A Novel Nomogram for Predicting the Risk of Premature Delivery Based on the Thyroid Function in Pregnant Women

BackgroundMaternal thyroid dysfunction and autoantibodies were associated with preterm delivery. However, recommendations for cutoff values of thyroperoxidase antibody (TPOAb) positivity and thyroid-stimulating homone (TSH) associated with premature delivery are lacking.ObjectiveTo identify the pregnancy-specific cutoff values for TPOAb positivity and TSH associated with preterm delivery. To develop a nomogram for the risk prediction of premature delivery based on maternal thyroid function in singleton pregnant women without pre-pregnancy complications.MethodsThis study included data from the International Peace Maternity and Child Care Health Hospital (IPMCH) in Shanghai, China, between January 2013 and December 2016. Added data between September 2019 and November 2019 as the test cohort. Youden’s index calculated the pregnancy-specific cutoff values for TPOAb positivity and TSH concentration. Univariate and multivariable logistic regression analysis were used to screen the risk factors of premature delivery. The nomogram was developed according to the regression coefficient of relevant variables. Discrimination and calibration of the model were assessed using the C-index, Hosmer-Lemeshow test, calibration curve and decision curve analysis.Results45,467 pregnant women were divided into the training and validation cohorts according to the ratio of 7: 3. The testing cohort included 727 participants. The pregnancy-specific cutoff values associated with the risk of premature delivery during the first trimester were 5.14 IU/mL for TPOAb positivity and 1.33 mU/L for TSH concentration. Multivariable logistic regression analysis showed that maternal age, history of premature delivery, elevated TSH concentration and TPOAb positivity in the early pregnancy, preeclampsia and gestational diabetes mellitus were risk factors of premature delivery. The C-index was 0.62 of the nomogram. Hosmer-Lemeshow test showed that the Chi-square value was 2.64 (P = 0.955 > 0.05). Decision curve analysis showed a positive net benefit. The calibration curves of three cohorts were shown to be in good agreement.ConclusionsWe identified the pregnancy-specific cutoff values for TPOAb positivity and TSH concentration associated with preterm delivery in singleton pregnant women without pre-pregnancy complications. We developed a nomogram to predict the occurrence of premature delivery based on thyroid function and other risk factors as a clinical decision-making tool.

Performance of COVIDSeq and Swift normalase amplicon SARS-CoV-2 panels for SARS-CoV-2 Genomes Sequencing: Practical Guide and Combining FASTQ Strategy

The whole genomic sequencing (WGS) of SARS-CoV-2 has been performed extensively and is playing a crucial role in fighting against COVID-19 pandemic. Obtaining sufficient WGS data from clinical samples is often challenging especially from the samples with low viral load. We evaluated two SARS-CoV-2 sequencing protocols for their efficiency/accuracy and limitations. Sequence coverage of >95% was obtained by Swift normalase amplicon SARS-CoV-2 panels (SNAP) protocol for all the samples with Ct ≤ 35 and by COVIDSeq protocol for 97% of samples with Ct ≤ 30. Sample RNA quantitation obtained using digital PCR provided more precise cutoff values. The quantitative digital PCR cutoff values for obtaining 95% coverage are 10.5 copies/μL for SNAP protocol and 147 copies/μL for COVIDSeq protocol. Combining FASTQ files obtained from 2 protocols improved the outcome of sequence analysis by compensating for missing amplicon regions. This process resulted in an increase of sequencing coverage and lineage call precision.

Intraoperative lactic acid concentration during liver transplantation and cutoff values to predict early mortality: a retrospective analysis of 3,338 cases

Background: We aimed to explore intraoperative lactic acid (LA) level distribution during liver transplantation (LT) and determine the optimal cutoff values to predict post-LT 30-day and 90-day mortality.Methods: Intraoperative LA data from 3,338 patients were collected between 2008 to 2019 and all-cause mortalities within 30 and 90 days were retrospectively reviewed. Of the three LA levels measured during preanhepatic, anhepatic, and neohepatic phase of LT, the peak LA level was selected to explore the distribution and predict early post-LT mortality. To determine the best cutoff values of LA, we used a classification and regression tree algorithm and maximally selected rank statistics with the smallest P value.Results: The median intraoperative LA level was 4.4 mmol/L (range: 0.5–34.7, interquartile range: 3.0–6.2 mmol/L). Of the 3,338 patients, 1,884 (56.4%) had LA levels > 4.0 mmol/L and 188 (5.6%) had LA levels > 10 mmol/L. Patients with LA levels > 16.7 mmol/L and 13.5–16.7 mmol/L showed significantly higher 30-day mortality rates of 58.3% and 21.2%, respectively. For the prediction of the 90-day mortality, 8.4 mmol/L of intraoperative LA was the best cutoff value.Conclusions: Approximately 6% of the LT recipients showed intraoperative hyperlactatemia of > 10 mmol/L during LT, and those with LA > 8.4 mmol/L were associated with significantly higher early post-LT mortality.

Differences in Preoperative Gastric Ultrasound Findings Between Old and Young Surgical Patients: A Retrospective Case-Control Study

Background: Most gastric ultrasound studies have been conducted in young middle-aged patients. Although age is known to influence gastric ultrasound, comparisons of gastric ultrasound in elderly patients with young patients have not been well elucidated. This study aimed to 1) compare gastric ultrasound assessments between young and elderly patients, 2) determine whether the CSA cutoff values for elderly and young patients should be different, and 3) suggest CSA cutoff values for elderly patients.Methods: This retrospective case-control study evaluated the data of 120 patients who underwent elective surgery under general anesthesia between July 2019 and August 2020. Demographic and gastric ultrasound assessment data were retrieved. Patients were divided into the elderly group (n = 58, age: ≥65 years) and young group (n = 62, age: <65 years). The antral cross-sectional area (CSA) in the supine and right lateral decubitus positions (RLDP), semiquantitative three-point Perlas grade (grades 0, 1, and 2), and gastric volume were determined. CSAs according to different Perlas grades were compared between the two groups. The CSA cutoff values for predicting a high risk of pulmonary aspiration in both the groups were determined. Results: Among patients with Perlas grade 0 (empty stomach), the CSA supine and CSA RLDP were greater in the elderly group than in the young group (CSA supine: 5.12 ± 1.99 cm2 vs. 3.92 ± 0.19 cm2, P = 0.002, and CSA RLDP: 6.24 ± 0.43 cm2 vs. 4.58 ± 0.21 cm2, P = 0.002). The specificity, positive predictive value, and accuracy of the CSA decreased when the CSA cutoff value for the young group (CSA RLDP: 6.92 cm2) was applied to the elderly group. The CSA cutoff values for the elderly group were: CSA supine, 6.92 cm2 and CSA RLDP, 10.65 cm2.Conclusions: The CSA of the empty stomach was greater in elderly patients than in young patients. The CSA cutoff values for predicting pulmonary aspiration risk in elderly and young patients should be differentiated. We suggest that the following CSA cutoff values should be used for predicting pulmonary aspiration risk in elderly patients: CSA supine, 6.92 cm2 and CSA RLDP, 10.65 cm2.

Prognostic Significance of Preoperative Serum Carcinoembryonic Antigen Varies with Lymph Node Metastasis Status in Colorectal Cancer

Background. Preoperative serum level of carcinoembryonic antigen (pCEA) is generally recognized as a prognostic factor for colorectal cancer (CRC), but the stage-specific role of pCEA in colorectal cancer remains unclear. Objective. We investigated the prognostic significance of pCEA levels in different tumor stages of nonmetastatic CRC patients. Methods. Six hundred and fifteen CRC patients at stage I–III were retrospectively analyzed. All of them received curative tumor resection. The X-tile program was used to generate stage-specific cutoff values of pCEA for all patients and two subpopulations (lymph node-positive or -negative). The prognostic significance of pCEA was assessed using Kaplan–Meier analysis and Cox proportional hazards regression analysis. A nomogram model that combined pCEA score and clinical feature indexes was established and evaluated. Results. Two cutoff values were identified in the study population. At a cutoff value of 4.9 ng/mL, a significantly higher 5-year overall survival (OS) rate (82.16%) was observed in the pCEA-low group (<4.9 ng/mL) compared with 65.52% in the pCEA-high group (≥4.9 ng/mL). Furthermore, at the second cutoff value of 27.2 ng/mL, 5-year OS was found to be only 40.9%. Stratification analysis revealed that preoperative serum level of pCEA was an independent prognostic factor (OR = 1.991, P < 0.01 ) in the subpopulation of lymph node metastasis (stage III) patients, and the relative survival rates in the pCEA-low (≤4.9 ng/mL), pCEA-medium (4.9–27.2 ng/mL), and pCEA-high (≥27.2 ng/mL) groups were 73.4%, 60.5%, and 24.8%, respectively ( P < 0.05 ). However, no such effect was observed in the lymph node nonmetastasis (stage I and II) subgroup. The established nomogram showed acceptable predictive power of the 5-year OS rate (C-index: 0.612) in lymph node-positive CRC patients, with an area under the curve value of 0.772, as assessed by ROC curve analysis. Conclusions. Pretreatment serum CEA levels had different prognostic significance based on the lymph node metastasis status. Among stage III CRC patients, pCEA was an independent prognostic factor. Five-year OS rates could be predicted according to the individual pCEA level at the different cutoff values.

Assessment of gonadotropin concentrations stimulated by gonadotropin-releasing hormone analog by electrochemiluminescence (ECLIA) in girls with precocious puberty and premature thelarche

Objective: The aim of this study is to determine the cutoff values of gonadotropin response to gonadotropin-releasing hormone analogs (GnRHas) corresponding to the activation of the hypothalamic–pituitary–gonadal axis that could differentiate central precocious puberty (CPP) from premature thelarche (PT) and using the electrochemiluminescence assay method. Methods: A total of 49 girls underwent the stimulation test with the intramuscular injection of 3.75 mg leuprolide acetate. Based on the clinical and laboratory characteristics, they were divided into two groups: CPP (n = 22) and PT (n = 27). Baseline estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were collected before GnRHa administration, and LH and FSH at 60 and 120 min, respectively, after GnRHa administration. Results: The girls with CPP presented an increased height Z-score, advanced bone age, and higher baseline LH, FSH, estradiol, and LH/FSH ratio in relation to PT (p < 0.001). Stimulated LH differed significantly between the two groups, and the LH cutoff values were ≥4.29 IU/L (p < 0.001) and ≥3.95 IU/L at 60 and 120 min, respectively (p < 0.001). LH peak was found at 60 min after stimulation. Conclusions: The GnRHa test is effective in distinguishing CPP from PT, and a single sampling, at 60 min, with LH concentrations above 4.29 may be the parameter of choice with the advantage of greater convenience and practicality.

Prognostic Value of the Systemic Immune-Inflammation Index and Prognostic Nutritional Index in Patients With Medulloblastoma Undergoing Surgical Resection

Background: The progression and metastasis of cancers are associated with systematic immune inflammation and nutritional dysfunction. The systemic immune-inflammation index and prognostic nutritional index (PNI) have shown a prognostic impact in several malignancies. Therefore, our study aimed to evaluate immune inflammation and nutritional index prognostic significance in patients with medulloblastoma (MB).Methods: We retrospectively analyzed 111 patients with MB between 2001 and 2021 at our institution. The optimal cutoff values for systemic immune-inflammation index (SII), neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte counts ration (MLR), and PNI were evaluated with receiver operating characteristic (ROC) curve analysis. Clinical characteristics and SII, NLR, MLR, and PNI were tested with the Pearson's chi-squared test. The Kaplan–Meier survival curves and the Cox proportional hazards model were used to evaluate the effects of immune inflammation and nutritional index on overall survival (OS).Results: Receiver operating characteristic curve analysis determined the optimal SII, NLR, MLR, and PNI cutoff values of 2,278, 14.83, 0.219, and 56.5 that significantly interacts with OS and divided the patients into two groups. Comparative survival analysis exhibited that the high-SII cohort had significantly shorter OS (p = 0.0048) than the low-SII cohort. For the univariate analysis, the results revealed that preoperative hydrocephalus (p = 0.01), SII (p = 0.006), albumin–bilirubin score (ALBI) (p = 0.04), and coSII–PNI were predictors of OS. In the multivariate analysis, preoperative hydrocephalus (p &lt; 0.001), ALBI (p = 0.010), SII (p &lt; 0.001), and coSII–PNI as independent prognostic factors were significantly correlated with OS.Conclusion: The preoperative SII, ALBI, and coSII–PNI serve as robust prognostic biomarkers for patients with MB undergoing surgical resection.

The Potential Role of Circulating MicroRNAs in Male Rat Infertility Treated with Kaempferia parviflora

Background. Therapeutic strategies based on herbal plants and diets containing sufficient amounts of antioxidants and essential vitamins are very important factors in treating reproduction and male infertility worldwide. Thus, the aim of this study was to investigate the potential effects of Kaempferia parviflora (KP) on the role of some microRNAs in treated and nontreated infertile rats. In addition, the correlation of expressed microRNAs with sperm count, sperm motility, and sperm viability was identified. The probable use of these microRNAs as a diagnostic marker for predicting the clinical response of infertility to the treatment with KP was also achieved. Methods. In the present study, the potential effects of Kaempferia parviflora (KP) at different doses (140, 280, and 420 mg/kg) for six weeks on male rats with subinfertility were explored. In addition, the effect of KP on the expression of circulating microRNAs and its correlation with the parameters of sexual infertility was identified by performing both in vitro and in vivo assays. In vitro antioxidant activity, sperm functional analysis, serum testosterone, and expression of circulating microRNAs were conducted using colorimetric, ELISA, and real-time RT-PCR analysis, respectively. Results. Kaempferia parviflora (KP) at nontoxic doses of 140–420 mg/kg/day for six weeks significantly improved serum testosterone and epididymal sperm parameters (sperm count, motility, and sperm viability), increased testicular weight, and provided a reduction in the percentage of abnormal spermatozoon in infertile male rats. The expression of miR-328 and miR-19b significantly decreased, and miR-34 significantly increased in infertile rats treated with KP compared to infertile nontreated rats. After six weeks of KP therapy, the change in the expression levels of miRNAs was correlated positively with higher levels of serum testosterone and the measures of epididymal sperm parameters. The respective area under the receiver operating characteristic curve (AUC-ROC) was applied to predict the potential use of miR-328, miR-19b, and miR-34 in the diagnosis of male infertility in treated and nontreated infertile male rats. The data showed that AUC cutoff values of 0.91 for miR-328, 0.89 for miR-19b, and 0.86 for miR34 were the best estimated values for the clinical diagnosis of male rats with infertility. In rats treated with KP for six weeks, AUC cutoff values of 0.76 for miR-328, 0.79 for miR-19b, and 0.81 for miR-34 were the best cutoff values reported for the clinical response of infertility to KP therapy after six weeks. Conclusions. In this study, the improvement of male infertility might proceed via antioxidant and antiapoptotic pathways, which significantly improve spermatogenesis and aphrodisiac properties of males. In addition, the expression of miRNAs, miR-328, miR-34, and miR-19b, in KP-treated and nontreated infertile rats significantly correlated with increased serum testosterone levels and epididymal sperm parameters as well. MicroRNAs, miR-328, miR-34, and miR-19b, might be related to oxidative and apoptotic pathways that proceeded in spermatogenesis. Thus, the use of miRNAs could have a role as diagnostic, therapeutic, and predictive markers for assessing the clinical response of Kaempferia parviflora treatment for six weeks. This may have potential applications in the therapeutic strategies based on herbal plants for male infertility. However, in subsequent studies, the genetic regulatory mechanisms of the expressed miRNAs should be fully characterized.