Atmospheric concentrations of per- and polyfluoroalkyl substances and their emissions at a waste recycling facility producing refuse-derived paper and plastics densified fuel.

To better understand the types and concentrations of per- and polyfluoroalkyl substances (PFAS) emitted into the air from waste recycling facilities that produce refuse-derived paper and plastics densified fuel (RPF) from industrial waste, we conducted an air sampling campaign at a waste recycling facility in Japan. Both passive and active air sampling were conducted, and the samples collected were used to quantify the PFAS emitted into the air during the production of RPF. Overall, few ionic PFAS were detected in the air at the facility; however, high levels of neutral PFAS (8.21-53.4 ng/m3; 20.7-130 pmol/m3) were measured in the air near the heat molding machines. The two neutral PFAS detected at the highest concentrations were 6:2 fluorotelomer alcohol and 6:2 fluorotelomer methacrylate, which are currently unregulated under the Stockholm Convention, suggesting that product manufacturers have shifted away from using regulated PFAS. Small amounts of regulated PFAS such as 8:2 fluorotelomer methacrylate and 8:2 fluorotelomer acrylate were measured in some parts of the facility. Analysis of the concentrations of PFAS in the exhaust gas from the heat molding machines revealed neutral PFAS concentrations (537-2160 ng/m3; 1350-5040 pmol/m3) that were 1-2 orders of magnitude higher than those in the surrounding indoor air. The total emission of neutral PFAS from the facility to the environment was estimated to be 0.066-0.260 g/day (0.168-0.607 mmol/day), depending on whether air volume discharged as exhaust gas or as indoor ventilation was considered. A contribution analysis of the emissions revealed that treating the exhaust gas from the heat molding machines, which constitutes over 94 % of the total emissions, is very effective at reducing PFAS emissions from the facility.

High-throughput single telomere analysis using DNA microarray and fluorescent in situ hybridization.

The human telomere system is highly dynamic. Both short and long leucocyte average telomere lengths (aTL) are associated with an increased risk of cancer and early death, illustrating the complex relationship between TL and human health and the importance of assessing TL distributions with single TL analysis. A DNA microarray and telomere fluorescent in situ hybridization (DNA-array-FISH) approach was developed to measure the base-pair (bp) lengths of single telomeres. On average 32000 telomeres were measured per DNA sample with one microarray chip assaying 96 test DNA samples. Various telomere parameters, i.e. aTL and the frequency of short/long telomeres, were computed to delineate TL distribution. The intra-assay and inter-assay coefficient of variations of aTL ranged from 1.37% to 3.98%. The correlation coefficient (r) of aTL in repeated measurements ranged from 0.91 to 1.00, demonstrating high measurement precision. aTLs measured by DNA-array-FISH predicted aTLs measured by terminal restriction fragment (TRF) analysis with r ranging 0.87-0.99. A new accurate and high-throughput method has been developed to measure the bp lengths of single telomeres. The large number of single TL data provides an opportunity for an in-depth analysis of telomere dynamics and the complex relationship between telomere and age-related diseases.

Preoperative physiotherapy for improving the reserve capacity in a patient with esophageal cancer and frailty: A case report.

INTRODUCTION: Frailty is significantly correlated with a higher incidence of medical complications during hospitalization after esophagectomy. As frailty is thought to be a reversible condition, improving the reserve capacity through preoperative physical therapy is expected to reduce the risk of postoperative pulmonary complications (PPCs). Herein, we report our experience with preoperative physical therapy in a patient with esophageal cancer who was considered to have inadequate fitness for surgery owing to poor physical performance. CASE PRESENTATION: A 72-year-old man (height: 169.5 cm, weight: 54.7 kg, body mass index: 18.9 kg/m2) with esophagogastric junction tumors (cStage IIIA) was hospitalized and scheduled to undergo surgery based on preoperative screening. He was categorized as frail according to the revised Japanese version of the Cardiovascular Health Study criteria and the Mini Nutritional Assessment Short-Form indicated severe malnutrition. We focused on physical therapy to improve exercise tolerance and prevent PPCs and devised a short-term intensive physical therapy program comprising minimal exercises that the patient could perform efficiently. The program consisted of only inspiratory muscle training and aerobic exercises. His maximal inspiratory pressure (MIP) and 6-min walking distance improved by 30 cm H2O and 145 m, respectively, on the day before surgery compared with those on day 8. The percentage predicted value of the MIP improved from 56.6% at the start of physical therapy to 102.9% on the day before surgery. On day 43, the patient underwent subtotal esophagectomy and was able to ambulate on postoperative day 5 without respiratory complications. CONCLUSION: We conducted a short-term, intensive, and minimal preoperative physical therapy program for a patient with esophageal cancer who had physical frailty. Preoperative physical therapy to increase the reserve capacity may result in a favorable postoperative course even in patients with physical frailty.

Deficient RPE mitochondrial energetics leads to subretinal fibrosis in age-related neovascular macular degeneration.

Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). We found that overexpression of CPT1A in the RPE of Vldlr-/- mice suppresses epithelial-to-mesenchymal transition and fibrosis. Mechanistically, TGFß2 induces fibrosis by activating a Warburg-like effect, i.e. increased glycolysis and decreased mitochondrial respiration through ERK-dependent CPT1A degradation. Moreover, VLDLR blocks the formation of the TGFß receptor I/II complex by interacting with unglycosylated TGFß receptor II. In conclusion, VLDLR suppresses fibrosis by attenuating TGFß2-induced metabolic reprogramming, and CPT1A is a potential target for treating subretinal fibrosis.

Laparoscopic transabdominal preperitoneal repair for a patient with Laugier's and inguinal hernia.

BACKGROUND: Laugier's hernia is a very rare atypical femoral hernia and is challenging to diagnose preoperatively. Herein, we report a rare case of inguinal and Laugier's hernias treated with laparoscopic transabdominal preperitoneal repair. CASE PRESENTATION: A 63-year-old man was admitted to our hospital with right groin swelling for 4 years. Computed tomography revealed an indirect inguinal hernia with protrusion of the small intestine. The preoperative diagnosis was right indirect inguinal hernia; Laugier's hernia was unknown. The patient underwent laparoscopic transabdominal preperitoneal repair. During the surgery, part of the perivesical adipose tissue penetrated the lacunar ligament. It was located medial to the typical site of a femoral hernia. Thus, Laugier's hernia was diagnosed. Finally, laparoscopic transabdominal preperitoneal repair was performed for Laugier's hernia and inguinal hernia. The postoperative course was good, without recurrence. CONCLUSIONS: To our knowledge, this is the first reported case of inguinal and Laugier's hernia treated with laparoscopic transabdominal preperitoneal repair. Surgeons should be mindful that inguinal hernias can occur concurrently with other types of hernias, such as femoral hernias, including atypical variants like Laugier's hernia. Additionally, they should actively consider laparoscopic approaches such as transabdominal preperitoneal for femoral hernias. These approaches are beneficial for precise diagnosis, confirming the presence of other hernias, and simultaneously treating all coexisting inguinal hernias.

Reduced port laparoscopic rectopexy for full-thickness rectal prolapse.

BACKGROUND: Laparoscopic rectopexy is an established treatment option for full-thickness rectal prolapse. Recently, reduced port surgery (RPS) has emerged as a novel concept, offering reduced postoperative pain and improved cosmetic outcomes compared with conventional multiport surgery (MPS). This study aimed to evaluate the feasibility and safety of RPS for full-thickness rectal prolapse. METHODS: From October 2012 to December 2018, 37 patients (MPS: 10 cases, RPS: 27 cases) underwent laparoscopic rectopexy for full-thickness rectal prolapse. Laparoscopic posterior mesh rectopexy (Wells procedure) is the standard technique for full-thickness rectal prolapse at our hospital. RPS was performed using a multi-channel access device, with an additional 12-mm right-hand port. Short-term outcomes were retrospectively compared between MPS and RPS. RESULTS: No significant differences were observed between MPS and RPS in the median operative time, the median blood loss volume, the postoperative complication rates, and median hospital stay duration after surgery. CONCLUSION: Reduced port laparoscopic posterior mesh rectopexy may serve as an effective therapeutic option for full-thickness rectal prolapse. However, to establish the superiority of RPS over MPS, a prospective, randomized, controlled trial is warranted.

Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay.

PURPOSE: Posttreatment detection of ctDNA is strongly predictive of recurrence. Most minimal/molecular residual disease assays require prior tissue testing to guide ctDNA analysis, resulting in lengthy time to initial results and unevaluable patients. EXPERIMENTAL DESIGN: We assessed a tissue-free assay (Guardant Reveal) that bioinformatically evaluates >20,000 epigenomic regions for ctDNA detection in 1,977 longitudinally collected postoperative plasma samples from 342 patients with resected colorectal cancer. RESULTS: We observed sensitive and specific detection of minimal/molecular residual disease associated with clinically meaningful differences in recurrence-free intervals at each time point evaluated with a median lead time of 5.3 months. The longitudinal sensitivity in stage II or higher colon cancer was 81%. Sensitivity increased with serial measurement and varied by recurrence site: higher for liver (100%) versus lung (53%) and peritoneal (40%). Sensitivity among patients with rectal cancer was 60% owing to a high proportion of lung metastases. Specificity was 98.2% among 1,461 posttreatment samples (99.1% among those with follow-up longer than the upper IQR of the lead time observed in this study). CONCLUSIONS: Our data demonstrate the potential clinical utility of ctDNA as a tool to improve the management of stage II and higher colorectal cancer with a methodology that is noninvasive, accessible, and allows for rapid evaluation to inform clinical decisions.

Acquired Hemophilia A Diagnosed Based on Gross Hematuria: A Case Report and Literature Review.

Acquired hemophilia A (AHA) is an acquired bleeding disorder caused by neutralizing antibodies (inhibitors) against Coagulation Factor VIII (FVIII:C), causing sudden hemorrhagic symptoms (i.e., subcutaneous bleeding, intramuscular bleeding, and hematuria). Herein, this study is aimed at presenting a case of AHA diagnosed based on hematuria and reviewing patients who were diagnosed with AHA due to hematuria. A 67-year-old woman was referred to Atsugi City Hospital with painless gross hematuria that began 4 weeks before presentation. Contrast-enhanced computed tomography (eCT) revealed an approximately 2 cm mass in the right renal pelvis, and the patient's activated partial thromboplastin time (APTT) was elevated (61.4 s). The day after the endoscopic biopsy, the patient was in shock due to a large retroperitoneal hematoma. Although her condition stabilized after intravenous radioembolization, she underwent emergency surgeries several times because of rebleeding within the next 3 weeks. At that time, APTT was more prolonged at 106.4 s, and the FVIII:C level was 2%. Mixing tests showed an upwardly convex curve after 2-h incubation, indicating the presence of an inhibitor. Factor VIII inhibitor titer was ≥5.1 Bethesda unit (BU)/mL. A combined product of Plasma-Derived Factors VIIa and X (pd-FVIIa/FX), as second-line hemostatic therapy, as well as cyclophosphamide (CYP), were administered after Recombinant Activated Factor VIIa (rFVIIa) had been ineffective. Following this, the Factor VIII inhibitor titer was undetectable, FVIII:C levels were restored, and APTT decreased to within the normal range. Gross hematuria was significantly alleviated. However, the patient died of cytomegalovirus and fungal infections due to prolonged immunosuppressive therapy. Although AHA diagnosed based on hematuria may have a better prognosis than others, there have been occasional cases with severe outcomes. APTT, detected upon initial hematological testing in patients with hematuria, may be a potential indicator of an existing AHA.

Relationships between obsessive-compulsive disorder and the big five personality traits: A meta-analysis.

Although several studies have examined the relationships between obsessive-compulsive disorder (OCD) and the Big Five personality traits (i.e., neuroticism, extraversion, openness, agreeableness, and conscientiousness), the results have been inconsistent. Therefore, this meta-analysis comprehensively examined the relationships between OCD and these traits. In total, 23 studies (29 independent datasets) with 30,138 participants were analyzed. The pooled effect size was 0.34 (95% confidence interval [CI]: 0.28, 0.40) for neuroticism, -0.14 (95% CI: -0.18, -0.10) for extraversion, -0.04 (95% CI: -0.09, 0.02) for openness, -0.10 (95% CI: -0.16, -0.04) for agreeableness, and -0.03 (95% CI: -0.11, 0.05) for conscientiousness, indicating that OCD was associated with higher scores for neuroticism and lower scores for extraversion and agreeableness. Meta-regression and subgroup analyses indicated that heterogeneity was mainly due to differences in sample types and OCD measurement instruments. Sensitivity analysis showed that the results of the meta-analysis were robust. Overall, neuroticism was a maladaptive trait, whereas extraversion and agreeableness were adaptive traits for OCD. Although the results could be sample- and instrument-specific, our findings may inform preventions and interventions for OCD symptoms.

Candidate tumor-specific CD8+ T cell subsets identified in the malignant pleural effusion of advanced lung cancer patients by single-cell analysis.

Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8+ T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8+ T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified CXCL13, as a candidate gene expressed by tumor-specific T cells. In addition to expressing CXCL13, tumor-specific T cells were present in a higher proportion of T cells co-expressing PDCD1(PD-1)/TNFRSF9(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients (p = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8+ T cells in MPE, which are associated with patients' prognosis. (233 words).

Safety and efficacy of acalabrutinib and obinutuzumab in treatment-naive chronic lymphocytic leukemia: a Japanese phase 1 study.

This report focuses on part 3 of a multicenter, open-label, phase 1 study (NCT03198650) assessing the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of acalabrutinib plus obinutuzumab in Japanese patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL). Ten patients were included; median age was 68 years. With a median treatment duration of 27.2 months, treatment-emergent adverse events (AEs) occurred in all patients (grade ≥3, 70%), and the most common AEs were anemia and headache (40% each). One patient had a grade 4 AE of neutropenia (the only dose-limiting toxicity). PK results suggested no marked effects of concomitant obinutuzumab treatment on the exposure of acalabrutinib. PD assessment indicated that combination therapy provided >98% Bruton tyrosine kinase (BTK) occupancy. Overall response rate (ORR) was 100% with median duration of response (DoR) and median progression-free survival (PFS) not reached. Treatment with acalabrutinib plus obinutuzumab was generally safe and efficacious in adult Japanese patients with TN CLL.

Application of anti-vascular endothelial growth factor antibody restores the function of saliva secretion in a type 2 diabetes mouse model.

OBJECTIVES: Xerostomia, a common complication of type 2 diabetes, leads to an increased risk of caries, dysphagia, and dysgeusia. Although anti-vascular endothelial growth factor (VEGF) antibodies, such as ranibizumab (RBZ), have been used to treat diabetic retinopathy, their effects on the salivary glands are unknown. This study evaluated the effects of RBZ on salivary glands to reduce inflammation and restore salivary function in a mouse model of type 2 diabetes. METHODS: Male KK-Ay mice with type 2 diabetes (10-12 weeks old) were used. The diabetes mellitus (DM) group received phosphate-buffered saline, while the DM + RBZ group received an intraperitoneal administration of RBZ (100 µg/kg) 24 h before the experiment. RESULTS: Ex vivo perfusion experiments showed a substantial increase in salivary secretion from the submandibular gland (SMG) in the DM + RBZ group. In addition, the mRNA expression levels of TNF-α and IL-1ß were considerably lower in this group. In contrast, those of aquaporin 5 were substantially higher in the DM + RBZ group, as revealed by quantitative reverse transcription PCR. Furthermore, the number of lymphocyte infiltration spots in the SMG was notably lower in the DM + RBZ group. Finally, intracellular Ca2+ signaling in acinar cells was considerably higher in the DM + RBZ group than that in the DM group. CONCLUSION: Treating a type 2 diabetic mouse model with RBZ restored salivary secretion through its anti-inflammatory effects.

Comparative Efficacy and Acceptability of Treatment Strategies for Antipsychotic-Induced Akathisia: A Systematic Review and Network Meta-analysis.

BACKGROUND: Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear. DESIGN: We performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on July 24, 2023. We included randomized clinical trials comparing 1 or more treatment strategies for antipsychotic-induced akathisia against each other or control conditions. We included adults with schizophrenia or other psychiatric disorders treated with antipsychotics. The primary outcome was akathisia severity at posttreatment. Secondary outcomes included akathisia response, all-cause dropout, psychotic symptoms, and long-term akathisia severity. We synthesized data in random effects frequentist network meta-analyses and assessed confidence in the evidence using CINeMA. RESULTS: We identified 19 trials with 661 randomized participants (mean age 35.9 [standard deviation 12.0]; 36.7% [195 of 532] women). No trials examined dose reduction or switching of antipsychotics. Findings suggested 5-HT2A antagonists (k = 6, n = 108; standardized mean difference [SMD] -1.07 [95% confidence interval, -1.42; -0.71]) and beta-blockers (k = 8, n = 105; SMD -0.46 [-0.85; -0.07]) may improve akathisia severity, but confidence in the evidence was deemed low. We also found that benzodiazepines (k = 2, n = 13; SMD -1.62 [-2.64; -0.59]) and vitamin B6 (k = 3, n = 67; SMD -0.99 [-1.49; -0.50]) might also be beneficial, but confidence in the evidence was very low. Analyses of secondary outcomes did not provide additional insights. CONCLUSIONS: Our findings suggest that 5-HT2A antagonists, beta-blockers, and with a lesser certainty, benzodiazepines, and vitamin B6 might improve akathisia. Given the low to very low confidence in the evidence of add-on agents and the absence of evidence of their long-term efficacy, careful consideration of side effects is warranted. These recommendations are extremely preliminary and further trials are needed.

Distal gastrectomy and Roux-en-Y reconstruction for refractory reflux esophagitis after proximal gastrectomy and esophagogastric anastomosis reconstruction.

Refractory gastroesophageal reflux disease can develop after proximal gastrectomy and esophagogastrostomy. We introduce a new method that combines distal gastrectomy and Roux-en-Y reconstruction to treat refractory reflux esophagitis in patients who have undergone proximal gastrectomy and esophagogastric anastomosis reconstruction. This novel method may be useful not only for alleviating the symptoms of gastroesophageal reflux disease but also for preventing future esophageal malignancies arising from long-term reflux esophagitis.

Effect of Heparan Sulfate on Vasculogenesis and Dentinogenesis of Dental Pulp Stem Cells.

INTRODUCTION: Heparan sulfate (HS) is a major component of dental pulp tissue. We previously reported that inhibiting HS biosynthesis impedes endothelial differentiation of dental pulp stem cells (DPSCs). However, the underlying mechanisms by which exogenous HS induces DPSC differentiation and pulp tissue regeneration remain unknown. This study explores the impact of exogenous HS on vasculogenesis and dentinogenesis of DPSCs both in vitro and in vivo. METHODS: Human-derived DPSCs were cultured in endothelial and odontogenic differentiation media and treated with HS. Endothelial differentiation of DPSCs was investigated by real-time polymerase chain reaction and capillary sprouting assay. Odontogenic differentiation was assessed through real-time polymerase chain reaction and detection of mineralized dentin-like deposition. Additionally, the influence of HS on pulp tissue was assessed with a direct pulp capping model, in which HS was delivered to exposed pulp tissue in rats. Gelatin sponges were loaded with either phosphate-buffered saline or 101-102 µg/mL HS and placed onto the pulp tissue. Following a 28-day period, tissues were investigated by histological analysis and micro-computed tomography imaging. RESULTS: HS treatment markedly increased expression levels of key endothelial and odontogenic genes, enhanced the formation of capillary-like structures, and promoted the deposition of mineralized matrices. Treatment of exposed pulp tissue with HS in the in vivo pulp capping study induced formation of capillaries and reparative dentin. CONCLUSIONS: Exogenous HS effectively promoted vasculogenesis and dentinogenesis of DPSCs in vitro and induced reparative dentin formation in vivo, highlighting its therapeutic potential for pulp capping treatment.

Marital status after colorectal surgery in familial adenomatous polyposis: a nationwide multicenter study in Japan.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) experience psychological and social challenges concerning future events such as marriage and childbirth alongside the medical risks of colorectal cancer (CRC) and FAP-related disease. We retrospectively investigated the rate of marriage and childbirth postoperatively in Japanese patients with FAP. METHODS: We included 161 patients who had colorectal surgery and reported marital status from a national survey of 35 Japanese institutions. Participants were classified according to marital status: married before colectomy (80 patients), married after colectomy (13 patients), and unmarried (68 patients). RESULTS: The marriage rate for all 161 patients (57.8%, standardized ratio 0.95, 95% confidence interval [CI] 0.76-1.14) was comparable to that in the general Japanese population (57.1%). The marriage rate among the 81 patients who were unmarried before colectomy was low (16.0%); however, the standardized marital ratio (0.75, 95% CI 0.34-1.15) was not significantly lower than that of the general population. In multivariable logistic regression, younger age (born after 1980, odds ratio [OR] 0.12, p < 0.001) and genetic testing (OR 4.06, p = 0.001) were associated with postoperative marriage. Seventy-one percent of patients with FAP who married after colectomy became pregnant and achieved delivery. CONCLUSIONS: The marriage rate of patients with FAP was comparable to that of the general population whereas the rate after colectomy was low among patients with FAP. However, in patients with FAP, colorectal surgery itself may not lead to negative consequences in terms of fecundity.

Analysis of Genetic Structure and Genetic Diversity in Japanese Grey-Headed Lapwing Population Using mtDNA.

The grey-headed lapwing (Vanellus cinereus) is a wading species in East Asia. However, examples of regional population dynamics and genetic research are limited. To reconsider the natural history and current status of the grey-headed lapwing in Japan, we analyzed the genetic diversity of the Japanese grey-headed lapwing population. We collected 77 grey-headed lapwing samples from 12 locations across Japan during the breeding season and three individuals during the wintering season and extracted DNA; 496-bp sequences of the ND2, which form part of the mitochondrial DNA, were determined for genetic analysis of the population. Consequently, 10 haplotypes were detected in 80 individuals, and 67 individuals, 84% of the total, shared two haplotypes, namely Vc1 and Vc2. Furthermore, the results showed that the prevalence of Vc1 was higher mainly in northern Japan, while that of Vc2 was higher mainly in southern Japan. Genetic diversity analysis showed that the overall haplotype diversity in Japan was 0.617, which is not particularly low. The sequence of Vc1 was exactly the same as that of grey-headed lapwing in China. Our study revealed the genetic structure of the grey-headed lapwing, suggesting that as the grey-headed lapwing expanded its distribution area into southern Japan, many Vc2-positive individuals migrated southward, resulting in a higher detection rate of Vc2 in southern Japan.

Clinical Impact of a Local Triage System Using the Emergent Large Vessel Occlusion Screen with a Rotation System of Thrombectomy-Capable Hospitals.

Objective: Early intervention with mechanical thrombectomy (MT) is expected to improve the functional outcome in patients with large vessel occlusion (LVO); however, a method for the effective detection of these patients in a prehospital setting and early transport to MT-capable hospitals has not been established. This study aimed to analyze the clinical impact and diagnostic performance of the emergent large vessel occlusion (ELVO) screen and its influence on the transportation time. Methods: The emergency medical services (EMS) in one of the secondary medical areas in Akita, Japan, introduced a prehospital triage system employing an ELVO screen and a rotation system of three MT-capable hospitals on December 1, 2021. Patients who were transferred to each of the three hospitals involved in the rotation system according to a predefined priority list from December 2021 to November 2022 were included in the triage group. Patients who underwent MT in the three hospitals before the introduction of the triage system were assigned to the pre-triage group. We compared the transportation time parameters between the two groups and analyzed the performance of the ELVO screen for the diagnosis of LVOs. This study was approved by the institutional review boards of all three hospitals. Results: Time parameters were compared between the 37 and 42 patients who underwent MT and had detailed data in the triage (n = 351) and pre-triage (n = 43) groups, respectively. The time from door to puncture tended to decrease in the triage group in all hospitals, with one hospital showing a statistically significant shortening of 14 min (p = 0.018). In the triage group, 209 ELVO screen-positive patients were present, with 60 (28.7%) of these having LVO. The sensitivity, specificity, positive and negative predictive values, and area under the curve of the ELVO screen to detect LVO under the present triage system were 87.0%, 47.2%, 28.7%, 93.7%, and 0.671, respectively. Conclusion: The present study demonstrated that the introduction of a triage system may have shortened the time required for MT. ELVO screen may be considered a useful marker for screening LVO in prehospital settings in terms of the sensitivity and negative predictive value; however, further improvement may be necessary to reduce the rate of false positive results.

Spinal intradural pseudocyst formation in central nervous system superficial siderosis.

The figure shows tissue samples taken from three previous cases, revealing the cause of hemosiderin deposition in the central nervous system because of superficial siderosis.

Novel Insights Into the International Association for the Study of Lung Cancer Grading System for Lung Adenocarcinoma.

The new grading system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) defines prognostic subgroups on the basis of histologic patterns observed on surgical specimens. This study sought to provide novel insights into the IASLC grading system, with particular focus on recurrence-specific survival (RSS) and lung cancer-specific survival among patients with stage I adenocarcinoma. Under the IASLC grading system, tumors were classified as grade 1 (lepidic predominant with <20% high-grade patterns [micropapillary, solid, and complex glandular]), grade 2 (acinar or papillary predominant with <20% high-grade patterns), or grade 3 (≥20% high-grade patterns). Kaplan-Meier survival estimates, pathologic features, and genomic profiles were investigated for patients whose disease was reclassified into a higher grade under the IASLC grading system on the basis of the hypothesis that they would strongly resemble patients with predominant high-grade tumors. Overall, 423 (29%) of 1443 patients with grade 1 or 2 tumors classified based on the predominant pattern-based grading system had their tumors upgraded to grade 3 based on the IASLC grading system. The RSS curves for patients with upgraded tumors were significantly different from those for patients with grade 1 or 2 tumors (log-rank P < .001) but not from those for patients with predominant high-grade patterns (P = .3). Patients with upgraded tumors had a similar incidence of visceral pleural invasion and spread of tumor through air spaces as patients with predominant high-grade patterns. In multivariable models, the IASLC grading system remained significantly associated with RSS and lung cancer-specific survival after adjustment for aggressive pathologic features such as visceral pleural invasion and spread of tumor through air spaces. The IASLC grading system outperforms the predominant pattern-based grading system and appropriately reclassifies tumors into higher grades with worse prognosis, even after other pathologic features of aggressiveness are considered.