Efficiency of copy number variation sequencing combined with karyotyping in fetuses with congenital heart disease and the following outcomes.

BACKGROUND: Both copy number variant-sequencing (CNV-seq) and karyotype analysis have been used as powerful tools in the genetic aetiology of fetuses with congenital heart diseases (CHD). However, CNV-seq brings clinicians more confusions to interpret the detection results related to CHD with or without extracardiac abnormalities. Hence, we conducted this study to investigate the clinical value of CNV-seq in fetuses with CHD. RESULTS: A total of 167 patients with fetal CHD including 36 single CHD (sCHD), 41 compound CHD (cCHD) and 90 non-isolated CHD (niCHD) were recruited into the study. 28 cases (16.77%, 28/167) were revealed with chromosomal abnormalities at the level of karyotype. The pathogenic detection rate (DR) of CNV-seq (23.17%, 19/82) was higher than that of karyotyping (15.85%, 13/82) in 82 cases by CNV-seq and karyotyping simultaneously. The DR of pathogenic copy number variations (PCNVs) (31.43%) was higher in niCHD subgroup than that in sCHD and cCHD (9.52% and 23.08%). Conotruncal defect (CTD) was one of the most common heart malformations with the highest DR of PCNVs (50%) in 7 categories of CHD. In terms of all the pregnancy outcomes, 67 (40.12%) cases were terminated and 100 (59.88%) cases were live neonates. Only two among 34 cases with a pathogenic genetic result chose to continue the pregnancy. CONCLUSIONS: CNV-seq combined with karyotyping is a reliable and accurate prenatal technique for identifying pathogenic chromosomal abnormalities associated with fetal CHD with or without extracardiac abnormalities, which can assist clinicians to perform detailed genetic counselling with regard to the etiology and related outcomes of CHD.

Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections.

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients. Methods: Seventeen elderly patients (age ≥ 65 years) and six young critically ill patients (age < 65 years) were enrolled. Six to eight blood samples were collected during the 12 h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24 h at steady state (AUCss, 0-24 h). Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0-24 h nor normalized AUCss, 0-24 h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56 h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = -0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0-24 h (r = -0.414, p = 0.049). Patients with AUCss, 0-24 h ≥ 100 mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0-24 h < 50 mg·h/L or patients with AUCss, 0-24 h 50-100 mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose. Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023.

A novel shared decision-making (SDM) tool for anticoagulation management in atrial fibrillation: protocol for a prospective, cluster randomized controlled trial.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns. Shared decision-making (SDM) is an approach that involves patients and healthcare providers in making decisions about treatment options. This study aims to assess the effectiveness of a novel SDM tool for anticoagulation management in AF. METHODS: The study will be a prospective, cluster randomized controlled trial involving 440 patients with AF in 8 community health service centers (clusters) in Shanghai, China. The SDM group will receive anticoagulation management through the novel SDM tool, while the control group will receive standard care. The follow-up period will be at least 2 years. The primary outcome will be any bleeding event, while secondary outcomes include the accordance of stroke prophylaxis for AF according to the current guidelines, time in therapeutic range (TTR), the occurrences of major bleeding and thrombosis events, and patient knowledge, adherence, and satisfaction. DISCUSSION: This study will provide evidence of the effectiveness of shared decision-making in improving the appropriateness of OAC use in Chinese AF patients. The findings may inform the development of guidelines and policies for the management of AF and anticoagulation therapy in China and other countries. TRIAL REGISTRATION: ChiCTR ChiCTR2200062123. Registered on 23 July 2022.

With two episodes of right retromandibular angle subcutaneous emphysema during right upper molar crown preparation: A case report.

BACKGROUND: Subcutaneous emphysema is a well-known complication of oral surgery, especially during mandibular wisdom tooth extraction. However, subcutaneous emphysema secondary to dental procedures such as crown preparation is rare. The main symptom of emphysema is swelling and crepitus on palpation. Uncontrolled emphysema may spread along the fascial planes and cause deep space infections or a pneumomediastinum. CASE SUMMARY: In this paper, we report a 34-year-old female who underwent upper molar tooth preparation for crowns and subsequently developed extensive subcutaneous emphysema on the retromandibular angle on two different occasions. The treatment plan for this patient involved close observation of the airway, and administration of dexamethasone and antibiotics via intravenous drip or orally. Ice bag compression was quickly applied and medication was prescribed to alleviate discomfort and promote healing. Although the main reason is unclear, the presence of a fissure in the molar is an important clue which may contribute to the development of subcutaneous emphysema during crown preparation. It is imperative for dental professionals to recognize such pre-disposing factors in order to minimize the risk of complications. CONCLUSION: This case highlights the need for prompt diagnosis and management of subcutaneous emphysema because of the risk of much more serious complications. Awareness of relatively "benign" subcutaneous emphysema during any dental procedure is critical not only for inexperienced dentists, but also for those who work in rural and remote settings as members of surgical teams. In this study, we review the clinical presentation, mechanism, and differential diagnosis of subcutaneous emphysema.

Precise and comprehensive evaluation of perianal fistulas, classification and related complications using magnetic resonance imaging.

OBJECTIVE: This study aimed to comprehensively evaluate perianal fistulas and their related complications using magnetic resonance imaging (MRI). METHODS: We enrolled 115 eligible patients who underwent preoperative perianal MRI. Primary fistulas, internal and external openings, and related complications were evaluated using MRI. All fistulas were classified according to Park's classification, Standard Practice Task Force classification, St. James's grade, and the position of the internal opening. RESULTS: In total, 169 primary fistulas were detected in 115 patients; 73 (63.5%) patients had a single primary tract and 42 (36.5%) patients had multiple primary tracts, and 198 internal and 129 external openings were identified. Based on Park's classification, 150 (88.7%) primary fistulas were classified into the following types: intersphincteric (82, 54.7%), trans-sphincteric (58, 38.6%), suprasphincteric (8, 5.3%), extrasphincteric (1, 0.7%), and diffuse intersphincteric with trans-sphincteric (1, 0.7%) types. Based on St. James's grade, 149 fistulas were classified into grade 1 (52, 34.9%), grade 2 (30, 20.1%), grade 3 (20, 13.4%), grade 4 (38, 25.5%), and grade 5 (9, 6.1%). We detected 92 (54.4%) simple and 77 (45.6%) complex perianal fistulas and 72 (42.6%) high and 97 (57.4%) low perianal fistulas. Furthermore, we detected 32 secondary tracts in 23 (20.0%) patients and 87 abscesses in 60 (52.2%) patients. Levator ani muscle involvement and extensive soft tissue edema were detected in 12 (10.4%) and 24 (20.9%) patients, respectively. CONCLUSION: MRI is a valuable and comprehensive tool that can not only be used to determine the general condition of perianal fistulas but also to classify them and identify related complications.

Effects of social support, anxiety, and hope levels on cognitive bias in patients with nasogastric/nasoenteric tubes.

BACKGROUND: Unplanned extubation is a common adverse event and an important indicator of quality and safety of care. It is well recognized that the incidence of unplanned extubation of nasogastric/nasoenteric tubes is higher than that of other devices. Theory and previous research have suggested that cognitive bias in conscious patients with nasogastric/nasoenteric tubes may lead to unplanned extubation, and that social support, anxiety, and hope are influencing factors of cognitive bias. Therefore, the objective of this study was to investigate the effects of social support, anxiety, and hope levels on cognitive bias in patients with nasogastric/nasoenteric tubes. METHODS: In this cross-sectional study, 438 patients with nasogastric/nasoenteric tubes were selected from 16 hospitals in Suzhou from December 2019 to March 2022 by convenience sampling method. The participants were assessed using the General Information Questionnaire, Perceived Social Support Scale, Generalized Anxiety Disorder-7, Herth Hope Index, and Cognitive Bias Questionnaire for patients with nasogastric/nasoenteric tubes. The structural equation model was established with AMOS 22.0 software. RESULTS: The cognitive bias score of patients with nasogastric/nasoenteric tubes was 2.82±0.61. Patients' perceived levels of social support and hope were negatively correlated with their cognitive bias (r=-0.395 and -0.427, respectively, P<0.05), and anxiety was positively correlated with cognitive bias (r=0.446, P<0.05). Structural equation model analysis showed that anxiety had a direct positive effect on cognitive bias, with an effect value of 0.35 (P<0.001), and hope level had a direct negative effect on cognitive bias with an effect value of -0.33 (P<0.001). Social support had a direct negative effect on cognitive bias and was also shown to indirectly affect cognitive bias through anxiety and hope levels. The effect values were -0.22, -0.12, and -0.19 (P<0.001), for social support, anxiety, and hope, respectively. Social support, anxiety, and hope explained 46.2% of the total variation in cognitive bias. CONCLUSIONS: Moderate cognitive bias is noted in patients with nasogastric/nasoenteric tubes, and social support significantly affects cognitive bias. Anxiety and hope level play a mediating role in social support and cognitive bias. Positive psychological intervention and the obtention of positive support could improve the cognitive bias of patients with nasogastric/nasoenteric tubes.

45, X/ 46, X, psu idic (Y) (q11.2) Mosaicism in a Primary Amenorrhea Girl with Swyer Syndrome.

The female characters with a 46, XY karyotype, historically termed Swyer syndrome, are commonly divided into complete and partial gonadal dysgenesis. The former is completely made up of the 46, XY chromosome, while the latter results from 45, X/46, XY mosaicism. Both of them are sex chromosome disorders and are typically characterized by delayed puberty and primary amenorrhea due to disruption of the embryonic gonads into testes. In this report, we described a young female with mos 45, X [2]/46, X, psu idic (Y) (q11.2) [48] by karyotyping. Further copy number variation sequencing (CNV-seq) and fluorescent in situ hybridization (FISH) verified her chromosome alteration. The following gonadectomy and hormone replacement therapy were carried out, and the menstrual cycle recovered along with the development of bilateral breasts and uteruses. Herein, we aim to provide clinical management strategies for the patient with Swyer syndrome in clinical practice.

Missed diagnosis of lissencephaly after prenatal diagnosis: A case report.

RATIONALE: Lissencephaly (LIS) is a rare and serious cortical malformation characterized by a smooth or nearly smooth brain surface. With the progress of molecular genetics, platelet-activating factor acetylhydrolase brain isoform Ib is the most frequent type during the fetal period. Here, we report an infant with LIS who was missed although undergoing prenatal diagnosis. We aim to share our experiences and lessons. PATIENT CONCERNS: A 2-month-old male infant presented recurrent convulsions. Karyotype and copy number variation sequencing were conducted to be normal at the 23-week gestation because of bipedal varus and ventricular septal defect (2.3 mm). After birth, he suffered from epilepsy confirmed by video electroencephalogram exam, meanwhile, computed tomography and magnetic resonance imaging revealed pachygyria. The infant was diagnosed with LIS carrying a de-novo mutation c.817 C > T (p.Arg273 Ter,138) in exon 8 of platelet-activating factor acetylhydrolase brain isoform Ib (NM_000430) detected by whole-exome sequencing. DIAGNOSES: Based on the clinical characteristics, imaging, and genetic test findings, the infant was diagnosed with LIS. INTERVENTIONS: The patient was treated with topiramate and dose was adjusted according to the seizure frequency. OUTCOMES: The infant had recurrent seizures. The muscle tone of his extremities increased, and he could not look up or turn over actively at the age of 6 months. LESSONS: Comprehensive evaluation of a multi-disciplinary team should be recommended for patients with epilepsy and cerebral hypoplasia. Individuals with LIS during the fetal period might be missed due to atypical features. In fetuses with structural abnormalities, if karyotype and copy number variation sequencing are both normal, whole-exome sequencing may be an effective complementary means to detect pathogenic variants.

Corticosteroid treatment in severe patients with SARS-CoV-2 and chronic HBV co-infection: a retrospective multicenter study.

BACKGROUND: The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids on these patients. METHODS: This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2020 to Apr 18, 2020 in seven centers in China, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-cov-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroids effects was minimized using multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on propensity score. RESULTS: The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17-34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63-5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68-14.28, P = 0.004; OR, 5.64, 95% CI 1.95-16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57-7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors. CONCLUSIONS: In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with increased risk of 28-day and in-hospital mortality.

Haploinsufficiencies of FOXF1, FOXC2 and FOXL1 genes originated from deleted 16q24.1q24.2 fragment related with alveolar capillary dysplasia with misalignment of pulmonary veins and lymphedema-distichiasis syndrome: relationship to phenotype.

OBJECTIVE: We describe a fetus with a 2.12-Mb terminal deleted fragment in 16q associated with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) and lymphedema-distichiasis syndrome (LDS) and intend to provide a comprehensive prenatal management strategy for the fetuses with ACDMPV and LDS through reviewing other similar published studies. METHODS: The fetus presented a series of diverse structural malformations including congenital cardiovascular, genitourinary and gastro-intestinal anomalies in ultrasound at 23 + 5 weeks of gestation (GA). Amniocentesis was conducted for karyotype analysis and copy number variation sequencing (CNV-seq) after informed consent. RESULTS: The fetal karyotype was 46,XX, however the result of CNV-seq showed an approximately 2.12-Mb deletion in 16q24.1q24.2 (85220000-87340000) × 1 indicating pathogenicity. CONCLUSION: Genomic testing should be recommend as a first line diagnostic tool for suspected ACDMPV and/or LDS or other genetic syndromes for the fetuses with structural abnormalities in clinical practice.

A fetus with Bosch-Boonstra-Schaaf optic atrophy syndrome characterized by bilateral ventricle widening: A case report and related literature review.

RATIONALE: Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare neurodevelopmental disorder caused by loss-of-function variants in the Nuclear Receptor Subfamily 2 Group F Member 1 (NR2F1). Here, we report a case of fetal BBSOAS. The fetus is typically featured by bilateral ventricle widening in the late second trimester, meanwhile, a 7.94-Mb deletion fragment on 5q14.3q15 involving the whole NR2F1 gene was confirmed by copy number variation sequencing (CNV-Seq) combined with karyotyping analysis. Our aim is to provide comprehensive prenatal clinical management strategy for fetal BBSOAS. PATIENT CONCERNS: A 29-year-old primipara and her husband were referred to our prenatal diagnosis center due to the widening of bilateral ventricles at 29 + 1 weeks of gestation age. DIAGNOSES: Ultrasound revealed the fetal widening posterior horns of bilateral ventricles at the GA of 27 + 3 weeks, 11 mm on the left and 10 mm on the right. At the following 29 + 1 weeks, ultrasound showed the posterior horn of the left lateral ventricle: 12 mm while the width of the right decreased to 9 mm, and intracranial arachnoid cyst. Furthermore, MRI confirmed that intracranial cyst might originate from an enlarged cisterna venae magnae cerebri, with mild dilation of 13.5 mm on the left ventricle. The fetal karyotyping analysis and CNV-Seq detection confirmed a 7.94-Mb deleted fragment on 5q14.3q15 (89340000_97280000) through the amniocentesis at 29 + 4 weeks of GA. INTERVENTIONS: The fetus was closely monitored and underwent the following assessment by the multidisciplinary team. OUTCOMES: The pregnancy was terminated in the end. LESSONS: It is vital to use molecular and cytogenetical detections combined with a dynamic development history to make a definite diagnosis and evaluate the genetic status for the fetuses with BBSOAS.

Effect of empirical antifungal treatment on mortality in non-neutropenic critically ill patients: a propensity-matched retrospective cohort study.

To evaluate the effect of empirical antifungal treatment (EAFT) on mortality in critically ill patients without invasive fungal infections (IFIs). This was a single-center propensity score-matched retrospective cohort study involving non-transplanted, non-neutropenic critically ill patients with risk factors for invasive candidiasis (IC) in the absence of IFIs. We compared all-cause hospital mortality and infection-attributable hospital mortality in patients who was given EAFT for suspected IC as the cohort group and those without any systemic antifungal agents as the control group. Among 640 eligible patients, 177 patients given EAFT and 177 control patients were included in the analyses. As compared with controls, EAFT was not associated with the lower risks of all-cause hospital mortality [odds ratio (OR), 0.911; 95% CI, 0.541-1.531; P = 0.724] or infection-attributable hospital mortality (OR, 1.149; 95% CI, 0.632-2.092; P = 0.648). EAFT showed no benefit of improvement of infection at discharge, duration of mechanical ventilation, and antibiotic-free days. However, the later initiation of EAFT was associated with higher risks of all-cause hospital mortality (OR, 1.039; 95% CI, 1.003 to 1.076; P = 0.034) and infection-attributable hospital mortality (OR, 1.046; 95% CI, 1.009 to 1.085; P = 0.015) in patients with suspected IC. This effect was also found in infection-attributable hospital mortality (OR, 1.042; 95% CI, 1.005 to 1.081; P = 0.027) in septic patients with suspected IC. EAFT failed to decrease hospital mortality in non-neutropenic critically ill patients without IFIs. The timing may be critical for EAFT to improve mortality in these patients with suspected IC. ChiCTR2000038811, registered on Oct 3, 2020.

Pregnant outcomes of critically ill pregnant patients with pulmonary hypertension: A multicenter retrospective study.

Objective: To identify the pregnancy outcomes and risk factors of critically ill pulmonary hypertension (PH) patients with intensive care unit (ICU) admission. Methods: The multicenter, retrospective cohort study was performed on 60,306 parturients from January 2013 to December 2018 in China. Diagnosis of PH was based on the estimation of systolic pulmonary arterial pressure (sPAP) via echocardiography. Patients were stratified by sPAP into three groups, mild (30-50 mmHg), moderate (51-70 mmHg), and severe (>70 mmHg). The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of in-hospital death, heart failure, and sustained arrhythmias requiring treatment. The secondary outcome was fetal adverse clinical events (FACE), a composite of fetal/neonatal death, prematurity, small birth weight, and fetal distress. Results: A total of 181 pregnant patients were enrolled, including 101 patients with mild PH, 31 with moderate PH, and 49 with severe PH. The maternal median age was 32 (27, 35) years and 37% were nulliparous. The MACE occurred in 59 (59/181, 32.6%) women, including in-hospital death in 13 (13/181, 7.2%), heart failure in 53 (53/181, 29.3%), and sustained arrhythmias in 7 (7/181, 3.9%). The incidence of FACE was as high as 66.3% (120/181). Compared with mild and moderate PH patients, patients with severe PH had a significantly higher mortality rate (22.4 vs. 1.51%, P < 0.001) and MACE incidence (51.0 vs. 25.8%, P = 0.001). Although the incidence of FACE in severe PH was slightly higher than that in mild to moderate PH, there was no significant difference (69.4 vs. 65.1%, P = 0.724). PH complicated with left heart disease (OR = 4.365, CI: 1.306-14.591), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (OR = 1.051, CI:1.015-1.088), and sPAP level estimated by echocardiography (OR = 1.021; CI: 1.003-1.040) were independently associated with MACE in multivariable regression (P < 0.05). Increased risk of FACE was noted for PH patients combined with eclampsia/preeclampsia (OR = 6.713; CI: 1.806-24.959). Conclusion: The incidence of MACE and FACE remained high in critically ill pregnant patients with PH, particularly moderate and severe PH in China. Further studies are warranted to identify subsets of women with PH at lower pregnant risks and seek more effective therapy to improve pregnancy outcomes.

A prenatal case of Simpson-Golabi-Behmel syndrome type 1 with a 0.26-Mb deletion fragment at Xq26.2 inherited from mother: Case report.

RATIONALE: The purpose of this report was to explore how to manage the fetus of Simpson-Golabi-Behmel syndrome type 1 (SGBS1) and to provide a definite diagnosis to guide the following genetic counseling for the pregnancy. PATIENT CONCERNS: A 24-year-old women, gravida 1, para 0, was 172 cm tall with weight 65 kg. She was referred to our center for counseling due to second-trimester ultrasound screening anomalies at 22 + 5 weeks of gestation age. Meanwhile the ultrasound examination indicated the overgrowth of the fetus. She and her husband were healthy and nonconsanguineous without family history. DIAGNOSES: The karyotype and copy number variations sequencing (CNV-seq) combined with fetal ultrasound manifestation confirmed the diagnosis of SGBS1. INTERVENTIONS: No treatment for the fetus. OUTCOMES: Pregnancy was terminated. LESSIONS: Once fetal overgrowth and other malformation are revealed in prenatal ultrasound, although without polyhydramnios and organomegaly, SGBS1 should be considered and further genetic testing such as CNV-seq and whole exon sequencing should be conducted to help clinicians provide a definite diagnosis to guide the following genetic counseling and the next pregnancy.

Systemic inflammation response index as a prognostic predictor in patients with acute ischemic stroke: A propensity score matching analysis.

Background: Acute ischemic stroke (AIS), the most common type of stroke, is a major cause of morbidity and mortality worldwide. A growing number of studies have demonstrated that inflammation is a critical mechanism in AIS. Being an easily available and effective inflammatory marker, the systemic inflammation response index (SIRI) shows a high association with mortality in patients with cancer and intracerebral hemorrhage. In this study, we evaluated the potential prognostic role of SIRI in critically ill patients with AIS. Methods: Clinic data were extracted from the Medical Information Mart data for the Intensive Care IV (MIMIC-IV) database. The optimal cutoff value of SIRI was determined by X-tile software. The primary outcome was the 90-day all-cause mortality, and the secondary outcomes were 30-day and 1-year all-cause mortality of patients with AIS. Cox proportional hazards regression analyses were used to assess the association between SIRI levels and all-cause mortality, and survival curves were estimated using the Kaplan-Meier method. Furthermore, a 1:1 propensity score matching (PSM) method was performed to balance the influence of potential confounding factors. Results: A total of 2,043 patients were included in our study. X-tile software indicated that the optimal cutoff value of the SIRI for 90-day mortality was 4.57. After PSM, 444 pairs of score-matched patients were generated. Cox proportional hazard model showed that after adjusting for possible confounders, high SIRI level (≥4.57) was independently associated with the 90-day all-cause mortality in the cohort before PSM (HR = 1.56, 95% CI: 1.30-1.89, p < 0.001) and the PSM subset (HR = 1.47, 95% CI: 1.16-1.86, p = 0.001). The survival curves showed that patients with SIRI ≥4.57 had a significantly lower 90-day survival rate in the cohort before PSM (56.7 vs. 77.3%, p < 0.001) and the PSM subset (61.0 vs. 71.8%, p = 0.001). Consistently, AIS patients with high SIRI levels (≥4.57) presented a significantly high risk of 30-day and 1-year all-cause mortality before and after PSM. Conclusion: A higher SIRI (≥4.57) was associated with a higher risk of 90-day, 30-day, and 1-year mortality and was an independent risk factor of mortality in patients with acute ischemic stroke.

Changes of serum levels of tumor necrosis factor (TNF-α) and soluble interleukin-2 receptor (SIL 2R) in patients with cervical cancer and their clinical significance.

OBJECTIVE: The goal of the current trial was to investigate the expression levels of tumor necrosis factor-α (TNF-α) and soluble interleukin-2 receptor (SIL-2R) in serum of patients with cervical cancer and analyze their clinical significance. METHODS: We randomly selected 50 cases of cervical cancer patients who came to our hospital from March 2018 to March 2020 as the experimental group and 50 cases of healthy adult women during the same period as the control group. The experimental group received laparoscopic radical hysterectomy. We compared two groups of patients' serum level of TNF-α and SIL-2R expression. The receiver operating characteristic (ROC) curve was used to determine the diagnostic efficacy of serum TNF-α and SIL-2R in cervical cancer. RESULTS: The expression levels of serum TNF-α and SIL-2R in the experimental group before radical hysterectomy were significantly higher than that one week after surgery; the preoperative serum TNF-α and SIL-2R expression levels of the experimental group were notably higher than those of the control group; and no marked difference in the expression levels of serum TNF-α and SIL-2R was observed between the control group and the experimental group one week after operation. The area under the curve of TNF-α was 0.846 (95% CI: 0.605~0.978), the diagnostic sensitivity was 81.54%, and the specificity was 70.12%; The area under the curve of SIL-2R is 0.813 (95% CI: 0.601~0.943), the diagnostic sensitivity was 80.13%, and the specificity was 69.97%. CONCLUSION: Serum levels of TNF-α and SIL-2R expression in patients with cervical cancer are usually noticeably elevated. After surgical treatment, the serum levels of TNF-α and SIL-2R expression will gradually become normal. It is of significant clinical relevance to detect the serum levels of TNF-α and SIL-2R expression for early diagnosis of intervention of cervical cancer.

Hollow POM@MOF-derived Porous NiMo6 @Co3 O4 for Biothiol Colorimetric Detection.

Developing highly active and sensitive peroxidase mimics for L -cysteine (L -Cys) colorimetric detection is very important for biotechnology and medical diagnosis. Herein, polyoxometalate-doped porous Co3 O4 composite (NiMo6 @Co3 O4 ) was designed and prepared for the first time. Compared with pure and commercial Co3 O4 , NiMo6 @Co3 O4 (n) composites exhibit the enhanced peroxidase-mimicking activities and stabilities due to the strong synergistic effect between porous Co3 O4 and multi-electron NiMo6 clusters. Moreover, the peroxidase-mimicking activities of NiMo6 @Co3 O4 (n) composites are heavily dependent on the doping mass of NiMo6 , and the optimized NiMo6 @Co3 O4 (2) exhibits the superlative peroxidase-mimicking activity. More importantly, a sensitive L -Cys colorimetric detection is developed with the sensitivity of 0.023 µM-1 and the detection limit at least 0.018 µM in the linear range of 1-20 µM, which is by far the best enzyme-mimetic performances, to the best our knowledge.

Sex Differences on Clinical Characteristics, Severity, and Mortality in Adult Patients With COVID-19: A Multicentre Retrospective Study.

Background: Coronavirus disease-2019 (COVID-19) epidemic is spreading globally. Sex differences in the severity and mortality of COVID-19 emerged. This study aims to describe the impact of sex on outcomes in COVOD-19 with a special focus on the effect of estrogen. Methods: We performed a retrospective cohort study which included 413 patients (230 males and 183 females) with COVID-19 from three designated hospitals in China with a follow up time from January 31, 2020, to April 17, 2020. Women over 55 were considered as postmenopausal patients according to the previous epidemiological data from China. The interaction between age and sex on in-hospital mortality was determined through Cox regression analysis. In addition, multivariate Cox regression models were performed to explore risk factors associated with in-hospital mortality of COVID-19. Results: Age and sex had significant interaction for the in-hospital mortality (P < 0.001). Multivariate Cox regression showed that age (HR 1.041, 95% CI 1.009-1.073, P = 0.012), male sex (HR 2.033, 95% CI 1.007-2.098, P = 0.010), the interaction between age and sex (HR 1.118, 95% CI 1.003-1.232, P = 0.018), and comorbidities (HR 9.845, 95% CI 2.280-42.520, P = 0.002) were independently associated with in-hospital mortality of COVID-19 patients. In this multicentre study, female experienced a lower fatality for COVID-19 than male (4.4 vs. 10.0%, P = 0.031). Interestingly, stratification by age group revealed no difference in-hospital mortality was noted in women under 55 compared with women over 55 (3.8 vs. 5.2%, P = 0.144), as well as in women under 55 compared with the same age men (3.8 vs. 4.0%, P = 0.918). However, there was significantly difference in women over 55 with men of the same age group (5.2 vs. 21.0%, P = 0.007). Compared with male patients, female patients had higher lymphocyte (P < 0.001) and high-density lipoprotein (P < 0.001), lower high sensitive c reaction protein level (P < 0.001), and lower incidence rate of acute cardiac injury (6.6 vs. 13.5%, P = 0.022). Conclusion: Male sex is an independent risk factor for COVID-19 in-hospital mortality. Although female mortality in COVID-19 is lower than male, it might not be directly related to the effect of estrogen. Further study is warranted to identify the sex difference in COVID-19 and mechanisms involved.

Risk factors for severe COVID-19 in middle-aged patients without comorbidities: a multicentre retrospective study.

BACKGROUND: Information regarding characteristics and risk factors of COVID-19 amongst middle-aged (40-59 years) patients without comorbidities is scarce. METHODS: We therefore conducted this multicentre retrospective study and collected data of middle-aged COVID-19 patients without comorbidities at admission from three designated hospitals in China. RESULTS: Among 119 middle-aged patients without comorbidities, 18 (15.1%) developed into severe illness and 5 (3.9%) died in hospital. ARDS (26, 21.8%) and elevated D-dimer (36, 31.3%) were the most common complications, while other organ complications were relatively rare. Multivariable regression showed increasing odds of severe illness associated with neutrophil to lymphocyte ratio (NLR, OR, 11.238; 95% CI 1.110-1.382; p < 0.001) and D-dimer greater than 1 µg/ml (OR, 16.079; 95% CI 3.162-81.775; p = 0.001) on admission. The AUCs for the NLR, D-dimer greater than 1 µg/ml and combined NLR and D-dimer index were 0.862 (95% CI, 0.751-0.973), 0.800 (95% CI 0.684-0.915) and 0.916 (95% CI, 0.855-0.977), respectively. SOFA yielded an AUC of 0.750 (95% CI 0.602-0.987). There was significant difference in the AUC between SOFA and combined index (z = 2.574, p = 0.010). CONCLUSIONS: More attention should be paid to the monitoring and early treatment of respiratory and coagulation abnormalities in middle-aged COVID-19 patients without comorbidities. In addition, the combined NLR and D-dimer higher than 1 µg/ml index might be a potential and reliable predictor for the incidence of severe illness in this specific patient with COVID-19, which could guide clinicians on early classification and management of patients, thereby relieving the shortage of medical resource. However, it is warranted to validate the reliability of the predictor in larger sample COVID-19 patients.

Effects of Polyoxometalates on the Hydroxylation of N-Heterocyclic Ligands.

Four polyoxometalate (POM)-based Cu complexes with the hydroxylated pyridine analogue 3-(2-hydroxylpyrid-4-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl (btpo), H3{[Cu2(btpo)2](PW12O40)}·2H2O (1), H3{[Cu2(btpo)2](PMo12O40)}·2H2O (2), H2{[Cu2(btpo)2](SiW12O40)·SO4 (3), and H4{[Cu4(btpo)4](SiW12O40)}·8H2O (4), were synthesized hydrothermally under acid conditions. Single-crystal X-ray structural analysis reveals that 3-(pyrid-4-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl was hydroxylated into btpo in compounds 1-4, again providing structural evidence for the Gillard mechanism, in which H2O as a weak nucleophile can attack the α-C atom of N-heterocyclic molecules at a lower pH value (ca. 1.0) with the help of POMs.