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Metabolomics to identify fingerprints of carotid atherosclerosis in nonobese metabolic dysfunction-associated fatty liver disease

J Transl Med. 2023 Jan 9;21(1):12. doi: 10.1186/s12967-022-03760-6.

ABSTRACT

BACKGROUND/AIMS: Nonobese metabolic dysfunction-associated fatty liver disease (MAFLD) is paradoxically associated with improved metabolic and pathological features at diagnosis but similar cardiovascular diseases (CVD) prognosis to obese MAFLD. We aimed to utilize the metabolomics to identify the potential metabolite profiles accounting for this phenomenon.

METHODS: This prospective multicenter cross-sectional study was conducted in China enrolling derivation and validation cohorts. Liquid chromatography coupled with mass spectrometry and gas chromatography-mass spectrometry were applied to perform a metabolomics measurement.

RESULTS: The study involved 120 MAFLD patients and 60 non-MAFLD controls in the derivation cohort. Controls were divided into two groups according to the presence of carotid atherosclerosis (CAS). The MAFLD group was further divided into nonobese MAFLD with/without CAS groups and obese MAFLD with/without CAS groups. Fifty-six metabolites were statistically significant for discriminating the six groups. Among the top 10 metabolites related to CAS in nonobese MAFLD, only phosphatidylethanolamine (PE 20:2/16:0), phosphatidylglycerol (PG 18:0/20:4) and de novo lipogenesis (16:0/18:2n-6) achieved significant areas under the ROC curve (AUCs, 0.67, p = 0.03; 0.79, p = 0.02; 0.63, p = 0.03, respectively). The combination of these three metabolites and liver stiffness achieved a significantly higher AUC (0.92, p < 0.01). In obese MAFLD patients, cystine was found to be significant with an AUC of 0.69 (p = 0.015), followed by sphingomyelin (SM 16:1/18:1) (0.71, p = 0.004) and de novo lipogenesis (16:0/18:2n-6) (0.73, p = 0.004). The combination of these three metabolites, liver fat content and age attained a significantly higher AUC of 0.91 (p < 0.001). The AUCs of these metabolites remained highly significant in the independent validation cohorts involving 200 MAFLD patients and 90 controls.

CONCLUSIONS: Diagnostic models combining different metabolites according to BMI categories could raise the accuracy of identifying subclinical CAS. Trial registration The study protocol was approved by the local ethics committee and all the participants have provided written informed consent (Approval number: [2014] No. 112, registered at the Chinese Clinical Trial Registry, ChiCTR-ChiCTR2000034197).

PMID:36624524 | DOI:10.1186/s12967-022-03760-6

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BLOod Test Trend for cancEr Detection (BLOTTED): protocol for an observational and prediction model development study using English primary care electronic health record data

Diagn Progn Res. 2023 Jan 10;7(1):1. doi: 10.1186/s41512-022-00138-6.

ABSTRACT

BACKGROUND: Simple blood tests can play an important role in identifying patients for cancer investigation. The current evidence base is limited almost entirely to tests used in isolation. However, recent evidence suggests combining multiple types of blood tests and investigating trends in blood test results over time could be more useful to select patients for further cancer investigation. Such trends could increase cancer yield and reduce unnecessary referrals. We aim to explore whether trends in blood test results are more useful than symptoms or single blood test results in selecting primary care patients for cancer investigation. We aim to develop clinical prediction models that incorporate trends in blood tests to identify the risk of cancer.

METHODS: Primary care electronic health record data from the English Clinical Practice Research Datalink Aurum primary care database will be accessed and linked to cancer registrations and secondary care datasets. Using a cohort study design, we will describe patterns in blood testing (aim 1) and explore associations between covariates and trends in blood tests with cancer using mixed-effects, Cox, and dynamic models (aim 2). To build the predictive models for the risk of cancer, we will use dynamic risk modelling (such as multivariate joint modelling) and machine learning, incorporating simultaneous trends in multiple blood tests, together with other covariates (aim 3). Model performance will be assessed using various performance measures, including c-statistic and calibration plots.

DISCUSSION: These models will form decision rules to help general practitioners find patients who need a referral for further investigation of cancer. This could increase cancer yield, reduce unnecessary referrals, and give more patients the opportunity for treatment and improved outcomes.

PMID:36624489 | DOI:10.1186/s41512-022-00138-6

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Donor site morbidity after computer assisted surgical reconstruction of the mandible using deep circumflex iliac artery grafts: a cross sectional study

BMC Surg. 2023 Jan 9;23(1):4. doi: 10.1186/s12893-022-01899-z.

ABSTRACT

BACKGROUND: Computer Assisted Design and Computer Assisted Manufacturing (CAD/CAM) have revolutionized oncologic surgery of the head and neck. A multitude of benefits of this technique has been described, but there are only few reports of donor site comorbidity following CAD/CAM surgery.

METHODS: This study investigated comorbidity of the hip following deep circumflex iliac artery (DCIA) graft raising using CAD/CAM techniques. A cross-sectional examination was performed to determine range of motion, muscle strength and nerve disturbances. Furthermore, correlations between graft volume and skin incision length with postoperative donor site morbidity were assessed using Spearman’s rank correlation, linear regression and analysis of variance (ANOVA).

RESULTS: Fifteen patients with a mean graft volume of 21.2 ± 5.7 cm3 and a mean incision length of 228.0 ± 30.0 mm were included. Patients reported of noticeable physical limitations in daily life activities (12.3 ± 11.9 weeks) and athletic activities (38.4 ± 40.0 weeks in mean) following surgery. Graft volume significantly correlated with the duration of the use of walking aids (R = 0.57; p = 0.033) and impairment in daily life activities (R = 0.65; p = 0.012). The length of the scar of the donor-site showed a statistically significant association with postoperative iliohypogastric nerve deficits (F = 4.4, p = 0.037). Patients with anaesthaesia of a peripheral cutaneous nerve had a larger mean scar length (280 ± 30.0 mm) than subjects with hypaesthesia (245 ± 10.1 mm) or no complaints (216 ± 27.7 mm).

CONCLUSIONS: Despite sophisticated planning options in modern CAD/CAM surgery, comorbidity of the donor site following iliac graft harvesting is still a problem. This study is the first to investigate comorbidity after DCIA graft raising in a patient group treated exclusively with CAD/CAM techniques. The results indicate that a minimal invasive approach in terms of small graft volumes and small skin incisions could help to reduce postoperative symptomatology. Trial registration Retrospectively registered at the German Clinical Trials Register (DRKS-ID: DRKS00029066); registration date: 23/05/2022.

PMID:36624485 | DOI:10.1186/s12893-022-01899-z

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A two-stage genome-wide association study identifies novel germline genetic variations in CACNA2D3 associated with radiotherapy response in nasopharyngeal carcinoma

J Transl Med. 2023 Jan 9;21(1):11. doi: 10.1186/s12967-022-03819-4.

ABSTRACT

BACKGROUND: Radiotherapy (RT) is the standard treatment for nasopharyngeal carcinoma (NPC). However, due to individual differences in radiosensitivity, biomarkers are needed to tailored radiotherapy to cancer patients. However, comprehensive genome-wide radiogenomic studies on them are still lacking. The aim of this study was to identify genetic variants associated with radiotherapy response in patients with NPC.

METHODS: This was a large‑scale genome-wide association analysis (GWAS) including a total of 981 patients. 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant loci were further genotyped using MassARRAY system and TaqMan SNP assays in the validation stages of 847 patients. This study used logistic regression analysis and multiple bioinformatics tools such as PLINK, LocusZoom, LDBlockShow, GTEx, Pancan-meQTL and FUMA to examine genetic variants associated with radiotherapy efficacy in NPC.

RESULTS: After genome-wide level analysis, 19 SNPs entered the validation stage (P < 1 × 10– 6), and rs11130424 ultimately showed statistical significance among these SNPs. The efficacy was better in minor allele carriers of rs11130424 than in major allele carriers. Further stratified analysis showed that the association existed in patients in the EBV-positive, smoking, and late-stage (III and IV) subgroups and in patients who underwent both concurrent chemoradiotherapy and induction/adjuvant chemotherapy.

CONCLUSION: Our study showed that rs11130424 in the CACNA2D3 gene was associated with sensitivity to radiotherapy in NPC patients.

TRIAL REGISTRATION NUMBER: Effect of genetic polymorphism on nasopharyngeal carcinoma chemoradiotherapy reaction, ChiCTR-OPC-14005257, Registered 18 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=9546 .

PMID:36624463 | DOI:10.1186/s12967-022-03819-4

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The changed endemic pattern of human adenovirus from species B to C among pediatric patients under the pressure of non-pharmaceutical interventions against COVID-19 in Beijing, China

Virol J. 2023 Jan 9;20(1):4. doi: 10.1186/s12985-023-01962-y.

ABSTRACT

BACKGROUND: Under the pressure of non-pharmaceutical interventions (NPIs) targeting severe acute respiratory syndrome coronavirus 2, the prevalence of human adenovirus (HAdV) was monitored before and after NPIs launched on Jan 24, 2020 in pediatric patients in Beijing, China.

METHODS: Respiratory samples collected from children hospitalized with acute respiratory infections from Jan 2015 to Dec 2021 were screened by direct immunofluorescence test or capillary electrophoresis-based multiplex PCR assay. The hexon, penton base, and fiber genes were amplified from HAdV positive specimens, then sequenced. For HAdV typing, phylogenetic trees were built by MEGA X. Then clinical data of HAdV positive cases were collected. All data were evaluated using SPSS Statistics 22.0 software.

RESULTS: A total of 16,097 children were enrolled and 466 (2.89%, 466/16,097) were HAdV-positive. The positive rates of HAdV varied, ranging from 4.39% (151/3,438) in 2018 to1.25% (26/2,081) in 2021, dropped from 3.19% (428/13,408) to 1.41% (38/2,689) from before to after NPIs launched (P < 0.001). There were 350 cases typed into nine types of species B, C, or E and 34 recorded as undetermined. Among them, HAdV-B3 (51.56%, 198/384) was the most prevalent types from 2015 to 2017, and HAdV-B7 (29.17%, 112/384) co-circulated with HAdV-B3 from 2018 to 2019. After NPIs launched, HAdV-B3 and B7 decreased sharply with HAdV-B7 undetected in 2021, while HAdV-C1 became the dominant one and the undetermined were more.

CONCLUSIONS: The endemic pattern of HAdV changed in Beijing because of the NPIs launched for COVID-19. Especially, the dominant types changed from HAdV-B to HAdV-C.

PMID:36624458 | DOI:10.1186/s12985-023-01962-y

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Who should operate patients presenting with emergent colon cancer? A comparison of short- and long-term outcome depending on surgical sub-specialization

World J Emerg Surg. 2023 Jan 9;18(1):3. doi: 10.1186/s13017-023-00474-y.

ABSTRACT

BACKGROUND: Colorectal cancer presents as emergencies in 20% of the cases. Emergency resection is associated with high postoperative morbidity and mortality. The specialization of the operating team in the emergency settings differs from the elective setting, which may have an impact on outcome. The aim of this study was to evaluate short- and long-term outcomes following emergent colon cancer surgery depending on sub-specialization of the operating team.

METHODS: This is a retrospective population study based on data from the Swedish Colorectal Cancer Registry (SCRCR). In total, 656 patients undergoing emergent surgery for colon cancer between 2011 and 2016 were included. The cohort was divided in groups according to specialization of the operating team: (1) colorectal team (CRT); (2) emergency surgical team (EST); (3) general surgical team (GST). The impact of specialization on short- and long-term outcomes was analyzed.

RESULTS: No statistically significant difference in 5-year overall survival (CRT 48.3%; EST 45.7%; GST 42.5%; p = 0.60) or 3-year recurrence-free survival (CRT 80.7%; EST 84.1%; GST 77.7%21.1%; p = 0.44) was noted between the groups. Neither was any significant difference in 30-day mortality (4.4%; 8.1%; 5.5%, p = 0.20), 90-day mortality (8.8; 11.9; 7.9%, p = 0.37) or postoperative complication rate (35.5%, 35.9 30.7, p = 0.52) noted between the groups. Multivariate analysis adjusted for case-mix showed no difference in hazard ratios for long-term survival or postoperative complications. The rate of permanent stoma after 3 years was higher in the EST group compared to the CRT and GST groups (34.5% vs. 24.3% and 23.9%, respectively; p < 0.0.5).

CONCLUSION: Surgical sub-specialization did not significantly affect postoperative complication rate, nor short- or long-term survival after emergent operation for colon cancer. Patients operated by emergency surgical teams were more likely to have a permanent stoma after 3 years.

PMID:36624451 | DOI:10.1186/s13017-023-00474-y

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Using the teach-back method to improve postpartum maternal-infant health among women with limited maternal health literacy: a randomized controlled study

BMC Pregnancy Childbirth. 2023 Jan 9;23(1):13. doi: 10.1186/s12884-022-05302-w.

ABSTRACT

AIM: This study aimed to evaluate the effects of using the teach-back method among women with limited maternal health literacy (LMHL) on maternal health literacy(MHL), postpartum health behaviours and maternal-infant health outcomes.

METHODS: A randomized controlled study was conducted in the obstetrics department of Anhui Provincial Hospital, China. A total of 258 pregnant women with LMHL were recruited at the point of admission to the hospital for birth and randomly assigned to the control group (n = 130), where women received routine education sessions, and the teach-back group (n = 128), where women received routine education sessions plus a teach-back intervention. The two groups were assessed in terms of MHL before and after the intervention, breastfeeding execution, uptake of 42-day postpartum check-ups, complete uptake of one-time recommended vaccines, and physical health outcomes. Statistical tests were employed for data analysis.

RESULTS: There was no significant difference between the two groups in terms of MHL and other social, demographic, and medical status at baseline. After the intervention, the teach-back group had a higher level of MHL (p < 0.001), better postpartum health behaviours in terms of exclusive breastfeeding within 24 hours postpartum (x2 = 22.853, p<0.001), exclusive breastfeeding within 42 days postpartum (x2 = 47.735, p<0.001), uptake of 42-day postpartum check-ups (x2 = 9.050, p = 0.003) and vaccination (x2 = 5.586, p = 0.018) and better maternal-infant health outcomes in terms of the incidence of subinvolution of the uterus (x2 = 6.499, p = 0.011), acute mastitis (x2 = 4.884, p = 0.027), postpartum constipation (x2 = 5.986, p = 0.014), overweight (x2 = 4.531, p = 0.033) and diaper dermatitis (x2 = 10.896, p = 0.001).

CONCLUSIONS: This study shows that the teach-back method is effective for enhancing MHL, leading to positive postpartum health behaviours, and improving postpartum maternal-infant health outcomes among women with LMHL. The teach-back method may play an important role in improving postpartum maternal-infant health and could be considered in maternal health education.

TRIAL REGISTRATION NUMBER: Our trial has been prospectively registered at ClinicalTrials.gov (Ref. No.: NCT04858945) and the enrollment date was 26/04/2021.

PMID:36624440 | DOI:10.1186/s12884-022-05302-w

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Systemic inhibition of 5-lipoxygenase by MK-886 exacerbates apical periodontitis bone loss in a mouse model

BMC Oral Health. 2023 Jan 10;23(1):11. doi: 10.1186/s12903-023-02712-w.

ABSTRACT

BACKGROUND: To investigate if 5-LO selective inhibitor (MK-886) could be used for systemic treatment of experimentally induced apical periodontitis in a mouse model.

METHODS: Twenty-four C57BL/6 mice were used. After coronal opening, a solution containing Escherichia coli LPS (1.0 µg/µL) was inoculated into the root canals of the lower and upper right first molars (n = 72 teeth). After 30 days apical periodontitis was established, and the animals were treated with MK-886 (5 mg/kg), a 5-LO inhibitor, for 7 and 14 days. The tissues were removed for histopathological and histometric analyses, evaluation of osteoclast number and gene expression for receptor activator of nuclear factor kappa-B (Tnfrsf11a), receptor activator of nuclear factor kappa-B ligand (Tnfsf11), osteoprotegerin (Tnfrsf11b), tartrate-resistant acid phosphatase (Acp5), matrix metalloproteinase-9 (Mmp9), cathepsin K (Ctsk) and calcitonin receptor (Calcr). Statistical data analysis was performed using Kruskal Wallis followed by Dunn’s tests (α = 0.05).

RESULTS: Administration of MK-886 for 7 days exerted no effect on apical periodontitis progression compared to LPS inoculation without treatment (p = 0.3549), while treatment for 14 days exacerbated bone loss (p < 0.0001). Administration of MK-886 enhanced osteoclastogenesis signaling and osteoclast formation within 7 days (p = 0.0005), but exerted no effect at 14 days (p > 0.9999). After 7 days of treatment, MK-886 induced mRNA expression for Acp5 (p = 0.0001), Calcr (p = 0.0003), Mmp9 (p = 0.0005) and Ctsk (p = 0.0008), however no effect in those gene expression was observed after 14 days (p > 0.05).

CONCLUSION: Systemic treatment with MK-886 exacerbated LPS-induced apical periodontitis in a mouse model.

PMID:36624436 | DOI:10.1186/s12903-023-02712-w

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Neural responses to social decision-making in suicide attempters with mental disorders

BMC Psychiatry. 2023 Jan 9;23(1):19. doi: 10.1186/s12888-022-04422-z.

ABSTRACT

BACKGROUND: Decision-making deficits have been reported in suicide attempters and may be a neuropsychological trait of vulnerability to suicidal behavior. However, little is known about how neural activity is altered in decision-making. This study aimed to investigate the neural responses in suicide attempters with mental disorders during social decision-making. Electroencephalography (EEG) were recorded from 52 patients with mental disorders with past suicide attempts (SAs = 26) and without past suicide attempts (NSAs = 26), as well as from 22 age- and sex- matched healthy controls (HCs) during the Ultimatum Game (UG), which is a typical paradigm to investigate the responses to fair and unfair decision-making.

METHODS: MINI 5.0 interview and self report questionnaire were used to make mental diagnosis and suicide behavior assessment for individuals. Event-related potential (ERP) and phase-amplitude coupling (PAC) were extracted to quantify the neural activity. Furthermore, Spearman correlation and logistic regression analyses were conducted to identify the risk factors of suicidal behavior.

RESULTS: ERP analysis demonstrated that SA patients had decreased P2 amplitude and prolonged P2 latency when receiving unfair offers. Moreover, SA patients exhibited greater negative-going feedback-related negativity (FRN) to unfair offers compared to fair ones, whereas such a phenomenon was absent in NSA and HC groups. These results revealed that SA patients had a stronger fairness principle and a disregard toward the cost of punishment in social decision-making. Furthermore, theta-gamma and beta-gamma PAC were involved in decision-making, with compromised neural coordination in the frontal, central, and temporal regions in SA patients, suggesting cognitive dysfunction during social interaction. Statistically significant variables were used in logistic regression analysis. The area under receiver operating characteristic curve in the logistic regression model was 0.91 for SA/HC and 0.84 for SA/NSA.

CONCLUSIONS: Our findings emphasize that suicide attempts in patients with mental disorders are associated with abnormal decision-making. P2, theta-gamma PAC, and beta-gamma PAC may be neuro-electrophysiological biomarkers associated with decision-making. These results provide neurophysiological signatures of suicidal behavior.

PMID:36624426 | DOI:10.1186/s12888-022-04422-z

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Establishment and validation of a simple nomogram for predicting early postpartum stress urinary incontinence among women with vaginal delivery: a retrospective study

BMC Womens Health. 2023 Jan 9;23(1):8. doi: 10.1186/s12905-023-02160-2.

ABSTRACT

BACKGROUND: Stress urinary incontinence (SUI) is a common public health issue that negatively impacts the quality of life for women worldwide, of which early detection and rehabilitation are consequently pivotal. The aim of this study is to establish a simple nomogram for identifying women at risk of postpartum SUI.

METHODS: A retrospective study was conducted in a tertiary specialized hospital in Shanghai, China. The study included only women with singleton, full-term, and vaginal deliveries. 2,441 women who delivered from July 2019 to November 2019 were included in the training cohort, and 610 women who delivered from January 2022 to February 2022 were included in the validation cohort. SUI was determined by the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF). Univariate and multifactorial logistical regression were used to identify independent risk factors for postpartum SUI and further construct the nomogram accordingly. Based on concordance statistics (C-statistics), calibration curves, and decision curve analyses, we evaluated the performance of the nomogram in the training cohort and the validation cohort. In addition, the model was validated internally in the training cohort through cross-validation.

RESULTS: There were no significant statistically differences in important baseline data such as age, pre-pregnancy BMI, and parity between the training and validation cohorts. SUI was observed in 431 (17.6%) and 125 (20.5%) women in the training and validation cohorts, respectively. According to the regression analysis, age, parity, second stage of labor, infant weight, and forceps delivery were included in the nomogram. The nomogram had a C-statistic of 0.80 (95% confidence interval [CI] 0.74-0.85) for predicting SUI. C-statistics were stable in both internally cross-validated training cohort (mean 0.81) and validation cohort (0.83 [95% CI 0.79-0.87]). The nomogram’s calibration curve was near the ideal diagonal line. Additionally, the model exhibited a positive net benefit from the decision curve analysis.

CONCLUSION: We have created a nomogram that can be utilized to quantify the risk of postpartum SUI for women with vaginal delivery. The model might contribute to predicting early postpartum SUI, thereby facilitating the management of SUI.

PMID:36624424 | DOI:10.1186/s12905-023-02160-2