Exploration of a Machine Learning Model Using Self-rating Questionnaires for Detecting Depression in Patients with Breast Cancer.

Objective: Given the long-term and severe distress experienced during breast cancer treatment, detecting depression among breast cancer patients is clinically crucial. This study aimed to explore a machine-learning model using self-report questionnaires to screen for depression in patients with breast cancer. Methods: A total of 327 patients who visited the breast cancer clinic were included in this study. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9), Beck Depression Inventory (BDI), and Hospital Anxiety and Depression Scale (HADS). The depression was evaluated according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition. The prediction model's performance based on supervised machine learning was conducted using MATLAB2022. Results: The BDI showed an area under the curve (AUC) of 0.785 when using the logistic regression (LR) classifier. The HADS and PHQ-9 showed an AUC of 0.784 and 0.756 when using the linear discriminant analysis, respectively. The combinations of BDI and HADS showed an AUC of 0.812 when using the LR. The combinations of PHQ-9, BDI, and HADS showed an AUC of 0.807 when using LR. Conclusion: The combination model with BDI and HADS in breast cancer patients might be better than the method using a single scale. In future studies, it is necessary to explore strategies that can improve the performance of the model by integrating the method using questionnaires and other methods.

Seasonal influences on the efficacy of anti-programmed cell death (ligand) 1 inhibitors in lung cancer.

BACKGROUND: Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. METHODS: A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. RESULTS: A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n = 173) had a significantly lower risk of progression or death from immunotherapy than the other group (n = 311) (PFS: hazard ratio [HR], 0.77 [95% confidence interval (CI), 0.62-0.96]; p = .018; OS: HR, 0.77 [95% CI, 0.1-0.98]; p = .032). In a propensity score-matched population, the winter group (n = 162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p = .009) than the other group (n = 162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p = .012). The trend toward longer survival in the winter group continued in subgroup analyses. CONCLUSIONS: Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.

Infection-related Hospitalizations During Immune Checkpoint Inhibitor Treatment Without Immunosuppressants.

Immunosuppressants are increasingly being used in the clinic to manage immune-related adverse effects. Consequently, the incidence of secondary infections associated with immunosuppression is increasing. However, little is known about primary infections during immune checkpoint inhibitor (ICI) treatment without immunosuppressants. We aimed to evaluate primary infectious diseases during antiprogrammed death ligand-1 immunotherapy without immunosuppressants. We retrospectively screened medical records of 233 patients who underwent ICI treatment for advanced non-small cell lung cancer between January 2014 and May 2018 at National Cancer Center, Republic of Korea. Subsequently, we evaluated the clinical characteristics and treatment outcomes of selected patients hospitalized for potential infectious disease without immunosuppressive treatment (n=80). Eight cases (3.4%) were identified as bacterial pneumonia (n=5) and cellulitis, inflamed epidermoid cyst, and wound infection (n=1 each). The bacterial pathogens Streptococcus pneumoniae and Haemophilus influenzae were identified in 4 patients with pneumonia. The period between the start of ICI treatment and infection varied between 3 and 189 days (median, 24.5 days). Five (62.5%) patients were infected within a month after ICI treatment initiation. All patients were treated with empirical antibiotics and discharged without complications. The median progression-free and overall survival for ICI treatment was 11.5 and 25.5 months, respectively. Six patients experienced ICI-associated adverse effects postinfection: Herpes zoster infection (n=4) and pneumonitis (n=2). Infectious disease independent of immunosuppression is a rare, but possible event in patients with lung cancer receiving ICI treatment. Clinical awareness would enable prompt diagnosis of primary infection during immunotherapy.

Changes of Locomotor Activity by Dopamine D2, D3 Agonist Quinpirole in Mice Using Home-cage Monitoring System.

Objective: : As dopamine is closely linked to locomotor activities, animal studies on locomotor activities using dopaminergic agents were widely done. However, most of animal studies were performed for a short period that there is a lack of longitudinal study on the effects of dopaminergic agents on locomotor activities. This study aimed to examine the longterm effect of a dopamine D2, D3 agonist quinpirole on locomotor activities in mice using a home-cage monitoring system. Methods: : The locomotor activities of Institute Cancer Research mice were measured by infrared motion detectors in home-cages under the 12-hour dark and 12-hour light condition for three days after the quinpirole injection. Quinpirole was injected at a concentration of 0.5 mg/kg intraperitoneally in the beginning of the dark phase. The locomotor activities before and after the quinpirole administration were compared by the Wilcoxon signed-rank test and one-way repeated measures ANOVA. Results: : After the quinpirole administration, the 24-hour total locomotor activity did not change (p = 0.169), but activities were significantly increased in the 12-hour dark phase sum (p = 0.013) and decreased in the 12-hour light phase sum (p = 0.009). Significant increases in the activities were observed in the dark-light difference (p = 0.005) and dark-light ratio (p = 0.005) as well. Conclusion: : This study suggests that quinpirole injection entrains the circadian rest-activity rhythm of locomotor activities. Therefore, quinpirole can be a drug that mediates locomotor activity as a dopamine agonist as well as a modulator of the circadian rhythms.

Percutaneous Cementoplasty for the Pelvis in Bone Metastasis: 12-Year Experience.

BACKGROUND: In advanced cancer patients, pelvic bone metastasis often causes pain and gait disturbance. The use of percutaneous bone cement [polymethylmethacrylate (PMMA)] injection for pain management and strengthening in pelvic bone metastasis has rarely been reported. To evaluate this method, we aimed to determine surgical outcomes and complications over a long-term follow-up period using a large patient group. PATIENTS AND METHODS: We retrospectively collected data from 178 patients who underwent percutaneous cementoplasty for pelvic metastatic lesions, 201 in total. Surgical outcomes evaluated included pain reduction and improvement of ambulation. Mortality within 1 month after procedure and pulmonary embolism caused by thrombus, fat, tumor emboli, or bone cement were investigated as surgical complications. For long-term survivors, pain relapse and mechanical failure were analyzed. The mean follow-up period was 12.6 months, and there were 159 fatalities at last follow-up. RESULTS: The mean regional pain numerical rating scale scores decreased from 6.1 preoperatively to 2.4 1 month after procedure (p < 0.01). Gait function was maintained, worsened, and uncheckable in 68%, 24%, and 8% of patients, respectively, 1 month after procedure. Of long-term survivors followed up for > 12 months (n = 53), there were no significant changes in serial plain radiographs, and regional pain aggravation was observed in 9%. Pulmonary cement embolism and bone cement implantation syndrome was observed in 11% and 10%, respectively. However, all patients with these complications were asymptomatic. CONCLUSIONS: Percutaneous cement injection into the pelvis is a feasible and safe palliative surgical option for patients with advanced malignancy in terms of pain reduction and maintenance of ambulatory function under regional anesthesia.

Prediction of Locomotor Activity by Infrared Motion Detector on Sleep-wake State in Mice.

OBJECTIVE: Behavioral assessments that effectively predict sleep-wake states were tried in animal research. This study aimed to examine the prediction power of an infrared locomotion detector on the sleep-wake states in ICR (Institute Cancer Research) mice. We also explored the influence of the durations and ways of data processing on the prediction power. METHODS: The locomotor activities of seven male mice in home cages were recorded by infrared detectors. Their sleep-wake states were assessed by video analysis. Using the receiver operating characteristic curve analysis, the cut-off score was determined, then the area under the curve (AUC) values of the infrared motion detector that predicted sleep-wake states were calculated. In order to improve the prediction power, the four ways of data processing on the prediction power were performed by Matlab 2013b. RESULTS: In the initial analysis of raw data, the AUC value was 0.785, but it gradually reached to 0.942 after data summation. The simple data averaging and summation among four different methods showed the maximal AUC value. The 10-minute data summation improved sensitivity (0.889) and specificity (0.901) significantly from the baseline value (sensitivity 0.615; specificity 0.936) (p < 0.001). CONCLUSION: This study suggests that the locomotor activity measured by an infrared motion detector might be useful to predict the sleep-wake states in ICR mice. It also revealed that only simple data summation may improve the predictive power. Using daily locomotor activities measured by an infrared motion detector is expected to facilitate animal research related to sleep-wake states.

Ceritinib-Induced Organizing Pneumonia in Lung Cancer: A Retrospective Analysis.

BACKGROUND: Ceritinib is a potent selective ALK inhibitor with a manageable safety profile. In anecdotal reports, ceritinib was associated with organizing pneumonia (OP), which could be confused with disease progression. OBJECTIVE: We aimed to delineate the characteristics of OP that occurs during treatment with ceritinib, and evaluate its clinical implications. PATIENTS AND METHODS: We retrospectively analyzed 44 lung cancer patients whose tumors harbored ALK or ROS1 fusions and who had received ceritinib. OP diagnosis was based on radiographic and clinical features. Four OP cases were pathologically confirmed. RESULTS: Among 44 patients, 22 OP events occurred in 16 (36.4%) patients. The median time to the first event was 17.2 weeks (range 6.7-68.7 weeks). All events were grade 1 or 2. Radiographic features were categorized into four patterns: nodular (54.6%), consolidation (27.3%), parenchymal band (4.5%), and ground-glass opacity (GGO) (13.6%). OP improved in 20 events with drug interruption or corticosteroids. The median duration of OP was 11.3 weeks (range 2-24 weeks). Tumor response rate was 75% in OP-positive and 42.9% in OP-negative groups. The median progression-free survival was 16.7 months [95% confidence interval (CI) 10.1-not applicable (NA)] in OP-positive and 5.4 months (95% CI 3.6-8.4) in OP-negative patients (P = 0.004). The median overall survival was 46.2 months (95% CI 38.1-NA) in OP-positive and 10.5 months (95% CI 6.2-18.9) in OP-negative patients (P < 0.001). CONCLUSION: OP occurs frequently during ceritinib treatment and must be distinguished from disease progression. OP could be reversible without fatal complications and its occurrence is associated with better survival outcomes.

Initial M Staging of Rectal Cancer: FDG PET/MRI with a Hepatocyte-specific Contrast Agent versus Contrast-enhanced CT.

BackgroundThe performance of PET/MRI in the determination of distant metastases (M stage) in rectal cancer relative to the current practice with contrast material-enhanced CT is largely unknown.PurposeTo compare the staging of clinical M stage rectal cancer with fluorine 18 fluorodeoxyglucose (FDG) PET/MRI (including dedicated liver and rectal MRI) to that of chest and abdominopelvic CT and dedicated rectal MRI.Materials and MethodsFrom January 2016 to August 2017, patients with newly diagnosed advanced mid to low rectal cancers were recruited for this prospective study (clinicaltrials.gov identifier: NCT0265170). Participants underwent both FDG PET/MRI with dedicated liver and rectal MRI and chest and abdominopelvic CT (the standard-of-care protocol) within 3 weeks of each other. Thereafter, M stage assessment performance was determined by using findings from 6-month clinical follow-up or biopsy as the reference standard. Performance was compared between protocols. Agreement in M stage classification was also assessed. Nonparametric statistical analyses were performed, and P < .05 indicated a significance difference.ResultsSeventy-one participants (28 women; mean age ± standard deviation, 61 years ± 9; age range, 39-79 years) were enrolled. The M stage could not be determined with the standard-of-care protocol in 22 of the 71 participants (31%; 95% confidence interval [CI]: 20.5%, 43.1%) because of indeterminate lesions. However, among these participants, PET/MRI correctly helped identify all 14 (100%; 95% CI: 76.8%, 100%) without metastases and seven of eight (88%; 95% CI: 47.4%, 99.7%) who were later confirmed to have metastases. PET/MRI showed high specificity for ruling out metastatic disease compared with the standard-of-care protocol (98% [54 of 55 participants] vs 72% [40 of 55 participants], respectively; P < .001), without increasing the number of participants with missed metastasis (6% [one of 16 participants] vs 6% [one of 16 participants]; P > .99).ConclusionPET/MRI with dedicated rectal and liver MRI can facilitate the staging work-up of newly diagnosed advanced rectal cancers by helping assess indeterminate lesions, metastases, and incidental findings better than contrast-enhanced CT, obviating for additional imaging work-up.© RSNA, 2019Online supplemental material is available for this article.Clinical trial registration no. NCT02651701.

Accuracy of Model-Based Iterative Reconstruction for CT Volumetry of Part-Solid Nodules and Solid Nodules in Comparison with Filtered Back Projection and Hybrid Iterative Reconstruction at Various Dose Settings: An Anthropomorphic Chest Phantom Study.

OBJECTIVE: To investigate the accuracy of model-based iterative reconstruction (MIR) for volume measurement of part-solid nodules (PSNs) and solid nodules (SNs) in comparison with filtered back projection (FBP) or hybrid iterative reconstruction (HIR) at various radiation dose settings. MATERIALS AND METHODS: CT scanning was performed for eight different diameters of PSNs and SNs placed in the phantom at five radiation dose levels (120 kVp/100 mAs, 120 kVp/50 mAs, 120 kVp/20 mAs, 120 kVp/10 mAs, and 80 kVp/10 mAs). Each CT scan was reconstructed using FBP, HIR, or MIR with three different image definitions (body routine level 1 [IMR-R1], body soft tissue level 1 [IMR-ST1], and sharp plus level 1 [IMR-SP1]; Philips Healthcare). The SN and PSN volumes including each solid/ground-glass opacity portion were measured semi-automatically, after which absolute percentage measurement errors (APEs) of the measured volumes were calculated. Image noise was calculated to assess the image quality. RESULTS: Across all nodules and dose settings, the APEs were significantly lower in MIR than in FBP and HIR (all p < 0.01). The APEs of the smallest inner solid portion of the PSNs (3 mm) and SNs (3 mm) were the lowest when MIR (IMR-R1 and IMR-ST1) was used for reconstruction for all radiation dose settings. (IMR-R1 and IMR-ST1 at 120 kVp/100 mAs, 1.06 ± 1.36 and 8.75 ± 3.96, p < 0.001; at 120 kVp/50 mAs, 1.95 ± 1.56 and 5.61 ± 0.85, p = 0.002; at 120 kVp/20 mAs, 2.88 ± 3.68 and 5.75 ± 1.95, p = 0.001; at 120 kVp/10 mAs, 5.57 ± 6.26 and 6.32 ± 2.91, p = 0.091; at 80 kVp/10 mAs, 5.84 ± 1.96 and 6.90 ± 3.31, p = 0.632). Image noise was significantly lower in MIR than in FBP and HIR for all radiation dose settings (120 kVp/100 mAs, 3.22 ± 0.66; 120 kVp/50 mAs, 4.19 ± 1.37; 120 kVp/20 mAs, 5.49 ± 1.16; 120 kVp/10 mAs, 6.88 ± 1.91; 80 kVp/10 mAs, 12.49 ± 6.14; all p < 0.001). CONCLUSION: MIR was the most accurate algorithm for volume measurements of both PSNs and SNs in comparison with FBP and HIR at low-dose as well as standard-dose settings. Specifically, MIR was effective in the volume measurement of the smallest PSNs and SNs.

Characterization of Tendon-Specific Markers in Various Human Tissues, Tenocytes and Mesenchymal Stem Cells.

Background: Unlike bone, cartilage, or muscle, tendon-specific markers are not well established. The purpose of the study was to investigate expression pattern and level of 6 well-known tendon-specific markers, in various human musculoskeletal tissues, tenocytes, and mesenchymal stem cells (MSCs). Methods: Musculoskeletal tissue samples of tendon, bone, cartilage, nerve, muscle, and fat were obtained from patients undergoing orthopedic surgery. Tenocytes, MSCs from bone marrow, adipose tissue, and umbilical cord were isolated from each tissue and cultured. Six tendon-specific markers, scleraxis (Scx), tenomodulin (TNMD), thrombospondin-4 (TSP-4), tenascin-C (TNC), type I collagen (Col I), and type III collagen (Col III) were investigated in tendon tissue, tenocytes, and MSCs. Results: mRNA levels of 6 tendon-specific markers were significantly higher in tendon tissue that in other connective tissues levels of Scx, TNMD, TSP-4, and Col III immediately decreased after plating tenocytes in culture dishes whereas those of TNC and Col I did not. In comparison with tendon tissue, mRNA levels pattern of Scx, TNMD, and TSP-4 in tenocytes were significantly higher than that in MSCs, but lower than in tendon tissue whereas expression pattern of TNC, Col I and III showed different pattern with each other. Conclusion: This study demonstrated that 6 commonly used tendon-specific markers were mainly expressed in tendon tissue, but that expression level and pattern of the tendon-specific markers with respect to kinds of tissues, culture duration of tenocytes and sources of MSCs.

Cone-Beam CT Virtual Navigation-Guided Percutaneous Needle Biopsy of Suspicious Pleural Metastasis: A Pilot Study.

Objective: To evaluate the diagnostic performance of cone-beam computed tomography (CBCT) virtual navigation-guided percutaneous pleural biopsy for suspected malignant pleural disease. Materials and Methods: This study enrolled 59 patients (31 males and 28 females; mean age, 63.4 years) with suspected malignant pleural disease diagnosed with CBCT from December 2010 to December 2016. Sixty-three CBCT-guided biopsies were performed using a coaxial system with 18- or 20-gauge cutting needles. Procedural details, diagnostic performance, radiation exposure, and complication rates were investigated. Results: The mean diameter perpendicular to the pleura of 51 focal and 12 diffuse pleural lesions was 1.53 ± 0.76 cm. The mean distance from the skin to the target was 3.40 ± 1.51 cm. Mean numbers of CT acquisitions and biopsies were 3.21 ± 0.57 and 3.05 ± 1.54. Total procedure time and coaxial introducer indwelling time were 11.87 ± 5.59 min and 8.78 ± 4.95 min, respectively. The mean dose area product was 12013.61 ± 7969.59 mGym2. There were 48 malignant, 10 benign, and 5 indeterminate lesions. Sensitivity, specificity, and diagnostic accuracy were 93.8% (45/48), 100% (10/10), and 94.8% (55/58), respectively. Positive and negative predictive values for malignancy were 100% (45/45) and 76.9% (10/13), respectively. Four patients (6.8%) with benign pathology during initial biopsy but still showing a high suspicion of malignancy underwent repeat biopsy and three of them were finally diagnosed with malignant pleural disease. There were three cases of minimal pneumothorax and no grave procedure-related complications. Conclusion: Cone-beam computed tomography-guided biopsy is an accurate and safe diagnostic technique for suspected malignant pleural lesion with reasonable radiation exposure and procedure time.

Unusual Presentation of Multiple Myeloma.

Malignancy is an independent risk factor of venous thromboembolism, although it is difficult to determine whether occult cancer is the cause of unprovoked VTE. About 25% of patients with VTE remain idiopathic. Here, the authors report the case of a 63-year-old woman with a history of unprovoked VTE some 10 months previously who presented with recurrent cough and dyspnea of 6 months duration and was finally diagnosed to have multiple myeloma.

Validation of prediction models for risk stratification of incidentally detected pulmonary subsolid nodules: a retrospective cohort study in a Korean tertiary medical centre.

OBJECTIVES: To validate the performances of two prediction models (Brock and Lee models) for the differentiation of minimally invasive adenocarcinoma (MIA) and invasive pulmonary adenocarcinoma (IPA) from preinvasive lesions among subsolid nodules (SSNs). DESIGN: A retrospective cohort study. SETTING: A tertiary university hospital in South Korea. PARTICIPANTS: 410 patients with 410 incidentally detected SSNs who underwent surgical resection for the pulmonary adenocarcinoma spectrum between 2011 and 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Using clinical and radiological variables, the predicted probability of MIA/IPA was calculated from pre-existing logistic models (Brock and Lee models). Areas under the receiver operating characteristic curve (AUCs) were calculated and compared between models. Performance metrics including sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were also obtained. RESULTS: For pure ground-glass nodules (n=101), the AUC of the Brock model in differentiating MIA/IPA (59/101) from preinvasive lesions (42/101) was 0.671. Sensitivity, specificity, accuracy, PPV and NPV based on the optimal cut-off value were 64.4%, 64.3%, 64.4%, 71.7% and 56.3%, respectively. Sensitivity, specificity, accuracy, PPV and NPV according to the Lee criteria were 76.3%, 42.9%, 62.4%, 65.2% and 56.3%, respectively. AUC was not obtained for the Lee model as a single cut-off of nodule size (≥10 mm) was suggested by this model for the assessment of pure ground-glass nodules. For part-solid nodules (n=309; 26 preinvasive lesions and 283 MIA/IPAs), the AUC was 0.746 for the Brock model and 0.771 for the Lee model (p=0.574). Sensitivity, specificity, accuracy, PPV and NPV were 82.3%, 53.8%, 79.9%, 95.1% and 21.9%, respectively, for the Brock model and 77.0%, 69.2%, 76.4%, 96.5% and 21.7%, respectively, for the Lee model. CONCLUSIONS: The performance of prediction models for the incidentally detected SSNs in differentiating MIA/IPA from preinvasive lesions might be suboptimal. Thus, an alternative risk calculation model is required for the incidentally detected SSNs.

Mechanical stabilization of proteolytically degradable polyethylene glycol dimethacrylate hydrogels through peptide interaction.

Balancing enhancement of neurite extension against loss of matrix support in synthetic hydrogels containing proteolytically degradable and bioactive signaling peptides to optimize tissue formation is difficult. Using a systematic approach, polyethylene glycol hydrogels containing concurrent continuous concentration gradients of the laminin derived bioactive signaling peptide, Ile-Lys-Val-Ala-Val (IKVAV), and collagen derived matrix metalloprotease degradable peptide, GPQGIWGQ, were fabricated and characterized. During proteolytic degradation of the concentration gradient hydrogels, the IKVAV and IWGQ cleavage fragment from GPQGIWGQ were found to interact and stabilize the bulk Young's Modulus of the hydrogel. Further testing of discrete samples containing GPQGIWGQ or its cleavage fragments, GPQG and IWGQ, indicates hydrophobic interactions between the peptides are not necessary for mechanical stabilization of the hydrogel, but changes in the concentration ratio between the peptides tethered in the hydrogel and salts and ions in the swelling solution can affect the stabilization. Encapsulation of human induced pluripotent stem cell derived neural stem cells did not reduce the mechanical properties of the hydrogel over a 14 day neural differentiation culture period, and IKVAV was found to maintain concentration dependent effects on neurite extension and mRNA gene expression of neural cytoskeletal markers, similar to previous studies. As a result, this work has significant implications for the analysis of biological studies in matrices, as the material and mechanical properties of the hydrogel may be unexpectedly temporally changing during culture due to interactions between peptide signaling elements, underscoring the need for greater matrix characterization during the degradation and cell culture. STATEMENT OF SIGNIFICANCE: Greater emulation of the native extracellular matrix is necessary for tissue formation. To achieve this, matrices are becoming more complex, often including multiple bioactive signaling elements. However, peptide signaling in polyethylene glycol matrices and amino acids interactions between peptides can affect hydrogel material and mechanical properties, but are rarely studied. The current study identifies such an interaction between laminin derived peptide, IKVAV, and collagen derived matrix metalloprotease degradable peptide, GPQGIWGQ. Previous studies using these peptides did not identify their interactions' ability to mechanically stabilize the hydrogel during degradation. This work underscores the need for greater matrix characterization and consideration of bioactive signaling element effects temporally on the matrix's material and mechanical properties, as they can contribute to cellular response.

Cone beam computed tomography virtual navigation-guided transthoracic biopsy of small (≤ 1 cm) pulmonary nodules: impact of nodule visibility during real-time fluoroscopy.

OBJECTIVE: To evaluate the impact of nodule visibility during real-time fluoroscopy and other biopsy-related variables on the diagnostic accuracy and complication rates of cone beam CT (CBCT) virtual navigation (VN)-guided percutaneous transthoracic needle biopsies (PTNBs) of small (≤1 cm) pulmonary nodules. METHODS: Patients (99 males and 114 females; age, 62.1 ± 11.1 years) who underwent CBCT VN-guided biopsies for lung nodules ≤ 1 cm were retrospectively reviewed. The visibility of target nodules was assessed on the captured fluoroscopy images. Diagnostic accuracies were calculated and logistic regression analyses were performed to determine independent influencing factors for the correct diagnosis and complications (pneumothoraxes and hemoptysis) in CBCT VN-guided PTNBs, respectively. RESULTS: Among 213 nodules, 63 (29.6%) were invisible on real-time fluoroscopy during VN. The diagnostic accuracy of CBCT VN-guided PTNBs for the invisible nodules was 76.7%, while for the visible nodules was 89.1% (p = 0.042). In the logistic regression analysis, the visibility of a target nodule (odds ratio = 2.49, p = 0.047) was the only independent influencing factor for a correct diagnosis. As regards complication rates, nodule visibility was not a significant factor for the occurrence of a pneumothorax or hemoptysis. CONCLUSION: Although nodule visibility on real-time fluoroscopy was an affecting factor for the correct diagnosis, CBCT VN-guided PTNB was feasible for the invisible nodules with diagnostic accuracy of 76.7%. Advance in knowledge: CBCT VN-guided PTNB can be tried safely for the subcentimeter-sized pulmonary nodules regardless of their fluoroscopic visibility.

Risk factors for haemoptysis after percutaneous transthoracic needle biopsies in 4,172 cases: Focusing on the effects of enlarged main pulmonary artery diameter.

OBJECTIVES: To evaluate the risk factors for haemoptysis after cone-beam computed tomography (CBCT)-guided percutaneous transthoracic needle biopsy (PTNB), particularly on whether the enlargement of main pulmonary artery diameter (mPAD) is a risk factor for PTNB-related haemoptysis. METHODS: 4,172 cases of CBCT-guided PTNBs in 3,840 patients were retrospectively included in this study. Various data including mPAD measured on preprocedural CT images were evaluated using logistic regression analyses to determine significant risk factors for both haemoptysis and severe haemoptysis, designated as when blood transfusion, vascular embolisation or cardiopulmonary resuscitation were required to manage patients with haemoptysis. RESULTS: Haemoptysis occurred in 5.78 % (241/4172) of all PTNB procedures, while severe haemoptysis occurred in 0.18 % (7/4172). Female sex, history of antiplatelet or anticoagulative drugs, prolonged activated partial thromboplastin time, subsolid nodules, cavitary nodules and long pleura-to-target distance were revealed to be independent risk factors for haemoptysis, while mPAD enlargement (> 29.5 mm) was not. Regarding severe haemoptysis, however, mPAD enlargement was demonstrated to be an independent risk factor along with the presence of subsolid and cavitary target nodules. CONCLUSION: mPAD enlargement was not a significant risk factor for PTNB-related haemoptysis; however, it was a significant risk factor for severe haemoptysis. KEY POINTS: • mPAD enlargement was a significant risk factor for severe PTNB-related haemoptysis. • mPAD can be useful in screening high-risk patients for severe haemoptysis. • Subsolid or cavitary nodule was another significant risk factor for severe haemoptysis.

Time-dependent analysis of incidence, risk factors and clinical significance of pneumothorax after percutaneous lung biopsy.

OBJECTIVES: To evaluate the time-dependent incidence, risk factors and clinical significance of percutaneous lung biopsy (PLB)-related pneumothorax. METHODS: From January 2012-November 2015, 3,251 patients underwent 3,354 cone-beam CT-guided PLBs for lung lesions. Cox, logistic and linear regression analyses were performed to identify time-dependent risk factors of PLB-related pneumothorax, risk factors of drainage catheter insertion and those of prolonged catheter placement, respectively. RESULTS: Pneumothorax occurred in 915/3,354 PLBs (27.3 %), with 230/915 (25.1 %) occurring during follow-ups. Risk factors for earlier occurrence of PLB-related pneumothorax include emphysema (HR=1.624), smaller target (HR=0.922), deeper location (HR=1.175) and longer puncture time (HR=1.036), while haemoptysis (HR=0.503) showed a protective effect against earlier development of pneumothorax. Seventy-five cases (8.2 %) underwent chest catheter placement. Mean duration of catheter placement was 3.2±2.0 days. Emphysema (odds ratio [OR]=2.400) and longer puncture time (OR=1.053) were assessed as significant risk factors for catheter insertion, and older age (parameter estimate=1.014) was a predictive factor for prolonged catheter placement. CONCLUSION: PLB-related pneumothorax occurred in 27.3 %, of which 25.1 % developed during follow-ups. Smaller target size, emphysema, deeply-located lesions were significant risk factors of PLB-related pneumothorax. Emphysema and older age were related to drainage catheter insertion and prolonged catheter placement, respectively. KEY POINTS: • One-fourth of percutaneous lung biopsy (PLB)-related pneumothorax occurs during follow-up. • Smaller, deeply-located target and emphysema lead to early occurrence of pneumothorax. • Emphysema is related to drainage catheter insertion for PLB-related pneumothorax. • Older age may lead to prolonged catheter placement for PLB-related pneumothorax. • Tailored management can be possible with time-dependent information of PLB-related pneumothorax.

Concentration dependent survival and neural differentiation of murine embryonic stem cells cultured on polyethylene glycol dimethacrylate hydrogels possessing a continuous concentration gradient of n-cadherin derived peptide His-Ala-Val-Asp-Lle.

N-cadherin cell-cell signaling plays a key role in the structure and function of the nervous system. However, few studies have incorporated bioactive signaling from n-cadherin into tissue engineering matrices. The present study uses a continuous gradient approach in polyethylene glycol dimethacrylate hydrogels to identify concentration dependent effects of n-cadherin peptide, His-Ala-Val-Asp-Lle (HAVDI), on murine embryonic stem cell survival and neural differentiation. The n-cadherin peptide was found to affect the expression of pluripotency marker, alkaline phosphatase, in murine embryonic stem cells cultured on n-cadherin peptide containing hydrogels in a concentration dependent manner. Increasing n-cadherin peptide concentrations in the hydrogels elicited a biphasic response in neurite extension length and mRNA expression of neural differentiation marker, neuron-specific class III ß-tubulin, in murine embryonic stem cells cultured on the hydrogels. High concentrations of n-cadherin peptide in the hydrogels were found to increase the expression of apoptotic marker, caspase 3/7, in murine embryonic stem cells compared to that of murine embryonic stem cell cultures on hydrogels containing lower concentrations of n-cadherin peptide. Increasing the n-cadherin peptide concentration in the hydrogels facilitated greater survival of murine embryonic stem cells exposed to increasing oxidative stress caused by hydrogen peroxide exposure. The combinatorial approach presented in this work demonstrates concentration dependent effects of n-cadherin signaling on mouse embryonic stem cell behavior, underscoring the need for the greater use of systematic approaches in tissue engineering matrix design in order to understand and optimize bioactive signaling in the matrix for tissue formation. STATEMENT OF SIGNIFICANCE: Single cell encapsulation is common in tissue engineering matrices. This eliminates cellular access to cell-cell signaling. N-cadherin, a cell-cell signaling molecule, plays a vital role in the development of neural tissues, but has not been well studied as a bioactive signaling element in neural tissue engineering matrices. The present study uses a systematic continuous gradient approach to identify concentration dependent effects of n-cadherin derived peptide, HAVDI, on the survival and neural differentiation of murine embryonic stem cells. This work underscores the need for greater use to combinatorial strategies to understand the effect complex bioactive signaling, such as n-cadherin, and the need to optimize the concentration of such bioactive signaling within tissue engineering matrices for maximal cellular response.

Predictors of pneumothorax following endoscopic valve therapy in patients with severe emphysema.

BACKGROUND: Endoscopic valve implantation is an effective treatment for patients with advanced emphysema. Despite the minimally invasive procedure, valve placement is associated with risks, the most common of which is pneumothorax. This study was designed to identify predictors of pneumothorax following endoscopic valve implantation. METHODS: Preinterventional clinical measures (vital capacity, forced expiratory volume in 1 second, residual volume, total lung capacity, 6-minute walk test), qualitative computed tomography (CT) parameters (fissure integrity, blebs/bulla, subpleural nodules, pleural adhesions, partial atelectasis, fibrotic bands, emphysema type) and quantitative CT parameters (volume and low attenuation volume of the target lobe and the ipsilateral untreated lobe, target air trapping, ipsilateral lobe volume/hemithorax volume, collapsibility of the target lobe and the ipsilateral untreated lobe) were retrospectively evaluated in patients who underwent endoscopic valve placement (n=129). Regression analysis was performed to compare those who developed pneumothorax following valve therapy (n=46) with those who developed target lobe volume reduction without pneumothorax (n=83). FINDING: Low attenuation volume% of ipsilateral untreated lobe (odds ratio [OR] =1.08, P=0.001), ipsilateral untreated lobe volume/hemithorax volume (OR =0.93, P=0.017), emphysema type (OR =0.26, P=0.018), pleural adhesions (OR =0.33, P=0.012) and residual volume (OR =1.58, P=0.012) were found to be significant predictors of pneumothorax. Fissure integrity (OR =1.16, P=0.075) and 6-minute walk test (OR =1.05, P=0.077) were also indicative of pneumothorax. The model including the aforementioned parameters predicted whether a patient would experience a pneumothorax 84% of the time (area under the curve =0.84). INTERPRETATION: Clinical and CT parameters provide a promising tool to effectively identify patients at high risk of pneumothorax following endoscopic valve therapy.

Predictors of clinical outcome in emphysema patients with atelectasis following endoscopic valve therapy: A retrospective study.

BACKGROUND AND OBJECTIVE: The aim of endoscopic valve therapy in patients with emphysema is complete lobar atelectasis of the most emphysematous lobe. However, even after the radiological advent of atelectasis, great variability in clinical outcomes can be observed. METHODS: The baseline clinical measures (vital capacity (VC), forced expiratory flow in 1 s (FEV1 ), residual volume (RV) and 6-min walk test (6-MWT)) and computed tomography variables (low attenuation volume (LAV) of the target lobe, LAV% of the target and the ipsilateral untreated lobe and LAV of the target lobe to LAV of the target lung and to LAV of the total lung) of 77 patients with complete atelectasis following valve therapy were retrospectively examined to determine their impact on patient´s outcome (changes in VC, FEV1 , RV and 6-MWT from baseline to the time of atelectasis). RESULTS: Low attenuation volume of the target lobe to LAV of the target lung predicts a significant FEV1 improvement in patients with complete lobar atelectasis following valve therapy. A 10% difference in that computed tomography predictor was associated with a 82-mL improvement in FEV1 (P = 0.006). Lower 6-MWT scores, low VC and high RV at baseline were significantly associated with greater improvement in the respective parameter (all P < 0.001). CONCLUSION: Low attenuation volume of the target lobe to LAV of the target lung and baseline clinical measures seem to significantly predict clinical outcomes in patients with complete lobar atelectasis following valve treatment.