CET Group Research Articles

Luminal shape and aortic remodelling after total arch replacement for type A aortic dissection: conventional and frozen elephant trunks.

This study was performed to assess postoperative aortic remodelling (AR) after total arch replacement (TAR) for acute type A aortic dissection (AAD) with a frozen elephant trunk (FET) or conventional elephant trunk (cET). Furthermore, the shape of the residual true lumen (TL) was analyzed based on elliptical Fourier analysis (EFA) and evaluated as a predictor of AR. This study involved patients who underwent TAR with a cET or FET for AAD from December 2006 to January 2023 at five institutions. AR was assessed at the levels of the 4th thoracic vertebra (Th4), Th7, Th10, and above the coeliac trunk. The shape of the residual TL at all four levels was analyzed based on EFA to calculate shape patterns as principal component (PC) values. Inverse probability of treatment weighting (IPTW) was performed for adjustment between the groups. In total, 180 patients (88 with cET and 92 with FET) were enrolled. The complete AR rate, defined as false lumen remodelling throughout the entire descending thoracic aorta, was significantly higher in the FET than cET group (63.4% vs 32.0%, P = 0.0013). The IPTW-adjusted Fine-Gray regression model revealed that the mean PC2 (hazard ratio, 0.22; P < 0.001) and PC3 (hazard ratio, 0.24; P = 0.009) of the four levels were independent predictors of complete AR. In AAD repair, the AR rate was significantly higher with use of the FET than cET. The shape patterns of the residual TL can be an important reference for predicting postoperative AR.

Efficacy of high-intensity interval and continuous endurance trainings on cecal microbiota metabolites and inflammatory factors in diabetic rats induced by high-fat diet.

Physical exercise is known to modulate the intestinal microbiota composition and control the symptoms of metabolic syndrome. In this research, we intend to investigate and compare the effect of high-intensity interval and continuous endurance trainings (HIIT and CET) on cecal microbiota metabolites and inflammatory factors in diabetic rats. A number of Wistar rats were made diabetic by a high-fat diet and trained under two types of exercise protocols, HIIT and CET. After taking samples from the cecal tissue and serum of rats to reveal the effect of exercise, three microbial species from the Firmicute and Bacteroid phyla, which are the main types of intestinal microbes, and their metabolites include two short-chain fatty acids (SCFAs), butyrate and propionate and also, the inflammatory factors TLR4 and IL6 were analyzed through quantitative polymerase chain reaction (qPCR), high-performance liquid chromatography (HPLC), and Enzyme-linked immunosorbent assay (ELISA) methods. In general, exercise while increasing the representative of Firmicute has caused a relative reduction of Bacteroides and improved the concentration of SCFAs. In this regard, HIIT outperforms CET in up-regulating Akkermansia and Butyrivibrio expression, and butyrate and propionate metabolites concentration. Also, both exercises significantly reduced cecal expression of TLR4 and sera concentration of IL6 compared to the diabetic group, although the reduction rate was higher in the CET group than in HIIT. Our findings suggest that some symptoms of metabolic syndrome such as intestinal dysbiosis and the resulting metabolic disorders are better controlled by HIIT and inflammation by CET. Certainly, more extensive research on other contributing factors could help clarify the results.

Central executive training for ADHD: Impact on organizational skills at home and school. A randomized controlled trial.

The current randomized controlled trial (RCT) was the first to examine the benefits of central executive training (CET, which trains the working components of working memory [WM]) for reducing organizational skills difficulties relative to a carefully matched neurocognitive training intervention (inhibitory control training [ICT]). A carefully phenotyped sample of 73 children with attention-deficit/hyperactivity-impulsivity disorder (ADHD; ages 8-13, M = 10.15, SD = 1.43; 20 girls; 73% White/Non-Hispanic) participated in a preregistered RCT of CET versus ICT (both 10-week treatments). Parent-rated task planning, organized actions, and memory/materials management data were collected at pretreatment, posttreatment, and 2-4 month follow-up; teacher ratings were obtained at pretreatment and 1-2 month follow-up. CET was superior to ICT for improving organizational skills based on teacher report (Treatment × Time interaction: d = 0.61, p = .01, BF₁₀ = 31.61). The CET group also improved significantly based on parent report, but this improvement was equivalent in both groups (main effect of time: d = 0.48, p < .001, BF₁₀ = 3.13 × 10⁷; Treatment × Time interaction: d = 0.29, p = .25, BF₀₁ = 3.73). Post hocs/preregistered planned contrasts indicated that CET produced significant and clinically meaningful (number needed to treat = 3-8) pre/post gains on all three parent (d = 0.50 -0.62) and all three teacher (d = 0.46 -0.95) subscales, with gains that were maintained at 1-2 month (teacher report) and 2-4 month follow-up (parent report) for five of six outcomes. Results provide strong initial evidence that CET produces robust and lasting downstream improvements in school-based organizational skills for children with ADHD based on teacher report. These findings are generally consistent with model-driven predictions that ADHD-related organizational problems are secondary outcomes caused, at least in part, by underdeveloped working memory abilities. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risk of consecutive esotropia after surgery for intermittent exotropia according to passive duction force.

To determine the relationship between consecutive esotropia (ET) and passive duction force (PDF) in patients with intermittent exotropia (XT). The study enrolled 70 patients in whom PDF was measured under general anesthesia prior to XT surgery. The preferred eye for fixation (PE) and the nonpreferred eye for fixation (NPE) were determined using a cover-uncover test. The patients were subdivided into two groups according to the angle of deviation at 1 month postoperation: (1) consecutive ET (CET group), >10 prism diopters (PD) of ET; and (2) non-CET (NCET group), ≤10 ET or residual exodeviation. The relative PDF of the medial rectus muscle (MRM) was obtained by subtracting the ipsilateral PDF of the lateral rectus muscle (LRM) from the PDF of the MRM. The PDFs for the LRM in the PE in the CET and NCET groups were 47.28 g and 58.59 g, respectively (p = 0.147), and 56.18 g and 46.59 g for the MRM (p = 0.11), and in the NPE were 59.84 g and 55.25 g, respectively, for the LRM (p = 0.993), and 49.12 g and 50.53 g, respectively, for the MRM (p = 0.81). However, in the PE, the PDF in the MRM was larger in the CET group than in the NCET group (p = 0.045), which was positively associated with the postoperatively overcorrected angle of deviation (p = 0.017). An increased relative PDF in the MRM in the PE was a risk factor for consecutive ET after XT surgery. Quantitative evaluation of the PDF could be considered when planning strabismus surgery to achieve the desired surgical outcome.

Role of hemoperfusion combined with hemodialysis in acute severe organophosphorus pesticide poisoning: a meta-analysis

Abstract Background Acute severe organophosphorus pesticide poisoning is a common severe emergency in developing countries. Our meta-analysis aimed to clarify the efficacy of hemoperfusion combined with hemodialysis on acute severe organophosphorus pesticide poisoning. Methods Several databases were searched. After formulating relevant inclusion and exclusion criteria, qualified studies were included, and the data were extracted. The outcome indicators were the success rate of rescue, the time of hospitalization, the incidence of complications, the time for the cholinesterase level to return to normal, the coma time, and the atropine dosage. The results were analyzed using risk ratios, weighted mean difference, standard mean difference, and 95% confidence interval. The Cochrane Collaboration tool was used to assess the risk of bias in all the included studies. In terms of statistical methods, we used RevMan software (version 5.3; The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and Stata (versions 14 and 16; StataCorp, College Station, TX, USA) for the data analysis. Results We included 92 randomized controlled trials with 6899 participants. Compared with the conventional emergency treatment group (CET group), the hemoperfusion group (HP + CET group), and the hemodialysis group (HD + CET group), the use of hemoperfusion combined with hemodialysis based on CET (HP + HD + CET group) significantly increased the success rate of rescue and reduced hospitalization time, the incidence of complications, time for cholinesterase level to return to normal, coma time, and atropine dosage. Conclusion Hemoperfusion combined with hemodialysis is effective in the treatment of acute severe organophosphorus pesticide poisoning. In the future, more scientifically designed, large-scale, high-quality, multicenter randomized controlled trials are needed to validate this study further.

Effectiveness of Unsupervised Exercise Therapy After Endovascular Treatment for an Iliac Occlusive Lesion.

Exercise therapy has acceptable outcomes for patients with intermittent claudication (IC), but there are few reports on the results of continuous unsupervised exercise therapy after endovascular treatment (EVT) for an iliac lesion. The aim of this study is to analyze the long-term outcomes of unsupervised exercise therapy for patients after EVT. A retrospective analysis was performed in 76 patients (93 limbs) with IC who underwent iliac EVT from 2012 to 2020 at our hospital. Maintenance of unsupervised exercise therapy was evaluated at 6months after EVT. Long-term outcomes such as primary patency, clinically driven target lesion revascularization (CD-TLR), survival, and major adverse cardiovascular events (MACE) were compared between patients who continued (cET group) or discontinued (dET group) unsupervised exercise therapy. A total of 28 patients (37%) continued unsupervised exercise therapy until 6months after EVT for an iliac lesion. There were no differences in patient background and procedural details between the cET and dET groups. The follow-up rate was 96% in a median follow-up period of 35 [25 - 42]months. The mean exercise time in the cET group was 52 ± 18minutes daily, with a mean frequency of 5.8 ± 1.1days per week. The median step count in the cET group was 5559 ± 2908 steps daily. At 3years, the cET group had significantly higher rates for primary patency (97% vs 71%, P = .002), and freedom from CD-TLR (97% vs 79%, P = .007); and a tendency for higher survival (100% vs 94%, P = .074), and higher freedom from MACE (89% vs 73%, P = .12). The findings of this study suggested superior long-term outcomes, including primary patency, freedom from CD-TLR, survival, and freedom from MACE, in patients who maintained continuous unsupervised exercise therapy after EVT.

Does central executive training and/or inhibitory control training improve emotion regulation for children with attention-deficit/hyperactivity disorder? A randomized controlled trial.

Approximately 48-54% of children with attention-deficit/hyperactivity disorder (ADHD) have impairing difficulties with emotion regulation, and these difficulties are not ameliorated by first-line ADHD treatments. Working memory and inhibitory control represent promising intervention targets given their functional, if not causal, links with ADHD-related emotion dysregulation. This preregistered randomized controlled trial tested whether two digital therapeutic training protocols that have been previously shown to improve working memory (Central Executive Training [CET]) and inhibitory control (Inhibitory Control Training [ICT]) can improve emotion regulation in a sample of 94 children with ADHD aged 8-13 years (M = 10.22, SD = 1.43; 76% White/non-Hispanic; 29 girls). Results of Bayesian mixed model ANOVAs indicated both treatment groups demonstrated significant decreases in emotion dysregulation relative to pre-treatment at immediate post-treatment (parent report; d = 1.25, BF10 = 8.04 × 1013, p < 0.001), at 1-2 months after completing treatment (teacher report; d = 0.99, BF10 = 1.22 × 106, p < 0.001), and at 2-4-months follow-up (parent report; d = 1.22, BF10 = 1.15 × 1014, p < 0.001). Contrary to our hypotheses, the CET and ICT groups demonstrated equivalent reductions in emotion dysregulation and maintenance of effects. Exploratory analyses revealed that results were robust to control for informant expectancies, ADHD medication status/changes, in-person vs. at-home treatment, child age, and time from treatment completion to post-treatment ratings. To determine whether working memory and inhibitory control are causally linked with ADHD-related emotion dysregulation, future studies should include active control conditions that do not train executive functions prior to making decisions about the clinical utility of CET/ICT for the treatment of emotion dysregulation in ADHD. [https://clinicaltrials.gov/], identifier [NCT03324464].

Volume Changes in the Descending Aorta after Frozen Elephant Trunk and Conventional Hemi-Arch Repair after Acute Type A Aortic Dissection.

The aim of this study was to compare the mortality rates, re-intervention rates, and volumetric changes in aortas following surgery, in terms of the true lumen and false lumen changes, using conventional hemi-arch repair (CET) and frozen elephant trunk (FET) techniques. During the period from 2015 to 2018, 66 patients underwent surgical treatment for acute aortic dissection (Debakey type 1). Demographic and procedure-related data were evaluated. We measured volumetric change before surgical treatment, at discharge, and at 12- and 24-month time points based on computed tomography angiography. The study cohort was divided into two groups (FET vs. CET). The mean age of the patients was 56.9 ± 9.4 years in the FET group versus 63.6 ± 11 years in the CET group (p = 0.063). The mean follow-up time was 24 ± 6 and 25 ± 5 months for the FET and CET groups, respectively. There were no significant differences between the two groups in terms of the medical histories of the cohorts. The results showed a significant increase in true lumen volume after the FET procedure (within 24 months postoperatively; p = 0.005), and no significant changes in total (p = 0.392) or false lumen (p = 0.659) volumes were noted. After the CET procedure, there were significant increases in total and false lumen volumes (p = 0.013, p = 0.042), while no significant change in true lumen was observed (p = 0.219). The volume increase in true lumen after the FET procedure was higher compared to the CET group at all postoperative time points (at discharge, 12 months, and 24 months) without significant evidence (p = 0.416, p = 0.422, p = 0.268). At two years, the volume increase in false lumen was significantly higher among the CET group compared to the FET group (p = 0.02). The Kaplan–Meier curve analysis showed that patients who underwent the CET procedure underwent significantly more re-interventions due to false lumen expansion of the descending aorta (p = 0.047). Present study results indicate that the true and false lumen changes in the aorta following the FET and CET procedures were different. FET led to a significant increase in true lumen volume, while false lumen volume remained stable; however, after the CET procedure, significant false lumen enlargement was noted at mid-term follow-up time points. The re-intervention rate after CET was higher due to false lumen expansion.

L-Glutamine supplementation enhances glutathione peroxidase and paraoxonase-1 activities in HDL of exercising older individuals.

Oxidative stress is an important factor in the formation of atherosclerotic plaques. High-density lipoprotein (HDL) harbors paraoxonase-1 (PON-1) and glutathione peroxidase (GPx), key enzymes in the protection against the harmful effects of oxidative stress. Although exercise training can increase both HDL-c content and its antioxidant action, and glutamine (Gln) intake also promotes GPx-based defenses, the association between exercise training and Gln in the regulation of PON-1 activity was not explored. Therefore, the objective of this study was to investigate the effects of Gln supplementation on the redox balance and on the total HDL antioxidant capacity by evaluation of the activity of PON-1 and GPx enzymes in physically exercised elderly individuals compared to non-exercised ones. Fifty-one practitioners of a combined exercise training program (CET, age: 71.9±5.7years) and 32 non-practitioners (NP, age: 73±6.3years) participated in the study. CET and NP groups were separated into 2 subgroups according to the supplementation: Gln, 0.3g/kg/day + 10g maltodextrin (CET-Gln, n=26; and NP-Gln, n=16) or placebo, 10g maltodextrin (CET-PL, n=25; and NP-PL, n=16). Blood samples were drawn at baseline and after 30days after commencement of the supplementation for biochemical and enzyme activity analyses. Increased HDL-c, total peroxidase (PRx), and GPx activities were found in both CET-Gln and NP-Gln after the supplementation period, compared to baseline, in opposition to CET-PL and NP-PL groups. PON-1 activity increased only in CET-Gln. In both CET-Gln and NP-Gln groups, there was a reduction of the total peroxides/PRx, iron/PRx, and total peroxides/GPX ratios after supplementation. In CET-Gln, thiobarbituric acid-reactive substances (TBARS)/PRx and TBARS/GPx ratios were also lower after supplementation. CET-Gln and CET-PL subgroups had lower glycemia than NP-Gln and NP-PL, either at baseline or after the supplementation periods. The other parameters were unchanged after supplementation [total cholesterol, LDL-c, triglycerides, non-HDL cholesterol, total peroxides, TBARS, iron serum, Trolox-equivalent antioxidant capacity (TEAC), and uric acid]. Gln supplementation can increase glutathione peroxidase activity regardless the individuals were physically active or sedentary, but the PON-1 activity only increased in physically active individuals. These results show the potential of Gln supplementation in the maintenance of the vascular redox balance, with potential implications for atherogenesis protection.

Better Response to Influenza Virus Vaccination in Physically Trained Older Adults Is Associated With Reductions of Cytomegalovirus-Specific Immunoglobulins as Well as Improvements in the Inflammatory and CD8+ T-Cell Profiles.

Chronic cytomegalovirus (CMV) infection is a trigger factor for the development of immunosenescence and negatively impacts the immune response to influenza virus vaccination (IVV) in older adults. However, the role of physical exercise training in this context is unknown. Thus, the aim of this study was to investigate whether the regular practice of combined exercise training can improve the specific antibody response to IVV in CMV-seropositive older adults. Eighty older adults were distributed into two groups—non-practitioners (NP, n = 31, age = 74.06 ± 6.4 years) and practitioners of combined exercise training (CET, n = 49, age = 71.7 ± 5.8 years)—for at least 12 months. Both volunteer groups were submitted to IVV and blood samples were collected before (pre) and 30 days after (post) the vaccination. Concerning the specific antibody response to IVV, higher serum levels of specific immunoglobulin A (IgA) were found in the CET group post- than pre-vaccination (p < 0.01), whereas higher levels of specific immunoglobulin M (IgM) were observed both in the NP (p < 0.05) and CET (p < 0.001) groups post-vaccination as compared to the pre-vaccination values. Serum levels of specific immunoglobulin G (IgG) for IVV and CMV, as well as interleukin 6 (IL-6) and IL-10, were similar between the time points evaluated. However, the IL-10/IL-6 ratio post-vaccination was higher (p < 0.05) in the CET group than that before vaccination. Negative correlations were observed between the specific IgG levels for IVV and CMV only in the CET group, both pre- and post-vaccination. In addition, negative correlations were found between IL-10 and specific IgG for CMV in all volunteer groups pre- and post-vaccination, whereas a positive correlation between IL-10 and specific-IgG for IVV pre- and post-vaccination was observed in the CET group. In addition, with the hemagglutination inhibition (HAI) assay, it was found that 32.2% of the NP group and 32.6% of the CET group were responders to IVV and displayed reductions in the CMV serostatus (p < 0.05 and p < 0.001, respectively) and increases in naive and effector CD8+ T cells post-vaccination (p < 0.01). However, only the responders from the CET group showed significant reductions in the ratio of effector to naive CD8+ T cells (p < 0.05) and increased IL-10 levels post-vaccination (p < 0.001). In summary, this study demonstrates that the improvement in the response to IVV in CMV-seropositive older adults was related to an anti-inflammatory status and enhancement of naive CD8+ T cells, particularly associated with regular practice of CET.

Short- and mid-term outcomes of the frozen elephant-trunk procedure for degenerative aortic arch aneurysm.

The frozen elephant-trunk (FET) procedure is used widely in total aortic arch replacement (TAR) surgery; however, its safety, effectiveness, and long-term outcomes compared with those of the conventional elephant trunk (cET) procedure for degenerative aneurysms are unclear. Between July, 2011 and August, 2019, 126 patients underwent elective total aortic arch replacement at our institution. We compared the short- and mid-term outcomes of 60 patients who underwent the FET procedure (FET group) with those of 66 patients who underwent cET (cET group). The in-hospital mortality rate tended to be lower in the FET group than in the cET group (p = 0.12). There were two cases of paraplegia (3.3%) in the FET group and in none in the cET group. The all-cause mortality at the 3-year follow-up did not differ significantly between the groups (p = 0.31). The FET group required more unexpected interventions at the surgical site in the mid-term period. FET was associated with a shorter operative time and lower surgical mortality than cET. Although the mid-term total aortic arch replacement outcomes of FET were acceptable, careful imaging observation is necessary because reinterventions were required more frequently.

A Prospective Real-World Multi-Center Study to Evaluate Progression-Free and Overall Survival of Radiotherapy with Cetuximab and Platinum-Based Chemotherapy with Cetuximab in Locally Recurrent Head and Neck Cancer.

Simple SummaryDespite recent developments in immune checkpoint inhibitors, the treatment of locoregionally recurrent head and neck squamous cell cancer (HNSCC) remains challenging. Prospective data comparing re-irradiation with systemic treatment are not available. The SOCCER trial represents a prospective non-interventional multicenter trial that enrolled patients with locoregionally recurrent HNSCC treated with cetuximab in combination with re-radiotherapy or chemotherapy. A total of 192 patients were analyzed. Radiotherapy combined with cetuximab had superior progression-free and overall survival compared to chemotherapy with cetuximab. This highlights the high efficacy of local re-radiotherapy in combination with cetuximab in patients with locoregionally recurrent HNSCC.Treatment options of locoregional recurrent head and neck squamous cell cancer (HNSCC) include both local strategies as surgery or re-radiotherapy and systemic therapy. In this prospective, multi-center, non-interventional study, patients were treated either with platinum-based chemotherapy and cetuximab (CT + Cet) or re-radiotherapy and cetuximab (RT + Cet). In the current analysis, progression-free survival (PFS) and overall survival (OS) were compared in patients with locoregional recurrence. Four hundred seventy patients were registered in 97 German centers. After exclusion of patients with distant metastases, a cohort of 192 patients was analyzed (129 CT + Cet, 63 RT + Cet). Radiotherapy was delivered as re-irradiation to 70% of the patients. The mean radiation dose was 51.8 Gy, whereas a radiation dose of ≥60 Gy was delivered in 33% of the patients. Chemotherapy mainly consisted of cisplatin/5-flurouracil (40%) or carboplatin/5-flurouracil (29%). The median PFS was 9.2 months in the RT + Cet group versus 5.1 months in the CT + Cet group (hazard ratio for disease progression or death, 0.40, 95% CI, 0.27–0.57, p < 0.0001). Median OS was 12.8 months in the RT + Cet group versus 7.9 months in the CT + Cet group (hazard ratio for death, 0.50, 95% CI, 0.33–0.75, p = 0.0008). In conclusion, radiotherapy combined with cetuximab improved survival compared to chemotherapy combined with cetuximab in locally recurrent HNSCC.

Comparison of sprint interval and continuous endurance training on oxidative stress and antioxidant adaptations in young healthy adults

Background: Different intensities of exercise induce varying levels of reactive oxygen species, causing oxidative stress. However, regular physical training enhances the antioxidant system and protects tissues by oxidative stress. This study aimed to investigate the difference in markers between time-efficient low-volume high intensity interval (sprint interval training: SIT) and traditional high-volume low-intensity methods (continuous endurance training: CET) regarding oxidative stress and antioxidant levels. Material and methods: Fifteen male volunteers were divided into two groups according to their VO2max levels. The SIT program consisted of 4–6 Wingate all-out sprints with a 4.5 min recovery, while CET consisted of 30–50 min cycling at 60% VO2max for seven weeks. Total oxidant status (TOS), total antioxidant status (TAS), plasma malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels were examined in pre and post-intervention. Results: Increases in GSH-Px (30% vs. 55%), TOS (33% vs. 18%) and a significant decrease in MDA (8.6%, p&lt;0.003; 6.8%, p&lt;0.016) in CET and SIT were observed, respectively. By contrast, TAS decreased (62%) after CET and increased (17%) after SIT. No significant differences in these parameters were reported after the training period between SIT and CET groups. Conclusions: SIT was suggested as a safe exercise model to improve general health and the performance of traditional CET.

Efficacy of second and subsequent lines of chemotherapy for recurrent and metastatic head and neck cancer

ObjectiveThe increase in treatment options resulted in successful treatment with multiple lines of chemotherapy for recurrent and metastatic (RM) head and neck cancer (HNC). The present study aimed to elucidate the beneficial effect of successive treatment for RM-HNC. MethodsWe included 78 patients with RM-HNC who received one or multiple lines of chemotherapy from January 2008 to December 2019. We divided the patients into three groups according to treatment period: January 2008 to November 2012 included those who underwent cancer chemotherapy only with cytotoxic agents (Tox group), December 2012 to March 2017 included those who received cytotoxic agents and cetuximab (Cet group), and March 2017 to December 2019 included those who received cytotoxic agents, cetuximab and immune checkpoint inhibitor nivolumab (Nivo group). Moreover, we compared the overall survival of the three groups. ResultsIn total, 18, 33, and 27 patients were included in the Tox, Cet, and Nivo groups, respectively. The median overall survival were 8.5 months in the Tox group, 16 months in the Cet group, and 19 months in the Nivo group, and the difference in the result was significant. ConclusionsSuccessive treatment with second and subsequent lines of chemotherapy in patients with RM-HNC improves prognosis.

Customized Frozen Embryo Transfer after Identification of the Receptivity Window with a Transcriptomic Approach Improves the Implantation and Live Birth Rates in Patients with Repeated Implantation Failure

The aim of this prospective study was to evaluate outcome benefits expected in repeated implantation failure (RIF) patients (n = 217) after customized embryo transfer based upon identification of the receptivity window by transcriptomic approach using the Win-Test. In this test, the expression of 11 endometrial genes known to be predictive of endometrial receptivity is assessed by RT-PCR in biopsies collected during the implantation window (6–9 days after the spontaneous luteinizing hormone surge during natural cycles, 5–9 days after progesterone administration during hormone replacement therapy cycles). Then, patients underwent either customized embryo transfer (cET, n = 157 patients) according to the Win-Test results or embryo transfer according to the classical procedure (control group, n = 60). Pregnancy and live birth rates were compared in the two groups. The Win-Test showed that in 78.5% of women, the receptivity window lasted less than 48 h, although it could be shorter (< 24 h, 9.5%) or longer (> 48 h, 12%). This highlighted that only in 20% of patients with RIF the endometrium would have been receptive if the classical embryo transfer protocol was followed. In the other 80% of patients, the receptivity window was delayed by 1–3 days relative to the classical timing. This suggests that implantation failure could be linked to inadequate timing of embryo transfer. In agreement, both implantation (22.7% vs. 7.2%) and live birth rates per patient (31.8% vs. 8.3%) were significantly higher in the cET group than in the control group. cET on the basis of the Win-Test results could be proposed to improve pregnancy and live birth rates.ClinicalTrials.gov ID: NCT04192396; December 5, 2019, retrospectively registered.

A Retrospective Exploration of Targeted Maintenance Therapy in Advanced Colorectal Cancer: Based on the Background of Chinese Patient Assistance Program.

Background: Maintenance therapy with bevacizumab (Bev) in patients with colorectal cancer (CRC) provides progression-free survival (PFS) benefits. However, the role of maintenance therapy with an anti-EGFR monoclonal antibody has not been established.Methods: Eligible CRC patients were assigned to maintenance therapy with cetuximab (Cet; Cet group) or Bev (Bev group). PFS, the duration of maintenance therapy, and safety were analyzed. Cox multivariate regression analyses were performed to determine independent prognostic factors.Results: A total of 143 eligible patients were assigned to the Cet (n = 79) or Bev (n = 64) groups. In the Cet group, all patients had KRAS wild-type. The baseline characteristics were well-balanced between the two groups, except for a higher percentage of patients with a left-sided primary tumor in the Cet group than in the Bev group (86.1 vs. 62.5%, P < 0.0001). The median PFS was not significantly different between the Cet group and the Bev group: 5.9 months (95% CI 2.30–9.50) vs. 7.0 months (95% CI 3.69–10.31) (HR 1.17, 95% CI 0.77–1.79, P = 0.45). The median duration of maintenance therapy in the Cet group was shorter than that in the Bev group: 4.0 months (95% CI 1.94–5.99) vs. 4.8 months (95% CI 2.68–6.98) (HR 0.90, 95% CI 0.61–1.33; P = 0.59). The subgroup analyses showed that the median PFS for the first maintenance therapy and the second maintenance therapy were 3.2 months (95% CI 1.69–4.78) and 5.2 months (95% CI 1.58–8.83), respectively (HR 0.89, 95% CI 0.44–1.81; P = 0.75).Conclusions: This study suggests that maintenance therapy with Cet or Bev can be considered an appropriate option following induction chemotherapy for selected patients with advanced CRC. Multiple maintenance therapy seems to confer survival benefits in advanced CRC. Maintenance therapy with Cet after first-line induction chemotherapy seems to be associated with greater survival benefits.

L-Glutamine Supplementation Improves the Benefits of Combined-Exercise Training on Oral Redox Balance and Inflammatory Status in Elderly Individuals.

Although regular combined aerobic-resistance exercises can ameliorate the inflammatory status and redox balance in elderly population, it is unclear whether protein or specific amino acid supplementation could improve such benefits. Therefore, we aimed to evaluate the inflammatory status and redox indexes through of the saliva of 34 elderly subject nonpractitioners (NP group, 73.3 ± 6.6 years) and 49 elderly subject practitioners of a combined-exercise training in moderate intensity (CET group, 71.9 ± 5.8 years) before (pre) and after (post) 30 days of supplementation with L-glutamine (Gln) or placebo (PL). Our results showed that, both in pre- and postsupplementation, the salivary levels of nitric oxide (NO·) and TNF-α were lower, whereas the levels of uric acid and IL-10 (as well as IL-10/TNF-α ratio) were higher in the CET groups than in the NP groups. In postsupplementation, both groups supplemented with Gln (NP-Gln and CET-Gln) showed higher salivary uric acid levels compared to baseline. In addition, lower NO· levels were found in the CET-Gln group postsupplementation than presupplementation values. Whereas the CET-Gln group showed lower GSH levels postsupplementation, NP-Gln subjects showed lower GSSG levels at the same time point, both compared to baseline. Interestingly, salivary peroxidase activity was lower only in NP groups (NP-PL and NP-Gln) postsupplementation than baseline values. A positive significant correlation between salivary peroxidase activity and GSH levels, and also between salivary peroxidase activity and uric acid levels were observed in the CET-Gln group both pre- and postsupplementation. No differences were found in albumin, total antioxidant activity (TEAC), and reducing power analysis between groups, pre- or postsupplementation. In conclusion, the elderly subjects from the CET group showed a better inflammatory response and redox balance and, for the first time, it was shown that daily supplementation with Gln for 30 days can improve these benefits with putative association with a healthy aging.

Circulatory and ventilatory power in diabetic patients: Secondary analysis of a randomized controlled trial.

Circulatory (CP) and ventilatory power (VP) have been used to improve the prognostic accuracy of cardiopulmonary exercise tests in cardiovascular disease, such as coronary artery disease. However, the effects of combined resistance and aerobic exercise program on VP and CP, especially in type 2 diabetes patients, have not been adequately investigated. Thus, this new parameter can be useful to prescribe exercise programs more assertive for this population. The present study aimed to assess the effect of 3 months of combined resistance and aerobic exercise training (CET) on CP and VP in patients with type 2 diabetes. A randomized controlled trial was conducted involving 48 diabetic patients with an average age of 52.4 (±8.01) years old. The subjects were randomized into two groups: sedentary (SG, n = 15) and the CET group (n = 19). Cardiopulmonary exercise testing (symptom-limited incremental) was performed on a cycle ergometer, and the following parameters were measured: relative VO2 , VE /VCO2 slope, linear relationship between oxygen uptake and minute ventilation, and VCO2 . CET was performed with 30-min aerobic and 30-min resistance exercises three times a week for 12 weeks. Significant (p < .05) and clinical (d ≥ .80) differences were observed that favoured CET compared with SG for the following variables: heart rate, workload, VO2 relative peak, circulatory power peak, and VCO2 peak. Although no statistical difference was observed for ventilatory power, there was a clinical difference (p > .05 and d ≥ 0.80) that favoured CET. Three months of combined exercise training improved VP and CP indices in patients with type 2 diabetes when compared with a sedentary group.

A Mobile Phone App Featuring Cue Exposure Therapy As Aftercare for Alcohol Use Disorders: An Investigator-Blinded Randomized Controlled Trial

BackgroundCue exposure therapy (CET) is a psychological approach developed to prepare individuals with alcohol use disorder (AUD) for confronting alcohol and associated stimuli in real life. CET has shown promise when treating AUD in group sessions, but it is unknown whether progressing from group sessions to using a mobile phone app is an effective delivery pathway.ObjectiveThe objectives of this study were to investigate (1) whether CET as aftercare would increase the effectiveness of primary treatment with cognitive behavior therapy, and (2) whether CET delivered through a mobile phone app would be similarly effective to CET via group sessions.MethodsA total of 164 individuals with AUD were randomized to one of three groups: CET as group aftercare (CET group), CET as fully automated mobile phone app aftercare (CET app), or aftercare as usual. Study outcomes were assessed face-to-face at preaftercare, postaftercare, and again at 6 months after aftercare treatment. Generalized mixed models were used to compare the trajectories of the groups over time on drinking, cravings, and use of urge-specific coping skills (USCS).ResultsIn all, 153 of 164 individuals (93%) completed assessments both at posttreatment and 6-month follow-up assessments. No differences in the trajectories of predicted means were found between the experimental groups (CET group and app) compared with aftercare as usual on drinking and craving outcomes over time. Both CET group (predicted mean difference 5.99, SE 2.59, z=2.31, P=.02) and the CET app (predicted mean difference 4.90, SE 2.26, z=2.31, P=.02) showed increased use of USCS compared to aftercare as usual at posttreatment, but this effect was reduced at the 6-month follow-up. No differences were detected between the two experimental CET groups on any outcomes.ConclusionsCET with USCS delivered as aftercare either via group sessions or a mobile phone app did not increase the effectiveness of primary treatment. This suggests that CET with USCS may not be an effective psychological approach for the aftercare of individuals treated for AUD.Trial RegistrationClinicalTrials.gov NCT02298751; https://clinicaltrials.gov/ct2/show/NCT02298751

Changes in KRAS mutations in patients with oral mucosa and tongue cancer (OMTC) undergoing medical treatment with cetuximab (Cet).

e17524 Background: Mutations in KRAS are known to be predictors of anti-EGFR therapy efficacy. Besides the mutation status of the treatment-naive tumors the changes in the level of mutant DNA during medical treatment are also of clinical interest for the individualization of the treatment. The purpose of the study was to detect somatic single nucleotide polymorphism (SNP) activating mutations in KRAS exon 2 in patients (pts) with OMTC undergoing chemotherapy (CT)±Cetuximab (Cet). Methods: Extracellular DNA samples were obtained from plasma of pts with OMTC (T3-4No-1Mo) undergoing CT (CDDP+5FU)+Cet (group A) before treatment and in 2 weeks after. Patients undergoing CT (CDDP+5FU, no Cet) were included in Group B. 7 activating mutations in KRAS exon 2 were detected by Droplet Digital PCR method (DD PCR) with "KRAS Screening Multiplex Kit" (BioRad, USA). Results: Samples from 28 pts were included. The frequency of SNP activating in KRAS exon 2 before treatment was 25%. In the group A (n = 12) KRAS mutations were not found or the level of mutant DNA did not exceed 1%. No significant changes were found in this group after treatment. The group B (n = 16) had some KRAS variations the majority of which did not change after treatment. However, 2 pts had a sharp increase in mutant DNA: from 0.03% before CT in both cases to 17.04% and 56.38% -after treatment (p &lt; 0.01). Conclusions: Medical treatment, especially CT, could cause the changes in activating mutations in KRAS exon 2 in pts with OMTC. Revealing of these changes is of great importance for the following treatment options. Detection of mutant extracellular DNA by DD PCR could be valuable to monitor their status during the treatment.