Machine Learning Approaches for Assessing Risk Factors of Adrenal Insufficiency in Patients Undergoing Immune Checkpoint Inhibitor Therapy.

Adrenal insufficiency is a rare, yet life-threatening immune-related adverse event of immune checkpoint inhibitors (ICIs). This study aimed to establish a risk scoring system for adrenal insufficiency in patients receiving anti-programmed cell death 1 (PD-1) or anti-programmed cell death-ligand 1 (PD-L1) agents. Moreover, several machine learning methods were utilized to predict such complications. This study included 209 ICI-treated patients from July 2015 to February 2021, excluding those with prior adrenal insufficiency, previous steroid therapy, or incomplete data to ensure data integrity. Patients were continuously followed up at Gyeongsang National University Hospital, with morning blood samples taken for basal cortisol level measurements, facilitating a comprehensive analysis of their adrenal insufficiency risk. Using a chi-squared test and logistic regression model, we derived the odds ratio and adjusted odds ratio (AOR) through univariate and multivariable analyses. This study utilized machine learning algorithms, such as decision trees, random forests, support vector machines (SVM), and logistic regression to predict adrenal insufficiency in patients treated with ICIs. The performance of each algorithm was evaluated using metrics like accuracy, sensitivity, specificity, precision, and the area under the receiver operating characteristic curve (AUROC), ensuring rigorous assessment and reproducibility. A risk scoring system was developed from the multivariable and machine learning analyses. In a multivariable analysis, proton pump inhibitors (PPIs) (AOR 4.5), and α-blockers (AOR 6.0) were significant risk factors for adrenal insufficiency after adjusting for confounders. Among the machine learning models, logistic regression and elastic net showed good predictions, with AUROC values of 0.75 (0.61-0.90) and 0.76 (0.64-0.89), respectively. Based on multivariable and machine learning analyses, females (1 point), age ≥ 65 (1 point), PPIs (1 point), α-blockers (2 points), and antipsychotics (3 points) were integrated into the risk scoring system. From the logistic regression curve, patients with 0, 1, 2, 4, 5, and 6 points showed approximately 1.1%, 2.8%, 7.3%, 17.6%, 36.8%, 61.3%, and 81.2% risk for adrenal insufficiency, respectively. The application of our scoring system could prove beneficial in patient assessment and clinical decision-making while administering PD-1/PD-L1 inhibitors.

Application of the postnatal urinary tract dilation classification system to predict the need for surgical intervention among neonates and young infants.

PURPOSE: The aim of this study was to validate the postnatal urinary tract dilation (UTD) classification system by correlating it with the need for surgical intervention. METHODS: Young infants who underwent ultrasound (US) examinations for prenatal hydronephrosis were retrospectively identified. The kidney units (KUs; right, left, or bilateral) were graded from UTD P0 (very low risk) to P3 (high risk) based on seven US criteria from the UTD system. Surgery-free survival curves were constructed using the Kaplan-Meier method. Univariable and multivariable Cox proportional-hazards regression analysis clustered by patients was performed. Interobserver agreement was analyzed using the weighted kappa coefficient. RESULTS: In total, 504 KUs from 336 patients (mean age, 18.3±15.9 days; range, 1 to 94 days; males, n=276) were included, with a median follow-up of 24.2 months. Fifty-eight KUs underwent surgical intervention. Significant differences were observed among the Kaplan-Meier curves stratified into UTD groups (P<0.001). The presence of anterior-posterior renal pelvic diameter ≥15 mm (hazard ratio [HR], 8.602; 95% confidence interval [CI], 1.558 to 43.065), peripheral calyceal dilation (HR, 8.190; 95% CI, 1.558 to 43.065), ureteral dilation (HR, 2.619; 95% CI, 1.274 to 5.380), parenchymal thickness abnormality (HR, 3.371; 95% CI, 1.574 to 7.223), bladder abnormality (HR, 12.209; 95% CI, 3.616 to 41.225) were significantly associated with the occurrence of surgery. The interobserver agreement was moderate to almost perfect agreement for US features (κ=0.564-0.898) and substantial for final UTD grades (κ=0.716). CONCLUSION: The UTD classification system is reliable and appropriately stratifies the risk of surgical intervention.

Diagnostic performance of the 2021 Korean thyroid imaging reporting and data system in pediatric thyroid nodules.

OBJECTIVES: To evaluate the diagnostic performance of 2021 K-TIRADS biopsy criteria for detecting malignant thyroid nodules in a pediatric population, making comparisons with 2016 K-TIRADS. METHODS: This retrospective study included pediatric patients with histopathologically confirmed diagnoses. The diagnostic performance of 2021 K-TIRADS was compared with that of 2016 K-TIRADS. Simulation studies were performed by changing biopsy cut-off sizes for K-TIRADS 5 to 1.0 cm (K-TIRADS5-1.0cm) and 0.5 cm (K-TIRADS5-0.5cm), and for K-TIRADS 4 to 1.0 cm (K-TIRADS4-1.0cm) and 1.0-1.5 cm (K-TIRADS4-1.0~1.5cm). Subgroup analysis was performed in small (< 1.5 cm) and large nodules (≥ 1.5 cm). RESULTS: Two hundred seventy-seven thyroid nodules (54.9% malignant) from 221 pediatric patients were analyzed. All simulated 2021 K-TIRADS showed higher accuracy than 2016 K-TIRADS. Compared with 2021 K-TIRADS5-1.0cm, 2021 K-TIRADS5-0.5cm showed lower specificity (51.6% vs. 47.9%; p = 0.004) but higher sensitivity (77.2% vs. 90.3%; p < 0.001) and accuracy (62.7% vs. 68.9%; p < 0.001). Compared with 2021 K-TIRADS4-1.0cm, 2021 K-TIRADS4-1.0~1.5cm showed higher specificity (44.9% vs. 47.9%; p = 0.018) without significant difference in other diagnostic measures. Compared with 2016 K-TIRADS, 2021 K-TIRADS (biopsy cut-offs, 0.5 cm for K-TIRADS 5; 1.0-1.5 cm for K-TIRADS 4) showed higher sensitivity (34.0% vs. 67.3%; p < 0.001) while maintaining specificity (89.4% vs. 88.2%; p = 0.790) in small nodules, and higher specificity (5.9% vs. 25.4%; p < 0.001) while maintaining sensitivity (100% vs. 98.7%; p = 0.132) in large nodules. CONCLUSIONS: In pediatric patients, 2021 K-TIRADS showed superior diagnostic accuracy to 2016 K-TIRADS, especially with a biopsy cut-off of 0.5 cm for K-TIRADS 5 and 1.0-1.5 cm for K-TIRADS 4. KEY POINTS: • All simulated 2021 K-TIRADS showed higher accuracy than 2016 K-TIRADS. • 2021 K-TIRADS with cut-off size for K-TIRADS 5 of 0.5 cm showed lower specificity but higher sensitivity and accuracy than that of 1.0 cm. • Compared with 2016 K-TIRADS, 2021 K-TIRADS (biopsy cut-offs, 0.5 cm for K-TIRADS 5; 1.0-1.5 cm for K-TIRADS 4) showed higher sensitivity while maintaining specificity in small nodules, and higher specificity while maintaining sensitivity in large nodules.

Risk of malignancy in patients with psoriasis according to treatment modalities in Korea: a nationwide cohort study.

Intrinsic immunologic disparity of psoriasis itself, along with chronic inflammation and immunomodulatory anti-psoriatic treatments could be associated with increased risk of malignancy. We aimed to estimate the risk of malignancy in patients with psoriasis by treatment modality compared with that in individuals without psoriasis in Korea. We conducted a nationwide cohort study using the claims database of the National Health Insurance Service from January 2005 to December 2018. A total of 255,471 patients with psoriasis, and age- and sex-matched non-psoriasis participants (1:1 ratio) were enrolled. The adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)] for malignancy without nonmelanoma skin cancer (NMSC) were 1.10 [1.08-1.12] in patients with psoriasis, 1.13 [1.00-1.27], 1.05 [0.97-1.13], and 1.24 [0.84-1.83] in phototherapy, non-biologic systemics, and biologics cohort, respectively. Among the non-biologic systemics cohort, patients treated with cyclosporin showed higher risk of malignancy without NMSC (aHR [95% CI], 1.20 [1.04-1.39]). The risk of malignancy without NMSC in patients with psoriasis was higher than that in individuals without psoriasis. Phototherapy and biologics were not associated with significant increase of risk; however, cyclosporin appeared to increase its risk. Dermatologists should be vigilant about this potential risk while managing patients with psoriasis.

Diagnostic Performance of Five Adult-based US Risk Stratification Systems in Pediatric Thyroid Nodules.

Background The validation of adult-based US risk stratification systems (RSSs) in the discrimination of malignant thyroid nodules in a pediatric population remains lacking. Purpose To estimate and compare the diagnostic performance of pediatric US RSSs based on five adult-based RSSs in the discrimination of malignant thyroid nodules in a pediatric sample. Materials and methods Pediatric patients (age ≤18 years) with histopathologically confirmed US-detected thyroid nodules at a tertiary referral hospital between January 2000 and April 2020 were analyzed retrospectively. The diagnostic performance of US-based fine-needle aspiration biopsy (FNAB) criteria in thyroid cancer detection was estimated. The following sensitivity analyses were performed: (a) scenario 1: nodules smaller than 1 cm, with the highest category additionally biopsied; (b) scenario 2, application of American College of Radiology Thyroid Imaging Reporting and Data System nodule size cutoffs to other RSSs; (c) scenario 3, scenarios 1 and 2 together. Generalized estimating equations (GEEs) were used for estimation. Results A total of 277 thyroid nodules in 221 pediatric patients (median age, 16 years [interquartile range {IQR}, 13-17]; 172 female; 152 of 277 patients [55%] malignant) were analyzed. The GEE-estimated sensitivity and specificity ranged from 70% to 78% (104 to 119 of 152 patients, based on each reader's interpretation) and from 42% to 78% (49 of 124 patients to 103 of 125 patients). In scenario 1, the missed malignancy rate was reduced from 32%-38% (41 of 134 patients to 34 of 83 patients) to 15%-21% (eight of 59 patients to 28 of 127 patients). In scenario 2, the unnecessary biopsy rate was reduced from 35%-39% (60 of 176 patients to 68 of 175 patients) to 20%-34% (18 of 109 patients to 62 of 179 patients). The highest accuracy was noted in scenario 3 (range, 71%-81%; 199 of 277 patients to 216 of 262 patients). Conclusion The diagnostic performances of the fine-needle aspiration biopsy criteria of five adult-based risk stratification systems were acceptable in the pediatric population and were improved by applying the American College of Radiology Thyroid Imaging Reporting and Data System size cutoff for nodules 1 cm or larger and allowing biopsy of the highest category nodules smaller than 1 cm. © RSNA, 2022 Online supplemental material is available for this article.

Association between Genetic Polymorphism of GSTP1 and Toxicities in Patients Receiving Platinum-Based Chemotherapy: A Systematic Review and Meta-Analysis.

Platinum-based chemotherapy regimens have been proven to be effective in various cancers; however, considerable toxicities may develop and can even lead to treatment discontinuation. Diverse factors may influence adverse treatment events, with pharmacogenetic variations being one prime example. Polymorphisms within the glutathione S-transferase pi 1 (GSTP1) gene may especially alter enzyme activity and, consequently, various toxicities in patients receiving platinum-based chemotherapy. Due to a lack of consistency in the degree of elevated complication risk, we performed a systematic literature review and meta-analysis to determine the level of platinum-associated toxicity in patients with the GSTP1 rs1695 polymorphism. We conducted a systematic search for eligible studies published before January 2022 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between the rs1695 polymorphism and various toxicities. Ten eligible studies met the inclusion criteria. The pooled ORs for hematological toxicity and neutropenia in the patients with the variant (G) allele were 1.7- and 2.6-times higher than those with the AA genotype (95% CI 1.06-2.73 and 1.07-6.35), respectively. In contrast, the rs1695 polymorphism resulted in a 44% reduced gastrointestinal toxicity compared to wild-type homozygotes. Our study found that the GSTP1 rs1695 polymorphism was significantly correlated with platinum-induced toxicities. The study also revealed that rs1695 expression exhibited tissue-specific patterns and thus yielded opposite effects in different tissues. A personalized chemotherapy treatment based on these polymorphisms may be considered for cancer patients in the future.

Neoplastic Etiology and Natural Course of Pituitary Stalk Thickening.

CONTEXT: Pituitary stalk thickening (PST) is often identified on magnetic resonance imaging (MRI), either incidentally or during diagnostic workup of hypopituitarism. However, the neoplastic etiology and natural course of PST are not fully understood, although this knowledge is required to establish diagnostic and surveillance strategies. OBJECTIVE: This work aimed to investigate the neoplastic etiology and natural course of PST. METHODS: MEDLINE/PubMed and EMBASE databases were searched up to February 2021 to identify original research investigating the etiologies of PST. The proportion of neoplastic etiology in patients with PST was meta-analytically pooled. Supplementary analysis exploring factors suggesting neoplasm was also performed. For initially indeterminate cases without confirmed diagnosis, the proportion of patients showing progression of PST during follow-up was evaluated. RESULTS: Eighteen studies covering 1368 patients with PST were included. The pooled proportion of neoplasm was 45.2% (95% CI, 33.3%-57.8%), with substantial heterogeneity across studies (I2 = 93%). The most common neoplasm was germ cell tumor (14.0% of study population), followed by Langerhans cell histiocytosis (10.2%) and metastasis (4.7%). The studies on pediatric populations and those with more than 50% of patients having at least one pituitary hormone deficiency tended to show a higher proportion of neoplasm. The pituitary stalk was thicker in neoplasms, but the difference was not significant (pooled mean difference, 2.08 mm; P = .08). In initially indeterminate cases, 18.5% (95% CI, 7.6%-38.3%) showed progression of PST during follow-up. CONCLUSION: PST was commonly confirmed to be neoplastic, especially in pediatric populations. As isolated PST frequently progresses, follow-up imaging is essential in initially indeterminate cases.

Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) System for Pediatric Patients with Hepatoblastoma: A Retrospective, Hospital-Based Cohort Study in South Korea.

PURPOSE: In 2017, the Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system was introduced. We aimed to evaluate the accuracy of CHIC-HS System for the prediction of event-free survival (EFS) in Korean pediatric patients with hepatoblastoma. MATERIALS AND METHODS: This two-center retrospective study included consecutive Korean pediatric patients with histopathologically confirmed hepatoblastoma from March 1988 through September 2019. We compared EFS among four risk groups according to the CHIC-HS system. Discriminatory ability of CHIC-HS system was also evaluated using optimism-corrected C-statistics. Factors associated with EFS were explored using multivariable Cox regression analysis. RESULTS: We included 129 patients (mean age, 2.6±3.3 years; female:male, 63:66). The 5-year EFS rates in the very low, low, intermediate, and high-risk groups, according to the CHIC-HS system were 90.0%, 82.8%, 73.5%, and 51.3%, respectively. The CHIC-HS system aligned significantly well with EFS outcomes (p=0.004). The optimism-corrected C index of CHIC-HS was 0.644 (95% confidence interval [CI], 0.561 to 0.727). Age ≥ 8 (vs. age ≤ 2; hazard ratio [HR], 2.781; 95% CI, 1.187 to 6.512; p=0.018), PRE-Treatment EXTent of tumor (PRETEXT) stage IV (vs. PRETEXT I or II; HR, 2.774; 95% CI, 1.228 to 5.974; p=0.009), and presence of metastasis (HR, 2.886; 95% CI, 1.457 to 5.719; p=0.002), which are incorporated as the first three nodes in the CHIC-HS system, were independently associated with EFS. CONCLUSION: The CHIC-HS system aligned significantly well with EFS outcomes in Korean pediatric patients with hepatoblastoma. Age group, PRETEXT stage, and presence of metastasis were independently associated with EFS.

Factors Associated with Thyroid-Related Adverse Events in Patients Receiving PD-1 or PD-L1 Inhibitors Using Machine Learning Models.

Targets of immune checkpoint inhibitors (ICIs) regulate immune homeostasis and prevent autoimmunity by downregulating immune responses and by inhibiting T cell activation. Although ICIs are widely used in immunotherapy because of their good clinical efficacy, they can also induce autoimmune-related adverse events. Thyroid-related adverse events are frequently associated with anti-programmed cell death 1 (PD-1) or anti-programmed cell death-ligand 1 (PD-L1) agents. The present study aims to investigate the factors associated with thyroid dysfunction in patients receiving PD-1 or PD-L1 inhibitors and to develop various machine learning approaches to predict complications. A total of 187 patients were enrolled in this study. Logistic regression analysis was conducted to investigate the association between such factors and adverse events. Various machine learning methods were used to predict thyroid-related complications. After adjusting for covariates, we found that smoking history and hypertension increase the risk of thyroid dysfunction by approximately 3.7 and 4.1 times, respectively (95% confidence intervals (CIs) 1.338-10.496 and 1.478-11.332, p = 0.012 and 0.007). In contrast, patients taking opioids showed an approximately 4.0-fold lower risk of thyroid-related complications than those not taking them (95% CI 1.464-11.111, p = 0.007). Among the machine learning models, random forest showed the best prediction, with an area under the receiver operating characteristic of 0.770 (95% CI 0.648-0.883) and an area under the precision-recall of 0.510 (95%CI 0.357-0.666). Hence, this study utilized various machine learning models for prediction and showed that factors such as smoking history, hypertension, and opioids are associated with thyroid-related adverse events in cancer patients receiving PD-1/PD-L1 inhibitors.

Outcome of staging chest CT and identification of factors associated with lung metastasis in children with hepatoblastoma.

OBJECTIVES: To evaluate the outcome of staging chest CT and to identify clinicoradiological factors predictive of lung metastasis in patients with hepatoblastoma based on the 2017 PRE-Treatment EXTent of tumor (PRETEXT) system. METHODS: This bi-center study retrospectively identified patients diagnosed with hepatoblastoma between January 1998 and September 2019 in two tertiary hospitals. The primary outcome was the proportion of the patients who had lung metastasis at staging chest CT. The diagnostic accuracy of staging chest CT was calculated based on the 2017 PRETEXT criteria. The secondary outcome was the identification of factors predictive of lung metastasis using multivariable logistic regression. RESULTS: In total, 123 patients (median age, 1 year; interquartile range, 0-4 years; 59 female) were included. Among those, 28% (35/123; 95% confidence interval [CI], 21-37%) had lung metastasis at staging chest CT. The overall accuracy of staging chest CT was 96.8%. The proportion of lung metastasis in patients with stage I, II, III, and IV was 0%, 24% (12 of 49; 95% CI, 14-38%), 23% (9 of 40; 95% CI, 12-38%), and 56% (14 of 25; 95% CI, 37-73%), respectively. Multifocality (adjusted odds ratio, 6.7; 95% CI, 2.7-17.5; p < .001) and male sex (adjusted odds ratio, 3.1; 95% CI, 1.2-8.6; p = .02) were associated with the presence of lung metastasis. CONCLUSIONS: Twenty-eight percent of the patients with hepatoblastoma had lung metastasis at staging chest CT. Multifocality and male sex were predictive factors for lung metastasis on staging chest CT. KEY POINTS: • The proportion of lung metastasis in patients with hepatoblastoma was 28%. • The overall accuracy of staging chest CT was 97% based on the 2017 PRETEXT system. • Hepatic tumor multifocality and male sex were predictors of lung metastasis.

Recent improvement in survival outcomes and reappraisal of prognostic factors in hepatoblastoma.

BACKGROUND: Prognostic factors in hepatoblastoma need to be reevaluated considering the advances in treatment modalities. The study aimed to evaluate current outcomes of hepatoblastoma and reappraise the association of prognostic factors, including pre-treatment extent of tumor (PRETEXT) stage with annotation factors and Children's Hepatic tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system, with survival outcomes. METHODS: We evaluated 103 consecutive patients with hepatoblastoma retrospectively according to the treatment period based on the introduction of a liver transplantation program. RESULTS: The 5-year overall survival (OS), event-free survival (EFS), and transplant-free survival rates were 80.2%, 74.2%, and 61.8%, respectively. EFS and OS were improved significantly from 58.6% to 81.6% (P = 0.024) and from 58.6% to 90.8% (P < 0.001), respectively, in the late period (N = 74) compared with the early period (N = 29). The PRETEXT stage was significant or marginally significant for EFS and OS in the early period but not in the late period. The P, F, R, and C factors were significant for OS and EFS in the early period. However, in the late period, only the P factor was significant for OS, and the F and M factors were significant for EFS. The CHIC-HS system was significant or marginally significant for EFS in both the early and late periods; however, it was significant for OS only in the early period. CONCLUSION: Survival rates were significantly improved in children with hepatoblastoma, especially in those with advanced PRETEXT stages with positive annotation factors and in a high-risk CHIC-HS group. Prognostic factors had different clinical implications with evolved treatment modalities.

Diagnostic performance of adult-based ATA and ACR-TIRADS ultrasound risk stratification systems in pediatric thyroid nodules: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the diagnostic performance of adult-based "American College of Radiology- Thyroid Imaging Reporting And Data System" (ACR-TIRADS) and "American Thyroid Association" (ATA) in the pediatric population. METHODS: MEDLINE/PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for articles investigating the diagnostic performance of each stratification system (ACR-TIRADS or ATA) and evaluated them according to three aspects: (a) the risk of malignancy in each category; (b) diagnostic performance using the classic indicators (sensitivity, specificity); and (c) diagnostic performance regarding fine needle aspiration/biopsy recommendation. In addition to pathologic diagnosis, we allowed imaging follow-up as the reference standard for benign nodules. RESULTS: Eight articles (1036 thyroid nodules) were included. For ACR-TIRADS, the pooled risk of malignancy in category was as follows: category 5 (59.3%); 4 (20.7%); 3 (11.0%); 2 (6.0%), and 1 (5.5%). For nodules of high suspicion of malignancy (category 4 or 5), the pooled sensitivity and specificity were 0.84 and 0.64. For ATA, the pooled risk of malignancy was as follows: category 5 (55.4%); 4 (34.2%); 3 (12.2%); and 2 (7.5%). For nodules of high suspicion of malignancy (category 4 or 5), the pooled sensitivity and specificity were 0.90 and 0.50. For category 5 nodules, the pooled specificity was significantly higher in ACR-TIRADS (p = 0.02). For ACR-TIRADS, the missed malignancy rate was 21.7% and the unnecessary biopsy rate was 62.7%. Information was not sufficient for this calculation with ATA. CONCLUSIONS: The diagnostic performance of ACR-TIRADS and ATA in the pediatric population was somewhat modest. Large studies are mandatory for further validation and future amendments. KEY POINTS: • The pooled sensitivity and specificity for highly suspicious nodules (category 4 or 5) for ACR-TIRADS were 0.84 and 0.64, and for ATA were 0.90 and 0.50, respectively. • When applying ACR-TIRADS for children, the pooled missed malignancy rate (21.7%) and unnecessary biopsy rates (62.7%) are still reasonably high. Insufficient information was available to perform these calculations for the ATA system. • Current risk stratification systems, especially ACR-TIRADS, require modification by focusing more on increasing the sensitivity and decreasing the missed malignancy rate. Lowering size cut-off for biopsy would be a reasonable option.

Ability of Pelvic Magnetic Resonance Imaging to Predict Clinical Course of Perianal Fistula in Paediatric Crohn's Disease Patients.

BACKGROUND AND AIMS: Evidence is limited regarding clinical course and magnetic resonance imaging [MRI] features of perianal fistula [PAF] in Korean children with Crohn's disease [CD]. We investigated MRI features of PAF and associations with long-term outcomes. METHODS: We retrospectively analysed 243 patients with pelvic MRI for diagnosis of CD. Incidence of clinically evident PAF at diagnosis was determined, as were the proportions of patients with clinical failure [failure to achieve fistula healing within 1 year] and recurrence [new/recurrent PAF after fistula healing within 1 year]. Associations between outcomes and MRI features, specified in modified Van Assche index and MAGNIFI-CD, were evaluated. Associations between later development of clinically evident PAF and subclinical PAF detected on MRI at diagnosis were evaluated. RESULTS: Among 243 included patients, 108 [44.4%] and 76 [31.3%] had clinically evident and subclinical PAF at diagnosis, respectively; 66.4% of the patients with clinically evident PAF achieved fistula healing within 1 year, and 32.7% of those patients developed recurrence. Fistula length and dominant features of the tracts were associated with clinical failure, and fistula length was associated with recurrence. Clinically evident PAF developed in 17.0% of the patients without clinically evident PAF at diagnosis. We did not find statistically significant association between subclinical PAF and later development of clinically evident PAF [adjusted hazard ratio, 2.438; p = 0.15]. CONCLUSIONS: A considerable proportion of Korean paediatric CD patients had clinically evident and subclinical PAF. Fistula length and dominant feature of the tract on MRI are useful predictors of outcomes.

Assessment of native liver fibrosis using ultrasound elastography and serological fibrosis indices in children with biliary atresia after the Kasai procedure.

BACKGROUND: Validated non-invasive examinations are necessary to monitor liver fibrosis in children with biliary atresia (BA) after the Kasai procedure. PURPOSE: To evaluate the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE), transient elastography (TE), and the serologic biomarkers of aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score for evaluating native liver fibrosis in children with BA. MATERIAL AND METHODS: We retrospectively reviewed same-day 2D-SWE and TE liver stiffness (LS) measurements of 63 patients with BA who underwent the Kasai procedure. The APRI and FIB-4 score were computed. Hepatic fibrosis was categorized into three clinical categories based on the ultrasound (US) hepatic morphology and clinical manifestations of liver cirrhosis: I, pre-cirrhotic liver state (n = 15); II, US and/or clinical signs of liver cirrhosis with compensated liver function (n = 27); and III, liver cirrhosis with decompensated liver function (n = 21). We compared area under the receiver operating characteristic curve (AUC) data among 2D-SWE, TE, APRI, and FIB-4 score. Combined evaluation of serologic fibrosis indices and US elastography was conducted and AUCs of combinations were analyzed. RESULTS: 2D-SWE, TE, APRI, and FIB-4 score showed good to excellent diagnostic accuracy for differentiating clinical categories (AUCs 0.779-0.955). AUC values were significantly increased after adding TE to FIB-4 score for detecting liver cirrhosis (P = 0.02). CONCLUSION: 2D-SWE, TE, APRI, and FIB-4 score are accurate non-invasive markers for monitoring native liver fibrosis in patients with BA. Combined use of serologic markers and US elastography could yield more accurate diagnoses of liver fibrosis than serologic markers alone.

Analysis of Risk Factors for Hepatotoxicity Induced by Immune Checkpoint Inhibitors.

Although hepatotoxicity induced by immune checkpoint inhibitors (ICPIs) can cause severe clinical complications, the risk factors associated with hepatotoxicity have rarely been investigated. The purpose of this study was to determine the potential risk factors for the incidence of hepatotoxicity and for time to ICPI-induced hepatotoxicity. Patients who received ICPIs (atezolizumab, nivolumab, pembrolizumab, and ipilimumab) were included in this retrospective 2-center study. Collected data included sex, age, body weight, body surface area, Eastern Cooperative Oncology Group performance status, underlying disease, liver metastasis, programmed cell death ligand-1 expression, interval from previous chemotherapy, and concomitant drug use. Among the 194 patients, patients who experienced hepatotoxicity after ICPI administration was 64.4% (n=125) in all grade and 10.8% (n=21) in grade III or higher. Multivariate analysis showed that patients aged 30-50 and 50-70 years had increased risks of hepatotoxicity by 4.9-fold (95% confidence interval, 1.3-18.0) and 2.7-fold (95% confidence interval, 1.3-5.5), respectively, compared with those older than 70 years. The use of acetaminophen increased the occurrence of hepatotoxicity by 2.1 times; the attributable risk was 53.2%. Male patients and patients younger than 65 years had around 1.5-fold increased hazard of time to reach hepatotoxicity. Patients treated with 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors had a 4.7-fold higher risk of grade III-IV hepatotoxicity compared with those without HMG-CoA reductase inhibitors; the attributable risk was 78.8%. In conclusion, close monitoring of liver function is recommended, especially in male patients, patients younger than 65 years old, and when there is concomitant use of hepatotoxic drugs including acetaminophen and HMG-CoA reductase inhibitors.

Incidence of Occult Spinal Dysraphism Among Infants With Cutaneous Stigmata and Proportion Managed With Neurosurgery: A Systematic Review and Meta-analysis.

Importance: Occult spinal dysraphism (OSD) is the most common congenital spinal anomaly. Cutaneous anomalies such as skin dimples or deviated gluteal folds are well known as stigmata of OSD and are indicators for further evaluation; however, the association between cutaneous anomalies and OSD has not been systemically evaluated. Objective: To evaluate the incidence of OSD and the proportion of OSD cases managed with a neurosurgical intervention among neonates or infants with various cutaneous stigmata. Data Sources: PubMed and Embase databases were searched for studies published up to July 25, 2018, that evaluated the proportion of OSD cases in neonates or infants with cutaneous stigmata. Search terms included ultrasound, dysraphism, dimple, and infant or neonate. The search was limited to English-language publications. Study Selection: Two reviewers selected the studies evaluating the incidence of OSD among neonates or infants with cutaneous stigmata. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for data extraction were followed. Pooled proportions of OSD cases and OSD cases that were managed with a neurosurgical intervention were obtained using the generalized linear mixed model and maximum likelihood method. Main Outcome and Measures: The pooled incidence of OSD and OSD cases managed with neurological surgery among patients with cutaneous stigmata was the primary outcome. This outcome was also evaluated in each subgroup, and heterogeneity was explored using subgroup analysis. Results: A total of 15 studies, involving 6558 neonate or infant patients with various cutaneous stigmata, were included. The pooled proportion of OSD cases among the patients with cutaneous stigmata was 2.8% (95% CI, 2.1%-3.8%; I2 = 51.6%), and the proportion managed with neurological surgery was 0.6% (95% CI, 0.3%-1.3%; I2 = 66.4%). Cases with combined stigmata showed a significantly higher association with OSD than those with a single stigma (10.5% [95% CI, 6.9%-15.8%] vs 2.3% [%, 95% CI, 1.5%-3.5%]; P < .001). The pooled proportion of OSD cases among patients with an atypical dimple was significantly higher than among those with simple dimple (8.8% [95% CI, 4.5%-16.6%] vs 0.6% [95% CI of 1.4%-2.1%]; P = .001). Conclusions and Relevance: The proportion of OSD in healthy, asymptomatic patients with midline cutaneous stigmata was low, and the proportion of patients who underwent a neurosurgical intervention was even lower. However, a careful evaluation as well as potential spinal magnetic resonance imaging is recommended for neonates or infants with combined stigmata or an atypical dimple for possible high-risk lesions.

Prognostic Factors for Event-Free Survival in Pediatric Patients with Hepatoblastoma Based on the 2017 PRETEXT and CHIC-HS Systems.

This study aimed to evaluate the prognostic value of variables used in the 2017 PRE-Treatment EXTent of tumor (PRETEXT) system and the Children's Hepatic tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system in pediatric patients with hepatoblastoma. A retrospective analysis of data from the pediatric hepatoblastoma registry of a tertiary referral center was conducted to evaluate the clinical and imaging variables (annotation factors) of the PRETEXT staging system. The primary outcome was event-free survival (EFS). Data from 84 patients (mean age: 2.9 ± 3.5 years) identified between 1998 and 2017 were included. Univariable Cox proportional hazards analysis revealed that PRETEXT annotation factors P (portal vein involvement), F (multifocality of tumor), and M (distant metastasis) showed a significant negative association with EFS. Multivariable Cox proportional hazard analysis showed that factor F was the strongest predictor (HR (hazard ratio), 2.908; 95% CI (confidence interval), 1.061-7.972; p = 0.038), whereas factor M showed borderline significance (HR, 2.416; 95% CI, 0.918-6.354; p = 0.074). The prediction model based on F and M (F + M) showed good performance to predict EFS (C-statistic, 0.734; 95% CI, 0.612-0.854). In conclusion, the PRETEXT annotation factor F was the strongest predictor of EFS, and the F + M model showed good performance to predict EFS in pediatric patients with hepatoblastoma.

Comparison of whole-body MRI, bone scan, and radiographic skeletal survey for lesion detection and risk stratification of Langerhans Cell Histiocytosis.

Accurate risk stratification according to the extent of Langerhans cell histiocytosis (LCH) determined on whole-body evaluation is important for determining the treatment plans and prognosis in patients with LCH. This study aimed to compare the lesion detectability and the accuracy of risk stratification of skeletal survey, bone scan, and whole-body magnetic resonance imaging (WB-MRI) in patients with LCH. Patients with newly-diagnosed LCH who underwent all three imaging modalities were retrospectively included (n = 46). The sensitivity and mean number of false-positives per patient for LCH lesions, and the accuracy of risk stratification of each modality were assessed. WB-MRI had significantly higher sensitivity (99.0%; 95% confidence interval, 93.2-99.9%) than skeletal survey (56.6%; p < 0.0001) and bone scan (38.4%; p < 0.0001) for LCH lesions, and there were no significant differences in the number of false-positives per patient (p > 0.017). WB-MRI tended to have higher accuracy for the risk stratification than skeletal survey and bone scan (concordance rate of 0.98, 0.91, and 0.83, respectively), although the differences were not significant (overall p-value 0.066). In conclusion, WB-MRI had higher detectability for LCH lesions than skeletal survey and bone scan, while the three whole-body imaging modalities had comparable accuracy in the initial risk stratification of LCH.

Two Cases of Chloromethylisothiazolinone and Methylisothiazolinone-associated Toxic Lung Injury.

Previous animal studies have not conclusively determined the association between exposure to humidifier disinfectants (HDs) containing 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and/or 2-methyl-4-isothiazolin-3-one (MIT) and development of HD-associated lung injuries. Nonetheless, patients exposed to HDs containing only CMIT and/or MIT showed clinically similar lung injuries to those exposed to HDs containing polyhexamethylene guanidine (PHMG) or oligo (2-[2-ethoxy]ethoxyethyl) guanidinium chloride (PGH). Here, we report twin sisters with lung injuries associated with exposure to CMIT/MIT-containing HDs. At 6 months of age, a younger twin sister presented with the 3-day history of cough, sputum, and respiratory difficulty. Chest radiography revealed multiple patchy consolidation and ground-glass opacities with pneumothorax and pneumomediastinum. Thoracostomy was performed due to pneumothorax at admission and she was discharged at 11 days of hospitalization. At 5 years of age, multiple tiny nodules and faint centrilobular ground-glass opacities were observed with the small pneumatocele. The elder sister visited a tertiary hospital due to dyspnea at 12 months of age. Chest radiography showed consolidation, pneumomediastinum, and pulmonary interstitial emphysema. There was no response to the administration of immunosuppressant drugs and antifibrotic agents. At 5 years of age, chest CT revealed ground-glass opacity and multiple tiny centrilobular ground-glass opacities nodules in both lungs with exercise intolerance.

Sacrococcygeal teratomas in newborns: a comprehensive review for the radiologists.

Sacrococcygeal teratomas are the most common solid tumor in newborn infants. The diagnosis is not difficult in many cases; however, there should be additional information on imaging studies in order to manage those infants properly. Details include histology, morphologic classification, complications such as rupture, bleeding, and mass effects on the adjacent structures. Although imaging features cannot accurately predict the histologic subtypes of the tumors, thorough evaluation of the imaging features can help distinguish malignant tumors from benign tumors. In this article, pathogenesis, histological characteristics, clinical considerations, and morphologic characteristics will be discussed.