Clinical Role of Upfront F-18 FDG PET/CT in Determining Biopsy Sites for Lung Cancer Diagnosis.

PURPOSE: This study aimed to investigate the impact of FDG PET/CT timing for biopsy site selection in patients with stage IV lung cancer regarding complications and diagnostic yield. METHODS: This retrospective analysis was performed on 1297 patients (924 men and 373 women with a mean age of 71.4 ± 10.2 years) who underwent percutaneous needle biopsy (PNB) for stage IV lung cancer diagnosis in two hospitals. Data collected included the patient's characteristics, order date of the biopsy and PET/CT exams, biopsy target site (lung or non-lung), guidance modality, complications, sample adequacy, and diagnostic success. Based on the order date of the PNB and PET/CT exams, patients were categorized into upfront and delayed PET/CT groups. RESULTS: PNB for non-lung targets resulted in significantly lower rates of minor (8.1% vs. 16.2%), major (0.2% vs. 3.4%), and overall complications (8.3% vs. 19.6%) compared to PNB for lung targets (p < 0.001 for all types of complications). Compared to the delayed PET/CT group, the upfront PET/CT group exhibited a lower probability of lung target selection of PNB (53.9% vs. 67.1%, p < 0.001), including a reduced incidence of major complications (1.0% vs. 2.9%, p = 0.031). Moreover, there was no significant difference in the occurrence of minor and total complications between the two groups. Upfront PET/CT and delayed PET/CT groups showed no significant difference regarding sample adequacy and diagnostic success. CONCLUSIONS: Upfront PET/CT may have an impact on the selection of the biopsy site for patients with advanced lung cancer, which could result in a lower rate of major complications with no change in the diagnostic yield. Upfront PET/CT demonstrates potential clinical implications for enhancing the safety of lung cancer diagnosis in clinical practice.

Efficacy of Bronchial Artery Embolization for Clinically Suspected Bronchial Dieulafoy's Disease.

BACKGROUND: The efficacy of bronchial artery embolization (BAE) for bronchial Dieulafoy's disease (BDD) has not been well established. OBJECTIVE: This study aimed to evaluate the safety and efficacy of BAE in patients with clinically suspected BDD presenting with major hemoptysis, and to describe angiographic findings. METHODS: 17 patients (all men; mean age, 53.5 years) diagnosed with clinically suspected BDD by bronchoscopy (n = 7) or CT angiography (CTA) (n = 10) and who underwent BAE after directional and segmental localization of the target bronchus were enrolled. BAE was performed at the culprit bronchial artery traveling toward the target bronchus, regardless of the pathologic angiographic findings. Angiographic findings and clinical outcomes of BAE, including technical and clinical success, complication, recurrent hemoptysis, and follow-up imaging, were retrospectively reviewed. RESULTS: Representative angiographic findings included parenchymal hypervascularity prominent in the lobe where the BDD was located (82.4%), bronchial artery hypertrophy (70.6%), and contrast extravasation into the bleeding bronchus (17.6%). BAE was technically successful in all patients. All hemoptysis ceased within 24 h. No procedure-related complications occurred. During a mean follow-up of 491.9 days, 1 (6%) patient experienced recurrent hemoptysis. Follow-up bronchoscopy or CT performed in 10 (58.8%) patients showed the disappearance of pre-existing lesions (n = 9) or glue cast within the target bronchial artery (n = 1). CONCLUSION: Bronchial angiography showed pathologic findings in most patients with clinically suspected BDD. BAE assisted by bronchoscopy or CTA localization is a safe and effective treatment for patients with clinically suspected BDD with excellent short- to mid-term results.

Genetic variants in key necroptosis regulators predict prognosis of non-small cell lung cancer after surgical resection.

BACKGROUND: Necroptosis is a regulated inflammatory cell death which plays a significant role in cancer development and progression. In this study, we evaluated whether genetic variants in key regulators of necroptosis may affect survival outcome of non-small cell lung cancer (NSCLC) patients after surgical resection. METHODS: A total of 674 patients who underwent curative surgery were included. Fifteen genetic variants in key regulators of necroptosis (RIPK1, RIPK3, and MLKL) were selected. The association of these variants with survival outcomes was evaluated. RESULTS: Two variants, RIPK1 rs17548629C > T and MLKL rs877375G > C, were associated with better overall survival and disease-free survival in multivariate analyses. When the patients were divided according to histology, the associations were significant only in adenocarcinoma, but not in squamous cell carcinoma. RIPK1 rs17548629 C-to-T change was associated with significantly increased luciferase activity by modulating the binding of miR-642a. Promoter assays showed a significantly increased promoter activity in MLKL rs877375C allele compared to G allele. Consistently, the mRNA expression level of RIPK1 and MLKL showed significant positive correlation with RIPK1 rs17548629C-to-T and MLKL rs877375G-to-C changes. CONCLUSION: Two genetic variants in key regulators in necroptosis, RIPK1 rs17548629C > T and MLKL rs877375G > C, may be used as biomarkers to predict survival outcomes in surgically resected NSCLC patients.

Ultrasound-guided lung biopsy for small (≤2 cm) subpleural lung lesions: comparison of diagnostic yield and safety with larger lesions.

Background: Ultrasound (US)-guided percutaneous core needle biopsy (PCNB) has been used to diagnose subpleural lung lesions with high diagnostic performance and acceptable complication rates. However, with regard to the role of US-guided needle biopsy for the diagnosis of small (≤2 cm) subpleural lesions, limited information is available. Methods: From April 2011 to October 2021, a total of 572 US-guided PCNBs in 572 patients were retrospectively reviewed. The lesion size, pleural contact length (PCL), lesion location, and operator's experience were analyzed. Computed tomography features including peri-lesional emphysema, air-bronchogram, and cavitary change were also included in image analysis. The patients were divided into three groups according to lesion size (lesions ≤2 cm vs. 2 cm< lesions ≤5 cm vs. lesions >5 cm). The sample adequacy, diagnostic success rate, diagnostic accuracy, and complication rate was calculated. For statistical analysis, one-way ANOVA, Kruskal-Wallis test, or the chi-square test were used. Results: The overall sample adequacy, diagnostic success rate, and diagnostic accuracy were 96.2%, 82.9%, and 90.4%, respectively. In the subgroup analysis, sample adequacy (93.1% vs. 96.1% vs. 96.9%, P=0.307), diagnostic success rate (75.0% vs. 81.6% vs. 85.7%, P=0.079), and diagnostic accuracy (84.7% vs. 90.8% vs. 90.5%, P=0.301) were not significantly different. Operator's experience (OR, 0.64; 95% CI: 0.49-0.80; P<0.001), lesion size (OR, 0.68; 95% CI: 0.54-0.83; P<0.001), PCL (OR, 0.68; 95% CI: 0.52-0.84; P=0.001), and presence of air-bronchogram (OR, 14.36; 95% CI: 4.18-48.53; P<0.001) were independently associated with complication rate. Conclusions: US-guided PCNB performed by an experienced radiologist could be an effective and safe diagnostic approach for subpleural lesions, even in small lesions.

Efficacy and safety of Tuina for chronic nonspecific low back pain: A PRISMA-compliant systematic review and meta-analysis.

OBJECTIVE: Chronic nonspecific low back pain (CNLBP) is a serious medical and social problem resulting in functional decline and decreased work ability. Tuina, a form of manual therapy, has been sparsely used to treat patients with CNLBP. To systematically assess the efficacy and safety of Tuina for patients with CNLBP. METHODS: Multiple English and Chinese literature databases were searched until September 2022 for randomized controlled trials (RCTs) of Tuina in the treatment of CNLBP. The methodological quality was assessed using the Cochrane Collaboration's tool, and certainty of the evidence was determined with the online Grading of Recommendations, Assessment, Development and Evaluation tool. RESULTS: Fifteen RCTs with 1390 patients were included. Tuina demonstrated a significant effect on pain (SMD: -0.82; 95% CI -1.12 to -0.53; P < .001; I2 = 81%) and physical function (SMD: -0.91; 95% CI -1.55 to -0.27; P = .005; I2 = 90%) when compared to control. However, Tuina resulted in no significant improvement for quality of life (QoL) (SMD: 0.58; 95% CI -0.04 to 1.21; P = .07; I2 = 73%;) compared to control. The Grading of Recommendations, Assessment, Development and Evaluation evidence quality was determined to be low level for pain relief, physical function, and QoL measurements. Only six studies reported adverse events; none were serious. CONCLUSION: Tuina might be an effective and safe strategy for treating CNLBP in terms of pain and physical function, but not for QoL. The study results should be interpreted with caution for their low-level evidence. More multicenter, large-scale RCTs with a rigorous design are required to further confirm our findings.

Peritumoral imaging features of thymic epithelial tumors for the prediction of transcapsular invasion: beyond intratumoral analysis

PURPOSE: The purpose of this study was to differentiate cases without transcapsular invasion (Masaoka-Koga stage I) from cases with transcapsular invasion (Masaoka-Koga stage II or higher) in patients with thymic epithelial tumors (TETs) using tumoral and peritumoral computed tomography (CT) features. METHODS: This retrospective study included 116 patients with pathological diagnoses of TETs. Two radiologists evaluated clinical variables and CT features, including size, shape, capsule integrity, presence of calcification, internal necrosis, heterogeneous enhancement, pleural effusion, pericardial effusion, and vascularity grade. Vascularity grade was defined as the extent of peritumoral vascular structures in the anterior mediastinum. The factors associated with transcapsular invasion were analyzed using multivariable logistic regression. In addition, the interobserver agreement for CT features was assessed using Cohen's or weighted kappa coefficients. The difference between the transcapsular invasion group and that without transcapsular invasion was evaluated statistically using the Student's t-test, Mann-Whitney U test, chi-square test, and Fisher's exact test. RESULTS: Based on pathology reports, 37 TET cases without and 79 with transcapsular invasion were identified. Lobular or irregular shape [odds ratio (OR): 4.19; 95% confidence interval (CI): 1.53-12.09; P = 0.006], partial complete capsule integrity (OR: 5.03; 95% CI: 1.85-15.13; P = 0.002), and vascularity grade 2 (OR: 10.09; 95% CI: 2.59-45.48; P = 0.001) were significantly associated with transcapsular invasion. The interobserver agreement for shape classification, capsule integrity, and vascularity grade was 0.840, 0.526, and 0.752, respectively (P < 0.001 for all). CONCLUSION: Shape, capsule integrity, and vascularity grade were independently associated with transcapsular invasion of TETs. Furthermore, three CT TET features demonstrated good reproducibility and help differentiate between TET cases with and without transcapsular invasion.

The Safety and Efficacy of Low-Dose Naltrexone in Patients with Fibromyalgia: A Systematic Review.

Fibromyalgia (FM) is a chronic pain sensitivity syndrome characterized by diffuse musculoskeletal pain and many other systemic manifestations. Low-dose naltrexone (LDN) has been increasingly used as an off-label treatment option in FM. However, current evidence on the safety and efficacy of LDN in patients with FM is not well known. To systematically assess the current evidence on the safety and efficacy of LDN use in the treatment of FM. A comprehensive bibliographic search was conducted on EBM Reviews - Cochrane Central Register of Controlled Trials, EBM Reviews - Cochrane Database of Systematic, Embase, Ovid MEDLINE(R) and Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions and Scopus databases in September 2022. Inclusion criteria were articles that were published in English, focusing on clinical trials involving LDN for the treatment of FM. Two reviewers independently screened and extracted the data. A qualitative analysis was used due to the high methodological heterogeneity between studies. The electronic search produced 805 articles. After applying the inclusion criteria, 9 articles (one RCT, two case reports, two case series, and four pilot trials) were selected for evaluation. LDN intervention protocols, study designs, and follow-up periods were different among the included studies. Overall, LDN was found to be effective in the symptomatic management of FM, and of the 78% of included studies that evaluated for safety, no severe adverse events were reported. Proving the efficacy and safety of low-dose naltrexone is a future possibility based on current study data, but the level of scientific evidence is limited. Future well-designed trials with large sample sizes are required.

Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma.

OBJECTIVE: This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. METHODS: Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. RESULTS: Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A>G in an enhancer which is expected to regulate the expression of ribosomal protein S3 (RPS3) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36-0.97, p = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09-1.91, p = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. CONCLUSION: This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.

Unilateral Pulmonary Vein Atresia Initially Presenting as Interstitial Lung Disease in an Elderly Female: Serial Chest Radiograph Changes and Its Literature Review.

Unilateral pulmonary vein atresia (PVA) is a rare congenital cardiovascular anomaly occurring after the common pulmonary vein fails to incorporate into the left atrium. It is most commonly diagnosed in childhood, and diagnosis after reaching adulthood is extremely rare. Dyspnea on exertion and hemoptysis are common clinical features in adult PVA patients, whereas lung parenchymal abnormalities are indirect signs of PVA, which can manifest as interstitial lung disease. Herein, we present the case of a 62-year-old female diagnosed with unilateral PVA presenting as unilateral interstitial lung disease and report the changes in her chest radiographs over 12 years.

Genetic variants in LKB1/AMPK/mTOR pathway are associated with clinical outcomes of chemotherapy in non-small cell lung cancer.

This study was conducted to investigate the relationship between genetic variants in LKB1/AMPK/mTOR pathway and treatment outcomes of patients with non-small cell lung cancer (NSCLC) treated with chemotherapy. A total of 379 patients with NSCLC who underwent first-line paclitaxel-cisplatin chemotherapy was enrolled. The associations between 19 single nucleotide variants (SNVs) in the LKB1/AMPK/mTOR pathway and the chemotherapy response and overall survival (OS) were analyzed. Among the SNVs analyzed, AKT1 rs2494750G>C and TSC1 rs2809244C>A were associated with clinical outcomes after chemotherapy in multivariate analyses. The AKT1 rs2494750G>C was significantly associated with a better response to chemotherapy (adjusted odds ratio [aOR]: 1.92, 95% confidence interval [CI]: 1.02-3.62, p = 0.04). The TSC1 rs2809244C>A were significantly associated with better OS (adjusted hazard ratio [aHR]: 0.79, 95% CI: 0.62-0.99, p = 0.04). When stratified by tumor histology, AKT1 rs2494750G>C exhibited a significant association with the chemotherapy response only in adenocarcinoma and TSC1 rs2809244C>A was also significantly associated with OS only in adenocarcinoma. This result suggests that the AKT1 rs2494750G>C and TSC1 rs2809244 C>A may be useful for predicting the clinical outcome of first-line paclitaxel-cisplatin chemotherapy in NSCLC.

Dietary Supplements for Pain Relief in Patients with Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Pain is the most frequently encountered symptom by patients with fibromyalgia (FM). Dietary supplements (DSs) in particular have a proven impact as a possible adjunctive therapy for symptom management in FM. However, there is currently no conclusive review outlining the evidence for DSs in pain management in FM. This study aims to assess currently available studies evaluating the use of DSs for pain relief in FM. Randomized controlled trials regarding the use of DSs on adult FM patients were included for evidence synthesis. Study results indicated that DSs significantly relieved pain in FM (SMD 1.23; 95% CI 0.02-2.43, P = 0.046) but did not improve quality of life (QoL) (SMD 0.73; 95% CI -0.07-1.53, P = 0.075) in the data. Adverse events of DSs varied from mild to severe, with the most common being gastrointestinal symptoms and androgenic side effects in 5.7% and 3.9% of patients, respectively. More well-designed RCTs are required in the future. The protocol for this review has been published on PROSPERO (CRD42020149941).

Importance of CT image normalization in radiomics analysis: prediction of 3-year recurrence-free survival in non-small cell lung cancer.

OBJECTIVES: To analyze whether CT image normalization can improve 3-year recurrence-free survival (RFS) prediction performance in patients with non-small cell lung cancer (NSCLC) relative to the use of unnormalized CT images. METHODS: A total of 106 patients with NSCLC were included in the training set. For each patient, 851 radiomic features were extracted from the normalized and the unnormalized CT images, respectively. After the feature selection, random forest models were constructed with selected radiomic features and clinical features. The models were then externally validated in the test set consisting of 79 patients with NSCLC. RESULTS: The model using normalized CT images yielded better performance than the model using unnormalized CT images (with an area under the receiver operating characteristic curve of 0.802 vs 0.702, p = 0.01), with the model performing especially well among patients with adenocarcinoma (with an area under the receiver operating characteristic curve of 0.880 vs 0.720, p < 0.01). CONCLUSIONS: CT image normalization may improve prediction performance among patients with NSCLC, especially for patients with adenocarcinoma. KEY POINTS: • After CT image normalization, more radiomic features were able to be identified. • Prognostic performance in patients was improved significantly after CT image normalization compared with before the CT image normalization. • The improvement in prognostic performance following CT image normalization was superior in patients with adenocarcinoma.

Ginseng for the Treatment of Chronic Fatigue Syndrome: A Systematic Review of Clinical Studies.

BACKGROUND: Chronic fatigue syndrome (CFS) is a complex and often disabling chronic condition emerging worldwide, with no curative or definitive therapy yet identified. Ginseng has been widely used to treat fatigue in other patient groups and conditions; however, a systematic review focusing solely on the impact of ginseng on fatigue in patients with CFS has not been performed. OBJECTIVE: This study aimed to assess the current state of evidence regarding ginseng for CFS. METHODS: Multiple databases were searched from inception to October 2020. All data was extracted independently and in duplicates. Outcomes of interest included the effectiveness and safety of ginseng in patients with CFS. RESULTS: 2 studies enrolling 68 patients were deemed eligible, including one randomized clinical trial and one prospective observational study. The certainty of evidence in the effectiveness outcome was low and moderate from both studies, while the safety evidence was very low as reported from one study. CONCLUSION: Study findings highlight a potential benefit of ginseng therapy in the treatment of CFS. However, we are not able to draw firm conclusions due to limited clinical studies. The paucity of data warrants limited confidence. There is a need for future rigorous studies to provide further evidence.

Exonuclease 1 genetic variant is associated with clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma.

Pemetrexed is an anti-folate agent which is one of the most frequently used chemotherapy agents for non-squamous non-small cell lung cancer (NSCLC) patients. However, clinical response to pemetrexed chemotherapy and survival outcome of patients varies significantly. We evaluated whether the genetic variants in miRNA target sites may affect the treatment outcome of pemetrexed chemotherapy in lung adenocarcinoma patients. One hundred SNPs in miRNA binding regions in cancer-related genes were obtained from the crosslinking, ligation, and sequencing of hybrids (CLASH) and CancerGenes database, and the associations with the response to pemetrexed chemotherapy and survival outcomes were investigated in 314 lung adenocarcinoma patients. Two polymorphisms, EXO1 rs1047840G>A and CAMKK2 rs1653586G>T, were significantly associated with worse chemotherapy response (adjusted odds ratio [aOR] = 0.41, 95% CI = 0.24-0.68, P = 0.001, under dominant model; and aOR = 0.33, 95% CI = 0.16-0.67, P = 0.002, under dominant model, respectively) and worse OS (adjusted hazard ratio [aHR] = 1.34, 95% CI = 1.01-1.77, P = 0.04, under dominant model; and aHR = 1.50, 95% CI = 1.06-2.13, P = 0.02, under dominant model, respectively) in multivariate analyses. Significantly increased luciferase activity was noted in EXO1 rs1047840 A allele compared to G allele. In conclusion, two SNPs in miRNA binding sites, especially EXO1 rs1047840G>A, were associated with the chemotherapy response and survival outcome in lung adenocarcinoma patients treated with pemetrexed.

Risk factors for heel pressure injury in cardiovascular intensive care unit patients.

This study analyzed the risk factors for heel pressure injury in cardiovascular intensive care unit patients with the aim of laying the groundwork for preventive nursing interventions. We conducted a retrospective case-control study of 92 patients who were admitted to the cardiovascular surgical or medical intensive care unit of a university hospital in South Korea between January and December 2017. Of these patients, 31 and 61 were included to the heel pressure injury group and the non-heel pressure injury group, respectively. Data on their demographic, disease-related, and intensive care unit treatment characteristics, as well as the degree of pressure injury, were collected from the hospital's electronic medical records using a standardized form. Cardiac surgery (P < .001), operation time (P = .001), use of a mechanical ventilator (P < .001), use of vasoconstrictors (P < .001), use of sedative drugs (P < .001), and extracorporeal membrane oxygenation treatment (P < .001) were identified as significant risk factors for heel pressure injury. A total of 22 patients (71%) from the heel pressure injury group developed deep tissue injury, and 16 patients (51.6%) who received extracorporeal membrane oxygenation treatment developed heel pressure injury.

Clinical adaptation of synthetic MRI-based whole brain volume segmentation in children at 3 T: comparison with modified SPM segmentation methods.

PURPOSE: To validate the use of synthetic magnetic resonance imaging (SyMRI) volumetry by comparing with child-optimized SPM 12 volumetry in 3 T pediatric neuroimaging. METHODS: In total, 106 children aged 4.7-18.7 years who underwent both synthetic and 3D T1-weighted imaging and had no abnormal imaging/neurologic findings were included for the SyMRI vs. SPM T1-only segmentation (SPM T1). Forty of the 106 children who underwent an additional 3D T2-weighted imaging were included for the SyMRI vs. SPM multispectral segmentation (SPM multi). SPM segmentation using an age-appropriate atlas and inverse-transforming template-space intracranial mask was compared with SyMRI segmentation. Volume differences between SyMRI and SPM T1 were plotted against age to evaluate the influence of age on volume difference. RESULTS: Measurements derived from SyMRI and two SPM methods showed excellent agreements and strong correlations except for the CSF volume (CSFV) (intraclass correlation coefficients = 0.87-0.98; r = 0.78-0.96; relative volume difference other than CSFV = 6.8-18.5% [SyMRI vs. SPM T1] and 11.3-22.7% [SyMRI vs. SPM multi]). Dice coefficients of all brain tissues (except CSF) were in the range 0.78-0.91. The Bland-Altman plot and age-related volume difference change suggested that the volume differences between the two methods were influenced by the volume of each brain tissue and subject's age (p < 0.05). CONCLUSION: SyMRI and SPM segmentation results were consistent except for CSFV, which supports routine clinical use of SyMRI-based volumetry in pediatric neuroimaging. However, caution should be taken in the interpretation of the CSF segmentation results.

Role of Chest Computed Tomography in Patients Hospitalized with Community-Acquired Complicated Parapneumonic Effusion or Empyema.

BACKGROUND: Data regarding predictors of the outcome in patients with community-acquired complicated parapneumonic effusion (CPPE) or empyema are insufficient. The aim of the present study was to investigate the prognostic factors in these patients. METHODS: Patients with community-acquired pneumonia (CAP) were classified into a CPPE or empyema group and a control group. The patients with CPPE or empyema were further divided into longer and shorter length of stay (LOS) groups, and clinical variables and computed tomographic (CT) findings were compared between the 2 groups. RESULTS: Of outcome variables, LOS was significantly longer in the CPPE or empyema group than in the control group (13 days [interquartile range, 10‒17 days] versus 8 days [6‒12 days], p < 0.001), whereas 30-day mortality and in-hospital mortality were not significantly different between the 2 groups. Patients with CPPE or empyema were divided into shorter LOS (<14 days) and longer LOS (≥14 days) groups. Pneumonia severity index (PSI) class IV‒V (odds ratio [OR], 2.79; 95% confidence interval [CI]: 1.35, 5.76; p = 0.006), increased attenuation of extrapleural fat (OR, 2.26; 95% CI: 1.06, 4.80; p = 0.034), and pleural microbubbles (OR 3.93; 95% CI: 1.03, 14.98; p = 0.045) were independent predictors for prolonged LOS in CAP patients with CPPE or empyema. CONCLUSIONS: Increased attenuation of extrapleural fat and pleural microbubbles assessed with CT and PSI class IV‒V independently predicted prolonged LOS in CAP patients with CPPE or empyema. These findings may be helpful to identify patients who need more intensive evaluation and intervention.

Genetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma.

We investigated the association between genetic variants in the histone modification regions and the prognosis of lung adenocarcinoma after curative surgery. Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The SNPs were analyzed in a discovery set (n = 166) and a validation set (n = 238). The associations of the SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed. A total of 279 SNPs were selected for genotyping. Among these, CAPN1 rs17583C>T was significantly associated with better OS and DFS (P = 0.001 and P = 0.007, respectively), and LINC00959 rs4751162A>G was significantly associated with worse DFS (P = 0.008). Luciferase assays showed a significantly lower promoter activity of CAPN1 in the rs17583 T allele than C allele (P = 0.008), and consistently the CT + TT genotypes had significantly lower CAPN1 expression than CC genotype (P = 0.01) in clinical samples. The rs4751162 G allele had higher promoter activity of GLRX3 than A allele (P = 0.05). The motif analyses and ChIP-qPCR confirmed that the variants are located in the active promoter/enhancer regions where transcription factor binding occurs. This study showed that genetic variants in the histone modification regions could predict the prognosis of lung adenocarcinoma after surgery.

Nuclear Pore Glycoprotein 62 Genetic Variant rs9523 is Associated with Clinical Outcomes of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Lung Adenocarcinoma Patients.

INTRODUCTION: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have represented the prototype of targeted therapy in NSCLC. Patients with EGFR-mutant lung adenocarcinoma extract an extraordinary clinical benefit from EGFR-TKIs. However, the extent and duration of these responses are heterogeneous, suggesting the existence of genetic modifiers affecting an individual's response to TKIs. We investigated whether genetic variants in miRNA binding sites are associated with the clinical outcome of EGFR-TKIs in lung adenocarcinoma patients. METHODS: One hundred SNPs at miRNA binding sites in cancer-related genes were selected for the analysis using the crosslinking, ligation and sequencing of hybrids (CLASH) and CancerGenes database. qRT-PCR and luciferase assays were conducted to evaluate the functional relevance of the SNPs. RESULTS: NUP62 rs9523A>G were significantly associated with worse response to EGFR-TKIs, overall survival (OS), and progression-free survival (PFS). The other three SNPs (DVL2 rs2074216G>A, ARF1 rs11541557G>T, and UHRF1 rs2261988C>A) were significantly associated with worse OS and PFS. The rs9523A>G was significantly associated with decreased NUP62 expression in tumor tissues. In addition, a significantly decreased luciferase activity was noted in NUP62 rs9523 G allele compared to A allele. CONCLUSION: Genetic variants in miRNA binding sites, especially NUP62 rs9523A>G, may be useful in predicting the clinical outcomes of EGFR-mutant lung adenocarcinoma patients treated with EGFR-TKIs.

CT-derived 3D-diaphragm motion in emphysema and IPF compared to normal subjects.

Image registration-based local displacement analysis enables evaluation of respiratory motion between two computed tomography-captured lung volumes. The objective of this study was to compare diaphragm movement among emphysema, idiopathic pulmonary fibrosis (IPF) and normal subjects. 29 normal, 50 emphysema, and 51 IPF subjects were included. A mass preserving image registration technique was used to compute displacement vectors of local lung regions at an acinar scale. Movement of the diaphragm was assumed to be equivalent to movement of the basal lung within 5 mm from the diaphragm. Magnitudes and directions of displacement vectors were compared between the groups. Three-dimensional (3D) and apico-basal displacements were smaller in emphysema than normal subjects (P = 0.003, P = 0.002). Low lung attenuation area on expiration scan showed significant correlations with decreased 3D and apico-basal displacements (r = - 0.546, P < 0.0001; r = - 0.521, P < 0.0001) in emphysema patients. Dorsal-ventral displacement was smaller in IPF than normal subjects (P < 0.0001). The standard deviation of the displacement angle was greater in both emphysema and IPF patients than normal subjects (P < 0.0001). In conclusion, apico-basal movement of the diaphragm is reduced in emphysema while dorsal-ventral movement is reduced in IPF. Image registration technique to multi-volume CT scans provides insight into the pathophysiology of limited diaphragmatic motion in emphysema and IPF.