Months In Group Research Articles

An acceptance and commitment therapy and mindfulness group intervention for the psychological and physical well-being of adults with body mass indexes in the overweight or obese range: The Mind&Life randomized controlled trial

This trial aimed to assess the effect of an acceptance and commitment therapy (ACT) and mindfulness-based intervention on the various psychological and physical issues associated with obesity. A parallel group randomized controlled trial was conducted with 142 adults with body mass indexes in the overweight or obesity range seeking treatment. Participants were assigned either to the ACT and mindfulness-based group intervention (Mind&Life intervention) plus treatment as usual (TAU) or the TAU-only condition. Individuals receiving the Mind&Life intervention with TAU showed more adherence to the Mediterranean diet, and greater decrease in external eating, weight, and visceral fat both at posttreatment and at 6-month follow-up. Moreover, they displayed a greater reduction in total protein and animal protein intake and GPT enzymes level. By 6-month follow-up, the Mind&Life group experienced a lower impact of weight on quality of life than TAU participants. However, Mind&Life intervention completers showed greater restrained eating levels at follow-up. Overall, this study suggests that an ACT and mindfulness-based group intervention could produce improvements in the impact of weight on quality of life, some eating behaviors, dietary habits, and weight and body composition parameters of people facing weight-related challenges.

Changes of lung function and inflammatory factors in rat models of coal workers' pneumoconiosis

Objective: To observe the changes of lung function and inflammatory factors in rat models of coal workers' pneumoconiosis at different time points. Methods: In June 2021, 96 healthy male SD rats with SPF grade were divided into 1, 3, and 6-month control group and dust staining group (coal dust group, coal silica dust group, quartz group) according to random number table method, with 8 rats in each group. After one week of adaptive feeding, a one-time non-exposed tracheal perfusion method (1 ml/ piece) was used. The dust dyeing group was given 50 g/L coal dust, coal silica mixed dust and quartz dust suspension, respectively, and the control group was given 0.9% normal saline solution. At 1, 3 and 6 months after perfusion, lung function was detected by animal lung function apparatus, then all lung tissues and alveolar lavage fluid were killed, and lung histopathological morphological changes were observed by HE staining, and the contents of interleukin (IL-1β), IL-18, IL-4 and IL-10 in alveolar lavage fluid were detected by ELISA. One-way analysis of variance was used to compare groups. Two factors (inter-group treatment factor (4 levels) and observation time factor (3 levels) ) were used in the analysis of the effects of inter-group treatment and treatment time on related indicators. Results: HE staining results showed that coal spot appeared in the lung tissue of coal dust group, coal spot and coal silicon nodule appeared in the lung tissue of coal dust group, and silicon nodule appeared in the lung tissue of quartz group. Compared with the control group, the forced vital capacity (FVC) and forced expiratory volume at 0.2 second (FEV(0.2)) of rats in the dust staining group had interaction between the treatment and treatment time (P<0.05). With the increase of dust dyeing time, FVC and FEV(0.2) decreased significantly at 3-6 months of dust dyeing, and the maximum gas volume per minute (MVV) decreased significantly at 1-3 months of dust dyeing (P<0.05). The lowest lung function index was in quartz group, followed by coal-silica group and coal-dust group. There were statistically significant differences in the main effect and interaction effect of the pro-inflammatory factor IL-18 among all groups in treatment and treatment time (IL-18: F=70.79, 45.97, 5.90, P<0.001), and interaction existed. The highest content of inflammatory factors in alveolar lavage fluid of all dust groups was quartz group, followed by coal silica group and coal dust group. There were significant differences in the main effect and interaction effect of anti-inflammatory factors between groups and treatment time (IL-4: F=41.55, 33.01, 5.23, P<0.001, <0.001, <0.001; IL-10: F=7.46, 20.80, 2.91, P=0.002, <0.001, 0.024), and there was interaction. The highest content of anti-inflammatory factor was in quartz group, followed by coal silica group and coal dust group. Conclusion: Lung function decreased and levels of inflammatory fators increased in rat models of coal workers' pneumoconiosis, with the quartz group being the most severely damaged. Lung function is mainly impaired in thrid-six months, and the content of inflammatory factors begins to change in first-thrid months. MVV are the earliest and most obvious in lung function. IL-18 is suitable for monitoring changes in the pro-inflammatory response of coal workers' pneumoconiosis, and IL-10 is suitable for monitoring changes in anti-inflammatory response.

Effects of Social Isolation and Loneliness on Heart Failure Self-care: A Cross-sectional Analysis.

Patients with heart failure (HF) who engage in effective HF self-care have better quality of life, and lower risks of all-cause and HF-related hospital readmission and mortality. It is unclear whether social isolation and loneliness, which are prevalent among patients with HF and known to affect other self-care behaviors, can predict HF self-care. The aim was to explore the relationship between social isolation, loneliness, and HF self-care. This was a cross-sectional secondary analysis (n = 49) of the GEtting iNTo Light Exercise for HF randomized controlled trial, a 6-month home-based live group gentle exercise intervention for patients with HF. Measures included the following: 6-item Lubben Social Network Scale for social isolation, Patient-Reported Outcomes Measurement Information System Social Isolation survey for loneliness, Self-Care of Heart Failure Index, and Patient-Reported Outcomes Measurement Information System Depression survey. Multiple linear regression modeling was used to examine the relationships of 4 HF self-care processes to social isolation and loneliness, adjusting for depression and grouping (control group or intervention group). Scores indicating less social isolation predicted higher self-care maintenance (B = 0.937, P = .015), monitoring (B = 0.799, P = .041), and management (B = 1.812, P < .001). Loneliness did not predict HF self-care. To our knowledge, this is the first study to predict HF self-care using distinct measures for social isolation and loneliness. Patients who were less socially isolated engaged in better HF self-care; loneliness had no relationship with HF self-care. Prospective studies are needed to investigate causal relationships between social isolation and HF-self-care engagement to determine the effect on outcomes such as hospital readmission and mortality.

Low thoracic skeletal muscle is a risk factor for 6-month mortality of severe community-acquired pneumonia in older men in intensive care unit

BackgroundPatients with severe community-acquired pneumonia (sCAP) admitted to the intensive care unit (ICU) often exhibit muscle catabolism, muscle weakness, and/or atrophy, all related to an increased morbidity and mortality. However, the relationship between thoracic skeletal muscle mass and sCAP-related mortality has not been well-studied. Early recognition of sarcopenia in ICU patients with sCAP would benefit their prognosis.MethodsA retrospective study was conducted in Taizhou Hospital of Zhejiang Province, involving 101 patients with sCAP admitted in the ICU between December 2022 and February 2023. We measured the cross-sectional aera of the pectoralis, intercostal, paraspinal, serratus, and latissimus muscles at the T4 vertebral level (T4CSA) using chest computed tomography. Discriminatory thresholds were established by performing receiver operating characteristic curve analysis, with a designated cutoff value of 96.75 cm2 for male patients. This cohort was classified into mortality and survival groups based on a 6-month post-admission outcome. Univariate and multifactorial logistic regression analyses were performed to validate the correlation between low thoracic skeletal muscle area and prognostic outcomes.ResultsThe mean age of the patients was 75.39 ± 12.09 years, with an overall 6-month mortality of 73.27%. T4CSA of the 6-month survival group was significantly larger than that in the mortality group for overall cohort. The T4CSA in the survival group was significantly larger than that in the mortality group (104.29 ± 23.98cm2 vs. 87.44 ± 23.0cm2, p = 0.008). T4CSA predicted the 6-month mortality from sCAP in males with an AUC of 0.722 (95% confidence interval (CI), 0.582–0.861). The specificity and sensitivity were 71.4% and 71.1%, respectively, (p < 0.05). No significant difference was observed between the two groups in terms of T4CSA.ConclusionsThis study revealed that low thoracic skeletal muscle mass increased the risk of all-cause 6-month mortality in ICU patients with sCAP, particularly among male patients.

Examining the Impact of Health Belief Model-Based Education on Reproductive Health and Family Planning Attitudes Among Married Women

Introduction: Reproductive health services include maternal, child, and newborn health, family planning, fertility issues, and reproductive education, primarily benefiting women. Aim: It was aimed to examine the effects of Health Belief Model based instruction on married women protective attitudes toward reproductive health. Method: The study was designed as a quasi-experimental method with unequal groups for pre-test and posttest comparison. A total of 175 women, 35 in the experimental group, 70 in the control group-1, and 70 in the control group-2, who met the study criteria and were determined by a comprehensive power analysis, were included in the study. The pre-test data were collected using the Personal Information Form, the Married Women’s Reproductive Health Attitudes Determination Scale, and the Family Planning Attitude Scale. Experimental group were given a 3-month group training structured according to the health belief model. Results: Between-group differences were not statistically significant at baseline regarding mean knowledge and the constructs of the scales used (p &gt; 0.05). After the training, it was determined that the Reproductive Health Attitudes Determination Scale and Family Planning Attitude Scale sub-dimensions and total scores of compared to the control groups, the experimental group had a significantly higher (p &lt; 0.05). Similarly, it was noted that following the training, the experimental group's use of efficient family planning techniques and breast self-examination techniques increased noticeably (p &lt; 0.05). Conclusion: According to the results, training was determined to have been given had a positive effect on protective attitudes towards reproductive health.

One-Month Duration Compared with Twelve-Month Duration of Dual Antiplatelet Therapy in Elective Angioplasty for Coronary Artery Disease: Bleeding and Ischaemic Outcomes.

Background/Objectives: The need to determine the safest duration of dual antiplatelet therapy duration after elective angioplasty to reduce bleeding events without an adverse effect on major adverse cardiovascular events (MACE) remains a challenge. Methods: In this investigator-initiated, single-centre cohort study, we identified all patients who underwent PCI for de novo coronary disease for stable angina between January 2015 and November 2019. We compared 1-month and 12-month durations of dual antiplatelet therapy (DAPT) to determine if there was any difference in the primary outcome of major bleeding. The secondary outcome was a patient-oriented composite endpoint of all-cause mortality; any myocardial infarction, stroke, or revascularisation; and the individual components of this composite endpoint. Data were analysed using Cox regression models and cumulative hazard plots. Results: A total of 1025 patients were analysed, of which 340 received 1 month of DAPT and 685 received 12 months of DAPT. There was no difference in major bleeding between the two groups (2.6% vs. 2.5% respectively). On univariable cox regression analysis, no characteristics were predictors of major bleeding. A proportion of 99.7% of patients in the 1-month DAPT arm were treated with a DCB strategy, whilst 93% in the 12-month DAPT group were treated with a DES. There was no difference between the two groups with regards to the composite patient-oriented MACE (11% vs. 12%, respectively) or any individual component of this. These results were unchanged after propensity score matched analysis. Conclusions: A 1-month duration of DAPT, for which 99.7% of patients were treated with a DCB strategy, appears safe and effective when compared with a 12-month duration of DAPT with no difference in major bleeding or MACE.

Assessment of blood viral load in asymptomatic and symptomatic cases of congenital cytomegalovirus infection.

This study aimed to retrospectively evaluate the baseline and follow-up viral loads and viral clearance times in cases followed for asymptomatic and symptomatic congenital cytomegalovirus (cCMV) infection between August 2010 and August 2022. Among 93 cases, they had asymptomatic (n: 55) and symptomatic (n: 38). The median baseline blood viral load detected in the symptomatic cCMV (ScCMV) infection (13 054 IU/mL) was significantly higher than that of asymptomatic cCMV (AcCMV) infection (4636 IU/mL) (p < 0.013). There was no difference in median viral clearance times (75 and 90 days, respectively) in baseline viremic cases in the ScCMV and AcCMV infection groups. There were no differences in median baseline blood viral load (6930 IU/mL and 14 268 IU/mL, respectively) and median viral clearance times (75 and 85 days, respectively) between the 6-week and 6-month antiviral treatment group. No correlation was found between baseline blood viral load, clinical severity, and the number of systems involved. However, in initial viremic cases, the viral load threshold for a symptomatic case was 8856 IU/mL, with 85.7% sensitivity and 54.5% specificity.

The Effect of Intracanal Medicaments on the Healing of Apical Periodontitis.

Apical periodontitis is a prevalent inflammatory condition affecting the tissues surrounding the root apex of a tooth. The selection of appropriate intracanal medicaments for its management remains a topic of ongoing research. This study aimed to investigate the effect of calcium hydroxide and triple antibiotic paste on the healing of apical periodontitis. A total of 304 teeth from 215 patientswith apical periodontitis were included in this observational study. Patients were randomly assigned to three groups: Group A (calcium hydroxide), Group B (triple antibiotic paste), and Group C (control). Baseline characteristics were recorded, and follow-up assessments were conducted at three, six, and 12 months. Parameters such as reduction in apical radiolucency, presence of periapical healing, bleeding on probing (BOP) percentage, clinical attachment level (CAL), and periodontal depth were evaluated. At baseline, the three groups exhibited similar distributions of apical periodontitis parameters. Over the 12-month follow-up, Group A and Group B demonstrated a significant reduction in apical radiolucency compared to Group C (p < 0.05). The presence of periapical healing was more frequent in Group A (85%) and Group B (80%) compared to Group C (60%). Group A showed the lowest mean BOP percentage (15.2 ± 3.5), followed by Group B (18.6 ± 4.2) and Group C (22.1 ± 4.8). Similarly, Group A demonstrated the highest mean CAL (5.8 ± 0.9 mm) and the lowest mean periodontal depth (3.2 ± 0.6 mm). Group B exhibited intermediate values for CAL (5.2 ± 1.1 mm) and periodontal depth (3.6 ± 0.8 mm). In this study, both calcium hydroxide and triple antibiotic paste demonstrated potential therapeutic effects in promoting healing and reducing apical radiolucency compared to the control group. Calcium hydroxide exhibited the most favorable outcomes, with a higher presence of periapical healing, lower BOP percentage, and superior CAL and periodontal depth measurements. These findings contribute to the understanding of intracanal medicaments' effectiveness in apical periodontitis management.

Roles of MDA-LDL/OX-LDL/LOX-1 and TNF-α/TLR4/NF-κB Signaling Pathways in Myocardial Damage by Implantations of Cardiac Pacemakers in Elderly Patients.

Permanent pacemakers are an established treatment for sick sinus syndrome and high-grade atrioventricular block. Permanent cardiac pacemaker implantations may damage the myocardium. This study evaluated markers of myocardial injury, oxidative stress and inflammation in elderly patients with permanent pacemaker implantations. Various markers were measured at 1, 2, 3 and 4 months after permanent pacemaker implantations in elderly patients. The levels of high-sensitivity troponin T (hsTnT), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), malondialdehyde-modified low-density lipoprotein (MDA-LDL), oxidized low-density lipoprotein (OX-LDL), tumour necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) were increased in 2-month group compared with control and 1- month groups (P<0.001), and were further increased at 4-month group compared with 2- and 3- month groups after pacemaker implantations (P<0.001). Patients with dual-chamber pacemakers had higher levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB than patients with single chamber pacemakers (P<0.001). Patients who underwent the pacemakers with the active fixation leads had raised levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB compared patients with pacemakers using the passive fixation leads (P<0.001). Myocardial blood flows in 3-month and 4-month groups were lower than 1-month and 2-month groups (P<0.001). Levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB were elevated in elderly patients with permanent pacemaker implantations and the activations of oxidative stress and pro-inflammatory signalling pathways may be associated with myocardial damages and ischemia after pacemaker implantations in elderly patients.

Protocol for neonatal pain assessment and management: Application of the ALPS Neo scale in routine care

Background and objectives. Neonatal pain research has advanced, disproving earlier beliefs that neonates cannot feel pain due to immature nervous systems. Incomplete myelination slows but does not prevent pain conduction. Pain responses start around 7.5 weeks post-conception, with pain receptors throughout the body by 20 weeks. Pain pathways are established by 22 weeks, but full modulation develops by 32 weeks, making preterm infants more sensitive. Nociceptors detect pain through A-delta (sharp pain) and C-fibers (dull pain). Tissue damage releases chemicals that lower the pain threshold. Pain is classified as nociceptive, somatic, or visceral and can be acute or chronic. Early pain exposure affects later responses. Validated pain scales for neonates include COVERS, PIPP, NIPS, NFCS, and ALPS Neo. Current practice emphasizes preventing and treating pain to minimize stress. Materials and methods. This study at Life Memorial Hospital will analyze patients over 1 month and over 6 months, with ethical approval obtained beforehand. Inclusion criteria: neonates with a gestational age over 35 weeks, birth weight over 2000 grams, needing routine care. Exclusion criteria: neonates needing respiratory support/sedation or with abnormal neurological exams. We will use the ALPS Neo pain assessment scale for its reliability and ease of integration into daily care, aiming to reduce pain or stress duration. Patients will be scored on facial expression, breathing, extremity tone, hand/foot activity, and activity level. Scores of 3-5 will prompt non-pharmacological interventions. Scores above 5 will require frequent reassessments and possible pharmacological intervention. The medical team will be trained on the ALPS Neo scale and non-pharmacological pain reduction methods. Pain from procedures like vaccinations will be assessed during the first two days of life. Initially, control patients will be evaluated without interventions. Over the next 6 months, patients will receive non-pharmacological interventions, including non-nutritive sucking, sucrose, Kangaroo Mother Care, swaddling, and maternal milk or formula. Our group aims to establish an evidence-based protocol for pain assessment and management and to use it in prospective research in which the objectives would be to use a pain scale for more accurate pain data from procedures, identify and reduce the most painful procedures, evaluate and improve the effectiveness of pain management strategies. Conclusions. This observational study at Life Memorial Hospital will use the ALPS Neo pain assessment scale to improve neonatal pain management within the Kangaroo Mother Care program. By comparing a 1-month control group with a 6-month group, we aim to identify and reduce procedural pain. The ALPS Neo scale will enable precise pain assessment and targeted non-pharmacological interventions, potentially guiding future pain management strategies. The choice of ALPS Neo, which is familiar to our team, will ease training and implementation. Success may lead to exploring scales with objective measures, though ALPS Neo will initially drive our improvements in pain management.

Safety and efficacy of Kaffes intraductal self-expanding metal stents in the management of post-liver transplant anastomotic strictures.

Endoscopic management is the first-line therapy for post-liver-transplant anastomotic strictures. Although the optimal duration of treatment with plastic stents has been reported to be 8-12 months, data on safety and duration for metal stents in this setting is scarce. Due to limited access to endoscopic retrograde cholangiopancreatography (ERCP) during the coronavirus disease 2019 pandemic in our centre, there was a change in practice towards increased usage and length-of-stay of the Kaffes biliary intraductal self-expanding stent in patients with suitable anatomy. This was mainly due to the theoretical benefit of Kaffes stents allowing for longer indwelling periods compared to the traditional plastic stents. To compare the safety and efficacy profile of different stenting durations using Kaffes stents. Adult liver transplant recipients aged 18 years and above who underwent ERCP were retrospectively identified during a 10-year period through a database query. Unplanned admissions post-Kaffes stent insertion were identified manually through electronic and scanned medical records. The main outcome was the incidence of complications when stents were left indwelling for 3 months vs 6 months. Stent efficacy was calculated via rates of stricture recurrence between patients that had stenting courses for ≤ 120 d or > 120 d. During the study period, a total of 66 ERCPs with Kaffes insertion were performed in 54 patients throughout their stenting course. In 33 ERCPs, the stent was removed or exchanged on a 3-month interval. No pancreatitis, perforations or deaths occurred. Minor post-ERCP complications were similar between the 3-month (abdominal pain and intraductal migration) and 6-month (abdominal pain, septic shower and embedded stent) groups - 6.1% vs 9.1% respectively, P = 0.40. All strictures resolved at the end of the stenting course, but the stenting course was variable from 3 to 22 months. The recurrence rate for stenting courses lasting for up to 120 d was 71.4% and 21.4% for stenting courses of 121 d or over (P = 0.03). There were 28 patients that were treated with a single ERCP with Kaffes, 21 with removal after 120 d and 7 within 120 d. There was a significant improvement in stricture recurrence when the Kaffes was removed after 120 d when a single ERCP was used for the entire stenting course (71.0% vs 10.0%, P = 0.01). Utilising a single Kaffes intraductal fully-covered metal stent for at least 4 months is safe and efficacious for the management of post-transplant anastomotic strictures.

Migration characteristics and risk assessment of chemical hazardous substances in infant teether toys

Teether is a special toy used for infants oral contact. In this paper, a residual and migration detection method was developed using gas chromatography–tandem mass spectrometry for 20 screened hazardous substances in teethers. Fifteen substances were detected in 59 samples, with residual amounts and detection rates ranging from 0.01 mg⋅kg−1 to 106.15 mg⋅kg−1 and from 3.39 % to 84.7 % respectively. Then, 12 substances were detected in simulated saliva at migration levels ranging from 0.0143 mg⋅kg−1 to 20.03 mg⋅kg−1, with detection rates ranging from 1.69 % to 76.3 %. Statistically, the average migration rate of each substance ranged from 8.18 % to 53.28 % depending on the properties of the substance and the sample. The exposure risk of infants to teethers was evaluated separately for two age groups. The hazard quotient (HQ) and hazard index (HI) values for the analytes were higher in the 3–12-month age group than in the 12–24-month age group. The HQ values of triphenylphosphine oxide, benzocaine, and N-methylformanilide were relatively high, with averages of 1.2 × 10−2, 2.5 × 10−3, and 1.6 × 10−3, respectively, and the max HI of the 12 substances was 0.04. The HI and HQ values of the analytes were all below 1, indicating that the non-carcinogenic risks of analytes in teethers are at an acceptable level.

The value of synthetic MRI in detecting the brain changes and hearing impairment of children with sensorineural hearing loss.

Sensorineural hearing loss (SNHL) can arise from a diverse range of congenital and acquired factors. Detecting it early is pivotal for nurturing speech, language, and cognitive development in children with SNHL. In our study, we utilized synthetic magnetic resonance imaging (SyMRI) to assess alterations in both gray and white matter within the brains of children affected by SNHL. The study encompassed both children diagnosed with SNHL and a control group of children with normal hearing {1.5-month-olds (n = 52) and 3-month-olds (n = 78)}. Participants were categorized based on their auditory brainstem response (ABR) threshold, delineated into normal, mild, moderate, and severe subgroups.Clinical parameters were included and assessed the correlation with SNHL. Quantitative analysis of brain morphology was conducted using SyMRI scans, yielding data on brain segmentation and relaxation time.Through both univariate and multivariate analyses, independent factors predictive of SNHL were identified. The efficacy of the prediction model was evaluated using receiver operating characteristic (ROC) curves, with visualization facilitated through the utilization of a nomogram. It's important to note that due to the constraints of our research, we worked with a relatively small sample size. Neonatal hyperbilirubinemia (NH) and children with inner ear malformation (IEM) were associated with the onset of SNHL both at 1.5 and 3-month groups. At 3-month group, the moderate and severe subgroups exhibited elevated quantitative T1 values in the inferior colliculus (IC), lateral lemniscus (LL), and middle cerebellar peduncle (MCP) compared to the normal group. Additionally, WMV, WMF, MYF, and MYV were significantly reduced relative to the normal group. Additionally, SNHL-children with IEM had high T1 values in IC, and LL and reduced WMV, WMF, MYV and MYF values as compared with SNHL-children without IEM at 3-month group. LL-T1 and WMF were independent risk factors associated with SNHL. Consequently, a prediction model was devised based on LL-T1 and WMF. ROC for training set, validation set and external set were 0.865, 0.806, and 0.736, respectively. The integration of T1 quantitative values and brain volume segmentation offers a valuable tool for tracking brain development in children affected by SNHL and assessing the progression of the condition's severity.

Time-dependent effects of high-fat diet on cognition and cerebral insulin signaling: Window for recovery and potential therapeutic target

While high-fat diet (HFD)-induced obesity is a major threat to global public health, the effect of HFD on cognition and insulin signaling during ageing remains controversial. The aim of this study was to characterize the dynamic alterations in cognition and cerebral insulin signaling during 6-month HFD consumption, and to investigate the potential therapeutic target and optimal timing to rescue obesity-related cognitive deficits. In the present study, impaired memory retention induced by 2-month HFD was recovered after 4 months on HFD. Prolonged (6-month) HFD did not further enhance tau hyperphosphorylation and β-amyloid deposition, which was consistent with the alleviation of memory retention. In brain insulin signaling, 2-month HFD increased IRS-1 and p-IRS-1(Ser307)/IRS-1, while decreasing pAKT(Ser473)/AKT, PI3K and mTOR; 4-month HFD decreased IRS-1 and pAKT(Ser473)/AKT, while increasing AKT; 6-month HFD increased IRS-1, pAKT(Ser473)/AKT, and mTOR, while decreasing p-IRS-1(Ser307)/IRS-1, PI3K and AKT. Notably, bioinformatic analysis revealed a rhythmic process presented only in 4-month HFD group, with Srebf1 emerging as a link between circadian rhythms and insulin signaling pathway. These results suggest that prolonged HFD prevents further cognitive decline and the progression of Alzheimer’s disease (AD)-related pathologies during ageing. Moreover, there may be a window for recovery, in which Srebf1 acts as a self-recovery switch to address obesity-related cognitive disorders in elders.

Different dosage forms of gonadotropin-releasing hormone agonist with endocrine therapy in premenopausal hormone receptor-positive breast cancer.

Despite the wide use of a 3-month gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression in premenopausal breast cancer patients, it remains unclear whether it is as effective and safe as a 1-month GnRH agonist regimen when combined with selective estrogen receptor modulators or aromatase inhibitors, especially in younger patients. This retrospective cohort study included 1109 premenopausal hormone receptor-positive breast cancer patients treated with GnRH agonist plus selective estrogen receptor modulator or aromatase inhibitor. The estradiol (E2) inhibition rate within 1-24 months after treatment with 1-month or 3-month GnRH agonist in cohorts and different subgroups was analyzed. Following 1:1 propensity score matching, 950 patients with a mean age of 39 years and a median follow-up of 46 months were included. Both the 1-month and 3-month groups achieved more than 90% E2 inhibition within 24 months (94.53% vs 92.84%, with a 95% confidence interval for the difference ranging from -4.78% to 1.41%), confirming the noninferiority of 3-month GnRH agonist. Both 1-month and 3-month GnRH agonist rapidly and consistently reduced E2 levels. Of the patients, 60 (6.3%) experienced incomplete ovarian function suppression, with similar rates in the 1-month and 3-month groups (5.5% vs 7.2%). Incomplete ovarian function suppression mainly occurred within the first 12 months, with age younger than 40 years and no prior chemotherapy being the risk factors. Similar disease-free survival and overall survival were found in the 1-month and 3-month groups and in patients with complete and incomplete ovarian function suppression (P > .05). The ovarian function suppression with 3-month GnRH agonist was not inferior to that with 1-month GnRH agonist, regardless of age or combination with a selective estrogen receptor modulator or an aromatase inhibitor.

Adjuvant icotinib of 12 months or 6 months versus observation following adjuvant chemotherapy for resected EGFR-mutated stage II–IIIA non-small-cell lung cancer (ICTAN, GASTO1002): A randomized phase 3 trial.

8004 Background: The efficacy, safety and ideal treatment duration of adjuvant icotinib (first-generation EGFR tyrosine kinase inhibitor) for patients with completely resected EGFR-mutated non-small-cell lung cancer (NSCLC) after adjuvant chemotherapy were not known in 2014, when this study was initiated. This phase 3 trial investigated whether icotinib following adjuvant chemotherapy improves clinical outcomes compared with observation in stage II-IIIA NSCLC harboring EGFR mutation. Methods: This is a multicenter, randomized, open-label, phase 3 trial. From July 2014 to December 2021, patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after platinum-based adjuvant chemotherapy were enrolled. Patients were assigned in a 1:1:1 ratio to receive icotinib (125mg, three times daily) for 12 months, icotinib for 6 months or to observation. The primary endpoint was disease-free survival (DFS) in the intention-to-treat population. Results: This trial was terminated early due to slow accrual.A total of 251 patients were randomized, with 84 patients in the 12-month icotinib group, 84 patients in the 6-month icotinib group, and 83 patients in the observation group. Baseline characteristics were balanced between the groups. After a median follow-up of 61.4 months, 6 months of icotinib significantly improved DFS (HR: 0.41, 95% CI, 0.27-0.62; P = 0.000025) and overall survival (OS, HR: 0.56, 95% CI, 0.32-0.98; P = 0.041) compared with observation. Adjuvant icotinib of 12 months also significantly improved DFS (HR: 0.40, 95% CI, 0.27-0.61; P = 0.000014) and OS (HR: 0.55, 95% CI, 0.32-0.96; P = 0.035) compared with observation. Adjuvant icotinib of 12 months did not improve DFS (HR: 0.97; P = 0.89) and OS (HR: 1.00; P = 0.99) compared with 6 months of this drug. Median DFS was 61.8 months (95% CI, 43.3 to 80.3) for the 12-month icotinib group, 63.2 months (95% CI, 44.8 to 81.6) for the 6-month icotinib group compared with 23.7 months (95% CI, 16.5 to 30.9) for the observation group. The 5-year DFS and OS for the 12-month icotinib, 6-month icotinib and observation groups were 51.3%, 50.1% and 24.8%; and 74.5%, 74.0% and 65.1%; respectively. No differences in efficacy pertaining to icotinib duration were found in any of the subgroups. Rates of adverse events of grade 3 or higher were 8.3%, 5.9% and 2.4% for the 12-month icotinib, 6-month icotinib and observation groups, respectively. The safety profile remained similar to the previous reports for icotinib. Conclusions: Adjuvant icotinib for 12 months and 6 months provide a significant DFS and OS benefit compared with observation in patients with completely resected EGFR-mutated stage II-IIIA NSCLC with a manageable safety profile. Nevertheless, 12 months of icotinib had no additional benefit compared with 6 months. Clinical trial information: NCT01996098 .

How overall survival is conditioned in the progression to treatment with cyclin inhibitors plus endocrine treatment in metastatic breast cancer with luminal phenotype.

e13079 Background: CDK4/6 inhibitors plus endocrinotherapy (ET) is the standard first-line treatment for metastatic breast cancer with a luminal phenotype. However, the response to this treatment is highly dependent on its previous efficacy. Methods: We analyzed the overall survival in a cohort of 127 patients with metastatic luminal breast cancer in progression after treatment with CDK4/6 inhibitors plus ET. Results: The median age of the group was 67 years (41-96), the interval time between initial diagnosis and first recurrence was 0 in 41 (32%), 1-60 months in 37 (29%) and more than 60 months in 39 (38%). The first line in the metastatic setting was CDK4/6 plus ET in 81 patients (64%), ET in 15 (12%) and 31 (24%) were treated with chemotherapy. The status of HER2 expression was HER2 low in 77% and 43 % had visceral metastases disease. The median progression-free survival for the patients treated with CDK4/6 inhibitors plus ET was 9 months, with a total of deaths of 69 (55%). Overall survival after progression on CDK4/6 plus ET was 38 months (28 – 47) and the most important factor for overall survival was the response time to treatment with CDK4/6 inhibitors plus ET. Conclusions: The most important factor for overall survival is the duration of treatment with CDK4/6 inhibitors plus ET. Patients with a response time of less than 6 months had a median overall survival after progression of 11 months (3 – 19), while the 6- to 12-month group had a median of 39 months (19 – 59) and the group with more than 12 months had the best prognosis with a median overall survival of 53 months (37 – 68). We need to improve the new treatment options for patients who respond for less than 6 months to treatment with CDK4/6 plus ET.

Left bundle branch vs biventricular pacing for cardiac resynchronization therapy

Abstract Background/Introduction Left bundle branch pacing (LBBP) has emerged as a predominant conduction system pacing technique for reducing QRS duration in patients with intrinsic left bundle branch block (LBBB). It represents a potentially optimal alternative to cardiac resynchronization therapy (CRT) through biventricular pacing (BiVP). Purpose This study aims to compare the efficacy of LBBP-CRT with BiVP-CRT in patients experiencing heart failure with reduced left ventricular ejection fraction. Methods This single-center prospective study involved patients with heart failure and reduced ventricular ejection fraction, encompassing both ischemic and nonischemic cardiomyopathy. LBBP-CRT was employed when BiVP was unsuccessful for any reason, with LBBP-CRT implanted during the same procedure. After 3 and 6 months of preplanned follow-up, comparisons were made between the New York Heart Association (NYHA) functional class and QRS duration in the BiVP-CRT and LBBP-CRT groups. Results Sixty consecutive patients were included in the study (39 males, mean age 64.1 ± 10.6 years, LVEF 29.6% ± 5.6%). All patients completed follow-up, with 32 receiving LBBP-CRT and 28 receiving BiVP-CRT. All 32 LBBP-CRT patients achieved LBB capture, with 14 undergoing selective LBBP and 18 undergoing nonselective LBBP. The LBBP-CRT group exhibited shorter procedure and x-ray exposure times ((11.95 ± 5.77 vs 18.66 ± 10.12). The LBBP lead demonstrated a lower LBB capture threshold at implantation (0.7 ± 0.26 V vs. 1.1 ± 0.40 V; p= 0.039) compared to the CS LV lead in the BiVP-CRT group. Pacing parameters remained stable at the 6-month follow-up (0.72 ± 0.20 V vs. 1.1 ± 0.57 V; p=0.07). During the 3 and 6-month follow-up, pacing parameters remained stable in both groups. Only one patient in the LBBP-CRT group experienced dislodgment of the CS LV lead two days after the procedure, while no patients in the LBBP-CRT group had lead dislodgment. QRS duration significantly shortened in LBBP (171.6 ± 14.3 ms to 131.5 ± 12.5 ms; p=0.047) and remained not significantly shortened in BiVP (174.7 ± 14.1 ms to 150.6 ± 12.9 ms; p=0.06). Both LBBP and BiVP demonstrated improvement in NYHA functional class at the 3 and 6-month follow-up, with statistically significant differences observed between the two groups (change in NYHA functional class from baseline to 6 months -1.2 ± 0.1 vs -0.94 ± 0.11 p=0.047). Throughout the 6-month follow-up, neither the LBBP-CRT nor BiVP-CRT groups experienced rehospitalizations for heart failure, ventricular arrhythmia events, or all-cause death. Conclusions In this series, LBBP-CRT exhibited improvements in NYHA functional class and significantly shortened QRS duration when compared to BiVP-CRT in patients with reduced left ventricular ejection fraction and LBBB.

Focused Ultrasound-Mediated Disruption of the Blood-Brain Barrier for AAV9 Delivery in a Mouse Model of Huntington's Disease.

Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. There are no cures for HD, but the genetic basis of this disorder makes gene therapy a viable approach. Adeno-associated virus (AAV)-miRNA-based therapies have been demonstrated to be effective in lowering HTT mRNA; however, the blood-brain barrier (BBB) poses a significant challenge for gene delivery to the brain. Delivery strategies include direct injections into the central nervous system, which are invasive and can result in poor diffusion of viral particles through the brain parenchyma. Focused ultrasound (FUS) is an alternative approach that can be used to non-invasively deliver AAVs by temporarily disrupting the BBB. Here, we investigate FUS-mediated delivery of a single-stranded AAV9 bearing a cDNA for GFP in 2-month-old wild-type mice and the zQ175 HD mouse model at 2-, 6-, and 12-months. FUS treatment improved AAV9 delivery for all mouse groups. The delivery efficacy was similar for all WT and HD groups, with the exception of the zQ175 12-month cohort, where we observed decreased GFP expression. Astrocytosis did not increase after FUS treatment, even within the zQ175 12-month group exhibiting higher baseline levels of GFAP expression. These findings demonstrate that FUS can be used to non-invasively deliver an AAV9-based gene therapy to targeted brain regions in a mouse model of Huntington's disease.

Long-term Effects of COVID-19 on Vascular Parameters—A Prospective Longitudinal Ultrasound Clinical Study

Objective: To investigate the longitudinal effects of COVID-19 on major vascular structures and parameters and clinical outcomes. Design: Observational prospective trial. Setting: Post-COVID-19 research clinic established by University of Louisville Division of Infectious Diseases. Participants: The study population consisted of 72 post-COVID-19 individuals and 11 non-COVID-19 infected participants in the control group. The participants were recruited from adult hospitals and from the community. The enrollment started in October 2020 and follow-up periods were at 3, 6, and 12 months from their initial COVID-19 diagnosis. Interventions: The participants were interviewed for medical and COVID-19 infection history. Samples of white blood cell (WBC), C-reactive protein (CRP), and D-dimer were taken at each visit. Certified sonographers performed vascular ultrasound on the study participants. Measurements and Main Results: Median intima-media thickness (IMT) was increased in mild/asymptomatic (0.80 mm) and severe/critical (0.90 mm) groups when compared with controls (0.60 mm; P &lt; .001 for both groups). In the asymptomatic/mild group, 6-month median IMT (0.88 mm) was increased, compared with the 3-month group (0.75 mm), with P = .026. Increased age was associated with decreased mean arterial blood velocities (cm/s): common carotid ( r = −0.236, P = .032), internal carotid ( r = −0.208, P = .048), and subclavian artery mean velocity ( r = −0.357, P = .003). We did not find any instance of deep vein thrombosis. Median D-dimer, CRP, and WBC in the control group differed from asymptomatic/mild COVID-19 group ( P = .026, .011, and .003, respectively). Moreover, WBC in the asymptomatic/mild group and moderate COVID-19 group differed from severe/critical group ( P = .025 and P = .027, respectively); CRP also differed between asymptomatic/mild group and severe/critical group ( P = .014). Conclusions: There were differences in intima-media lumen thickness (IMT), arterial velocities, and inflammatory markers in post-COVID-19 patients. There was no instance of deep vein thrombosis in this post-COVID-19 study cohort. The increased IMT might infer atherosclerosis, which has shown to increase cardiovascular risks. It is not yet known whether the increase in IMT due to COVID should be treated in the same way as non-COVID-19 atherosclerosis—through statins, for example—or whether regular cardiovascular risk reduction would be useful. Clinical trial and mechanistic studies should be performed to further our understanding of COVID-19-related vascular pathologies.