Usefulness of longitudinal nodule-matching algorithm in computer-aided diagnosis of new pulmonary metastases on cancer surveillance CT scans.

Background: Detecting new pulmonary metastases by comparing serial computed tomography (CT) scans is crucial, but a repetitive and time-consuming task that burdens the radiologists' workload. This study aimed to evaluate the usefulness of a nodule-matching algorithm with deep learning-based computer-aided detection (DL-CAD) in diagnosing new pulmonary metastases on cancer surveillance CT scans. Methods: Among patients who underwent pulmonary metastasectomy between 2014 and 2018, 65 new pulmonary metastases missed by interpreting radiologists on cancer surveillance CT (Time 2) were identified after a retrospective comparison with the previous CT (Time 1). First, DL-CAD detected nodules in Time 1 and Time 2 CT images. All nodules detected at Time 2 were initially considered metastasis candidates. Second, the nodule-matching algorithm was used to assess the correlation between the nodules from the two CT scans and to classify the nodules at Time 2 as "new" or "pre-existing". Pre-existing nodules were excluded from metastasis candidates. We evaluated the performance of DL-CAD with the nodule-matching algorithm, based on its sensitivity, false-metastasis candidates per scan, and positive predictive value (PPV). Results: A total of 475 lesions were detected by DL-CAD at Time 2. Following a radiologist review, the lesions were categorized as metastases (n=54), benign nodules (n=392), and non-nodules (n=29). Upon comparison of nodules at Time 1 and 2 using the nodule-matching algorithm, all metastases were classified as new nodules without any matching errors. Out of 421 benign lesions, 202 (48.0%) were identified as pre-existing and subsequently excluded from the pool of metastasis candidates through the nodule-matching algorithm. As a result, false-metastasis candidates per CT scan decreased by 47.9% (from 7.1 to 3.7, P<0.001) and the PPV increased from 11.4% to 19.8% (P<0.001), while maintaining sensitivity. Conclusions: The nodule-matching algorithm improves the diagnostic performance of DL-CAD for new pulmonary metastases, by lowering the number of false-metastasis candidates without compromising sensitivity.

Chemical Characterization of the Precipitate Found in and Its Effect on Drug Release of the Scutellaria†baicalensis-Coptis†chinensis Extract.

Precipitate generation is a challenging issue during the production of herbal decoction as it affects the stability and bioavailability of active compounds. Here we explored the composition of the natural precipitate formed from and its effect on drug release of Scutellaria baicalensis-Coptis chinensis paired extract (SCPE). Furthermore, the surface morphology of the SCPE precipitate was also investigated. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to chemical component analysis and field emission scanning electron microscope (FE-SEM) was performed to particle observation. Baicalin (BA), berberine (BBR) and starch-arginine-rich polymers were abundant in the SCPE precipitate. FE-SEM micrographs showed spheroidal shaped particles in the SCPE supernatant, while spherical and porous tissue-shaped particles in the SCPE precipitate. In vitro drug release of baicalin and berberine contained in the precipitate may increase as the polymer is removed. The presence of polymer-related interactions were confirmed by the greater increase in solubility of baicalin upon addition of arginine and polymer. This was also supported by the solubility decrease of the BA-BBR complex in polymer solution and the gelation of the BA-BBR complex in arginine solution. Our results provide a scientific basis for elucidating the pharmaceutical properties of the decoction of S. baicalensis-C. chinensis-based herbal medicine.

Accelerometer-derived physical activity and sedentary behavior patterns among Korean adults.

PURPOSE: This study aimed to provide an overview of accelerometer-derived physical activity (PA) and sedentary behavior (SB) patterns among Korean adults. We also investigated the association between participant characteristics and the likelihood of adherence to moderate-to-vigorous physical activity (MVPA), SB, and the MVPA-SB guidelines. METHODS: Data from the 2014-2017 Korea National Health and Nutrition Examination Survey were used. The study involved a nationally representative sample of 2,260 Korean adults aged ≥20 years. Accelerometers were used to measure PA and SB for seven days. Multivariate logistic regression models were used to assess the association between the participant characteristics and the likelihood of adhering to the MVPA, SB, and MVPA-SB guidelines. RESULTS: SB (60.61%), light intensity (26.22%), and lifestyle activities (9.4%) accounted for the majority of the participants' days. MVPA and vigorous physical activity (VPA) accounted for 3.72% and 0.06% of the days, respectively. The MVPA guidelines were more likely to be adhered to by men, older adults, participants with higher education, non-smokers, and individuals without multimorbidity. Participants with higher education and household income were less likely to adhere to the SB guidelines. Women (OR=0.51), participants with high education levels (OR=0.54), current smokers (OR=0.47), and patients with multimorbidity (OR=0.46) were less likely to adhere to the MVPA-SB guidelines. CONCLUSION: This study found that participants were predominantly sedentary, with only a small proportion engaging in VPA. There were differences related to demographic factors and health status. Most Korean adults do not adhere to the recommended MVPA-SB guidelines, and that is a serious public health concern. These findings highlight the need to promote PA and reduce SB through public health policies and interventions, particularly for adults facing PA barriers.

Crystal structure of [1,2,4]triazolo[4,3-b]pyridazine derivatives as BRD4 bromodomain inhibitors and structure-activity relationship study.

BRD4 contains two tandem bromodomains (BD1 and BD2) that recognize acetylated lysine for epigenetic reading, and these bromodomains are promising therapeutic targets for treating various diseases, including cancers. BRD4 is a well-studied target, and many chemical scaffolds for inhibitors have been developed. Research on the development of BRD4 inhibitors against various diseases is actively being conducted. Herein, we propose a series of [1,2,4]triazolo[4,3-b]pyridazine derivatives as bromodomain inhibitors with micromolar IC50 values. We characterized the binding modes by determining the crystal structures of BD1 in complex with four selected inhibitors. Compounds containing [1,2,4] triazolo[4,3-b]pyridazine derivatives offer promising starting molecules for designing potent BRD4 BD inhibitors.

The Role and Clinical Outcomes of Endoscopic Spine Surgery of Treating Spinal Metastases; Outcomes of 29 Cases From 8 Countries.

OBJECTIVE: We aim to report the outcomes and feasibility of endoscopic spine surgery used to treat symptomatic spinal metastases patients. This is the most extensive series of spinal metastases patients who underwent endoscopic spine surgery. METHODS: A worldwide collaborative network group of endoscopic spine surgeons, named 'ESSSORG,' was established. Patients diagnosed with spinal metastases who underwent endoscopic spine surgery from 2012 to 2022 were retrospectively reviewed. All related patient data and clinical outcomes were gathered and analyzed before the surgery and the followtime period of 2 weeks, 1 month, 3 months, and 6 months. RESULTS: A total of 29 patients from South Korea, Thailand, Taiwan, Mexico, Brazil, Argentina, Chile, and India, were included. The mean age was 59.59 years, and 11 of them were female. The total number of decompressed levels was 40. The technique was relatively equal (15 uniportal; 14 biportal). The average length of admission was 4.41 days. Of all patients with an American Spinal Injury Association Impairment Scale of D or lower before surgery, 62.06% reported having at least one recovery grade after the surgery. Almost all clinical outcomes parameters statistically significantly improved and maintained from 2 weeks to 6 months after the surgery. Few surgical-related complications (4 cases) were reported. CONCLUSION: Endoscopic spine surgery is a valid option for treating spinal metastases patients as it could yield comparable results to other minimally invasive spine surgery techniques. As the aim is to improve the quality of life, this procedure is valuable and holds value in palliative oncologic spine surgery.

The Bcl-2/Bcl-xL Inhibitor ABT-263 Attenuates Retinal Degeneration by Selectively Inducing Apoptosis in Senescent Retinal Pigment Epithelial Cells.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.

Evaluation of the efficacy and safety of conventional and interlaminar full-endoscopic decompressive laminectomy to treat lumbar spinal stenosis (ENDO-F trial): Protocol for a prospective, randomized, multicenter trial.

Lumbar spinal stenosis is a common spinal degenerative condition. Minimally invasive interlaminar full-endoscopic decompressive laminectomy provides greater patient satisfaction and faster recovery than open decompressive laminectomy. The aim of our randomized controlled trial will be to compare the safety and efficacy of interlaminar full-endoscopic laminectomy and open decompressive laminectomy. Our trial will include 120 participants (60 per group) who will undergo surgical treatment for lumbar spinal stenosis. The primary outcome will be the Oswestry Disability Index measured at 12 months postoperatively. Secondary patient-reported outcomes will include back and radicular leg pain measured via a visual analog scale; the Oswestry Disability Index; the Euro-QOL-5 Dimensions score measured at 2 weeks and at 3, 6, and 12 months postoperatively; and patient satisfaction. The functional measures will include time to return to daily activities postoperatively and walking distance/time. The surgical outcomes will include postoperative drainage, operation time, duration of hospital stay, postoperative creatine kinase (an indicator of muscle injury) level, and postoperative surgical scarring. Magnetic resonance and computed tomography images and simple radiographs will be obtained for all patients. The safety outcomes will include surgery-related complications and adverse effects. All evaluations will be performed by a single assessor at each participating hospital who will be blinded to group allocation. The evaluations will be conducted preoperatively and at 2 weeks and 3, 6, and 12 months postoperatively. The randomized, multicenter design of the trial, blinding, and justification of the sample size will reduce the risk of bias in our trial. The results of the trial will provide data regarding the use of interlaminar full-endoscopic laminectomy as an alternative to open decompressive laminectomy that results in similar surgical findings with less invasiveness. Trial registration: This trial is registered at cris.nih.go.kr. (KCT0006198; protocol version 1; 27 May 2021).

The Related Mechanisms Predicted through Network-Based Pharmacological Analysis and the Anti-Inflammatory Effects of Fraxinus rhynchophylla Hance Bark on Contact Dermatitis in Mice.

Fraxinus rhynchophylla Hance bark has been used to treat patients with inflammatory or purulent skin diseases in China, Japan, and Korea. This study was undertaken to determine the mechanism responsible for the effects of F. rhynchophylla and whether it has a therapeutic effect in mice with contact dermatitis (CD). In this study, the active compounds in F. rhynchophylla, their targets, and target gene information for inflammatory dermatosis were investigated using network-based pharmacological analysis. Docking analysis was conducted using AutoDock Vina. In addition, the therapeutic effect of an ethanolic extract of F. rhynchophylla (EEFR) on skin lesions and its inhibitory effects on histopathological abnormalities, inflammatory cytokines, and chemokines were evaluated. Finally, its inhibitory effects on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways were observed in RAW 264.7 cells. In our results, seven active compounds were identified in F. rhynchophylla, and six were associated with seven genes associated with inflammatory dermatosis and exhibited a strong binding affinity (<-6 kcal/mol) to prostaglandin G/H synthase 2 (PTGS2). In a murine 1-fluoro-2,4-dinitrobenzene (DNFB) model, topical EEFR ameliorated the surface symptoms of CD and histopathological abnormalities. EEFR also reduced the levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues and inhibited PTGS2, the nuclear translocation of NF-κB (p65), and the activation of c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. In conclusion, the bark of F. rhynchophylla has potential use as a therapeutic or cosmetic agent, and the mechanism responsible for its effects involves the suppression of inflammatory mediators, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB)-α degradation, the nuclear translocation of NF-κB, and JNK phosphorylation.

Is navigation beneficial for transforaminal endoscopic lumbar foraminotomy? A preliminary comparison study with fluoroscopic guidance.

PURPOSE: The primary purpose of this study was to determine radiation exposure of the surgeon during transforaminal endoscopic lumbar foraminotomy (TELF). Secondary purpose of this study was to compare clinical and radiologic outcomes between TELF under C-arm fluoroscopic guidance (C-TELF) and O-arm navigation-guided TELF (O-TELF). METHODS: The author reviewed patients' medical records who underwent TELF at our institute from June 2015 to November 2022. A total of 40 patients were included (18 patients with C-TELF and 22 with O-TELF). Basic demographic data were collected. Preoperative/postoperative visual analog scale (VAS) and Oswestry Disability Index (ODI) were recorded at the outpatient clinic. Radiologic features were compared on X-rays at each follow-up. The degree of foraminal expansion was measured/compared through MRI. In the C-TELF group, the amount of exposure was calculated with a dosimeter. RESULTS: Average surgeon's effective dose in the C-TELF group was 0.036 mSv. In the case of the O-TELF group, there was no radiation exposure during operation. However, the operation time in the O-TELF group was about 37 min longer than that in the C-TELF group. There were significant improvements in VAS/ODI after operation in both groups. Complications were identified in three patients. CONCLUSION: O-TELF showed similarly favorable clinical and radiologic outcomes to C-TELF in lumbar foraminal stenosis, including complication rate. Compared to C-TELF, O-TELF has an advantage of not wearing a lead apron since the operator is not exposed to radiation. However, the operation time was longer with O-TELF due to O-arm setting time. Because there are pros and cons, the choice of surgical method depends on the surgeon's preference.

Sesquiterpenoids Isolated from the Rhizomes of Genus Atractylodes.

Atractylodes plants have been used in traditional herbal medicine to treat gastrointestinal diseases and contain various chemical compounds. Sesquiterpenoids are the most important therapeutic compounds in Atractylodes rhizomes. Based on studies reported from 2000 to 2022, we classified sesquiterpenoids by their chemical skeletons and original resources. Moreover, we discussed their biosynthesis and physicochemical and pharmacological features. We reported sesquiterpenoids with skeletal moieties, such as monocyclic sesquiterpenes (bisabolene- and elemene-type), bicyclic sesquiterpenes (eudesmane-, isopterocarpolone-, hydroxycarissone-, eremophilane-, bisesquiterpenoid-, guaiane- and spirovetivane-type and eudesmane lactones) and tricyclic sesquiterpenes (cyperene- and patchoulene-type), with their biosynthetic pathways, chemical modifications and in vivo metabolites. The pharmacological activities of sesquiterpenoids as anti-inflammatory, anti-tumor, anti-diabetic and anti-microbial and for treating gastrointestinal disorders have been reported for this genus.

ID-Checker Technology for the Highly Selective Macroscale Delivery of Anticancer Agents to the Cancer Cells.

Cancer cells deploy several glucose transport protein (GLUT) channels on the cell membranes to increase glucose uptake. Cancer cells die within 24 h in the absence of glucose. Thus, preventing the deployment of GLUT channels can deprive them of glucose, resulting in apoptosis within 24 h. Herein, we developed the ID-Checker with a glucose tag that ensures its highly specific macroscale delivery of anticancer agents to the cancer cells through the GLUT channels. ID-Checker presented here showed IC50 values of 0.17-0.27 and 3.34 µM in cancer and normal cell lines, respectively. ID-Checker showed a selectivity index of 12.5-20.2, which is about 10-20 times higher than that of known anticancer agents such as colchicine. ID-Checker inhibits the microtubule formation, which results in the prevention of the deployment of GLUT channels in 6 h and kills the cancer cells within 24 h without any damage to normal cells.

BMS794833 inhibits macrophage efferocytosis by directly binding to MERTK and inhibiting its activity.

Myeloid epithelial reproductive proto-oncogene tyrosine kinase (MERTK) plays an essential role in modulating cancer immune tolerance by regulating macrophage efferocytosis. Studies are underway to develop small-molecule chemicals that inhibit MERTK as cancer immunotherapeutic agents, but these efforts are in their early stages. This study identified BMS794833, whose primary targets are MET and VEGFR2, as a potent MERTK inhibitor and developed a real-time efferocytosis monitoring system. The X-ray cocrystal structure revealed that BMS794833 was in contact with the ATP-binding pocket and the allosteric back pocket, rendering MERTK inactive. Homogeneous time-resolved fluorescence kinetic and Western blotting analyses showed that BMS794833 competitively inhibited MERTK activity in vitro and inhibited the autophosphorylation of MERTK in macrophages. We developed a system to monitor MERTK-dependent efferocytosis in real time, and using this system, we confirmed that BMS794833 significantly inhibited the efferocytosis of differentiated macrophages. Finally, BMS794833 significantly inhibited efferocytosis in vivo in a mouse model. These data show that BMS794833 is a type II MERTK inhibitor that regulates macrophage efferocytosis. In addition, the real-time efferocytosis monitoring technology developed in this study has great potential for future applications.

Juglone and KPT6566 Suppress the Tumorigenic Potential of CD44+CD133+ Tumor-Initiating Caco-2 Cells In Vitro and In Vivo.

Pin1, a cis/trans isomerase of peptidyl-prolyl peptide bonds, plays a crucial role in the pathogenesis of many human cancers. Although chemical inhibitors of Pin1 show potent antitumor therapeutic properties against various cancers, their effect on colorectal cancer, especially colorectal tumor-initiating cells, remains unknown. Here, we investigated the effect of Juglone and KPT6566 on Caco-2 cells and tumor-initiating Caco-2 cells. Juglone and KPT6566 inhibited cell growth and colony formation, and induced apoptosis of Caco-2 cells. We also found that Juglone and KPT6566 downregulated expression of G1-phase-specific cyclins and cyclin-dependent kinases in a time-dependent manner, consistent with suppression of Caco-2 cell proliferation and colony formation. Although tumor-initiating cells are thought to be responsible for resistance to traditional chemotherapeutic drugs, our experiments demonstrate that Juglone or KPT6566 kill both tumor-initiating and non-tumor-initiating Caco-2 cells with equal or similar efficacy. Finally, when CD44+CD133+ tumor-initiating Caco-2 cells were injected into NSG mice, Juglone or KPT6566 led to a meaningful reduction in tumor volume and mass compared with tumors isolated from mice that received control treatment. Overall, these results indicate that chemical Pin1 inhibitors may be a valuable therapeutic option against colorectal tumor-initiating cancer cells.

Comparative study of the efficacy and safety of minimally invasive interlaminar full-endoscopic discectomy versus conventional microscopic discectomy in single-level lumbar herniated intervertebral disc (ENDO-F Trial): a multicenter, prospective, randomized controlled trial protocol.

BACKGROUND: Advances in minimally invasive surgery have expanded the indications for interlaminar full-endoscopic discectomy. Although the clinical outcomes for this approach may be equivalent to those of conventional microscopic discectomy, the supporting evidence is still based on small, single-center, prospective, and retrospective studies. Therefore, a multicenter randomized controlled trial is warranted. METHODS: This will be a prospective, multicenter, randomized controlled trial comparing the efficacy and safety of interlaminar full-endoscopic discectomy to those of conventional microscopic discectomy. The trial will enroll 100 participants with a lumbar disc herniation, 50 in each group. The primary outcome will be the Oswestry Disability Index (ODI) score at 12 months post-surgery. Secondary outcomes will be back and leg pain (visual analog scale); the ODI; the EuroQol-5-dimension score; patient satisfaction; and walking distance/time and time to return to daily activities post-surgery. Surgical outcomes will include postoperative drainage, operative time, duration of hospital stay, postoperative creatine kinase level as an indicator of muscle injury, and postoperative scarring. Postoperative magnetic resonance imaging, computed tomography, and simple radiography will be performed to evaluate radiographic outcomes between the two surgical approaches. Surgery-related complications and adverse effects will be evaluated as safety outcomes. A single assessor at each participating hospital, blinded to group allocation, will assess the enrolled participants at baseline, at 2 weeks, and at 3, 6, and 12 months postoperatively. DISCUSSION: This trial is designed to determine whether interlaminar full-endoscopic discectomy is clinically comparable to microscopic discectomy to treat lumbar disc herniations. All efforts will be made to reduce bias, including adequate sample size, blinded analyses, and multicenter prospective registration. The outcomes will inform practice, providing the evidence needed for using interlaminar full-endoscopic over microscopic discectomy by confirming the potential of this technique to improve patient satisfaction and clinical outcomes. TRIAL REGISTRATION: Clinical Research Information Service; cris.nih.go.kr. (KCT0006277); protocol version (v1, June 8, 2021).

Volumetric analysis of pulmonary nodules: reducing the discrepancy between the diameter-based volume calculation and voxel-counting method.

Background: When assessing the volume of pulmonary nodules on computed tomography (CT) images, there is an inevitable discrepancy between values based on the diameter-based volume calculation and the voxel-counting method, which is derived from the Euclidean distance measurement method on pixel/voxel-based digital image. We aimed to evaluate the ability of a modified diameter measurement method to reduce the discrepancy, and we determined a conversion equation to equate volumes derived from different methods. Methods: Two different anthropomorphic phantoms with subsolid and solid nodules were repeatedly scanned under various settings. Nodules in CT images were detected and segmented using a fully automated algorithm and the volume was calculated using three methods: the voxel-counting method (Vvc ), diameter-based volume calculation (Vd ), and a modified diameter-based volume calculation (Vd+ 1), in which one pixel spacing was added to the diameters in the three axes (x-, y-, and z-axis). For each nodule, Vd and Vd +1 were compared to Vvc by computing the absolute percentage error (APE) as follows: APE =100 × (V - Vvc )/Vvc . Comparisons between APEd and APEd+1 according to CT parameter setting were performed using the Wilcoxon signed-rank test. The Jonckheere-Terpstra test was used to evaluate trends across the four different nodule sizes. Results: The deep learning-based computer-aided diagnosis (DL-CAD) successfully detected and segmented all nodules in a fully automatic manner. The APE was significantly less with Vd+1 than with Vd (Wilcoxon signed-rank test, P<0.05) regardless of CT parameters and nodule size. The APE median increased as the size of the nodule decreased. This trend was statistically significant (Jonckheere-Terpstra test, P<0.001) regardless of volume measurement method (diameter-based and modified diameter-based volume calculations). Conclusions: Our modified diameter-based volume calculation significantly reduces the discrepancy between the diameter-based volume calculation and voxel-counting method.

Detection and Quantification of Tp53 and p53-Anti-p53 Autoantibody Immune Complex: Promising Biomarkers in Early Stage Lung Cancer Diagnosis.

Lung cancer is a leading cause of death worldwide, claiming nearly 1.80 million lives in 2020. Screening with low-dose computed tomography (LDCT) reduces lung cancer mortality by about 20% compared to standard chest X-rays among current or heavy smokers. However, several reports indicate that LDCT has a high false-positive rate. In this regard, methods based on biomarker detection offer excellent potential for developing noninvasive cancer diagnostic tests to complement LDCT for detecting stage 0∼IV lung cancers. Herein, we have developed a method for detecting and quantifying a p53-anti-p53 autoantibody complex and the total p53 antigen (wild and mutant). The LOD for detecting Tp53 and PIC were 7.41 pg/mL and 5.74 pg/mL, respectively. The detection ranges for both biomarkers were 0-7500 pg/mL. The known interfering agents in immunoassays such as biotin, bilirubin, intra-lipid, and hemoglobin did not detect Tp53 and PIC, even at levels that were several folds higher levels than their normal levels. Furthermore, the present study provides a unique report on this preliminary investigation using the PIC/Tp53 ratio to detect stage I-IV lung cancers. The presented method detects lung cancers with 81.6% sensitivity and 93.3% specificity. These results indicate that the presented method has high applicability for the identification of lung cancer patients from the healthy population.

Clinical features and long-term prognosis of acute fibrinous and organizing pneumonia histologically confirmed by surgical lung biopsy.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare interstitial pneumonia characterized by intra-alveolar fibrin deposition and organizing pneumonia. The clinical manifestations and long-term prognosis of AFOP are unclear. Our objective was to investigate the clinical features and prognosis of AFOP. METHODS: We identified patients diagnosed with AFOP by surgical lung biopsy between January 2011 and May 2018 at Seoul National University Bundang Hospital. We retrospectively reviewed clinical and radiologic findings, treatment, and outcomes of AFOP. RESULTS: Fifteen patients with histologically confirmed lung biopsies were included. The median follow-up duration was 2.4 (range, 0.1-82) months. The median age was 55 (range, 33-75) years, and four patients were immunocompromised. Fever was the most common clinical presentation (86.7%). Patchy ground-glass opacities and/or consolidations were the most predominant findings on chest computed tomography images. Nine patients (60%) received mechanical ventilator care, and eight patients (53.3%) died. The non-survivors tended to have slightly higher body mass index (BMI) and a long interval between symptom onset and diagnosis than the survivors, but these findings were not statistically significant. Among seven survivors, five patients were discharged without dyspnea and oxygen supplement. CONCLUSIONS: The clinical course of AFOP was variable. Although AFOP was fatal, most of the patients who recovered from AFOP maintained normal life without supplemental oxygen therapy and respiratory symptoms.

Reliability of cephalometric landmark identification on three-dimensional computed tomographic images.

Our aims were to evaluate the reliability of three-dimensional (3D) cephalometric landmark identification in 3D images, and to propose an improved protocol for determining these landmarks. Computed tomographic (CT) images of 13 landmarks were obtained. One that did not show any artifacts, asymmetry in maxillofacial structures, or bony defects, was selected. Two orthodontic practitioners identified 3D cephalometric landmarks 10 times at one-week intervals. The distances of 26 landmarks were measured on the basis of three reference planes (coronal, horizontal, and sagittal). Ten mean (SD) measurements from each examiner were calculated, and the maximum and minimum values and the difference from the 10 measurements of each one were measured at a 95% confidence interval. Interexaminer differences for the three planes were found in the upper right first molar, point A, both gonions, left orbitale, and both porions. The lower right first molar, foramen magnum, gnathion, nasion, and pogonion showed interexaminer differences in two planes. Menton, basion, posterior nasal spine, upper and lower left first molar, and right mental foramen showed interexaminer differences in only one plane. With reference to intraexaminer differences, poor repeatability was observed for gonion, orbitale, condylion, and porion. Reliable 3D landmarks are the meeting point of sutures, distinct structures at converging planes, landmarks positioned in the midline, distinct anatomical structures such as the mental foramen, and teeth using multiplanar views.

The active von Frey filament test: A new technique to evaluate hand tactile sensation in continuous variable units.

The von Frey filament test (vF) is a mainstay of clinical examination. However, its results can be affected by touch speed and other potentially confounding factors. Moreover, the differences between two adjacent filament levels are too large to detect subtle changes. Active vF (AvF) was developed to induce in-depth sensory change. The present study hypothesized that AvF produces different patterns of fingertip sensation; consequently, it could be used as a new assessment tool for neural impairment. The aim of the study was to provide preliminary normative comparative vF and AvF data. This study prospectively examined 32 healthy participants, using AvF and vF. The index and the fifth finger volar pad were examined using AvF and vF, without visual stimulation. The correlation between AvF and vF measurements was evaluated. In addition, differences according to innervation zone, right versus left hand, and gender, and the correlation between AvF values and subjects' age were analyzed. Mean AvF value was significantly higher and had greater variance than vF (111.3 ± 46.9 vs. 24.1 ± 9.8; P < 0.01). The Spearman correlation coefficient between AvF and vF was 0.341. Values were similar in the index and fifth fingers and right and left hands. However, values were significantly different between women and men. The correlation between age and AvF values was 0.259. AvF provided more precise values, with continuous units for tactile sensation, excluding tester-dependent factors. Furthermore, AvF and vF values may not be correlated.