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Author(s): Ji Yong Kim [1]; Jae Kwang Yun [1]; Geon Dong Lee [1]; Sehoon Choi [1]; Hyeong Ryul Kim [1]; Yong-Hee Kim [1]; Seung-Il Park [1]; Dong Kwan Kim (corresponding [...], BACKGROUND: Standard antibiotic treatment for nontuberculous mycobacteria pulmonary disease (NTMPD) has unsatisfactory success rates. Pulmonary resection is considered adjunctive therapy for patients with refractory disease or severe complications, but surgical indications and extent of resection remain unclear. We present surgical treatment outcomes for NTMPD and analyzes risk factors for unfavorable outcomes. METHODS: We conducted a retrospective investigation of medical records for patients diagnosed with NTMPD who underwent surgical treatment at Asan Medical Center between 2007 and 2021. We analyzed clinical data including microbiological and surgical outcomes. RESULTS: A total of 71 NTMPD patients underwent thoracic surgery. Negative conversion of acid-fast bacillus (AFB) culture following pulmonary resection was observed in 51 (73.9%) patients. In terms of long-term outcomes, negative conversion was sustained in 38 cases (55.1%). Mortality occurred in 7 patients who underwent pulmonary resections for NTMPD. Statistically significant associations with factors for recurrence or non-negative conversion of AFB culture were found in older age (odds ratio [OR] =1.093, 95% confidence interval [CI]: 1.029-1.161, P = 0.004), male sex (OR = 0.251, 95% CI: 0.071-0.892, P = 0.033), and extensive NTMPD lesions involving three lobes or more (OR = 5.362, 95% CI: 1.315-21.857, P = 0.019). Interstitial lung disease (OR = 13.111, 95% CI: 1.554-110.585, P = 0.018) and pneumonectomy (OR = 19.667, 95% CI: 2.017-191.797, P = 0.018) were statistically significant risk factors for postoperative mortality. CONCLUSION: Pulmonary resection can be an effective adjuvant treatment option for NTMPD patients, with post-operative antibiotic treatment as the primary treatment. Careful patient selection is crucial, considering the associated risk factors and resectability due to complications and recurrence. Keywords: Complication, nontuberculous mycobacteria pulmonary disease, pulmonary resection, recurrence

Purpose: This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC). Materials and Methods: From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared. Results: In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96–1.46) and 1.58 (1.31–1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease. Conclusion: The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns. [ABSTRACT FROM AUTHOR]

Purpose: The International Association for the Study of Lung Cancer suggests further subdivision of pathologic N (pN) category in non–small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups. Materials and Methods: This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal. Results: Among 996 eligible patients, 211 (21.2%), 394 (39.6%), and 391 (39.3%) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT category, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49 to 0.90; p=0.009) and was comparable to that of N2a2 disease (HR, 1.12; 95% CI, 0.83 to 1.49; p=0.46). Conclusion: Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC. [ABSTRACT FROM AUTHOR]

Multipurpose halls are designed to host various performances. However, achieving the ideal reverberation time (RT) for each of the different performance types can be challenging. This study investigates five halls of various sizes to determine the effects of sound-absorbing devices on variable RTs in multipurpose halls. The composition and sound absorption properties of the finishing materials were investigated in areas where sound-absorbing devices were not applied. Further, the changes in the room acoustic parameters of these medium-sized multipurpose halls were analyzed using computer-based acoustic simulations to find a suitable answer among the various solutions tested. By applying sound-absorbing devices (resonant-type) to 25% of the walls and ceilings of the target halls, the absorption and reflection modes displayed a variability range of more than 0.5 s in the bass-mid frequency (250–500 Hz). However, a variable range of 0.18 s was found in the high frequency (2000 Hz). To improve the low variable range in the high frequency, a partial application of a high-frequency high-performance sound absorption banner (porous-type) was used to secure a variable range of 0.35 s in the high frequency. Variable sound-absorbing devices should be considered to achieve effective RT variation for all frequencies. [ABSTRACT FROM AUTHOR]

Clinical translation of current cancer vaccine research has been hampered by limited antitumor immune responses due to inefficient antigen delivery and presentation, suboptimal DC and T cell activation. Biomaterial‐based nanovaccine offers targeted antigen delivery, protection from degradation in vivo, and prolonged tumor therapeutic efficacy. This study introduces a lipid‐coated deoxycholic acid‐survivin nanoassembly (DA‐L‐DSA). Survivin, overexpressed in several cancer cells and involved in cancer cell growth and immune evasion, is selected as a tumor‐associated antigen. An major histocompatibility complex class I binding epitope of survivin is engineered into the nanoassembly. R848, TLR 7/8 agonist, and SD‐208, TGF‐beta receptor1 kinase inhibitor, are coencapsulated into the nanoassembly as potent adjuvants to boost DC maturation and enhance antigen presentation. The DA‐L‐DSA effectively stimulates the maturation of dendritic cells, migrates into lymph nodes, and enhances T‐cell activation and Th1 response. A substantial influx of cytotoxic T lymphocytes into primary tumors is observed in a murine melanoma model and demonstrates anti‐metastatic effects in a spontaneous breast cancer metastasis model. Furthermore, DA‐L‐DSA exhibits a remarkable synergistic effect in the combination therapy with immune checkpoint inhibitors alleviating immunosuppressive tumor microenvironment. Taken together, these findings suggest DA‐L‐DSA as a promising immuno‐therapeutic platform that could be applicable to diverse intractable cancers. [ABSTRACT FROM AUTHOR]

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

The safety of both employees and the motoring public is of paramount importance to Caltrans, resulting in a continuing effort to improve the operating vehicle fleet. The potential safety changes that are the focus of this project are those that involve safety equipment enhancement over and above the original specifications for the vehicle or outside of the scope of the original equipment design or purpose, such as rear view backup video cameras.The motivation for this project was Division of Equipment (DOE) managers' need for an objective strategy to address safety equipment deployment issues. These include determining where equipment changes should be made, whether statewide or only in specific locations, what types of vehicles will be involved, and how the changes should be made, for example, immediately retrofitting certain vehicles or changing the specifications for future vehicles.Neither question needs to be answered on an absolute basis; for example, it may be appropriate to immediately retrofit particular vehicles in certain locations while changing the specifications for new vehicles to be deployed in other locations. Additionally, the problem may have non-equipment solutions such as changes to policies and procedures.

High-Occupancy Vehicle (HOV) lane programs are widely adopted in metropolitan areas in an effort to reduce congestion by encouraging carpooling. However, the operation of HOV lanes may result in traffic interactions that affect safety performance. In this paper, historical data from a number of freeway corridors in California are used to illustrate the distribution of collisions on different lanes on the freeway. The peak hours’ data, when compared to those in the non-peak hours, from all corridors indicate that more interactions due to traffic weaving near the HOV lanes might lead to a greater concentration on the inside lanes of the corridors. In addition, a comparison of corridors with continual access with those with dedicated ingress/egress sections also implies that the restricted entrance and exit into the HOV lanes could cause more intense and challenging lane-changing actions and subsequently a greater proportion of collisions near the HOV lanes. The collision data presented in this paper demonstrate the phenomena of collision concentration near HOV lanes, presumably caused by traffic merging and weaving. The results from this study provide valuable insights into the planning of HOV operations and in the identification of safety countermeasures for such facilities.

High-Occupancy Vehicle (HOV) lane programs are widely adopted in metropolitan areas in an effort to reduce congestion by encouraging carpooling. However, the operation of HOV lanes may result in traffic interactions that affect safety performance. In this paper, historical data from a number of freeway corridors in California are used to illustrate the distribution of collisions on different lanes on the freeway. The peak hours’ data, when compared to those in the non-peak hours, from all corridors indicate that more interactions due to traffic weaving near the HOV lanes might lead to a greater concentration on the inside lanes of the corridors. In addition, a comparison of corridors with continual access with those with dedicated ingress/egress sections also implies that the restricted entrance and exit into the HOV lanes could cause more intense and challenging lane-changing actions and subsequently a greater proportion of collisions near the HOV lanes. The collision data presented in this paper demonstrate the phenomena of collision concentration near HOV lanes, presumably caused by traffic merging and weaving. The results from this study provide valuable insights into the planning of HOV operations and in the identification of safety countermeasures for such facilities.

Background: Thymic cysts are a rare benign disease that needs to be distinguished from low-risk thymoma. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a non-invasive imaging technique used in the differential diagnosis of thymic epithelial tumours, but its usefulness for thymic cysts remains unclear. Our study evaluated the utility of visual findings and quantitative parameters of [18F]FDG PET/CT for differentiating between thymic cysts and low-risk thymomas. Methods: Patients who underwent preoperative [18F]FDG PET/CT followed by thymectomy for a thymic mass were retrospectively analyzed. The visual [18F]FDG PET/CT findings evaluated were PET visual grade, PET central metabolic defect, and CT shape. The quantitative [18F]FDG PET/CT parameters evaluated were PET maximum standardized uptake value (SUVmax), CT diameter (cm), and CT attenuation in Hounsfield units (HU). Findings and parameters for differentiating thymic cysts from low-risk thymomas were assessed using Pearson's chi-square test, the Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. Results: Seventy patients (18 thymic cysts and 52 low-risk thymomas) were finally included. Visual findings of PET visual grade (P < 0.001) and PET central metabolic defect (P < 0.001) showed significant differences between thymic cysts and low-risk thymomas, but CT shape did not. Among the quantitative parameters, PET SUVmax (P < 0.001), CT diameter (P < 0.001), and CT HU (P = 0.004) showed significant differences. In ROC analysis, PET SUVmax demonstrated the highest area under the curve (AUC) of 0.996 (P < 0.001), with a cut-off of equal to or less than 2.1 having a sensitivity of 100.0% and specificity of 94.2%. The AUC of PET SUVmax was significantly larger than that of CT diameter (P = 0.009) and CT HU (P = 0.004). Conclusions: Among the [18F]FDG PET/CT parameters examined, low FDG uptake (SUVmax ≤ 2.1, equal to or less than the mediastinum) is a strong diagnostic marker for a thymic cyst. PET visual grade and central metabolic defect are easily accessible findings. [ABSTRACT FROM AUTHOR]

Background In patients with esophageal squamous cell carcinoma (ESCC), accurately predicting a pathologic complete response (pCR) to preoperative chemoradiotherapy (PCRT) has the potential to enable an active surveillance strategy without esophagectomy. We aimed to establish a reliable multiparameter nomogram model that combines tumor characteristics, imaging modalities, and hematologic markers to predict pCR in patients with ESCC who underwent PCRT and esophagectomy. Methods We retrospectively reviewed the medical records of 457 patients with ESCC who received PCRT followed by esophagectomy between January 2005 and October 2020. The nomogram model was developed using logistic regression analysis with a training cohort and externally validated with a validation cohort. Results In the training and validation cohorts, 44.2% (126/285) and 48.3% (83/172) of patients, respectively, achieved pCR after PCRT. The 5-year rates of overall survival, progression-free survival, and freedom from local progression in the training cohort were 51.6%, 48.5%, and 77.6%, respectively. The parameters included in the nomogram were histologic grade, clinical N stage, maximum standardized uptake value on positron emission tomography, and post-PCRT biopsy. Hematologic markers were significantly associated with survival outcomes but not with pCR. The area under the receiver operating characteristic curve of the nomogram was 0.717, 0.704, and 0.707 for the training cohort, internal validation cohort, and external validation cohort, respectively. Conclusion Our nomogram model based on four parameters obtained from standard clinical practice demonstrated good performance in both the training and validation cohorts and could be useful to aid clinical decision-making to determine whether surgery or active surveillance strategy should be pursued. [ABSTRACT FROM AUTHOR]