Symposium 1 “Department-specific Treatment Strategies for Reflux Disease” — Introduction

2018 ◽  
Vol 69 (2) ◽  
pp. 83-83
Author(s):  
H. Kuwano ◽  
N. Oridate
2020 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Leandro C. D. Breda ◽  
Isabela G. Menezes ◽  
Larissa N. M. Paulo ◽  
Sandro Rogério de Almeida

Chromoblastomycosis (CBM) is a neglected, chronic, and progressive subcutaneous mycosis caused by different species of fungi from the Herpotrichiellaceae family. CBM disease is usually associated with agricultural activities, and its infection is characterized by verrucous, erythematous papules, and atrophic lesions on the upper and lower limbs, leading to social stigma and impacts on patients’ welfare. The economic aspect of disease treatment is another relevant issue. There is no specific treatment for CBM, and different anti-fungal drug associations are used to treat the patients. However, the long period of the disease and the high cost of the treatment lead to treatment interruption and, consequently, relapse of the disease. In previous years, great progress had been made in the comprehension of the CBM pathophysiology. In this review, we discuss the differences in the cell wall composition of conidia, hyphae, and muriform cells, with a particular focus on the activation of the host immune response. We also highlight the importance of studies about the host skin immunology in CBM. Finally, we explore different immunotherapeutic studies, highlighting the importance of these approaches for future treatment strategies for CBM.


2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.


Author(s):  
Sanne ten Hoorn ◽  
Dirkje W. Sommeijer ◽  
Faye Elliott ◽  
David Fisher ◽  
Tim R. de Back ◽  
...  

Abstract Background Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location. Methods Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively. Results When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75, P = 0.003 and HR 0.12, 95% CI 0.04–0.36, P < 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71, P = 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96, P = 0.034). Conclusions The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.


2015 ◽  
Vol 112 (3) ◽  
pp. 851-856 ◽  
Author(s):  
Mona Meyer ◽  
Jüri Reimand ◽  
Xiaoyang Lan ◽  
Renee Head ◽  
Xueming Zhu ◽  
...  

Glioblastoma (GBM) is a cancer comprised of morphologically, genetically, and phenotypically diverse cells. However, an understanding of the functional significance of intratumoral heterogeneity is lacking. We devised a method to isolate and functionally profile tumorigenic clones from patient glioblastoma samples. Individual clones demonstrated unique proliferation and differentiation abilities. Importantly, naïve patient tumors included clones that were temozolomide resistant, indicating that resistance to conventional GBM therapy can preexist in untreated tumors at a clonal level. Further, candidate therapies for resistant clones were detected with clone-specific drug screening. Genomic analyses revealed genes and pathways that associate with specific functional behavior of single clones. Our results suggest that functional clonal profiling used to identify tumorigenic and drug-resistant tumor clones will lead to the discovery of new GBM clone-specific treatment strategies.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3146
Author(s):  
Patricia Fernández-Nogueira ◽  
Gemma Fuster ◽  
Álvaro Gutierrez-Uzquiza ◽  
Pere Gascón ◽  
Neus Carbó ◽  
...  

Breast cancer (BrCa) is the leading cause of death among women worldwide, with about one million new cases diagnosed each year. In spite of the improvements in diagnosis, early detection and treatment, there is still a high incidence of mortality and failure to respond to current therapies. With the use of several well-established biomarkers, such as hormone receptors and human epidermal growth factor receptor-2 (HER2), as well as genetic analysis, BrCa patients can be categorized into multiple subgroups: Luminal A, Luminal B, HER2-enriched, and Basal-like, with specific treatment strategies. Although chemotherapy and targeted therapies have greatly improved the survival of patients with BrCa, there is still a large number of patients who relapse or who fail to respond. The role of the tumor microenvironment in BrCa progression is becoming increasingly understood. Cancer-associated fibroblasts (CAFs) are the principal population of stromal cells in breast tumors. In this review, we discuss the current understanding of CAFs’ role in altering the tumor response to therapeutic agents as well as in fostering metastasis in BrCa. In addition, we also review the available CAFs-directed molecular therapies and their potential implications for BrCa management.


2021 ◽  
Author(s):  
Yu Xiong ◽  
Jinyuan Hu ◽  
Chen Xuan ◽  
Jiayu Tian ◽  
Kaiyue Tan ◽  
...  

Abstract BackgroundLiver fibrosis develops from various chronic liver diseases, and there is currently a lack of specific treatment strategies. Yiqi Rougan decoction (YQRG) is a traditional Chinese medicine that has shown durative effects in the treatment of liver fibrosis; however, the mechanism associated with YQRG-related improvements in liver fibrosis remains to be experimentally determined. This study evaluated the therapeutic effect of YQRG on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and its molecular mechanism. MethodsWe used low-, medium-, and high-dose YQRG to treat CCl4-induced liver fibrosis in rats, followed by assessment of liver injury and fibrosis according to liver appearance, body weight, liver mass index, histopathologic examination, and serum testing. Additionally, we performed transcriptome analysis using RNA-sequencing (RNA-seq) technology, including cluster, Gene Ontology (GO), and pathway analyses, to identify differentially expressed genes (DEGs), and protein and gene expression were detected by immunofluorescence (IFC), western blot, and real-time quantitative PCR. ResultsThe results showed that YQRG effectively alleviated CCl4-induced liver injury and fibrosis in rats, including observations of improved liver function, decreased activity of hepatic stellate cells (HSCs), and decreased extracellular matrix (ECM) deposition. Moreover, we identified downregulated and upregulated DEGs in the model group relative to the control and YQRG-treated groups, with GO analysis revealing their enrichment in biological processes, such as endoplasmic reticulum stress (ERS), apoptosis, and autophagy. Furthermore, pathway analysis showed that YQRG treatment downregulated the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/AKT) signalling pathways and upregulated other signalling pathways, including those related to peroxisome proliferator-activated receptors(PPAR) and AMP-activated protein kinase(AMPK), with these finding subsequently verified experimentally. ConclusionThese findings showed that YQRG improved CCl4-induced liver fibrosis through multiple mechanisms and pathways, offering critical insight into the YQRG-related therapeutic mechanism and promoting further research into its potential application.


Author(s):  
Matthew J. Cummings ◽  
Barnabas Bakamutumaho ◽  
Nicholas Owor ◽  
John Kayiwa ◽  
Joyce Namulondo ◽  
...  

The global burden of sepsis is concentrated in sub-Saharan Africa, where extensive pathogen diversity and limited laboratory capacity challenge targeted antimicrobial management of life-threatening infections. In this context, established and emerging rapid pathogen diagnostics may stratify sepsis patients into subgroups with prognostic and therapeutic relevance. In a prospective cohort of adults (age ≥18 years) hospitalized with suspected sepsis in Uganda, we stratified patients using rapid diagnostics for HIV, tuberculosis (TB), malaria, and influenza, and compared clinical characteristics and 30-day outcomes across these pathogen-driven subgroups. From April 2017 to August 2019, 301 adults were enrolled (median age, 32 years [interquartile range, 26–42 years]; female, n = 178 [59%]). A total of 157 patients (53%) were HIV infected. Sixty-one patients (20%) tested positive for malaria, 52 (17%), for TB (including 49 of 157 [31%] HIV-infected patients), and 17 (6%), for influenza. Co-infection was identified in 33 (11%) patients. The frequency of multi-organ failure, including shock and acute respiratory failure, was greatest among patients with HIV-associated TB. Mortality at 30 days was 19% among patients with malaria, 40% among patients with HIV-associated TB, 32% among HIV-infected patients without microbiological evidence of TB, 6% among patients with influenza, and 11% among patients without a pathogen identified. Despite improvements in anti-retroviral delivery, the burden of sepsis in Uganda remains concentrated among young, HIV-infected adults, with a high incidence of severe HIV-associated TB. In parallel with improvements in acute-care capacity, use of rapid pathogen diagnostics may enhance triage and antimicrobial management during emergency care for sepsis in sub-Saharan Africa, and could be used to enrich study populations when trialing pathogen-specific treatment strategies in the region.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Susy Lam ◽  
Joseph Y Chu

BACKGROUND: An article published in Neurology Asia(2006;11:13-18) by Chu etal provided essential data to investigate whether specific genetic or environmental differences exist within the diabetic-Chinese stroke community. Insight into distinctive epidemiologic and cerebrovascular patterns will bring forth effectively focused treatment and prevention. From that basis, we hypothesized: Chinese who had stroke-history within 15 years are more commonly diabetic than Europeans, and Chinese more frequently have small vessels disease (SVD) than Europeans. METHODS: Patients seen during 2001-2011 at the Toronto Queensway Professional Center Neurology clinic and at William Osler Health System, Brampton Site, were investigated. Chinese diabetic stroke patients were selected by last name and birth country; similarly diagnosed European patients were age-sex matched correspondingly. Risk factors were acknowledged if patients were given explicit medical treatments. Otherwise, guideline values were obtained from the WHO criteria. Data was collected through screening patient charts for the following: diabetic prevalence through screening stroke patients (122 Chinese, 880 European) excluding TIAs, subarachnoid and subdural haemorrhages; etiology and stroke type comparison in patients with DM (48 Chinese, 127 European); risk factors differences between Chinese and Europeans with DM. Odds ratios and unpaired two-sample t-testing were used to confirm significance. RESULTS: Significance confirmed (P<0.05): Chinese had higher DM and stroke incidence than Europeans (28.7% vs. 23.2%). Diabetic Chinese more frequently had SVD (51.1% vs. 44.1%), specifically lacunar stroke (47.9% vs. 36.4%). The co-morbidity of SVD risk factors of hypertension, hyperlipidemia and overweight were more frequent in Chinese (Table 1.0). Furthermore, SVD frequency dominated over large vessels disease (LVD) in the Chinese (Table 1.1). Table 1.0 - RISK FACTOR INCIDENCE Overweight HBP HPL Chinese, SVD 26.9% 53.8% 36.5% European, SVD 16.5% 33.1% 23.6% OR Chinese/Euro.1.86 2.36 1.86 Table 1.1 - STROKE TYPE AND RISK Overweight, SVD Overweight, LVD Hyperlipidemia, SVD Hyperlipidemia, LVD Hypertension, SVD Hypertension, LVD : Chinese 26.9% 7.7% 36.5% 15.0% 53.8% 25.0% OR SVD/LVD 4.42 3.26 3.50 European 16.5% 7.9% 23.6% 15.0% 33.1% 26.0% OR SVD/LVD 2.32 1.76 1.41 CONCLUSIONS: Chinese with stroke are more frequently diabetic than Europeans. Diabetic Chinese are especially susceptible to small vessels disease and certain stroke risk factors are more frequent compared to the Europeans. Risk factor prevalence and stroke types differ considerably between Chinese and Europeans within Toronto, which may imply that specific treatment strategies are required to target towards each population.


2020 ◽  
Vol 12 ◽  
pp. 117957352090739 ◽  
Author(s):  
Konstantina G Yiannopoulou ◽  
Sokratis G Papageorgiou

Disease-modifying treatment strategies for Alzheimer disease (AD) are still under extensive research. Nowadays, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance: 3 cholinesterase inhibitors and memantine. To block the progression of the disease, therapeutic agents are supposed to interfere with the pathogenic steps responsible for the clinical symptoms, classically including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation. Other underlying mechanisms are targeted by neuroprotective, anti-inflammatory, growth factor promotive, metabolic efficacious agents and stem cell therapies. Recent therapies have integrated multiple new features such as novel biomarkers, new neuropsychological outcomes, enrollment of earlier populations in the course of the disease, and innovative trial designs. In the near future different specific agents for every patient might be used in a “precision medicine” context, where aberrant biomarkers accompanied with a particular pattern of neuropsychological and neuroimaging findings could determine a specific treatment regimen within a customized therapeutic framework. In this review, we discuss potential disease-modifying therapies that are currently being studied and potential individualized therapeutic frameworks that can be proved beneficial for patients with AD.


2009 ◽  
Vol 101 (02) ◽  
pp. 271-278 ◽  
Author(s):  
Veronique Fremeaux-Bacchi ◽  
Christoph Licht

SummaryMembranoproliferative glomerulonephritis (MPGN) is a chronic progressive renal disease that is diagnosed on the basis of renal histological features. Several MPGN subtypes have been defined by the localization and composition of glomerular deposits (electron dense, Ig and C3). MPGN II or dense deposit disease (DDD) which is defined by the occurrence of electron dense deposits within the lamina densa of the glomerular basement membrane (GBM) is strongly associated with dysregulation of the alternative complement pathway (AP). However, C3 Nephritic Factor (C3NeF), an autoantibody against the alternative C3 convertase C3bBb, and mutations in regulatory proteins of the AP have also been identified in other subtypes of MPGN and even in glomerulonephritis with mesangial C3 deposits. Clinically, MPGN is characterized by proteinuria (up to nephrotic range) and hypertension, frequent progression to end-stage kidney disease and disease recurrence after renal transplantation. The age of onset varies from childhood to adulthood. In the following we will review our current knowledge of pathogenesis of MPGN and will present a novel classification system of the disease based on pathogenesis rather than on morphology. A better understanding of the pathogenesis of MPGN is crucial for the development of novel, specific treatment strategies.


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