A novel de novo synonymous variant in GREB1L impacts the mRNA splicing associated with aplasia of the urogenital system.

GREB1-like retinoic acid receptor coactivator (GREB1L) gene is associated with autosomal dominant renal hypodysplasia/aplasia 3 (RHDA3) and deafness, autosomal dominant 80 (DFNA80). Among the GREB1L variants reported, most of them are missense or frameshift, while no pathogenic synonymous variants have been recorded. Classical theory paid little attention to synonymous variants and classified it as nonpathogenic; however, recent studies suggest that the variants might be equally important. Here, we report a 7-year-old girl with new symptoms of clitoromegaly, uterovaginal, and ovarian agenesis as well as right kidney missing. A novel de novo GREB1L synonymous variant (NM_001142966: c.4731C>T, p.G1577=) was identified via whole exome sequencing. The variant was predicted to be disease-causing through in silico analysis and was classified as likely pathogenic. Minigene splicing assays confirmed a 6 bp deletion in mutant cDNA comparing with the wild type, leading to two amino acids lost in GREB1L protein. Secondary and tertiary structure modeling showed alterations in protein structure. Our finding reveals a novel GREB1L variant with a new phenotype of urogenital system and is the first to report a pathogenic synonymous variant in GREB1L which affects mRNA splicing, suggesting synonymous variants cannot be ignored in prenatal diagnosis and genetic counseling.

Association between severity of nonalcoholic fatty liver disease and major adverse cardiovascular events in patients assessed by coronary computed tomography angiography.

BACKGROUND: The effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear. METHODS: A total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan-Meier analysis were used to assess poor prognosis. RESULTS: During the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54-5.66]; p = 0.001) and CAD-RADS categories 3-5 (HR = 16.31[6.34-41.92]; p < 0.001) were independent risk factors for MACEs. The Kaplan-Meier analysis showed that moderate to severe NAFLD patients had a worsen prognosis than mild NAFLD patients (log-rank p < 0.001). Moreover, the combined receiver operating characteristic curve of the severity of NAFLD and CAD-RADS category showed a good predicting performance for the risk of MACEs, with an area under the curve of 0.849 (95% CI = 0.786-0.911). CONCLUSION: The severity of NAFLD was independent risk factor for MACEs in patients with obstructive CAD, having CAD-RADS 3-5 categories on CCTA.

[Application of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency].

OBJECTIVE: To explore the value of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency (PID). METHODS: Clinical data was collected from four couples with a childbearing history of PID who had sought genetic counseling and undergone genetic testing at Henan Provincial People's Hospital from February 2017 to December 2021. Whole exome sequencing (WES) was performed on both partners of each couple, and candidate variants were validated by Sanger sequencing and fluorescent quantitative PCR. Prenatal diagnosis was conducted on fetuses of these couples after confirming the variants. RESULTS: A total of six variants were detected in four genes including IL2RG, BTK, CYBB, and DUOX2. Among these, the c.1265G>A and c.3329G>A variants of the DUOX2 gene and the c.676C>T variant of the IL2RG gene were previously known as pathogenic variants. On the other hand, the Exon5_8del variant of the IL2RG gene, the c.184_185delAC variant of the BTK gene, and the c.472A>T variant of the CYBB gene were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the IL2RG: Exon5_8del, BTK: c.184_185delAC and CYBB: c.472A>T variants were classified as likely pathogenic (PVS1+PM2_Supporting+PP4).Prenatal diagnosis was conducted for three couples during their subsequent pregnancies, and the results revealed that the fetuses had the wild-type genotypes at the c.184_185 position of the BTK gene, the c.472 position of the CYBB gene, and the c.676 position of the IL2RG gene. Follow-up examinations one year after birth has found no abnormality in the infants. CONCLUSION: WES is an important tool to infer and analyze the carrier status for couples who had given births to children died of PID and improve the positive detection rate.

The Effect of Metabolic Syndrome on Colorectal Cancer Prognosis after Primary Surgery.

PURPOSE: The purpose of this study was to explore whether metabolic syndrome (MetS) affects the prognosis of colorectal cancer (CRC) patients after primary surgery and to analyze the effect of the specific components of MetS on CRC prognosis. METHODS: The PubMed, Embase and Cochrane Library databases were searched from inception to July 29, 2021. Overall survival (OS) and disease-free survival (DFS) were compared between the MetS group and the non-MetS group. RESULTS: The studies included in the meta-analysis included 4773 patients. All seven studies compared OS between the two groups, and after pooling all hazard ratios (HRs), no significant difference was found between the MetS group and the non-MetS group (HR = 1.17, 95% CI = 0.91 to 1.49, P = 0.21). Four studies compared DFS between the MetS group and the non-MetS group after pooling all the HRs, and there was no difference between the MetS group and the non-MetS group (HR = 1.05, 95% CI = 0.74 to 1.49, P = 0.21). Among the specific components of MetS, high fasting plasma glucose levels (HR = 1.25, 95% CI = 1.00 to 1.58, P = 0.05) had a marginally significant association with poor OS. CONCLUSION: MetS may not affect the prognosis of CRC after primary surgery. However, high fasting plasma glucose levels might contribute to poor OS.

The Effect of Bilirubin on Clinical Outcomes of Patients With Colorectal Cancer Surgery: A Ten-Year Volume Single-Center Retrospective Study.

The current study aimed to evaluate the effect of bilirubin on the outcomes of colorectal cancer (CRC) in patients who underwent radical CRC surgery. The levels of serum bilirubin, including total bilirubin (TBil), direct bilirubin (DBil) and indirect bilirubin (IBil), were divided into higher groups and lower groups according to the median. Multivariate logistic regression was performed to analyze the independent predictors for overall complications and major complications. For TBil, the hospitalization time of the higher TBil group was longer than that of the lower TBil group (p = 0.014 < 0.05). For DBil, the higher DBil group had longer operation times (p < 0.01), more intraoperative bleeding (p < 0.01), longer hospital stays (p < 0.01), and higher rates of overall complications (p < 0.01) and major complications (p = 0.021 < 0.05) than the lower DBil group. For the IBil group, blood loss during operation (p < 0.01) and hospital stays (p = 0.041 < 0.05) in the higher IBil group were lower than those in the lower IBil group. In terms of complications, we found that DBil was an independent predictor for overall complications (p < 0.01, OR = 1.036, 95% CI = 1.014-1.058) and major complications (p = 0.043, HR= 1.355, 95% CI= 1.009-1.820). Higher preoperative DBil increase the risk of complications after primary CRC surgery.

Two nomograms based on radiomics models using triphasic CT for differentiation of adrenal lipid-poor benign lesions and metastases in a cancer population: an exploratory study.

OBJECTIVES: To investigate the effectiveness of CT-based radiomics nomograms in differentiating adrenal lipid-poor benign lesions and metastases in a cancer population. METHODS: This retrospective study enrolled 178 patients with cancer history from three medical centres categorised as those with adrenal lipid-poor benign lesions or metastases. Patients were divided into training, validation, and external testing cohorts. Radiomics features were extracted from triphasic CT images (unenhanced, arterial, and venous) to establish three single-phase models and one triphasic radiomics model using logistic regression. Unenhanced and triphasic nomograms were established by incorporating significant clinico-radiological factors and radscores. The models were evaluated by the receiver operating characteristic curve, Delong's test, calibration curve, and decision curve. RESULTS: Lesion side, diameter, and enhancement ratio resulted as independent factors and were selected into nomograms. The areas under the curves (AUCs) of unenhanced and triphasic radiomics models in validation (0.878, 0.914, p = 0.381) and external testing cohorts (0.900, 0.893, p = 0.882) were similar and higher than arterial and venous models (validation: 0.842, 0.765; testing: 0.814, 0.806). Unenhanced and triphasic nomograms yielded similar AUCs in validation (0.903, 0.906, p = 0.955) and testing cohorts (0.928, 0.946, p = 0.528). The calibration curves showed good agreement and decision curves indicated satisfactory clinical benefits. CONCLUSION: Unenhanced and triphasic CT-based radiomics nomograms resulted as a useful tool to differentiate adrenal lipid-poor benign lesions from metastases in a cancer population. They exhibited similar predictive efficacies, indicating that enhanced examinations could be avoided in special populations. KEY POINTS: • All four radiomics models and two nomograms using triphasic CT images exhibited favourable performances in three cohorts to characterise the cancer population's adrenal benign lesions and metastases. • Unenhanced and triphasic radiomics models had similar predictive performances, outperforming arterial and venous models. • Unenhanced and triphasic nomograms also exhibited similar efficacies and good clinical benefits, indicating that contrast-enhanced examinations could be avoided when identifying adrenal benign lesions and metastases.

Nomogram Using CT Radiomics Features for Differentiation of Pneumonia-Type Invasive Mucinous Adenocarcinoma and Pneumonia: Multicenter Development and External Validation Study.

BACKGROUND. Pneumonia-type invasive mucinous adenocarcinoma (IMA) and pneumonia show overlapping chest CT features as well as overlapping clinical characteristics. OBJECTIVE. The purpose of our study was to develop and validate a nomogram combining clinical and CT-based radiomics features to differentiate pneumonia-type IMA and pneumonia. METHODS. This retrospective study included 314 patients (172 men, 142 women; mean age, 60.3 ± 14.5 [SD] years) from six hospitals who underwent noncontrast chest CT showing consolidation and were diagnosed with pneumonia-type IMA (n = 106) or pneumonia (n = 208). Patients from three hospitals formed a training set (n = 195) and a validation set (n = 50), and patients from the other three hospitals formed the external test set (n = 69). A model for predicting pneumonia-type IMA was built using clinical characteristics that were significant independent predictors of this diagnosis. Radiomics features were extracted from CT images by placing ROIs on areas of consolidation, and a radiomics signature of pneumonia-type IMA was constructed. A nomogram for predicting pneumonia-type IMA was constructed that combined features in the clinical model and the radiomics signature. Two cardiothoracic radiologists independently reviewed CT images in the external test set to diagnose pneumonia-type IMA. Diagnostic performance was compared among models and radiologists. Decision curve analysis (DCA) was performed. RESULTS. The clinical model included fever and family history of lung cancer. The radiomics signature included 15 radiomics features. DCA showed higher overall net benefit from the nomogram than from the clinical model. In the external test set, AUC was higher for the nomogram (0.85) than for the clinical model (0.71, p = .01), radiologist 1 (0.70, p = .04), and radiologist 2 (0.67, p = .01). In the external test set, the nomogram had sensitivity of 46.9%, specificity of 94.6%, and accuracy of 72.5%. CONCLUSION. The nomogram combining clinical variables and CT-based radiomics features outperformed the clinical model and two cardiothoracic radiologists in differentiating pneumonia-type IMA from pneumonia. CLINICAL IMPACT. The findings support potential clinical use of the nomogram for diagnosing pneumonia-type IMA in patients with consolidation on chest CT.

CT-based radiomics nomogram for differentiation of adrenal hyperplasia from lipid-poor adenoma: an exploratory study.

BACKGROUND: To establish and verify a radiomics nomogram for differentiating isolated micronodular adrenal hyperplasia (iMAD) from lipid-poor adenoma (LPA) based on computed tomography (CT)-extracted radiomic features. METHODS: A total of 148 patients with iMAD or LPA were divided into three cohorts: a training cohort (n = 72; 37 iMAD and 35 LPA), a validation cohort (n = 36; 22 iMAD and 14 LPA), and an external validation cohort (n = 40; 20 iMAD and 20 LPA). Radiomics features were extracted from contrast-enhanced and non-contrast CT images. The least absolute shrinkage and selection operator (LASSO) method was applied to develop a triphasic radiomics model and unenhanced radiomics model using reproducible radiomics features. A clinical model was constructed using certain laboratory variables and CT findings. Radiomics nomogram was established by selected radiomics signature and clinical factors. Nomogram performance was assessed by calibration curve, the areas under receiver operating characteristic curves (AUC), and decision curve analysis (DCA). RESULTS: Eleven and eight extracted features were finally selected to construct an unenhanced radiomics model and a triphasic radiomics model, respectively. There was no significant difference in AUC between the two models in the external validation cohort (0.838 vs. 0.843, p = 0.949). The radiomics nomogram inclusive of the unenhanced model, maximum diameter, and aldosterone showed the AUC of 0.951, 0.938, and 0.893 for the training, validation, and external validation cohorts, respectively. The nomogram showed good calibration, and the DCA demonstrated the superiority of the nomogram compared with the clinical factors model alone in terms of clinical usefulness. CONCLUSIONS: A radiomics nomogram based on unenhanced CT images and clinical variables showed favorable performance for distinguishing iMAD from LPA. In addition, an efficient unenhanced model can help avoid extra contrast-enhanced scanning and radiation risk.

MRI-based radiomics nomogram for differentiation of solitary metastasis and solitary primary tumor in the spine.

BACKGROUND: Differentiating between solitary spinal metastasis (SSM) and solitary primary spinal tumor (SPST) is essential for treatment decisions and prognosis. The aim of this study was to develop and validate an MRI-based radiomics nomogram for discriminating SSM from SPST. METHODS: One hundred and thirty-five patients with solitary spinal tumors were retrospectively studied and the data set was divided into two groups: a training set (n = 98) and a validation set (n = 37). Demographics and MRI characteristic features were evaluated to build a clinical factors model. Radiomics features were extracted from sagittal T1-weighted and fat-saturated T2-weighted images, and a radiomics signature model was constructed. A radiomics nomogram was established by combining radiomics features and significant clinical factors. The diagnostic performance of the three models was evaluated using receiver operator characteristic (ROC) curves on the training and validation sets. The Hosmer-Lemeshow test was performed to assess the calibration capability of radiomics nomogram, and we used decision curve analysis (DCA) to estimate the clinical usefulness. RESULTS: The age, signal, and boundaries were used to construct the clinical factors model. Twenty-six features from MR images were used to build the radiomics signature. The radiomics nomogram achieved good performance for differentiating SSM from SPST with an area under the curve (AUC) of 0.980 in the training set and an AUC of 0.924 in the validation set. The Hosmer-Lemeshow test and decision curve analysis demonstrated the radiomics nomogram outperformed the clinical factors model. CONCLUSIONS: A radiomics nomogram as a noninvasive diagnostic method, which combines radiomics features and clinical factors, is helpful in distinguishing between SSM and SPST.

The advanced lung cancer inflammation index is a prognostic factor for gastrointestinal cancer patients undergoing surgery: a systematic review and meta-analysis.

BACKGROUND: The advanced lung cancer inflammation index (ALI) is a comprehensive assessment indicator that can reflect inflammation and nutrition conditions. However, there are some controversies about whether ALI is an independent prognostic factor for gastrointestinal cancer patients undergoing surgical resection. Thus, we aimed to clarify its prognostic value and explore the potential mechanisms. METHODS: Four databases including PubMed, Embase, the Cochrane Library, and CNKI were used for searching eligible studies from inception to June 28, 2022. All gastrointestinal cancers, including colorectal cancer (CRC), gastric cancer (GC), esophageal cancer (EC), liver cancer, cholangiocarcinoma, and pancreatic cancer were enrolled for analysis. We focused on prognosis most in the current meta-analysis. Survival indicators, including overall survival (OS), disease-free survival (DFS), and cancer-special survival (CSS) were compared between the high ALI group and the low ALI group. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was submitted as a supplementary document. RESULTS: We finally included fourteen studies involving 5091 patients in this meta-analysis. After pooling the hazard ratios (HRs) and 95% confidence intervals (CIs), ALI was found to be an independent prognostic factor for both OS (HR = 2.09, I2 = 92%, 95% CI = 1.53 to 2.85, P < 0.01), DFS (HR = 1.48, I2 = 83%, 95% CI = 1.18 to 1.87, P < 0.01), and CSS (HR = 1.28, I2 = 1%, 95% CI = 1.02 to 1.60, P = 0.03) in gastrointestinal cancer. After subgroup analysis, we found that ALI was still closely related to OS for CRC (HR = 2.26, I2 = 93%, 95% CI = 1.53 to 3.32, P < 0.01) and GC (HR = 1.51, I2 = 40%, 95% CI = 1.13 to 2.04, P = 0.006) patients. As for DFS, ALI also has a predictive value on the prognosis of CRC (HR = 1.54, I2 = 85%, 95% CI = 1.14 to 2.07, P = 0.005) and GC (HR = 1.37, I2 = 0%, 95% CI = 1.09 to 1.73, P = 0.007) patients. CONCLUSION: ALI affected gastrointestinal cancer patients in terms of OS, DFS, and CSS. Meanwhile, ALI was a prognostic factor both for CRC and GC patients after subgroup analysis. Patients with low ALI had poorer prognoses. We recommended that surgeons should perform aggressive interventions in patients with low ALI before the operation.

Phylogenomics, plastome structure and species identification in Mahonia (Berberidaceae).

BACKGROUND: Elucidating the phylogenetic relationships within species-rich genera is essential but challenging, especially when lineages are assumed to have been going through radiation events. Mahonia Nutt. (Berberidaceae) is a genus with cosmopolitan distribution, comprising approximately 100 species, two of which are known as Caulis Mahoniae (M. bealei and M. fortunei) with crucial pharmacological significance in Chinese herbal medicine. Mahonia is a taxonomically challenging genus, and intrageneric phylogenetic relationships still need to be explored using genome data. Universal DNA barcodes and floral morphological attributes have limited discriminatory power in Mahonia. RESULTS: We sequenced 17 representative plastomes and integrated three published plastome data together to conduct comparative and phylogenetic analyses. We found that Mahonia and Berberis share a large IR expansion (~ 12 kb), which is recognized as a typical character of Berberideae. Repeated sequences are revealed in the species of Mahonia, which are valuable for further population genetic studies. Using a comparative plastome analysis, we determined eight hypervariable regions whose discriminative power is comparable to that of the whole plastid genomes. The incongruence of the ITS and the plastome tree topologies may be ascribed to ancestral hybridization events and/or to incomplete lineage sorting. In addition, we suggest that leaf epidermal characters could help to distinguish closely related species in Mahonia. CONCLUSIONS: We propose an integrative approach combining special barcodes and micromorphological traits to circumscribe Mahonia species. The results cast a new light on the development of an integrative method for accurate species circumscription and provide abundant genetic resources for further research on Mahonia.

Preoperative hypokalemia can increase complications after colorectal cancer surgery: a propensity score matching analysis.

BACKGROUND: Whether hypokalemia can affect the short-term outcomes of CRC patients after radical surgery remains unclear. The purpose of this study was to investigate the impact of preoperative hypokalemia on the short-term outcomes for colorectal cancer (CRC) patients who underwent radical CRC surgery using propensity score matching (PSM). METHODS: We retrospectively enrolled consecutive CRC patients from Jan 2011 to Dec 2021 in a single-center hospital. Hypokalemia was defined as a serum potassium concentration < 3.5 mmol/L. The short-term outcomes were compared between the hypokalemia group and the normal blood potassium group. In addition, univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for overall complications. RESULTS: A total of 6183 CRC patients who underwent radical surgery were included in this study, of whom 390 (6.3%) patients were diagnosed with hypokalemia before surgery. After 1:1 ratio PSM, there were 390 patients in the hypokalemia group and in the normal potassium group. No significant difference was found between the two groups after PSM in terms of baseline information (p > 0.05). Regarding short-term outcomes, the hypokalemia group had a longer hospital stay (p = 0.028), a higher proportion of overall complications (p = 0.048) and a higher incidence of postoperative pneumonia (p = 0.008) after PSM. Moreover, hypokalemia (p = 0.036, OR = 1.291, 95% CI = 1.017-1.639) was an independent risk factor for overall complications. CONCLUSION: Preoperative hypokalemia could increase complications after CRC surgery and prolong the hospital stay. Moreover, preoperative hypokalemia was an independent risk factor for overall complications.

Higher body mass index was associated with better prognosis in diabetic patients with stage II colorectal cancer.

PURPOSE: The purpose of this study is to analyze the effect of body mass index (BMI) on patients with concurrent colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM). METHODS: Patients who underwent primary radical CRC surgery from Jan 2011 to Jan 2020 were retrospectively collected. The perioperative information, overall survival (OS) and disease-free survival (DFS) were compared between the higher BMI group and the lower BMI group. RESULTS: A total of 574 patients with concurrent CRC and T2DM were included in this study. The higher BMI group had higher portion of hypertension (p < 0.01) and coronary heart disease (CHD) (p < 0.01). Furthermore, the higher BMI group had better OS (p = 0.016) and DFS (p = 0.040) than the lower BMI group in stage II CRC. In multivariate analysis, age (OS: p = 0.002, HR = 2.016, 95% CI = 1.307-3.109/ DFS: p = 0.003, HR = 1.847, 95% CI = 1.230-2.772), TNM stage (OS: p < 0.01, HR = 1.667, 95% CI = 1.281-2.169/ DFS: p = 0.001, HR = 1.545, 95% CI = 1.207-1.977), overall complications (OS: p = 0.004, HR = 1.837, 95% CI = 1.218-2.880/ DFS: p = 0.006, HR = 1.783, 95% CI = 1.184-2.686) and major complications (OS: p = 0.005, HR = 2.819, 95% CI = 1.376-5.774/ DFS: p = 0.014, HR = 2.414, 95% CI = 1.196-4.870) were independent factors of OS and DFS. Moreover, BMI (p = 0.019, HR = 0.413, 95% CI = 0.197-0.864) was an independent factor of OS in stage II CRC. CONCLUSION: Higher BMI was associated with better OS in diabetic patients with stage II CRC.

The short-term and oncologic outcomes of younger VS older colorectal cancer patients undergoing primary surgery: a propensity score matching analysis.

PURPOSE: The purpose of the current study is to analyze the difference of short-term and oncologic outcomes between younger and older colorectal cancer (CRC) patients who underwent primary CRC surgery using a propensity score matching (PSM) analysis. METHODS: We retrospectively collected CRC patients who underwent primary surgery in a single clinical database from Jan 2011 to Jan 2020. The short-term and oncologic outcomes were compared between younger aged group and older aged group. RESULTS: A total of 4599 patients were included in this study, and there were 4196 patients in older aged group and 403 patients in younger aged group. After 1:1 ratio PSM, there were 401 patients in each group. No significant difference was found in terms of baseline information after PSM (p>0.05). Younger aged group had larger retrieved lymph nodes before (p<0.001) and after PSM (p=0.001) than older aged group. In multivariate analysis, younger age was an independent predictor of better overall survival (OS) (p<0.001, HR=2.303, 95% CI=1.658-3.199) and disease-free survival (DFS) (p=0.008, HR=1.425, 95% CI=1.098-1.850). In terms of different tumor stage after PSM, younger aged group had better OS than older group in stage II (p<0.001) and stage IV (p=0.028) CRC, and younger aged group had better DFS than older group in stage II (p=0.016) CRC. CONCLUSION: Younger CRC patients had larger retrieved lymph nodes and better prognosis than older CRC patients after primary CRC surgery.

Comparison of surgical and oncologic outcomes in very elderly patients (≥ 80 years old) and elderly (65-79 years old) colorectal cancer patients: a propensity score matching.

PURPOSE: The purpose of this study was to investigate the short-term outcomes and prognosis of elderly and very elderly colorectal cancer (CRC) patients after primary CRC surgery using propensity score matching (PSM). METHODS: This study retrospectively collected the medical records of CRC patients ≥ 65 years old undergoing primary CRC surgery from Jan 2011 to Jan 2020. Short-term outcomes, overall survival (OS) and disease-free survival (DFS) were compared between very elderly CRC patients (≥ 80 years old) and elderly CRC patients (65-79 years old). RESULTS: A total of 2084 patients were enrolled for analysis. After PSM, 331 very elderly patients were matched to 331 elderly patients. In terms of short-term outcomes, the very elderly patients had longer postoperative hospital stays (p = 0.007) after PSM. In terms of OS, it was found that age (p < 0.01, HR = 1.878, 95% CI 1.488-2.371), tumor stage (p < 0.01, HR = 1.865, 95% CI 1.603-2.170), overall complications (p < 0.01, HR = 1.514, 95% CI 1.224-1.872) and major complications (p = 0.001, HR = 2.012, 95% CI 1.319-3.069) were independent prognostic factors. For DFS, age (p < 0.01, HR = 1.816, 95% CI 1.579-2.088), tumor stage (p < 0.01, HR = 1.816, 95% CI 1.579-2.088), overall complications (p = 0.002, HR = 1.379, 95% CI 1.128-1.685) and major complications (p = 0.002, HR = 1.902, 95% CI 1.259-2.874) were found to be independent prognostic factors. Moreover, elderly patients had a better OS and DFS than very elderly patients. CONCLUSION: Very elderly patients had a poorer prognosis than elderly patients after primary CRC surgery. Surgeons should be cautious when treating very elderly CRC patients.

Predictors associated with planned and unplanned admission to intensive care units after colorectal cancer surgery: a retrospective study.

PURPOSE: The purpose of the current study is to identify the predictors of planned and unplanned admission to intensive care units (ICU) after colorectal cancer (CRC) surgery. METHODS: We retrospectively collected CRC patients' information from January 2016 to June 2021 in a single clinical center. The predictors of planned and unplanned admission to ICU after CRC surgery were analyzed. RESULTS: A total of 4263 patients were included in this study and there were 349 (8.2%) CRC patients who were admitted to ICU. There were 34 (9.7%) CRC patients in unplanned ICU admission group and 315 (90.3%) CRC patients in planned ICU admission group. Older age (p < 0.01, OR = 1.093, 95% CI = 1.079-1.108), male (p = 0.013, OR = 0.721, 95% CI = 0.557-0.933), lower body mass index (BMI) (p = 0.001, OR = 0.932, 95% CI = 0.896-0.971), type 2 diabetes mellitus (T2DM) (p = 0.035, OR = 1.422, 95% CI = 1.024-1.975), coronary heart disease (CHD) (p = 0.036, OR = 1.579, 95% CI = 1.031-2.420), colon cancer (p = 0.002, OR = 1.475, 95% CI = 1.149-1.894), advanced tumor stage (p = 0.003, OR = 1.265, 95% CI = 1.082-1.478), longer operation time (p = 0.005, OR = 1.002, 95% CI = 1.001-1.003), and larger blood loss (p < 0.01, OR = 1.002, 95% CI = 1.001-1.002) were independent predictors of planned ICU admission. Older age (p < 0.01, OR = 1.062, 95% CI = 1.029-1.097) and longer operation time (p = 0.003, OR = 1.004, 95% CI = 1.001-1.007) were independent predictors of unplanned ICU admission. CONCLUSION: Cautions should be paid for CRC patients with predictive factors to avoid unnecessary ICU admission.

Does temporary ileostomy via specimen extraction site affect the short outcomes and complications after laparoscopic low anterior resection in rectal cancer patients? A propensity score matching analysis.

PURPOSE: The purpose of the current study was to compare the outcomes of temporary stoma through the specimen extraction site (SSES) and stoma through a new site (SNS) after laparoscopic low anterior resection. METHODS: The rectal cancer patients who underwent laparoscopic low anterior resection plus temporary ileostomy were recruited in a single clinical database from Jun 2013 to Jun 2020. The SSES group and the SNS group were compared using propensity score matching (PSM) analysis. RESULTS: A total of 257 rectal cancer patients were included in this study, there were 162 patients in the SSES group and 95 patients in the SNS group. After 1:1 ratio PSM, there was no difference in baseline information (p > 0.05). The SSES group had smaller intraoperative blood loss (p = 0.016 < 0.05), shorter operation time (p < 0.01) and shorter post-operative hospital stay (p = 0.021 < 0.05) than the SNS group before PSM. However, the SSES group shorter operation time (p = 0.006 < 0.05) than the SNS group after PSM, moreover, there was no significant difference in stoma-related complications (p > 0.05). In the multivariate analysis, longer operation time was an independent factor (p = 0.019 < 0.05, OR = 1.006, 95% CI = 1.001-1.011) for the stoma-related complications. CONCLUSION: Based on the current evidence, the SSES group had smaller intraoperative blood loss, shorter operation time and shorter post-operative hospital stay before PSM, and shorter operation time after PSM. Therefore, SSES might be superior than SNS after laparoscopic low anterior resection for rectal cancer patients.

[Analysis of a Chinese pedigree affected with dyschromatosis symmetrica hereditaria due to a novel variant of ADAR gene].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree. RESULTS: The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual. CONCLUSION: The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.

[Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with Usher syndrome due to novel compound heterozygous variants of PCDH15 gene].

OBJECTIVE: To analyze the clinical features and genetic variant in a patient with Usher syndrome. METHODS: Whole exome sequencing was carried out for the patient. Suspected variants were validated by Sanger sequencing of her parents and fetus. RESULTS: The proband was found to harbor compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene (NM_033056), which were respectively inherited from her father and mother. The same variants were not detected in 100 healthy controls. Based on the guidelines of the American Society of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2+PP4). By prenatal diagnosis, her fetus was found to carry the c.4095_4096insA variant. After birth, the child has passed neonatal hearing screening test, and no abnormal auditory and visual function was found after the first year. CONCLUSION: The compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene probably underlay the Usher syndrome is this proband.

Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study.

BACKGROUND: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).