clinical challenge
Recently Published Documents


TOTAL DOCUMENTS

778
(FIVE YEARS 266)

H-INDEX

35
(FIVE YEARS 7)

2022 ◽  
Vol 15 (1) ◽  
pp. 88
Author(s):  
Renata Zajączkowska ◽  
Ewelina Rojewska ◽  
Agata Ciechanowska ◽  
Katarzyna Pawlik ◽  
Katarzyna Ciapała ◽  
...  

Neuropathic pain remains a difficult clinical challenge due to its diverse aetiology and complex pathomechanisms, which are yet to be fully understood. Despite the variety of available therapies, many patients suffer from ineffective pain relief; hence, the search for more efficacious treatments continues. The new gabapentinoid, mirogabalin has recently been approved for clinical use. Although its main mechanism of action occurs at the α2σ-1 and α2σ-2 subunits of calcium channels and is well documented, how the drug affects the disturbed neuropathic interactions at the spinal cord level has not been clarified, which is crucial information from a clinical perspective. The findings of our study suggest that several indirect mechanisms may be responsible for the beneficial analgesic effect of mirogabalin. This is the first study to report that mirogabalin enhances the mRNA expression of spinal antinociceptive factors, such as IL-10 and IL-18BP, and reduces the concentration of the pronociceptive substance P. Importantly, mirogabalin improves the morphine-, buprenorphine-, oxycodone-, and ketamine-induced antinociceptive effects in a neuropathic pain model. Our findings support the hypothesis that enhancing opioid and ketamine analgesia by combining these drugs with mirogabalin may represent a new strategy for the effective pharmacotherapy of neuropathic pain.


Author(s):  
Yi Sun ◽  
Lihua Tan ◽  
Zhaoqian Yao ◽  
Lujuan Gao ◽  
Ji Yang ◽  
...  

Limited options of antifungals and the emergence of drug resistance in fungal pathogens has been a multifaceted clinical challenge. Combination therapy represents a valuable alternative to antifungal monotherapy.


2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Chengcheng Xu ◽  
Meng Bao ◽  
Xiaorong Fan ◽  
Jin Huang ◽  
Changhong Zhu ◽  
...  

Abstract Background Intrauterine adhesion (IUA) is one of the leading causes of infertility and the main clinical challenge is the high recurrence rate. The key to solving this dilemma lies in elucidating the mechanisms of endometrial fibrosis. The aim of our team is to study the mechanism underlying intrauterine adhesion fibrosis and the origin of fibroblasts in the repair of endometrial fibrosis. Methods Our experimental study involving an animal model of intrauterine adhesion and detection of fibrosis-related molecules. The levels of molecular factors related to the endothelial-to-mesenchymal transition (EndMT) were examined in a rat model of intrauterine adhesion using immunofluorescence, immunohistochemistry, qPCR and Western blot analyses. Main outcome measures are levels of the endothelial marker CD31 and the mesenchymal markers alpha-smooth muscle actin (α-SMA) and vimentin. Results Immunofluorescence co-localization of CD31 and a-SMA showed that 14 days after moulding, double positive cells for CD31 and a-SMA could be clearly observed in the endometrium. Decreased CD31 levels and increased α-SMA and vimentin levels indicate that EndMT is involved in intrauterine adhesion fibrosis. Conclusions Endothelial cells promote the emergence of fibroblasts via the EndMT during the endometrial fibrosis of intrauterine adhesions.


2022 ◽  
Vol 12 ◽  
Author(s):  
Li Wang ◽  
Xiaomo Li ◽  
Yurong Cheng ◽  
Jing Yang ◽  
Si Liu ◽  
...  

HER2 amplification/overexpression is a common driver in a variety of cancers including gallbladder cancer (GBC). For patients with metastatic GBC, chemotherapy remains the standard of care with limited efficacy. The combination of HER2 antibody trastuzumab plus chemotherapy is the frontline treatment option for patients with HER2-positive breast cancer and gastric cancer. Recently, this regime also showed antitumor activity in HER2-positive GBC. However, resistance to this regime represents a clinical challenge. Camrelizumab is a novel PD-1 antibody approved for Hodgkin lymphoma and hepatocellular carcinoma in China. In this study, we presented a HER2-positive metastatic GBC patient who was refractory to trastuzumab plus chemotherapy but experienced significant clinical benefit after the addition of camrelizumab. Our case highlights the potential of immunotherapy in combination with HER2-targeted therapy in HER2-positive GBC. We also demonstrated that two immune-related adverse events (irAEs) associated with camrelizumab can be managed with an anti-VEGF agent apatinib. This case not only highlights the importance of irAE management in patients treated with camrelizumab, but also demonstrates the potential of PD-1 antibody plus trastuzumab in HER2-positive GBC patients who have developed resistance to chemotherapy and trastuzumab-based targeted therapy.


Author(s):  
Antoine Rousseau ◽  
Sonia Burrel ◽  
Julie Gueudry ◽  
Claire Deback ◽  
Oscar Haigh ◽  
...  
Keyword(s):  

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 25
Author(s):  
Marta R. Casanova ◽  
Rui L. Reis ◽  
Albino Martins ◽  
Nuno M. Neves

Peripheral nerve injury still remains a major clinical challenge, since the available solutions lead to dysfunctional nerve regeneration. Even though autologous nerve grafts are the gold standard, tissue engineered nerve guidance grafts are valid alternatives. Nerve growth factor (NGF) is the most potent neurotrophic factor. The development of a nerve guidance graft able to locally potentiate the interaction between injured neurons and autologous NGF would be a safer and more effective alternative to grafts that just release NGF. Herein, a biofunctional electrospun fibrous mesh (eFM) was developed through the selective retrieval of NGF from rat blood plasma. The neurite outgrowth induced by the eFM-NGF systems was assessed by culturing rat pheochromocytoma (PC12) cells for 7 days, without medium supplementation. The biological results showed that this NGF delivery system stimulates neuronal differentiation, enhancing the neurite growth more than the control condition.


Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6181
Author(s):  
Javier Bregante ◽  
Anna Schönbichler ◽  
Daniel Pölöske ◽  
Lina Degenfeld-Schonburg ◽  
Garazi Monzó Contreras ◽  
...  

Constitutive activation of FLT3 by ITD mutations is one of the most common genetic aberrations in AML, present in ~1/3 of cases. Patients harboring FLT3-ITD display worse clinical outcomes. The integration and advancement of FLT3 TKI in AML treatment provided significant therapeutic improvement. However, due to the emergence of resistance mechanisms, FLT3-ITD+ AML remains a clinical challenge. We performed an unbiased drug screen to identify 18 compounds as particularly efficacious against FLT3-ITD+ AML. Among these, we characterized two investigational compounds, WS6 and ispinesib, and two approved drugs, ponatinib and cabozantinib, in depth. We found that WS6, although not yet investigated in oncology, shows a similar mechanism and potency as ponatinib and cabozantinib. Interestingly, ispinesib and cabozantinib prevent activation of AXL, a key driver and mechanism of drug resistance in FLT3-ITD+ AML patients. We further investigated synergies between the selected compounds and found that combination treatment with ispinesib and cabozantinib or ponatinib shows high synergy in FLT3-ITD+ AML cell lines and patient samples. Together, we suggest WS6, ispinesib, ponatinib and cabozantinib as novel options for targeting FLT3-ITD+ AML. Whether combinatorial tyrosine kinase and kinesin spindle blockade is effective in eradicating neoplastic (stem) cells in FLT3-ITD+ AML remains to be determined in clinical trials.


Author(s):  
Sizhen Wang ◽  
Jie Li ◽  
Zhiqiang Ma ◽  
Linhong Sun ◽  
Lei Hou ◽  
...  

As a severe clinical challenge, escharotomy and infection are always the core concerns of deep burn injuries. However, a usual dressing without multifunctionality leads to intractable treatment on deep burn wounds. Herein, we fabricated a sequential therapeutic hydrogel to solve this problem. Cross-linked by modified polyvinyl alcohol (PVA-SH/ε-PL) and benzaldehyde-terminated F127 triblock copolymers (PF127-CHO), the hydrogel demonstrated excellent mechanical properties, injectability, tissue adhesiveness, antibacterial activity, biocompatibility, and satisfactory wound cleaning through both in vitro and in vivo assays. Additionally, based on the conception of “sequential therapy,” we proposed for the first time to load bromelain and EGF into the same hydrogel in stages for wound cleaning and healing. This work provides a strategy to fabricate a promising wound dressing for the treatment of deep burn wounds with injectability and improved patients’ compliance as it simplified the process of treatment due to its “three in one” characteristic (antibacterial activity, wound cleaning, and healing effects); therefore, it has great potential in wound dressing development and clinical application.


2021 ◽  
pp. 028418512110558
Author(s):  
Pan Yang ◽  
Yajie Tang ◽  
Hongying Wang ◽  
Xiangxiang Zhang ◽  
Boyang Yang

Background Early diagnosis of biliary atresia (BA) is an important clinical challenge. Purpose To summarize the latest diagnostic performance of different ultrasonic (US) features for BA. Material and Methods MeSH terms “biliary atresia” and “ultrasonography” and related hyponyms were used to search PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Eligible articles were included and data were retrieved. The methodologic quality was assessed by version 2 of the Quality Assessment of Diagnostic Accuracy Studies tool. Estimated sensitivity and specificity of each US feature were calculated by Stata 14.0. Results Fifty eligible studies on 5622 patients were included. Respective summary sensitivity and specificity were 77% (95% CI=69–84) and 98% (95% CI=96–99) for triangular cord sign (TCS) in 32 studies, 86% (95% CI=78–92) and 86% (95% CI=72–94) for shear wave elastography (SWE) in seven studies, 75% (95% CI=65–83) and 92% (95% CI=86–95) for gallbladder and biliary system abnormality (GBA) in 25 studies, and 81% (95% CI=69–90) and 79% (95% CI=67–87) for hepatic artery (HA) enlargement in seven studies. The overall US features from 11 studies yielded a summary sensitivity of 84% (95% CI=72–92) and specificity of 86% (95% CI=77–92). Conclusion TCS and GBA were the two most widely accepted US features currently used for differential diagnosis of BA. The newly developed SWE was an objective and convenient method with good diagnostic performance. HA enlargement can be used as an auxiliary sign.


2021 ◽  
Vol 32 ◽  
pp. S1395
Author(s):  
D. Martínez Bedoya ◽  
R. Gustave ◽  
F. Corlazzoli ◽  
V. Dutoit ◽  
D. Migliorini
Keyword(s):  

Sign in / Sign up

Export Citation Format

Share Document