ERBB2 amplification in gastric cancer: a genomic insight into ethnic disparities.

Overall, gastric adenocarcinoma (GC) incidence rates have declined in recent years, but racial/ethnic disparities persist. Individuals who identify as Hispanic/Spanish/Latino are diagnosed with GC at younger ages and have poorer outcomes than non-Hispanic individuals. However, our understanding of GC biology across racial/ethnic groups remains limited. We assessed tumor genomic patterns by race/ethnicity among 1019 patients with primary GC in the AACR Project GENIE Consortium. Hispanic individuals presented with significantly higher rates of ERBB2/HER2 amplification vs other racial/ethnic groups (Hispanic: 13.9% vs 9.8% non-Hispanic White, 8.1% non-Hispanic Asian, and 11.0% non-Hispanic Black; p < .001, FDR adjusted q < 0.001). Hispanic patients also had higher odds of an ERBB2 amplification vs non-Hispanic whites in adjusted models (OR = 2.52, 95%CI = 1.20-5.33, p = .015). These findings underscore the important role of genomic factors in GC disparities. Ensuring equitable access to genomic profiling and targeted therapies, such as trastuzumab for HER2-overexpressing GC, is a promising avenue to mitigate GC disparities and improve outcomes.

Large-scale integration of omics and electronic health records to identify potential risk protein biomarkers and therapeutic drugs for cancer prevention and intervention.

Identifying risk protein targets and their therapeutic drugs is crucial for effective cancer prevention. Here, we conduct integrative and fine-mapping analyses of large genome-wide association studies data for breast, colorectal, lung, ovarian, pancreatic, and prostate cancers, and characterize 710 lead variants independently associated with cancer risk. Through mapping protein quantitative trait loci (pQTL) for these variants using plasma proteomics data from over 75,000 participants, we identify 365 proteins associated with cancer risk. Subsequent colocalization analysis identifies 101 proteins, including 74 not reported in previous studies. We further characterize 36 potential druggable proteins for cancers or other disease indications. Analyzing >3.5 million electronic health records, we uncover five drugs (Haloperidol, Trazodone, Tranexamic Acid, Haloperidol, and Captopril) associated with increased cancer risk and two drugs (Caffeine and Acetazolamide) linked to reduced colorectal cancer risk. This study offers novel insights into therapeutic drugs targeting risk proteins for cancer prevention and intervention.

Lifestyle factors, genetic susceptibility to obesity and their interactions on coronary artery disease risk: A cohort study in the UK Biobank.

OBJECTIVE: We aimed to evaluate potential modifying effects of genetic susceptibility to obesity on the association of lifestyle factors with coronary artery disease (CAD) risk. METHODS: A total of 328,606 participants (54% women) were included using data from the UK Biobank. We evaluated the risk of developing CAD associated with obesity-related polygenic scores (PGSs) and healthy lifestyle scores (HLSs). HLSs were constructed using six lifestyle factors. Obesity PGSs were created using genetic variants identified by genome-wide association studies, including 941 variants for body mass index (BMI) and 457 for waist-to-hip ratio (WHR). Both HLSs and PGSs were categorized into three groups. RESULTS: During a 9-year median follow-up, 14,541 participants developed CAD. An unhealthy lifestyle was significantly associated with an increased CAD risk (hazard ratio [HR] = 2.24, 95% confidence interval [CI] = 2.09-2.40). High BMI and WHR PGSs were each significantly associated with an increased CAD risk (HRBMI = 1.23, 1.17-1.29; HRWHR = 1.15, 1.09-1.21). Lifestyle factors explained 41% (95% CI = 38%-45%) of CAD, while genetic variants for BMI explained only 10% (7%-14%). Risks of CAD were increased with poorer HLS independent of obesity-related PGSs. Individuals with the most unhealthy lifestyle and highest BMI PGS had the highest risk of CAD risk (HR = 2.59, 95% CI = 2.26-2.97), compared with participants with the healthiest lifestyle and lowest BMI PGS. CONCLUSIONS: While the observational nature of the study precludes the establishment of causality, our study provides supports for a causal association between obesity and CAD risk and the importance of lifestyle modification in the prevention of CAD.

Large-Scale Cancer Genomic Analysis Reveals Significant Disparities between Microsatellite Instability and Tumor Mutational Burden.

BACKGROUND: Microsatellite instability (MSI) and tumor mutational burden (TMB) are predictive biomarkers for pan-cancer immunotherapy. The interrelationship between MSI-high (MSI-H) and TMB-high (TMB-H) in human cancers and their predictive value for immunotherapy in lung cancer remain unclear. METHODS: We analyzed somatic mutation data from the Genomics Evidence Neoplasia Information Exchange (n = 46,320) to determine the relationship between MSI-H and TMB-H in human cancers using adjusted multivariate regression models. Patient survival was examined using the Cox proportional hazards model. The association between MSI and genetic mutations was assessed. RESULTS: Patients (31-89%) with MSI-H had TMB-low phenotypes across 22 cancer types. Colorectal and stomach cancers showed the strongest association between TMB and MSI. TMB-H patients with lung cancer who received immunotherapy exhibited significantly higher overall survival [HR, 0.61; 95% confidence interval (CI), 0.44-0.86] and progression-free survival (HR, 0.65; 95% CI, 0.47-0.91) compared to the TMB-low group; no significant benefit was observed in the MSI-H group. Patients with TMB and MSI phenotypes showed further improvement in overall survival and PFS. We identified several mutated genes associated with MSI-H phenotypes, including known mismatch repair genes and novel mutated genes, such as ARID1A and ARID1B. CONCLUSIONS: Our results demonstrate that TMB-H and/or a combination of MSI-H can serve as biomarkers for immunotherapies in lung cancer. IMPACT: These findings suggest that distinct or combined biomarkers should be considered for immunotherapy in human cancers because notable discrepancies exist between MSI-H and TMB-H across different cancer types.

MRI-based breast cancer radiogenomics using RNA profiling: association with subtypes in a single-center prospective study.

BACKGROUND: There are few prospective studies on the correlations between MRI features and whole RNA-sequencing data in breast cancer according to molecular subtypes. The purpose of our study was to explore the association between genetic profiles and MRI phenotypes of breast cancer and to identify imaging markers that influences the prognosis and treatment according to subtypes. METHODS: From June 2017 to August 2018, MRIs of 95 women with invasive breast cancer were prospectively analyzed, using the breast imaging-reporting and data system and texture analysis. Whole RNA obtained from surgical specimens was analyzed using next-generation sequencing. The association between MRI features and gene expression profiles was analyzed in the entire tumor and subtypes. Gene networks, enriched functions, and canonical pathways were analyzed using Ingenuity Pathway Analysis. The P value for differential expression was obtained using a parametric F test comparing nested linear models and adjusted for multiple testing by reporting Q value. RESULTS: In 95 participants (mean age, 53 years ± 11 [standard deviation]), mass lesion type was associated with upregulation of CCL3L1 (sevenfold) and irregular mass shape was associated with downregulation of MIR421 (sixfold). In estrogen receptor-positive cancer with mass lesion type, CCL3L1 (21-fold), SNHG12 (11-fold), and MIR206 (sevenfold) were upregulated, and MIR597 (265-fold), MIR126 (12-fold), and SOX17 (fivefold) were downregulated. In triple-negative breast cancer with increased standard deviation of texture analysis on precontrast T1-weighted imaging, CLEC3A (23-fold), SRGN (13-fold), HSPG2 (sevenfold), KMT2D (fivefold), and VMP1 (fivefold) were upregulated, and IGLC2 (73-fold) and PRDX4 (sevenfold) were downregulated (all, P < 0.05 and Q < 0.1). Gene network and functional analysis showed that mass type estrogen receptor-positive cancers were associated with cell growth, anti-estrogen resistance, and poor survival. CONCLUSION: MRI characteristics are associated with the different expressions of genes related to metastasis, anti-drug resistance, and prognosis, depending on the molecular subtypes of breast cancer.

IgA nephropathy with minimal change disease associated with primary Sjögren's syndrome: A case report.

RATIONALE: Only 1 case of IgA nephropathy (IgAN) with minimal change disease (MCD) associated with primary Sjögren's syndrome (SS) has been reported. We additionally describe IgAN with MCD associated with primary SS. PATIENT CONCERNS: A 80-year-old woman visited our hospital complaining of generalized edema that had started 4 weeks prior. She reported a sense of thirst and dry eye for the last 5 years. DIAGNOSES: Her initial laboratory findings were compatible with nephrotic syndrome; both the antinuclear antibody (1:80) and anti-SS-A (Ro) antibody (200 U/mL) tests were positive. A salivary gland scan revealed markedly decreased uptake for both the parotid and submandibular glands. The Schirmer test was positive. The random urine protein/creatinine ratio was 10 mg/mg. Renal biopsy was compatible with IgAN with superimposed MCD. INTERVENTIONS: Furosemide was intravenously administered with intermittent albumin infusion for her edema control. She was started on prednisone 40mg daily for 6 weeks, which was tapered to 5 mg for another 6 months after starting prednisolone. OUTCOMES: Over the next 6 months, her edema improved and the proteinuria decreased significantly. LESSONS: Physician should suspect IgA with MCD when patient with SS clinically showed nephrotic syndrome, and perform renal biopsy for pathologically diagnosis and appropriate treatment.

Combined effect of external treatment of herbal medicine and tuina in congenital muscular torticollis: Systematic review and meta-analysis.

BACKGROUND: Congenital muscular torticollis (CMT) is the third most common musculoskeletal disease in children. With no standardized treatment method hence, so it is necessary to find an effective treatment method that can be received comfortably by children. This review assessed the efficacy of an external treatment of herbal medicine (ETHM) with tuina for CMT in children. METHODS: This study searched the English, Chinese, and Korean databases (total of 10) until June 7 2022, without any language restrictions. All included studies were randomized clinical trials (RCTs) of ETHM with tuina as an intervention comparted to the same tuina alone according to the inclusion and exclusion criteria. The mean differences (MD), standardized mean differences (SMD), risk ratio (RR) with the 95% confidence interval (CI), and risk of bias (ROBs) were calculated using Review Manager Version 5.4 software. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) rating system was used to assess the quality of evidence. The publication bias was evaluated using a funnel plot, the Egger test, the fail-safe N test, and the Duval and Tweedle's trim and fill method using Review Manager Version 5.4 software, the software R Version 4.1.1 and R studio Version 1.4.1106 program. RESULTS: Nineteen RCTs with 1710 patients were included in the meta-analysis. ETHM plus tuina improved the outcomes of the total effective rate (TER) [RR 1.21, 95% CI:1.15 to 1.26, P < .001], sternocleidomastoid (SCM) muscle thickness [MD: -1.82, 95% CI: -2.23 to -1.41, P < .001], cervical rotation range [MD: 13.43, 95% CI: 10.41-16.45, P < .001] and lateral flexion range [MD: 8.50, 95% CI: 6.15-10.85, P < .001], tissue elasticity grade [SMD: -0.46; 95% CI: -0.71 to -0.22, P = .0002], muscle elasticity scores [RR: 1.56; 95% CI: 1.04 to 2.34, P = .03], and clinical symptom and sign scores [SMD: -0.78; 95% CI: -1.09 to -0.47, P < .001]. CONCLUSIONS: ETHM plus tuina have a combined effect on CMT children. However, further studies with high-quality clinical trials are needed to obtain more robust clinical evidence.

Polygenic Risk Scores Associated with Tumor Immune Infiltration in Common Cancers.

It is largely unknown whether genetic susceptibility contributes to tumor immune infiltration in common cancers. We systematically investigated the association between polygenic risk scores (PRSs) and tumor immune infiltration in common cancers. First, we constructed a PRS for common cancers using the risk variants identified in previous genome-wide association studies. Then, we analyzed 139 immune traits predicted by previous studies by examining gene expression data in tumor tissues from The Cancer Genome Atlas (TCGA). We applied regression analyses to evaluate the associations between PRS and immune traits for each cancer overall and stratified by stage, including 2160 pathologically confirmed cases of breast, colorectal, lung, ovarian, pancreatic, and prostate cancers in the White population. At a nominal (p < 0.05) significance level, we identified 31 significant associations between PRS and immune traits. In the analyses stratified by stage for breast, colorectal, lung adenocarcinoma, and lung squamous cell carcinoma, we identified 65 significant associations, including 56 associations that were undetected by the overall analysis. This study provides evidence for genetic risk factors affecting immune infiltration and provides novel insights into the role of genetic susceptibility in immune responses, underlying cancer development, prognosis, and the potential role of an early diagnostic or therapeutic targeting strategy.

The neutrophil-to-lymphocyte ratio may indicate when to start hemodialysis.

We evaluated whether the neutrophil-to-lymphocyte ratio (NLR) could aid dialysis decision-making in combination with the clinical presentation and biochemical findings. We retrospectively evaluated the medical records of 279 patients who commenced chronic maintenance hemodialysis. We compared the laboratory findings at 6 months before dialysis to those at dialysis initiation. NLR cutoffs and risk factors for each of six uremic symptoms were determined. Mean age was 60.7 years and mean estimated glomerular filtration rate (eGFR) was 5.7 ± 2.5 mL/min/1.73 m2 at the time of hemodialysis and 7.7 ± 3.8 mL/min/1.73 m2 6 months earlier (p < 0.001). The mean NLR increased significantly from 2.5 ± 1.0 to 4.9 ± 2.8 (p < 0.001). The NLR was positively correlated with the C-reactive protein level (r = 0.202, p = 0.009) and negatively correlated with those of albumin (r = -0.192, p = 0.001) and total CO2 (r = -0.134, p = 0.023). The NLR cutoffs for neurological and gastrointestinal symptoms as determined using receiver operator curve analysis were 2.4 (area under the curve [AUC] 0.976; 95% confidence interval [CI] 0.960-0.993; sensitivity 92.2%; specificity 94.7%) and 3.6 (AUC 0.671; 95% CI 0.588-0.755; sensitivity 68.1%; specificity 63.5%), respectively. On multiple linear regression analysis of neurological symptoms, the NLR was a significant predictor (ß = -0.218, p = 0.017), as was age (ß = 0.314, p = 0.037). In conclusion, the NLR may serve as a supplementary marker predicting uremic symptoms and a need for hemodialysis in stage 5 CKD patients.

Page kidney following spontaneous subcapsular hematoma immediately after kidney transplantation: a case report.

BACKGROUND: Page kidney (PK) is the occurrence of kidney hypoperfusion and ischemia due to pressure on the kidney by a subcapsular hematoma (SH), a mass, or fluid collection. SH after renal transplantation may result in kidney ischemia and graft loss. CASE PRESENTATION: We present a rare case of early spontaneous SH in an allograft kidney that led to a decrease in renal function. A 56-year-old male patient underwent deceased donor kidney transplantation. After declamping, appropriate renal perfusion and immediate diuresis were observed, with no evidence of SH. However, his urinary output abruptly decreased 6 h postoperatively. Abdominal ultrasonography showed 28 mm deep SH on transplant and the resistive index (RI) increased to 0.98-1 and diastolic flow reversal was observed. Surgical interventions were performed 2 days after transplantation, following a further decrease in urinary output. Serum creatinine decreased to 2.2 mg/dL, urinary output increased to an average of 200 cc per hour and the RI value was decreased to 0.7 on POD 7. CONCLUSION: In patients with abrupt decreased renal function after transplantation, SH should be suspected and the presence of PK should be determined using Doppler USG. In these cases, surgical intervention may avoid allograft dysfunction.

Impact of phase angle and sarcopenia estimated by bioimpedance analysis on clinical prognosis in patients undergoing hemodialysis: A retrospective study.

ABSTRACT: Bioimpedance analysis (BIA) has been widely used in the evaluation of body composition in patients undergoing maintenance hemodialysis. We conducted this study to evaluate impact of phase angle (PA) and sarcopenia measured by BIA on clinical prognosis in these patients.This longitudinal retrospective study enrolled patients who underwent hemodialysis between January 2016 and March 2019. The patients were stratified into higher (> 4°) and lower (≤ 4.0°) PA groups. Sarcopenia was defined when the appendicular skeletal muscle mass was < 20 kg in men and < 15 kg in women.Of the 191 patients, 63.4% were men. The mean age was 64.2 ±â€Š12.4 years. The lower PA group was older, had a higher proportion of women, a lower body mass index, lower albumin, cholesterol, uric acid, and phosphorus levels, and a higher incidence of history of coronary artery disease than the higher PA group. Linear regression analysis revealed that PA was significantly associated with body mass index (B = 0.18, P = .005), serum albumin (B = 0.23, P = .001), and creatinine levels (B = 0.32, P < .001). During a median follow-up of 16.7 months, 14.1% (n = 27) of patients experienced major adverse cardiovascular events and 11.0% (n = 21) died. Kaplan-Meier survival analysis showed that the higher PA group had significantly better survival, regardless of sarcopenia. Multivariate Cox analyses revealed that lower PA (0.51 [0.31-0.85], P = .010), higher IDWG (1.06 [1.01-1.12], P = .028) and C-reactive protein level (1.01 [1.01-1.02], P < .001), and a history of coronary artery disease (3.02 [1.04-8.77], P = .042) were significantly related to all-cause mortality after adjusting for other covariates.PA measured by BIA was an independent factor in the prediction of mortality in maintenance hemodialysis patients, regardless of sarcopenia. Intervention studies are needed to confirm if the improvement in PA is associated with better clinical outcome.

Acute kidney injury due to direct infiltration by lymphoplasmacytic lymphoma secreting IgG paraproteins: A case report.

INTRODUCTION: Waldenström's macroglobulinemia is a lymphoplasmacytic lymphoma (LPL) associated with a monoclonal immunoglobulin M protein. Although acute kidney injury (AKI) due to immunoglobulin M paraprotein infiltration into the renal interstitium has been reported, there has been no report of AKI with invasion of the immunoglobulin G paraprotein into the renal interstitium in a patient with LPL. PATIENT CONCERNS: A 65-year-old male was admitted to our hospital with fatigue and decreased renal function. He complained of a 3-kg weight loss in the last 3 months. DIAGNOSIS: The initial blood urea nitrogen and serum creatinine levels were 55.9 and 1.83 mg/dL, respectively. Serum protein electrophoresis revealed a monoclonal component (3.5 g/dL) in the gamma region and immunofixation electrophoresis showed an immunoglobulin G kappa monoclonal protein. Renal pathology revealed that CD3-CD20+ CD138+ lymphoid cells had infiltrated the renal interstitium. A bone marrow biopsy was compatible with LPL. INTERVENTIONS: Intravenous methylprednisolone (1 mg/kg) was administered after confirming the renal pathological findings. OUTCOMES: Serum creatinine decreased to 0.8 mg/dL 14 days after treatment. CONCLUSIONS: Physicians should recognize LPL secreting various immunoglobulins as a possible cause of AKI when renal failure of unknown etiology and serum immunoglobulin paraprotein is present. A kidney biopsy should be performed for definitive diagnosis and appropriate management.

Chemical fluorescence-based dye staining for 3-dimensional histopathology analysis.

Tissue clearing for 3-dimensional (3D) imaging is increasingly utilized in many biomedical applications, including the pathological examination of human biopsy specimens. Although many protocols offer rapid and efficient tissue clearing (>1 d), immunofluorescence labeling of thick specimens is a highly time-consuming process. The use of low molecular weight chemical dyes has potential benefits in terms of speed and quality of 3D labeling. Accordingly, we tested several chemical dyes to assess their potential applications in 3D imaging. The combination of SYTO 16 and eosin (S&E) was found to be a potential fluorescent version of the hematoxylin-eosin (H&E) stain. Furthermore, picrosirius red (for collagen), Congo red (for senile plaques), and fluorescent Nissl (for neurons in the normal brain or blood vessels in the injured brain) stains can be used alone or in combination with antibody labeling. As chemical labeling requires a relatively short incubation time (<1 d), fluorescent chemical dyes could expedite the 3D imaging process.

External treatment of herbal medicine with tuina in congenital muscular torticollis: A protocol for systematic review and meta-analysis.

BACKGROUND: This study is the protocol to evaluate the clinical evidence for external treatments using herbal medicine (ETHM) with tuina as a congenital muscular treatment (CMT) in pediatrics. METHODS: Eleven databases will be searched until June 2022, without any language restrictions: four English databases (MEDLINE, Pubmed, EMBASE, and The Cochrane Central Register of Database of Controlled Trials), three Chinese databases (China National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan Fang Database), and four Korean electronic databases (Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, National Digital Science Links, and Research Information Sharing Service). This review will include randomized clinical trials (RCTs) of ETHM with tuina as an intervention versus the same tuina. All published RCTs for any ETHM for CMT will be included. Non-RCTs, RCT protocol, animal studies, case reports, reviews, and surveys will be excluded. The methodological quality assessment will be performed using the Cochrane risk of bias (ROBs). Review Manager version 5.4. will be used for the data synthesis and quantitative analysis. RESULTS AND DISCUSSIONS: The systematic review and meta-analysis will provide evidence for ETHM as a treatment of CMT. The evidence can help clinicians and patients recognize more effective therapeutic and safe inventions. INPLASY REGISTRATION NUMBER: INPLASY202210017.

Integrative treatment of herbal medicine with western medicine on coronary artery lesions in children with Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a major cause of coronary artery lesions (CALs) in children. Approximately 10% to 20% of children treated with intravenous immunoglobulin are intravenous immunoglobulin-resistant. This study evaluated the efficacy and safety of adding herbal medicine to conventional western medicines versus conventional western medicines alone for CALs in children with KD. METHODS: This study searched 9 electronic databases until August 31, 2021. The inclusion criteria were the randomized controlled trials (RCTs) that assessed the CALs in children with KD and compared integrative treatment with conventional western treatments. Two authors searched independently for RCTs, including eligible articles that fulfilled the inclusion criteria, extracted data, and assessed the methodological quality using the Cochrane risk of bias tool. Meta-analysis was conducted using Cochrane Collaboration's Review Manager 5.4 software. The effect size was presented as the risk ratio (RR), and the fixed-effect models were used to pool the results. RESULTS: The finally selected 12 studies included a total of 1030 KD patients. According to a meta-analysis, the integrative treatment showed better results than the conventional treatment in the CAL prevalence rate (RR = 2.00; 95% confidence interval [CI], 1.49-2.71; P < .00001), CAL recovery rate (RR = 1.27; 95% CI, 1.05-1.54; P = .02), and total effective rate (RR = 1.17; 95% CI, 1.11-1.23; P < .00001). Only 2 studies referred to the safety of the treatment. The asymmetrical funnel plot of the CAL prevalence rate indicated the possibility of potential publication bias. CONCLUSIONS: This review found the integrative treatment to be more effective in reducing the CAL prevalence rate and increasing the CAL recovery rate and total effective rate in KD patients than conventional western treatment. However, additional well-designed RCTs will be needed further to compensate restrictions of insufficient trials on safety, methodological quality, and publication bias.

Incidence, risk factors, and prognosis of acute kidney injury in hospitalized patients with acute cholangitis.

BACKGROUND: The association between acute cholangitis (AC) and acute kidney injury (AKI) remains unclear. We investigated the incidence, and clinical course of AKI in patients with AC, and the long-term prognosis. METHODS: We performed a single-center retrospective study of patients hospitalized with AC in a tertiary care center from January 2011 to December 2017. The risk factors for AKI were evaluated, and AKI severity was analyzed using the Systemic Inflammatory Response System (SIRS), quick sequential organ failure assessment (qSOFA) score, and 2018 Tokyo Guidelines (TG) grade. To calculate the relative risk of death based on AKI, hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained using Cox's proportional hazard models. RESULTS: A total of 1,438 patients with AC were included, of whom 18.2% (n = 261) developed AKI. AKI patients were older, and had a lower systolic blood pressure and more comorbidities including hypertension (HT), chronic kidney disease, and cardiovascular accidents. Disease severity (as assessed by SIRS, qSOFA, and the Tokyo Guidelines grade) was higher in the AKI group, as was the in-hospital mortality rate. Multivariate analysis revealed that age, HT, SIRS and qSOFA scores ≥ 2, and TG grade of III were significant risk factors for AKI. Kaplan-Meier analysis revealed significantly higher mortality in the AKI than non-AKI group. AKI (HR = 1.853; 95% CI: 1.115-3.079) and TG grade III (HR = 2.139; 95% CI: 1.190-3,846) were independent predictors of all-cause AC mortality, even after adjusting for all covariates. The annual rate of decline in the estimated glomerular filtration rate was faster in the AKI than non-AKI group (2.9 ± 6.7 vs. 0.5 ± 5.3 mL/min/1.73 m2/year, p < 0.001). CONCLUSIONS: AKI development increased AC severity and mortality. Our results suggest that clinicians should monitor AKI status and perform appropriate management as soon as possible.

Prospective Study on Prophylactic Micafungin Sodium against Invasive Fungal Disease during Neutropenia in Pediatric & Adolescent Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.

BACKGROUND: Invasive fungal diseases (IFDs) increase the mortality rate of patients with neutropenia who receive chemotherapy or have previously undergone hematopoietic stem cell transplantation (HSCT). Micafungin is a broad-spectrum echinocandin with minimal toxicity and low drug interactions. We therefore investigated the efficacy and safety of prophylactic micafungin in pediatric and adolescent patients who underwent autologous HSCT. METHODS: This was a phase II, prospective, single-center, open-label, and single-arm study. From November 2011 to February 2017, 125 patients were screened from Seoul National University Children's Hospital, Korea, and 112 were enrolled. Micafungin was administered intravenously at a dose of 1 mg/kg/day (maximum 50 mg/day) from day 8 of autologous HSCT until neutrophil engraftment. Treatment success was defined as the absence of proven, probable, or possible IFD up to 4 weeks after therapy. RESULTS: The study protocol was achieved without premature interruption in 110 patients (98.2%). The reasons interrupting micafungin treatment included early death (n = 1) and patient refusal (n = 1). Treatment success was achieved in 109 patients (99.1%). Only one patient was diagnosed with probable IFD. No patients were diagnosed with possible or proven IFD. In the full analysis set, 21 patients (18.8%) experienced 22 adverse events (AEs); however, all AEs were classified as "unlikely" related to micafungin. No patient experienced grade IV AEs nor discontinued treatment, and none of the deaths were related to micafungin. CONCLUSIONS: Our study demonstrated that micafungin is a safe and effective option for antifungal prophylaxis in pediatric patients who underwent autologous HSCT, with promising efficacy without significant AEs.

Derivation of YCMi005-A, a human-induced pluripotent stem cell line, from a patient with dilated cardiomyopathy carrying missense variant in TPM1 (p. Glu192Lys).

Dilated cardiomyopathy (DCM) is one of the leading causes of heart transplantation. The clinical feature of DCM is characterized by enlarged heart and impaired function of the left or both ventricles, while its etiology is varied. In this study, we generated YCMi005-A, a human-induced pluripotent stem cell (hiPSC) line from a patient with DCM carrying the missense mutation of p.Glu192Lys in the TPM1 genes. YCMi005-A, an established hiPSC, showed the normal karyotype (46, XX) and high expression of pluripotency markers. In addition, it was confirmed that YCMi005-A has the differentiation potential assessed by staining of three germ layer markers.

Distinct Genomic Landscapes in Early-Onset and Late-Onset Endometrial Cancer.

PURPOSE: The spectrum of somatic mutations among women with endometrial cancer (EC) younger than 50 years (early-onset EC) remains unknown. We investigated distinct somatic mutation patterns among early-onset and late-onset (age ≥ 50 years) EC patients. METHODS: This cohort study included individuals age 18+ years diagnosed with pathologically confirmed EC in the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE, v9.1) consortium. We explored tumor mutational burden (TMB) and genomic patterns of EC by age at clinical sequencing using multivariable regression models adjusted for race, ethnicity, histology, sequencing assay, sample type, and TMB. RESULTS: Among 2,425 women with EC, 176 (7.3%) had early-onset EC and 1,923 (79.3%) had nonhypermutated (< 17.78 mutations/Mb) tumors. TMB significantly differed across age and histology groups. Among nonhypermutated ECs, early-onset patients had significantly lower odds of presenting with nonsilent FGFR2 and PIK3R1 somatic mutations compared with late-onset EC patients in adjusted models (FGFR2: odds ratio [OR] = 0.18, 95% CI, 0.04 to 0.76; PIK3R1: OR = 0.54, 95% CI, 0.31 to 0.92). By contrast, early-onset EC patients had increased odds of presenting with nonsilent CTNNB1 and BRCA2 mutations compared with late-onset patients (CTNNB1: OR = 3.32, 95% CI, 2.14 to 5.16; BRCA2: OR = 4.01, 95% CI, 1.55 to 10.38). Subsequent analyses stratified by race, ethnicity, and tumor histology identified distinct patterns of APC, KMT2D, KMT2C, and KRAS by race, ethnicity, and PTEN and APC patterns by histologic subtypes. CONCLUSION: Early-onset EC harbors a unique genomic landscape compared with late-onset disease. A distinct molecular phenotype of early-onset EC provides novel insights into a unique etiology and may yield clinical implications for developing targeted treatment modalities for younger patients.