Functional Outcomes Associated With Blood Pressure Decrease After Endovascular Thrombectomy.

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

Effectiveness of endovascular treatment for in-hospital stroke vs. community-onset stroke: a propensity score-matched analysis.

BACKGROUND: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment. METHODS: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis. RESULTS: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups. CONCLUSION: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients.

Cancer signature ensemble integrating cfDNA methylation, copy number, and fragmentation facilitates multi-cancer early detection.

Cell-free DNA (cfDNA) sequencing has demonstrated great potential for early cancer detection. However, most large-scale studies have focused only on either targeted methylation sites or whole-genome sequencing, limiting comprehensive analysis that integrates both epigenetic and genetic signatures. In this study, we present a platform that enables simultaneous analysis of whole-genome methylation, copy number, and fragmentomic patterns of cfDNA in a single assay. Using a total of 950 plasma (361 healthy and 589 cancer) and 240 tissue samples, we demonstrate that a multifeature cancer signature ensemble (CSE) classifier integrating all features outperforms single-feature classifiers. At 95.2% specificity, the cancer detection sensitivity with methylation, copy number, and fragmentomic models was 77.2%, 61.4%, and 60.5%, respectively, but sensitivity was significantly increased to 88.9% with the CSE classifier (p value < 0.0001). For tissue of origin, the CSE classifier enhanced the accuracy beyond the methylation classifier, from 74.3% to 76.4%. Overall, this work proves the utility of a signature ensemble integrating epigenetic and genetic information for accurate cancer detection.

Accurate Detection of Urothelial Bladder Cancer Using Targeted Deep Sequencing of Urine DNA.

Patients with hematuria are commonly given an invasive cystoscopy test to detect bladder cancer (BC). To avoid the risks associated with cystoscopy, several urine-based methods for BC detection have been developed, the most prominent of which is the deep sequencing of urine DNA. However, the current methods for urine-based BC detection have significant levels of false-positive signals. In this study, we report on uAL100, a method to precisely detect BC tumor DNA in the urine without tumor samples. Using urine samples from 43 patients with BC and 21 healthy donors, uAL100 detected BC with 83.7% sensitivity and 100% specificity. The mutations identified in the urine DNA by uAL100 for BC detection were highly associated with BC tumorigenesis and progression. We suggest that uAL100 has improved accuracy compared to other urine-based methods for early BC detection and can reduce unnecessary cystoscopy tests for patients with hematuria.

The technique of laparoscopic and robotic extended cholecystectomy for gallbladder cancer.

The application of minimally invasive surgery for gallbladder cancer (GBC) is yet controversial. This article discusses the techniques of laparoscopic and robotic extended cholecystectomy. A 69-year-old male diagnosed with cT1-2N0 GBC underwent laparoscopic surgery, and a 55-year-old male with cT2N1 GBC underwent robotic surgery after preoperative chemotherapy. Nonanatomical partial hepatectomy with lymphadenectomy was performed. Liver parenchymal dissection was performed using Cavitron Ultrasonic Surgical Aspirator laparoscopically and Maryland bipolar dissector and Harmonic scalpel robotically. The operation time was 180 and 220 minutes, and the estimated blood loss was 140 and 130 mL, respectively. The final pathologies were pT1bN0 and pT2aN1, for which patients received adjuvant chemotherapy. There was no evidence of recurrence at 33 and 18 months without complications. Both laparoscopic and robotic extended cholecystectomy can be safely performed with the robotic surgical system as an effective alternative for GBC requiring liver resection with radical lymphadenectomy.

Technique and perioperative outcomes of single-port robotic surgery using the da Vinci SP platform in urology.

OBJECTIVE: To describe surgical technique for single port robotic surgery using the da Vinci SP system and report the perioperative outcomes. PATIENTS AND METHODS: Between Jan 2019 and Jan 2021, single-port robotic urologic surgeries were performed in 120 patients by a single surgeon. Clinicopathologic data and perioperative outcomes were collected. All surgical procedures were performed with a transperitoneal approach through an umbilical single port. Additional assistant port was used in complex procedures for malignant disease. Surgeries were carried out using both above and below camera position for effective retraction. For reconstructive surgery using intestine, an extra-intracorporeal hybrid method was used. Surgical procedures involving both kidney and pelvis were performed without change of patient position or trocar placement. RESULTS: Mean age was 62.7 years and 102 patients were male. For oncologic indication, 105 patients underwent surgeries including 66 radical prostatectomy, 25 partial nephrectomy, six radical nephrectomies, five nephroureterectomy and three radical cystectomy with urinary diversion. Fifteen cases with benign indication included four ureterolithotomy, seven uretero/pyeloplasty, three ureteroneocystostomy, and one ileal ureter reconstruction. All surgeries were performed successfully without conversion to other surgical approach. Clavien-Dindo grade III complication occurred in two patients. CONCLUSIONS: The da Vinci SP system provides a new robotic surgical platform for single port surgery while maintaining the major features of robotic surgery similar to multi-port surgery. Various single port urologic surgeries can be safely performed with this platform.

The Impact of Social Supports on the Excessive Alcohol Use of the Middle-Aged Adults in South Korea: Do All Types of Social Supports Have Positive Effects on Excessive Alcohol Users?

The purpose of the study is to discuss the necessity of interventions on excessive alcohol use among middle-aged adult Koreans and attempt to investigate the effect of social supports including family support and friend support on excessive alcohol use. To achieve these goals, a self-administered online survey was conducted on middle-aged adult Koreans from 40 to 59 years old sampled through the convenience allocation extraction method, with responses of a total of 767 samples analyzed. The results from the analysis was that the support of the family reduced excessive alcohol use, whereas the support of friends provoked excessive alcohol use. Based on these results, the necessity of a distinction in the different types of social supports for interventions in excessive alcohol use was revealed. In addition, several practical and political implications for the alleviation of excessive alcohol use among middle-aged adults are recommended.

Urinary microbiome profile in men with genitourinary malignancies.

PURPOSE: Recent advances in molecular biology technology have allowed identification of microbial communities in the urinary tract, and urinary microbiome is associated with various urological diseases. In this study, we aimed to characterize the urinary microbiome of genitourinary malignancies. MATERIALS AND METHODS: Metagenomic analysis of urinary DNA was performed in 85 patients including 30 with bladder cancer (BC), 27 with prostate cancer (PC), 12 with renal cancer (RC), and 16 with non-cancer (NC). 16S rRNA gene sequencing was conducted after amplification of the V3-V4 region. RESULTS: PC and RC had significantly lower Shannon index than BC, and beta diversity showed significantly different microbiome composition between four groups. We identified six genera of Cutibacterium, Peptoniphilus, Sphingomonas, Staphylococcus, Micrococcus, and Moraxella, which showed significantly different abundance between the four groups. When each of the malignancies were compared to NC at the species level, Micrococcus sp. was significantly increased in BC. We also identified 12 and five species with increased populations in PC and RC, respectively. Of these, Cutibacterium acnes, Cutibacterium granulosum, Peptoniphilus lacydonensis, and Tessaracoccus were significantly increased in both PC and RC. CONCLUSIONS: Urinary microbiome composition was different depending on the type of genitourinary malignancies, and we identified bacteria that are significantly associated with each type of malignancy. Specifically, several bacterial species were associated both PC and RC, suggesting that PC and RC share a similar pathogenesis-related urinary microbiome.

Germline pathogenic variants in unselected Korean men with prostate cancer.

PURPOSE: Prostate cancer is one of the most heritable cancers and prostate cancer with germline mutations is associated with aggressive features and a poor prognosis. We investigated germline variants in unselected Korean men with prostate cancer. MATERIALS AND METHODS: In this study, we prospectively collected buccal swab DNA from 120 unselected Korean men with prostate cancer, and performed massively parallel sequencing. Identified germline variants were interpreted according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology 2015 guidelines. RESULTS: Of the 120 patients, 30 had regional or metastatic disease and 10, 34, 25, and 21 patients were categorized as having low, intermediate, high, or very high-risk disease, respectively. Of the 88 germline variants, 6 pathologic or likely pathogenic variants were identified in 7 patients (5.8%) with BRCA2 (1.7%), HOXB13 (1.7%), PALB2 (0.8%), ATM (0.8%), and MSH2 (0.8%). Of 7 patients, 2 possessed intermediate risk disease that was not included in the recommendation for genetic testing. We identified the Gly132Glu variant, which was different from the Gly84Glu variant of the HOXB13 gene in Western populations. CONCLUSIONS: This study presents the first analysis of germline variants in unselected Korean men with prostate cancer. Our results showed comparable germline prevalence with previous studies and provides evidence for the necessity of genetic testing in Korean men with prostate cancer.

Pilot and Feasibility Studies in Rehabilitation Research: A Review and Educational Primer for the Physiatrist Researcher.

ABSTRACT: Pilot and feasibility studies are conducted early in the clinical research pathway to evaluate whether a future, definitive study can or should be done and, if so, how. Poor planning and reporting of pilot and feasibility studies can compromise subsequent research efforts. Inappropriate labeling of studies as pilots also compromises education. In this review, first, a systematic survey of the current state of pilot and feasibility studies in rehabilitation research was performed, and second, recommendations were made for improvements to their design and reporting. In a random sample of 100 studies, half (49.5%) were randomized trials. Thirty (30.0%) and three (3.0%) studies used "pilot" and "feasibility" in the study title, respectively. Only one third (34.0%) of studies provided a primary objective related to feasibility. Most studies (92.0%) stated an intent for hypothesis testing. Although many studies (70.0%) mentioned outcomes related to feasibility in the methods, a third (30.0%) reported additional outcomes in the results and discussion only or commented on feasibility anecdotally. The reporting of progression plans to a main study (21.0%) and progression criteria (4.0%) was infrequent. Based on these findings, it is recommended that researchers correctly label studies as a pilot or feasibility design based on accepted definitions, explicitly state feasibility objectives, outcomes, and criteria for determining success of feasibility, justify the sample size, and appropriately interpret and report the implications of feasibility findings for the main future study.

Plasma osteoprotegerin levels are associated with the presence and burden of cerebral small vessel disease in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Osteoprotegerin (OPG) is a component of the tumor necrosis factor receptor superfamily. Several studies have shown a relationship between OPG and cardiovascular diseases. We hypothesized that there is a relationship between plasma OPG levels and cerebral small vessel disease (SVD). METHODS: Patients diagnosed with their first cerebral ischemic infarction between April 2014 and March 2017 were enrolled. All the enrolled patients were evaluated through the hospital stroke protocol, including routine blood tests, brain imaging, and measuring the plasma OPG levels. The presence and burden of cerebral SVD [cerebral microbleeds (CMBs), asymptomatic lacunar infarction (ALI), high-grade perivascular space (HPVS), high-grade white matter hyperintensity (HWMH)], and total SVD score were assessed through brain magnetic resonance imaging. RESULTS: Of the 270 patients included in our study, 158 (58.5%) were men. The mean age of the patients was 63.8 ± 11.6 years. In multivariable analysis, plasma OPG levels were positively associated with the presence and burden of each cerebral SVD. The odds ratios (OR) of CMBs, ALI, HPVS, and HWMH for the association of OPG per standard deviation (SD) increase were 1.58 [95% confidence interval (CI), 1.09-2.27], 1.40 (95% CI, 1.04-1.88), 1.88 (95% CI, 1.27-2.78), and 1.47 (95% CI, 1.04-2.08), respectively. Plasma OPG levels were positively correlated with total SVD score (beta = 0.211, standard error = 0.061, p-value = 0.009, R2 = 0.275). CONCLUSIONS: Plasma OPG levels correlate with the presence and burden of cerebral SVD in patients with acute ischemic stroke.

Voltage-Tunable Ultra-Steep Slope Atomic Switch with Selectivity over 1010.

Atomic switch-based selectors, which utilize the formation of conductive filaments by the migration of ions, are researched for cross-point array architecture due to their simple structure and high selectivity. However, the difficulty in controlling the formation of filaments causes uniformity and reliability issues. Here, a multilayer selector with Pt/Ag-doped ZnO/ZnO/Ag-doped ZnO/Pt structure by the sputtering process is presented. A multilayer structure enables control of the filament formation by preventing excessive influx of Ag ions. The multilayer selector device exhibits a high on-current density of 2 MA cm-2 , which can provide sufficient current for the operation with the memory device. Also, the device exhibits high selectivity of 1010 and a low off-current of 10-13 A. The threshold voltage of selector devices can be controlled by modulating the thickness of the ZnO layer. By connecting a multilayer selector device to a resistive switching memory, the leakage current of the memory device can be reduced. These results demonstrate that a multilayer structure can be used in a selector device to improve selectivity and reliability for use in high-density memory devices.

Tracheostomy During the COVID-19 Pandemic: Comparison of International Perioperative Care Protocols and Practices in 26 Countries.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has led to a global surge in critically ill patients requiring invasive mechanical ventilation, some of whom may benefit from tracheostomy. Decisions on if, when, and how to perform tracheostomy in patients with COVID-19 have major implications for patients, clinicians, and hospitals. We investigated the tracheostomy protocols and practices that institutions around the world have put into place in response to the COVID-19 pandemic. DATA SOURCES: Protocols for tracheostomy in patients with severe acute respiratory syndrome coronavirus 2 infection from individual institutions (n = 59) were obtained from the United States and 25 other countries, including data from several low- and middle-income countries, 23 published or society-endorsed protocols, and 36 institutional protocols. REVIEW METHODS: The comparative document analysis involved cross-sectional review of institutional protocols and practices. Data sources were analyzed for timing of tracheostomy, contraindications, preoperative testing, personal protective equipment (PPE), surgical technique, and postoperative management. CONCLUSIONS: Timing of tracheostomy varied from 3 to >21 days, with over 90% of protocols recommending 14 days of intubation prior to tracheostomy. Most protocols advocate delaying tracheostomy until COVID-19 testing was negative. All protocols involved use of N95 or higher PPE. Both open and percutaneous techniques were reported. Timing of tracheostomy changes ranged from 5 to >30 days postoperatively, sometimes contingent on negative COVID-19 test results. IMPLICATIONS FOR PRACTICE: Wide variation exists in tracheostomy protocols, reflecting geographical variation, different resource constraints, and limited data to drive evidence-based care standards. Findings presented herein may provide reference points and a framework for evolving care standards.

Exploring pharmacogenetic difference using adverse event database: an example of clopidogrel and cardiovascular events.

Background: Poor clopidogrel metabolizers, carrying a cytochrome P450 2C19 loss-of-function allele, are more frequent among East Asians than Caucasians/White. Materials & methods: The Korea adverse event reporting system database and a case/noncase study design were used to examine the disproportionality of cardiovascular events following clopidogrel use. The US FDA's adverse event reporting system database was also analyzed for comparison. Results: In the Korea adverse event reporting system data, the clopidogrel reporting odds ratio for cardiovascular events was 7.34, more than double that of ticagrelor. In the FDA's adverse event reporting system data, the clopidogrel reporting odds ratio was 4.69, lower than that of ticagrelor. Adjustment for covariates did not change the trend. Conclusion: Considering the prevalence of poor clopidogrel metabolizers and the reported cardiovascular events among Koreans, rigorous clinical management is required for clopidogrel users.

Comparison of Four Commercial Kits for Isolation of Urinary Cell-Free DNA and Sample Storage Conditions.

Urinary cell-free DNA (cfDNA) is an attractive body fluid for liquid biopsy. In this study, we compared the efficiencies of four commercial kits for urinary cell-free DNA (cfDNA) isolation and of various sample storage conditions. Urinary cfDNA was isolated from 10 healthy individuals using four commercial kits: QIAamp Circulating Nucleic Acid Kit (QC; Qiagen), MagMAX™ Cell-Free DNA Isolation Kit (MM; Applied Biosystems), Urine Cell-Free Circulating DNA Purification Midi Kit (NU; Norgen Biotek), and Quick-DNA™ Urine Kit (ZQ; Zymo Research). To assess the isolation efficiency, an Agilent 2100 Bioanalyzer with High Sensitivity DNA chips was used, and cfDNA yield was defined as the amount of cfDNA obtained from 1 mL of urine. MM and QC provided the highest cfDNA yield in the 50-300 bp range, and MM and NU gave the highest cfDNA yield in the 50-100 bp range. In particular, the NU kit was efficient for isolation of more fragmented cfDNA in the range of 50-100 bp with the lowest cellular genomic DNA contamination. ZQ had the best cost-efficiency for isolating the same amount of urinary cfDNA. Samples stored at -70 °C with the addition of 10 mM EDTA resulted in the highest cfDNA yield 3 months after sample collection.

Single-port robot-assisted radical prostatectomy with the da Vinci SP system: A single surgeon's experience.

Purpose: To report an initial single-surgeon experience with single-port robot-assisted radical prostatectomy (SP-RARP) using the da Vinci SP surgical system (Intuitive Surgical, USA). Materials and Methods: Between December 2018 and October 2019, a single surgeon performed SP-RARP in 20 patients with prostate cancer. SP-RARP was performed using the conventional approach through an umbilical port with a GelPOINT access system (Applied Medical, USA) and an additional assist port. During surgery, the camera was placed in the 6- or 12-o'clock position, and a traction arm was placed in the counterpart position for upward or downward traction. Clinicopathologic data, perioperative data, and short-term surgical outcomes were analyzed. Results: Of 20 patients, 45% of patients had pT3 or greater disease and 45% had Gleason grade 4 to 5, respectively. In 11 patients that underwent lymph node dissection, the median number of lymph nodes removed was 19 (interquartile range [IQR], 14-22). Median operative time was 245 minutes (IQR, 200-255), and median console time was 190 minutes (IQR, 165-210). Median blood loss was 200 mL (IQR, 150-300 mL), and there were no intraoperative complications or open conversion. In 10 patients with a follow-up period longer than 3 months, one patient experienced biochemical recurrence, and all patients required 0 to 1 pads per day. Of seven patients that were potent before surgery, four recovered erectile function sufficient for intercourse. Conclusions: Our report shows the safety and feasibility of SP-RARP, and that the associated surgical outcomes with short-term follow-up are satisfactory.

Prolyl hydroxylase-3 is a novel renal cell carcinoma biomarker.

Purpose: The aim of this study was to determine the suitability of serum prolyl hydroxylase-3 (PHD3) as a diagnostic or monitoring biomarker of renal cell carcinoma (RCC). Materials and Methods: Between October 2013 and March 2015, we prospectively recruited study participants. The RCC group consisted of 56 patients who underwent radical or partial nephrectomy. The control group included 56 healthy kidney donors and 13 patients with benign renal masses. Blood from the RCC patients was sampled prior to surgery and again 1 and 3 months after the operation. Serum PHD3 levels were measured via enzyme-linked immunosorbent assay and compared between RCC patients and controls. Results: RCC patients had higher serum PHD3 levels than controls (0.79±0.17 ng/mL vs. 0.73±0.09 ng/mL, p=0.023), with an area under curve (AUC) of 0.668. With a cutoff value of 0.761 ng/ml, the sensitivity, specificity, positive predictive value, and negative predictive value were 66.1%, 68.1%, 28.8%, and 37.3%, respectively. No significant difference in PHD3 level was observed between healthy kidney donors and patients with benign renal masses. The predictive performance of PHD3 was improved in subgroup analyses of RCC patients with a tumor size >2 cm (n=40) or clear-cell histology (n=44), with AUCs of 0.709 and 0.688, respectively. Among 37 patients with PHD3 levels greater than the cutoff value of 0.761 ng/mL, the postoperative PHD3 levels at 1 and 3 months were significantly lower than the preoperative PHD3 levels (both p<0.001). Conclusions: Serum PHD3 represents a novel RCC biomarker that shows acceptable diagnostic performance.

Diagnostic Accuracy of Radiologic Methods for Ankle Syndesmosis Injury: A Systematic Review and Meta-Analysis.

: Misdiagnosis and inadequate treatment of syndesmosis could result in significant long-term morbidity including pain, instability, and degenerative changes of the ankle joint. The objective of this systematic review and meta-analysis was to determine whether radiologic tests accurately and reliably diagnose ankle syndesmosis injury. Medline, Embase, and Cochrane were searched. The database search resulted in 258 full text articles that we assessed for eligibility, we used eight studies that met all the inclusion criteria. In subgroup meta-analysis, the sensitivity analysis showed significant differences only in the MRI (Magnetic Resonance Imaging), and specificity was not statistically significant. In diagnostic meta-analysis, the pooled sensitivity and specificity were 0.528 and 0.984 for X-rays, 0.669 and 0.87 for CT (Computed Tomography), and 0.929 and 0.865 for MRI, all respectively. For sensitivity, MRI showed significantly sensitivity as higher than the other methods, and we detected no significance for specificity. Syndesmosis injuries differed significantly in the accuracy of radiological methods according to the presence of accompanied ankle fractures. In patients with fractures, simple radiography has good specificity, and CT and MRI have high sensitivity and specificity irrespective of fracture; in particular, MRI has similar accuracy to gold standard arthroscopic findings.