Transient albuminuria in the setting of short-term severe hyperglycemia in type 1 diabetes.

In a cohort of 1817 children with type 1 diabetes (T1D), short-term hyperglycemia was associated with transient albuminuria (11 % during new-onset T1D without diabetic ketoacidosis (DKA), 12 % during/after DKA, 6 % during routine screening). Our findings have implications regarding future risk of diabetic kidney disease and further investigation is needed.

Contrast-enhanced Imaging in Peripheral Pulmonary Lesions: The Role in US-guided Biopsies.

Purpose To compare the tissue adequacy and diagnostic accuracy of US-guided biopsies of peripheral pulmonary lesions (PPLs) with and without contrast agents. Materials and Methods A retrospective study was conducted at four medical centers in patients with PPLs who underwent US-guided percutaneous transthoracic needle biopsy (PTNB) between January 2017 and October 2022. The patients were divided into contrast-enhanced US (CEUS) and US groups based on whether prebiopsy CEUS evaluation was performed. Tissue adequacy and the diagnostic accuracy of PTNB, stratified by lesion size, were analyzed and compared between groups. A propensity score matching (PSM) analysis was conducted using the nearest-neighbor matching method. Results A total of 1027 lesions were analyzed, with 634 patients (mean age, 59.4 years ± 13.0 [SD]; 413 male) in the US group and 393 patients (mean age, 61.2 years ± 12.5; 270 male) in the CEUS group. The CEUS group produced more acceptable samples than the US group (98.2% vs 95.7%; P = .03) and achieved higher diagnostic accuracy (96.9% vs 94.2%; P = .04), with no evidence of a difference in sensitivity (96.7% vs 94.0%; P = .06). PSM and stratified analyses (n = 358 per group) indicated higher tissue adequacy (99.0% vs 95.7%; P = .04) and diagnostic accuracy (98.5% vs 92.9%; P = .006) in the CEUS group compared with the US group for 2-7-cm PPLs but not for lesions larger than 7 cm. Conclusion PTNB with prebiopsy CEUS evaluation demonstrated significantly better tissue adequacy and diagnostic accuracy compared with US guidance alone for PPLs ranging from 2 to 7 cm, with similar biopsy performance achieved between groups for lesions larger than 7 cm. Keywords: Contrast Material, Thoracic Diseases, Ultrasonography, Image-Guided Biopsy © RSNA, 2024.

Nomogram Based on US and Clinicopathologic Characteristics: Axillary Nodal Evaluation Following Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer.

BACKGROUND: To develop a convenient modality to predict axillary response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this multi-center study, a total of 1019 breast cancer patients with biopsy-proven positive lymph node (LN) receiving NAC were randomly assigned to the training and validation groups at a ratio of 7:3. Clinicopathologic and ultrasound (US) characteristics of both primary tumors and LNs were used to develop corresponding prediction models, and a nomogram integrating clinicopathologic and US predictors was generated to predict the axillary response to NAC. RESULTS: Axillary pathological complete response (pCR) was achieved in 47.79% of the patients. The expression of estrogen receptor, human epidermal growth factor receptor -2, Ki-67 score, and clinical nodal stage were independent predictors for nodal response to NAC. Location and radiological response of primary tumors, cortical thickness and shape of LNs on US were also significantly associated with nodal pCR. In the validation cohort, the discrimination of US model (area under the curve [AUC], 0.76) was superior to clinicopathologic model (AUC, 0.68); the combined model (AUC, 0.85) demonstrates strong discriminatory power in predicting nodal pCR. Calibration curves of the nomogram based on the combined model demonstrated that substantial agreement can be observed between the predictions and observations. This nomogram showed a false-negative rates of 16.67% in all patients and 10.53% in patients with triple negative breast cancer. CONCLUSION: Nomogram incorporating routine clinicopathologic and US characteristics can predict nodal pCR and represents a tool to aid in treatment decisions for the axilla after NAC in breast cancer patients.

Comprehensive evaluation of serum hepatic proteins in predicting prognosis among cancer patients with cachexia: an observational cohort study.

BACKGROUND: Hepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia. METHODS: This multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan-Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL). RESULTS: C-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28-1.80, P < 0.001), prealbumin (HR = 1.42, 95%CI = 1.19-1.69, P < 0.001), and transferrin (HR = 1.50, 95%CI = 1.25-1.80, P < 0.001) were independent risk factors for long-term survival in cancer patients with cachexia. In subgroup analysis, the prognostic value of low albumin was significant in patients with upper gastrointestinal, hepatobiliary and pancreatic, and colorectal cancers; low prealbumin was significant in colorectal cancer; and low transferrin was significant in patients with upper gastrointestinal and colorectal cancer. All three hepatic proteins were valuable as prognostic predictors for patients with advanced (Stage III and IV) cancer with cachexia. The risks of 90-days mortality and impaired QoL were higher in cachexia patients with low albumin, prealbumin, and transferrin levels. CONCLUSION: Low albumin, prealbumin, and transferrin levels were all independent prognostic factors affecting patients with cancer cachexia, especially in patients in the advanced stages. These results highlight the value of routinely checking serum hepatic proteins in clinical practice to predict the prognosis of patients with cancer cachexia.

Child Opportunity Index and Pediatric Intensive Care Outcomes: A Multicenter Retrospective Study in the United States.

OBJECTIVES: To evaluate for associations between a child's neighborhood, as categorized by Child Opportunity Index (COI 2.0), and 1) PICU mortality, 2) severity of illness at PICU admission, and 3) PICU length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Fifteen PICUs in the United States. PATIENTS: Children younger than 18 years admitted from 2019 to 2020, excluding those after cardiac procedures. Nationally-normed COI category (very low, low, moderate, high, very high) was determined for each admission by census tract, and clinical features were obtained from the Virtual Pediatric Systems LLC (Los Angeles, CA) data from each site. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 33,901 index PICU admissions during the time period, median patient age was 4.9 years and PICU mortality was 2.1%. There was a higher percentage of admissions from the very low COI category (27.3%) than other COI categories (17.2-19.5%, p < 0.0001). Patient admissions from the high and very high COI categories had a lower median Pediatric Index of Mortality 3 risk of mortality (0.70) than those from the very low, low, and moderate COI groups (0.71) ( p < 0.001). PICU mortality was lowest in the very high (1.7%) and high (1.9%) COI groups and highest in the moderate group (2.5%), followed by very low (2.3%) and low (2.2%) ( p = 0.001 across categories). Median PICU LOS was between 1.37 and 1.50 days in all COI categories. Multivariable regression revealed adjusted odds of PICU mortality of 1.30 (95% CI, 0.94-1.79; p = 0.11) for children from a very low versus very high COI neighborhood, with an odds ratio [OR] of 0.996 (95% CI, 0.993-1.00; p = 0.05) for mortality for COI as an ordinal value from 0 to 100. Children without insurance coverage had an OR for mortality of 3.58 (95% CI, 2.46-5.20; p < 0.0001) as compared with those with commercial insurance. CONCLUSIONS: Children admitted to a cohort of U.S. PICUs were often from very low COI neighborhoods. Children from very high COI neighborhoods had the lowest risk of mortality and observed mortality; however, odds of mortality were not statistically different by COI category in a multivariable model. Children without insurance coverage had significantly higher odds of PICU mortality regardless of neighborhood.

Association between a novel nutrition-inflammation prognostic grading system and overall survival in hospitalized adults with cancer: A retrospective cohort study.

BACKGROUND: Malnutrition and increased systemic inflammatory responses are highly prevalent in patients with cancer and they have a negative effect on prognosis. We aimed to develop a nutrition-inflammation prognostic grading system (NIPGS) for patients with cancer, which incorporates the Nutritional Risk Screening 2002 (NRS 2002) and C-reactive protein (CRP) levels. METHODS: This multicenter retrospective cohort study totally included 6891 patients diagnosed with cancer. A 4 × 4 matrix incorporating the four NRS 2002 categories within each of the four CRP categories was constructed. Groups with approximate hazard ratios (HRs) were clustered into one grade. The NIPGS consists of four grades, with the survival rate gradually decreasing from Grades 1 to 4. The primary outcome was overall survival (OS) and comprehensive survival analyses were performed. RESULTS: During a median follow-up of 18.70 months, 2818 death cases occurred. Kaplan-Meier curve showed the survival rate decreased from Grades 1 to 4 of NIPGS (P < 0.001). The NIPGS was an independent risk factor associated with OS adjusting for confounders, with HRs increasing from 1.22 (95% confidence interval [CI], 1.09-1.36; P < 0.001) in Grade 2, 1.58 (95% CI, 1.39-1.80; P < 0.001) in Grade 3 to 1.92 (95% CI, 1.73-2.13; P < 0.001) in Grade 4. A high NIPGS grade was also associated with an increased risk of short-term mortality, poor quality of life, and longer hospital stay and expenses. Two internal validation cohorts confirmed the results of our study. CONCLUSION: The NIPGS could be an effective prognostic tool for patients with cancer.

Modified Controlling Nutritional Status (mCONUT) serves as a promising prognostic factor in patients with cancer cachexia.

BACKGROUND: Malnutrition and systemic inflammation are considered 2 hallmarks of cancer cachexia. Our study aimed to construct a modified Controlling Nutritional Status by introducing C-reactive protein as an inflammatory parameter and investigate its prognostic value in patients with cancer cachexia. METHODS: This multicenter cohort study included 5221 patients with cancer, among whom 1719 were diagnosed with cachexia. Concordance index and receiver operating characteristic curves were used to compare prognostic values between the 2 systems. The primary outcome was overall survival, and comprehensive survival analyses were performed. The secondary outcomes were short-term survival, malnutrition, and quality of life. RESULTS: During the median follow-up of 17.47 mo, 813 deaths were recorded. The modified Controlling Nutritional Status was more accurate than Controlling Nutritional Status in predicting survival in patients with cancer cachexia. Patients in the high Controlling Nutritional Status/modified Controlling Nutritional Status group had a significantly shorter overall survival. Multivariate Cox analysis confirmed high Controlling Nutritional Status (hazard ratio = 1.34, 95% CI, 1.13-1.58; P < 0.001) and modified Controlling Nutritional Status (hazard ratio = 1.46; 95% CI, 1.26-1.69; P < 0.001) were independent risk factors for survival, adjusting for confounders. In subgroup analyses, a high modified Controlling Nutritional Status score had a significantly negative effect on survival in cachexia patients with upper gastrointestinal and colorectal cancer, especially for advanced-stage (stages III and IV) patients. The risk of short-term mortality and experiencing malnutrition rose to 1.48 and 1.13 times, respectively, in the high modified Controlling Nutritional Status group, as well as that for poorer life quality. CONCLUSION: The modified Controlling Nutritional Status group comprehensively reflects nutritional, immune, and inflammatory status and serves as a powerful prognostic scoring system in patients with cancer cachexia.

Delta Radiomics Based on Longitudinal Dual-modal Ultrasound Can Early Predict Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

RATIONALE AND OBJECTIVES: To develop a monitoring model using radiomics analysis based on longitudinal B-mode ultrasound (BUS) and shear wave elastography (SWE) to early predict pathological response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this prospective study, 112 breast cancer patients who received NAC between September 2016 and March 2022 were included. The BUS and SWE data of breast cancer were obtained prior to treatment as well as after two and four cycles of NAC. Radiomics features were extracted followed by measuring the changes in radiomics features compared to baseline after the second and fourth cycles of NAC (△R [C2], △R [C4]), respectively. The delta radiomics signatures were established using a support vector machine classifier. RESULTS: The area under receiver operating characteristic curve (AUC) values of △RBUS (C2) and △RBUS (C4) for predicting the response to NAC were 0.83 and 0.84, while those of △RSWE (C2) and △RSWE (C4) were 0.88 and 0.90, respectively. △RSWE exhibited significantly superior performance to △RBUS for predicting NAC response (Delong test, p < 0.01). No significant differences were observed in the performances between △R (C2) and △R (C4) based on BUS or SWE data. The longitudinal dual-modal ultrasound radiomics (LDUR) model had an excellent discrimination, good calibration and clinical usefulness, with the AUC, sensitivity and specificity of 0.97, 95.52% and 91.11%, respectively. CONCLUSION: The LDUR model achieved excellent performance in predicting the pathological response to chemotherapy during the early stages of NAC for breast cancer.

A comprehensive analysis of the association between anemia and systemic inflammation in older patients with cancer.

PURPOSE: Our study aimed to comprehensively analyze the association between anemia and systemic inflammation in older patients with cancer. METHODS: This multicenter prospective cohort study included 4955 older patients with cancer between 2013 and 2020. Logistic regression analysis was performed to investigate risk factors of anemia, reporting odds ratios (ORs), and 95% confidence intervals (CIs). Comprehensive survival analyses, including Kaplan-Meier curve, Cox proportional risk model, and subgroup analysis, were performed. RESULTS: The participants' median age was 70.0 (interquartile range [IQR]=67.0-74.0) years, with 3293 (66.5%) males and 1662 (33.5%) females. There were 1717 (34.7%) older patients with cancer diagnosed with anemia. High neutrophil-to-lymphocyte ratio (NLR) was an independent risk factor associated with anemia (adjusted OR=1.97, 95%CI=1.73-2.24, P<0.001). In older patients with cancer and different anemia levels, the median overall survival was significantly shorter in those with a high NLR. In multivariate Cox analysis, high NLR served as a negative factor, independently affecting survival. The anemia-inflammation prognostic grading system showed a significant survival discriminative performance in older patients with cancer. After adjusting for confounders, high grades were independent risk factors for survival (grade 2: hazard ratio [HR] = 1.38, 95%CI = 1.26-1.52, P<0.001; grade 3: HR=1.82 95%CI = 1.59-2.09, P<0.001). This grading system was beneficial in determining survival in patients with lung, digestive tract, and urogenital cancers. CONCLUSIONS: Increased systemic inflammation is an independent risk factor for anemia. A high inflammatory status is also associated with poor survival in older cancer patients at different anemia levels. The anemia-inflammation grading system is beneficial for determining the prognosis in older patients with cancer.

A promising prognostic grading system incorporating weight loss and inflammation in patients with advanced cancer.

BACKGROUND: Involuntary weight loss and increased systemic response are frequently observed in patients with cancer, especially in advanced stages. This study aimed to develop a powerful weight loss and inflammation grading system (WLAIGS) and investigate its prognostic performance in patients with advanced cancer. METHODS: This multicentre prospective cohort study included 11 423 patients with advanced cancer. A 4 × 4 matrix representing four different per cent weight loss (WL%) categories within each of the four different neutrophil-to-lymphocyte ratio (NLR) categories (16 possible combinations of WL% and NLR) was constructed. The WLAIGS consisted of four grades, with hazard ratios (HRs) for overall survival (OS) gradually increasing from grade 1 to grade 4. Survival analyses, including Kaplan-Meier curve, Cox proportional hazards regression, and sensitivity analysis, were performed to investigate the association between WLAIGS and OS. The secondary outcomes were short-term survival, malnutrition, and quality of life. Two internal validation cohorts with a 7:3 ratio were used to validate the results. RESULTS: The median age of patients with advanced cancer in our study was 59.00 (interquartile range, 50.00-66.00) years. There were 6877 (60.2%) and 4546 (39.8%) male and female participants, respectively. We totally recorded 5046 death cases during the median follow-up of 17.33 months. The Kaplan-Meier curve showed that the survival rate decreased from grade 1 to grade 4 in patients with advanced cancer (log-rank P < 0.001). The WLAIGS was an independent risk factor associated with OS adjusting for confounders, with HRs increasing from 1.20 (95% confidence interval (CI), 1.11-1.29; P < 0.001) in grade 2, 1.48 (95% CI, 1.38-1.60; P < 0.001) in grade 3 to 1.73 (95% CI, 1.58-1.89; P < 0.001) in grade 4. In each weight loss% group (2.5 ≤ WL% < 6.0; 6.0 ≤ WL% < 11.0, WL% ≥ 11.0), a NLR above 3 was associated with shorter survival and served as an independent prognostic predictor. The risk of short-term mortality, malnutrition, and poor quality of life increased with WLAIGS grade. Two internal validation cohorts confirmed that the WLAIGS independently identified the survival of patients with advanced cancer. CONCLUSIONS: The WLAIGS, which reflects malnutrition and systemic inflammation status, is a robust and convenient tool for predicting the prognosis of patients with advanced cancer.

Comparison analysis of PD-1/PD-L1 inhibitors plus lenvatinib or gemcitabine/cisplatin as first-line treatment for patients with advanced intrahepatic cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive primary liver cancer, with increasing incidence worldwide. Effective first-line treatments for advanced ICC patients are currently limited. Therefore, our study aimed to assess the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in combination with gemcitabine/cisplatin (GC) and lenvatinib as first-line treatment in advanced ICC patients. Methods: This retrospective cohort study included 51 advanced ICC patients, among whom 25 patients were administered with PD-1/PD-L1 plus lenvatinib and 26 patients were administered with PD-1/PD-L1 plus GC. Baseline characteristics including demographic information, medical history, clinical characteristics, laboratory data, and imaging examination were collected. The primary endpoints were progression-free survival (PFS) and sixth- and ninth-month overall survival (OS) rate. Survival curve was plotted by the Kaplan-Meier method. A Cox proportion risk model was performed to investigate independent risk factors of PFS and OS. The secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events. Results: The median age of advanced ICC patients in our study was 58.0 (95% confidence interval [95% CI] = 48.0-72.4) years, with 33 male and 18 female patients. Patients in the PD-1/PD-L1 inhibitors plus lenvatinib group were more likely to be in ECOG grade above 1, develop ascites, and have an elevated level of ALT. The ORR was 16.0% in the PD-1/PD-L1 inhibitors plus lenvatinib group and 23.1% in the GC group (p = 0.777). The DCR was 52.0% in the lenvatinib group and 46.2% in the GC group (p = 0.676). The combination treatment of PD-1/PD-L1 inhibitors plus lenvatinib was associated with longer PFS than the GC group; however, it was not statistically significant (lenvatinib: 9.5 months, GC: 5.1 months, p = 0.454). The sixth-month and ninth-month OS rates were 82.0% and 76.9% in the lenvatinib group and 87.4% and 71.5% in the GC group. After adjusting for confounders, multivariate Cox regression analysis showed that ECOG grade above 1 was an independent risk factor for PFS (hazard ratio [HR] = 3.388, 95% CI = 1.312-8.746, p = 0.012) and OS (HR = 4.220, 95% CI = 1.131-15.742, p = 0.032). Conclusion: PD-1/PD-L1 inhibitors in combination with lenvatinib or GC all demonstrated significant efficacy and safety as first-line treatment in patients with advanced ICC. As for patients who refuse or are intolerant to chemotherapy, PD-1/PD-L1 plus lenvatinib would be recommended.

Anti-cancer treatment within two weeks serves as a risk factor for clinical outcomes among cancer patients with COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in infections among patients with cancer. Our study aimed to investigate the potential adverse impact of anti-cancer treatments within 2 weeks of COVID-19 infection on clinical outcomes in patients with cancer. Methods: This retrospective cohort study analyzed 70 cancer patients with COVID-19 infection from the First Hospital of Jilin University in Changchun City, Jilin Province, between March and June 2022. Data on demographic characteristics, vaccination status, COVID-19 clinical classification, symptoms, complications, tumor-related characteristics, laboratory examinations and medical interventions were extracted from electronic medical record. The primary outcome of our study was Intensive Care Unit (ICU) admission. Logistic regression model was performed to investigate the association between anti-cancer treatments within 2 weeks after COVID-19 infection and the risk of ICU admission. Results: Of the 70 patients enrolled in this study, 37 received anti-cancer treatments within 2 weeks after COVID-19 infection. Patients receiving anti-cancer treatment were more likely to experience non-mild COVID-19, require oxygen therapy, develop acute respiratory distress syndrome (ARDS) and exhibit elevated inflammatory levels. The risk of ICU admission (P<0.001) and 30-day mortality after reverse transcriptase polymerase chain reaction (RT-PCR) negative conversion (P=0.007) was significantly higher in patients receiving anti-cancer treatments. In multivariate Logistic regression analysis, non-mild classification of COVID-19, anti-cancer treatments within 2 weeks and ECOG > 1were all independently associated with ICU admission after adjusting for confounder factors. The risk of ICU admission rose to 43.63 times (95% confidence interval=1.31-1452.94, P=0.035) in patients receiving anti-cancer treatments within 2 weeks. Conclusion: Anti-cancer treatments within 2 weeks of COVID-19 infection increase the risk of ICU admission and 30-day mortality after RT-PCR negative conversion in patients with cancer. It may be recommended to postpone cancer-related treatments for more than 2 weeks in cancer patients with COVID-19 infection.

Deep Learning Model Based on Dual-Modal Ultrasound and Molecular Data for Predicting Response to Neoadjuvant Chemotherapy in Breast Cancer.

RATIONALE AND OBJECTIVES: To carry out radiomics analysis/deep convolutional neural network (CNN) based on B-mode ultrasound (BUS) and shear wave elastography (SWE) to predict response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this prospective study, 255 breast cancer patients who received NAC between September 2016 and December 2021 were included. Radiomics models were designed using a support vector machine classifier based on US images obtained before treatment, including BUS and SWE. And CNN models also were developed using ResNet architecture. The final predictive model was developed by combining the dual-modal US and independently associated clinicopathologic characteristics. The predictive performances of the models were assessed with five-fold cross-validation. RESULTS: Pretreatment SWE performed better than BUS in predicting the response to NAC for breast cancer for both the CNN and radiomics models (P < 0.001). The predictive results of the CNN models were significantly better than the radiomics models, with AUCs of 0.72 versus 0.69 for BUS and 0.80 versus 0.77 for SWE, respectively (P = 0.003). The CNN model based on the dual-modal US and molecular data exhibited outstanding performance in predicting NAC response, with an accuracy of 83.60% ± 2.63%, a sensitivity of 87.76% ± 6.44%, and a specificity of 77.45% ± 4.38%. CONCLUSION: The pretreatment CNN model based on the dual-modal US and molecular data achieved excellent performance for predicting the response to chemotherapy in breast cancer. Therefore, this model has the potential to serve as a non-invasive objective biomarker to predict NAC response and aid clinicians with individual treatments.

Characterization of the genomic and transcriptional structure of chicken NRG4 gene.

Neuregulin 4 (NRG4) is an important adipocytokine, which plays crucial roles in maintaining energy balance, regulating glucose and lipid metabolism, and preventing non-alcoholic fatty liver disease in mammals. At present, the genomic organization, transcript and protein isoforms of human NRG4 gene have been fully explored. Previous studies in our laboratory have shown that the NRG4 gene is expressed in chicken adipose tissue, but the chicken NRG4 (cNRG4) genomic structure, transcript and protein isoforms are still unknown. To this end, in this study, the genomic and transcriptional structure of the cNRG4 gene were systematically investigated using rapid amplification of cDNA ends (RACE) and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the coding region (CDS) of the cNRG4 gene was small, but it had a very complex transcriptional structure characterized by multiple transcription start sites, alternative splicing, intron retention, cryptic exons, and alternative polyadenylation, thus leading to production of four 5?UTR isoforms (cNRG4 A, cNRG4 B, cNRG4 C, and cNRG4 D) and six 3?UTR isoforms (cNRG4 a, cNRG4 b, cNRG4 c, cNRG4 d, cNRG4 e, and cNRG4 f) of the cNRG4 gene. The cNRG4 gene spanned 21,969 bp of genomic DNA (Chr.10:3,490,314~3,512,282) and consisted of 11 exons and 10 introns. Compared with the cNRG4 gene mRNA sequence (NM_001030544.4), two novel exons and one cryptic exon of the cNRG4 gene were identified in this study. Bioinformatics analysis, RT-PCR, cloning and sequencing analysis showed that the cNRG4 gene could encode three protein isoforms (cNRG4-1, cNRG4-2 and cNRG4-3). This study lays a foundation for further research on the function and regulation of the cNRG4 gene.

Protocol-Driven Initiation and Weaning of High-Flow Nasal Cannula for Patients With Bronchiolitis: A Quality Improvement Initiative.

OBJECTIVES: Bronchiolitis is the most common cause for nonelective infant hospitalization in the United States with increasing utilization of high-flow nasal cannula (HFNC). We standardized initiation and weaning of HFNC for bronchiolitis and quantified the impact on outcomes. Our specific aim was to reduce hospital and ICU length of stay (LOS) by 10% between two bronchiolitis seasons after implementation. DESIGN: A quality improvement (QI) project using statistical process control methodology. SETTING: Tertiary-care children's hospital with 24 PICU and 48 acute care pediatric beds. PATIENTS: Children less than 24 months old with bronchiolitis without other respiratory diagnoses or underlying cardiac, respiratory, or neuromuscular disorders between December 2017 and November 2018 (baseline), and December 2018 and February 2020 (postintervention). INTERVENTIONS: Interventions included development of an HFNC protocol with initiation and weaning guidelines, modification of protocol and respiratory assessment classification, education, and QI rounds with a focus on efficient HFNC weaning, transfer, and/or discharge. MEASUREMENTS AND MAIN RESULTS: A total of 223 children were included (96 baseline and 127 postintervention). The primary outcome metric, average LOS per patient, decreased from 4.0 to 2.8 days, and the average ICU LOS per patient decreased from 2.8 to 1.9 days. The secondary outcome metric, average HFNC treatment hours per patient, decreased from 44.0 to 36.3 hours. The primary and secondary outcomes met criteria for special cause variation. Balancing measures included ICU readmission rates, 30-day readmission rates, and adverse events, which were not different between the two periods. CONCLUSIONS: A standardized protocol for HFNC management for patients with bronchiolitis was associated with decreased hospital and ICU LOS, less time on HFNC, and no difference in readmissions or adverse events.

The benefit of contrast-enhanced ultrasound in biopsies for focal liver lesions: a retrospective study of 820 cases.

OBJECTIVE: This study compared the performance between ultrasound (US)- and contrast-enhanced US (CEUS)-guided liver biopsies and evaluated the benefit of CEUS in percutaneous biopsy for focal liver lesions (FLLs). METHODS: We performed a retrospective study of 820 patients with FLLs, who underwent percutaneous liver biopsy in our center between 2017 and 2019. The patients were divided into two groups based on whether US (n = 362) or CEUS (n = 458) used before a biopsy. The two groups were compared based on specimen adequacy for pathological diagnosis and diagnostic accuracy of liver biopsy. Stratification analysis was performed based on lesion and protocol characteristics to provide detailed information for selecting the imaging guidance for biopsy. RESULTS: Compared with the US group, the CEUS group yielded more acceptable samples (97.6% vs. 99.4%, p < 0.05) and improved diagnostic accuracy (92.6% vs. 96.4%, p < 0.05), and achieved better sensitivity (92.5% vs. 96.2%, p < 0.05) for liver biopsies, especially in FLLs ≥ 5 cm, heterogeneous hypoechoic FLLs, or FLLs with an obscure boundary. The CEUS group showed significantly higher accuracy compared with the US group pertaining to single-puncture biopsies (100% vs. 92.7%, p < 0.05) or biopsies with punctures ≤ 2 (97.6% vs. 94.3%, p < 0.05). CONCLUSION: CEUS achieved an enhanced success rate for sampling and diagnostic accuracy of liver biopsies, especially in FLLs ≥ 5 cm, heterogeneous hypoechoic FLLs, or FLLs with an obscure boundary. CEUS can be used to decrease the number of punctures needed, which might increase the safety of liver biopsy. KEY POINTS: • CEUS can help confirm an adequate biopsy site, increasing the sampling success rate and diagnostic accuracy of the liver biopsy. • CEUS can be used to decrease the number of punctures needed to improve the safety of liver biopsy. • It is recommended to use CEUS guidance for liver biopsies, especially with FLLs ≥ 5 cm, heterogeneous hypoechoic FLLs, or FLLs with an obscure boundary.

Combining conventional ultrasound and sonoelastography to predict axillary status after neoadjuvant chemotherapy for breast cancer.

OBJECTIVE: To determine the ability of conventional ultrasound (US) combined with shear wave elastography (SWE) to reveal axillary status after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: From September 2016 to December 2021, 201 patients with node-positive breast cancer who underwent NAC were enrolled in this prospective study. Conventional US features of axillary lymph nodes and SWE characteristics of breast lesions after NAC were analyzed. The diagnostic performances of US, SWE, and their combination were assessed using multivariate logistic regression and receiver operator characteristic curve (ROC) analyses. RESULTS: The area under the ROC curve (AUC) for the ability of conventional US features to determine axillary status after NAC was 0.82, with a sensitivity of 85.23%, a specificity of 67.39%, and an accuracy of 76.11%. Shear wave velocity (SWV) displayed moderate performance for predicting axilla status after NAC with SWVmean demonstrating an AUC of 0.85. Cortical thickness and shape of axillary nodes and SWVmean of breast tumors were independently associated with axillary nodal metastasis after NAC. Compared to conventional US, the combination of conventional US of axillary lymph nodes with SWE of breast lesions achieved a significantly higher AUC (0.90 vs 0.82, p < 0.01, Delong's test) with a sensitivity of 87.50%, improved specificity of 82.61% and accuracy of 85.00%. CONCLUSIONS: Breast SWE was independently associated with residual metastasis of axillary node after NAC in patients with initially diagnosed positive axilla. Combining SWE with conventional US showed good diagnostic performance for axillary node disease after NAC. KEY POINTS: • Breast SWE can serve as a supplement to axilla US for the evaluation of the axilla after NAC. • The combination of axilla US with breast SWE may be a promising method to facilitate less-invasive treatment in patients receiving NAC.

Association of Acute Kidney Injury During Diabetic Ketoacidosis With Risk of Microalbuminuria in Children With Type 1 Diabetes.

Importance: Diabetic kidney disease is among the most important causes of end-stage kidney disease worldwide. Risk factors for diabetic kidney disease remain incompletely defined. Recent studies document a high frequency of acute kidney injury (AKI) during diabetic ketoacidosis (DKA) in children, raising the question of whether these AKI episodes might contribute to future risk of diabetic kidney disease. Objective: To determine whether episodes of AKI occurring during DKA in children are associated with increased risk of development of microalbuminuria. Design, Setting, and Participants: This retrospective review of medical records included children with type 1 diabetes with 1 or more urine albumin levels measured during routine diabetes care from 2 university-affiliated urban tertiary children's hospitals in the United States from January 2006 to December 2019. Age at diagnosis of diabetes, hemoglobin A1c levels, episodes of DKA, pH and creatinine levels during DKA, and urine albumin and creatinine measurements were analyzed. Cox proportional hazards regression models were used to identify variables affecting the hazard rate for microalbuminuria development. Analyses began January 2021 and ended May 2021. Exposures: Episodes of DKA and episodes of AKI occurring during DKA. Main Outcomes and Measures: AKI occurrence and AKI stage were determined from serum creatinine measurements during DKA using Kidney Disease: Improving Global Outcomes criteria. Microalbuminuria was defined as urine albumin-to-creatinine ratio of 30 mg/g or more or excretion of 30 mg or more of albumin in 24 hours. Results: Of 2345 children, the mean (SD) age at diagnosis was 9.4 (4.4) years. One or more episodes of DKA occurred in 963 children (41%), and AKI occurred during DKA in 560 episodes (47%). In multivariable models adjusting for the associations of age at diagnosis and mean hemoglobin A1c level since diagnosis, each episode of AKI during DKA was associated with a hazard ratio of 1.56 (95% CI, 1.3-1.87) for development of microalbuminuria. Four or more episodes increased the hazard rate by more than 5-fold. DKA episodes without AKI did not significantly increase the hazard rate for microalbuminuria development after adjusting for other covariates. Conclusions and Relevance: These data demonstrate that episodes of AKI occurring during DKA in children with type 1 diabetes are significantly associated with risk of developing microalbuminuria. Greater efforts are necessary to reduce the frequency of DKA.

Clinical Features and Microvascular Complications Risk Factors of Early-onset Type 2 Diabetes Mellitus.

The aim of this research was to study the clinical features and microvascular complications risk factors of early-onset type 2 diabetes mellitus (T2DM). We analyzed the clinical data from 1421 T2DM inpatients at Wuhan Union Hospital. Subjects were divided into early-onset T2DM group (diagnostic age <40 years) and late-onset T2DM group (diagnostic age >40 years). All subjects underwent a standardized assessment of microvascular complications. Data were compared with independent-samples t test or Chi-square test. Multiple logistic regression was used to determine the risk factors of microvascular complications. Patients with early-onset T2DM were more inclined to have a lower systolic blood pressure (SBP), a longer duration of diabetes and higher levels of body mass index (BMI), uric acid (UA), fasting plasma glucose (FPG), total cholesterol (TC)- triglyceride (TG) and glycosylated hemoglobin (HbA1c) than those with late-onset T2DM (P<0.05). The prevalence of diabetic retinopathy (DR) was significantly higher and that of diabetic peripheral neuropathy (DPN) was significantly lower in early-onset group than in late-onset group (P<0.05). For DN, UA was an independent risk factor in early-onset T2DM. SBP and TG were independent risk factors in late-onset T2DM. For DR, duration of diabetes and SBP were independent risk factors in early-onset T2DM. Duration of diabetes, SBP and HbA1c were independent risk factors in late-onset T2DM. This study demonstrated that the clinical characteristics of early-onset T2DM were metabolic disorders, including glucose metabolism, lipid metabolism and amino acid metabolism. Early-onset T2DM was more likely to be associated with DR. The potential pathogenesis of early and late-onset T2DM might be different. The management of metabolic risk factors especially HbA1c, SBP, TG and UA is advised to be performed in the early stage of diabetes.

Induced marine fungus Chondrostereum sp. as a means of producing new sesquiterpenoids chondrosterins I and J by using glycerol as the carbon source.

Chondrostereum sp., a marine fungus isolated from a soft coral Sarcophyton tortuosum, can yield hirsutane framework sesquiterpenoids. However, the metabolites profiles vary dramatically with the composition change of the culture media. This fungus was cultured in a liquid medium containing glycerol as the carbon source, and two new metabolites, chondrosterins I and J (1 and 2), were obtained. Their structures were elucidated primarily based on MS, NMR and X-ray single-crystal diffraction data. By comparison with the known hirsutane sesquiterpenoids, chondrosterins I and J have unique structural features, including a methyl was migrated from C-2 to C-6, and the methyl at C-3 was carboxylated. Compound 2 exhibited potent cytotoxic activities against the cancer cell lines CNE-1 and CNE-2 with the IC50 values of 1.32 and 0.56 µM.