Immunohistochemistry of p53 surrogates TP53 mutation as an accurate predictor for early-relapse of surgically resected stage I-III lung adenocarcinoma.

Introduction: TP53 is a strong tumor suppressor gene; its deactivation contributes to carcinogenesis and influences clinical outcomes. However, the prognostic influence of p53 deactivation on early relapse in patients with surgically resected non-small cell lung cancer remains unclear. Materials and methods: A cohort of 170 patients with primary stage I through III lung adenocarcinoma (LADC) and lung squamous cell carcinoma who underwent complete resection at Tokyo Medical and Dental University was screened for TP53 mutations using panel testing, and association studies between TP53 mutations and clinical data, including histology and postoperative recurrence, were performed. The association between TP53 mutations and postoperative recurrence was validated using data from 604 patients with MSK-IMPACT from The Cancer Genome Atlas. Additional immunohistochemistry for p53 was performed on some subsets of the Tokyo Medical and Dental University population. Results: Mutations in TP53 were recurrently observed (35.9%; 61 out of 170) in the Tokyo Medical and Dental University cohort. In the histology-stratified analysis, patients with LADC histology showed TP53 mutations that were associated with poor relapse-free survival (log-rank test; P = .020), whereas patients with lung squamous cell carcinoma histology showed TP53 mutations that were not (P = .99). The poor prognosis of TP53 mutation-positive LADCs was validated in The Cancer Genome Atlas-LADC cohort (log-rank test; P = .0065). Additional immunohistochemistry for p53 in patients with LADC histology in the Tokyo Medical and Dental University cohort showed a significant correlation between TP53 mutations and abnormal IHC pattern of p53 (Cramer's correlation coefficient V = 0.67). Conclusions: TP53 mutation is a potential marker for worse prognosis in surgically resected LADC; immunohistochemistry for p53 could be a surrogate method to identify patients with LADC with a worse prognosis.

[Actinomycosis Empyema:Report of a Case].

A 73-year-old man was referred to our hospital with a right pleural effusion. Chest computed tomography( CT) showed multifocal pleural effusion, and chest drainage was performed. Actinomyces meyeri was detected in the pleural fluid culture. Despite antibiotic treatment, the patient's condition did not improve, and a curettage was performed for empyema. The chest tube was removed on postoperative day 7 and the patient was discharged home uneventfully on day 21. Intravenous antibiotics were given for 16 days, followed by oral antibiotics for 6 months. Actinomycosis empyema is a rare disease with no established duration of treatment, but a total of 6 to 12 months of treatment is generally recommended.

Broadband Quasielastic Scattering Spectroscopy Using a Multiline Frequency Comblike Spectrum in the Hard X-Ray Region.

We developed a novel quasielastic scattering spectroscopy system that uses a multiline frequency comblike resolution function to overcome the limit on the accessible timescale imposed by the inherent single-energy resolution of conventional spectroscopy systems. The new multiline system possesses multiple resolutions and can efficiently cover a wide time range, from 100 ps to 100 ns, where x-ray-based dynamic measurement techniques are being actively developed. It enables visualization of the relaxation shape and wave-number-dependent dynamic behavior using a two-dimensional detector, as demonstrated for the natural polymer polybutadine without deuteration.

The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study.

Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163+PD-L1+ macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68+, CD163+, and CK+ cells with PD-L1+ phenotypes had higher B7-H3 expression compared to PD-L1- cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies.

Early Ambulation Following Lung Resection Surgery: Impact on Short-term Outcomes in Patients with Lung Cancer.

OBJECTIVES: Previous studies indicated that early ambulation following lung resection can prevent postoperative pulmonary complications (PPCs). However, some patients fail to achieve early ambulation owing to factors such as postoperative nausea, vomiting, or pain, particularly on postoperative day 1. This study aimed to address the critical clinical question: Is ambulation for ≥10 m during initial pulmonary rehabilitation necessary after lung resection surgery? METHODS: This retrospective observational cohort study included 407 patients who underwent lung resection surgery for lung cancer between January 2021 and December 2022. Twelve patients with a performance status of ≥2 and 21 patients lacking pulmonary rehabilitation prescriptions were excluded. Patients were categorized into the "early ambulation" group, which included individuals ambulating ≥10 m during rehabilitation on the first postoperative day, and the "delayed ambulation" group. The primary outcome was PPC incidence, with secondary outcomes encompassing pleural drain duration, hospital length of stay, and Δ6-minute walk distance (Δ6MWD: postoperative 6MWD minus preoperative 6MWD). RESULTS: The early and delayed ambulation groups comprised 315 and 59 patients, respectively. Significant disparities were noted in the length of hospital stay (7 [6-9] days vs. 8 [6-11] days, P = 0.01), pleural drainage duration (4 [3-5] days vs. 4 [3-6] days, P = 0.02), and Δ6MWD (-70 m vs. -100 m, P = 0.04). However, no significant difference was observed in PPC incidence (20.6% vs. 32.2%, P = 0.06). CONCLUSIONS: Ambulation for ≥10 m during initial pulmonary rehabilitation after lung resection surgery may yield short-term benefits as evidenced by improvements in various outcomes. However, it may not significantly affect the PPC incidence.

Efficient Separation of Methanol Single-Micron Droplets by Tailing Phenomenon Using a PDMS Microfluidic Device.

Microdroplet-based fluidic systems have the advantages of small size, short diffusion time, and no cross-contamination; consequently, droplets often provide a fast and precise reaction environment as well as an analytical environment for individual molecules. In order to handle diverse reactions, we developed a method to create organic single-micron droplets (S-MDs) smaller than 5 µm in diameter dispersed in silicone oil without surfactant. The S-MD generation microflow device consists of a mother droplet (MoD) generator and a tapered separation channel featuring multiple side channels. The tapered channel enhanced the shear forces to form tails from the MoDs, causing them to break up. Surface treatment with the fluoropolymer CYTOP protected PDMS fluid devices from organic fluids. The tailing separation of methanol droplets was accomplished without the use of surfactants. The generation of tiny organic droplets may offer new insights into chemical separation and help study the scaling effects of various chemical reactions.

Examination of knee extensor and valgus moment arms of the patellar tendon in older individuals with and without knee osteoarthritis.

BACKGROUND: Joint moment arm is a major element that determines joint torque. This study aimed to investigate factors associated with knee extensor and valgus moment arms of the patellar tendon in older individuals with and without knee osteoarthritis. METHODS: Thirty-six participants with knee osteoarthritis (mean age, 78.1 ± 6.0 years) and 43 healthy controls (mean age, 73.0 ± 6.3 years) were analyzed. Magnetic resonance images (MRI) from the knee joint and thigh were acquired using a 3.0 T MRI scanner. The three-dimensional moment arm was defined as the distance between the contact point of the tibiofemoral joint and the patellar tendon line. The three-dimensional moment arm was decomposed into sagittal and coronal components, which were calculated as knee extensor and valgus moment arms, respectively. Quadriceps muscle volume, epicondylar width, bisect offset, Insall-Salvati ratio, and Kellgren-Lawrence grade were assessed. Multiple regression analyses were performed in the healthy control and knee osteoarthritis groups, with knee extensor and valgus moment arms as dependent variables. FINDINGS: Knee extensor moment arm was significantly associated with epicondylar width and the Insall-Salvati ratio in the healthy control group and with Kellgren-Lawrence grade, epicondylar width, and quadriceps muscle volume in the knee osteoarthritis group. Valgus knee moment arm was significantly associated with bisect offset in both the groups. INTERPRETATION: Knee size, osteoarthritis severity, and quadriceps muscle volume affect the knee extensor moment arm in knee osteoarthritis, whereas lateral patellar displacement affects the valgus knee moment arms in older individuals with and without knee osteoarthritis.

Characteristics of Acute Cartilage Response After Mechanical Loading in Patients with Early-Mild Knee Osteoarthritis.

This study determined whether the acute cartilage response, assessed by cartilage thickness and echo intensity, differs between patients with early-mild knee osteoarthritis (OA) and healthy controls. We recruited 56 women aged ≥ 50 years with Kellgren-Lawrence (KL) grade ≤ 2 (age, 70.6 ± 7.4 years; height, 153.7 ± 5.2 cm; weight, 51.9 ± 8.2 kg). Based on KL grades and knee symptoms, the participants were classified into control (KL ≤ 1, asymptomatic, n = 27) and early-mild knee OA groups (KL 1 and symptomatic, KL 2, n = 29). Medial femoral cartilage thickness and echo intensity were assessed using ultrasonographic B-mode images before and after treadmill walking (15 min, 3.3 km/h). To investigate the acute cartilage response, repeated-measures analysis of covariance (groups × time) with adjusted age, external knee moment impulse, steps during treadmill walking, and cartilage thickness at pre-walking was performed. A significant interaction was found at the tibiofemoral joint; after walking, the cartilage thickness was significantly decreased in the early-mild knee OA group compared to the control group (p = 0.002). At the patellofemoral joint, a significant main effect of time was observed, but no interaction was detected (p = 0.802). No changes in cartilage echo intensity at either the tibiofemoral or patellofemoral joints, and no interactions were noted (p = 0.295 and p = 0.063). As acute cartilage response after walking, the thickness of the medial tibiofemoral joint in the early-mild knee OA was significantly reduced than that in the control group. Thus, greater acute deformation after walking might be a feature found in patients with early-mild knee OA.

Towards Industrially Important Applications of Enhanced Organic Reactions by Microfluidic Systems.

This review presents a comprehensive evaluation for the manufacture of organic molecules via efficient microfluidic synthesis. Microfluidic systems provide considerably higher control over the growth, nucleation, and reaction conditions compared with traditional large-scale synthetic methods. Microfluidic synthesis has become a crucial technique for the quick, affordable, and efficient manufacture of organic and organometallic compounds with complicated characteristics and functions. Therefore, a unique, straightforward flow synthetic methodology can be developed to conduct organic syntheses and improve their efficiency.

Understanding muscle coordination during gait based on muscle synergy and its association with symptoms in patients with knee osteoarthritis.

OBJECTIVE: We aimed to investigate the muscle coordination differences between a control group and patients with mild and severe knee osteoarthritis (KOA) using muscle synergy analysis and determine whether muscle coordination was associated with symptoms of KOA. METHOD: Fifty-three women with medial KOA and 19 control patients participated in the study. The gait analyses and muscle activity measurements of seven lower limb muscles were assessed using a motion capture system and electromyography. Gait speed and knee adduction moment impulse were calculated. The spatiotemporal components of muscle synergy were extracted using non-negative matrix factorization, and the dynamic motor control index during walking (walk-DMC) was computed. The number of muscle synergy and their spatiotemporal components were compared among the mild KOA, severe KOA, and control groups. Moreover, the association between KOA symptoms with walk-DMC and other gait parameters was evaluated using multi-linear regression analysis. RESULTS: The number of muscle synergies was lower in mild and severe KOA compared with those in the control group. In synergy 1, the weightings of biceps femoris and gluteus medius in severe KOA were higher than that in the control group. In synergy 3, the weightings of higher tibial anterior and lower gastrocnemius lateralis were confirmed in the mild KOA group. Regression analysis showed that the walk-DMC was independently associated with knee-related symptoms of KOA after adjusting for the covariates. CONCLUSIONS: Muscle coordination was altered in patients with KOA. The correlation between muscle coordination and KOA may be attributed to the knee-related symptoms. Key points • Patients with knee osteoarthritis (OA) experienced a deterioration in muscle coordination when walking. • Loss of muscle coordination was associated with severe knee-related symptoms in knee OA. • Considering muscle coordination as a knee OA symptom-related factor may provide improved treatment.

The clinical results of bi-cruciate vs posterior stabilized total knee arthroplasty for flexion contracture in osteoarthritic knee.

BACKGROUND: The improvement of flexion contracture is important in knee arthroplasty since residual flexion contracture postoperatively is associated with decreased quality of life and patient satisfaction. In this study, we investigated the effect of bi-cruciate stabilized (BCS)-type total knee arthroplasty (TKA) as compared to posterior stabilized (PS)-type TKA on osteoarthritic primary knees with flexion contractures. METHODS: 59 TKAs from January 2014 to December 2020, of which 30 were PS-type TKAs (NexGen LPS-flexⓇ; 76.3 years, BMI 27.5) and 29 BCS-type TKAs (Journey IIⓇ; 72.5 years, BMI 28.6), were performed for knee osteoarthritis with preoperative flexion contracture of 15° or greater. Full extension was obtained intraoperatively during all TKAs. Clinical outcomes, radiological evaluations, and the amount of additional distal femoral osteotomy during TKA were evaluated in a retrospective study design. RESULTS: The range of motion improved in the both groups. Postoperative flexion contracture was significantly improved in the BCS group. Knee Society Score improved significantly in both groups, with no difference between the two groups. The amount of additional distal femoral osteotomy was 2.5 ± 1.3 mm for the PS group, and 1.8 ± 1.5 mm for the BCS group, showing a significant difference (p = 0.04). DISCUSSION: The BCS-type TKA significantly improved preoperative flexion contracture and reduced the amount of additional distal femoral osteotomy compared to PS-type TKA. This is attributed to the anterior cam in the BCS-type TKA, which leads to a smaller amount of protrusion of the posterior femoral condyle from the posterior margin of the tibial component in the BCS-type in knee extension, as compared to the PS-type.

Long-term outcome of patients with peripheral ground-glass opacity-dominant lung cancer after sublobar resections.

OBJECTIVE: This study aimed to evaluate the long-term prognosis of patients with peripheral small ground-glass opacity-dominant lung cancer after sublobar resection. We have already reported the 5-year safety and efficacy of sublobar resection and report the long-term outcomes after a 10-year follow-up period. METHODS: Between May 2009 and April 2011, 333 patients with radiologically noninvasive peripheral lung cancer were enrolled from 51 institutions (median age, 62 years at registration) and followed up until May 6, 2021. Of these patients, sublobar resections with wedge resection as the first choice were performed in 314 patients (258 wedge resections and 56 segmentectomies), conversion lobectomies were performed in 11 patients, and 8 patients were ineligible. RESULTS: The 10-year relapse-free survival and overall survival for the 314 patients with sublobar resections were 98.6% (95% confidence interval, 96.2-99.5) and 98.5% (95% confidence interval, 96.1-99.4), respectively. There was 1 local recurrence at the resection margin. Among the patients, second cancers were observed in 43 patients (13.4%; 95% confidence interval, 9.8-17.6), of which 18 were second lung cancers (5.8%; 95% confidence interval, 3.5-8.9). CONCLUSIONS: Peripheral ground-glass opacity-dominant lung cancer is cured by sublobar resection, with wedge resection as the first choice, and the indications for other treatment options should be further investigated. The incidence of second cancer is similar to that in the general Japanese population.

The possibility of mutations of RAS signaling genes and/or TP53 in combination as a negative prognostic impact on pathological stage I non-small cell lung cancer.

BACKGROUND: The recurrence rate of non-small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high-risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis. MATERIALS AND METHODS: A cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer-associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA). RESULTS: Mutations in TP53, RAS signaling genes KRAS and HRAS, and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse-free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log-rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log-rank test, p = 0.10). CONCLUSION: Mutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC.

[Esophagectomy for Bronchogenic Cyst within the Esophageal Muscle Layer with Dysphagia:Report of a Case].

A 26-year-old man referred to our hospital because of dysphagia and a mediastinal tumor detected on chest computed tomography (CT). A contrast-enhanced CT revealed a 12 cm long cystic tumor along the right thoracic esophagus. An upper gastrointestinal endoscopy showed no abnormalities in the esophageal mucosa, and an unclear boundary between the tumor and the esophageal wall was observed by echography. In surgery, the tumor and the esophagus were in one lump, and esophagectomy was performed. On the fourth postoperative day, esophagogastric anastomosis was performed with poststernal reconstruction, and the patient was discharged home on the 38th postoperative day. Pathological examination revealed that the mass was a cystic lesion within the esophageal muscular layer, and the cyst wall was coated with airway-like multi-lineal hairy epithelium, which led to the diagnosis of a bronchogenic cyst. Even if the cyst is within the esophageal muscularis layer, bronchogenic cyst should be considered in the differential.

[Pulmonary Herniation Requiring Reconstructive Surgery Caused by Minimally Invasive Cardiac Surgery:Report of a Case].

A 72-year-old man who underwent aortic valve replacement by a minimally invasive cardiac surgery (MICS) approach two years ago was visited our hospital complaining of swelling and pain in the right anterior chest. A chest computed tomography (CT) scan showed that the right upper lobe protruded beyond the right second intercostal space and outside the thorax. He was diagnosed as a right intercostal lung hernia and underwent chest wall reconstruction with a substitute method. Postoperative course was uneventful without any evidence of recurrence. Postoperative intercostal lung hernias in MICS may increase with the increment in MICS, and it is necessary to accumulate cases as one of the complications.

Efficient Synthesis of a Schiff Base Copper(II) Complex Using a Microfluidic Device.

The efficient synthesis of amino acid Schiff base copper(II) complexes using a microfluidic device was successfully achieved. Schiff bases and their complexes are remarkable compounds due to their high biological activity and catalytic function. Conventionally, products are synthesized under reaction conditions of 40 °C for 4 h using a beaker-based method. However, in this paper, we propose using a microfluidic channel to enable quasi-instantaneous synthesis at room temperature (23 °C). The products were characterized using UV-Vis, FT-IR, and MS spectroscopy. The efficient generation of compounds using microfluidic channels has the potential to significantly contribute to the efficiency of drug discovery and material development due to high reactivity.

Spontaneous Thrombosis of a Hepatic Pseudoaneurysm Following Blunt Liver Injury.

Hepatic pseudoaneurysm (HPA) is a rare complication of liver injury in children. Prophylactic embolization is preferable to prevent life-threatening hemorrhage due to pseudoaneurysm rupture. We present the case of a four-year-old boy who sustained a grade III liver injury from blunt abdominal trauma. He was conservatively managed since he was hemodynamically stable. Follow-up contrast-enhanced computed tomography (CECT) performed 10 days following the injury revealed an HPA measuring 4 mm × 4 mm × 3 mm. Herein, we chose conservative treatment for HPA as the patient was asymptomatic and hemodynamically stable. Conservative treatment was successful, and HPA spontaneously resolved 23 days following the injury without radiologic or surgical intervention. Although there are studies reporting asymptomatic HPAs that have spontaneously resolved, the natural history of HPAs remains unknown. Conservative treatment may be an option for asymptomatic HPA; however, to identify factors contributing to spontaneous thrombosis, further evaluation is needed.

High density and proximity of CD8+ T cells to tumor cells are correlated with better response to nivolumab treatment in metastatic pleural mesothelioma.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. METHODS: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD-L1 positive cells, cell density, and cell-to-cell distance were analyzed by multiplex immunofluorescence. RESULTS: PD-L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. CONCLUSIONS: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.