Real-world incidences and risk factors of immune-related adverse events in patients treated with immune checkpoint inhibitors: A nationwide retrospective cohort study.

Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) are rare but fatal, requiring systemic steroid use. Therefore, to examine the outcomes, incidence, timing, and risk factors of ICI-associated steroid-requiring severe irAEs, we conducted a nationwide, retrospective, cohort study utilizing the Korean Health Insurance and Review Assessment database. We identified 357,010 patients with lung cancer, bladder cancer, or skin melanoma, eligible for ICI reimbursement in Korea between January 2012 to June 2020. Steroid-requiring severe irAEs following ICI treatment or treatment-emergent AEs following cytotoxic chemotherapy were defined as moderate- or high-dose steroid administration for over 2 consecutive days, along with corresponding ICD-10 codes indicating affected organ systems. The ICI-exposed group (N = 10,118) was compared to a matched cohort of 55,436 ICI-unexposed patients treated with cytotoxic chemotherapy. Incidences of acute severe irAEs requiring moderate- and high-dose steroids were higher in the ICI-exposed group (1.95% and 6.42%, respectively). The ICI-exposed group also had a higher risk of developing delayed severe irAEs requiring moderate- and high-dose steroid use (3.89% and 7.39%). Male sex, high comorbidity index, or previously diagnosed autoimmune diseases were associated with an increased risk of severe irAEs. Notably, 27.4-38.8% of the patients experienced recurrent severe irAEs after re-challenge with ICIs following moderate- or high-dose steroid use, with the severity matching the initial episode. Steroid-requiring severe irAEs were significantly more prevalent among patients exposed to ICIs than among those treated with chemotherapy in acute and delayed periods.

Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study.

BACKGROUND: The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. OBJECTIVE: We evaluated the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. METHODS: We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. RESULTS: Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors. CONCLUSIONS: The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs.

Changes in tuberculosis risk after transplantation in the setting of decreased community tuberculosis incidence: a national population-based study, 2008-2020.

BACKGROUND: Transplant recipients are immunocompromised and vulnerable to developing tuberculosis. However, active tuberculosis incidence is rapidly declining in South Korea, but the trend of tuberculosis infection among transplant recipients has not been elucidated. This study aimed to evaluate the risk of active tuberculosis after transplantation, including risk factors for tuberculosis and standardized incidence ratios, compared with that in the general population. METHODS: This retrospective study was conducted based on the South Korean health insurance review and assessment database among those who underwent transplantation (62,484 recipients) between 2008 and 2020. Tuberculosis incidence was compared in recipients treated during higher- (2010-2012) and lower-disease burden (2016-2018) periods. Standardized incidence ratios were analyzed using the Korean Tuberculosis Surveillance System. The primary outcome was the number of new tuberculosis cases after transplantation. RESULTS: Of 57,103 recipients analyzed, the overall cumulative incidence rate 1 year after transplantation was 0.8% (95% confidence interval [CI]: 0.7-0.8), significantly higher in the higher-burden period than in the lower-burden period (1.7% vs. 1.0% 3 years after transplantation, P < 0.001). Individuals who underwent allogeneic hematopoietic stem cell transplantation had the highest tuberculosis incidence, followed by those who underwent solid organ transplantation and autologous hematopoietic stem cell transplantation (P < 0.001). The overall standardized incidence ratio was 3.9 (95% CI 3.7-4.2) and was the highest in children aged 0-19 years, at 9.0 (95% CI 5.7-13.5). Male sex, older age, tuberculosis history, liver transplantation, and allogeneic hematopoietic stem cell transplantation were risk factors for tuberculosis. CONCLUSIONS: Transplant recipients are vulnerable to developing tuberculosis, possibly influenced by their immunocompromised status, solid organ transplant type, age, and community prevalence of tuberculosis. Tuberculosis prevalence by country, transplant type, and age should be considered to establish an appropriate tuberculosis prevention strategy for high-risk groups.

Incidence and Features of Lymphoid Proliferation and Lymphomas after Solid Organ or Hematopoietic Stem Cell Transplantation in a National Database Cohort.

PURPOSE: Post-transplantation lymphoproliferative disorders (PTLDs) after hematopoietic stem transplantation (HCT) or solid organ transplantation (SOT) result in poorer outcomes, including death. There are limited large cohort data on the incidence and natural course of PTLD in Asians. MATERIALS AND METHODS: We investigated PTLD using Korean national health insurance claims data of 47,518 patients who underwent HCT or SOT in 2008-2020. Patient demographics, time and type of PTLD diagnosis, type of PTLD treatment, and death data were collected. We used Fine and Gray subdistribution hazard models to calculate the cumulative incidence and risk factors for PTLD. RESULTS: During median follow-up of 5.32 years, PTLD occurred in 294 of 36,945 SOT patients (0.79%) and 235 of 10,573 HCT patients (2.22%). Cumulative incidence of PTLD were 0.49% at 1 year, 1.02% at 5 years, and 1.50% at 10 years post-transplantation. Age < 20 years (subdistribution hazard ratio [SHR] of 1.67 in age 10-19, SHR 1.51 in age 0-9), HCT (SHR 3.02), heart transplantation (SHR 2.27), and liver transplantation (SHR 1.47) were significant risk factors for PTLD. The presence of PTLD was associated with an increased risk of death (hazard ratio of 2.84). Overall, 5-year survival of PTLD patients was 68.9% (95% confidence interval, 64.9 to 73.2). CONCLUSION: We observed a steady increase in PTLD over 10 years after HCT or SOT in this large cohort study. Pediatric age group, HCT, liver transplantation, and heart transplantation were suggested to be risk factors for PTLD, and PTLD was associated with a higher risk of death.

Harmful effect of repetitive intravenous iodinated contrast media administration on the long-term renal function of patients with early gastric cancer.

This retrospective study investigated whether repetitive exposure to intravenous iodinated contrast media (ICM) affects long-term renal function in patients who undergo curative surgery for early gastric cancer (EGC) collected from the Korean Health Insurance and Review Assessment (HIRA) database. Patients diagnosed with gastric cancer between January 2010 and December 2013 underwent regular computed tomography (CT) scans to monitor for extragastric recurrence. Patients who already had chronic kidney disease (CKD) before cancer diagnosis or had undergone chemotherapy or repeated surgery were excluded. A nested case-control study design was chosen to analyze the effect of repetitive ICM exposure to long-term renal function by comparing patients who developed CKD 2 years after cancer diagnosis and patients who did not. Among 59,971 patients collected according to inclusion and exclusion criteria, 1021 were diagnosed with CKD 2 years after cancer diagnosis. Using 1:5 matching after adjusting for age, sex and date of cancer diagnosis, 5097 control patients were matched to 1021 CKD patients. Conditional logistic regression showed that the number of CTs taken using ICM slightly increased the odds of CKD (odds ratio, 1.080; 95% confidence interval (CI): 1.059, 1.100; P < 0.0001). Thus, the administration of ICM might contribute to chronic renal function impairment.

Does high [18F]FDG uptake always mean poor prognosis? Colon cancer with high-level microsatellite instability is associated with high [18F]FDG uptake on PET/CT.

OBJECTIVES: High-level microsatellite instability (MSI-high) is generally associated with higher F-18 fluorodeoxyglucose ([18F]FDG) uptake than stable microsatellite (MSI-stable) tumors. However, MSI-high tumors have better prognosis, which is in contrast with general understanding that high [18F]FDG uptake correlates with poor prognosis. This study evaluated metastasis incidence with MSI status and [18F]FDG uptake. METHODS: We retrospectively reviewed 108 right-side colon cancer patients who underwent preoperative [18F]FDG PET/CT and postoperative MSI evaluations using a standard polymerase chain reaction at five Bethesda guidelines panel loci. The maximum standard uptake value (SUVmax), SUVmax tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were measured using SUV 2.5 cut-off threshold. Student's t-test or Mann-Whitney U test was performed for continuous variables, and χ2 test or Fisher's exact test was performed for categorical variables (p value of < 0.05 for statistical significance). Medical records were reviewed for metastasis incidence. RESULTS: Our study population had 66 MSI-stable and 42 MSI-high tumors. [18F]FDG uptake was higher in MSI-high tumors than MSI-stable tumors (TLR, median (Q1, Q3): 7.95 (6.06, 10.54) vs. 6.08 (4.09, 8.82), p = 0.021). Multivariable subgroup analysis demonstrated that higher [18F]FDG uptake was associated with higher risks of distant metastasis in MSI-stable tumors (SUVmax: p = 0.025, MTV: p = 0.008, TLG: p = 0.019) but not in MSI-high tumors. CONCLUSION: MSI-high colon cancer is associated with high [18F]FDG uptake, but unlike MSI-stable tumors, the degree of [18F]FDG uptake does not correlate with the rate of distant metastasis. CLINICAL RELEVANCE STATEMENT: MSI status should be considered during PET/CT assessment of colon cancer patients, as the degree of [18F]FDG uptake might not reflect metastatic potential in MSI-high tumors. KEY POINTS: • High-level microsatellite instability (MSI-high) tumor is a prognostic factor for distant metastasis. • MSI-high colon cancers had a tendency of demonstrating higher [18F]FDG uptake compared to MSI-stable tumors. • Although higher [18F]FDG uptake is known to represent higher risks of distant metastasis, the degree of [18F]FDG uptake in MSI-high tumors did not correlate with the rate at which distant metastasis occurred.

Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding.

BACKGROUND & AIMS: Hemostatic powders have been clinically used in the treatment of gastrointestinal bleeding. We investigated the non-inferiority of a polysaccharide hemostatic powder (PHP), compared with conventional endoscopic treatments, for peptic ulcer bleeding (PUB). METHODS: This study was a prospective multi-center, randomized, open-label, controlled trial at 4 referral institutions. We consecutively enrolled patients who had undergone emergency endoscopy for PUB. The patients were randomly assigned to either a PHP or conventional treatment group. In the PHP group, diluted epinephrine was injected, and the powder was applied as a spray. Conventional endoscopic treatment included the use of electrical coagulation or hemoclipping after injection of diluted epinephrine. RESULTS: Between July 2017 and May 2021, 216 patients were enrolled in this study (PHP group, 105; control group, 111). Initial hemostasis was achieved in 92 of 105 patients (87.6%) in the PHP group and 96 of 111 patients (86.5%) in the conventional treatment group. Re-bleeding did not differ between the 2 groups. In subgroup analysis, the initial hemostasis failure rate in the conventional treatment group was 13.6% for Forrest IIa cases; however, there was no initial hemostasis failure in the PHP group (P = .023). Large ulcer size (≥15 mm) and chronic kidney disease with dialysis were independent risk factors for re-bleeding at 30 days. No adverse events were associated with PHP use. CONCLUSIONS: PHP is not inferior to conventional treatments and could be useful in initial endoscopic treatment for PUB. Further studies are needed to confirm the re-bleeding rate of PHP. CLINICALTRIALS: gov, Number: NCT02717416).

Association Between Proton Pump Inhibitor Exposure and Acute Kidney Injury After Cardiac Surgery.

OBJECTIVE: To evaluate the association of preoperative proton pump inhibitor (PPI) exposure with incident acute kidney injury (AKI) after cardiac surgery. PATIENTS AND METHODS: The Severance cardiac surgery cohort included 9860 cardiac surgery patients aged 18 years or older. The National Health Insurance Service-senior cohort included 2933 patients aged 60 years or older who underwent cardiac surgery. Preoperative PPI exposure was defined as a PPI prescription within 3 weeks prior to cardiac surgery. Primary outcomes were postoperative AKI and AKI requiring dialysis (AKI-dialysis). RESULTS: In the Severance cardiac surgery cohort after propensity score matching for PPI exposure, incident AKI (44.0% [472 of 1073] vs 40.5% [1304 of 3219]) and AKI-dialysis (5.8% [62 of 1073] vs 3.7% [119 of 3219]) were more common in patients exposed to PPI than in those who were not. Hospital and intensive care unit stay durations were longer among PPI-exposed than PPI-nonexposed patients. Multivariable conditional logistic analyses revealed that PPI exposure was significantly associated with incident AKI (adjusted odds ratio [AOR], 1.21; 95% CI, 1.03 to 1.42; P=.02) and AKI-dialysis (AOR, 1.74; 95% CI, 1.15 to 2.63; P=.009). The National Health Insurance Service-Senior cohort had similar results, revealing a significant association between PPI exposure and incident AKI-dialysis (AOR, 1.87; 95% CI, 1.25 to 2.81; P=.003). Discontinuation of PPI prior to operation was associated with a lower odds of AKI development in both cohorts. CONCLUSION: Preoperative PPI exposure may be a modifiable risk factor for AKI among patients undergoing cardiac surgery.

Impact of thyroid cancer on the cancer risk in patients with non-alcoholic fatty liver disease or dyslipidemia.

The raised prevalence of obesity has increased the incidence of obesity-related metabolic diseases such as dyslipidemia (DL) and non-alcoholic fatty liver disease (NAFLD), along with the development and progression of various types of cancer, including thyroid cancer. In this study, we investigated whether thyroid cancer in patients with DL and NAFLD could be a risk factor for other cancers. To achieve our goal, we generated two independent cohorts from our institution and from the National Health Insurance System in South Korea. Based on the ICD-10 code, we conducted exact matching (1:5 matching) and estimated the overall risk of thyroid cancer for other cancers in patients with DL or NAFLD. Univariate and multivariate analyses showed that the hazard ratio (HR) of thyroid cancer was 2.007 (95% Confidence Interval [CI], 1.597-2.522) and 2.092 (95% CI, 1.546-2.829), respectively in the institutional cohort and 1.329 (95% CI, 1.153-1.533) and 1.301 (95% CI, 1.115-1.517), respectively in the nationwide cohort. Risk analysis revealed a significant increase in the HR in lip, tongue, mouth, lung, bone, joint, soft tissue, skin, brain, male cancers and lymphoma after thyroid cancer occurred. Thyroid cancer in patients with DL or NAFLD might be a valuable factor for predicting the development of other cancers.

Risk of cancer, tuberculosis and serious infections in patients with ankylosing spondylitis, psoriatic arthritis and psoriasis treated with IL-17 and TNF-α inhibitors: a nationwide nested case-control analysis.

OBJECTIVES: Targeting interleukin (IL)-17 and tumour necrosis factor (TNF)-α is recommended for the management of severe/refractory ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis (PsO); however, safety data comparing these agents, especially in a large Asian population are unavailable. METHODS: Patients with AS, PsA and PsO were searched using the Health Insurance Review and Assessment Service database, defined according to the International Classification of Diseases-10 and unique insurance codes for rare diseases. By including patients newly diagnosed with AS, PsA, and PsO between 2010-2020, the outcomes of cancer, tuberculosis (TB) and serious infections following IL-17 and TNF-α inhibitor usage were evaluated. To investigate the association between treatments and outcomes, nested case-control analyses matching patients to controls (maximum of 1:10 ratio) according to index age, sex, index year, and follow-up duration were performed. RESULTS: Among 40322, 4953, and 5347 patients with AS, PsA, and PsO, respectively, three different datasets were generated to evaluate incidence of outcomes. Conditional logistic regression analysis revealed that cyclosporine use (odds ratio [OR] 2.286, p=0.0176) increased cancer, and a higher Charlson Comorbidity Index (CCI) score (OR 1.085, p=0.0406) and IL-17 inhibitor use only (OR 0.126, p=0.0457) showed a positive and negative association with TB, respectively. Serious infections increased in patients with high CCI scores (OR 1.117, p<0.0001), cyclosporine users (OR 1.445, p=0.0098), and medical-aided individuals (OR 1.667, p<0.0001). CONCLUSIONS: In this nationwide cohort of IL-17 and TNF-α inhibitor users, both treatments conferred comparable risk of cancer and serious infections, while IL-17 inhibitors may be advantageous for TB.

Risk of Dental Discoloration and Enamel Dysplasia in Children Exposed to Tetracycline and Its Derivatives.

PURPOSE: To examine the risk of dental abnormalities after exposure to tetracycline and its derivatives (TCs) in Korean children. MATERIALS AND METHODS: Children aged 0-17 years with a claim for prescriptions of TCs between 2002 and 2015 were identified from the Sample Research Database 2.0 of the National Health Insurance Service. Children not exposed to TCs were selected as the control group by matching sex and age (1:4). Cumulative incidence rate and relative risk of dental abnormalities after TCs exposure were investigated. RESULTS: The 10-year cumulative incidence rate in the 0-12 years group was 3.1% [95% confidence interval (CI), 2.3-3.9]. The 10-year cumulative incidence rates were 7.0%, 1.9%, and 1.6% in the 0-7, 8-12, and 13-17 years age groups (95% CI: 4.7-9.3, 1.2-2.6, and 1.3-1.9, respectively). There was no significant difference in the risk of dental abnormalities according to TC exposure among the age groups of 0-7 years [adjusted hazard ratio (aHR)=1.0], 8-12 years (aHR=1.1), and 13-17 years (aHR=1.2). CONCLUSION: Short-term exposure to TCs does not appear to increase the risk of dental abnormalities in children aged 0-7 and 0-12 years. Restrictions on the use of TCs in children aged 8-12 years, in some countries, may warrant consideration.

Periodontal disease and cancer risk: A nationwide population-based cohort study.

Background: Although emerging evidence suggests that periodontitis might increase the risk of cancer, comorbidity and lifestyle behaviors, such as smoking and body mass index (BMI), may have confounded this reported association. This study aimed to investigate whether chronic periodontitis is associated with cancer risk using a large, nationwide database. Methods: We conducted a population-based, retrospective cohort study using data from the Korean National Health Insurance Cohort Database obtained between January 2003 and December 2015. We included 713,201 individuals without a history of cancer who were followed up to 10 years. Confounding factors included demographic factors (age, sex, income, and residential area), lifestyle behaviors (smoking history and BMI), and comorbidities, such as hypertension, diabetes, heart failure, and pulmonary disease, using the Charlson Comorbidity Index. Multivariable Cox regression analysis was applied to estimate the adjusted hazard ratio (aHR) for cancer risk. Results: Of the 713,201 participants, 53,075 had periodontitis and were placed in the periodontitis group; the remaining 660,126 individuals were included as the control group. Overall, the cumulative incidence of cancer in the periodontitis group was 2.2 times higher than that in the control group. The periodontitis group had an increased risk of total cancer compared to the control group after adjusting for age, sex, comorbidities, BMI, and smoking history (aHR, 1.129; 95% confidence interval [CI], 1.089-1.171; P<0.0001). When examining specific cancer types, significant associations were also observed between periodontitis and stomach cancer (aHR, 1.136; 95% CI, 1.042-1.239; P=0.0037), colon cancer (aHR, 1.129; 95% CI, 1.029-1.239; P=0.0105), lung cancer (aHR, 1.127; 95% CI, 1.008-1.260; P=0.0353), bladder cancer (aHR, 1.307; 95% CI, 1.071-1.595; P=0.0085), thyroid cancer (aHR, 1.191; 95% CI, 1.085-1.308; P=0.0002), and leukemia (aHR, 1.394; 95% CI, 1.039-1.872; P=0.0270). There was no significant association between the development of secondary malignancy and periodontitis in cancer survivors who were alive 5 years after they were diagnosed with the primary malignancy. Conclusions: Periodontal disease, including periodontitis, was associated with increased risk of cancer, which persisted after controlling for confounding factors. Further prospective research is warranted to establish a causal relationship.

Matched Versus Mixed COVID-19 Vaccinations in Korean Solid Organ Transplant Recipients: An Observational Study.

BACKGROUND: Solid organ transplant recipients (SOTRs) are vulnerable to severe coronavirus disease 2019 (COVID-19) and exhibit poor antibody responses to COVID-19 vaccines. Herein, we compared the humoral immunogenicity of a mixed vaccine (ChAdOx1 nCoV-19 [ChAd]/BNT162b2 [BNT]) with that of conventional matched vaccines (mRNA, adenoviral vector [AdV-Vec]) in SOTRs. METHODS: Serum samples were collected at Severance Hospital (Seoul, Korea) between September and October 2021 (14 d-5 mo after COVID-19 vaccination; V2). The severe acute respiratory syndrome coronavirus 2 antispike IgG titer (BAU/mL; ELISA) and neutralization inhibition (percentage; neutralization assay) were compared between vaccination groups overall and stratified by V2 (poststudy vaccination visit) timing. RESULTS: Of the 464 participants, 143 (31%) received mRNA vaccines, 170 (37%) received AdV-Vec vaccines, and 151 (33%) received mixed vaccines (all ChAd/BNT). The geometric mean titer for the ChAd/BNT group was 3.2-fold higher than that of the AdV-Vec group (geometric mean ratio, 3.2; confidence interval, 1.9-5.4) but lower than that of the mRNA group (geometric mean ratio, 0.4; confidence interval, 0.2-0.7). Neutralization inhibition in the ChAd/BNT group was 32%, which was higher than that in the AdV-Vec group (21%; P < 0.001) but lower than that in the mRNA group (55%; P = 0.02). There was no difference in geometric mean titer by V2 timing (ChAd/BNT, 45 versus 31, days 14-60; mRNA, 28 versus 15, days 61-150). CONCLUSIONS: The ChAd/BNT group showed higher humoral immunogenicity than the AdV-Vec group, with similar immunogenicity to the mRNA vaccine. Nevertheless, immunogenicity following the primary vaccination series was poor in all vaccine groups, supporting the justification for booster vaccination in SOTRs.

Osteonecrosis in Korean Paediatric and Young Adults with Acute Lymphoblastic Leukaemia or Lymphoblastic Lymphoma: A Nationwide Epidemiological Study.

Osteonecrosis (ON) is a serious complication of acute lymphocytic leukaemia (ALL) or lymphoblastic lymphoma (LBL) treatment, and there is little information regarding ON in Korean paediatric and young adult patients. This retrospective cohort study assessed the cumulative incidence of and risk factors for ON using national health insurance claims data from 2008 to 2019 in 4861 ALL/LBL patients. The Kaplan-Meier method was used to estimate the cumulative incidence of ON according to age groups; the Cox proportional hazard regression model was used to identify risk factors related to ON development after diagnosing ALL/LBL. A cause-specific hazard model with time-varying covariates was used to assess the effects of risk factors. Overall, 158 (3.25%) patients were diagnosed with ON, among whom 23 underwent orthopaedic surgeries. Older age, radiotherapy (HR = 2.62, 95% confidence interval (CI) 1.87-3.66), HSCT (HR = 2.40, 95% CI 1.74-3.31), steroid use and anthracycline use (HR = 2.76, CI 1.85-4.14) were related to ON in the univariate analysis. In the multivariate analysis, age and steroid and asparaginase use (HR = 1.99, CI 1.30-3.06) were factors associated with ON. These results suggest that Korean patients with ALL/LBL who used steroids and asparaginase should be closely monitored during follow-up, even among young adult patients.

Coexisting and Second Primary Cancers in Patients with Uveal Melanoma: A 10-Year Nationwide Database Analysis.

Uveal melanoma is the most common intraocular tumor in adults. Metastatic disease occurs in about 30% of patients, for which there is currently no effective treatment. More than half of patients are long-term survivors, and it is well established that cancer survivors are prone to developing second primary cancers. In this study, we analyzed 10 years' worth of data from the nationwide database to determine the rates of coexisting malignancies and second primary cancers associated with uveal melanoma. The mean annual incidence of uveal melanoma was 1.1 per million. Approximately 43% of patients had coexisting cancers. The most common coexisting cancer was lung cancer (10%) followed by liver cancer (6%) and non-Hodgkin lymphoma (6%). In patients whose first cancer in their lifetime was uveal melanoma, the 10-year cumulative incidence of second primary cancers was 22% (95% confidence interval, 9-31%). The age- and sex-adjusted standard incidence rates was 3.61 (95% confidence interval, 2.61-4.86). The most common second primary cancers were lung cancer and hepatocellular carcinoma, followed by prostate, thyroid, pancreatic, and ovarian cancers. Age was the only factor associated with second primary cancer development. Our findings will be helpful in providing counseling for cancer screening in uveal melanoma patients.

SpO2/FiO2 as a predictor of high flow nasal cannula outcomes in children with acute hypoxemic respiratory failure.

The high-flow nasal cannula (HFNC) is a useful treatment modality for acute hypoxemic respiratory failure (AHRF) in children. We compared the ability of the oxygen saturation to fraction of inspired oxygen ratio (S/F) and arterial oxygen partial pressure to fraction of inspired oxygen ratio (P/F) to predict HFNC outcomes in children with AHRF. This study included children treated with HFNC due to AHRF from April 2013 to March 2019 at the Severance Children's Hospital. HFNC failure was defined as the need for mechanical ventilation. Trends of S/F and P/F during HFNC were analyzed. To predict HFNC outcomes, a nomogram was constructed based on predictive factors. A total of 139 patients with arterial blood gas data were included in the S/F and P/F analyses. S/F < 230 at initiation showed high prediction accuracy for HFNC failure (area under the receiver operating characteristic curve: 0.751). Univariate analyses identified S/F < 230 at HFNC initiation and < 200 at 2 h (odds ratio [OR] 12.83, 95% CI 5.06-35.84), and hemato-oncologic disease (OR 3.79, 95% CI 1.12-12.78) as significant predictive factors of HFNC failure. The constructed nomogram had a highly predictive performance, with a concordance index of 0.765 and 0.831 for the exploratory and validation groups, respectively. S/F may be used as a predictor of HFNC outcomes. Our nomogram with S/F for HFNC failure within 2 h may prevent delayed intubation in children with AHRF.

Robotic single-site versus multi-port myomectomy: a case-control study.

BACKGROUND: This study aimed to evaluate the compatibility of robotic single-site (RSS) myomectomy in comparison with the conventional robotic multi-port (RMP) myomectomy to achieve successful surgical outcomes with reliability and reproducibility. METHODS: This retrospective case-control study was performed on 236 robotic myomectomies at a university medical center. After 1:1 propensity score matching for the total myoma number, total myoma diameter, and patient age, 90 patients in each group (RSS: n = 90; RMP: n = 90) were evaluated. Patient demographics, preoperative parameters, intraoperative characteristics, and postoperative outcome measures were analyzed. RESULTS: The body mass index, parity, preoperative hemoglobin levels, mean maximal myoma diameter, and anatomical type of myoma showed no mean differences between RSS and RMP myomectomies. The RSS group was younger, had lesser number of myomas removed, and had a smaller sum of the maximal diameter of total myomas removed than the RMP group. After propensity score matching, the total operative time (RSS: 150.9 ± 57.1 min vs. RMP: 170 ± 74.5 min, p = 0.0296) was significantly shorter in the RSS group. The RSS group tended to have a longer docking time (RSS: 9.8 ± 6.5 min vs. RMP: 8 ± 6.2 min, p = 0.0527), shorter console time (RSS: 111.1 ± 52.3 min vs. RMP: 125.8 ± 65.1 min, p = 0.0665), and shorter time required for in-bag morcellation (RSS: 30.1 ± 17.2 min vs. RMP: 36.2 ± 25.7 min, p = 0.0684). The visual analog scale pain score 1 day postoperatively was significantly lower in the RSS group (RSS: 2.4 ± 0.8 days vs. RMP: 2.7 ± 0.8 days, p = 0.0149), with similar consumption of analgesic drugs. The rate of transfusion, estimated blood loss during the operation, and length of hospital stay were not different between the two modalities. No other noticeable complications were observed in either group. CONCLUSIONS: Da Vinci RSS myomectomy is a compatible option with regard to reproducibility and safety, without significantly compromising the number and sum of the maximal diameter of myomas removed. The advantage of shorter total operative time and less pain with the same amount of analgesic drugs in RSS myomectomy will contribute to improving patient satisfaction.

Renal growth slope in children with congenital and acquired solitary functioning kidneys.

PURPOSE: This study aimed to analyze the renal growth slope in children with congenital and acquired solitary functioning kidneys. METHODS: This retrospective study included all renal ultrasonography examinations performed in children in the agenesis, multicystic dysplastic kidney (MCDK), or nephrectomy group between September 2002 and February 2019. We reviewed the images and recorded the contralateral kidney size only when there was no focal lesion. Linear mixed model or piecewise linear mixed model analyses with a time point of 24 months of age were performed. RESULTS: There were 132 patients, including 26 patients in the agenesis group, 35 in the MCDK group, and 71 in the nephrectomy group. The nephrectomy group showed the largest baseline kidney size (7.4 cm vs. 5.3 cm in the agenesis group [P<0.001] and 5.2 cm in the MCDK group [P<0.001]) and the smallest overall growth slope (0.04 cm/mo vs. 0.06 cm/mo in the agenesis group [P=0.004] and 0.07 cm/mo in the MCDK group [P<0.001]). However, considering the time point of 24 months for reaching adult renal function, there were significant changes in slope, from 0.1 cm/mo before 24 months of age to 0.03 cm/mo after 24 months of age in all three groups (P<0.001), without a significant difference among the groups. CONCLUSION: Significant changes were found in the renal growth slope before and after 24 months of age, with no significant difference between congenital and acquired solitary functioning kidneys.

A Single-Center Retrospective Analysis of Periprocedural Variables Affecting Local Tumor Progression after Radiofrequency Ablation of Colorectal Cancer Liver Metastases.

Background Local tumor progression (LTP) is associated with poorer survival in patients undergoing radiofrequency ablation (RFA) for colorectal liver metastasis (CLM). An algorithmic strategy to predict LTP may help in selection of patients who would benefit most from RFA for CLM. Purpose To estimate local tumor progression-free survival (LTPFS) following RFA of CLM and develop an algorithmic strategy based on clinical variables. Materials and Methods In this retrospective study, between March 2000 and December 2014, patients who underwent percutaneous RFA for CLM were randomly split into development (60%) and internal validation (40%) data sets. Kaplan-Meier method was used to estimate LTPFS and overall survival (OS) rates. Independent factors affecting LTPFS in the development data set were investigated by using multivariable Cox proportional hazard regression analysis. Risk scores were assigned to the risk factors and applied to the validation data set. Results A total of 365 patients (mean age, 60 years ± 11 [standard deviation]; 259 men) with 512 CLMs were evaluated. LTPFS and OS rates were 85% and 92% at 1 year, 73% and 41% at 5 years, 72% and 30% at 10 years, and 72% and 28% at 15 years, respectively. Independent risk factors for LTP included tumor size of 2 cm or greater (hazard ratio [HR], 3.8; 95% CI: 2.3, 6.2; P < .001), subcapsular tumor location (HR, 1.9; 95% CI: 1.1, 3.1; P = .02), and minimal ablative margin of 5 mm or less (HR, 11.7; 95% CI: 4.7, 29.2; P < .001). A prediction model that used the risk factors had areas under the curve of 0.89, 0.92, and 0.90 at 1, 5, and 10 years, respectively, and it showed significantly better areas under the curve when compared with the model using the minimal ablative margin of 5 mm or less alone. Conclusion Radiofrequency ablation provided long-term control of colorectal liver metastases. Although minimal ablative margin of 5 mm or less was the most dominant factor, the multifactorial approach including tumor size and subcapsular location better predicted local tumor progression-free survival. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Soulen and Sofocleous in this issue.

MRI Ancillary Features for LI-RADS Category 3 and 4 Observations: Improved Categorization to Indicate the Risk of Hepatic Malignancy.

OBJECTIVE. The purpose of this study was to investigate whether ancillary features can help stratify malignancy risk in Liver Imaging Reporting and Data System (LI-RADS) category 3 (LR-3) and 4 (LR-4) observations. MATERIALS AND METHODS. This retrospective longitudinal study included 106 LR-3 or LR-4 observations on gadolinium-enhanced MRI obtained from January 2014 to December 2015 in 80 patients who were treatment naïve and at risk (mean age, 58.0 ± 10.7 [SD] years; 60 men). The presence of major and ancillary features, the category determined using only major features, and the final category adjusted by the application of ancillary features were retrospectively analyzed. MRI features were compared using generalized estimating equations, and cumulative incidence curves for malignancy were compared using log-rank tests with a resampling extension. RESULTS. At 6-month follow-up, the cumulative incidence of observations initially categorized as LR-4, observations upgraded to LR-4, observations initially categorized as LR-3, and observations downgraded to LR-3 were 62.5%, 29.7%, 6.2%, and 0%, respectively. The cumulative incidence of malignancy did not differ between observations categorized by major feature as LR-3 and LR-4 (p = 0.12), but was higher in final observations categorized as LR-4 than in those categorized as LR-3 (p < 0.001). Among observations categorized by major feature as LR-3, the cumulative incidence of malignancy was higher in observations upgraded to LR-4 than in observations that were initially graded as LR-3 (p = 0.03), which showed differences in the frequency of restricted diffusion and mild-to-moderate T2-weighted hyperintensity (p < 0.001 for both). CONCLUSION. Final categories determined with ancillary features, instead of categories determined by major features only, can help indicate malignancy risk in LR-3 and LR-4 observations on MRI.