A quantification method of somatic mutations in normal tissues and their accumulation in pediatric patients with chemotherapy.

Somatic mutations are accumulated in normal human tissues with aging and exposure to carcinogens. If we can accurately count any passenger mutations in any single DNA molecule, since their quantity is much larger than driver mutations, we can sensitively detect mutation accumulation in polyclonal normal tissues. Duplex sequencing, which tags both DNA strands in one DNA molecule, enables accurate count of such mutations, but requires a very large number of sequencing reads for each single sample of human-genome size. Here, we reduced the genome size to 1/90 using the BamHI restriction enzyme and established a cost-effective pipeline. The enzymatically cleaved and optimal sequencing (EcoSeq) method was able to count somatic mutations in a single DNA molecule with a sensitivity of as low as 3 × 10-8 per base pair (bp), as assessed by measuring artificially prepared mutations. Taking advantages of EcoSeq, we analyzed normal peripheral blood cells of pediatric sarcoma patients who received chemotherapy (n = 10) and those who did not (n = 10). The former had a mutation frequency of 31.2 ± 13.4 × 10-8 per base pair while the latter had 9.0 ± 4.5 × 10-8 per base pair (P < 0.001). The increase in mutation frequency was confirmed by analysis of the same patients before and after chemotherapy, and increased mutation frequencies persisted 46 to 64 mo after chemotherapy, indicating that the mutation accumulation constitutes a risk of secondary leukemia. EcoSeq has the potential to reveal accumulation of somatic mutations and exposure to environmental factors in any DNA samples and will contribute to cancer risk estimation.

Vitamin D administration increases serum alanine concentrations in thermally injured mice.

Thermal or burn injury results in profound metabolic changes in the body. This can contribute to muscle atrophy, bone loss, as well as suppression of the immune system. While the mechanisms that underlie this hypermetabolic response remain unclear, patients with burn injury often have low circulating levels of vitamin D. Vitamin D has been shown to regulate bone formation as well as regulate muscle function. We sought to clarify the effects of vitamin D administration on skeletal muscle function following thermal injury using a mouse model. We found that thermal injury resulted in decreased vitamin D levels as well as decreased bone mineral density. Branched chain amino acid (BCAA)s levels were also significantly enhanced in the serum following burn injury. Vitamin D administration reversed the decrease in bone marrow-derived mesenchymal stem cell (BM-MSC)s observed post burn injury. Interestingly, vitamin D administration also resulted in increased tricarboxylic acid cycle (TCA) cycle metabolites in muscle which was decreased after burn conditions, enhanced the supply of alanine and glutamine in the blood which could contribute to gluconeogenesis and wound healing. Therefore, vitamin D supplementation after burn injury may have effects not only in bone metabolism, but may affect substrate metabolism in other organs/tissues.

Surgically resected sarcomatoid carcinoma of the lung: a nationwide retrospective study in 2010.

BACKGROUND: Sarcomatoid carcinoma of the lung is a rare histological type of non-small cell lung cancer with a poor prognosis. We aimed to investigate the clinicopathological characteristics and prognostic factors of surgically resected sarcomatoid carcinoma of the lung. METHODS: We retrospectively reviewed 14999 patients who underwent surgical resection for non-small cell lung cancer accumulated by the Japanese Joint Committee of Lung Cancer Registry in 2010. Clinicopathological characteristics and survival were compared between the sarcomatoid carcinoma and other non-small cell cancer groups. The prognostic factors in the sarcomatoid carcinoma group were identified using a multivariate Cox proportional hazard model. RESULTS: Patients with sarcomatoid carcinoma comprised 1.4% of all patients. The sarcomatoid carcinoma group demonstrated a more aggressive pathology with presentation at more advanced stages, requiring more frequent extensive surgical resections. The sarcomatoid carcinoma group had remarkably poorer overall and recurrence-free survival than the other non-small cell lung cancer group. Adjuvant chemotherapy was associated with improved survival for pathological stage II-III sarcomatoid carcinoma cases rather than for pathological stage I disease. In the multivariate analysis, larger tumor size, lymphatic permeation, and no adjuvant chemotherapy were associated with the sarcomatoid carcinoma group's overall and recurrence-free survival. CONCLUSIONS: Surgically resected sarcomatoid carcinoma of the lung has a higher aggressive and metastatic potential and a worse prognosis than other non-small cell lung cancers. Adjuvant chemotherapy, which was associated with enhanced survival in patients with pathological stage II-III of the disease, could be considered for treating patients with pathological stage II-III sarcomatoid carcinoma of the lung.

Detection of circulating tumor cells in patients with lung cancer using a rare cell sorter: a pilot study.

BACKGROUND: We developed a Rare Cell Sorter (RCS) for collecting single cell including circulating tumor cells (CTCs). This single-institution pilot study evaluated the ability of this device to detect tumor-like cells in patients with lung cancer and confirmed their genuineness based on the epidermal growth factor receptor (EGFR) mutation concordance with tissue samples. METHODS: This study included patients treated for lung cancer from September 2021 to August 2022 in University of Tsukuba Hospital. Peripheral blood samples were obtained before surgery or during periodic medical checks for patients treated with drugs. We used the RCS to capture cells based on size. The cells were stained, and the Hoechst-positive, CD45-negative, and epithelial celladhesion molecule (EpCAM)- positive cells were defined as CTCs, were collected. The presumptive CTCs were counted and tested using digital droplet polymerase chain reaction for EGFR mutations and compared with the tissue EGFR status to check concordance. RESULTS: Eighteen patients were included in this study and CTCs were detected in 6 patients (33%). The CTCs from three patients showed EGFR mutation, and the EGFR mutation status of CTCs concorded with that of tissue samples in 83% of the cases (5/6). Only one CTC showed a different status from the tissue, and the concordance rate of EGFR status between CTCs and the tissue was 96% (24/25). CONCLUSION: The ability of the RCS to detect CTCs in patients with lung cancer was demonstrated based on the concordance of EGFR status in this pilot study. This novel hybrid method of CTC recovery using the RCS has the potential to recover a wide range of CTCs regardless of EpCAM. Further validation through a large-scale study is needed.

Impact of Renal Congestion in Patients With Secondary Mitral Regurgitation After Mitral Transcatheter Edge-to-Edge Repair.

BACKGROUND: Renal congestion is a potential prognostic factor in patients with heart failure and recently, assessment has become possible with intrarenal Doppler ultrasonography (IRD). The association between renal congestion assessed by IRD and outcomes after mitral transcatheter edge-to-edge repair (TEER) is unknown, so we aimed to clarify renal congestion and its prognostic implications in patients with mitral regurgitation (MR) who underwent TEER using MitraClip system.Methods and Results: Patients with secondary MR who underwent TEER and were assessed for intrarenal venous flow (IRVF) by IRD were classified according to their IRVF pattern as continuous or discontinuous. Of the 105 patients included, 78 patients (74%) formed the continuous group and 27 (26%) were the discontinuous group. Kaplan-Meier analysis revealed significant prognostic power of the IRVF pattern for predicting the composite outcome of all-cause death and heart failure rehospitalization (log-rank P=0.0257). On multivariate Cox regression analysis, the composite endpoint was independently associated with the discontinuous IRVF pattern (hazard ratio, 3.240; 95% confidence interval, 1.300-8.076; P=0.012) adjusted using inverse probability of treatment weighting. CONCLUSIONS: IRVF patterns strongly correlated with clinical outcomes without changes in renal function. Thus, they may be useful for risk stratification after mitral TEER for patients with secondary MR.

Impact of the MitraClip G4 System on Routine Practice and Outcomes in Patients With Secondary Mitral Regurgitation.

BACKGROUND: The MitraClip G4 system is a new iteration of the transcatheter edge-to-edge repair system. We assessed the impact of the G4 system on routine practice and outcomes in secondary mitral regurgitation (2°MR).Methods and Results: Consecutive patients with 2°MR treated with either the MitraClip G2 (n=89) or G4 (n=63) system between 2018 and 2021 were included. Baseline characteristics, procedures, and outcomes were compared. Inverse probability of treatment weighting and Cox regression were used to adjust for baseline differences. Baseline characteristics were similar, except for a lower surgical risk in the G4 group (Society of Thoracic Surgeons Predicted Risk of Mortality ≥8: 38.1% vs. 56.2%; P=0.03). In the G4 group, more patients had short (≤2 mm) coaptation length (83.7% vs. 54.0%; P<0.001) and fewer clips were used (17.5% vs. 36.0%; P=0.02). Acceptable MR reduction was observed in nearly all patients, with no difference between the G4 and G2 groups (100% vs. 97.8%, respectively; P=0.51). The G4 group had fewer patients with high transmitral gradients (>5mmHg; 3.3% vs. 13.6%; P=0.03). At 1 year, there was no significant difference between groups in the composite endpoint (death or heart failure rehospitalization) after baseline adjustment (10.5% vs. 20.2%; hazard ratio 0.39; 95% confidence interval 0.11-1.32; P=0.13). CONCLUSIONS: The G4 system achieved comparable device outcomes to the early-generation G2, despite treating more challenging 2°MR with fewer clips.

High-efficiency EGFR genotyping using cell-free DNA in bronchial washing fluid.

BACKGROUND: EGFR mutation testing is required for treatment of lung adenocarcinoma using epidermal growth factor receptor-tyrosine kinase inhibitor. However, the amounts of tumor tissue or tumor cells obtained by bronchoscopy are often insufficient. Bronchial washing fluid, obtained by lavage with saline after tumor biopsy or brushing, and the supernatant of bronchial washing fluid are thought to contain cell-free DNA that would be potentially applicable for EGFR testing. METHODS: From among patients with suspected adenocarcinoma or non-small cell lung carcinoma diagnosed from biopsy or surgical specimens at the University of Tsukuba Hospital between 2015 and 2019, cell-free DNAs from 80 specimens of supernatant of bronchial washing fluid (50 with EGFR mutation and 30 with wild type EGFR) and 8 blood serum samples were examined for EGFR mutation using droplet digital PCR. RESULTS: Among the 50 patients harboring EGFR mutation, the rate of positivity for cell-free DNA extracted from supernatant of bronchial washing fluid was 80% (40/50). In nine of the EGFR mutation-positive cases, tumor cells were not detected by either biopsy or cytology, but the mutation was detected in four cases (4/9, 44%). Comparison of the cell-free DNA mutation detection rate between supernatant of bronchial washing fluid and blood serum in six cases showed that mutations were detected from the former in all cases (6/6, 100%), but from the latter in only one case (1/6, 17%). CONCLUSIONS: Using supernatant of bronchial washing fluid samples, the detection rate of EGFR mutation was high, and EGFR mutations were detectable even when no tumor cells had been detectable by biopsy or cytology. Supernatant of bronchial washing fluid might be an effective sample source for EGFR mutation testing.

Imaging characteristics and clinical outcomes of hemodialysis vs. non-hemodialysis patients undergoing transcatheter aortic valve replacement: a Japanese single-center experience.

In 2021, Japan approved transcatheter aortic valve replacement (TAVR) for end-stage renal disease patients on hemodialysis (ESRD-HD). Yet, clinical/anatomical differences and outcomes between patients with and without ESRD-HD remain underexplored. This single-center study enrolled consecutive patients who underwent TAVR with the SAPIEN 3 between 2021 and 2023. Baseline characteristics and outcomes up to 1 year were compared. Inverse probability treatment weighting (IPTW) approach and Cox regression were used. Among 287 eligible patients, 59 had ESRD-HD. Patients with ESRD-HD were predominantly male (59.2% vs. 40.7%; p = 0.01), younger (78.0 [73.5-83.5] vs. 84.0 [79.8-88.0]; < 0.001), with lower body mass index (21.4 [19.6-23.3] vs. 22.9 [20.3-25.3]; p = 0.02], higher surgical risk (Society of Thoracic Surgeons Predicted Risk of Mortality ≧8%: 28 [47.5%] vs. 34 [14.9%]; p < 0.001), and more peripheral artery disease (25.4% vs. 4.8%; p < 0.001). Patients with ESRD-HD had a significantly higher prevalence of severely calcified femoral arteries (12.5% vs. 2.6%; p < 0.001). However, there were no differences in the computed-tomographic (CT) anatomical characteristics of the aortic valve complex (AVC), including the aortic valve calcium score (1995 [1372-3374] vs. 2195 [1380-3172]; p = 0.65) or the presence of moderate or severe left ventricular outflow tract calcification (4.3% vs. 5.2%; p > 0.99). Major vascular complications were rare, and technical (98.3% vs. 98.7%; p > 0.99) and device success (75.9% vs. 82.4%; p = 0.26) rates were high in both. At 1 year, there were no significant differences in a composite endpoint of death, stroke, major bleeding, or myocardial infarction (32.4% vs. 33.2%; HR 1.12; 95% CI 0.45-2.80; p = 0.81), nor its components after baseline adjustment.

Prognostic value of transvalvular flow rate in patients with low-gradient severe aortic stenosis: A dobutamine stress echocardiography study.

BACKGROUNDS: There are limited data on the clinical relevance of transvalvular flow rate (Qmean ) at rest (Qrest) and at peak stress (Qstress ) during dobutamine stress echocardiography (DSE) in patients with low-gradient severe aortic stenosis (LG-SAS). METHODS: We retrospectively analyzed the clinical data of patients with LG-SAS who underwent DSE. LG-SAS was defined as an aortic valve (AV) area index of < .6 cm2 /m2 and a mean AV pressure gradient (AVPG) of < 40 mm Hg. The primary endpoint included all-cause death and heart failure hospitalization. RESULTS: Of 100 patients (mean age 79.5 ± 7.3 years; men, 45.0%; resting left ventricular ejection fraction [LVEF] 52.1% ± 15.9%; resting stroke volume index 35.8 ± 7.7 mL/m2 ; Qrest 171.8 ± 34.9 mL/s), the primary endpoint occurred in 51 patients during a median follow-up of 2.84 (interquartile range 1.01-5.21) years. When the study patients were divided into three subgroups based on Qrest and Qstress , the multivariate analysis showed that Qrest < 200 mL/s and Qstress ≥200 mL/s (hazard ratio 3.844; 95% confidence interval 1.143-12.930; p = .030), as well as Qrest and Qstress < 200 mL/s (hazard ratio 9.444; 95% confidence interval 2.420-36.850; p = .001), were significantly associated with unfavorable outcomes with Qrest and Qstress ≥200 mL/s as a reference after adjusting for resting LVEF, resting mean AVPG, chronic kidney disease, New York Heart Association functional class III/IV, and AV replacement. CONCLUSIONS: Flow conditions based on the combination of Qrest and Qstress are helpful for risk stratification in LG-SAS patients.

Prognostic value of extraaortic-valvular cardiac damage in patients with moderate aortic stenosis and reduced left ventricular ejection fraction.

PURPOSE: The extraaortic-valvular cardiac damage (EVCD) Stage has shown potential for risk stratification for patients with aortic stenosis (AS). This study aimed to examine the usefulness of the EVCD Stage in risk stratification of patients with moderate AS and reduced left ventricular ejection fraction (LVEF). METHODS: Clinical data from patients with moderate AS (aortic valve area, .60-.85 cm2/m2; peak aortic valve velocity, 2.0-4.0 m/s) and reduced LVEF (LVEF 20%-50%) were analyzed during 2010-2019. Patients were categorized into three groups: EVCD Stages 1 (LV damage), 2 (left atrium and/or mitral valve damage), and 3/4 (pulmonary artery vasculature and/or tricuspid valve damage or right ventricular damage). The primary endpoint included a composite of cardiac death and heart failure hospitalization, with non-cardiac death as a competing risk. RESULTS: The study included 130 patients (mean age 76.4 ± 6.8 years; 62.3% men). They were categorized into three groups: 26 (20.0%) in EVCD Stage 1, 66 (50.8%) in Stage 2, and 48 (29.2%) in Stage 3/4. The endpoint occurred in 54 (41.5%) patients during a median follow-up of 3.2 years (interquartile range, 1.4-5.1). Multivariate analysis indicated EVCD Stage 3/4 was significantly associated with the endpoint (hazard ratio 2.784; 95% confidence interval 1.197-6.476; P = .017) compared to Stage 1, while Stage 2 did not (hazard ratio 1.340; 95% confidence interval .577-3.115; P = .500). CONCLUSION: The EVCD staging system may aid in the risk stratification of patients with moderate AS and reduced LVEF.

Practical methods to differentiate thymic malignancies by positron-emission tomography and tumor markers.

PURPOSE: An accurate diagnosis of thymic malignancies is important, but challenging due to the broad range of differential diagnoses. This study aims to evaluate the efficacy of PET/CT and tumor markers for diagnosing thymic malignancies. METHODS: Patients admitted to our department between January 2012 and December 2021 with primary anterior mediastinal tumors were retrospectively evaluated. We evaluated the relationship between the maximum standardized uptake value (SUVmax), tumor markers, and pathological diagnosis in four groups: thymic carcinoma, thymoma, lymphoma, and others. RESULTS: In total, 139 patients were included in this study. The SUVmax was significantly higher in lymphoma, thymic carcinoma, and thymoma, in that order. The cytokeratin 19 fragment (CYFRA 21-1) was significantly higher in thymic carcinoma than in the other groups. An ROC curve analysis indicated that the optimal cut-off values of SUVmax for thymic carcinoma plus lymphoma and CYFRA 21-1 for thymic carcinoma were 7.97 (AUC = 0.934) and 2.95 (AUC = 0.768), respectively. Using a combination of cut-off values (SUVmax = 8, CYFRA 21-1 = 3), the accuracy rate for diagnosing thymic carcinoma was 91.4%. CONCLUSIONS: The SUVmax and CYFRA 21-1 levels are significant indicators for the diagnosis of thymic carcinoma. Combining these indicators resulted in a more accurate diagnosis of thymic malignancies, which could facilitate the decision-making process for determining the optimal treatment strategies.

Preoperative risk-factors for secondary spontaneous pneumothorax surgery in Japan: a nationwide database study.

PURPOSE: We aimed to identify preoperative risk factors for secondary spontaneous pneumothorax surgery. METHODS: The National Clinical Database of Japan, with six annual datasets from 2014 to 2019, was used. All patients who underwent surgery for secondary spontaneous pneumothorax were included, excluding those < 15 years old and those with incomplete data. The effects of preoperative risk factors were analyzed for operative mortality (mortality during hospitalization or within 30 days, regardless of hospitalization status), 30-day mortality, and postoperative respiratory morbidities. RESULTS: Of the 18,309 patients enrolled in the study, operative mortality, 30-day mortality, and postoperative respiratory morbidities were observed in 654 (3.6%), 343 (1.9%), and 2258 (12.3%) patients, respectively. Increasing age, male sex, body mass index < 18.5 or > 30, performance status > 2, emergent surgery, interstitial pneumonia, and diabetes in preoperative co-morbidity, tumors, and other diseases in underlying lung disease were significant risk factors for operative mortality. Those for 30-day mortality included autoimmune disease instead of male sex and diabetes, while those for postoperative respiratory morbidities included lymphangiomyomatosis instead of a body mass index > 30. CONCLUSION: We identified many preoperative risk factors for operative mortality, 30-day mortality, and postoperative respiratory morbidities in secondary spontaneous pneumothorax surgery. These findings will assist in selecting appropriate surgical candidates.

Relationship between changes in pulmonary function and patient-reported outcomes of lung cancer surgery.

PURPOSE: To investigate the relationship between changes in pulmonary function (PF) and patient-reported outcomes (PROs) of lung cancer surgery. METHODS: We recruited 262 patients who underwent lung resection for lung cancer, to evaluate the PROs, using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and the Lung Cancer 13-question supplement (LC13). The patients underwent PF tests and PRO assessments preoperatively (Pre) and 1 year after surgery (Y1). Changes were calculated by subtracting the value at Pre from the value at Y1. We set two cohorts: patients under the ongoing protocol (Cohort 1) and patients who were eligible for lobectomy with clinical stage I lung cancer (Cohort 2). RESULTS: Cohorts 1 and 2 comprised 206 and 149 patients, respectively. In addition to dyspnea, changes in PF were also correlated with scores for global health status, physical and role function scores, fatigue, nausea and vomiting, pain, and financial difficulties. Absolute correlation coefficient values ranged from 0.149 to 0.311. Improvement of emotional and social function scores was independent of PF. Sublobar resection preserved PF more than lobectomy did. Wedge resection mitigated dyspnea in both cohorts. CONCLUSION: The correlation between PF and PROs was found to be weak; therefore, further studies are needed to improve the patient's postoperative experience.

Sex-specific emphysematous changes evaluated by a three-dimensional computed tomography volumetric analysis among patients with smoking histories who underwent resection for lung cancer.

PURPOSE: The present study evaluated the sex-specific susceptibility to the development of emphysema in patients with smoking histories who underwent lung cancer surgeries. METHODS: Lung cancer patients with smoking histories who underwent lung resection at the University of Tsukuba Hospital, Japan, were enrolled. Radiologic emphysematous changes were analyzed using three-dimensional computed tomography (3D-CT). The volume proportion of emphysematous lung per unit of smoking and the relationship between emphysematous change and clinicopathologic factors were evaluated. RESULTS: Radiologic emphysematous changes analyzed using 3D-CT per pack-year smoked, defined as the Smoking-Emphysema Index (SEI), were greater in females than males. The difference was more profound in adenocarcinoma patients than in non-adenocarcinoma patients (0.70 ± 2.30 vs. 0.21 ± 0.28, P = 0.037). CONCLUSION: Female lung cancer patients are more susceptible to smoking-induced emphysema than males. The SEI may be an effective indicator for evaluating smoking-induced emphysema.

Newer versus Early Generation of the MitraClip for Primary Mitral Regurgitation: A Japanese Single-Center Experience.

Background: The MitraClip G4 system is the latest version of the transcatheter edge-to-edge repair (TEER) system for mitral regurgitation (MR). We aimed to investigate the impact of the new system on routine clinical practice and patient outcomes in the treatment of primary MR. Methods: Consecutive patients with primary MR who underwent TEER with either the MitraClip G2 or G4 between 2018 and 2021 were enrolled from a single center registry. Baseline clinical and echocardiographic characteristics as well as procedural and clinical outcomes up to 1 year were compared between groups. Technical and device success were defined in accordance with the Mitral Valve Academic Research Consortium criteria. Results: Among 71 patients with primary MR, 34 were treated with G2 and 37 were treated with G4. Patients treated with G4 had lower surgical risk (7.74 [5.04, 14.97] vs. 5.26 [3.98, 6.40]; p < 0.01) than those with G2. There were no significant differences in other baseline clinical variables between groups. On baseline echocardiography, MR volume and flail gap were significantly greater in the G4 group than in the G2 group (regurgitant volume: 63 [41-76] mL vs. 68 [62-84] mL; p = 0.04, flail gap: 4.5 [3.5-5.5] mm vs. 5.4 [4.5-7.1] mm; p = 0.04). Technical success was achieved in over 95% of both groups with no significant difference (p > 0.99). Device success was achieved in 61.8% of the G2 group, while in 70.3% of the G4 group (p = 0.47). Post-procedural MR severity was comparable (p = 0.42) and there was no significant difference in the occurrence of mitral stenosis (p = 0.61) between groups. Among patients who reached 1-year follow-up (n = 54), there was no significant difference between groups in a composite endpoint of death or heart failure rehospitalization (10.5% vs. 20.2%; HR 0.61; 95% CI 0.17-2.22; p = 0.45). Residual heart failure symptoms (NYHA ≥ 3) at 1 year were observed in 3.7% of the G2 group, while no patient in the G4 group (p > 0.99). Conclusions: The MitraClip G4 system achieved comparable device outcomes to the early-generation device (G2), despite treating more severe primary MR with a larger flail gap.

Healthcare costs for hospitalized COVID-19 patients in a Japanese university hospital: a cross-sectional study.

BACKGROUND: A health-economic evaluation related to COVID-19 is urgently needed to allocate healthcare resources efficiently; however, relevant medical cost data in Japan concerning COVID-19 are scarce. METHODS: This cross-sectional study investigated the healthcare cost for hospitalized COVID-19 patients in 2021 at Keio University Hospital. We calculated the healthcare costs during hospitalization using hospital claims data and investigated the variables significantly related to the healthcare cost with multivariable analysis. RESULTS: The median healthcare cost per patient for the analyzed 330 patients was Japanese yen (JPY) 1,304,431 (US dollars ~ 11,871) (interquartile range: JPY 968,349-1,954,093), and the median length of stay was 10 days. The median healthcare cost was JPY 798,810 for mild cases; JPY 1,113,680 for moderate I cases; JPY 1,643,909 for moderate II cases; and JPY 6,210,607 for severe cases. Healthcare costs increased by 4.0% for each additional day of hospitalization; 1.26 times for moderate I cases, 1.64 times for moderate II cases, and 1.84 times for severe cases compared to mild cases; and 2.05 times for cases involving ICU stay compared to those not staying in ICU. CONCLUSIONS: We clarified the healthcare cost for hospitalized COVID-19 patients by severity in a Japanese university hospital. These costs contribute as inputs for forthcoming health economic evaluations for strategies for preventing and treating COVID-19.

Perioperative outcomes of minimally invasive surgery for large malignant thymic epithelial tumors and for total thymectomy.

PURPOSE: Minimally invasive surgery (MIS) for thymic tumors is now accepted widely, in line with improved surgical techniques; however, we occasionally encounter complicated cases of large tumors or of total thymectomy requiring prolonged operative duration or conversion to an open procedure (OP). We reviewed patients registered in a nationwide database to identify the technical feasibility of MIS for thymic epithelial tumors. METHODS: Data on patients treated surgically between 2017 and 2019 were extracted from the National Clinical Database of Japan. Clinical factors and operative outcomes were calculated by tumor diameter using trend analyses. Perioperative outcomes of MIS for non-invasive thymoma were investigated using propensity score-matched analyses. RESULTS: MIS was performed in 46.2% of the patients. The operative duration and conversion rate increased with the tumor diameter (p < .001). After propensity score-matching, operative duration and postoperative hospital stay were shorter (p < .001), and the transfusion rate was lower (p = .007) in patients who underwent MIS than in those who underwent OP for thymomas ≥ 5 cm. Among patients who underwent total thymectomy, blood loss was less (p < .001) and the postoperative hospital stay was shorter (p < .001) in those who underwent MIS than in those who underwent OP. There were no significant differences in postoperative complications and mortality. CONCLUSIONS: MIS is technically feasible even for large non-invasive thymomas or for total thymectomy, although the operative duration and open conversion rate increase with the tumor diameter.

Three-dimensional analysis reveals a high incidence of lung adenocarcinoma in the upper region.

PURPOSE: The lung is a unique organ with a ventilation-perfusion mismatch, which can cause inhomogeneous incidence rates of lung cancer depending on the location in the lung. We aimed to evaluate the incidence of lung adenocarcinoma in each lobe by analyzing the incidence per unit volume, to evaluate the incidence without being affected by differences in the size of each lobe or in the size of the lungs between individuals. METHODS: The number of adenocarcinomas in each lobe was counted. Lung volumes were measured using a three-dimensional computer workstation. The tumor incidence per unit volume was analyzed based on the number of tumors in each lobe. RESULTS: The number of tumors per unit volume was 0.467 in the right upper lobe (RUL), 0.182 in the right middle lobe, 0.209 in the right lower lobe, 0.306 in the left upper segment (LUS), 0.083 in the left lingular segment, and 0.169 in the left lower lobe. The tumor incidence rate of RUL + LUS was 2.269 times that of the other lobes, a value that was significantly higher when using the bootstrap method (p < 0.001). CONCLUSIONS: The incidence of adenocarcinoma per unit volume in both upper lobes was higher than that in other lobes.

The consecutive impact of COVID-19 on thoracic surgical procedures in Japan: an analysis of data from the National Clinical Database.

PURPOSE: The current study was designed to analyze the impact of the COVID-19 pandemic on general thoracic surgeries in Japan. METHODS: Changes in surgeries for lung cancer and metastatic lung tumors were evaluated based on National Clinical Database data regarding cancer screening. RESULTS: In 2021, surgeries for primary lung cancer increased by 3.4% compared to 2020, which, given the increase from 2014 to 2019, indicates an overall 11.1% decrease. In contrast, surgeries for metastatic lung tumors in 2021 decreased by 5.8% compared to 2020, which, given the increase from 2014 to 2020, indicates an overall 9.2% decrease. Half of the primary diseases for metastatic lung tumor were cases of colorectal cancer. Low anterior resection procedures in 2020 decreased by 5.5% compared to 2019. Lung and colon cancer screening examinees in 2021 were increased compared to 2020; however, they still showed respective decreases of 11% and 9.0% compared to 2019. CONCLUSIONS: Surgeries for primary lung cancer still decreased substantially during the COVID-19 pandemic. The continued stagnation of screening was responsible for this decrease. Surgeries for metastatic lung tumors decreased profoundly, and the decrease in screening for primary tumors was responsible for this reduction. Our findings emphasize the significance of maintaining cancer screening efforts, even during a pandemic.

Myeloid Progenitor Inhibitory Factor-1 (CCL23) Inhibits Lung Leukocyte Recruitment in a Primate Cardiopulmonary Bypass-Induced Pulmonary Ischaemia Model.

BACKGROUND: Bone marrow (BM)-derived polymorphonuclear leukocytes (PMNs) and monocytes (MO) induced by cardiopulmonary bypass (CPB) are highly proteolytic and cause postoperative lung injury. Although CCL23/Myeloid progenitor inhibitory factor-1 is a human CC chemokine with potent suppressor effects on myeloid progenitor cells, in vivo inhibitory effects on BM-derived leukocyte kinetics associated with CPB are unknown. METHODS: Two-hour CPB was surgically performed in cynomolgus monkeys and BM-derived leukocytes kinetics were monitored postoperatively by flow cytometry with 5'-bromo-2'-deoxyuridine (BrdU) and cytokine ELISA. Monkeys were given CCL23 (n=5) or saline (control, n=5) intravenously daily for 3 days before BrdU labelling and peripheral blood/bronchoalveolar lavage fluid (BALF) timepoint sampling to reveal BrdU-labelled cells. Levels of cytokines, CD11b, and L-selectin were considered leukocytic activation markers. RESULTS: The CCL23 treatment significantly prolonged BM transit of leukocytes (PMNs, 118.4±11.7-95.5±4.1 hours [control]; MO, 91.6±5.0-62.0±3.0 hours [control]) and reduced their alveolar appearance. The BM pool size of MO was decreased by CCL23 but PMNs were unaffected. CD11b, L-selectin expression of PMNs and MO during CPB, and post-surgical increases of interleukin (IL)-6, IL-8, TNF-α, MCP-1, and PMN elastase in the BALF were not suppressed. CONCLUSIONS: CCL23 treatment slows turnover of PMN and MO progenitors in BM and suppresses their circulatory release and lung recruitment. CCL23 has inhibitory effects specifically on the CPB-induced BM response and could hold value for preventing CPB-induced lung injury.