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To reduce diabetes-related complications and to avoid futile procedures, foot and ankle surgeons need to understand the relative timings of catastrophic events, their incidence, and probabilities of transitions between disease states in diabetes in different patient populations. For this study, we tracked medical events (including an initial diagnosis of diabetes, ulcer, wound care, osteomyelitis, amputation, and reamputation, in order of severity) and the time between each such event in patients with diabetes, stratifying by sex, race, and ethnicity. We found that the longest average duration between the different lower extremity states was a diagnosis of diabetes to the occurrence of ulcer at 1137 days (38 months). The average durations of amputation to reamputation, osteomyelitis, wound care, and ulcer were 18, 49, 23, and 18 days, respectively. The length of each disease transition for females was greater, while those of the Hispanic population were shorter than in the total cohort. This knowledge may permit surgeons to time and tailor treatments to their patients, and help patients to address, delay, or avoid complications. [ABSTRACT FROM AUTHOR]

Diamond Blackfan Anemia (DBA) is a rare macrocytic red blood cell aplasia that usually presents within the first year of life. The vast majority of patients carry a mutation in one of approximately 20 genes that results in ribosomal insufficiency with the most significant clinical manifestations being anemia and a predisposition to cancers. Nemo-like Kinase (NLK) is hyperactivated in the erythroid progenitors of DBA patients and inhibition of this kinase improves erythropoiesis, but how NLK contributes to the pathogenesis of the disease is unknown. Here we report that activated NLK suppresses the critical upregulation of mitochondrial biogenesis required in early erythropoiesis. During normal erythropoiesis, mTORC1 facilitates the translational upregulation of Transcription factor A, mitochondrial (TFAM), and Prohibin 2 (PHB2) to increase mitochondrial biogenesis. In our models of DBA, active NLK phosphorylates the regulatory component of mTORC1, thereby suppressing mTORC1 activity and preventing mTORC1- mediated TFAM and PHB2 upregulation and subsequent mitochondrial biogenesis. Improvement of erythropoiesis that accompanies NLK inhibition is negated when TFAM and PHB2 upregulation is prevented. These data demonstrate that a significant contribution of NLK on the pathogenesis of DBA is through loss of mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

Image-enhanced endoscopy has attracted attention as a method for detecting inflammation and predicting outcomes in patients with ulcerative colitis (UC); however, the procedure requires specialist endoscopists. Artificial intelligence (AI)–assisted image-enhanced endoscopy may help nonexperts provide objective accurate predictions with the use of optical imaging. We aimed to develop a novel AI-based system using 8853 images from 167 patients with UC to diagnose "vascular-healing" and establish the role of AI-based vascular-healing for predicting the outcomes of patients with UC. This open-label prospective cohort study analyzed data for 104 patients with UC in clinical remission. Endoscopists performed colonoscopy using the AI system, which identified the target mucosa as AI-based vascular-active or vascular-healing. Mayo endoscopic subscore (MES), AI outputs, and histologic assessment were recorded for 6 colorectal segments from each patient. Patients were followed up for 12 months. Clinical relapse was defined as a partial Mayo score >2 The clinical relapse rate was significantly higher in the AI-based vascular-active group (23.9% [16/67]) compared with the AI-based vascular-healing group (3.0% [1/33)]; P =.01). In a subanalysis predicting clinical relapse in patients with MES ≤1, the area under the receiver operating characteristic curve for the combination of complete endoscopic remission and vascular healing (0.70) was increased compared with that for complete endoscopic remission alone (0.65). AI-based vascular-healing diagnosis system may potentially be used to provide more confidence to physicians to accurately identify patients in remission of UC who would likely relapse rather than remain stable. [Display omitted] [ABSTRACT FROM AUTHOR]

Rotational malleolar fractures result in a high prevalence of intra-articular pathologies; therefore, routine arthroscopic assessment may be beneficial in the surgical treatment of ankle fractures. However, the clinical studies regarding the effectiveness of arthroscopy thus far have mixed results. We investigated the efficacy of concurrent arthroscopy during the treatment of malleolar fractures using a large U.S. healthcare data set. Those who had arthroscopy were compared with those who did not, during the surgical treatment of malleolar fractures, while adjusting for covariates of clinical relevance. The analysis showed that concurrent arthroscopy is protective against postoperative repeat surgery (OR = 0.13, 95CI = 0.02-0.41) and wound dehiscence (OR = 0.18, 95CI = 0.03-0.56). The number of added arthroscopy cases needed to avoid one repeat surgery was 74, while that of wound dehiscence was 52. Further studies are needed to determine if routine use of arthroscopy is justifiable in the surgical treatment of malleolar fractures, given the additional costs and time to the healthcare system. [ABSTRACT FROM AUTHOR]

Parent bodies of carbonaceous chondrites that initially contained metallic iron potentially exert strong reduction power during aqueous alteration to generate molecular hydrogen in excess of hydrogen solubility in water-rich fluids. The surplus hydrogen escapes from the system, which is subsequently supplied to overlying regions in planetesimals. Based on this concept, we conducted chemical equilibrium modeling of the aqueous alteration and simulated gaseous H 2 migration within the icy planetesimal that has a melted mantle and an icy shell during the early stages of radiogenic heating. In the chemical equilibrium modeling, we simulated the aqueous alteration of chondritic rocks at 0–350 °C and a water/rock mass ratio of 0.2–10 with initial CO 2 contents of 0–10 mol% in the fluid. The results showed that the mineral assemblage and solution composition change with the temperature, water/rock mass ratio, and initial fluid composition. The reproduced mineral paragenesis and abundance well explain those of carbonaceous chondrites. Furthermore, it was revealed that the initial H 2 fugacity of the system influences not only the stability of minerals and solution compositions, but also the preservation potential of organic molecules. Indeed, within these parameter spaces, the modeling results account for the organic/inorganic carbon-rich alterations reported for the Tagish Lake meteorite, Ceres, and Ryugu. Simulations of gaseous H 2 migration in a planetesimal revealed that gaseous H 2 in the deep interior can be transported to the interface with an icy shell even if the permeability is low. Moreover, it is highly possible that an H 2 -rich layer would have been widely formed just below the icy shell. Therefore, it is expected that H 2 -rich regions beneath the ice layer in planetesimals have substantial potential for the synthesis and preservation of organic molecules. These results imply that the alteration of carbonaceous chondrite parent bodies and C-complex asteroids is characterized by not only the type of parent bodies (e.g., formation age and distance from the Sun) but also the locations within their parent bodies. [ABSTRACT FROM AUTHOR]

"Limb salvage" efforts, such as performing minor amputations before infections spread proximally from the foot to decrease major lower extremity amputation, are an important part of healthcare today. It is unclear whether these efforts are preventing the number of major amputations and improving patients' quality of life and the cost-effectiveness of the U.S. healthcare system. Rates of non-traumatic lower extremity amputation (NLEA) among patients with diabetes decreased in the early 2000s but rebounded in the 2010s. We analyzed the proportion of major amputations and differences in amputation rates between age groups in Texas. Patient data was extracted from the Texas Hospital Discharge Data Public Use Data File. Population estimates were obtained from the Texas Population Estimates Program from 2011 to 2015 and from intercensal estimates provided by the U.S. Census Bureau from 2006 to 2010. Raw numbers of minor, major, and all NLEA surgeries and the ratio of major amputations to total amputations per year were reported for each age group. Poisson regression and Joinpoint analyses were performed to capture these changes in trends. Rates of amputations increased, with significant decreasing relative prevalence of major amputations. Patients aged 45 to 64 with diabetes are likely driving these increases. Rates of lower extremity amputation in patients with diabetes increased from 2009 to 2015. This holds for all and minor amputations. In contrast, the ratio of major to all amputations decreased from 2010. Utilization of major and minor amputation differs between age groups, remaining stable in the youngest subjects, with minor amputation rates increasing in those aged 45 to 64. [ABSTRACT FROM AUTHOR]