest trend of paronychia is imperative and pressing. A systematic literature search was performed based on Web of Science Core Collection and Science Citation Index Expanded. The search parameters encompassed keywords associated with paronychia from 1980 to 2023, and rigorous data cleaning procedures were executed to maintain the analysis's relevance and dependability, supplemented by a thorough examination of abstracts and titles. Visibility analysis was conducted with Citespace and VOSviewer tools to explore the publication trends, collaborative networks, and impactful studies. A total of 595 articles were included in this study. The annual publication trends exhibited a significant increase since 1990, reached a peak of 41 articles in 2021. Collaborative relationships among countries demonstrated strong connections, with the United States leading in both publication volume, citation records and international cooperation. Keyword analysis indicated that in recent years, a substantial body of research has concentrated on paronychia issues caused by epidermal growth factor receptor inhibitors (EGFRI)-class drugs, such as Gefitinib, Erlotinib, and Afatinib, in the context of tumor treatment. In this area, most of the recent hotspots are not focused on the basic research about paronychia due to the basic research about traditional paronychia already reached a relative mature stage. However, with the widespread clinical application of EGFRI anticancer drugs, the incidence of drug-induced paronychia is inevitably on the rise. Therefore, with the expanding diversity in the etiology of paronychia, this area deserves a multiple discipline cooperation with a much wider international communication.

Efficacy and safety of filgotinib in patients with moderately active rheumatoid arthritis and an inadequate response to methotrexate.

Clinical trials restricted to moderately active RA are limited. Filgotinib is approved for treating moderate to severe active RA. This post hoc analysis assessed efficacy and safety of filgotinib in moderately active RA. In FINCH 1, patients with active moderate to severe RA and inadequate response to methotrexate received filgotinib 200 mg or 100 mg (FIL200/FIL100) once daily, adalimumab 40 mg every 2 weeks, or placebo, all with methotrexate (n = 1,755). This subgroup analysis was conducted in patients with a moderate baseline Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP; >3.2 to ≤ 5.1; n = 425 [24.2%]). A higher proportion of patients achieved DAS28-CRP <2.6, Clinical Disease Activity Index (CDAI) remission (≤2.8), low disease activity (LDA) (DAS28-CRP ≤3.2 or CDAI ≤10), and American College of Rheumatology (ACR20/50/70) responses with FIL200 and FIL100 vs placebo at Weeks 12 and 24. Week 12 ACR20 response rates (primary end point) were 77.9%, 67.8%, and 43.8%, respectively. ∼75% of patients achieved DAS28-CRP LDA by week 24 with either filgotinib dose. FIL200 and FIL100 elicited greater improvements in patient-reported outcomes than placebo. The efficacy of filgotinib, maintained through week 52, was comparable to that of adalimumab. Frequency of adverse events (AEs) was similar with filgotinib and adalimumab. Infections were the most common AEs; incidence rates were 40-53% in active treatment groups. In this subpopulation with moderately active RA, the efficacy and safety of filgotinib were similar to those in the overall FINCH 1 population (patients with active moderate to severe RA). NCT02889796.

CRISPR/Cas12a-assisted hyperbranched rolling circle amplification technique for NF-kB p50 detection by electrochemiluminescence biosensor

Transcription factors play crucial roles in governing gene expression and are implicated in various physiological and pathological processes. Here, we propose a novel electrochemiluminescence (ECL) biosensor for the sensitive and specific detection of the transcription factor NF-kB p50, utilizing CRISPR/Cas12a-assisted hyperbranched rolling circle amplification (HRCA) technology. The biosensor achieves a remarkable limit of detection (LOD) of 3.6 fM and demonstrates excellent specificity against interfering proteins. Optimization of experimental parameters further enhances the biosensor’s performance, ensuring its reliability and accuracy. In addition, validation in real biological samples confirms the feasibility of biosensor for practical applications, offering a promising tool for clinical trials and disease diagnosis.

The role of radical cystectomy and lymphadenectomy in the management of bladder cancer with clinically positive lymph node involvement.

The role of radical cystectomy and pelvic lymph node dissection in muscle-invasive bladder cancer (MIBC) with clinically positive lymph nodes is debated. This review examines the role of surgery in treating patients with clinical N1 and more advanced nodal involvement (N2-N3) within a multimodal treatment approach. For clinical N1 disease, guidelines typically recommend neoadjuvant chemotherapy followed by surgery. However, for N2-N3 disease, guidelines vary. Advances in diagnostics, systemic therapies, and surgical recovery have improved the prognosis for these patients. Research is increasingly identifying MIBC patients, including those with positive nodes, who may achieve complete pathologic response and long-term survival, supporting the role of surgery even in advanced nodal stages. Managing MIBC with clinically positive lymph nodes, especially in N2-N3 disease, requires a tailored approach. While neoadjuvant chemotherapy followed by radical cystectomy is standard for N1 disease, the role of surgery in advanced nodal stages is growing because of better patient selection and treatment strategies. Emerging evidence suggests that consolidative surgery may improve outcomes in these complex cases.