Anatomical assessments of injectate spread stratified by the volume of the intertransverse process block at the T2 level.

BACKGROUND: This cadaveric study aimed to analyze injectate spread to target nerves during a single-injection, ultrasound-guided intertransverse process block. METHODS: An ultrasound-guided intertransverse process block with three different injectate volumes was administered to 12 cadavers. Each hemithorax was subjected to computer-generated random allocation of 10, 15, or 20 mL ultrasound-guided, single-injection intertransverse process block at the T2 vertebral level. Latex dye solution was injected into each hemithorax in accordance with the allocated volume. The presence of dye at the nerve root in the sympathetic chain and intercostal nerves at various injection levels was examined via dissection. RESULTS: Injectate spread into the dorsal rami was observed in seven of eight (87.5%), seven of eight (87.5%), and all eight (100%) of the 10, 15, and 20 mL specimens, respectively. In all 20 mL specimens, consistent staining of the dorsal rami, spinal nerve, and dorsal root ganglion was observed. CONCLUSIONS: An injectate volume of 20 mL was required for consistent staining of the dorsal rami, spinal nerve, and dorsal root ganglion in an intertransverse process block. Although an augmented injectate volume was associated with an increased likelihood of target nerve staining, consistent staining of the sympathetic ganglion, rami communicans, and ventral ramus was not observed, even at a volume of 20 mL. The current study presents initial findings suggesting that as opposed to a sympathetic ganglion block, a 20 mL intertransverse process block may act as a feasible substitute for dorsal root ganglion, spinal nerve, and medial branch blocks within a clinical context.

Impact of family history of prostate cancer on disease progression for prostatic cancer patients undergoing active surveillance: A systematic review and meta-analysis.

PURPOSE: To evaluate how a family history of prostate cancer influences the progression of the disease in individuals with prostate cancer undergoing active surveillance. MATERIALS AND METHODS: We conducted a thorough literature search in PubMed/MEDLINE, Embase, and Cochrane Library up to June 2023. This systematic review was registered in PROSPERO (CRD42023441853). The study evaluated the effects of family history of prostate cancer (intervention) on disease progression (outcome) in prostate cancer patients undergoing active surveillance (population) and compared them to those without a family history (comparators). For time to disease progression outcomes, the extracted data were synthesized using the inverse variance method on the log hazard ratios scale. RESULTS: A total of eight studies were incorporated into this systematic review and meta-analysis. The combined hazard ratio for unadjusted disease progression was 1.06 (95% confidential interval [CI] 0.66-1.69; p=0.82). The combined hazard ratio for adjusted disease progression was 1.31 (95% CI 1.16-1.48; p<0.0001). All the enlisted studies demonstrated high quality based on the Newcastle-Ottawa scale. The certainty of evidence for univariate and multivariate analysis of disease progression was very low and low, respectively. Publication bias for all studies was not significant. CONCLUSIONS: For individuals with prostate cancer opting for active surveillance, a family history of prostate cancer may serve as an independent risk factor associated with an elevated risk of disease progression. Clinicians should be counseled about the increased risk of disease progression in patients with a family history of prostate cancer undergoing active surveillance.

White matter microstructural integrity as a key to effective propagation of gamma entrainment in humans.

Gamma entrainment through sensory stimulation has the potential to reduce the pathology of Alzheimer's disease in mouse models. However, clinical trials in Alzheimer's disease (AD) patients have yielded inconsistent results, necessitating further investigation. This single-center pre-post intervention study aims to explore the influence of white matter microstructural integrity on gamma rhythm propagation from the visual cortex to AD-affected regions in 31 cognitively normal volunteers aged ≥ 65. Gamma rhythm propagation induced by optimal FLS was measured. Diffusion tensor imaging was employed to assess the integrity of white matter tracts of interest. After excluding 5 participants with a deficit in steady-state visually evoked potentials, 26 participants were included in the final analysis. In the linear regression analyses, gamma entrainment was identified as a significant predictor of gamma propagation (p < 0.001). Furthermore, the study identified white matter microstructural integrity as a significant predictor of gamma propagation by flickering light stimulation (p < 0.05), which was specific to tracts that connect occipital and temporal or frontal regions. These findings indicate that, despite robust entrainment of gamma rhythms in the visual cortex, their propagation to other regions may be impaired if the microstructural integrity of the white matter tracts connecting the visual cortex to other areas is compromised. Consequently, our findings have expanded our understanding of the prerequisites for effective gamma entrainment and suggest that future clinical trials utilizing visual stimulation for gamma entrainment should consider white matter tract microstructural integrity for candidate selection and outcome analysis.

Zinc Action in Vascular Calcification.

Although zinc's involvement in bone calcification is well-established, its role in vascular calcification, characterized by abnormal calcium and phosphorus deposition in soft tissues and a key aspect of various vascular diseases, including atherosclerosis, remains unclear. This review focuses on zinc's action in vascular smooth muscle cell (VSMC) calcification, including the vascular calcification mechanism. Accumulated research has indicated that zinc deficiency induces calcification in VSMCs and the aorta, primarily through apoptosis accompanied by a downregulation of smooth muscle cell markers. Moreover, zinc deficiency-induced vascular calcification operates independently of the action of alkaline phosphatase (ALP) activity, typically associated with osteogenic processes, but is partly regulated via inorganic phosphate transporter-1 (Pit-1). To date, research has shown that zinc regulates vascular calcification through a mechanism distinct from that of osteogenic calcification, providing insight into its dual effects on physiological and pathological calcification and thereby explaining the "zinc paradox," wherein zinc simultaneously increases osteoblastic calcification and decreases VSMC calcification.

3D engineered scaffold for large-scale Vigil immunotherapy production.

Previously, we reported successful cellular expansion of a murine colorectal carcinoma cell line (CT-26) using a three-dimensional (3D) engineered extracellular matrix (EECM) fibrillar scaffold structure. CCL-247 were grown over a limited time period of 8 days on 3D EECM or tissue culture polystyrene (TCPS). Cells were then assayed for growth, electroporation efficiency and Vigil manufacturing release criteria. Using EECM scaffolds, we report an expansion of CCL-247 (HCT116), a colorectal carcinoma cell line, from a starting concentration of 2.45 × 105 cells to 1.9 × 106 cells per scaffold. Following expansion, 3D EECM-derived cells were assessed based on clinical release criteria of the Vigil manufacturing process utilized for Phase IIb trial operation with the FDA. 3D EECM-derived cells passed all Vigil manufacturing release criteria including cytokine expression. Here, we demonstrate successful Vigil product manufacture achieving the specifications necessary for the clinical trial product release of Vigil treatment. Our results confirm that 3D EECM can be utilized for the expansion of human cancer cell CCL-247, justifying further clinical development involving human tissue sample manufacturing including core needle biopsy and minimal ascites samples.

Effects of aquatic versus land-based exercise on irisin and fibroblast growth factor 21 expression and triiodothyronine and free fatty acid levels in elderly women.

BACKGROUND: This study investigated the impacts of exercise on irisin and fibroblast growth factor 21 (FGF-21) expression, as well as triiodothyronine (T3 ) and free fatty acid (FFA) levels in elderly women. METHODS: Thirty women aged 65 to 70 years (10 per group) were randomly assigned to aquatic exercise, land exercise, and control groups. The aquatic and land groups engaged in 3 exercise sessions per week (60 min/session) for 16 weeks. The intensity was progressively increased every 4 weeks. RESULTS: Irisin and FGF-21 levels significantly increased in the aquatic exercise group. In the posttest, the aquatic exercise group had the highest irisin levels. Significant findings were observed for irisin and FGF-21 for the main effect between aquatic and band exercise groups (p<0.05 for both), the main effect between measurement times (p<0.01 and p<0.001, respectively), and the interaction effect (p<0.05 and p<0.001, respectively). The irisin level was significantly higher in the aquatic than in the land group 30 minutes after the last session (p<0.05). In both exercise groups, T3 levels were significantly higher 30 minutes after the final session (p<0.05) than before the program. The FFA level was significantly higher in the aquatic exercise group than the others. In the aquatic group, FFA levels were significantly higher 30 minutes after both the first (p<0.01) and the last (p<0.001) session compared to pre-program values. CONCLUSION: Differences in exercise type and environment can promote fat metabolism by stimulating hormonal changes that induce brown fat activity and browning.

Successful open surgical treatment for persistent type II endoleak following thoracic endovascular aortic repair: a case report.

BACKGROUND: The occurrence of type II endoleaks after endovascular repair of aortic aneurysm has gradually gained increasing attention. We present a case of a patient with an expanding aneurysm after thoracic endovascular aortic repair (TEVAR) for a type II endoleak, in which successful direct ligations of the intercostal artery were performed using a sac incision without cardiopulmonary bypass (CPB) or graft replacement. CASE PRESENTATION: A 62-year-old male patient, previously treated with TEVAR for a descending thoracic aortic aneurysm, presented with ongoing chest discomfort. Based on the diagnosis of a growing aneurysm and type II endoleak, the patient was prepared for CPB and aortic cross-clamping, as a precautions against the possibility of a type I endoleak. A longitudinal opening of the thoracic aortic aneurysm sac was performed following left thoracotomy. Visual confirmation identified the T5 level intercostal artery as the source of the endoleak, and after confirming the absence of a type I endoleak, multiple ligations were applied to the intercostal artery. Follow-up computed tomography confirmed the absence of endoleaks or sac growth. CONCLUSION: In a case involving TEVAR for a thoracic aortic aneurysm, open suture ligations were used to treat type II endoleaks without having to resort to CPB, resulting in successful outcomes.

Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other than DNMT3A (non- DNMT3A CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes. Methods: In this study, we examined the prospective associations between CHIP and CKD progression events in four cohorts of CKD patients (total N = 5,772). The primary outcome was a composite of 50% kidney function decline or kidney failure. The slope of eGFR decline was examined as a secondary outcome. Mendelian randomization techniques were then used to investigate potential causal effects of CHIP on eGFR decline. Finally, kidney function was assessed in adenine-fed CKD model mice having received a bone marrow transplant recapitulating Tet2 -CHIP compared to controls transplanted wild-type bone marrow. Results: Across all cohorts, the average age was 66.4 years, the average baseline eGFR was 42.6 ml/min/1.73m 2 , and 24% had CHIP. Upon meta-analysis, non- DNMT3A CHIP was associated with a 59% higher relative risk of incident CKD progression (HR 1.59, 95% CI: 1.02-2.47). This association was more pronounced among individuals with diabetes (HR 1.29, 95% CI: 1.03-1.62) and with baseline eGFR ≥ 30 ml/min/1.73m (HR 1.80, 95% CI: 1.11-2.90). Additionally, the annualized slope of eGFR decline was steeper among non- DNMT3A CHIP carriers, relative to non-carriers (ß -0.61 ± 0.31 ml/min/1.73m 2 , p = 0.04). Mendelian randomization analyses suggested a causal role for CHIP in eGFR decline among individuals with diabetes. In a dietary adenine mouse model of CKD, Tet2 -CHIP was associated with lower GFR as well as greater kidney inflammation, tubular injury, and tubulointerstitial fibrosis. Conclusion: Non- DNMT3A CHIP is a potentially targetable novel risk factor for CKD progression.

Balloon-expandable cobalt chromium stent versus self-expandable nitinol stent for the Atherosclerotic Iliac Arterial Disease (SENS-ILIAC Trial) Trial: a randomized controlled trial.

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).

Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.

Surgical and regenerative treatment options for empty nose syndrome: A systematic review.

Objectives: Patients with empty nose syndrome usually suffer from paradoxical nasal congestion, nasal dryness, epistaxis and suffocation. Conservative management is general option for the empty nose syndrome. However, there are several patients who continually complain of symptoms. If symptoms persist, surgical options are considered. Therefore, we reviewed surgical and regenerative treatment options of empty nose syndrome. Methods: PubMed, Embase, Scopus, Cochrane Register of Controlled Trials, and Google Scholar were searched from the earliest date provided in the database until December 2022. In the studies, treatment outcomes were measured by patient symptom scores such as Sino-Nasal Outcome Test (SNOT-20, 22, and 25), and Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) along with various clinical examiniations. Results: Twenty-eight studies were analyzed. Submucosal injectable materials, allografts/xenografts/cadaveric implants, autologous implants, and synthetic implants were used. Among them, polyethylene implant was most commonly used (23.3%), followed by autologous, homologous, or cadaveric costal cartilage (20%). The most common administration site was the anterior-inferior lateral nasal wall. Most of the studies showed that surgical intervention brought significant improvements in clinical findings including endoscopic exam, acoustic rhinometry, and CT, as well as patients reporting nasal symptom-, psychological-, or overall health-related quality of life questionnaires. However, several studies did not confirm improvement effects in some psychological-related questionnaires or saccharin transit time. The average follow-up duration was 12.0 (2.0-27.6) months. Postoperative adverse effects were reported in only two studies. Conclusion: Several surgical options and recent tissue regeneration techniques have shown its positive efficacy in treating empty nose syndrome. However more detailed investigations with a larger number and a randomized control study are needed to establish a standardized protocol in treating empty nose syndrome patients.

An Approach to Selection of Face-Lift Techniques for Different Types of Faces: An Analysis of 1000 Asian Patients Over 9 Years.

BACKGROUND: A face-lift or rhytidectomy is the procedure most directly associated with rejuvenation. There are several surgical techniques for face-lifts, but criteria for the selection of techniques, based on the patient's face shape, are lacking. In this study, we report on our experience with specific indication criteria for each technique and the consequent achievement of good outcomes. METHODS: From 2015 to 2023, 1 surgeon performed face-lifts on 1000 patients. Three different superficial musculoaponeurotic system (SMAS) techniques (SMAS dissection, SMASectomy, and SMAS plication) were applied depending on the degree of sagging of the patient's lower face, lateral facial profile, and SMAS mobility and condition. Superficial musculoaponeurotic system dissection was considered for the improvement of a square face, sagging jowls, and marionette lines. Superficial musculoaponeurotic system plication was applied with patients with less sagging jowls and prominent zygoma with concave lateral facial profile. SMASectomy was applied with patients with convex lateral facial profiles or when the SMAS was too thin or damaged. Patient postoperative satisfaction was surveyed using the FACE-Q score 1 year post surgery. RESULTS: Most of the patients attained natural-looking and long-lasting aesthetic outcomes and exhibited high satisfaction. The patients indicated that they looked about 11.2 ± 5.2 years younger than their actual age after the surgery. The mean satisfaction scores for each facial feature were as follows: cheeks (91.1 ± 7.8), marionette lines (88.5 ± 13.6), lower face and jawline (92.5 ± 14.2), under chin (87.8 ± 15.1), and neck (86.2 ± 18.5). Complications such as facial nerve injury, infection, hematoma, and flap necrosis were very rare. CONCLUSIONS: Establishing criteria for the selection of face-lift surgical techniques based on the degree of lower face sagging, lateral facial profile, and SMAS mobility and condition led to good outcomes. These criteria can be used by physicians to determine the most effective face-lift surgery technique based on a patient's individual features, which may improve surgical outcomes.

Teaching clinical reasoning: principles from the literature to help improve instruction from the classroom to the bedside.

Clinical reasoning has been characterized as being an essential aspect of being a physician. Despite this, clinical reasoning has a variety of definitions and medical error, which is often attributed to clinical reasoning, has been reported to be a leading cause of death in the United States and abroad. Further, instructors struggle with teaching this essential ability which often does not play a significant role in the curriculum. In this article, we begin with defining clinical reasoning and then discuss four principles from the literature as well as a variety of techniques for teaching these principles to help ground an instructors' understanding in clinical reasoning. We also tackle contemporary challenges in teaching clinical reasoning such as the integration of artificial intelligence and strategies to help with transitions in instruction (e.g., from the classroom to the clinic or from medical school to residency/registrar training) and suggest next steps for research and innovation in clinical reasoning.

Exploring 40 years of Korean medical education conference themes.

PURPOSE: The Korean Society of Medical Education (KSME) was founded in 1983 and celebrated its 40th anniversary in 2023. This study examines the evolution of topics discussed at KSME conferences from 1971 through 2023, highlighting shifts in the focus of medical education. METHODS: We analyzed 90 KSME conferences over 5 decades (1970s, 1980s, 1990s, 2000s, and 2010s), categorizing the topics into three eras based on emerging themes and continuity. RESULTS: Consequently, 37 topics covered at the conference were categorized. Ten topics continuously appeared from the 1970s to the 2010s, including future directions of medical education, teaching methods, faculty development, and curriculum. The topics from the 1970s to the 1990s included 14 areas, such as medical education evaluation, non-undergraduate curriculum, community-related, and research. Thirteen new topics emerged after the 2000s, such as social accountability, student support, professionalism, and quality improvements. The most common topics under innovations in medical education, a case of curriculum innovation at universities that began after 2000, were clinical clerkship, curriculum development, and medical humanities. CONCLUSION: KSME's selection of conference topics has been strategically aligned with societal needs and the evolving landscape of medical education. Future topics should continue to address relevant societal and educational challenges.

Long-term clinical outcomes of image-guided percutaneous coronary intervention in acute myocardial infarction from the Korea Acute Myocardial Infarction Registry.

Imaging modalities for percutaneous coronary intervention (PCI), such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), have increased in the current PCI era. However, their clinical benefits in acute myocardial infarction (AMI) have not been fully elucidated. This study investigated the long-term outcomes of image-guided PCI in patients with AMI using data from the Korean Acute Myocardial Infarction Registry. A total of 9,271 patients with AMI, who underwent PCI with second-generation drug-eluting stents between November 2011 and December 2015, were retrospectively examined, and target lesion failure (TLF) at 3 years (defined as the composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) was evaluated. From the registry, 2,134 patients (23.0%) underwent image-guided PCI (IVUS-guided: n = 1,919 [20.6%]; OCT-guided: n = 215 patients [2.3%]). Based on propensity score matching, image-guided PCI was associated with a significant reduction in TLF (hazard ratio: 0.76; 95% confidence interval: 0.59-0.98, p = 0.035). In addition, the TLF incidence in the OCT-guided PCI group was comparable to that in the IVUS-guided PCI group (5.3% vs 4.7%, p = 0.903). Image-guided PCI, including IVUS and OCT, is associated with favorable clinical outcomes in patients with AMI at 3 years post-intervention. Additionally, OCT-guided PCI is not inferior to IVUS-guided PCI in patients with AMI.

A comparative study of blood viscometers of 3 different types.

 The greater the viscosity of the blood, the more difficult its flow becomes, leading to an increased incidence of diseases caused by blood circulation disorders. These diseases are commonly associated with the cardiovascular and cerebrovascular systems. High blood viscosity is a primary cause of circulatory system diseases. Studies have shown that accurately measuring blood viscosity and applying this data in clinical trials can help prevent circulatory system diseases. Viscosity data can vary depending on the measurement methods used, even when these methods are based on hydrodynamic principles. Despite using approved blood viscometers, the results often differ depending on the type of viscometer used, potentially causing confusion within the medical field. Informing the medical community about these differences and the level of error associated with each measurement method can help reduce this confusion. To our knowledge, the degree of difference in viscosity measurement results due to different measurement methods and the reasons for these differences have not yet been thoroughly explored. In this study, we selected three blood viscosity measurement methods registered with the Ministry of Food and Drug Safety of Korea to analyze the same canine blood. The viscosity measurements were carried out using each device and compared. The parallel plate and scanning capillary methods yielded similar viscosity values, while the cone plate method showed lower viscosity values. The viscosity of blood, as measured by the three viscometers, differed, indicating that more experimental data must be accumulated to evaluate the cause of these differences. In this paper, we identified several causes of inconsistency and suggested measures to avoid this confusion. However, confirming that the test results show systematic differences is expected to assist clinicians who diagnose and prescribe treatments based on blood viscosity results. The findings of this comparative study are anticipated to serve as a starting point for establishing guidelines or standards for blood viscosity measurement methods.

Molecular genomic and epigenomic characteristics related to aspirin and clopidogrel resistance.

BACKGROUND: Mediators, genomic and epigenomic characteristics involving in metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (ALOX) and hepatic activation of clopidogrel have been individually suggested as factors associated with resistance against aspirin and clopidogrel. The present multi-center prospective cohort study evaluated whether the mediators, genomic and epigenomic characteristics participating in arachidonic acid metabolism and clopidogrel activation could be factors that improve the prediction of the aspirin and clopidogrel resistance in addition to cardiovascular risks. METHODS: We enrolled 988 patients with transient ischemic attack and ischemic stroke who were evaluated for a recurrence of ischemic stroke to confirm clinical resistance, and measured aspirin (ARU) and P2Y12 reaction units (PRU) using VerifyNow to assess laboratory resistance 12 weeks after aspirin and clopidogrel administration. We investigated whether mediators, genotypes, and promoter methylation of genes involved in COX and ALOX metabolisms and clopidogrel activation could synergistically improve the prediction of ischemic stroke recurrence and the ARU and PRU levels by integrating to the established cardiovascular risk factors. RESULTS: The logistic model to predict the recurrence used thromboxane A synthase 1 (TXAS1, rs41708) A/A genotype and ALOX12 promoter methylation as independent variables, and, improved sensitivity of recurrence prediction from 3.4% before to 13.8% after adding the mediators, genomic and epigenomic variables to the cardiovascular risks. The linear model we used to predict the ARU level included leukotriene B4, COX2 (rs20417) C/G and thromboxane A2 receptor (rs1131882) A/A genotypes with the addition of COX1 and ALOX15 promoter methylations as variables. The linear PRU prediction model included G/A and prostaglandin I receptor (rs4987262) G/A genotypes, COX2 and TXAS1 promoter methylation, as well as cytochrome P450 2C19*2 (rs4244285) A/A, G/A, and *3 (rs4986893) A/A genotypes as variables. The linear models for predicting ARU (r = 0.291, R2 = 0.033, p < 0.01) and PRU (r = 0.503, R2 = 0.210, p < 0.001) levels had improved prediction performance after adding the genomic and epigenomic variables to the cardiovascular risks. CONCLUSIONS: This study demonstrates that different mediators, genomic and epigenomic characteristics of arachidonic acid metabolism and clopidogrel activation synergistically improved the prediction of the aspirin and clopidogrel resistance together with the cardiovascular risk factors. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03823274.

Memristive Monte Carlo DropConnect crossbar array enabled by device and algorithm co-design.

Device and algorithm co-design aims to develop energy-efficient hardware that directly implements complex algorithms and optimizes algorithms to match the hardware's characteristics. Specifically, neuromorphic computing algorithms are constantly growing in complexity, necessitating an ongoing search for hardware implementations capable of handling these intricate algorithms. Here, we present a memristive Monte Carlo DropConnect (MC-DC) crossbar array developed through a hardware algorithm co-design approach. To implement the MC-DC neural network, stochastic switching and analog memory characteristics are required, and we achieved them using Ag-based diffusive selectors and Ru-based electrochemical metalization (ECM) memristors, respectively. The devices were integrated with a one-selector one-memristor (1S1M) structure, and their well-matched operating voltages and currents enabled stochastic readout and deterministic analog programming. With the integrated hardware, we successfully demonstrated the MC-DC operation. Additionally, the selector allowed for the control of switching polarity, and by understanding this hardware characteristic, we were able to modify the algorithm to fit it and further improve the network performance.

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Relationship between proteinuria and changes in antepartum and postpartum choroidal thickness in patients with pre-eclampsia.

Pre-eclampsia (PE) is a hypertensive disorder characterised by systemic vascular resistance and endothelial dysfunction. It is known to influence choroidal thickness (CT). No previous studies have explored the antepartum and postpartum changes in CT with respect to the protein-creatinine ratio (PCR), a measure of proteinuria that is a clinical hallmark of PE. This study evaluated the correlations between antepartum and postpartum CT and the PCR in patients with PE. In this retrospective study, sixty-six eyes (66 patients) were analysed. The patients were divided into two groups according to the median PCR value (2.36 mg/mg): low PCR group (< 2.36 mg/mg) and high PCR group (≥ 2.36 mg/mg). Ophthalmologic clinical data were collected and assessed. We observed higher antepartum CT and higher mean arterial pressure in high PCR group than in low PCR group. Moreover, postpartum CT decreased significantly in high PCR group. In the multivariate analysis, CT changes were correlated with antepartum CT and antepartum PCR after logarithm transformation. In conclusion, a greater decrease in CT was observed in high PCR group than in low PCR group. Further, the antepartum PCR showed a correlation with the extent of CT reduction.