Development and external validation of a novel nomogram for screening Chinese Lynch syndrome: based on a multicenter, population study

Background: This multicenter study aimed to reveal the genetic spectrum of colorectal cancer (CRC) with deficient mismatch repair (dMMR) and build a screening model for Lynch syndrome (LS). Methods: Through the immunohistochemical (IHC) screening of mismatch repair protein results in postoperative CRC patients, 311 dMMR cases, whose germline and somatic variants were detected using the ColonCore panel, were collected. Univariate and multivariate logistic regression analysis was performed on the clinical characteristics of these dMMR individuals, and a clinical nomogram, incorporating statistically significant factors identified using multivariate logistic regression analysis, was constructed to predict the probability of LS. The model was validated externally by an independent cohort. Results: In total, 311 CRC patients with IHC dMMR included 95 identified MMR germline variant (LS) cases and 216 cases without pathogenic or likely pathogenic variants in MMR genes (non-Lynch-associated dMMR). Of the 95 individuals, approximately 51.6%, 28.4%, 14.7%, and 5.3% cases carried germline MLH1, MSH2, MSH6, and PMS2 pathogenic or likely pathogenic variants, respectively. A novel nomogram was then built to predict the probability of LS for CRC patients with dMMR intuitively. The receiver operating characteristic (ROC) curve informed that this nomogram-based screening model could identify LS with a higher specificity and sensitivity with an area under curve (AUC) of 0.87 than current screening criteria based on family history. In the external validation cohort, the AUC of the ROC curve reached 0.804, inferring the screening model’s universal applicability. We recommend that dMMR-CRC patients with a probability of LS greater than 0.435 should receive a further germline sequencing. Conclusion: This novel screening model based on the clinical characteristic differences between LS and non-Lynch-associated dMMR may assist clinicians to preliminarily screen LS and refer susceptible patients to experienced specialists.

Download Full-text

Confirmatory germline testing for presumed germline pathogenic variants using tumor-only testing.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e22524 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e22524-e22524

Author(s):

Tomohiro Kondo ◽

Takahiro Yamada ◽

Masahiro Yoshioka ◽

Masakazu Nishigaki ◽

Yoshihiro Yamamoto ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Logistic Regression Analysis ◽

Multivariate Logistic Regression Analysis ◽

Tumor Board ◽

Genomic Profiling ◽

Multivariate Logistic Regression ◽

Pathogenic Variants ◽

Comprehensive Genomic Profiling ◽

Germline Testing

e22524 Background: Presumed germline pathogenic variants (PGPVs) can be detected in tumor tissues using comprehensive genomic profiling. Clinicians and patients can decide whether to conduct confirmatory germline testing or not. However, the promoting and obstructive factors for confirmatory germline testing are unclear. Methods: This single institutional retrospective study aimed to identify factors related to confirmatory germline testing in patients with PGPVs. Between April 2015 and April 2019, 270 consecutive patients with cancers of unknown primary site, rare tumors, or solid tumors refractory to standard chemotherapy, who underwent tumor-only comprehensive genomic profiling were reviewed. PGPVs were proposed to be disclosed as variants to the patients by our institutional molecular tumor board. Univariate logistic regression analysis was conducted to investigate the relationship between each patient’s characteristics and confirmatory germline testing. Factors showing a statistical relationship (p < 0.10 in univariate analyses) were included in multivariate logistic regression analysis with a backward selection of variables. Statistical significance was set at p < 0.05. Results: Of the 270 patients who underwent tumor-only comprehensive genomic profiling, 77 possessed PGPVs. The most common PGPVs were TP53 (n = 56), APC (n = 9), PTEN (n = 7), RB1 (n = 6), and BRCA2 (n = 6). Among the 77 patients, only 11 (14.3%) chose to undergo confirmatory germline testing. Multivariate logistic regression analysis revealed that the person disclosing the results (experienced oncologists with knowledge of cancer genome medicine vs. others, odds ratio [OR]: 27.7, 95% confidence interval [CI]: 4.60–167) and study period (OR: 0.110, 95% CI: 0.015–0.787) were independently and significantly associated with confirmatory germline testing. Conclusions: These findings indicate that fostering genomic competency in oncologists and collaborating with genetic experts would facilitate cancer patients and their families to receive genetic medical services in the process of cancer genomic profiling.

Download Full-text

The association between hypoglycemia and glycemic variability in elderly patients with type 2 diabetes: cross-sectional study

10.21203/rs.3.rs-128672/v1 ◽

2020 ◽

Author(s):

Takahisa Handa ◽

Akinobu Nakamura ◽

Aika Miya ◽

Hiroshi Nomoto ◽

Hiraku Kameda ◽

...

Keyword(s):

Type 2 Diabetes ◽

Logistic Regression ◽

Regression Analysis ◽

Elderly Patients ◽

Logistic Regression Analysis ◽

Roc Curve ◽

Multivariate Logistic Regression Analysis ◽

Glycemic Variability ◽

Multivariate Logistic Regression

Abstract BackgroundThis study aimed to explore predictive factors of time below target glucose range (TBR) ≥ 1% among patients’ characteristics and glycemic variability (GV) indices using continuous glucose monitoring data in elderly patients with type 2 diabetes.MethodsWe conducted a prospective observational study on 179 (71 female) Japanese outpatients with type 2 diabetes aged ≥ 65 years. The characteristics of the participants with TBR ≥ 1% were evaluated by multivariate logistic regression analysis. Receiver-operating characteristic (ROC) curve analyses of GV indices, comprising coefficient of variation (CV), standard deviation, and mean amplitude of glycemic excursions, were performed to identify the optimal index for the identification of patients with TBR ≥ 1%.ResultsIn the multivariate logistic regression analysis, none of the clinical characteristics, including HbA1c and C-peptide index, were independent markers for TBR ≥ 1%, while all three GV indices showed significant associations with TBR ≥ 1%. Among the three GV indices, CV showed the best performance based on the area under the curve in the ROC curve analyses.ConclusionsAmong elderly patients with type 2 diabetes, CV reflected TBR ≥ 1% most appropriately among the GV indices examined.Trial registration: UMIN-CTR: UMIN000029993. Registered 16 November 2017

Download Full-text

Serum Interleukin-33 is a Predictor of Depression in Patients with Acute Ischemic Stroke

Current Neurovascular Research ◽

10.2174/1567202617999210101223635 ◽

2021 ◽

Vol 17 ◽

Author(s):

Zhenlei Chen ◽

Rongrong Zhang ◽

Yanping Wu ◽

Qing Fu ◽

Xinyue Qin

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Ischemic Stroke ◽

Roc Curve ◽

Independent Predictor ◽

Multivariate Logistic Regression Analysis ◽

Multivariate Logistic Regression ◽

Prognosis Factor ◽

Interleukin 33

Objective: The study aimed to investigate the relationship between serum interleukin-33 (IL-33) concentrations and poststroke depression (PSD) in patients with acute ischemic stroke (AIS). Methods: Serum IL-33 concentrations were determined using an enzyme-linked immunosorbent assay. Patients were assigned to the PSD group after a six-month follow-up if their score on the 17- item Hamilton Rating Scale for Depression was ≥7 or to the non-PSD group if their score was <7. IL-33 was used to predict the risk of PSD using multivariate logistic regression analysis, while a receiver operating characteristic (ROC) curve was used to analyze the accuracy of PSD prediction. In addition, the modified Rankin scale (mRS) was used for follow-up scoring six months after disease onset. Results: A total of 151 AIS patients and 40 healthy controls were included in this study. ROC curve results showed that the area under the curve was 0.684 (95% confidence interval: 0.594-0.774,Ρ=0.001) for IL-33 as a predictor of PSD. When the IL-33 concentration was ≤71.85 ng/L, prediction sensitivity and specificity were 77.5% and 57.3%, respectively. Multivariate logistic regression analysis showed that IL-33 concentration of ≤71.85 ng/L was an independent predictor of PSD (95% CI: 1.129-7.515, P=0.027). The follow-up mRS data showed that serum IL-33 is a protective prognosis factor in patients with AIS (95% CI: 0.954-0.997, P=0.024). Conclusions: Serum IL-33 is an independent predictor of PSD and a protective prognosis factor in patients with AIS.

Download Full-text

Predictive Value of a Noninvasive Serological Hepatic Fibrosis Scoring System in Cirrhosis Combined with Oesophageal Varices

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2018/7671508 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6

Author(s):

Feiyue Zhang ◽

Tong Liu ◽

Pan Gao ◽

Sujuan Fei

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Hepatic Fibrosis ◽

Roc Curve ◽

Predictive Value ◽

Scoring System ◽

Multivariate Logistic Regression Analysis ◽

Scoring Systems ◽

Oesophageal Varices ◽

Multivariate Logistic Regression

Objective. In recent years, the noninvasive serological scoring system has become a research hotspot in predicting hepatic fibrosis and has achieved good results. However, it has rarely been applied to the prediction of oesophageal varices. The aim of the study was to evaluate the predictive value of the four following scoring systems in cirrhosis combined with oesophageal varices: aspartate and platelet ratio index (APRI), aspartate aminotransferase-alanine aminotransferase ratio (AAR), FIB-4, and S index. Methods. A total of 153 patients with cirrhosis were categorized into groups with or without oesophageal varices. In addition, cirrhosis patients with oesophageal varices were further divided into mild, moderate, and severe grades. The rank sum test was used to compare the significant differences of APRI, AAR, FIB-4, and S index between the two groups of cirrhosis patients with or without oesophageal varices. A ROC curve was generated to compare the area under the curve of the three groups and to obtain the corresponding optimal prediction value. Moreover, multivariate logistic regression analysis was employed to assess the predictive factors for cirrhosis combined with oesophageal varices. Results. 44 patients had no oesophageal varices and 108 patients had oesophageal varices. Of the 108 patients with oesophageal varices, 43 were mild, 32 were moderate, and 33 were severe. The rank sum test indicated that the APRI, FIB-4, and S index were statistically significant between two groups (P < 0.05), while no significant difference was detected in terms of AAR between the two groups (P > 0.05). In addition, all four scoring systems were statistically significant between nonoesophageal varices group and severe oesophageal varices group (P < 0.05). In the ROC curve of oesophageal varices, the AUC values of APRI, FIB-4, and S index for predicting oesophageal varices were 0.681, 0642, and 0.673, respectively. However, in the ROC curve of severe oesophageal varices, the AUC values of APRI, AAR, FIB-4, and S index were 0.729, 0.648, 0.673, and 0.695, respectively. Multivariate logistic regression analysis indicated that APRI and FIB-4 were predictors of disease progression (P < 0.05). Conclusion. AAR harboured a poor predictive value for oesophageal varices, APRI can be used as a reference index for the prediction of severe oesophageal varices, and the S index harboured potential value in predicting the degree of progression of cirrhosis.

Download Full-text

Development and External Validation of a Nomogram for Early Predicting in-hospital Mortality of Patients with SARS-CoV-2 Pneumonia: A Two-Center, Retrospective Analysis

10.21203/rs.3.rs-27780/v1 ◽

2020 ◽

Author(s):

Miao Luo ◽

Junlin Lu ◽

Jing Liu ◽

Shuli Xia ◽

Shuang Wei

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Regression Analysis ◽

Hospital Mortality ◽

External Validation ◽

Multivariate Logistic Regression Analysis ◽

Curve Analysis ◽

Multivariate Logistic Regression ◽

Factors Associated ◽

Death Cases

Abstract Background At present, the death cases with SARS-CoV-2 pneumonia are continuing to increase globally. However, the information on death cases and predictive methods are substantial lacking. We aimed to develop a nomogram, which was validated by both internal and external cohorts, for early predicting mortality in hospitalized patients with SARS-CoV-2 pneumonia.Methods We retrospectively collected data on 1,540 patients confirmed SARS-CoV-2 pneumonia from two hospitals. Multivariate logistic regression analysis was performed to examine factors associated with in-hospital mortality. We investigated the mortality related risk factors and their weights, thereafter designed and validated a predictive nomogram model to facilitate early discrimination of in-hospital death. We assessed the nomogram performance by examining calibration (calibration plots and Hosmer–Lemeshow calibration test) and discrimination (AUROC). We also plotted survival curves and decision curves to evaluate the clinical usefulness of the nomogram.Results In the 1,540 patients from two centers, 248 cases died (16.1%). In the predictive nomogram calculated by a multivariate logistic regression analysis, eight independent risk factors associated mortality included age ≥ 60 years (odd ratio(OR) = 2.840; 95%CI, 1.467–5.495; P = 0.002), respiratory rate ≥ 30 breaths per minute (OR = 3.308; 95%CI, 1.408–7.770; P = 0.006), neutrophil count ≥ 7 × 109/L (OR = 3.084; 95%CI, 1.667–5.707; P < 0.001), lymphocyte count ≤ 0.8 × 109/ L (OR = 4.688; 95%CI, 2.500-8.791; P < 0.001), d-dimer ≥ 1.5 µg/mL(OR = 2.159; 95%CI, 1.169–3.989; P = 0.014), lactate dehydrogenase ≥ 350U/L(OR = 4.385; 95%CI, 2.299–8.362; P < 0.001), procalcitonin ≥ 0.1 ng/mL(OR = 4.972; 95%CI, 2.537–9.746; P < 0.001), and presence of myocardial injury (OR = 2.289; 95%CI, 1.260–4.160; P = 0.007) on admission. Calibration curves showed good fitting of the nomogram model with no statistical significance (P = 0.740) by Hosmer-Lemeshow test. This predictive nomogram had better predictive ability than CURB-65 score in training set (AUROC = 0.956 vs 0.828,P < 0.001). The good predictive performance of the nomogram is suggested by calibration, discrimination, and survival curve analysis, whether in the training, internal or external validation set. The decision curve analysis showed that predicting mortality risk applying this nomogram would be better than having all patients or none patients.Conclusions This nomogram is a reliable prognostic method that can accurately and early predict in-hospital mortality in patients with SARS-CoV-2 pneumonia. It can guide clinicians to improve their abilities to evaluate patient prognosis, enhance patient stratification, make earlier and reasonable decisions.Trail registration: This is a retrospective observational study without a trial registration number.

Download Full-text

Efficacy of flurbiprofen axetil for preventing postanesthetic shivering in patients undergoing gynecologic laparotomy surgeries

JA Clinical Reports ◽

10.1186/s40981-020-00403-x ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Atsushi Kotera

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Postoperative Pain ◽

Logistic Regression Analysis ◽

Pain Control ◽

Multivariate Logistic Regression Analysis ◽

Multivariate Logistic Regression ◽

Postoperative Pain Control ◽

Flurbiprofen Axetil ◽

Postanesthetic Shivering

Abstract Background Postanesthetic shivering is an unpleasant adverse event in surgical patients. A nonsteroidal anti-inflammatory drug has been reported to be useful in preventing postanesthetic shivering in several previous studies. The aim of this study was to evaluate the efficacy of flurbiprofen axetil being a prodrug of a nonsteroidal anti-inflammatory drug for preventing postanesthetic shivering in patients undergoing gynecologic laparotomy surgeries. Method This study is a retrospective observational study. I collected data from patients undergoing gynecologic laparotomy surgeries performed between October 1, 2019, and September 30, 2020, at Kumamoto City Hospital. All the patients were managed with general anesthesia with or without epidural analgesia. The administration of intravenous 50 mg flurbiprofen axetil for postoperative pain control at the end of the surgery was left to the individual anesthesiologist. The patients were divided into two groups: those who had received intravenous flurbiprofen axetil (flurbiprofen group) and those who had not received intravenous flurbiprofen axetil (non-flurbiprofen group), and I compared the frequency of postanesthetic shivering between the two groups. Additionally, the factors presumably associated with postanesthetic shivering were collected from the medical charts. Intergroup differences were assessed with the χ2 test with Yates’ correlation for continuity category variables. The Student’s t test was used to test for differences in continuous variables. Furthermore, a multivariate logistic regression analysis was performed to elucidate the relationship between the administration of flurbiprofen axetil and the incidence of PAS. Results I retrospectively examined the cases of 141 patients aged 49 ± 13 (range 21-84) years old. The overall postanesthetic shivering rate was 21.3% (30 of the 141 patients). The frequency of postanesthetic shivering in the flurbiprofen group (n = 31) was 6.5%, which was significantly lower than that in the non-flurbiprofen group (n = 110), 25.5% (p value = 0.022). A multivariate logistic regression analysis showed that administration of flurbiprofen axetil was independently associated with a reduced incidence of postanesthetic shivering (odds ratio 0.12; 95% confidence interval, 0.02-0.66, p value = 0.015). Conclusions My result suggests that intraoperative 50 mg flurbiprofen axetil administration for postoperative pain control is useful to prevent postanesthetic shivering in patients undergoing gynecologic laparotomy surgeries.

Download Full-text

The association between hypoglycemia and glycemic variability in elderly patients with type 2 diabetes: a prospective observational study

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00656-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Takahisa Handa ◽

Akinobu Nakamura ◽

Aika Miya ◽

Hiroshi Nomoto ◽

Hiraku Kameda ◽

...

Keyword(s):

Type 2 Diabetes ◽

Logistic Regression ◽

Regression Analysis ◽

Observational Study ◽

Elderly Patients ◽

Prospective Observational Study ◽

Multivariate Logistic Regression Analysis ◽

Glycemic Variability ◽

Multivariate Logistic Regression

Abstract Background This study aimed to explore predictive factors of time below target glucose range (TBR) ≥ 1% among patients’ characteristics and glycemic variability (GV) indices using continuous glucose monitoring data in elderly patients with type 2 diabetes. Methods We conducted a prospective observational study on 179 (71 female) Japanese outpatients with type 2 diabetes aged ≥ 65 years. The characteristics of the participants with TBR ≥ 1% were evaluated by multivariate logistic regression analysis. Receiver-operating characteristic (ROC) curve analyses of GV indices, comprising coefficient of variation (CV), standard deviation, and mean amplitude of glycemic excursions, were performed to identify the optimal index for the identification of patients with TBR ≥ 1%. Results In the multivariate logistic regression analysis, none of the clinical characteristics, including HbA1c and C-peptide index, were independent markers for TBR ≥ 1%, while all three GV indices showed significant associations with TBR ≥ 1%. Among the three GV indices, CV showed the best performance based on the area under the curve in the ROC curve analyses. Conclusions Among elderly patients with type 2 diabetes, CV reflected TBR ≥ 1% most appropriately among the GV indices examined. Trial registration UMIN-CTR: UMIN000029993. Registered 16 November 2017

Download Full-text

Risk factors for tissue expander infection in scar reconstruction: a retrospective cohort study of 2374 consecutive cases

Burns & Trauma ◽

10.1093/burnst/tkaa037 ◽

2020 ◽

Vol 8 ◽

Author(s):

Chen Dong ◽

Minhui Zhu ◽

Luguang Huang ◽

Wei Liu ◽

Hengxin Liu ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Regression Analysis ◽

Treatment Failure ◽

Logistic Regression Analysis ◽

Disease Duration ◽

Multivariate Logistic Regression Analysis ◽

Tissue Expansion ◽

Multivariate Logistic Regression ◽

Hematoma Evacuation

Abstract Background Tissue expansion is used for scar reconstruction owing to its excellent clinical outcomes; however, the complications that emerge from tissue expansion hinder repair. Infection is considered a major complication of tissue expansion. This study aimed to analyze the perioperative risk factors for expander infection. Methods A large, retrospective, single-institution observational study was carried out over a 10-year period. The study enrolled consecutive patients who had undergone tissue expansion for scar reconstruction. Demographics, etiological data, expander-related characteristics and postoperative infection were assessed. Univariate and multivariate logistic regression analysis were performed to identify risk factors for expander infection. In addition, we conducted a sensitivity analysis for treatment failure caused by infection as an outcome. Results A total of 2374 expanders and 148 cases of expander infection were assessed. Treatment failure caused by infection occurred in 14 expanders. Multivariate logistic regression analysis identified that disease duration of ≤1 year (odds ratio (OR), 2.07; p < 0.001), larger volume of expander (200–400 ml vs <200 ml; OR, 1.74; p = 0.032; >400 ml vs <200 ml; OR, 1.76; p = 0.049), limb location (OR, 2.22; p = 0.023) and hematoma evacuation (OR, 2.17; p = 0.049) were associated with a high likelihood of expander infection. Disease duration of ≤1 year (OR, 3.88; p = 0.015) and hematoma evacuation (OR, 10.35; p = 0.001) were so related to high risk of treatment failure. Conclusions The rate of expander infection in patients undergoing scar reconstruction was 6.2%. Disease duration of <1 year, expander volume of >200 ml, limb location and postoperative hematoma evacuation were independent risk factors for expander infection.

Download Full-text

Donepezil Combined with DL-3-n-Butylphthalide Delays Cognitive Decline in Patients with Mild to Moderate Alzheimer’s Disease: A Multicenter, Prospective Cohort Study

Journal of Alzheimer s Disease ◽

10.3233/jad-201381 ◽

2021 ◽

Vol 80 (2) ◽

pp. 673-681

Author(s):

Jin Wang ◽

Xiaojuan Guo ◽

Wenhui Lu ◽

Jie Liu ◽

Hong Zhang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Logistic Regression ◽

Regression Analysis ◽

Cohort Study ◽

Prospective Cohort ◽

Daily Living ◽

Multivariate Logistic Regression Analysis ◽

Multivariate Logistic Regression ◽

Significant Difference

Background: Vascular factors and mitochondria dysfunction contribute to the pathogenesis of Alzheimer’s disease (AD). DL-3-n-butylphthalide (NBP) has an effect in protecting mitochondria and improving microcirculation. Objective: The aim was to investigate the effect of donepezil combined NBP therapy in patients with mild-moderate AD. Methods: It was a prospective cohort study. 92 mild-moderate AD patients were classified into the donepezil alone group (n = 43) or the donepezil combined NBP group (n = 49) for 48 weeks. All patients were evaluated with Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog), Clinician’s Interview-Based Impression of Change plus caregiver input (CIBIC-plus), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI) every 12 weeks. All patients were monitored for adverse events (AEs). The efficacy was analyzed using multivariate logistic regression analysis. Results: The multivariate logistic regression analysis showed that the changes of ADAS-cog score (OR = 2.778, 95% CI: [1.087, 7. 100], p = 0.033) and ADCS-ADL score (OR = 2.733, 95% CI: [1.002, 7.459], p = 0.049) had significant difference between donepezil alone group and donepezil combined NBP group, while the changes of NPI (OR = 1.145, 95% CI: [0.463, 2.829], p = 0.769), MMSE (OR = 1.563, 95% CI: [0.615, 3.971], p = 0.348) and CIBIC-plus (OR = 2.593, 95% CI: [0.696, 9.685], p = 0.156) had no significant difference. The occurrence of AEs was similar in the two groups. Conclusion: Over the 48-week treatment period, donepezil combined NBP group had slower cognitive decline and better activities of daily living in patients with mild to moderate AD. These indicated that the multi-target therapeutic effect of NBP may be a new choice for AD treatment.

Download Full-text