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21.
Liam Masterson James Howard Jazmina Gonzalez-Cruz Christopher Jackson Catherine Barnett Lewis Overton Howard Liu Rahul Ladwa Fiona Simpson Margie McGrath Ben Wallwork Terry Jones Christian Ottensmeier Melvin L.K. Chua Chris Perry Rajiv Khanna Benedict Panizza Sandro Porceddu Matt Lechner 《International journal of cancer. Journal international du cancer》2020,146(8):2305-2314
Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules. 相似文献
22.
《European annals of otorhinolaryngology, head and neck diseases》2020,137(1):47-51
Endolymphatic hydrops features excess endolymph in the membranous labyrinth, and is a marker of Menière's disease. Between the early 1980s and late 2000s, MRI in Menière's disease aimed purely to rule out tumor or malformation as differential diagnoses for the pressure disorder. Progress in high-resolution MRI, however, now enables excess endolymph to be visualized in the membranous labyrinth, differentiating saccule and utricle in Menière's disease and in other clinical presentations such as cochleovestibular schwannoma. More recently, non-visibility of the saccule was demonstrated in a subgroup of Menière's disease patients, and utricle atelectasis in case of uni- or bilateral vestibular areflexia. Endolymph quantification remains highly controversial in terms of grading approach, but a simple semiology based on excess or deficient visualization of endolymph according to the compartment sheds light on the pathophysiological mechanisms of cochleovestibular disorder and may in future allow effective monitoring of medical and surgical treatment. 相似文献
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《Foot and Ankle Surgery》2020,26(2):193-197
BackgroundThe aim of this study was to compare the radiographic and functional results between fixation and non-fixation in the Cotton osteotomy for the treatment of adult acquired flatfoot.MethodsA retrospective, case-controlled study of consecutive stage IIB posterior tibial tendon dysfunction (PTTD) patients treated with the same bony reconstructive surgery including cotton osteotomy between 2013 and 2017. Meary’s angle, the medial arch sag angle (MASA), and medial cuneiform cobb angle (MCCA) were evaluated pre-operation, at first weight bearing after surgery, and 12 months post operation.ResultsForty feet were included in the study. The cotton osteotomy utilized screw fixation (n = 20) or non-fixation technique (n = 20). No significant differences between groups were found in pre-operative and follow-up radiographic parameters, union rate, and functional results.ConclusionThe non-fixation with press fit technique is a reliable procedure for Cotton osteotomy and as effective as screw fixation.Level of evidenceLevel III, case control study 相似文献
25.
Jiao-Tian Xu Yuan Qian Wei Wang Xiao-Xiang Chen Yang Li Yu Li Zhi-Yong Yang Xiao-Bin Song Di Lu Xing-Li Deng 《中国神经再生研究》2020,(1):112-119
Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease,but its specific mechanism of action is still unclear.Stromal cell-derived factor-1 and its receptor,chemokine receptor 4(CXCR4),are important regulators of cell migration.We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease.A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway,and then treated with 5μL of neural stem cell suspension(1.5×104/L)in the right substantia nigra.Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation.Parkinson-like behavior in rats was detected using apomorphine-induced rotation.Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Using quantitative real-time polymerase chain reaction,the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured.In addition,western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4.Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation,increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra,and enhanced the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Injection of AMD3100 inhibited the aforementioned effects.These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease.This study was approved by the Animal Care and Use Committee of Kunming Medical University,China(approval No.SYXKK2015-0002)on April 1,2014. 相似文献
26.
Michelle Moffa Ryan Cronk Donald Fejfar Sarah Dancausse Leslie Acosta Padilla Jamie Bartram 《International journal of hygiene and environmental health》2019,222(3):335-346
Background
There are well-established relationships between health and homelessness, and shelters can facilitate the transmission of diseases and contribute to their prevention. Adequate environmental health conditions and hygiene behaviors in homeless shelters are fundamental to the health of their clients, a marginalized population. We report the status of environmental health conditions and hygiene behaviors in homeless shelters and associated health outcomes; interventions to improve these conditions, behaviors, and outcomes; and obstacles to improvement.Methods
PubMed, Web of Science, Scopus, and EBSCOhost were searched for peer-reviewed studies, and additional sources for grey literature. Studies were included if they reported primary data on one or more environmental health condition or hygiene behavior in homeless shelters.Results
Twenty-eight studies were included in the review. Insufficient ventilation systems, unhygienic bedding, and overcrowding were the most documented environmental health and hygiene deficiencies in homeless shelters, and tuberculosis infections and skin diseases were the most documented associated health outcomes among clients. Studies frequently recommended or described implementation of behavioral and administrative controls, ventilation system improvements, and ultraviolet germicidal irradiation fixtures.Discussion
Most studies addressed airborne transmission of tuberculosis and were conducted in high-income countries, revealing an imbalance in the literature. Insufficient resources and the transience of clients are barriers to improving hygiene behaviors and environmental conditions in homeless shelters. Further investment and research into ensuring adequate hygiene and environmental health in this setting can protect and promote the health and well-being of people experiencing homelessness. 相似文献27.
Andy KH Lim 《World journal of gastroenterology : WJG》2020,26(10):1020-1028
Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium,phosphate,urate and intracellular proteins such as myoglobin into the circulation,which may cause complications including acute kidney injury,electrolyte disturbance and cardiac instability.Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis.Typically,there is an increase in serum aminotransferases,namely aspartate aminotransferase and alanine aminotransferase.This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy.However,muscle can also be a source of the increased aminotransferase activity.This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association.It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases,and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury.Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury.This review also explores potential approaches to improve the accuracy of our diagnostic tools,so that excessive or unnecessary liver investigations can be avoided. 相似文献
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Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles.Most of the Alzheimer’s drugs targeting amyloidβhave been failed in clinical trials.Particularly,tau pathology connects greatly in the pathogenesis of Alzheimer’s disease.Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron.Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved.The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its conformation and structural state.Therefore,aberrant phosphorylation,as well as truncation of tau protein,has come into focus as significant mechanisms that make tau protein in a pathological entity.Furthermore,the shape-shifting nature of tau advocates to comprehend the progression of Alzheimer’s disease precisely.In this review,we emphasize the recent studies about the toxic and shape-shifting nature of tau in the pathogenesis of Alzheimer’s disease. 相似文献