Impact of Epithelial Claudin-4 and Leukotriene B4 Receptor 2 in Normoganglionic Hirschsprung Disease Colon on Post Pull-through Enterocolitis.

PURPOSE: To investigate whether Leukotriene B4 receptor 2 (BLT-2), an upstream regulator of tight junction protein (TJP) Claudin-4, and TJPs could be etiologic factors in Hirschsprung-associated enterocolitis (HAEC) after pull-through (PT) for Hirschsprung disease (HD). METHODS: Normoganglionic colon (HD-N) and aganglionic rectum (HD-A) specimens from rectal/rectosigmoid (R/RS) or descending/transverse (D/T) HD were assessed using quantitative polymerase chain reaction (qPCR) for Occludin, TJP-1, TJP-2, Junctional adhesion molecule (JAM)-1, JAM-2, Claudin-1, Claudin-3, Claudin-4, and BLT-2 and immunoblotting for Claudin-4 using fresh specimens obtained intraoperatively (2021-2024; n = 17; R/RS = 15 and D/T = 2). Claudin-4 immunohistochemistry was also evaluated quantitatively using preserved (n = 29; R/RS = 20 and D/T = 9; 2009-2021) and fresh HD specimens for comparison with anorectal malformation patients having colostomy closure as controls (n = 42) and between HD-A versus HD-N, R/RS versus D/T, and HAEC (+) versus HAEC (-). Technically inadequate or transitional zone PT were excluded. RESULTS: Subjects were 123 PT cases. Mean ages at PT/colostomy closure (years) were R/RS: 2.7 ± 2.9, D/T: 1.6 ± 2.2, and controls: 1.4 ± 0.7. Postoperative HAEC occurred 18 times in 14 PT cases (grade I = 5, grade II = 13). Post-PT HAEC was significantly more frequent in D/T (50.0% versus 6.4%; p < 0.001); Claudin-4 was significantly lower in HD-N from post-PT HAEC cases, especially D/T (p < 0.05) on immunohistochemistry. Claudin-4 was significantly lower in HD-N/HD-A compared with controls on immunoblotting (p < 0.05) and immunohistochemistry (p < 0.001). qPCR showed TJP-1, TJP-2, JAM-1, JAM-2, Claudin-4, and BLT-2 were significantly lower in HD-N/HD-A compared with controls. CONCLUSIONS: Lower Claudin-4 and BLT2 in post-PT HAEC HD-N (especially D/T) suggests generalized epithelial barrier derangement with possible etiologic implications for HAEC. LEVEL OF EVIDENCE: Ⅱ.

Evaluating perioperative stresses in children by noninvasive modalities using salivary cortisol and autonomic reactivity.

PURPOSE: Salivary cortisol (SalC) and low to high pulse ratio (LHR) were used for evaluating perioperative stresses in children. METHODS: Children aged 6 months-16 years having elective general (thoracic/abdominal) or minor (open/minimally invasive: MI) procedures underwent pulse monitoring during AM (08:00-12:00) and PM (17:00-21:00) saliva collections from the day before surgery (S-1) to 3 days after surgery (S + 3). SalC/LHR were correlated with age, sex, caregiver attendance, operative time, and surgical site/approach using mixed model analysis and face/numeric pain rating scales (FRS/NRS). RESULTS: Mean ages (years): minor-open (n = 31) 4.7 ± 2.0, thoracic-open (n = 2) 8.7 ± 4.9, thoracic-MI (n = 6) 9.6 ± 6.1, abdominal-open (n = 14) 4.3 ± 4.1, and abdominal-MI (n = 32) 8.0 ± 5.0. Postoperative SalC increased rapidly and decreased to preoperative levels by S + 3 (p < 0.001). LHR increased slightly without decreasing (p = 0.038). SalC correlated positively with operative time (p = 0.036) and open surgery (p = 0.0057), and negatively with age (p < 0.0001) and caregiver attendance (p < 0.001). SalC correlated positively with FRS (n = 51) at S + 2(PM) (p = 0.023), S + 3(AM) (p < 0.001), S + 3(PM) (p = 0.012) and NRS (n = 34) at S + 1(AM) (p = 0.031), S + 3(AM) (p < 0.044). LHR positively correlated with age (p = 0.0072), female sex (p = 0.0047), and caregiver attendance (p = 0.0026). Postoperative SalC after robotic-assisted MI was significantly lower than after open surgery at S + 2(AM) (p = 0.020). CONCLUSIONS: SalC correlated with pain. Caregiver attendance effectively alleviated stress.

The Current Achievements of Multi-Gene Panel Tests in Clinical Settings for Patients with Non-Small-Cell Lung Cancer.

Some multi-gene panel tests have been implemented in clinical settings to guide targeted therapy in non-small-cell lung cancer (NSCLC) in Japan. The current performance of multi-gene panel tests under the condition that the Oncomine Dx Target Test (ODxTT) and Amoy Dx® Pan Lung Cancer PCR panel (AmoyDx-multi) are available remains relatively unknown. We retrospectively reviewed consecutive patients with NSCLC, whose FFPE samples were considered for genetic testing. We assessed the submission rates, the success rates, and the driver oncogene detection rates of multi-gene panel tests. A total of 225 patients were histologically newly diagnosed with NSCLC or diagnosed with a recurrence of NSCLC without a previous multi-gene panel test at our institution. Among the 225 patients, the FFPE samples of 212 patients (94.2%) were submitted for multi-gene panel testing, including 191 samples (84.9%) for the ODxTT and 21 samples (9.3%) for the AmoyDx-multi. Among the 212 samples submitted to multi-gene panel tests, the success rate was 99.5% (211/212). The detection rate of driver oncogene alterations for all histologies was 52.4% (111/212), and that for adenocarcinoma was 69.7% (106/152). A favorable submission rate and success rate of multi-gene panel tests were shown, along with a favorable detection rate in recent clinical settings.

Physical Activity Using a Wearable Device as an Alternative to Performance Status in Patients With Advanced Lung Cancer.

Importance: The Eastern Cooperative Oncology Group Performance Status (ECOG PS) is extensively used to guide treatment decisions in patients with advanced lung cancer. However, its assessment is subjective, potentially leading to discordance among observers. Objective: To investigate the association between measured physical activity and ECOG PS, as well as the potential prognostic value of physical activity measurements in patients with advanced lung cancer. Design, Setting, and Participants: This single-institution, prospective observational study enrolled 119 patients with advanced lung cancer scheduled to receive systemic therapy as outpatients at Matsusaka Municipal Hospital in Mie, Japan. Participants wore the wearable device amuelink (Sony) for up to 14 days to measure physical activity, including metabolic equivalent tasks, distance walked, and number of steps taken. ECOG PS was assessed at enrollment, which took place from December 2021 to August 2022. Main Outcomes And Measures: The primary end point was estimating the area under the curve (AUC) for classification into ECOG PS of 2 or higher using physical activity measurements. An analysis of the association with survival was also conducted. Results: Among the 119 patients (median [range] age, 72 (32-88) years; 71 [59.7%] male), mean distance walked (MDW) had the highest diagnostic value for classifying an ECOG PS of 2 or greater, with an AUC of 0.818 (95% CI, 0.703-0.934). Moreover, MDW was also associated with 6-month survival, with an AUC of 0.806 (95% CI, 0.694-0.918). Survival curves significantly diverged based on the MDW threshold, indicating a potential association with survival outcome (hazard ratio, 0.17; 95% CI, 0.05-0.57). Conclusions and Relevance: The cohort study suggests that MDW, as measured by a wearable device, was associated with ECOG PS and may serve as a predictor of health status alongside ECOG PS categories. It demonstrates the potential of objectively measured physical activity in complementing subjective ECOG PS assessments in patients with advanced lung cancer. Further research is needed to confirm the prognostic value of physical activity measurements.

The tyrosine kinase inhibitor nintedanib enhances the efficacy of 90 Y-labeled B5209B radioimmunotherapy targeting ROBO1 without increased toxicity in small-cell lung cancer xenograft mice.

BACKGROUND: Small cell lung cancer (SCLC) has a poor prognosis, and Roundabout homolog 1 (ROBO1) is frequently expressed in SCLC. ROBO1-targeted radioimmunotherapy (RIT) previously showed tumor shrinkage, but regrowth with fibroblast infiltration was observed. The fibroblasts would support tumor survival by secreting growth factors and cytokines. Inhibition of fibroblasts offers a candidate strategy for increasing RIT efficacy. Here, we evaluated the efficacy of combination therapy with 90 Y-labeled anti-ROBO1 antibody B5209B ( 90 Y-B5209B) and the tyrosine kinase inhibitor nintedanib in SCLC xenograft mice. METHODS: Subcutaneous NCI-H69 SCLC xenograft mice were divided into four groups: saline, nintedanib alone, RIT alone, and a combination of RIT with nintedanib (combination). A single dose of 7.4 MBq of 90 Y-B5209B was injected intravenously. Nintedanib was orally administered at a dose of 400 µg five times a week for 4 weeks. Tumor volumes and body weights were measured regularly. Tumor sections were stained with hematoxylin and eosin or Masson trichrome. RESULTS: All six tumors in the combination therapy group disappeared, and four tumors showed no regrowth. Although RIT alone induced similar tumor shrinkage, regrowth was observed. Prolonged survival in the combination therapy group was found compared with the other groups. Temporary body weight loss was observed in RIT and combination therapy. There is no difference in fibroblast infiltration between RIT alone and the combination. CONCLUSION: Nintedanib significantly enhanced the anti-tumor effects of RIT with the 90 Y-B5209B without an increase in toxicity. These findings encourage further research into the potential clinical application of combining RIT with nintedanib.

Disruption of a licorice cellulose synthase-derived glycosyltransferase gene demonstrates its in planta role in soyasaponin biosynthesis.

KEY MESSAGE: CRISPR-Cas9-mediated disruption of a licorice cellulose synthase-derived glycosyltransferase gene, GuCSyGT, demonstrated the in planta role of GuCSyGT as the enzyme catalyzing 3-O-glucuronosylation of triterpenoid aglycones in soyasaponin biosynthesis. Triterpenoid glycosides (saponins) are a large, structurally diverse group of specialized metabolites in plants, including the sweet saponin glycyrrhizin produced by licorice (Glycyrrhiza uralensis) and soyasaponins that occur widely in legumes, with various bioactivities. The triterpenoid saponin biosynthetic pathway involves the glycosylation of triterpenoid sapogenins (the non-sugar part of triterpenoid saponins) by glycosyltransferases (GTs), leading to diverse saponin structures. Previously, we identified a cellulose synthase-derived GT (CSyGT), as a newly discovered class of triterpenoid GT from G. uralensis. GuCSyGT expressed in yeast, which could transfer the sugar glucuronic acid to the C3 position of glycyrrhetinic acid and soyasapogenol B, which are the sapogenins of glycyrrhizin and soyasaponin I, respectively. This suggested that GuCSyGT is involved in the biosynthesis of glycyrrhizin and soyasaponin I. However, the in planta role of GuCSyGT in saponin biosynthesis remains unclear. In this study, we generated GuCSyGT-disrupted licorice hairy roots using CRISPR-Cas9-mediated genome editing and analyzed the saponin content. This revealed that soyasaponin I was completely absent in GuCSyGT-disrupted lines, demonstrating the in planta role of GuCSyGT in saponin biosynthesis.

Clinicopathological and Molecular Characteristics Promoting PD-L1 Expression in Early-stage Lung Adenocarcinoma and Squamous Cell Carcinoma.

BACKGROUND/AIM: Lung adenocarcinoma and lung squamous cell carcinoma represent the most prevalent subtypes of non-small cell lung cancer eligible for surgery in the early stages. The emergence of immune checkpoint inhibitors as adjuvant therapy has shown promising potential in improving the postoperative prognosis of patients with lung cancer. Hence, a comprehensive understanding of the clinicopathological and molecular features of programmed cell death ligand-1 (PD-L1) expression in lung adenocarcinoma and squamous cell carcinoma is crucial. PATIENTS AND METHODS: In this retrospective study, we conducted a comparative analysis of clinicopathological features associated with the expression of PD-L1, stratifying patients who underwent surgical resection into two distinct groups: 289 patients with lung adenocarcinoma and 66 with lung squamous cell carcinoma. Furthermore, we investigated the associations between the expression of PD-L1 and genetic alterations in well-established oncogenic driver mutations. RESULTS: Among the cases, 52.9% exhibited negative PD-L1 expression, 32.9% had low PD-L1 expression, and 12.3% had high PD-L1 expression in adenocarcinoma, while the PD-L1 expression in squamous cell carcinoma showed a near-even distribution. Notably, male sex, smoking history, the presence of invasive pathological factors, and disease progression significantly influenced PD-L1 expression in adenocarcinoma, whereas none of these factors were associated with PD-L1 expression in squamous cell carcinoma. Additionally, the distribution of PD-L1 expression varied based on the type of specific driver gene mutation in adenocarcinoma. CONCLUSION: The present study revealed clinicopathological and molecular differences between lung adenocarcinoma and squamous cell carcinoma patients promoting the expression of PD-L1.

Close-to-lesion transbronchial biopsy: a novel technique to improve suitability of specimens for genetic testing in patients with peripheral pulmonary lesions.

Bronchoscopy with radial-probe endobronchial ultrasound, a guide sheath, and electromagnetic navigation can improve the diagnostic yield of peripheral lung nodules. However, the suitability of specimens for genetic analysis remains unsatisfactory. We hypothesized that a transbronchial biopsy performed after closely approaching the bronchoscope tip to the lesion might provide more suitable specimens for genetic analysis. We enrolled 155 patients with peripheral pulmonary lesions who underwent bronchoscopy with a thin or ultrathin bronchoscope. Bronchoscopy was performed using virtual bronchoscopic navigation and radial-probe endobronchial ultrasound with a guide sheath. The bronchoscope tip was placed closer to the lesion during bronchoscopy to collect larger specimens with higher malignant cell content. The patients who underwent a close-to-lesion biopsy had higher rates of overall diagnostic yield, histopathological diagnostic yield, and specimen quality for genetic testing than those who did not. The significant determinants of the specimen's suitability were the close-to-lesion approach, within-the-lesion image, the use of standard 1.9-mm-forceps, and the number of cancer-cell-positive specimens. The significant predictors of the specimen's suitability for genetic analysis were close-to-lesion biopsy and the number of malignant cell-positive tissue samples. This study demonstrates that the close-to-lesion transbronchial biopsy significantly improves the suitability of bronchoscopic specimens for genetic analysis.

Refractory response to entrectinib for ROS-1 rearranged NSCLC with concurrent de novo TP53 mutation showing good response to CNS lesion, but poor duration of response: A case report.

Entrectinib, a ROS-1 inhibitor, has been shown to be effective for patients with ROS-1 fused NSCLC, and has been established as the standard of care for this population. Entrectinib has been shown to achieve a better response to brain metastasis due to the characteristic of the drug having a weak interaction with P-glycoprotein and, even in prospective studies, the intracranial response is higher. Patients have been known to acquire resistance to molecularly targeted drugs such as EGF-TKIs or ALK-TKIs during targeted therapy. Similarly, the mechanisms of resistance to entrectinib have been reported, but information about the effects of TP53 mutation with entrectinib are still limited. Here, we experienced a case of a patient with ROS-1 fusion and concurrent TP53 mutation who was treated with entrectinib, resulting in a response to brain metastasis but rapid resistance to entrectinib. Our case demonstrates both the intracranial activity of entrectinib and the potential for resistance to entrectinib due to TP53 mutation.

Clinical importance of the range of detectable variants between the Oncomine Dx target test and a conventional single-gene test for EGFR mutation.

Although we have experienced some cases with discordant results between the Oncomine Dx target test (ODxTT) and conventional single gene tests for detecting EGFR alterations, the clinical efficacy of EGFR-TKIs in these discordant cases remains little known. We retrospectively reviewed consecutive patients with non-small-cell lung cancer whose FFPE samples were simultaneously submitted for the ODxTT, and a PNA-LNA PCR clamp test. We evaluated the clinical efficacy of EGFR-TKIs in patients with discordant results between the two tests, focusing on the common EGFR mutations. Among 444 successful results, 10 patients had discordant results for common EGFR mutations (9 Ex 19 deletion and 1 Ex 21 L858R mutation), and all of these were detected only by the PNA-LNA PCR clamp test. Among six discordant cases treated with EGFR-TKI, the mutations detected in 3 patients were not included in the list of detectable variants that are reportable by the ODxTT, while the mutations detected in the other 3 patients were included in the list. For all three discordant cases harboring the mutations not reportable by the ODxTT, good clinical responses were demonstrated. However, among the other three discordant cases harboring the mutations reportable by the ODxTT, only one patient had a clinical response with short duration. Among the discordant cases for common EGFR mutations between the ODxTT and the conventional single gene test, there are a certain number of suitable patients responsive to EGFR-TKIs, especially when the cause of the discordant results comes from the difference in the range of detectable variants that are reportable between the tests.

Physical Activity Estimated by the Wearable Device in Lung Disease Patients: Exploratory Analyses of Prospective Observational Study.

Background. Physical activity is a potential parameter to assess the severity or prognosis of lung disease. However, the differences in physical activity between healthy individuals and patients with lung disease remain unclear. Methods. The analyses in this report are a combined analysis of four cohorts, including a healthy control cohort, in a prospective study designed to evaluate wearable device-estimated physical activity in three cohorts: the lung cancer cohort, the interstitial pneumonia cohort, and the COPD cohort (UMIN000047834). In this report, physical activity in the lung disease cohort was compared with that in the healthy cohort. Subgroup analyses were performed based on age, sex, duration of wearable device use, and lung disease subtype. Results. A total of 238 cases were analyzed, including 216 patients with lung disease and 22 healthy cases. Distance walked and number of steps were significantly lower in the patient group compared to the healthy control group. ROC analysis for the diagnostic value of lung disease by mean distance walked and mean number of steps showed AUC of 0.764 (95%CI, 0.673 to 0.856) and 0.822 (95%CI, 0.740 to 0.905), respectively. There was a significant difference in physical activity by age, but not by gender nor by duration based on the threshold of 7 days of wearing the device. Conclusions. Lung disease decreases physical activity compared to healthy subjects, and aging may bias the estimation of physical activity. The distance walked or number of steps is recommended as a measure of physical activity, with a period of approximately one week and adjusted for age for future investigation.

Good Response of Advanced Thymic Carcinoma with Low PD-L1 Expression to Chemotherapy plus Pembrolizumab as First-Line Therapy and to Pembrolizumab as Maintenance Therapy: A Case Report.

Thymic carcinoma is a rare malignant tumor with a poor prognosis. No standard treatment is currently available. The present case was a 64-year-old male smoker with no symptoms referred to our hospital because of abnormal chest radiological findings. The CT study showed a tumor between the anterior mediastinum and the right lung upper lobe, multiple nodular shadows along the right pleura, and pleural effusion. A CT-guided needle biopsy revealed squamous cell carcinoma. However, the differential diagnosis between thymic carcinoma and primary lung cancer was difficult. Treatment with carboplatin, nanoparticle albumin-bound paclitaxel, and pembrolizumab was initiated. The CT scan showed tumor shrinkage and good clinical response after four treatment cycles. Therapy was switched to maintenance therapy with pembrolizumab alone. Imaging studies showed further tumor shrinkage after twelve cycles of maintenance therapy with pembrolizumab. Sixteen cycles of maintenance therapy were continued without performance status deterioration. An abnormal radiological finding was detected after a twelve-month exacerbation-free period. The diagnosis was thymic carcinoma. Treatment with lenvatinib was initiated, and tumor-size reduction was observed. This is the first report of a case showing a successful maintenance therapy with pembrolizumab after effective first-line therapy with a combination of carboplatin-based chemotherapy plus pembrolizumab in advanced thymic carcinoma.

Retroperitoneoscopic Surgery in Children Does Not Cause Pathological Desaturation in Cerebral/Renal Oxygenation on Near-Infrared Spectroscopy Compared with Laparoscopic and Thoracoscopic Surgery.

Introduction: Cerebral and renal regional oxygen saturation (C-rSO2 and R-rSO2, respectively) were monitored using near-infrared spectroscopy in pediatric patients (range: 0.3-14.3 years) during minimally invasive surgery (MIS) taking at least 3 hours performed by laparoscopy (Lap), thoracoscopy (Tho), or retroperitoneoscopy (Ret) from January 2019 to December 2021. Materials and Methods: Criteria compared were operative time, preoperative/intraoperative hemoglobin, blood loss, mean arterial pressure, arterial partial pressure of carbon dioxide (PaCO2), peripheral oxygen saturation (SpO2), C-rSO2, and R-rSO2. Pathological desaturation (PD) was defined as >20% decrease from baseline, and statistical significance as P < .05. Results: Subjects (n = 79) were similar for gender, age, and body mass index. MIS procedures were: Lap = 45, Tho = 20, Ret = 14; one Lap case required conversion for severe adhesions, not PD. Intraoperative PaCO2 (mmHg) was significantly higher in Tho (maximum: 59.5 ± 17.0, minimum: 39.9 ± 7.5) versus Lap (maximum: 39.9 ± 5.1, minimum: 34.6 ± 3.9) and Ret (maximum: 37.8 ± 4.2, minimum: 35.0 ± 3.3); P < .0001 (maximum), P = .0013 (minimum). Minimum intraoperative SpO2 was significantly lower in Tho (P < .0001). Mean operative times were significantly shorter in Tho (259 ± 114 minutes) versus Lap (433 ± 154 minutes) and Ret (342 ± 100 minutes); P < .0001, respectively. PD was absent during Ret (C-rSO2: 0/14 = 0% and R-rSO2: 0/14 = 0%). Differences in PD for Lap (C-rSO2: 7/45 = 15.6% and R-rSO2: 10/45 = 22.2%) and Tho (C-rSO2: 9/20 = 45.0%, and R-rSO2: 7/20 = 35.0%) were significant; P = .0028 for C-rSO2 and P = .0497 for R-rSO2. Hemoglobin and blood loss were similar. Conclusions: PD was absent during Ret, despite longer operative times. If Ret is indicated for a procedure, neurodevelopmental sequelae of MIS could be minimized.

An oldest-old non-small cell lung cancer patient with abscopal effect in a single lesion.

The abscopal effect without concomitant immunotherapy is a rare event, including among cases of lung cancer. Furthermore, the occurrence of limited abscopal effect for only a single lesion in the metastatic organ consistent with the irradiated organ would be an even more rare event. A 94-year-old man was diagnosed with advanced lung cancer with osteolytic bone metastases in his right iliac bone, and the right side of his axial vertebrae. After palliative radiation therapy to the right iliac lesion for pain relief without other anticancer therapy, the axial vertebral osteolytic lesion disappeared despite no reduction in the other lesions. This case furthers our understanding of the pathogenesis of the abscopal effect.

Comparison of the analytical performance of the Oncomine dx target test focusing on bronchoscopic biopsy forceps size in non-small cell lung cancer.

BACKGROUND: Next-generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide targeted therapy. Although the pathological diagnosis and biomarker tests for patients with advanced lung cancer have mostly been obtained with small biopsy samples, especially with bronchoscopic approaches, the performance for NGS with respect to the different sizes of biopsy forceps remains little known. METHODS: We retrospectively reviewed consecutive patients with non-small cell lung cancer, whose FFPE samples were obtained by endobronchial biopsy/transbronchial biopsy and were submitted for the Oncomine Dx Target Test (ODxTT). We compared the analytical performance for ODxTT with respect to the size of biopsy forceps. RESULTS: A total of 103 samples were identified. The success rate of the ODxTT for the group with all samples obtained with small forceps biopsies (70%) was lower than that of the group with some or all samples obtained with standard forceps biopsies (83%), although without a statistically significant difference (p = 0.20). With regard to the reason for unsuccessful analysis, the proportion of the samples which did not pass the nucleic acid concentration threshold in the former group (15%) was higher compared with that of the latter group (4%) (p = 0.08). The proportion of tissue size 4 mm2 or larger in the former group (70%) was lower than that in the latter group (93%) (p = 0.01). CONCLUSION: The analysis of ODxTT for specimens biopsied using only small forceps is prone to be unsuccessful due to an insufficient amount of nucleic acid.

Drastic transitions of excited state and coupling regime in all-inorganic perovskite microcavities characterized by exciton/plasmon hybrid natures.

Lead-halide perovskites are highly promising for various optoelectronic applications, including laser devices. However, fundamental photophysics explaining the coherent-light emission from this material system is so intricate and often the subject of debate. Here, we systematically investigate photoluminescence properties of all-inorganic perovskite microcavity at room temperature and discuss the excited state and the light-matter coupling regime depending on excitation density. Angle-resolved photoluminescence clearly exhibits that the microcavity system shows a transition from weak coupling regime to strong coupling regime, revealing the increase in correlated electron-hole pairs. With pumping fluence above the threshold, the photoluminescence signal shows a lasing behavior with bosonic condensation characteristics, accompanied by long-range phase coherence. The excitation density required for the lasing behavior, however, is found to exceed the Mott density, excluding the exciton as the excited state. These results demonstrate that the polaritonic Bardeen-Cooper-Schrieffer state originates the strong coupling formation and the lasing behavior.

The Potential of Digital Polymerase Chain Reaction for Improving Diagnostic Yield of Nontuberculous Mycobacteria Pulmonary Disease.

INTRODUCTION: Many patients with nontuberculous mycobacteria pulmonary disease are asymptomatic. The disease diagnosis is confirmed in only a small proportion of patients with radiological findings suspicious for nontuberculous mycobacteria pulmonary disease. Thus, many patients remained undiagnosed. Here, we evaluated the diagnostic value of digital polymerase chain reaction (PCR) in nontuberculous mycobacteria pulmonary disease. METHODS: We prospectively evaluated 123 patients with radiological findings suspicious for nontuberculous mycobacteria pulmonary disease. Digital PCR was performed using bronchial lavage fluid, sputum, saliva, blood, and urine. RESULTS: The culture of bronchial washing fluid was positive for nontuberculous mycobacteria in 53 patients and negative in 70. The positive detection rate of nontuberculous mycobacteria by digital PCR in patients with positive culture (n = 53) was as follows: bronchial lavage fluid 100%, sputum 62.9%, saliva 41.5%, blood 7.5%, and urine 3.8%. All patients with two or more positive partitions for nontuberculous mycobacteria in the digital PCR of bronchial lavage fluid showed nontuberculous mycobacteria growth in the bronchial lavage fluid culture. The digital PCR analysis of the bronchial lavage fluid showed a high sensitivity (100%), specificity (85.7%), positive predictive value (84.1%), negative predictive value (100%), and a high concordance rate (91.9%) with the bronchial lavage fluid culture results. In addition, the culture of bronchial lavage fluid was positive for nontuberculous mycobacteria in patients with two or more positive partitions in the digital PCR of sputum and saliva with a combined positive predictive value of 81.1%. CONCLUSION: Digital PCR analysis of nontuberculous mycobacteria in bronchial lavage fluid shows a high concordance rate with the bronchial lavage fluid culture results and a high positive predictive value using both sputum and saliva, suggesting the potential usefulness of dPCR for diagnosis of nontuberculous mycobacteria pulmonary disease in clinical practice.

Decreased incidence of intussusception during the COVID-19 pandemic. Trends in pediatric surgical emergencies.

PURPOSE: Recent reports suggest that the COVID-19 pandemic may be influencing disease morbidity. The purpose of this study was to investigate pandemic-related changes in the incidence of pediatric surgical emergencies. METHODS: Data from patients with one of 8 typical conditions considered to be pediatric emergencies who presented at 3 hospitals close to central Tokyo were collated retrospectively from accident and emergency (AE) department records for 2020 and compared with data for 3 years prior to 2020. RESULTS: All subjects had similar demographic profiles. The total number of pediatric AE attendances from 2017 to 2020 was 2880 (2017: n = 600, 2018: n = 736, 2019: n = 817, and 2020: n = 727). Annual attendances were similar. Of the 8 conditions, there were significantly less cases of intussusception in 2020 than previously (23/727; 3.1% versus 132/2153; 6.1%) p < 0.01 and the number of emergency surgical interventions for intussusception was also significantly less in 2020 (0/23; 0% versus 13/132; 9.8%) p < 0.01. CONCLUSION: The implementation of preventative measures to combat the COVID-19 pandemic in 2020 would appear to have influenced the etiopathogenesis of intussusception enough to significantly decrease its overall incidence and the requirement for emergency surgical intervention.