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1.
Autoimmune comorbid diseases associated with lichen planus: a nationwide case–control study
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Danielle E Whittier Elizabeth J Samelson Marian T Hannan Lauren A Burt David A Hanley Emmanuel Biver Pawel Szulc Elisabeth Sornay-Rendu Blandine Merle Roland Chapurlat Eric Lespessailles Andy Kin On Wong David Goltzman Sundeep Khosla Serge Ferrari Mary L Bouxsein Douglas P Kiel Steven K Boyd 《Journal of bone and mineral research》2022,37(3):428-439
Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
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Tien‐Yao Tsai Iat‐Lon Leong Ka‐Shun Cheng Lian‐Ru Shiao Tzu‐Hui Su Kar‐Lok Wong Paul Chan Yuk‐Man Leung 《Fundamental & clinical pharmacology》2019,33(1):52-62
A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca2+ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca2+ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation. 相似文献
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Micro‐evolution of the hepatitis B virus genome in hepatitis B e‐antigen‐positive carriers: Comparison of genotypes B and C at various immune stages
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Miju Bae Sung Woon Chung Chung Won Lee Up Huh Min Su Kim Seung Hwan Song 《Asian journal of surgery / Asian Surgical Association》2019,42(1):235-239
Background
In Leriche syndrome, postoperative graft thrombosis remains one of the most significant clinical challenges.Methods
We reviewed 51 patients who underwent surgery for aortoiliac occlusive disease at our hospital from January 2007 to December 2014. The factors associated with graft patency were determined using the Cox proportional hazard model.Results
The 2-year prosthetic graft patency rate was 72.5%. Younger age (p = 0.017, Odd ratio (OR) = 1.112), postoperative uncontrolled hypertension (p = 0.044, OR = 3.797), and associated Trans Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease II (TASC II) D femoropopliteal lesion (p = 0.008, OR = 11.139) were significantly related factors for prosthetic graft patency after surgical repair. The existing comorbidities of the patients that indicated the need for axillo-bifemoral bypass seemed to be related to lower graft patency or other complications.Conclusions
For better graft patency after an open surgical repair of Leriche syndrome, strict postoperative hypertension control and distal run-off resolution are necessary. 相似文献10.
Diabetes mellitus(DM) negatively affects the development and progression of chronic liver diseases(CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma(HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed. 相似文献