Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Favorable Clinical and Radiographic Results of Transtrochanteric Anterior Rotational Osteotomy for Collapsed Subchondral Insufficiency Fracture of the Femoral Head in Young Adults

Background:. Subchondral insufficiency fracture of the femoral head (SIF) occurs infrequently in young adults. As the collapsed SIF lesion is usually located at the anterior portion of the femoral head, young adults with SIF are considered to be candidates for transtrochanteric anterior rotational osteotomy, similar to patients with osteonecrosis of the femoral head (ON). In the present study, we assessed the clinical and radiographic results of anterior rotational osteotomy for the treatment of SIF as compared with ON. Methods:. We retrospectively reviewed 28 consecutive patients who underwent anterior rotational osteotomy for the treatment of unilateral SIF (7 patients) or unilateral ON (21 patients). The mean duration of follow-up was 3.7 years (range, 2.0 to 6.2 years). Clinical and radiographic assessments were performed with use of the Harris hip score (HHS), sequential radiographs, and single-photon emission computed tomography/computed tomography (SPECT/CT) with 99mTc-hydroxymethylene diphosphonate performed 5 weeks after surgery. Results:. The mean HHS (and standard deviation) in the SIF group improved significantly from 51.6 ± 11.7 preoperatively to 91.9 ± 7.1 at 1 year after surgery and to 96.9 ± 3.8 at the time of the latest follow-up (p = 0.0010 and 0.0002, respectively). Similarly, the mean HHS in the ON group improved significantly from 52.4 ± 13.7 preoperatively to 80.7 ± 10.0 at 1 year after surgery and to 88.2 ± 12.6 at the time of the latest follow-up (p 80% was achieved in association with smaller femoral neck-shaft varus angles in the SIF group (10.0° ± 4.2°) as compared with the ON group (15.3° ± 8.2°). Postoperative progression of collapse at the anteriorly rotated subchondral lesion was observed in 5 patients (23.8%) in the ON group but no patients in the SIF group. SPECT/CT images showed that rate of increased tracer uptake at the collapsed lesions in the SIF group was significantly higher than that in the ON group (p < 0.0001). Conclusions:. The present study suggested that the absence of progression of collapse and a sufficient postoperative intact ratio without the need for marked varus realignment may be associated with favorable results following anterior rotational osteotomy for the treatment of SIF in young adults. Level of Evidence:. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence

Exposed Artificial Plate Covered With Perifascial Areolar Tissue as a Nonvascularized Graft

Summary:. Perifascial areolar tissue (PAT) is a loose connective tissue on deep fascia, such as on the groin, thigh, or temporal region, which has abundant vascular plexus and mesenchymal stem cells. Nonvascularized PAT grafts can survive even on hypovascular wound beds. Therefore, PAT grafting is a possible alternative to conventional flap surgery to cover exposed bone or artifacts. In this article, we describe 2 cases of PAT grafting for the treatment of skin ulcers with exposed bone and artificial plate after mandible reconstruction. After negative-pressure wound therapy, PAT was used to covering exposed artificial plate for both cases, and a skin graft onto the PAT graft was performed in 1 case. The ulcers improved in both cases without recurrence. The gold-standard treatment of intractable ulcers and fistulas with an exposed tendon, bone, or artifact is coverage by a well-vascularized skin flap. However, PAT grafting has advantages in similar situations, occasionally together with skin grafting and/or negative-pressure wound therapy, because it is technically simple and less invasive

Oxygen saturation imaging as a useful tool for visualizing the mode of action of photodynamic therapy for esophageal cancer

Background and aims: Oxygen saturation (OS) imaging is a novel technique that directly measures and visualizes the tissue oxygen saturation at the surface of the GI tract. Our purpose was to evaluate the ability of OS imaging to visualize the action mode of photodynamic therapy (PDT). Methods: Eight patients with local recurrence after chemoradiotherapy for esophageal cancer were enrolled. OS imaging observation was performed before PDT, after 100 J/cm2 illumination and illumination completion, and on the second day. Results: OS imaging showed an extreme change in the hypoxic state in the illuminated area, although the change was near invisible on white-light imaging. The median tissue oxygen saturation value at the tumor lesion was 61.5% (range, 36%-91%) before PDT and significantly decreased immediately after illumination: 11% (range, 0%-57%) after 100 J/cm2 illumination, 1% (range, 0%-6%) at PDT completion, and 2% (range, 0%-12%) on the second day. Conclusions: OS imaging could be a useful tool to visualize changes after PDT

Distinct Progression and Efficacy of First-Line Osimertinib Treatment According to Mutation Subtypes in Metastatic NSCLC Harboring EGFR Mutations

Introduction: Osimertinib (OSI), a third-generation EGFR tyrosine kinase inhibitor, is the standard treatment for patients with naive EGFR-mutant NSCLC. Nevertheless, information on how the mutation subtype affects disease progression after the failure of OSI treatment is scarce. Methods: We retrospectively reviewed patients with EGFR-mutant NSCLC who received OSI as a first-line treatment between April 2015 and December 2021. Results: This study included 229 patients. The objective response rate was 71%, with intracranial and extracranial response rates of 71% and 90%, respectively. The median progression-free survival was 23.3 mo (95% confidence interval [CI]: 19.6–26.7), and the median overall survival was 33.7 mo (95% CI: 31.3–58.6). Multivariate analysis revealed that the EGFR exon 21 L858R point mutation (L858R) (hazard ratio [HR] = 1.56, 95% CI: 1.04–2.34, p = 0.0328) and liver metastasis (HR = 2.63, 95% CI: 1.53–4.49, p = 0.0004) were significant predictors of progression-free survival in OSI treatment. The concomitant disease progression involving the central nervous system metastasis was significantly more common in patients with L858R (p = 0.048), whereas concomitant disease progression involving primary lesions was significantly more common in patients with exon 19 deletion mutation (p = 0.01). In addition, the probability of disease progression over time was higher for L858R compared with that for exon 19 deletion mutation, in patients with central nervous system metastasis (log-rank test, p = 0.027). Conclusions: The mutation subtype had an impact not only on the clinical outcome of the first-line OSI treatment but also on progression patterns after OSI treatment in patients with NSCLC harboring EGFR mutations

Recent Status of Procedures in a Single Nationwide Cosmetic Surgery Group

Background:. Recently, cosmetic surgery demand has increased due to the spread of promotional social media in Japan. However, understanding the overall landscape remains difficult due to many clinics with varied procedure options. To understand the current trends and status of cosmetic surgery in Japan, we analyzed large-scale data from a group of clinics throughout the country. Methods:. We analyzed data from 152,457 patients in our database. The periods from September 2018 to August 2021 and September 2021 to February 2023 were defined as the first and second periods, respectively, and the statuses of procedures were compared between the two. Results:. Eye procedures were the most common (23.6%), followed by face-lifts (19.5%) and dark circles under the eyes (10.4%). Between the first and second periods, the number of procedures in the second period (128,898 cases) was overwhelmingly higher than that in the first period (23,559 cases). Orbital fat removal for dark circles under the eyes significantly increased (OR 2.97, 95%CI 2.78–3.17); procedures in provincial cities significantly increased (Kinki/Chugoku/Shikoku: OR 2.21, 95%CI 2.08–2.36); and procedures for patients with occupations where appearance is considered important, such as nightlife businesses or being a celebrity, decreased (celebrity: OR 0.44, 95%CI 0.38–0.51, nightlife business: OR 0.58, 95%CI 0.53–0.62). Conclusions:. In Japan, cosmetic surgery has become increasingly common in recent years, and the trend has been changing over time. In the future, it will be important to organize and enhance our large-scale database to disseminate more accurate and useful information

Clinical Characteristics and Pharmacokinetics Change of Long-Term Responders to Antiprogrammed Cell Death Protein 1 Inhibitor Among Patients With Advanced NSCLC

Introduction: Immune checkpoint inhibitors (ICIs) induce long-term, durable responses in patients with advanced NSCLC. Nevertheless, these responses are limited to a few patients, and most responders have disease progression. The purpose of this study was to determine the differences in clinical factors and blood drug concentrations between long-term responders (LTRs) and non-LTRs. Methods: We retrospectively analyzed consecutive patients with advanced NSCLC who received antiprogrammed cell death protein 1 (PD-1) inhibitor monotherapy (nivolumab) from December 22, 2015, to May 31, 2017. Patients who obtained a clinical benefit for more than 6 months were referred to as “responders”; among these, individuals who had a durable response for more than 2 years were defined as “LTRs.” Those with a clinical benefit for less than 2 years were defined as “non-LTRs.” Results: A total of 212 patients received anti–PD-1 inhibitor monotherapy. The responders accounted for 35% (75 of 212) of the patients. Of these, 29 (39%) were LTRs and 46 (61%) were non-LTRs. The overall response rate and median tumor shrinkage in the LTR group were significantly higher than those in the non-LTR group (76% versus 35%, p < 0.0001, and 66% versus 16%, p < 0.001, respectively). The groups had no significant difference in PD-L1 expression and serum drug concentration at 3- and 6-month post-treatment initiation. Conclusions: Significant tumor shrinkage was associated with a long-term response to an anti–PD-1 inhibitor. Nevertheless, the PD-L1 expression level and pharmacokinetic profile of the inhibitor could not be used to predict the durable response among the responders

High Pretreatment Mean Corpuscular Volume Can Predict Worse Prognosis in Patients With Esophageal Squamous Cell Carcinoma who Have Undergone Curative Esophagectomy

Objective:. To establish the prognostic value of mean corpuscular volume (MCV) in patients with esophageal squamous cell carcinoma (ESCC) who have undergone esophagectomy. Background:. The MCV increases in patients with high alcohol and tobacco consumption. Such a lifestyle can be a risk factor for malnutrition, comorbidities related to those habits, and multiple primary malignancies, which may be associated with frequent postoperative morbidity and poor prognosis. Methods:. This study included 1673 patients with ESCC who underwent curative esophagectomy at eight institutes between April 2005 and November 2020. Patients were divided into normal and high MCV groups according to the standard value of their pretreatment MCV. Clinical background, short-term outcomes, and prognosis were retrospectively compared between the groups. Results:. Overall, 26.9% of patients had a high MCV, which was significantly associated with male sex, habitual smoking and drinking, multiple primary malignancies, and malnutrition, as estimated by the body mass index, hemoglobin and serum albumin values, and the Geriatric Nutritional Risk Index. Postoperative respiratory morbidity (P = 0.0075) frequently occurred in the high MCV group. A high MCV was an independent prognostic factor for worse overall survival (hazard ratio, 1.27; 95% confidence interval, 1.049–1.533; P = 0.014) and relapse-free survival (hazard ratio, 1.23; 95% confidence interval, 1.047–1.455; P = 0.012). Conclusions:. A high MCV correlates with habitual drinking and smoking, malnutrition, and multiple primary malignancies and could be a surrogate marker of worse short-term and long-term outcomes in patients with ESCC who undergo esophagectomy

Comparative Outcomes of Laparoscopic Gastrectomy and Open Gastrectomy for Scirrhous Gastric Cancer: A Multicenter Retrospective Cohort Study

Objective:. A multicenter retrospective cohort study was performed to compare the outcomes of laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for scirrhous gastric cancer (GC) as a unique subtype also known as type 4 gastric cancer or linitis plastica. Background:. Although data on the efficacy and safety of LG as an alternative to OG are emerging, the applicability of LG to scirrhous GC remains unclear. Methods:. Patients with clinical type 4 GC undergoing gastrectomy at 13 hospitals from 2005 to 2015 were retrospectively reviewed. As the primary endpoint, we compared overall survival (OS) between the LG and OG groups. To adjust for confounding factors, we used multivariate Cox regression analysis for the main analyses and propensity-score matching for sensitivity analysis. Short-term outcomes and recurrence-free survival were also compared. Results:. A total of 288 patients (LG, 62; OG, 226) were included in the main analysis. Postoperative complications occurred in 25.8% and 30.1%, respectively (P = 0.44). No significant difference in recurrence-free survival was observed (P = 0.72). The 5-year OS rates were 32.4% and 31.6% in the LG and OG groups, respectively (P = 0.60). The hazard ratio (LG/OG) for OS was 0.98 (95% confidence interval [CI], 0.65–1.43) in the multivariate regression analysis. In the sensitivity analyses after propensity-score matching, the hazard ratio for OS was 0.92 (95% CI, 0.58–1.45). Conclusions:. Considering the hazard ratios and 95% CIs for OS, LG for scirrhous GC was not associated with worse survival than that for OG