A patient with a lung adenosquamous carcinoma harboring a de novo T790M mutation and huge nonbacterial vegetative growths successfully treated with osimertinib: A case report.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition; sterile vegetations attach to heart valves. NBTE is typically found in patients with malignancies or autoimmune disorders. Although surgical interventions are sometimes performed, the appropriate indication and timing are still unclear. Here, we describe a 72-year-old woman diagnosed with adenosquamous carcinoma of the lung. She was initially diagnosed as pT2aN0M0 and underwent RUL lobectomy. After nine months, lung cancer recurred, and she underwent treatment with cytotoxic chemotherapy. However, images showed progression after only one month. Rebiopsy revealed she had comutation of de novo EGFR L858R and T790M. Treatment was changed to gefitinib. After one month, she experienced loss of consciousness. Brain magnetic resonance imaging (MRI) showed multiple lesions resembling infarctions or metastases. Chest computed tomography (CT) revealed progression. Osimertinib was prescribed and she underwent echocardiography to rule out the possibility of a cardiogenic embolism. Surprisingly, severe mitral regurgitation and a massive vegetation on the mitral valve were found. Cardiologists recommended surgery due to the severity of the embolic event and valve dysfunction, but it was decided to continue antibiotics, osimertinib, and anticoagulants instead of surgery due to the patient's poor general condition and the possibility of NBTE. Six weeks later, the patient's condition markedly improved and echocardiography revealed a marked reduction in vegetation size. Clinicians should be aware that targeted therapy can be effective in treating severe cancer complications, such as NBTE, as evidenced by the successful treatment of lung cancer with osimertinib. This option should be considered, particularly for elderly lung cancer patients, before resorting to surgery as a first-line treatment for NBTE.

Correction: Kim et al. Assessment of Enhancement Kinetics Improves the Specificity of Abbreviated Breast MRI: Performance in an Enriched Cohort. Diagnostics 2023, 13, 136.

There were errors in the original publication [...].

Subcategorization of intermediate suspicion thyroid nodules based on suspicious ultrasonographic findings.

PURPOSE: This study compared the malignancy risk of intermediate suspicion thyroid nodules according to the presence of suspicious ultrasonographic (US) findings. METHODS: From January 2014 to December 2014, 299 consecutive intermediate suspicion thyroid nodules in 281 patients (mean age, 50.6±12.5 years) with final diagnoses were included in this study. Two radiologists retrospectively reviewed the US findings and subcategorized the intermediate suspicion category into nodules without suspicious findings and nodules with suspicious findings, including punctate echogenic foci, nonparallel orientation, or irregular margins. The malignancy rates were compared between the two subcategory groups. RESULTS: Of the 299 intermediate suspicion thyroid nodules, 230 (76.9%) were subcategorized as nodules without suspicious findings and 69 (23.1%) as nodules with suspicious findings. The total malignancy rate was 33.4% (100/299) and the malignancy rate of nodules with suspicious findings was significantly higher than that of nodules without suspicious findings (47.8% vs. 29.1%, P=0.004). In nodules with suspicious findings, the most common suspicious finding was punctate echogenic foci (48/82, 58.5%) followed by nonparallel orientation (22/82, 26.8%) and irregular margins (12/82, 14.6%). Thirteen nodules had two suspicious findings simultaneously. A linearly increasing trend in the malignancy rate was observed according to the number of suspicious US findings (P for trend=0.001). CONCLUSION: Intermediate suspicion thyroid nodules with suspicious findings showed a higher malignancy rate than those without suspicious findings. Further management guidelines for nodules with suspicious findings should differ from guidelines for nodules without suspicious findings, even in the same US category.

The first case report of Paragonimus westermani infection diagnosed by transbronchial lung cryobiopsy.

We report a case of pulmonary paragonimiasis diagnosed by transbronchial lung cryobiopsy (TBLC). TBLC is likely to be a superior method to transbronchial forceps biopsy because TBLC can get larger specimens, resulting in a higher chance of containing the eggs. A male patient aged 57 years presented with hemoptysis and dyspnea on exertion. His initial chest computed tomography scans showed a cavitary nodule with a peripheral ground-glass appearance, leading to a prescription of an oral antibiotic, with an initial assumption of pneumonia. A follow-up chest computed tomography, however, revealed an appearance of a new nodule adjacent to the original nodule. TBLC and transbronchial forceps biopsy were done to rule out lung cancer and eventually, the eggs of Paragonimus westermani were found using TBLC. Praziquantel was prescribed, showing improvements in symptoms and chest X-ray findings. TBLC has more potential to be utilized as a diagnostic method than transbronchial forceps biopsy because it has a better chance to confirm pulmonary paragonimiasis, which can be initially suspected as pulmonary tuberculosis or lung cancer.

MRI Findings Suggestive of Metastatic Axillary Lymph Nodes in Patients with Invasive Breast Cancer.

Purpose: This study aimed to investigate the diagnostic performance of features suggestive of nodal metastasis on preoperative MRI in patients with invasive breast cancer. Materials and Methods: We retrospectively reviewed the preoperative breast MRI of 192 consecutive patients with surgically proven invasive breast cancer. We analyzed MRI findings of axillary lymph nodes with regard to the size, long/short ratio, cortical thickness, shape and margin of the cortex, loss of hilum, asymmetry, signal intensity (SI) on T2-weighted images (T2WI), degree of enhancement in the early phase, and enhancement kinetics. Receiver operating characteristic (ROC) analysis, chi-square test, t test, and McNemar's test were used for statistical analysis. Results: Increased shorter diameter, uneven cortical shape, increased cortical thickness, loss of hilum, asymmetry, irregular cortical margin, and low SI on T2WI were significantly suggestive of metastasis. ROC analysis revealed the cutoff value for the shorter diameter and cortical thickness as 8.05 mm and 2.75 mm, respectively. Increased cortical thickness (> 2.75 mm) and uneven cortical shape showed significantly higher sensitivity than other findings in McNemar's test. Irregular cortical margins showed the highest specificity (100%). Conclusion: Cortical thickness > 2.75 mm and uneven cortical shape are more sensitive parameters than other findings, and an irregular cortical margin is the most specific parameter for predicting axillary metastasis in patients with invasive breast cancer.

Comparison of the Ultrasound Visibility of Tissue Markers in Metastatic Lymph Nodes after Neoadjuvant Chemotherapy in Patients with Breast Cancer.

This study aimed to investigate the differences in ultrasound (US) visibility for the localization of clipped metastatic lymph nodes after neoadjuvant chemotherapy (NAC), according to tissue marker type. This single-center retrospective study included 59 consecutive patients with breast cancer who underwent tissue marker insertion for histologically proven metastatic axillary lymph nodes before NAC, between March 2020 and August 2021. Two breast tissue markers were used: UltraClip™ (n = 29) and UltraCor™ Twirl™ (n = 30). The US visibility of tissue markers after NAC and the successful excision rate of the clipped lymph nodes were compared between the two types of tissue markers. UltraCor™ Twirl™ showed better overall US visibility than UltraClip™ after NAC (86.7% vs. 72.4%), but the difference was statistically insignificant. In the absence of residual metastatic lymph nodes on US after NAC (n = 32), UltraCor™ Twirl™ showed significantly better US visibility (83.3%, 15/18) than UltraClip™ (42.9%, 6/14; p = 0.027). The marker type was not associated with the successful excision of the clipped lymph node. UltraCor™ Twirl™ showed better US visibility than UltraClip™ in the metastatic axillary lymph nodes after NAC in the absence of residual suspicious lymph nodes on US.

Effects of Personal Low-Frequency Stimulation Device on Myalgia: A Randomized Controlled Trial.

Electrotherapy is commonly used for myalgia alleviation. Low-frequency stimulation (LFS) is primarily used for controlling acute and chronic pain and is a non-invasive therapy that can be easily performed with electric stimulation applied on the skin. However, little evidence exists regarding the pain alleviation effects of personal low-frequency stimulation device for home use. Moreover, no studies have compared myalgia alleviation effects between personal low-frequency stimulation (PLS) and physical therapy (PT), which are most commonly used for patients with myalgia in hospitals and clinics. Therefore, we aimed to investigate the pain alleviation effects of PLS in patients with myalgia and compare these effects with those of conventional PT (transcutaneous electrical nerve stimulation + ultrasound). In total, 39 patients with myalgia in the neck, shoulder, back, and waist areas were randomly assigned to the personal low-frequency stimulation group (PLSG: n = 20) and physical therapy group (PTG: n = 19). Both groups were treated for 3 weeks (20 min per session and 5 sessions per week). Patients were assessed for pain intensity by surface electromyography (sEMG), visual analogue scale (VAS) and a short-form McGill pain questionnaire (SF-MPQ) before and after the intervention period. Our results showed that PLSG showed a tendency of muscle relaxation with a significant decrease in sEMG in the neck (p = 0.0425), shoulder (p = 0.0425), and back (p = 0.0046) areas compared to the control group. However, there was no significant difference in waist area. Additionally, VAS scores significantly decreased between pre- and post-treatment in both PTG (p = 0.0098), and PLSG (p = 0.0304) groups, but there was no significance difference between the groups. With respect to SF-MPQ, the PLSG showed greater pain alleviation (5.23 ± 0.25) effects than the PTG (6.23 ± 0.25). Accordingly, our results suggest that PLS treatment using a home device might offer positive assistance in pain alleviation for patients with myalgia that is as equally effective as conventional PT treatment. However, further detailed studies are required considering larger samples to fully claim the effectiveness of this device.

Outcomes of patients presenting with elevated tumor marker levels but negative gadoxetic acid-enhanced liver MRI after a complete response to hepatocellular carcinoma treatment.

PURPOSE: Hepatocellular carcinoma (HCC) patients usually achieve a complete response after treatment. This study was aimed to assess the clinical outcome of HCC patients who had achieved a complete response but later presented with elevated tumor marker levels without an identifiable recurrent tumor on gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS: We retrospectively reviewed the clinical outcome of 58 HCC treated patients who had achieved a complete response but later was referred to our institution's multidisciplinary tumor board for a clinically suspected hidden HCC recurrence based on elevated tumor marker levels but negative gadoxetic acid-enhanced MRI. The imaging studies, tumor markers, and clinical information were reviewed. The total follow-up period was at least 15 months after the initial negative gadoxetic acid-enhanced MRI. RESULTS: Follow-up imaging studies detected an HCC lesion in 89.7% (n = 52/58) of the patients within the study period, and approximately half of the tumors (46.2%, n = 24/52) developed within 3 months. The most frequent site of recurrence was the liver (86.5%; n = 45/52), but extra-hepatic metastasis was also common (19.2%; n = 10/52). In 5.8% (n = 3/52), HCC reoccurred in the combined form of intra-hepatic and extra-hepatic recurrence. Extra-hepatic metastasis alone occurred in 13.5% (n = 7/52) of patients. CONCLUSIONS: HCC frequently recurred within a short interval in patients who achieved a complete response to treatment in the presence of increased tumor marker levels, even if gadoxetic acid-enhanced MRI was negative. Under such circumstances, we suggest a short-term follow-up including, but not limited to, gadoxetic acid-enhanced MRI along with systemic evaluation.

Magnetic resonance imaging-based texture analysis for the prediction of postoperative clinical outcome in uterine cervical cancer.

OBJECTIVES: Magnetic resonance imaging (MRI)-based texture analysis (MRTA) is a novel image analysis tool that offers objective information about the spatial arrangement of MRI signal intensity. We aimed to investigate the value of MRTA in predicting the postoperative clinical outcome of patients with uterine cervical cancer. METHODS: This retrospective study included 115 patients with surgically proven cervical cancer who underwent preoperative pelvic 3T-MRI, and MRTA was performed on T2-weighted images (T2), apparent diffusion coefficient (ADC) maps, and contrast-enhanced T1-weighted images (CE-T1). Filtration histogram-based texture analysis was used to generate six first-order statistical parameters [mean intensity, standard deviation (SD), mean of positive pixels (MPP), entropy, skewness, and kurtosis] at five spatial scaling factors (SSFs, 2-6 mm) as well as from unfiltered images. Cox proportional hazard models and time-dependent receiver operating characteristic analyses were used to evaluate the associations between parameters and recurrence-free survival (RFS). RESULTS: During a median follow-up of 36 months, tumor recurrence was found in 26 patients (22.6%). Multivariate analysis demonstrated that CE-T1 MPP and T2 kurtosis at SSF3-5, CE-T1 MPP at SSF6, and CE-T1 SD at unfiltered images were independent predictors of RFS (p < 0.05). Regarding the 2-year RFS for CE-T1 MPP and T2 kurtosis at SSF5, and CE-T1 MPP at SSF6, patients with > optimal cutoff values demonstrated significantly worse survival than those with ≤ optimal cutoff values (p < 0.05). CONCLUSION: Preoperative MRTA may be useful for predicting postoperative outcome in patients with cervical cancer.

Assessment of Enhancement Kinetics Improves the Specificity of Abbreviated Breast MRI: Performance in an Enriched Cohort.

Objective: To investigate the added value of kinetic information for breast lesion evaluation on abbreviated breast MRI (AB-MRI). Methods: This retrospective study analyzed 207 breast lesions with Breast Imaging Reporting and Data System categories 3, 4, or 5 on AB-MRI in 198 consecutive patients who had breast MRI for screening after breast cancer surgery between January 2017 and December 2019. All lesions were pathologically confirmed or stable on follow-up images for 2 years or more. Kinetic information of the lesions regarding the degree and rate of enhancement on the first post-contrast-enhanced image and the enhancement curve type from two post-contrast-enhanced images were analyzed on a commercially available computer-assisted diagnosis system. The diagnostic performances of AB-MRI with morphological analysis alone and with the addition of kinetic information were compared using the McNemar test. Results: Of 207 lesions, 59 (28.5%) were malignant and 148 (71.5%) were benign. The addition of an enhancement degree of ≥90% to the morphological analysis significantly increased the specificity of AB-MRI (29.7% vs. 52.7%, p < 0.001) without significantly reducing the sensitivity (94.9% vs. 89.8%, p = 0.083) compared to morphological analysis alone. Unnecessary biopsy could have been avoided in 34 benign lesions, although three malignant lesions could have been missed. For detecting invasive cancer, adding an enhancement degree ≥107% to the morphological analysis significantly increased the specificity (26.5% vs. 57.6%, p < 0.001) without significantly decreasing the sensitivity (94.6% vs. 86.5%, p = 0.083). Conclusion: Adding the degree of enhancement on the first post-contrast-enhanced image to the morphological analysis resulted in higher AB-MRI specificity without compromising its sensitivity.

Mechanical Changes of the Lumbar Intervertebral Space and Lordotic Angle Caused by Posterior-to-Anterior Traction Using a Spinal Thermal Massage Device in Healthy People.

BACKGROUND: The axial (horizontal) traction approach has been traditionally used for treatment of low back pain-related spinal disorders such as nuclear protrusion, primary posterolateral root pain, and lower thoracic disc herniation; however, it is known to have some technical limitations due to reductions of the spinal curve. Lumbar lordosis plays a pivotal function in maintaining sagittal balance. Recently, vertical traction and combination traction have been attracting attention due to improving therapeutic outcomes, although evidence of their clinical application is rare; therefore, this study was conducted to investigate the mechanical changes of lumbar intervertebral space, lordotic angle, and the central spinal canal area through vertical traction treatment using a spinal massage device in healthy participants. METHODS: In total, 10 healthy subjects with no musculoskeletal disorders and no physical activity restrictions participated. The participants lay on the experimental device (CGM MB-1901) in supine extended posture and vertical traction force was applied in a posterior-to-anterior direction on the L3-4 and L4-5 lumbar sections at level 1 (baseline) and level 9 (traction mode). Magnetic resonance (MR) images were recorded directly under traction mode using the MRI scanner. The height values of the intervertebral space (anterior, center, and posterior parts) and lordosis angle of the L3-4 and L4-5 sections were measured using Image J software and the central spinal canal area (L4-5) was observed through superimposition method using the MR images. All measurement and image analyses were conducted by 2 experienced radiologists under a single-blinded method. RESULTS: The average height values of the intervertebral space under traction mode were significantly increased in both L3-4 and L4-5 sections compared to baseline, particularly in the anterior and central parts but not in the posterior part. Cobb's angle also showed significant increases in both L3-4 and L4-5 sections compared to baseline (p < 0.001). The central spinal canal area showed a slightly expanded feature in traction mode. CONCLUSIONS: In this pilot experiment, posterior-to-anterior vertical traction on L3-4 and L4-5 sections using a spinal massage device caused positive and significant changes based on increases of the intervertebral space height, lumbar lordosis angle, and central spinal canal area compared to the baseline condition. Our results are expected to be useful as underlying data for the clinical application of vertical traction.

Use of a Spinal Thermal Massage Device for Anti-oxidative Function and Pain Alleviation.

Background: Elderly people are vulnerable to a variety of diseases, including chronic pain, which reduces their levels of physical fitness. Thermal massage has been shown to relieve pain and activate antioxidant enzymes. The objective of this study was to determine whether thermal massaging of the spinal column can reduce muscle pain and induce antioxidant function. Methods: This study included participants aged ≥60 years with lower back pain. The participants were assigned to either an experimental group who received spinal column thermal massage and standard rehabilitative treatment or a control group who received standard rehabilitative treatment only. Data from a total of 116 participants (61 and 55 in the control and experimental groups, respectively) were used for analysis. Participants were assessed before treatment and at 4 (POST1) and 8 weeks (POST2) post-treatment, using a pain numeric rating scale (PNRS) and the Roland and Morris Disability Questionnaire (RMDQ), and by measuring the serum levels of superoxide dismutase (SOD), serum glutathione-peroxidase (GPx), and serum catalase (CAT). Results: The extent of pain reduction, as measured by the PNRS, was greater in the experimental group. The RMDQ score in the control group decreased at POST1, but the decrease was not maintained at POST2, whereas the decrease in POST1 in the experimental group continued until POST2. SOD concentrations were significantly higher in the experimental group at POST1 and POST2, and GPx levels were significantly higher in the experimental group at POST2; however, there were no changes in CAT concentrations. Incidentally, there was a significant correlation between antioxidant activity and pain perception in the experimental group. Conclusions: The study findings suggest that spinal column thermal massage reduces pain more effectively, improves self-reported levels of disability, and increases the antioxidant enzyme levels. Thermal massage may, therefore, be useful in the prevention and treatment of diseases associated with oxidation.

Potential therapeutic mechanism of extremely low-frequency high-voltage electric fields in cells.

The aim of this survey was to provide background theory based on previous research to elucidate the potential pathway by which medical devices using extremely low-frequency high-voltage electric fields (ELF-HVEF) exert therapeutic effects on the human body, and to increase understanding of the AC high-voltage electrotherapeutic apparatus for consumers and suppliers of the relevant devices. Our review revealed that an ELF field as weak as 1-10 µ V/m can induce diverse alterations of membrane proteins such as transporters and channel proteins, including changes in Ca + + binding to a specific site of the cell surface, changes in ion (e.g., Ca + + ) influx or efflux, and alterations in the ligand-receptor interaction. These alterations then induce cytoplasmic responses within cells (Ca + + , cAMP, kinases, etc.) that can have impacts on cell growth, differentiation, and other functional properties by promoting the synthesis of macromolecules. Moreover, increased cytoplasmic Ca + + involves calmodulin-dependent signaling and consequent Ca + + /calmodulin-dependent stimulation of nitric oxide synthesis. This event in turn induces the nitric oxide-cGMP-protein kinase G pathway, which may be an essential factor in the observed physiological and therapeutic responses.

Highly enantioselective catalytic 1,3-dipolar cycloadditions of α-alkyl diazoacetates: efficient synthesis of functionalized 2-pyrazolines.

Highly enantioselective 1,3-dipolar cycloaddition reactions of α-substituted diazoacetates are accomplished by catalysis of the chiral oxazaborolidinium ion. Functionalized 2-pyrazolines are synthesized in high to excellent enantiomeric ratios (up to >99 : 1). The synthetic utility of 2-pyrazoline was expanded via preparation of 2,4-diamino ester compounds bearing a chiral quaternary carbon center.