Gut microbiome and metabolome signatures in liver cirrhosis-related complications.

Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight-mass spectrometry. Correlation analyses were performed targeting the gut- microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC > 0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusion: Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Preliminary analysis of predicting the first recurrence in patients with neovascular age-related macular degeneration using deep learning.

BACKGROUND: To predict, using deep learning, the first recurrence in patients with neovascular age-related macular degeneration (nAMD) after three monthly loading injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: Optical coherence tomography (OCT) images were obtained at baseline and after the loading phase. The first recurrence was defined as the initial appearance of a new retinal hemorrhage or intra/subretinal fluid accumulation after the initial resolution of exudative changes after three loading injections. Standard U-Net architecture was used to identify the three retinal fluid compartments, which include pigment epithelial detachment, subretinal fluid, and intraretinal fluid. To predict the first recurrence of nAMD, classification learning was conducted to determine whether the first recurrence occurred within three months after the loading phase. The recurrence classification architecture was built using ResNet50. The model with retinal regions of interest of the entire region and fluid region on OCT at baseline and after the loading phase is presented. RESULTS: A total of 1,444 eyes of 1,302 patients were included. The mean duration until the first recurrence after the loading phase was 8.20 ± 15.56 months. The recurrence classification system revealed that the model with the fluid region of OCT after the loading phase provided the highest classification performance, with an area under the receiver operating characteristic curve (AUC) of 0.725 ± 0.012. Heatmap analysis revealed that three pathological fluids, subsided choroidal neovascularization lesions, and hyperreflective foci were important areas for the first recurrence. CONCLUSIONS: The deep learning algorithm allowed for the prediction of the first recurrence for three months after the loading phase with adequate feasibility. An automated prediction system may assist in establishing patient-specific treatment plans and the provision of individualized medical care for patients with nAMD.

PIP5Kγ Mediates PI(4,5)P2/Merlin/LATS1 Signaling Activation and Interplays with Hsc70 in Hippo-YAP Pathway Regulation.

The type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family produces the critical lipid regulator phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the plasma membrane (PM). Here, we investigated the potential role of PIP5Kγ, a PIP5K isoform, in the Hippo pathway. The ectopic expression of PIP5Kγ87 or PIP5Kγ90, two major PIP5Kγ splice variants, activated large tumor suppressor kinase 1 (LATS1) and inhibited Yes-associated protein (YAP), whereas PIP5Kγ knockdown yielded opposite effects. The regulatory effects of PIP5Kγ were dependent on its catalytic activity and the presence of Merlin and LATS1. PIP5Kγ knockdown weakened the restoration of YAP phosphorylation upon stimulation with epidermal growth factor or lysophosphatidic acid. We further found that PIP5Kγ90 bound to the Merlin's band 4.1/ezrin/radixin/moesin (FERM) domain, forming a complex with PI(4,5)P2 and LATS1 at the PM. Notably, PIP5Kγ90, but not its kinase-deficient mutant, potentiated Merlin-LATS1 interaction and recruited LATS1 to the PM. Consistently, PIP5Kγ knockdown or inhibitor (UNC3230) enhanced colony formation in carcinoma cell lines YAP-dependently. In addition, PIP5Kγ90 interacted with heat shock cognate 71-kDa protein (Hsc70), which also contributed to Hippo pathway activation. Collectively, our results suggest that PIP5Kγ regulates the Hippo-YAP pathway by forming a functional complex with Merlin and LATS1 at the PI(4,5)P2-rich PM and via interplay with Hsc70.

Analysis of the Factors of Wound Healing Problems After Transtibial Amputation in Diabetic Patients.

Diabetes mellitus has a global impact, necessitating surgical intervention when conservative methods fail. Transtibial amputation (TTA) is commonly performed on diabetic patients, yet surgical site complications can lead to more procedures. This study aimed to identify factors linked to wound healing issues post-TTA in diabetics.A total of 181 patients who underwent TTA between 2004 and 2021 at a single hospital were included in the study. Exclusion criteria comprised trauma, non-diabetic mellitus, follow-up duration of less than 1 year, incomplete medical records, and surgeries performed by different surgeons. The comparison focused on underlying diseases other than diabetes between the group with wound problems and the group without. Additionally, factors impacting blood flow, such as presurgery hemoglobin levels, intraoperative blood transfusion, the use of antithrombotic or anticoagulant drugs, and the presence of procedures like percutaneous transluminal angioplasty (PTA) and bypass surgery, were analyzed.Among the 181 cases, 22.1% experienced problems at the surgical site while 77.9% did not. Statistical analysis revealed that age was a significant variable affecting wound healing problems after TTA in diabetic patients (p = .007). However, there were no significant differences in wound problems based on comorbidities other than diabetes (p = .209), gender (p = .677), preoperative anemia (p = .102), intraoperative blood transfusion (p = .633), the use of antithrombotic or anticoagulant medications (p = .556), and the performance of PTA or bypass surgery (p = .6).In conclusion, this study found that age was a significant variable affecting wound healing problems after TTA in diabetic patients. Although no association was observed between underlying diseases and wound healing problems, further investigation and cautious management of factors such as preoperative anemia, intraoperative blood transfusion, the use of antithrombotic or anticoagulant drugs, and the performance of PTA or bypass surgery are warranted to prevent complications and optimize wound healing outcomes in diabetic patients undergoing TTA.

Lipid kinase PIP5Kα contributes to Hippo pathway activation via interaction with Merlin and by mediating plasma membrane targeting of LATS1.

BACKGROUND: The Hippo pathway plays a critical role in controlled cell proliferation. The tumor suppressor Merlin and large tumor suppressor kinase 1 (LATS1) mediate activation of Hippo pathway, consequently inhibiting the primary effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid present in the plasma membrane (PM), binds to and activates Merlin. Phosphatidylinositol 4-phosphate 5-kinase α (PIP5Kα) is an enzyme responsible for PIP2 production. However, the functional role of PIP5Kα in regulation of Merlin and LATS1 under Hippo signaling conditions remains unclear. METHODS: PIP5Kα, Merlin, or LATS1 knockout or knockdown cells and transfected cells with them were used. LATS1, YAP, and TAZ activities were measured using biochemical methods and PIP2 levels were evaluated using cell imaging. Low/high cell density and serum starvation/stimulation conditions were tested. Colocalization of PIP5Kα and PIP2 with Merlin and LATS1, and their protein interactions were examined using transfection, confocal imaging, immunoprecipitation, western blotting, and/or pull-down experiments. Colony formation and adipocyte differentiation assays were performed. RESULTS: We found that PIP5Kα induced LATS1 activation and YAP/TAZ inhibition in a kinase activity-dependent manner. Consistent with these findings, PIP5Kα suppressed cell proliferation and enhanced adipocyte differentiation of mesenchymal stem cells. Moreover, PIP5Kα protein stability and PIP2 levels were elevated at high cell density compared with those at low cell density, and both PIP2 and YAP phosphorylation levels initially declined, then recovered upon serum stimulation. Under these conditions, YAP/TAZ activity was aberrantly regulated by PIP5Kα deficiency. Mechanistically, either Merlin deficiency or LATS1 deficiency abrogated PIP5Kα-mediated YAP/TAZ inactivation. Additionally, the catalytic domain of PIP5Kα directly interacted with the band 4.1/ezrin/radixin/moesin domain of Merlin, and this interaction reinforced interaction of Merlin with LATS1. In accordance with these findings, PIP5Kα and PIP2 colocalized with Merlin and LATS1 in the PM. In PIP5Kα-deficient cells, Merlin colocalization with PIP2 was reduced, and LATS1 solubility increased. CONCLUSIONS: Collectively, our results support that PIP5Kα serves as an activator of the Hippo pathway through interaction and colocalization with Merlin, which promotes PIP2-dependent Merlin activation and induces local recruitment of LATS1 to the PIP2-rich PM and its activation, thereby negatively regulating YAP/TAZ activity. Video Abstract.

Biomechanical microenvironmental stimulating effect of pulsed electromagnetic field on the regeneration of crush injured rat sciatic nerve.

This study evaluated the biomechanical microenvironmental stimulating effect of pulsed electromagnetic field (PEMF) on the regeneration of crush-injured rat sciatic nerve, when combined with bone marrow mesenchymal stem cells (BMSCs) and recombinant human nerve growth factor (rhNGF-ß), in the form of an adenoviral vector-mediated NGF. Sprague-Dawley rats were equally distributed into six groups; PBS, BMSC, NGF-Ad + BMSC, PEMF + PBS, PEMF + BMSC and PEMF + NGF-Ad + BMSC. The PBS group received PBS (volume: 10µL/rat), the BMSC group with BMSCs (1 × 106 cell/10 µL/rat) and NGF-Ad group with the rhNGF-ß Ad infected BMSCs (1 × 106 cell/10 µL/rat) immediate after right sciatic nerve crush injury. The PEMF groups were exposed to PEMF of 1mT, 50 Hz, 1 h/day. The rats were observed for 3 weeks. PEMF alone did not showed the positive effect compared with negative control group. The groups transplanted with BMSCs showed higher axonal regeneration compared with the groups without transplantation of the cells whether BMSC was infected with NGF-Ad or not and whether the animals received PEMF. PEMF + NGF-Ad + BMSC group showed the significantly highest number of axons than the other groups. Functionally, all groups showed marked improvement at 3 weeks postoperatively although the difference was not statistically significant among the groups. PEMF showed the positive effect when combined with BMSC and NGF-ad in aspect of number of axons. Therefore, combining the microenvironment stimulation methods of PEMF and conventional methods such as transplantation of stem cells and growth factor could be considered for the regeneration methods in the nerve damage.

BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non-Small Cell Lung Cancer.

PURPOSE: Resistance to third-generation EGFR inhibitors including osimertinib arises in part from the C797S mutation in EGFR. Currently, no targeted treatment option is available for these patients. We have developed a new EGFR tyrosine kinase inhibitor (TKI), BBT-176, targeting the C797S mutation. PATIENTS AND METHODS: Recombinant EGFR proteins and Ba/F3 cell lines, patient-derived cells, and patient-derived xenografts expressing mutant EGFRs were used to test the inhibitory potency and the anticancer efficacy of BBT-176 both in vitro and in vivo. Patient case data are also available from an ongoing phase I clinical trial (NCT04820023). RESULTS: The half maximal inhibitory concentration (IC50) of BBT-176 against EGFR 19Del/C797S, EGFR 19Del/T790M/C797S, and EGFR L858R/C797S proteins were measured at 4.36, 1.79, and 5.35 nmol/L, respectively (vs. 304.39, 124.82, and 573.72 nmol/L, for osimertinib). IC50 values of BBT-176 against Ba/F3 cells expressing EGFR 19Del/C797S, EGFR 19Del/T790M/C797S, EGFR L858R/C797S, and EGFR L858R/T790M/C797S were 42, 49, 183, and 202 nmol/L, respectively (vs. 869, 1,134, 2,799, and 2,685 nmol/L for osimertinib). N-ethyl-N-nitrosourea mutagenesis suggested that BBT-176 treatment does not introduce any secondary mutations in the EGFR gene but increases EGFR expression levels. Combined with the EGFR antibody cetuximab, BBT-176 effectively suppressed the growth of BBT-176-resistant clones. BBT-176 strongly inhibited the tumor growth, and in some conditions induced tumor regression in mouse models. In the clinical trial, two patients harboring EGFR 19Del/T790M/C797S in blood showed tumor shrinkage and radiologic improvements. CONCLUSIONS: BBT-176 is a fourth-generation EGFR inhibitor showing promising preclinical activity against NSCLC resistant to current EGFR TKI, with early clinical efficacy and safety.

Factors predictive of functional outcomes and quality of life in patients with fragility hip fracture: A retrospective cohort study.

To determine the predictors of functional outcomes and quality of life (QoL) of patients who were surgically treated for fragility hip fracture. This was a retrospective cohort study performed in the 3 tertiary rehabilitation facilities. A total of 165 patients who had undergone surgery for fragility hip fracture were followed up to 6 months postoperatively. The factors expected to be related to the functional outcomes and QoL at 6 months post-surgery were as follows: baseline demographics, fracture site, operation type, fall characteristics including fall location and fall direction, comorbidities, and initial functional status. The following were comorbidities: hypertension, diabetes mellitus, dementia, cerebrovascular accident, and osteoporosis. Functional outcome and QoL measures were represented using the Koval grade, functional ambulatory category (FAC), Berg balance scale, 4-m walking speed test, the Korean version of Mini-Mental State Examination, EuroQol 5-dimension (EQ-5D) questionnaire, the Korean version of Modified Barthel Index, and the Korean version of instrumental activities of daily living (K-IADL). For all tests, each patient was assessed immediately after transfer and at 6 months post-surgery. Multivariable regression analyses adjusting for factors mentioned above were as follows. Old age led to a significantly less favorable outcome on FAC and K-IADL at 6 months. Intertrochanteric fracture had a significantly positive impact on Koval at 6 months compared to femur neck and intertrochanteric fractures. Total hip replacement arthroplasty and bipolar hemiarthroplasty had a significantly positive impact on EQ-5D and FAC at 6 months respectively compared to other operation types. Fall characteristics didn't reveal any significant impact on functional outcomes and QoL. Patients with hypertension and diabetes mellitus had a significantly negative outcome on EQ-5D and K-IADL respectively. Among initial assessments of function and QoL, initial 4-m walking speed test, Korean version of Mini-Mental State Examination, K-IADL, and Korean version of Modified Barthel Index were independent predictors of function and QoL at 6 months. This study confirmed that age, fracture site, operation type, comorbidities, and initial physical and cognitive function significantly influenced recovery of function and QoL at 6 months in patients with fragility hip fractures.

Complexities of Prostate Cancer.

Prostate cancer has a long disease history and a wide variety and uncertainty in individual patients' clinical progress. In recent years, we have seen a revolutionary advance in both prostate cancer patient care and in the research field. The power of deep sequencing has provided cistromic and transcriptomic knowledge of prostate cancer that has not discovered before. Our understanding of prostate cancer biology, from bedside and molecular imaging techniques, has also been greatly advanced. It is important that our current theragnostic schemes, including our diagnostic modalities, therapeutic responses, and the drugs available to target non-AR signaling should be improved. This review article discusses the current progress in the understanding of prostate cancer biology and the recent advances in diagnostic and therapeutic strategies.

A randomized controlled trial of stem cell injection for tendon tear.

Tendons have limited reparative ability and perform a relatively simple mechanical function via the extracellular matrix. Thus, the injured tendon might be treated successfully by stem cell transplantation. We performed a randomized, controlled study to investigate the effects of mesenchymal stem cell injection for treating partial tears in the supraspinatus tendon. We enrolled 24 patients with shoulder pain lasting more than 3 months and partial tears in the supraspinatus tendon. Participants were assigned to three groups: stem cells in fibrin glue, normal saline/fibrin glue mixture, and normal saline only, with which intra-lesional injection was performed. Pain at activity and rest, shoulder function and tear size were evaluated. For safety measures, laboratory tests were taken and adverse events were recorded at every visit. Participants were followed up at 6, 12 weeks, 6, 12 months and 2 years after injection. The primary outcome measure was the improvement in pain at activity at 3 months after injection. Twenty-three patients were included in the final analysis. Primary outcome did not differ among groups (p = 0.35). A mixed effect model revealed no statistically significant interactions. Only time significantly predicted the outcome measure. All participants reported transient pain at the injection site. There were no differences in post-injection pain duration or severity. Safety measures did not differ between groups, and there were no persistent adverse events. Stem cell injection into supraspinatus partial tears in patients with shoulder pain lasting more than 3 months was not more effective than control injections.ClinicalTrials.gov Identifier: NCT02298023.

Magnetic resonance imaging analysis of screw in-type lateral anchor pull-out in large to massive rotator cuff repair in patients older than 60 years.

BACKGROUND: This study was performed to identify the incidence of screw in-type lateral anchor pull-out in patients older than 60 years who underwent rotator cuff repair for large to massive rotator cuff tear (RCT). METHODS: We reviewed 25 patients over 60 who were diagnosed with large to massive RCT and underwent arthroscopic rotator cuff repair in our hospital from March 2017 to February 2021. Preoperative tear size (anterior to posterior, medial to lateral) was measured via preoperative magnetic resonance imaging (MRI). All 25 patients underwent MRI scanning on postoperative day 1 and at 3 months after surgery. The change of anchor position was measured in axial views on MRI images postoperative day 1 and 3 months after surgery. And it was statistically compared according to bone mineral density (BMD), sex, and number of lateral anchors. RESULTS: Two MRIs (postoperative day 1 and 3 months) in 25 patients were compared. Anchor pull-out occurred in six patients during 3 months (6.7%), and the mean pull-out length difference was 1.56 mm (range, 0.16-2.58 mm). There was no significant difference in the number of pull-out anchors, degree of pull-out difference by comparing BMD (A, BMD≤-2.5; B, BMD>-2.5), sex, or number of anchors used in each surgery (C, two anchors; D, three anchors) (p>0.05). CONCLUSIONS: Pull-out of screw in-type anchors was rarely observed and the mean pull-out length difference was negligibly small in our study. The screw in-type lateral anchor seems to be a decent option without concern of anchor pull-out even in elderly patients.

Bioinformatic Analyses of Canonical Pathways of TSPOAP1 and its Roles in Human Diseases.

TSPO-associated protein 1 (TSPOAP1) is a cytoplasmic protein and is closely associated with its mitochondrial transmembrane protein partner translocator protein (TSPO). To decipher the canonical signalling pathways of TSPOAP1, its role in human diseases and disorders, and relationship with TSPO; expression analyses of TSPOAP1- and TSPO-associated human genes were performed by Qiagen Ingenuity Pathway Analysis (IPA). In the expression analysis, necroptosis and sirtuin signalling pathways, mitochondrial dysfunction, and inflammasome were the top canonical pathways for both TSPOAP1 and TSPO, confirming the close relationship between these two proteins. A distribution analysis of common proteins in all the canonical pathways predicted for TSPOAP1 revealed that tumor necrosis factor receptor 1 (TNFR1), vascular cell adhesion molecule 1 (VCAM1), cyclic AMP response element-binding protein 1 (CREB1), T-cell receptor (TCR), nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3), DNA-dependent protein kinase (DNA-PK or PRKDC), and mitochondrial permeability transition pore (mPTP) were the major interaction partners of TSPOAP1, highlighting the role of TSPOAP1 in inflammation, particularly neuroinflammation. An analysis of the overlap between TSPO and TSPOAP1 Homo sapiens genes and top-ranked canonical pathways indicated that TSPO and TSPOAP1 interact via voltage-dependent anion-selective channels (VDAC1/2/3). A heat map analysis indicated that TSPOAP1 has critical roles in inflammatory, neuroinflammatory, psychiatric, and metabolic diseases and disorders, and cancer. Taken together, this information improves our understanding of the mechanism of action and biological functions of TSPOAP1 as well as its relationship with TSPO; furthermore, these results could provide new directions for in-depth functional studies of TSPOAP1 aimed at unmasking its detailed functions.

Clinical Practice Guideline for Postoperative Rehabilitation in Older Patients With Hip Fractures.

OBJECTIVE: The incidence of hip fractures is increasing worldwide with the aging population, causing a challenge to healthcare systems due to the associated morbidities and high risk of mortality. After hip fractures in frail geriatric patients, existing comorbidities worsen and new complications are prone to occur. Comprehensive rehabilitation is essential for promoting physical function recovery and minimizing complications, which can be achieved through a multidisciplinary approach. Recommendations are required to assist healthcare providers in making decisions on rehabilitation post-surgery. Clinical practice guidelines regarding rehabilitation (physical and occupational therapies) and management of comorbidities/complications in the postoperative phase of hip fractures have not been developed. This guideline aimed to provide evidence-based recommendations for various treatment items required for proper recovery after hip fracture surgeries. METHODS: Reflecting the complex perspectives associated with rehabilitation post-hip surgeries, 15 key questions (KQs) reflecting the complex perspectives associated with post-hip surgery rehabilitation were categorized into four areas: multidisciplinary, rehabilitation, community-care, and comorbidities/complications. Relevant literature from four databases (PubMed, EMBASE, Cochrane Library, and KoreaMed) was searched for articles published up to February 2020. The evidence level and recommended grade were determined according to the grade of recommendation assessment, development, and evaluation method. RESULTS: A multidisciplinary approach, progressive resistance exercises, and balance training are strongly recommended. Early ambulation, weigh-bearing exercises, activities of daily living training, community-level rehabilitation, management of comorbidities/complication prevention, and nutritional support were also suggested. This multidisciplinary approach reduced the total healthcare cost. CONCLUSION: This guideline presents comprehensive recommendations for the rehabilitation of adult patients after hip fracture surgery.

Novel lateral whole-body dual-energy X-ray absorptiometry of lumbar paraspinal muscle mass: results from the SarcoSpine study.

BACKGROUND: Here, we aimed to propose novel lateral whole-body dual-energy X-ray absorptiometry (lateral DXA) as a simple tool for measuring spinal muscle mass and investigate the feasibility of lateral DXA to measure lumbar paraspinal muscle (LPM) mass compared with lumbosacral spine three-dimensional magnetic resonance imaging (3D MRI). METHODS: Twenty consecutive participants were enrolled from a prospective observational cohort (SarcoSpine study). Lateral DXA was scanned with each participant in the lateral decubitus position. The region of interest was defined to analyse the LPM mass. LPM total volume, LPM cross-sectional area at the L3 mid-vertebra and L4/5 mid-disc levels and each signal intensity were measured by 3D MRI. Isokinetic and isometric back extensor muscle strengths as well as back extensor endurance were examined. The correlation between lateral DXA-based mass (weight) and 3D MRI-based LPM volume was analysed. RESULTS: The mean age of the 20 participants (15 women, 5 men) was 72.2 ± 4.9 years. LPM mass by lateral DXA was positively correlated with LPM volume by 3D MRI (ß = 0.333, r = 0.692, p < 0.001) and negatively correlated with signal intensity of the total LPM (ß = -0.263, r = -0.530, p = 0.016). LPM mass was also correlated with appendicular limb muscle mass, handgrip strength and gait speed as well as back extensor endurance (r = 0.620, p = 0.004). CONCLUSIONS: Our data suggest that LPM mass assessed by lateral DXA was positively correlated with LPM volume by 3D MRI in older adults. Lateral DXA may be a potential substitute for the cross-sectional area measurement of LPM mass. Further studies are required to validate this lateral DXA technique.

Influence of comorbidities on functional outcomes in patients with surgically treated fragility hip fractures: a retrospective cohort study.

BACKGROUND: The incidence and number of fragility hip fractures are gradually increasing, resulting in a wide consumption of medical resources. Various factors affecting functional recovery in patients with fragility hip fractures are known, and comorbid diseases are one of them. The purpose of this study is to determine the effect of comorbidities on functional outcomes in patients surgically treated for fragility hip fractures, thereby contributing to the efficient distribution of medical resources. METHODS: This was a retrospective cohort study performed in the three tertiary rehabilitation facilities. A total of 211 patients (50 men and 161 women; average age 81.6 ± 6.7 years) who had undergone surgery for fragility hip fractures were followed up from immediately after transfer to the Department of Rehabilitation Medicine to 6 months postoperatively. Comorbidities referred to a summary of the following conditions: hypertension, diabetes mellitus, chronic liver disease, dementia, cerebrovascular accident, and osteoporosis. Functional outcomes included Koval's grade, Functional Ambulatory Category (FAC), Functional Independence Measure (FIM)-locomotion, Modified Rivermead Mobility Index, Berg Balance Scale (BBS), 4-Meter Walking speed Test (4MWT), the Korean version of the Mini-Mental State Examination(K-MMSE), Geriatric Depression Scale (GDS), EuroQol Five-Dimension (EQ-5D) questionnaire, the Korean version of the Modified Barthel Index (K-MBI), the Korean version of the Instrumental Activities of Daily Living (K-IADL), and Korean version of Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight scale (K-FRAIL). For all tests, each patient was assessed immediately after transfer and 6 months post-surgery. RESULTS: Multivariate linear regression analyses adjusted for age, sex, the initial variable of the functional outcomes, and comorbidities revealed that dementia had a significant negative impact on Koval's grade and K-FRAIL 6 months postoperatively. Diabetes mellitus had a significant negative impact on the FAC, GDS, EQ-5D, K-IADL, and K-FRAIL 6 months postoperatively. Patients with osteoporosis showed a significant negative outcome of FIM-locomotion 6 months postoperatively. A cerebrovascular accident revealed a significant negative impact on the BBS 6 months postoperatively. In addition, hypertension led to significantly less favorable outcomes of the K-FRAIL 6 months postoperatively. CONCLUSIONS: This study confirmed that comorbidities, particularly dementia and diabetes mellitus, significantly influence functional outcomes 6 months after fragility hip fracture surgeries.

Improvement of Corrosion Resistance of Stainless Steel Welded Joint Using a Nanostructured Oxide Layer.

In this study, we fabricated a nanoporous oxide layer by anodization to improve corrosion resistance of type 304 stainless steel (SS) gas tungsten arc weld (GTAW). Subsequent heat treatment was performed to eliminate any existing fluorine in the nanoporous oxide layer. Uniform structures and compositions were analyzed with field emission scanning electron microscope (FESEM) and X-ray diffractometer (XRD) measurements. The corrosion resistance of the treated SS was evaluated by applying a potentiodynamic polarization (PDP) technique and electrochemical impedance spectroscopy (EIS). Surface morphologies of welded SS with and without treatment were examined to compare their corrosion behaviors. All results indicate that corrosion resistance was enhanced, making the treatment process highly promising.

Measuring fucosylated alpha-fetoprotein in hepatocellular carcinoma: A comparison of µTAS and parallel reaction monitoring.

PURPOSE: Fucosylation of alpha-fetoprotein (AFP) is closely correlated with the diagnosis of patients with hepatocellular carcinoma (HCC). In current, a micro-total analysis system (µTAS) using immunoassay has been developed for determining fucosylated AFP EXPERIMENTAL DESIGN: We compared two analytical methods, µTAS and liquid chromatography-parallel reaction monitoring mass spectrometry (LC-PRM MS), for the measurement of fucosylated AFP in serum to evaluate the usefulness of the results. For this purpose, serum samples were used (cirrhosis, n = 105; HCC, n = 105), and we have discussed the analytical performance of these two methods RESULTS: We observed a correlation (R2  = 0.84) between LC-PRM MS and µTAS using samples where fucosylated levels were measured by both methods. The fucosylated level of AFP by LC-PRM MS better differentiated between cirrhosis and HCC patients than those by µTAS (AUC = 0.910 vs. 0.861), particularly in subgroups with a level of total AFP < 20 ng/mL (0.973 vs. 0.874) and in early stage (I and II) patients (0.922 vs. 0.835) CONCLUSIONS AND CLINICAL RELEVANCE: From this comparative study we can suggest that the LC-PRM MS is applicable in the measurement of fucosylated AFP from human serum and is more useful for early diagnosis of HCC. CLINICAL RELEVANCE: Fucosylation of AFP is used for the detection of HCC. A micro-total analysis system (µTAS) has been only developed for measuring fucosylation of AFP in clinical research. This study reports the fucosylation of AFP in human serum samples from cirrhosis and HCC patients using the µTAS and a LC-PRM MS to evaluate fucosylation of AFP from each method. As a result, LC-PRM MS is complementary to the conventional µTAS method. Furthermore, LC-PRM MS provides a higher diagnostic accuracy than the µTAS in patients with low AFP levels and an early stage.

Mononeuropathy multiplex associated with systemic vasculitis: A case report.

BACKGROUND: Vasculitis, a systemic disorder with inflammation of blood vessel walls, can develop broad spectrum of signs and symptoms according to involvement of various organs, and therefore, early diagnosis of vasculitis is challenging. We herein describe a patient who developed a special case of systemic vasculitis with mononeuropathy multiplex, rectal perforation and antiphospholipid syndrome (APS) presented with pulmonary embolism. CASE SUMMARY: A 61-year-old woman visited hospital with complaints of myalgia and occasional fever. She was initially diagnosed as proctitis and treated with antibiotics, however, there was no improvement. In addition, she also complained right foot drop with hypesthesia, and left 2nd and 3rd finger tingling sensation. She underwent nerve conduction study for evaluation, and it revealed sensorimotor polyneuropathy in the left arm and bilateral legs. Subsequent sural nerve biopsy strongly suggested vasculitic neuropathy. Based on nerve biopsy and clinical manifestation, she was diagnosed with vasculitis and treated with immuno-suppressive therapy. During treatment, sudden rectal perforation and pulmonary thromboembolism occurred, and further laboratory study suggested probable concomitant APS. Emergency Hartmann operation was performed for rectal perforation, and anti-coagulation therapy was started for APS. After few cycles of immunosuppressive therapy, tingling sensation and weakness in her hand and foot had been partially recovered and vasculitis was considered to be stationary. CONCLUSION: Vasculitis can be presented with a variety of signs and symptoms, therefore, clinicians should always consider the possibility of diagnosis.

Differential effects of dual antiplatelet therapy in patients presented with acute coronary syndrome vs. stable ischaemic heart disease after coronary artery bypass grafting.

AIMS: The current study sought to evaluate whether long-term clinical outcomes according to the use of dual antiplatelet therapy (DAPT) or single antiplatelet therapy (SAPT) differed between acute coronary syndrome (ACS) and stable ischaemic heart disease (SIHD) patients who underwent coronary artery bypass grafting surgery (CABG). METHODS AND RESULTS: Between January 2001 and December 2017, 3199 patients with ACS (55.3%) and 2583 with SIHD (44.7%) who underwent isolated CABG were enrolled. The study population was stratified using DAPT or SAPT in ACS patients and SIHD patients. The primary outcome was a cardiovascular death or myocardial infarction (MI) at 5 years. After CABG, DAPT was more frequently used in patients with ACS than in those with SIHD [n = 1960 (61.3%) vs. n = 1313 (50.8%), P < 0.001]. Among patients with ACS, the DAPT group showed a significantly lower risk of cardiovascular death or MI at 5 years than the SAPT group [DAPT vs. SAPT, 4.0% vs. 7.8%, hazard ratio (HR) 0.521, 95% confidence interval (CI) 0.339-0.799; P = 0.003]. In contrast, among patients with SIHD, there was no significant difference in the rate of cardiovascular death or MI at 5 years between the use of DAPT and SAPT (4.0% vs. 4.0%, HR 0.991, 95% CI 0.604-1.626; P = 0.971). These findings were robust to multiple sensitivity analyses and competing risk analysis. In the subgroup analysis, the use of DAPT was associated with a significantly lower risk of cardiovascular death or MI among SIHD patients with a previous percutaneous coronary intervention (PCI), with a significant interaction between the use of DAPT and PCI history (interaction P = 0.011). CONCLUSION: Among ACS patients who underwent CABG, the use of DAPT was associated with lower cardiovascular death or MI than the use of SAPT, but this was not the case in SIHD patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03870815.

A new type of oculocutaneous albinism with a novel OCA2 mutation.

Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders, characterized by hypopigmentation of the eyes, skin, and hair, which result in ocular abnormalities and a risk of developing skin cancer. Currently, there is no ophthalmologic procedure or drug that prevents the clinical features of OCA. Here, we report a new type of OCA in two, unrelated Korean families with the same OCA2 mutation. Affected individuals in this study are different from those of previous reports in two aspects: an inheritance pattern and clinical presentation. All reported patients with OCA have shown an autosomal recessive inheritance pattern, while our patients showed an autosomal dominant inheritance pattern. Small amounts of pigment can be acquired with age in OCA, but there is no substantial variation from adolescence to adulthood in this regard. A case where the patient attained normal pigmentation levels has never been reported. However, our patients displayed completely normal pigmentation in their late twenties. Whole exome sequencing and in-silico analysis revealed a novel mutation, OCA2 c.2338G>A p.(G780S) (NM_000275) with a high likelihood of pathogenicity. Sanger sequencing of p.G780S identified the same mutation in the affected individuals, which was not found in the family members with normal phenotype. We hypothesize that OCA2 G780S not only acts as a pathogenic variant of OCA but also induces pigmentation by enhancing the melanogenesis gene expression of other modifier genes, such as SLC45A2 and TPC2. These findings may provide further understanding of melanin biosynthesis and new treatment methods for OCA.