Efficacy Of Treatment Research Articles

Clinicopathologic features, demographics, disease burden, and therapeutics in alopecic sarcoidosis: a case series and systematic review.

Alopecic sarcoidosis is an uncommon cutaneous manifestation of sarcoidosis. Scarring and nonscarring alopecic sarcoidosis have been reported; however, information on the epidemiology, systemic disease associations, and treatment efficacy is limited. To address these gaps, we conducted a retrospective chart review and systematic literature review of alopecic sarcoidosis cases. Full-text English publications from PubMed, Scopus, and Google Scholar from inception to August 2023 were analyzed. Treatment evidence quality was assessed using the modified Oxford Centre for Evidence-Based Medicine rating scale. Three patients with biopsy-proven alopecic sarcoidosis were included as a case series, all demonstrating systemic sarcoidosis and 2 requiring multiple therapies. Among 1778 search results, 60 articles representing 77 cases of alopecic and scalp sarcoidosis were included. Patients were categorized into 4 distinct alopecic subgroups. Black patients constituted the majority of all subgroups. Extracutaneous sarcoidosis burden was high across all alopecic subgroups, with ocular disease appearing overrepresented. Topical and oral corticosteroids were the main treatments. Though scarring alopecia patients had poor outcomes despite receiving immunomodulators/cx, limited data suggest potential efficacy of tumor necrosis factor-alpha inhibitors. This study has a small sample size. Our findings underscore the importance of evidence-based strategies for improving alopecic sarcoidosis management. Prompt diagnosis and systemic evaluation, especially for scarring alopecia, are essential for timely intervention to optimize patient outcomes.

Identifying and Evaluating Biological Markers of Postherpetic Neuralgia: A Comprehensive Review.

Postherpetic neuralgia (PHN) manifests as persistent chronic pain that emerges after a herpes zoster outbreak and greatly diminishes quality of life. Unfortunately, its treatment efficacy has remained elusive, with many therapeutic efforts yielding less than satisfactory results. The research to discern risk factors predicting the onset, trajectory, and prognosis of PHN has been extensive. However, these risk factors often present as nonspecific and diverse, indicating the need for more reliable, measurable, and objective detection methods. The exploration of potential biological markers, including hematological indices, pathological insights, and supportive tests, is increasing. This review highlights potential biomarkers that are instrumental for the diagnosis, management, and prognosis of PHN while also delving deeper into its genesis. Drawing from prior research, aspects such as immune responsiveness, neuronal injury, genetic makeup, cellular metabolism, and pain signal modulation have emerged as prospective biomarkers. The immune spectrum spans various cell subtypes, with an emphasis on T cells, interferons, interleukins, and other related cytokines. Studies on nerve injury are directed toward pain-related proteins and the density and health of epidermal nerve fibers. On the genetic and metabolic fronts, the focus lies in the detection of predisposition genes, atypical protein manifestations, and energy-processing dynamics, with a keen interest in vitamin metabolism. Tools such as functional magnetic resonance imaging, electromyography, and infrared imaging have come to the forefront in the pain signaling domain. This review compiles the evidence, potential clinical implications, and challenges associated with these promising biomarkers, paving the way for innovative strategies for predicting, diagnosing, and addressing PHN.

Efficacy and Feasibility of Web-Based ACT-Enhanced Behavioral Treatment for Skin Picking in Adults: A Randomized Waitlist-Controlled Trial

Skin picking disorder is a chronic repetitive condition that impacts daily functioning and causes significant distress. Acceptance and commitment therapy (ACT) enhanced behavioral training (A-EBT) has shown promise in targeting skin picking symptoms but is not widely disseminated among providers. This study examines the efficacy and feasibility of an eight-week fully-automated online A-EBT program for skin picking disorder. Participants with skin picking disorder (N = 84) were randomized into either an online intervention (n = 43) or a waitlist control (n = 41). All participants completed self-report assessments at baseline, mid-, post-intervention, and 1-month follow-up. Analyses used multilevel linear modeling with the full intent-to-treat sample. Results demonstrated statistically stronger improvements from baseline to 1-month follow-up in the intervention condition compared to waitlist for skin picking symptoms (SMD=0.90), skin picking-related psychological flexibility (SMD=-0.82), and well-being (SMD=-0.31), with no significant effects on distress. Treatment effects were maintained at one-month follow-up, with 29.0% of intervention participants meeting responder status, compared to 0.1% of waitlist participants. High usability and acceptability scores provide preliminary evidence of its feasibility as a fully automated intervention. These findings suggest an automated online A-EBT program may be an effective and scalable treatment for individuals with skin picking disorder.

Inhibition of the Rho/MRTF pathway improves the response of BRAF-resistant melanoma to PD1/PDL1 blockade.

Metastatic cutaneous melanoma is a fatal skin cancer. Resistance to targeted and immune therapies limits the benefits of current treatments. Identifying and adding anti-resistance agents to current treatment protocols can potentially improve clinical responses. Myocardin-related transcription factor (MRTF) is a transcriptional coactivator whose activity is indirectly regulated by actin and the Rho family of GTPases. We previously demonstrated that development of BRAF inhibitor (BRAFi) resistance frequently activates the Rho/MRTF pathway in human and mouse BRAFV600E melanomas. In clinical trials, pretreatment with BRAFi reduces the benefit of immune therapies. We aimed to test the efficacy of concurrent treatment with our MRTF pathway inhibitor CCG-257081 and anti-PD1 in vivo and to examine its effects on the melanoma immune microenvironment. Because MRTF pathway activation upregulates the expression of immune checkpoint inhibitor genes/proteins, we asked whether CCG-257081 can improve the response to immune checkpoint blockade. CCG-257081 reduced the expression of PDL1 in BRAFi-resistant melanoma cells and decreased surface PDL1 levels on both BRAFi-sensitive and -resistant melanoma cells. Using our recently described murine vemurafenib-resistant melanoma model, we found that CCG-257081, in combination with anti-PD1 immune therapy, reduced tumor growth and increased survival. Moreover, anti-PD1/CCG-257081 co-treatment increased infiltration of CD8+ T cells and B cells into the tumor microenvironment and reduced tumor-associated macrophages. Here, we propose CCG-257081 as an anti-resistance and immune therapy-enhancing anti-melanoma agent.

CYSTOID MACULAR EDEMA IN BIRDSHOT RETINOCHOROÏDITIS: Long-Term Treatment Study in 142 Patients.

To assess the long-term efficacy and safety of treatments for cystoid macular edema in birdshot retinochoroïditis. Observational retrospective study of 142 HLA-A29-positive patients with cystoid macular edema; the main outcome was the optical coherence tomography intraretinal cysts resolution. During the mean follow-up of 75 months (12-178), 61.3% of patients were successfully treated using 1 to 3 treatment steps, while the others needed more steps. At 6 months, there were no significant effects on ME for anti-TNF (tumor necrosis factor) and IVIg (immunoglobulin) in contrast to antimetabolites (OR 1.98), systemic GCS (glucocorticosteroids), CsA (cyclosporine A) and tocilizumab (odds ratio closed to 2.7), intraocular injected GCS (odds ratio of 4.2), and interferon (odds ratio of 4.4). The percentages of therapeutic success trend to decrease from the initial three treatment steps to the subsequent treatment steps, for systemic GCS (84% to 70%), for anti-TNF (42% to 33%), and for CsA (71% to 33%); the success percentages did not decrease for injected GCS (83% to 89%). Macular edema recurrence occurred with the highest percentage for injected GCS (86.8%, P = 0.01) and the lowest for tocilizumab (10.5%, P = 0.001). Interferons-α and tocilizumab were associated with the lowest prednisone daily doses. The classical uveitic cystoid macular edema therapeutic algorithm could be adapted to birdshot retinochoroïditis.

Efficacy and safety of different pharmacological interventions in the treatment of tardive dyskinesia: a systematic review and network meta-analysis.

The aim of this study is to indirectly compare and rank the different drugs that have been studied in randomized clinical trials (RCTs) in patients with tardive dyskinesia (TD) in terms of their efficacy in ameliorating the symptoms of TD and safety. A network meta-analysis and a systematic review were registered prospectively on PROSPERO under the ID: CRD42023407823 and were conducted in accordance with the PRISMA-NMA guidelines. PubMed, Scopus, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Sciences, and Clinicaltrials.gov were searched to identify relevant records. Any parallel randomized blinded controlled clinical trials that studied the use of any medications in treating TD and assessed the symptoms using a functional scale that has been previously validated. The standardized mean difference of improvement along with the reported adverse events for each drug was extracted from each trial, and a network meta-analysis was conducted using a random-effects model. One thousand eight hundred seventeen patients in 33 RCTs were included in the analysis. Twenty-three different drugs were compared to placebo in terms of reduction in TD symptoms. Among these, valbenazine 80mg (SMD = - 1.66, 95%CI = [- 2.55; - 0.78]), valbenazine 40mg (- 1.00, [- 1.89; - 0.11]), and vitamin E (- 0.77, [- 1.45; - 0.1]) significantly reduced TD symptoms in comparison to placebo, while deutetrabenazine 36mg (- 1.00, [- 2.12; 0.11]) and reserpine (- 0.54, [- 1.09; 0.02]) did not significantly reduce symptoms. Some serious adverse events were reported for valbenazine and deutetrabenazine, which included mainly psychiatric symptoms such as depression, worsening of schizophrenia, and suicidal ideation, while mild adverse events were reported for other drugs, and their incidence in the treatment arms was comparable to those in the placebo arm. Valbenazine (80 and 40mg) and vitamin E demonstrated efficacy in treating tardive dyskinesia. However, the significant side effects of valbenazine should prompt further investigation of alternative treatment modalities.

Assessing factors of adherence and efficacy: A randomized controlled trial of a fully automated self-help A-EBT website.

Treatment for trichotillomania is notably limited, preventing suffering individuals from having access to treatment. To address this need, researchers have developed and tested asynchronous online interventions for adults with trichotillomania. A factor that may impact the efficacy of these programs is the use of phone check-ins (or similar coaching support) to improve treatment adherence in website treatment delivery. In the current study we evaluated the role of check-ins on treatment adherence and efficacy of a website delivering acceptance and commitment therapy-enhanced behavior therapy (A-EBT). A sample of 101 adults with trichotillomania were randomly assigned to an A-EBT web-based intervention with or without phone check-in support. Adherence to the web-based program was not significantly improved by check-ins and treatment outcomes did not vary by condition (with or without check-ins). However, adherence to the program across conditions, did predict treatment outcomes. The program was found to be effective at decreasing trichotillomania symptom severity and improving trichotillomania specific psychological inflexibility over time across check-in conditions. Our findings suggest that check-ins did not improve adherence to or efficacy of the program, thus supporting recent literature suggesting that check-ins do not necessarily improve program adherence.

Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review of the last decade.

Recurrent/metastatic adenoid cystic carcinoma (R/M AdCC) presents a clinical challenge with limited treatment options, particularly in the face of unsatisfactory efficacy from current therapeutic approaches. This review underscores the unmet clinical needs in managing R/M AdCC, emphasising the imperative for novel therapeutic strategies to address this critical gap. The primary objective of this review is to comprehensively analyse and assess trials investigating therapeutic approaches for R/M AdCC. Emphasis is placed on endpoints such as tumour response rates and progression-free survival. The specific interventions, populations, and outcomes examined in these trials will be detailed to provide a focused and informative systematic review. The systematic search spanned databases, including PubMed, EMBASE, and the Cochrane database of systematic reviews. Employing terms like "Carcinoma, Adenoid Cystic" and "trial," the search focused on English full-text articles from April 1, 2010, to August 9, 2023. Inclusion criteria encompassed studies with patients having R/M AdCC, involving drug interventions. Study quality was assessed using the Newcastle-Ottawa Scale for retrospective studies, Cochrane ROBINS-I tool for non-randomised trials, and the ROB-2 tool for randomised controlled trials. A total of 46 trials involving 1244 patients are included in this review, encompassing a variety of therapeutic approaches for R/M AdCC. Targeted therapies, particularly Apatinib at 500 mg, exhibit efficacy with a 47.1% objective response rate (ORR). Conversely, immunotherapeutic agents demonstrate suboptimal performance, with an overall ORR ranging from 0 to 18%. While Apatinib shows promise, the review underscores the imperative for a thorough exploration of drugs targeting unique mechanisms in the immunologically cold nature of R/M AdCC. Substantial progress in systemic therapy for R/M AdCC is evident, driven by early-phase clinical trials, particularly with promising outcomes in VEGF-2 inhibitors. However, challenges persist, notably in immunotherapy due to the cancer's immunologically cold nature. Ongoing research, prioritising early-stage trials, is crucial, emphasising exploration of emerging therapies like cell therapy and antibody-drug conjugates. Transitioning to Phase III trials is essential for more precise therapeutic insights. Collaborative efforts and a focus on personalised precision medicine are vital for overcoming challenges and advancing our understanding of treatment efficacy in this rare cancer.

A Novel Deep Learning Model for Drug-drug Interactions.

Drug-drug interactions (DDIs) can lead to adverse events and compromised treatment efficacy that emphasize the need for accurate prediction and understanding of these interactions. In this paper, we propose a novel approach for DDI prediction using two separate message-passing neural network (MPNN) models, each focused on one drug in a pair. By capturing the unique characteristics of each drug and their interactions, the proposed method aims to improve the accuracy of DDI prediction. The outputs of the individual MPNN models combine to integrate the information from both drugs and their molecular features. Evaluating the proposed method on a comprehensive dataset, we demonstrate its superior performance with an accuracy of 0.90, an area under the curve (AUC) of 0.99, and an F1-score of 0.80. These results highlight the effectiveness of the proposed approach in accurately identifying potential drugdrug interactions. The use of two separate MPNN models offers a flexible framework for capturing drug characteristics and interactions, contributing to our understanding of DDIs. The findings of this study have significant implications for patient safety and personalized medicine, with the potential to optimize treatment outcomes by preventing adverse events. Further research and validation on larger datasets and real-world scenarios are necessary to explore the generalizability and practicality of this approach.

The Role of Intracellular and Extracellular Vesicles in the Development of Therapy Resistance in Cancer.

Cancer is the second leading cause of global mortality and claims approximately 10 million lives annually. Despite advances in treatments such as surgery, chemotherapy, and immunotherapy, resistance to these methods has emerged. Multidrug resistance (MDR), where cancer cells resist diverse treatments, undermines therapy effectiveness, escalating mortality rates. MDR mechanisms include, among others, drug inactivation, reduced drug uptake, enhanced DNA repair, and activation of survival pathways such as autophagy. Moreover, MDR mechanisms can confer resistance to other therapies like radiotherapy. Understanding these mechanisms is crucial for improving treatment efficacy and identifying new therapeutic targets. Extracellular vesicles (EVs) have gathered attention for their role in cancer progression, including MDR development through protein transfer and genetic reprogramming. Autophagy, a process balancing cellular resources, also influences MDR. The intersection of EVs and autophagy further complicates the understanding of MDR. Both extracellular (exosomes, microvesicles) and intracellular (autophagic) vesicles contribute to therapy resistance by regulating the tumor microenvironment, facilitating cell communication, and modulating drug processing. While much is known about these pathways, there is still a need to explore their potential for predicting treatment responses and understanding tumor heterogeneity.

Current strategies for nonalcoholic fatty liver disease treatment (Review).

Nonalcoholic fatty liver disease (NAFLD), the most common chronic hepatic disease, has become a leading health problem worldwide. The present review summarized the methods and mechanisms to treat NAFLD, including the Mediterranean diet, physical activity and exercise, bariatric surgery and specific therapeutic agents, including statins, peroxisome proliferator‑activated receptor agonists, cenicriviroc and farnesoid X receptor agonists. Biologically active substances, such as peptides, alkaloids, polyphenolic compounds, silymarin, antibiotics, fatty acids, vitamins, probiotics, synbiotics and lamiaceae have also demonstrated actions that combat NAFLD. Considering their different mechanisms of action, combining some of them may prove an efficacious treatment for NAFLD. In this light, the present review describes recent progress and future prospects in treating NAFLD.

SEfficacy and safety of apatinib in the treatment of patients with platinum‑resistant ovarian cancer: A systematic review and network meta‑analysis.

At present, the optimal therapeutic approach for the treatment of platinum-resistant recurrent ovarian cancer remains to be fully elucidated. The present systematic review and network meta-analysis aimed to elucidate the relative efficacy and safety of apatinib, administered either as monotherapy or in conjunction with chemotherapy, compared with chemotherapy alone, for the treatment of platinum-resistant recurrent ovarian cancer. The PubMed, Embase and Wanfang Data electronic databases were searched, where the search spanned from the conception of the databases until April 2023. A quality evaluation was conducted and R software was used for network meta-analysis. Following inclusion and exclusion criteria screening, the present analysis included 17 clinical trials, combining data from 1,228 patients with platinum-resistant recurrent ovarian cancer categorized into the following three treatment cohorts: i) 555 patients who received apatinib plus chemotherapy; ii) 229 patients who received apatinib alone; and iii) 444 patients who underwent conventional chemotherapy. Results of the present study demonstrated that the co-administration of apatinib with either tegiol [odds ratio (OR), 2.54; 95% CI, 1.06-6.11] or etoposide (OR, 2.12; 95% CI, 1.20-3.74) significantly improved the objective response rate (ORR) compared with that following apatinib monotherapy. By contrast, gemcitabine monotherapy resulted in inferior ORR efficacy compared with that following apatinib (OR, 0.47; 95% CI, 0.23-0.95). In addition, combinations of apatinib with etoposide (OR, 1.32; 95% CI, 1.06-1.64) or paclitaxel (OR, 1.52; 95% CI, 1.04-2.23) demonstrated a significantly improved disease control rates (DCR) compared with those following apatinib alone. According to the area under the cumulative ranking analysis, apatinib and paclitaxel in combination was the most efficacious treatment modality in terms of DCR. In terms of safety, the incidence of adverse events, such as hand-foot syndrome [relative risk (RR), 4.23; 95% CI, 1.80-9.95] and hypertension (RR, 4.80; 95% CI, 1.53-15.05), was found to be significantly higher in patients treated with apatinib-containing therapies, compared with those treated with chemotherapy alone. Consequently, the present meta-analysis highlighted the potential of apatinib, particularly in combination with chemotherapy, as a therapeutic strategy for patients with platinum-resistant recurrent ovarian cancer.

Genetic association of SLC6A3 (dopamine transporter) gene polymorphisms with personality disorders and substance abuse disorders: a systematic review and meta-analysis.

Personality disorders (PD) are characterized by socially dysfunctional behavioral patterns that affect patients and show higher incidence rates within families. Substance abuse disorders (SAD) are exemplified by extensive and prolonged use of substances, including alcohol, nicotine, or illegal drugs. Genetic predisposition for both PD and SAD has been reported to involve gene variants regulating dopaminergic pathways. Yet, discrepancy among reported results necessitates further elucidation of potential hereditary-related risk factors. Because both disorders impose a societal burden, knowledge on the impact of certain genetic backgrounds on these diseases could help develop evidence-based strategies for efficacious treatment approaches. In the present study a systematic review was performed, and the association between dopamine transporter gene polymorphism (SLC6A3), particularly rs28363170 entailing a 40-bp variable number tandem repeat, and PD as well as SAD was investigated recruiting meta-analysis approach. Initial literature search for PD yielded 1577, from which nine fulfilled eligibility criteria to be used in a meta-analysis including 729 cases and 2113 controls. From the 934 studies retrieved for SAD, only 29 articles with 5221 cases and 4822 controls were used for meta-analysis. A statistically significant association was seen between rs28363170 (for the 9-repeat allele) and PD in European populations according to the co-dominant mode of inheritance. For SAD no statistically significant correlation under any mode of inheritance was observed. There was no indication of time-trend phenomena. Our findings demonstrate the association of SLC6A3 gene polymorphism with PD, thus underling the need to understand neurobiological mechanisms inherent to the above disorders to guide treatment strategies under the perspective of personalized medicine.

A Component of Mindfulness: Attention

The use of mindfulness-based interventions in many areas is increasing day by day. Having knowledge of the components of mindfulness is also important to know the mechanisms in which mindfulness-based interventions are effective. This study has aimed to examine potential attentional mechanisms of mindfulness. In this context, mindfulness has been defined and attention and attention models have been briefly discussed in the study. Then, the relationship between mindfulness and attention has been examined, and previous research findings examining mindfulness and attention are included. The studies on attention and mindfulness seem to have more inconsistent results when conducted with adults, whereas the studies in adolescents and children seem to have more consistent results revealing that mindfulness-based interventions improve the attentional skills of the youth. Knowing the relationship between mindfulness and attention will aid to maximize the efficacy of mindfulness-based interventions and it will be a crucial step in identifying the people that might benefit from mindfulness-based interventions

Effects of Transjugular Intrahepatic Portosystemic Shunt on Renal and Pulmonary Function in Hepatic Decompensation with and without Hepatorenal and Hepatopulmonary Syndromes: A Review.

Cirrhosis is often characterized by decreased liver function, ranging from a compensated, typically asymptomatic phase to a decompensated phase characterized by the appearance of ascites or variceal bleeding, and ultimately hepatorenal syndrome (HRS) or hepatopulmonary syndrome (HPS). The latter two complications are associated with a poor prognosis and limited treatment efficacy. In cases of ascites or variceal bleeding resistant to medical therapy, transjugular intrahepatic portosystemic shunt (TIPS) is effective and safe. Shunting blood by TIPS diverts portal blood to the systemic circulation, potentially increasing systemic blood volume and benefiting renal function. However, TIPS could also divert nitric oxide to the systemic circulation, potentially worsening systemic hypotension and perfusion, which could be detrimental to renal function. Available evidence indicates that TIPS often improves renal function in patients with portal hypertension, with or without HRS. No studies have shown persistently decreased renal function after TIPS. However, these data are insufficient to support a recommendation for the use of TIPS specifically for HRS. In patients without pre-existing HPS, TIPS does not appear to significantly affect pulmonary gas exchange. Results of TIPS in HPS have been inconsistent; some studies have shown improvement, but effects were transient. No studies have shown a persistent decline in pulmonary function after TIPS. The evidence supports the need for large randomized controlled trials to investigate the beneficial effects of TIPS for HRS. Similar pulmonary function data are less clear regarding TIPS for HPS. The aim of the current report was to review the literature regarding the effects of TIPS on renal and pulmonary function in hepatic decompensation, with or without the development of HRS or HPS.

Влияние распространенных бактериальных инфекций на индекс фрагментации ДНК сперматозоидов. Обзор литературы

Sperm DNA fragmentation is an important factor in male infertility, miscarriage and unsuccessful ART cycles. The purpose of thisreview wasto summarize and briefly analyze the available data on the effect of common infections of the male genitourinary tract on sperm DNA fragmentation (SDF), the mechanisms of their influence, efficacy and outcomes of treatment. Based on the results of these studies, it can be said that Chlamydia trachomatis, Ureaplasma spp. and Mycoplasma genitalium have a significant effect and lead to a pronounced increase in SDF. The effect of opportunistic bacteria on SDF depends on the type of microorganisms, their diversity and quantity. The presence of certain bacteria is associated with higher levels of ,some are presumably associated with beneficial effects and lower levels of SDF. Candidiasis can presumably affect SDF, but the available data are insufficient for an accurate answer. Treatment ofsuch infectionsleads to a decrease in sperm DNA fragmentation index, an increase in the effectiveness of ART and spontaneous pregnancy rates. Keywords: sperm DNA fragmentation, infection, male infertility, oxidative stress, fertility, semen analysis, sperm, sperm chromatin.

Multi-arm multi-stage survival trial design with arm-specific stopping rule

ABSTRACT Traditional two-arm randomized trial designs have played a pivotal role in establishing the efficacy of medical interventions. However, their efficiency is often compromised when confronted with multiple experimental treatments or limited resources. In response to these challenges, the multi-arm multi-stage designs have emerged, enabling the simultaneous evaluation of multiple treatments within a single trial. In such an approach, if an arm meets efficacy success criteria at an interim stage, the whole trial stops and the arm is selected for further study. However when multiple treatment arms are active, stopping the trial at the moment one arm achieves success diminishes the probability of selecting the best arm. To address this issue, we have developed a group sequential multi-arm multi-stage survival trial design with an arm-specific stopping rule. The proposed method controls the familywise type I error in a strong sense and selects the best promising treatment arm with a high probability.

A Prospective Study on Different Doses of Gammaglobulin Plus Aspirin in the Pediatric Kawasaki Disease and the Impacts on CRP and WBC Levels

Abstract Objective To evaluate the efficacy of different doses of gammaglobulin combined with aspirin in treating pediatric Kawasaki disease and its impact on C-reactive protein (CRP) and white blood cell (WBC) levels. Methods A prospective study was conducted with 150 children (3groups) diagnosed with Kawasaki disease. Group A received a higher dose of intravenous gammaglobulin (2.5 g/kg) combined with aspirin, Group B received a standard dose of intravenous gammaglobulin (2 g/kg) combined with aspirin, and Group C received a lower dose of intravenous gammaglobulin (1 g/kg) combined with aspirin. All groups received oral aspirin therapy (30 mg/kg/day) for a standard duration. The time to symptom improvement, treatment efficacy, laboratory parameters, and adverse reactions were monitored and analyzed. Results Group B showed a shorter time to symptom relief compared to Groups A and C, particularly in fever reduction, mucosal congestion, cervical lymph node enlargement, and limb symptoms. The total effective rate was higher in Group B compared to Groups A and C. Group B showed improvements in WBC, CRP, ESR, and PLT levels. Conclusion Standard-dose intravenous gammaglobulin combined with aspirin was more effective in treating pediatric Kawasaki disease compared to higher and lower doses. The treatment regimen in Group B resulted in shorter time to symptom relief, higher total effective rate, improved biochemical markers. Incidence of adverse reactions was similar among the three groups, demonstrating the safety of standard dosage.

Miniaturized protein profiling permits targeted signaling pathway analysis in individual circulating tumor cells to improve personalized treatment

BackgroundTraditional genomic profiling and mutation analysis of single cells like Circulating Tumor Cells (CTCs) fails to capture post-translational and functional alterations of proteins, often leading to limited treatment efficacy. To overcome this gap, we developed a miniaturized ‘protein analysis on the single cell level’ workflow—baptized ZeptoCTC. It integrates established technologies for single-cell isolation with sensitive Reverse Phase Protein Array (RPPA) analysis, thus enabling the comprehensive assessment of multiple protein expression and activation in individual CTCs.MethodsThe ZeptoCTC workflow involves several critical steps. Firstly, individual cells are labeled and isolated. This is followed by cell lysis and the printing of true single cell lysate preparations onto a ZeptoChip using a modified micromanipulator, CellCelector™. The printed lysates then undergo fluorescence immunoassay RPPA protein detection using a ZeptoReader. Finally, signal quantification is carried out with Image J software, ensuring precise measurement of multiple protein levels.ResultsThe efficacy of ZeptoCTC was demonstrated through various applications. Initially, it was used for measuring EpCAM protein expression, a standard marker for CTC detection, revealing higher levels in single MCF-7 over MDA-MB-231 tumor cells. Furthermore, in Capivasertib (Akt-inhibitor)-treated MCF-7 single cells, ZeptoCTC detected a 2-fold increase in the pAkt/Akt ratio compared to control cells, and confirmed co-performed bulk-cell western blot analysis results. Notably, when applied to individual CTCs from metastasized breast cancer patients, ZeptoCTC revealed significant differences in protein activation levels, particularly in measured pAkt and pErk levels, compared to patient-matched WBCs. Moreover, it successfully differentiated between CTCs from patients with different Akt1 genotypes, highlighting its potential to determine the activation status of druggable cancer driving proteins for individual and targeted treatment decision making.ConclusionsThe ZeptoCTC workflow represents a valuable tool in single cell cancer research, crucial for personalized medicine. It permits detailed analysis of key proteins and their activation status of targeted, cancer-driven signaling pathways in single cell samples, aiding in understanding tumor response, progression, and treatment efficacy beyond bulk analysis. The method significantly advances clinical investigations in cancer, improving treatment precision and effectiveness. The workflow will be applicable to protein analysis on other types of single cells like relevant in stem cell, neuropathology and hemopoietic cell research.

Validation of a deep learning model for automatic detection and quantification of five OCT critical retinal features associated with neovascular age-related macular degeneration

PurposeTo develop and validate a deep learning model for the segmentation of five retinal biomarkers associated with neovascular age-related macular degeneration (nAMD).Methods300 optical coherence tomography volumes from subject eyes with...