Tag: pubmed

Stat Med. 2021 Nov 15. doi: 10.1002/sim.9258. Online ahead of print.

ABSTRACT

Immunotherapies are increasingly used for treating patients with advanced-stage cancers. However, cancer immunotherapy trials often present delayed treatment effects and long-term survivors which result nonproportional hazard models and challenge the immunotherapy trial designs. In this article, we proposed a general random delayed cure rate model for designing cancer immunotherapy trials. A sample size formula is derived for a weighted log-rank test. The accuracy of sample size estimation is assessed and compared with the existing methods via simulation studies. The sensitivities for misspecifying the random delay time are also studied through simulations.

PMID:34779534 | DOI:10.1002/sim.9258

J Clin Invest. 2021 Nov 15;131(22):e148225. doi: 10.1172/JCI148225.

ABSTRACT

Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non-COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment.

PMID:34779418 | DOI:10.1172/JCI148225

J Dev Orig Health Dis. 2021 Nov 15:1-6. doi: 10.1017/S2040174421000635. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the association between prenatal and neonatal period exposures and the risk of childhood and adolescent nasopharyngeal carcinoma (NPC). From January 2009 to January 2016, a total of 46 patients with childhood and adolescent NPC (i.e., less than 18 years of age) who were treated at Sun Yat-sen University Cancer Center were screened as cases, and a total of 45 cancer-free patients who were treated at Sun Yat-sen University Zhongshan Ophthalmic Center were selected as controls. The association between maternal exposures during pregnancy and obstetric variables and the risk of childhood and adolescent NPC was evaluated using logistic regression analysis. Univariate analysis revealed that compared to children and adolescents without a family history of cancer, those with a family history of cancer had a significantly higher risk of childhood and adolescent NPC [odds ratios (OR) = 3.15, 95% confidence interval (CI) = 1.02-9.75, P = 0.046], and the maternal use of folic acid and/or multivitamins during pregnancy was associated with a reduced risk of childhood and adolescent NPC in the offspring (OR = 0.07, 95% CI = 0.02-0.25, P < 0.001). After multivariate analysis, only the maternal use of folic acid and/or multivitamins during pregnancy remained statistically significant. These findings suggest that maternal consumption of folic acid and/or multivitamins during pregnancy is associated with a decreased risk of childhood and adolescent NPC in the offspring.

PMID:34779376 | DOI:10.1017/S2040174421000635

Acta Medica (Hradec Kralove). 2021;64(3):158-164. doi: 10.14712/18059694.2021.27.

ABSTRACT

INTRODUCTION: The study of single nucleotide polymorphisms (SNPs) of the leptin receptor gene (LEPR) based on next generation genomic sequencing (NGS) data is becoming an increasingly important aspect of diagnosis, treatment and prevention of both metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) phenotypes.

MATERIAL AND METHODS: 35 obese children 6-18 years old were examined by the NGS method with bioinformatic analysis. The main group (n = 18) was formed by children with MUO, according to the recommendations of the expert group of the National Heart, Lung, and Blood Institute. The control group (n = 17) was represented by children with MHO. Statistical methods were used: analysis of variance, Wald’s sequential analysis, Spearman’s correlation analysis, analysis of nominal data and multiple discriminant analysis.

RESULTS: 10 types of non-synonymous SNPs (rs3790435, rs1137100, rs2186248, rs70940803, rs79639154, rs1359482195, rs1137101, rs1805094, rs13306520, rs13306522) of the LEPR gene in obese children have been identified. Multiple discriminant analysis demonstrated that the following LEPR SNPs are of greatest importance in the development of MUO: rs3790435, rs13306522, rs13306520. Analysis of nominal data revealed significant differences in the groups for Copy number variation (CNV) rs3790435 of the LEPR gene. Wald’s analysis allowed us to identify 6 important predictors of MUO (І ≥ 0.5): 2 CNV rs3790435 (Relative Risk, RR = 2, Prognostic coefficient, PC = +2.76); male gender of the child (RR = 1.3, PC = +1.35); rs3790435 (RR = 1.9, PC = +2.76); hyperleptinemia more than 40.56 ng/ml (RR = 2, PC = +3); CNV rs1359482195 ≥ 3 (RR = 1.9, PC = +5.8); SNP of the LEPR gene ≥4 (RR = 3.8, PC = +5.8).

CONCLUSION: Children with the genotype rs3790435 gene LEPR had signs of MUO more often.

PMID:34779381 | DOI:10.14712/18059694.2021.27

Ann Med. 2021 Dec;53(1):2132-2141. doi: 10.1080/07853890.2021.1999489.

ABSTRACT

BACKGROUND: Biomarkers of oxidative stress (OS) have been poorly explored in fungal peritonitis (FP). Potassium is a regulator of pro-oxidants and antioxidants. Albumin and vitamin B₁₂ (B₁₂) are vital antioxidant agents in the circulatory system. This study aimed to investigate the antioxidative role of serum potassium, albumin and B₁₂ in FP.

METHODS: Serum levels of potassium, albumin and B₁₂ were retrospectively analyzed in 21 patients with a confirmed diagnosis of FP, 105 bacterial peritonitis (BP) patients and 210 patients receiving peritoneal dialysis without peritonitis.

RESULTS: Serum levels of potassium, albumin and B₁₂ were lower in FP patients than in BP patients. Serum potassium concentration was statistically related to albumin concentration in peritonitis patients. Univariate and multivariate binary logistic regression analysis suggested that serum level of potassium and albumin were independent risk factors of FP when compared with BP. Lower potassium and B₁₂ levels were independently associated with higher rates of technique failure in peritonitis.

CONCLUSION: These findings suggest lower serum potassium, albumin and B₁₂ as potential oxidative stress markers of FP and raise the hypothesis that an increased level of OS could contribute to FP.KEY MESSAGESFP remains a serious complication of peritoneal dialysis (PD), with higher morbidity (1-23.8%) and mortality (2-25%), and oxidative stress plays a role in it.Our study suggested serum potassium, albumin and vitamin B₁₂ as potential oxidative stress markers of fungal peritonitis.

PMID:34779336 | DOI:10.1080/07853890.2021.1999489

Semin Ophthalmol. 2021 Nov 14:1-3. doi: 10.1080/08820538.2021.2003823. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the success rate of strabismus surgery in patients with varying levels of severity of cerebral palsy (CP).

DESIGN: A retrospective study was conducted.

PARTICIPANTS: Sixty-four patients with varying severity of CP were included.

METHODS: All patients with different CP severity levels underwent strabismus surgery. Success was defined as any postoperative heterotropia outcome of less than 10 prism diopters in primary position. Statistical analysis was conducted using chi-square.

RESULTS: The mean age at the time of strabismus surgery was 3.1 years, and the mean follow-up was 6.0 years. The most common types of strabismus were infantile-onset exotropia in 36 patients (56%) and infantile-onset esotropia in 28 patients (44%). Surgical success was found to be better in patients with mild GMFCS (GMFCS levels 1-2) with 68% having less than 10 PD of eso or exotropia in primary gaze, as compared to patients with severe GMFCS (GMFCS levels 3-5) (38% with 10 PD of heterotropia) (P < .05; χ2). Refractive errors included myopia (27.5% in mild cases and 41.6% in severe), emmetropia (10% in mild and 8.3% in severe) and hyperopia (62.5% in mild and 50% in severe). Around 50% of the mild cases had absent binocular fusion compared to 66.6% of those with severe CP. Amblyopia was found in 62.5% of the mild cases and 54.1% of the severe cases. Nystagmus was present in 25% with mild disease and 29.1% of those with severe disease.

CONCLUSION: Restoration of good ocular alignment in patients with CP is achievable in more than half of the cases. Patients with more severe CP have poorer outcomes than those with milder palsies. There appears to be no difference in outcomes between the different types of strabismus.

PMID:34779343 | DOI:10.1080/08820538.2021.2003823

J Reprod Infant Psychol. 2021 Nov 13:1-12. doi: 10.1080/02646838.2021.2001795. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnancy is a very important period in the development of attachment.

OBJECTIVE: To determine the correlation between prenatal attachment levels of healthy pregnant women and their styles of coping with stress and those of high-risk pregnant women.

METHOD: This descriptive study consisted of 76 women in their third-trimester of pregnancy hospitalised at the Obstetrics and Gynaecology service at a hospital and 210 women in their third-trimester of pregnancy who were experiencing a healthy pregnancy process and admitted to the Gynaecology Outpatient Clinic for pregnancy follow-up. The data were collected with the Personal Information Form, the Prenatal Attachment Inventory and the Stress Coping Styles Scale.

RESULTS: There was a statistically significant difference between the prenatal attachment levels of healthy and high-risk pregnant women. There was a positive correlation between the prenatal attachment levels and the self-confident and optimistic approaches among the styles of coping with stress in the healthy and high-risk pregnant women .

CONCLUSION: The attachment levels of the high-risk pregnant women were higher than were those of the healthy pregnant women. As the use of the self-confident and optimistic approach styles in coping with stress increases among healthy and high-risk pregnant women, so do their prenatal attachment levels.

PMID:34779334 | DOI:10.1080/02646838.2021.2001795

Scand J Surg. 2021 Nov 14:14574969211048707. doi: 10.1177/14574969211048707. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Current evidence suggests short-term survival benefit from endovascular aneurysm repair (EVAR) versus open surgical repair (OSR) in elective abdominal aortic aneurysm (AAA) procedures, but this benefit is lost during long-term follow-up. The aim of this study was to compare short- and mid-term all-cause mortality in patients with non-ruptured aneurysm treated by OSR and EVAR; and to assess the rate of complications and reinterventions, as well as to evaluate their impact on survival.

METHODS: The medical records of the non-ruptured AAA patients undergoing OSR or EVAR between 1 January 2011 and 31 December 2019 at Tartu University Hospital, Estonia, were retrospectively reviewed. We gathered survival data from the national registry (mean follow-up period was 3.7 ± 2.3 years).

RESULTS: A total of 225 non-ruptured AAA patients were treated operatively out of whom 95 (42.2%) were EVAR and 130 (57.8%) were OSR procedures. The difference in estimated all-cause mortality between the OSR and EVAR groups at day 30 was statistically irrelevant (2.3% vs 0%; p = 0.140), but OSR patients showed statistically significantly higher 5 year survival compared with EVAR patients (75.3% vs 50.0%, p = 0.002). Complication and reintervention rates for the EVAR and OSR groups did not differ statistically (26.3% vs 16.9%, p = 0.122; 10.5% vs 11.5%, p = 0.981, respectively). Multivariate analysis revealed that greater aneurysm diameter (p = 0.012), EVAR procedure (p = 0.016), male gender (p = 0.023), and cerebrovascular diseases (p = 0.028) were independently positively associated with 5-year mortality.

CONCLUSIONS: Thirty-day mortality, and complication and reintervention rates for EVAR and OSR after elective AAA repair were similar. Although the EVAR procedure is an independent risk factor for 5-year mortality, higher age and greater proportion of comorbidities among EVAR patients may influence not only the choice of treatment modality, but also prognosis.

PMID:34779283 | DOI:10.1177/14574969211048707

Drug Dev Ind Pharm. 2021 Nov 14:1-11. doi: 10.1080/03639045.2021.2001486. Online ahead of print.

ABSTRACT

Purpose of present study was to prepare and evaluate self-emulsifying drug delivery system (SEDDS) of curcumin (Cur) to enhance its solubility and percentage release for the evaluation of anti-inflammatory effect. Curcumin loaded SEDDS formulation was prepared, and zones of self-emulsification were recognized by dilution method for the construction of phase diagram. Lauroglycol FCC, Tween 80 (surfactant), and Transcutol HP (co-surfactant) were selected based on their solubility and highest emulsion region in phase diagram. Thermodynamic stability of Cur-SEDDS was calculated through globule size, zeta potential, polydispersity index (PDI), viscosity and pH. Cur-SEDDS were also characterized by encapsulation efficiency (EE %), FT-IR, in vitro release, and in vivo anti-inflammatory effect. Results revealed that droplet size of Cur-SEDDS was 19.77 ± 0.03 nm with their PDI 0.22 ± 0.19, zeta potential -19.33 ± 0.94 and viscosity 25.68 ± 0.86 cp. EE % of Cur-SEDDS was found to be 94.99 ± 0.38%, percentage release 65.83% compared with pure curcumin powder. The designed formulation possesses significant anti-inflammatory activity in paw edema when compared with positive control in carrageenan induced rat paw edema assay. Newly developed Cur-SEDDS with enhanced curcumin solubility, percentage release and better anti-inflammatory action may be an alternative source of oral delivery of curcumin.

PMID:34779318 | DOI:10.1080/03639045.2021.2001486

J Am Heart Assoc. 2021 Nov 15:e022303. doi: 10.1161/JAHA.121.022303. Online ahead of print.

ABSTRACT

Background Whether intravenous thrombolysis before mechanical thrombectomy provides additional benefit for functional outcome in acute ischemic stroke remains uncertain. We performed a meta-analysis to compare the outcomes of direct mechanical thrombectomy (dMT) to mechanical thrombectomy with bridging using intravenous thrombolysis (bridging therapy [BT]) in patients with acute ischemic stroke. Methods and Results We performed a literature search in the PubMed, Excerpta Medica database, and Cochrane Central Register of Controlled Trials from January 1, 2003, to April 26, 2021. We included randomized clinical trials and observational studies that reported the 90-day functional outcome in patients with acute ischemic stroke undergoing dMT compared with BT. The 12 included studies (3 randomized controlled trials and 9 observational studies) yielded 3924 participants (mean age, 68.0 years [SD, 13.1 years]; women, 44.2%; 1887 participants who received dMT and 2037 participants who received BT). A meta-analysis of randomized controlled trial and observational data revealed similar 90-day functional independence (odds ratio [OR], 1.04; 95% CI, 0.90-1.19), mortality (OR, 1.03; 95% CI, 0.78-1.36), and successful recanalization (OR, 0.93; 95% CI, 0.76-1.14) for patients treated with dMT or BT. Compared with those in the BT group, patients in the dMT group were less likely to experience symptomatic intracranial hemorrhage (OR, 0.68; 95% CI, 0.51-0.91; P=0.008) or any intracranial hemorrhage (OR, 0.71; 95% CI, 0.61-0.84; P<0.001). Conclusions In this meta-analysis of patients with acute ischemic stroke, we found no significant differences in 90-day functional outcome or mortality between dMT and BT, but a lower rate of symptomatic intracranial hemorrhage for dMT. These findings support the use of dMT without intravenous thrombolysis bridging therapy. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: 42021234664.

PMID:34779235 | DOI:10.1161/JAHA.121.022303