Multimodal Imaging Approach for Tumor Treatment Response Evaluation in the Era of Immunotherapy.

ABSTRACT: Immunotherapy is likely the most remarkable advancement in lung cancer treatment during the past decade. Although immunotherapy provides substantial benefits, their therapeutic responses differ from those of conventional chemotherapy and targeted therapy, and some patients present unique immunotherapy response patterns that cannot be judged under the current measurement standards. Therefore, the response monitoring of immunotherapy can be challenging, such as the differentiation between real response and pseudo-response. This review outlines the various tumor response patterns to immunotherapy and discusses methods for quantifying computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (PET) in the field of lung cancer. Emerging technologies in magnetic resonance imaging (MRI) and non-FDG PET tracers are also explored. With immunotherapy responses, the role for imaging is essential in both anatomical radiological responses (CT/MRI) and molecular changes (PET imaging). Multiple aspects must be considered when assessing treatment responses using CT and PET. Finally, we introduce multimodal approaches that integrate imaging and nonimaging data, and we discuss future directions for the assessment and prediction of lung cancer responses to immunotherapy.

3D airway geometry analysis of factors in airway navigation failure for lung nodules.

BACKGROUND: This study aimed to quantitatively reveal contributing factors to airway navigation failure during radial probe endobronchial ultrasound (R-EBUS) by using geometric analysis in a three-dimensional (3D) space and to investigate the clinical feasibility of prediction models for airway navigation failure. METHODS: We retrospectively reviewed patients who underwent R-EBUS between January 2017 and December 2018. Geometric quantification was analyzed using in-house software built with open-source python libraries including the Vascular Modeling Toolkit ( http://www.vmtk.org ), simple insight toolkit ( https://sitk.org ), and sci-kit image ( https://scikit-image.org ). We used a machine learning-based approach to explore the utility of these significant factors. RESULTS: Of the 491 patients who were eligible for analysis (mean age, 65 years +/- 11 [standard deviation]; 274 men), the target lesion was reached in 434 and was not reached in 57. Twenty-seven patients in the failure group were matched with 27 patients in the success group based on propensity scores. Bifurcation angle at the target branch, the least diameter of the last section, and the curvature of the last section are the most significant and stable factors for airway navigation failure. The support vector machine can predict airway navigation failure with an average area under the curve of 0.803. CONCLUSIONS: Geometric analysis in 3D space revealed that a large bifurcation angle and a narrow and tortuous structure of the closest bronchus from the lesion are associated with airway navigation failure during R-EBUS. The models developed using quantitative computer tomography scan imaging show the potential to predict airway navigation failure.

Clinical Utility of Tumor-Naïve Pre-surgical ctDNA Detection in Early-stage NSCLC.

PURPOSE: The use of tumor-informed circulating tumor DNA (ctDNA) testing in early-stage patients before surgery is limited mainly due to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected non-small cell lung cancer (NSCLC). METHOD: We analyzed pre-surgical plasma samples from 895 patients with EGFR and ALK-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histology, histological subtypes, and clinical-to-pathological TNM upstaging. RESULTS: Pre-surgical ctDNA detection was observed in 55 out of 414 (13%) patients with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (RFS) (2-year RFS 69% versus 91%; log-rank P<0.001), approaching that of clinical stage II LUAD. Pre-surgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict pre-surgical ctDNA detection. Moreover, pre-surgical ctDNA detection was predictive of the post-surgical discovery of IASLC G3 tumors (P<0.001) and pathological TNM upstaging (P<0.001). Notably, pre-surgical ctDNA detection strongly correlated with higher PD-L1 expression in tumors (positive rates 28% vs. 55%, P<0.001), identifying a subgroup likely to benefit from anti-PD-(L)-1 therapies. CONCLUSION: These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need of tumor tissue profiling. Furthermore, it is clinically useful in identifying high-risk patients who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

Computed tomography characteristics of cN0 primary non-small cell lung cancer predict occult lymph node metastasis.

RATIONALE: Occult lymph node metastasis (OLNM) is frequently found in patients with resectable non-small cell lung cancer (NSCLC), despite using diagnostic methods recommended by guidelines. OBJECTIVES: To evaluate the risk of OLNM in NSCLC patients using the radiologic characteristics of the primary tumor on computed tomography (CT). METHODS: We retrospectively reviewed clinicopathologic features of 2042 clinical T1-4N0 NSCLC patients undergoing curative intent pulmonary resection. Unique radiological features (i.e., air-bronchogram throughout the whole tumor, heterogeneous ground-glass opacity (GGO), mainly cystic appearance, endobronchial location), percentage of solid portion, and shape of tumor margin were analyzed via a stepwise approach. We used multivariable logistic regression to assess the relationship between OLNM and tumor characteristics. RESULTS: Compared with the other unique features, endobronchial tumors were associated with the highest risk of OLNM (OR = 3.9, 95% confidence interval (CI) = 2.29-6.62), and heterogeneous GGO and mainly cystic tumors were associated with a low risk of OLNM. For tumors without unique features, the percentage of the solid portion was measured, and solid tumors were associated with OLNM (OR = 2.49, 95% CI = 1.86-3.35). Among part-solid tumors with solid proportion > 50%, spiculated margin, and peri-tumoral GGO were associated with OLNM. CONCLUSIONS: The risk of OLNM could be assessed using radiologic characteristics on CT. This could allow us to adequately select optimal candidates for invasive nodal staging procedures (INSPs) and complete systematic lymph node dissection. CLINICAL RELEVANCE STATEMENT: These data may be helpful for clinicians to select appropriate candidates for INSPs and complete surgical systematic lymph node dissection in NSCLC patients. KEY POINTS: Lymph node metastasis status plays a key role in both prognostication and treatment planning. Solid tumors, particularly endobronchial tumors, were associated with occult lymph node metastasis (OLNM). The risk of OLNM can be assessed using radiologic characteristics acquired from CT images.

Enhancing Identification of High-Risk cN0 Lung Adenocarcinoma Patients Using MRI-Based Radiomic Features.

Purpose: To develop an MRI-based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space (STAS), and poorly differentiated patterns. Materials and Methods: As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, SUVmax (maximum standardized uptake value) on FDG PET/CT, and the mean ADC value on DWI, were considered together to build prediction models for high-risk pathologic features. Results: Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The MR-eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p<0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p<0.001), worse 4-year disease free survival (p<0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC 0.860 and 0.907, respectively). Conclusion: Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.

Cetacean Stranding Response Program and Spatial-Temporal Analysis in Taiwan, 1994-2018.

A national cetacean stranding response program in Taiwan has evolved significantly in the past three decades. Initially co-ordinated by National Taiwan University from 1994, the program transitioned to the Taiwan Cetacean Society in 1999, and local governments took on a more prominent role after 2009. A comprehensive stranding database (1994-2018) has been maintained, which documented 1320 stranding events involving 1698 animals from at least 27 species. The most commonly stranded species include finless porpoises, bottlenose dolphins, Kogia spp., and Risso's dolphins. The stranding rates varied annually and seasonally, with increases noted from an average of 16 events per year for the first 3 years to 44-58 events per year between 1997 and 2015, and a sharp rise to over 90 events per year for the period of the last three years. Seasonal variations were also significant, with higher stranding rates during the northeastern monsoon (NEM, October to next April) than that during southwestern monsoon (SWM, May to September). From the aspect of distribution, more frequent and even strandings occurred along the coast of northern Taiwan, while mass strandings were concentrated in the southwestern counties during NEM. Among all strandings, 390 events (29.5%) and 660 animals (38.9%) were live ones. Under great effort in rescuing and rehabilitating 52 cases, 15 cetacean individuals have been released since 2000. Additionally, there have been 56 mass strandings involving at least 11 species since 1994, predominated by pygmy killer whales, particularly during the NEM season along the southwest coast. This study not only contributes to our understanding of the stranding patterns and diversity of the cetaceans in Taiwan, but also provides valuable insights for future conservation strategies on cetaceans in the western Pacific.

Comparative Analysis of Clinical Characteristics and Prognosis Between Primary Lung Cancers Identified as Screening Detected and Incidentally Detected Pulmonary Nodules.

BACKGROUND/AIM: Although the importance of low-dose computed tomography (LDCT) screening is increasingly emphasized and implemented, many lung cancers continue to be incidentally detected during routine medical practices, and data on incidentally detected lung cancer (IDLC) remain scarce. This study aimed to investigate the clinical characteristics and prognosis of IDLCs by comparing them with screening-detected lung cancers (SDLCs). PATIENTS AND METHODS: In this retrospective study, subjects with cT1 (≤3 cm) pulmonary nodules detected on baseline computed tomography (CT), later pathologically confirmed as primary lung cancer in 2015, were included. Patients were categorized into IDLC and SDLC groups based on the setting of the first pulmonary nodule detection. RESULTS: Out of 457 subjects, 129 (28.2%) were IDLCs and 328 (71.8%) were SDLCs. The IDLC group, consisted of older individuals with a higher prevalence of smokers and underlying pulmonary disease, compared to the SDLC group. Adenocarcinomas were more frequently detected in SDLCs (87.5%) than in IDLCs (76.7%, p<0.001). The time to treatment initiation (TTI) and 5-year overall survival (OS) rates were similar. Multivariate analyses revealed underlying interstitial lung disease, DLCO, solidity of nodules and TNM stage as independent risk factors associated with mortality. Less than 30% of study participants would have been eligible for the current lung cancer screening program. CONCLUSION: The IDLC group was associated with older age, higher rate of smokers, underlying pulmonary disease, and non-adenocarcinoma histology. However, prognosis was similar to that of the SDLC group, attributable to the similarity in TNM stage, strict adherence to guidelines, and short TTI. Furthermore, less than 30% of the participants would have been suitable for the existing lung cancer screening program, indicating a potential need to reconsider the scope for screening candidates.

Impact of national health insurance and socioeconomic disparities on newborn hearing screening performance in South Korea: A nationwide population-based evaluation.

OBJECTIVES: This study aimed to assess the impact of national health insurance coverage on newborn hearing screening (NHS) outcomes by analyzing hearing questionnaires from the National Infant Health Check-up Program (NIHCP) in South Korea. METHODS: This study evaluated the performance and referral rates of NHS using nationwide data from 814,875 infants enrolled in the 4-month NIHCP from January 2017 to December 2019. This period encompasses the periods before and after the National Health Insurance in South Korea began covering NHS expenses in October 2018. The study also investigated household income levels to determine their relationship with participation in the NIHCP and NHS outcomes. RESULTS: The performance of NIHCP increased year-on-year, with NHS performance rates increasing from 88.5 % in 2017 to 91.5 % in 2019. Analysis by household income level revealed that the medical benefit recipients' group had the lowest NHS performance rate of 81.9 % in 2019, whereas that of the higher income level group exceeded 90 %. The NHS referral rate remained consistent at 0.9 % nationally during the study period. CONCLUSION: The inclusion of NHS in national insurance coverage positively influenced its performance rates across South Korea. Nevertheless, the data indicate the need for more focused and customized support for low-income families to enhance early hearing detection and interventions in newborns and infants.

MicroRNA-135b-5p Is a Pathologic Biomarker in the Endothelial Cells of Arteriovenous Malformations.

Arteriovenous malformations (AVMs) are congenital vascular anomalies with a poor prognosis. AVMs are considered intractable diseases, as there is no established approach for early diagnosis and treatment. Therefore, this study aimed to provide new evidence by analyzing microRNAs (miRNAs) associated with AVM. We present fundamental evidence for the early diagnosis and treatment of AVM by analyzing miRNAs in the endothelial cells of AVMs. This study performed sequencing and validation of miRNAs in endothelial cells from normal and AVM tissues. Five upregulated and two downregulated miRNAs were subsequently analyzed under hypoxia and vascular endothelial growth factor (VEGF) treatment by one-way analysis of variance (ANOVA). Under hypoxic conditions, miR-135b-5p was significantly upregulated in the AVM compared to that under normal conditions, corresponding to increased endothelial activity (p-value = 0.0238). VEGF treatment showed no significant increase in miR-135b-5p under normal conditions, however, a surge in AVM was observed. Under both hypoxia and VEGF treatment, comparison indicated a downregulation of miR-135b-5p in AVM. Therefore, miR-135b-5p was assumed to affect the pathophysiological process of AVM and might play a vital role as a potential biomarker of AVMs for application related to diagnosis and treatment.

Clinical usability of 3D gradient-echo-based ultrashort echo time imaging: Is it enough to facilitate diagnostic decision in real-world practice?

BACKGROUND: With recent advances in magnetic resonance imaging (MRI) technology, the practical role of lung MRI is expanding despite the inherent challenges of the thorax. The purpose of our study was to evaluate the current status of the concurrent dephasing and excitation (CODE) ultrashort echo-time sequence and the T1-weighted volumetric interpolated breath-hold examination (VIBE) sequence in the evaluation of thoracic disease by comparing it with the gold standard computed tomography (CT). METHODS: Twenty-four patients with lung cancer and mediastinal masses underwent both CT and MRI including T1-weighted VIBE and CODE. For CODE images, data were acquired in free breathing and end-expiratory images were reconstructed using retrospective respiratory gating. All images were evaluated through qualitative and quantitative approaches regarding various anatomical structures and lesions (nodule, mediastinal mass, emphysema, reticulation, honeycombing, bronchiectasis, pleural plaque and lymphadenopathy) inside the thorax in terms of diagnostic performance in making specific decisions. RESULTS: Depiction of the lung parenchyma, mediastinal and pleural lesion was not significant different among the three modalities (p > 0.05). Intra-tumoral and peritumoral features of lung nodules were not significant different in the CT, VIBE or CODE images (p > 0.05). However, VIBE and CODE had significantly lower image quality and poorer depiction of airway, great vessels, and emphysema compared to CT (p < 0.05). Image quality of central airways and depiction of bronchi were significantly better in CODE than in VIBE (p < 0.001 and p = 0.005). In contrast, the depiction of the vasculature was better for VIBE than CODE images (p = 0.003). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were significant greater in VIBE than CODE except for SNRlung and SNRnodule (p < 0.05). CONCLUSIONS: Our study showed the potential of CODE and VIBE sequences in the evaluation of localized thoracic abnormalities including solid pulmonary nodules.

A hidden pathophysiology of endolymphatic hydrops: case report of a patient with spontaneous intracranial hypotension presenting with sudden sensorineural hearing loss with vertigo.

Spontaneous intracranial hypotension (SIH) is characterized by decreased cerebrospinal fluid (CSF) volume due to leakage through the dural membrane. We present the case of a patient with SIH manifested by fluctuating low-frequency hearing loss, tinnitus, and vertigo. In this patient, endolymphatic hydrops in the cochlea and saccule were visualized by means of a special sequence of inner ear magnetic resonance imaging scans, with a gadolinium-based contrast agent administered intravenously. Endolymphatic hydrops is a potential underlying pathophysiology of SIH-associated hearing impairment. We hypothesize that SIH may be a rare cause of endolymphatic hydrops.

The Impact of the COVID-19 Pandemic on Bell's Palsy and Ramsay-Hunt Syndrome: A Multicenter Retrospective Study.

BACKGROUND: This article presents a comprehensive review of data on the impact of facial palsy during the coronavirus disease 2019 (COVID-19) pandemic. The possible causes and pathophysiological mechanisms of changes in the epidemiology of facial palsy during the COVID-19 pandemic are also discussed. METHODS: This multicenter retrospective cohort study included 943 patients diagnosed with Bell's palsy or Ramsay Hunt syndrome. This study compared patient demographics, comorbidities, symptoms, and treatments before the COVID-19 pandemic (from 2017 to 2019) and during the COVID-19 pandemic, from 2020 to 2022). RESULTS: Following the COVID-19 outbreak, there has been a significant increase in the number of cases of Bell's palsy, particularly among elderly individuals with diabetes. Bell's palsy increased after the COVID-19 outbreak, rising from 75.3% in the pre-COVID-19 era to 83.6% after the COVID-19 outbreak. The complete recovery rate decreased from 88.2% to 73.9%, and the rate of recurrence increased from 2.9% to 7.5% in patients with Bell's palsy. Ramsay Hunt syndrome showed fewer changes in clinical outcomes. CONCLUSION: This study highlights the impact of the COVID-19 pandemic on the presentation and management of facial palsy, and suggests potential associations with COVID-19. Notably, the observed increase in Bell's palsy cases among elderly individuals with diabetes emphasizes the impact of the pandemic. Identifying the epidemiological changes in facial palsy during the COVID-19 pandemic has important implications for assessing its etiology and pathological mechanisms of facial palsy disease.

Clinical Values of Whole-Body Blood Pool Scans and SPECT for Evaluation of Congenital Vascular Malformation.

Purpose: This study examines the diagnostic potential of whole-body blood pool scintigraphy (WBBPS) using technetium-99 m-labeled red blood cells to detect congenital vascular malformations (CVMs). It aims to compare its efficacy with traditional imaging techniques such as magnetic resonance imaging (MRI) and ultrasonography (USG), emphasizing its potential advantages in terms of characterization of lesions and capacity for whole-body assessment. Methods: The efficacy of WBBPS and single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging in diagnosing CVMs, comparing them with USG and MRI results, was evaluated in this retrospective study. Of the 38 patients, 21 were evaluated using these diagnostic methods, with CVMs classified according to the International Society for the Study of Vascular Anomalies guidelines. Also, this study aimed to elucidate the characteristics between WBBPS, SPECT/CT, USG, or MRI findings and their consistency with the final diagnosis. Results: A total of 21 participants were included in this study, with an average age of 17.7 years old, with female predominance (57.1%). The most common diagnosis was vascular malformations (VMs) (71.4%), followed by combined vascular malformations (14.3%) and lymphatic malformations (9.5%). WBBPS demonstrated positive results in 95.2% of cases. Distinct imaging patterns for each condition were observed, with WBBPS being crucial in locating lesions. Conclusion: The study findings suggested that WBBPS with SPECT/CT could be helpful in detecting occult VM lesions and ruling out a lymphatic malformation diagnosis. Thus, it can be employed in the evaluation of CVMs.

Analysis of Loudness Discomfort Level Tests in Tinnitus Patients.

INTRODUCTION: We aimed to investigate the clinical significance of loudness discomfort level (LDL) test in tinnitus patients and its relationship with pure-tone audiometry, tinnitogram and questionnaires. METHODS: We retrospectively reviewed the medical records of 320 tinnitus patients who visited a tertiary university hospital's tinnitus clinic and completed LDL tests between March 2020 and December 2022. Epidemiological data and psychoacoustic test results were collected. RESULTS: LDL showed no significant differences between frequencies for both ears. Mean LDL did not correlate with mean pure-tone average or hearing thresholds at each frequency. The hearing loss group had higher LDL at 8 kHz compared to the normal hearing group (p<0.01). Objective sound intolerance was found in a quarter, correlating with subjective hyperacusis, anxiety, and depression. Weak negative correlations were found between most of questionnaire's scores and LDL on the left side. Tinnitus loudness weak negatively correlated with LDL at most frequencies, except 8 kHz. DISCUSSION/CONCLUSION: Our findings suggest a notable association between LDL levels and emotional factors in tinnitus patients, rather than with auditory thresholds. While lateralized differences in LDL responses were observed, specifically on the left side, these preliminary results do not confirm a causal link and thus do not warrant changes to current clinical testing protocols without further research.

Postoperative Scar Management Using Laser Therapy for Breast Reconstruction With Latissimus Dorsi Flap.

BACKGROUND: Postoperative scar formation is inevitable, and a gold standard management has not been established to date. Due to the fact long and large scar formation occurs in reconstructive surgery, this study analyzed the relationship between various factors in patients who received breast reconstruction using latissimus dorsi (LD) flap to investigate appropriate and effective management approaches. PATIENTS AND METHODS: Twenty-seven patients who underwent breast reconstruction between June 2014 and January 2015 received laser therapy on their LD donor site at the Kyungpook National University Chilgok Hospital. Scar evaluation was performed on both the surgical scar and intact skin on the contralateral side. Scar evaluation was conducted at five specific points, 2 cm from the midpoint of the scar on each side. Laser treatment was performed at 4-week intervals, and patients were then followed-up for 6 months. To assess scars, gross images were taken using the same settings. In addition, spectrophotometry was used for color assessment, durometer for texture and pressure evaluation, and Vernier calipers and height gauges for a more precise and objective approach. RESULTS: The mean age of the participants was 45.7 years, and the mean body mass index was 22.1 kg/m2 The operator-evaluated scar scale scores were 107.2 and 97.3 in the experimental and control groups, respectively. In the patient-rated questionnaire, the scores were 62.3 and 59.4 in the experimental and control groups, respectively. CONCLUSION: When analyzing early-stage postoperative scars based on various factors, laser therapy is considered a very useful scar management approach. Additionally, when performing reconstructive surgery, tension force is regarded as a significant factor to take into account since it affects scar widening.

External Volume Expansion: Timing and Effects on the Rate of Fat Graft Retention in BALB/c Nude Mice.

BACKGROUND/AIM: Fat grafting has been widely used for soft-tissue augmentation. External volume expansion (EVE) is a favorable tool for improvement in the rate of fat graft retention. However, few studies have focused on the most appropriate time for its implementation. In this study, BALB/c nude mice were used to investigate the effective time for the implementation of external volume expansion to improve the rate of fat retention. MATERIALS AND METHODS: Sixteen mice were divided into four groups, and EVE was performed at different time points before or both before and after fat grafting. Fat tissue from a human donor was injected into the mice following EVE. Visual assessment, micro-computed tomography analysis, and histopathological evaluation were used to assess fat retention. RESULTS: After 10 weeks, the group that underwent EVE 5 days before fat grafting demonstrated a significantly higher preserved fat volume, as determined by micro-computed tomography (p<0.05). Moreover, the group that received additional EVE after fat grafting exhibited a higher retention rate compared to the groups receiving EVE only before grafting (p<0.05). Histopathological analysis indicated that swelling, edema, and inflammation were more pronounced in the group with EVE immediately before grafting, while angiogenesis and lipogenesis were more active in the group with additional EVE after grafting. CONCLUSION: EVE is a safe and effective approach for improving the rate of fat graft retentions. Furthermore, the timing of external tissue expansion plays a crucial role in fat retention. Based on our animal study, performing EVE immediately before and after fat grafting may be an effective strategy for enhancing the rate of fat graft retentions.

A Study on the Effectiveness of Helmet Therapy for Cranial Deformations According to Cranial Shape.

BACKGROUND: To investigate the effects of helmet therapy on plagiocephaly, according to head circumference, cephalic index (CI), and skull height. Plagiocephaly is a condition in which the skull is congenitally asymmetrical or affected by acquired factors such as compression in the womb or the habit of sleeping on one side. Although there are numerous studies on the effectiveness of helmet therapy for plagiocephaly, research on its effectiveness on skull shape is lacking. METHODS: We conducted a prospective study on 400 patients who underwent helmet therapy. The infants were enrolled and the therapy was explained to the caregiver when the child had positional plagiocephaly and had a cranial vault asymmetry (CVA) exceeding 10 mm or a CVA index (CVAI) exceeding 3.5%. The CVA and CVAI changes were compared to investigate the effectiveness of helmet therapy according to head circumference, CI, and skull height. RESULTS: A significant treatment effect was observed for CI values between 90 and 103. The treatment effect was found to increase with greater skull height. However, no significant difference was observed in the effectiveness of helmet therapy according to head circumference. CONCLUSIONS: According to the findings, the effectiveness of helmet therapy in children with positional plagiocephaly is greater for children with higher skulls and for those with CI values between 90 and 103; it is unrelated to head circumference. Based on these results, we can provide predictions of the effectiveness of helmet therapy to caregivers of children with positional plagiocephaly.

Role of invasive mediastinal nodal staging in survival outcomes of patients with non-small cell lung cancer and without radiologic lymph node metastasis: a retrospective cohort study.

Background: Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). Methods: In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. Findings: A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%-77%) for IMNS and 71.7% (95% CI: 68.6%-74.9%; p = 0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77-1.07), while 5-year RFS was 64.7% (95% CI: 61.5%-68.2%) and 67.5% (95% CI: 64.3%-70.9%; p = 0.35 (HR 1.08, 95% CI: 0.92-1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. Interpretation: IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. Funding: None.

Monthly Variation in Bell's Palsy Based on Population Data of Korea.

INTRODUCTION: Several studies have reported that the number of patients with Bell's palsy varied significantly by month and season. However, few studies have reported the monthly variation in Bell's palsy based on the whole population. We investigated the monthly variation in Bell's palsy in Korea during a long-term period based on whole population data. METHODS: This retrospective study used the data of the National Health Insurance Service of Korea, which included the entire Korean population from 2008 to 2020. The monthly incidence of Bell's palsy per 100,000 was evaluated in total and according to sex, age, and residence. RESULTS: The total average monthly incidence differed significantly by month, with the highest observed in January (9.1 per 100,000) and the lowest in June (7.7 per 100,000) (p < 0.001). The average monthly incidence according to sex, age, and residence also varied significantly by month, with most of the highest values noted in January and the lowest in June. CONCLUSION: There was significant monthly variation in the incidence of Bell's palsy, with the highest in January during the winter and the lowest in June during the summer, based on whole population data over a long-term period in Korea.

Machine learning model for circulating tumor DNA detection in chronic obstructive pulmonary disease patients with lung cancer.

Background: Patients with chronic obstructive pulmonary disease (COPD) have a high risk of developing lung cancer. Due to the high rates of complications from invasive diagnostic procedures in this population, detecting circulating tumor DNA (ctDNA) as a non-invasive method might be useful. However, clinical characteristics that are predictive of ctDNA mutation detection remain incompletely understood. This study aimed to investigate factors associated with ctDNA detection in COPD patients with lung cancer. Methods: Herein, 177 patients with COPD and lung cancer were prospectively recruited. Plasma ctDNA was genotyped using targeted deep sequencing. Comprehensive clinical variables were collected, including the emphysema index (EI), using chest computed tomography. Machine learning models were constructed to predict ctDNA detection. Results: At least one ctDNA mutation was detected in 54 (30.5%) patients. After adjustment for potential confounders, tumor stage, C-reactive protein (CRP) level, and milder emphysema were independently associated with ctDNA detection. An increase of 1% in the EI was associated with a 7% decrease in the odds of ctDNA detection (adjusted odds ratio =0.933; 95% confidence interval: 0.857-0.999; P=0.047). Machine learning models composed of multiple clinical factors predicted individuals with ctDNA mutations at high performance (AUC =0.774). Conclusions: ctDNA mutations were likely to be observed in COPD patients with lung cancer who had an advanced clinical stage, high CRP level, or milder emphysema. This was validated in machine learning models with high accuracy. Further prospective studies are required to validate the clinical utility of our findings.