The Prevalence and Risk Analysis of Cerebral Palsy and Other Neuro-Psychological Comorbidities in Children with Low Birth Weight in Taiwan: A Nationwide Population-Based Cohort Study.

Background: This study evaluated early childhood comorbidities of cerebral palsy (CP) in low birth weight (LBW) children and assessed the impact of maternal bio-psychosocial factors on CP risk in preterm infants of varying birth weights (BWs). Methods: Data from 15,181 preterm infants (2009-2013) and 151,810 controls were analyzed using Taiwan's National Health Insurance Research Database. CP prevalence and LBW-associated comorbidities were examined, and odds ratios (ORs) were calculated. Results: This study confirmed increasing prematurity and LBW rates in Taiwan, with LBW infants showing higher CP prevalence. Significant maternal risk factors included age extremes (<20 and >40 years). LBW infants exhibited higher risks for respiratory, circulatory, nervous system, and psycho-developmental comorbidities compared with controls, with the lowest BW having even higher ORs. Maternal factors such as family income, the number of hospital admissions, and length of hospital stay were remarkably correlated with BW and subsequent complications. Each additional gestational week crucially reduced the risk of complications in premature infants. Conclusions: LBW infants are at a higher risk for CP and various comorbidities, with maternal bio-psychosocial factors playing a critical role. Addressing these factors in prenatal care and interventions is essential to improve outcomes for premature infants.

Correction: Valuation of the EQ-5D-5L in Taiwan.

[This corrects the article DOI: 10.1371/journal.pone.0209344.].

Real-world osimertinib pretreatment experience in patients with epidermal growth factor receptor T790M mutation-positive locally advanced or metastatic non-small cell lung cancer.

Osimertinib has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) in clinical trials. However, real-world data on its effectiveness remain scarce. Taiwanese patients with T790M-positive locally advanced or metastatic NSCLC and progressive disease following treatment with at least one EGFR tyrosine kinase inhibitor (TKI) were enrolled from the osimertinib early access program. Of the 419 patients (mean age, 63 years; female, 67%), 53% were heavily pretreated (≥ third-line [3L]), making osimertinib a fourth-line (4L) intervention. The median progression-free survival (PFS) was 10.5 months (95% confidence interval [CI]: 8.95-11.41); the 18-month PFS rate was 26.5%. The median overall survival (OS) was 19.0 months (95% CI: 16.30-20.95); the 24-month OS rate was 40.9%. The objective response rate was 32.46%, and the disease control rate was 86.38%. The median time to treatment discontinuation of osimertinib monotherapy was 11.9 months (95% CI: 10.49-13.11). Subgroup analyses of median PFS and OS in the chemotherapy combination group vs. the osimertinib monotherapy group yielded no difference. Central nervous system (CNS) metastasis, number of prior lines of therapy, and types of initial EGFR-TKIs did not significantly impact outcomes. The median PFS values were 9.0 (95% CI: 5.18-11.34) and 10.9 (95% CI: 9.18-11.90) months with and without CNS metastasis, respectively, and 10.8 (95% CI: 8.59-12.69), 13.6 (95% CI: 10.89-16.3), and 9.2 (95% CI: 7.8-10.62) months for second-line (2L), 3L, and ≥4L therapy, respectively. In patients who received osimertinib as 2L therapy, the median PFS values in response to prior afatinib, erlotinib and gefitinib treatment were 11.2 (95% CI: 4.85-4.79), 10.5 (95% CI: 8.59-20.26) and 8.7 (95% CI: 7.21-16.79) months, respectively. Overall, real-world data from Taiwan support the clinical benefits of osimertinib in EGFR T790M -positive NSCLC.

A Nationwide Study on the Risks of Complications and Healthcare Costs of Snakebite Envenomation in Taiwan.

In Taiwan, six medically important venomous snakes, Trimeresurus stejnegeri stejnegeri, Protobothrops mucrosquamatus, Deinagkistrodon acutus, Daboia siamensis, Naja atra, and Bungarus multicinctus, are found. However, comprehensive research on the complications and associated healthcare costs of snakebite envenomation (SBE) is lacking. We retrospectively analyzed pertinent information from the Taiwan National Health Insurance Research Database dated January 2002 to December 2014. We investigated the risk factors for complications and their impact on healthcare costs. Among the 12,542 patients with SBE, those from N. atra or B. multicinctus were more likely to experience wound infections and neurological complications than were those from T. s. stejnegeri or P. mucrosquamatus. In addition, being female, being elderly, and having a Charlson Comorbidity Index equal to or greater than 3 points were associated with an increased likelihood of wound infections and psychological complications. The annual national economic burden averaged US$1,083,624, with an average healthcare cost of US$1,129 per SBE. Snakebite envenomations from N. atra or B. multicinctus, as well as various complications, resulted in significantly higher costs. It is crucial to comprehend the risk factors for complications and their role in increasing expenses to provide insight for tailored healthcare interventions, mitigate complications, and reduce the economic burdens associated with SBEs.

PROM2 upregulation promotes cancer cell migration and confers a poor prognosis in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) remains a difficult-to-treat disease with a poor prognosis. While prominin-1 (PROM1/CD-133) is largely investigated in a variety of malignancies, the role of prominin-2 (PROM2), the other member of the prominin family, has not been studied in LUSC. Transcriptomic data derived from matched tumor and adjacent non-tumorous lung tissues of LUSC patients were employed to conduct an in-depth analysis of the genetic and epigenetic regulation of prominin genes within LUSC, utilizing bioinformatic approaches. Furthermore, cellular behavior experiments were executed to discern the biological functions of PROM2. It was observed that PROM2, in contrast to PROM1, exhibited significant upregulation and overexpression at both the mRNA and protein levels in LUSC, and this upregulation was correlated with shortened patient survival. Transcriptomic analysis unveiled DNA methylation as an epigenetic regulatory mechanism associated with PROM2 expression. Notably, two transcription factors, CBFB and NRIP1, were identified as potential regulators of PROM2 expression. Subsequent in vitro investigations demonstrated that knocking down PROM2 led to the inhibition of cancer cell migration and the epithelial-to-mesenchymal transition (EMT). In summary, the pronounced upregulation of PROM2 in LUSC patients was linked to an unfavorable prognosis, possibly attributable to its influence on cancer cell migration and EMT. These findings suggest that PROM2 could serve as a promising diagnostic biomarker and therapeutic target in the management of LUSC. Consequently, further research into the mechanistic aspects and potential therapeutic interventions targeting PROM2 is warranted in the clinical context.

First Report of 'Candidatus Phytoplasma asteris'-related Strain (16SrI group) Associated with Small Leaves, Leaf Yellowing, and Shoot Proliferation of Morning Glory (Ipomoea biflora) in Taiwan.

Ipomoea biflora L., commonly known as morning glory, is an herbaceous vine plant in the Convolvulaceae family and is widespread at low elevations in Taiwan and other East Asian countries. In September 2023, six I. biflora plants exhibiting small leaves, leaf yellowing, and shoot proliferation were observed in a vacant lot in Taiwan Agricultural Research Institute (TARI), Wufeng District, Taichung, Taiwan, representing 100% disease incidence in the area. All the symptomatic morning glory climbed onto Murraya paniculata L. (common jasmine orange) which however showed no similar symptoms. The total DNA (two samples for each plant) from leaf tissues of three symptomatic morning glory plants, two asymptomatic morning glory plants, and one asymptomatic common jasmine orange was isolated by the CTAB method (Fulton et al. 1995) and used for PCR with the universal primers, P1 (Deng and Hiruki 1991)/P7 (Schneider et al. 1995), to amplify a fragment containing partial 16S rDNA. Expected 1.8-kb bands were amplified from DNA extracted from all symptomatic plants, whereas no PCR product was detected from that of the asymptomatic I.biflora and M. paniculata plants. Six PCR products were cloned and sequenced in the Biotechnology Center DNA-sequencing facility at National Chung Hsing University, and one representative sequence was selected and deposited in GenBank. BLAST analysis revealed that the obtained 16S rDNA sequence (PP230905) shared 99.92% identity with the following phytoplasma strains: rapeseed phyllody phytoplasma (CP055264), plumbago auriculata leaf yellowing phytoplasma (MN239503), and aster yellows phytoplasma (MK992774), which all belong to the 16SrI subgroup. The query 16S rDNA sequence shares 99.84% identity with that of the 'Candidatus Phytoplasma asteris' reference strain (M30790), suggesting that the phytoplasma is a 'Ca. Phytoplasma asteris'-related strain. A virtual restriction fragment length polymorphism (RFLP) analysis was conducted using iPhyClassifier tool (Zhao et al. 2009), and the pattern derived from the 16S rDNA fragment of the I. biflora phytoplasma was identical (similarity coefficient 1.00) to the reference pattern of 16SrI, subgroup B (onion yellows phytoplasma OY-M; AP006628). Six total DNA samples from symptomatic plants were used as templates to amplify 842 bp secA sequences with SecAfor1 and SecArev3 primers (Hodgetts et al. 2008), and one representative sequence was deposited in GenBank. The partial secA sequence (PP263636) showed 98.22% identity with that of Trema levigatum witches'-broom phytoplasma (MW032212) that also belongs to the 16SrI group (Wan et al. 2021). Phylogenetic analysis of both 16S rDNA and secA confirmed I. biflora phytoplasma as 16SrI, subgroup B. Taken together, we concluded that the morning glory phytoplasma in this study was a 'Ca. Phytoplasma asteris'-related strain belonging to the 16SrI group. To the best of our knowledge, this is the first report of a phytoplasma-infected I. biflora in Taiwan, suggesting morning glory as a new natural host of 16SrI phytoplasmas, alongside other plants like roselle and citrus (Tseng et al. 2014; Feng et al. 2015).

Comparative efficacy of acupuncture point stimulation treatments for dialysis patients with uremic pruritus: a systematic review and network meta-analysis.

Background: Uremic pruritus (UP) is a common complication of chronic kidney disease that causes sleep disturbances and increases all-cause mortality. Currently, the first-line medications for UP exhibit inadequate pruritus control with adverse effects. Various acupuncture point stimulation treatments (APSTs) have been shown to be effective as adjuvant therapies in UP, and a network meta-analysis can offer relative efficacy estimates for treatments for which head-to-head studies have not been performed. Methods: We conducted a random-effects network meta-analysis on a consistency model to compare the different APSTs for UP. The primary outcomes were the mean visual analog scale (VAS) score and effectiveness rate (ER). Results: The network meta-analysis retrieved 27 randomized controlled trials involving 1969 patients. Compared with conventional treatment alone, combination treatment with acupuncture (mean difference, -2.63; 95% confidence interval, -3.71 to -1.55) was the most effective intervention in decreasing VAS scores, followed by acupoint injection and massage (mean difference, -2.04; 95% confidence interval, -3.96 to -0.12). In terms of the ER, conventional treatment with acupuncture and hemoperfusion (risk ratio, 14.87; 95% confidence interval, 2.18 to 101.53) was superior to other therapeutic combinations. Considering the VAS score and ER, combination treatment with acupoint injection and massage showed benefits in treating UP. Conclusion: Our network meta-analysis provided relative efficacy data for choosing the optimal adjuvant treatment for UP. Combined treatment with acupuncture was more effective than conventional treatment only and was the most promising intervention for treating UP.Systematic review registration: PROSPERO (CRD42023425739: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023425739).

Challenges and Opportunities in Interdisciplinary Research and Real-World Data for Treatment Sequences in Health Technology Assessments.

With an ever-increasing number of treatment options, the assessment of treatment sequences has become crucial in health technology assessment (HTA). This review systematically explores the multifaceted challenges inherent in evaluating sequences, delving into their interplay and nuances that go beyond economic model structures. We synthesised a 'roadmap' of literature from key methodological studies, highlighting the evolution of recent advances and emerging research themes. These insights were compared against HTA guidelines to identify potential avenues for future research. Our findings reveal a spectrum of challenges in sequence evaluation, encompassing selecting appropriate decision-analytic modelling approaches and comparators, deriving appropriate clinical effectiveness evidence in the face of data scarcity, scrutinising effectiveness assumptions and statistical adjustments, considering treatment displacement, and optimising model computations. Integrating methodologies from diverse disciplines-statistics, epidemiology, causal inference, operational research and computer science-has demonstrated promise in addressing these challenges. An updated review of application studies is warranted to provide detailed insights into the extent and manner in which these methodologies have been implemented. Data scarcity on the effectiveness of treatment sequences emerged as a dominant concern, especially because treatment sequences are rarely compared in clinical trials. Real-world data (RWD) provide an alternative means for capturing evidence on effectiveness and future research should prioritise harnessing causal inference methods, particularly Target Trial Emulation, to evaluate treatment sequence effectiveness using RWD. This approach is also adaptable for analysing trials harbouring sequencing information and adjusting indirect comparisons when collating evidence from heterogeneous sources. Such investigative efforts could lend support to reviews of HTA recommendations and contribute to synthesising external control arms involving treatment sequences.

Clinical outcome of bevacizumab or ramucirumab combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as the first line therapy in susceptible EGFR-mutated advanced non-small-cell lung.

Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti- vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real-world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR-TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first-line EGFR-TKI with anti-VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high-grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti-VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR-TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large-scale registry-based cohort studies may be needed to validate our findings.

Intraoperative Hemodynamic Instability and Higher ASA Classification Increase the Risk of Developing Non-Surgical Complications following Orthopedic Surgeries.

(1) Background: Either pre-operative physical status or unstable hemodynamic changes has been reported to play a potential role in causing vital organ dysfunction. Therefore, we intended to investigate the impact of the American Society of Anesthesiologist (ASA) classification and intraoperative hemodynamic instability on non-surgical complications following orthopedic surgery. (2) Methods: We collected data on 6478 patients, with a mean age of 57.3 ± 16, who underwent orthopedic surgeries between 2018 and 2020. The ASA classification and hemodynamic data were obtained from an anesthesia database. Non-surgical complications were defined as a dysfunction of the vital organs. (3) Results: ASA III/IV caused significantly higher odds ratios (OR) of 17.49 and 40.96, respectively, than ASA I for developing non-surgical complications (p < 0.001). Non-surgical complications were correlated with a 20% reduction in systolic blood pressure (SBP), which was intraoperatively compared to the pre-operative baseline ((OR) = 1.38, p = 0.02). The risk of postoperative complications increased with longer durations of SBP < 100 mmHg, peaking at over 20 min ((OR) = 1.33, p = 0.34). (4) Conclusions: Extended intraoperative hypotension and ASA III/IV caused a significantly higher risk of adverse events occurring within the major organs. The maintenance of hemodynamic stability prevents non-surgical complications after orthopedic surgeries.

AMPK activation modulates IL-36-induced inflammatory responses by regulating IκBζ expression in the skin.

BACKGROUND AND PURPOSE: The interleukin (IL)-36 pathway is a critical player in the pathogenesis of pustular psoriasis. However, therapies targeting this pathway are limited or unaffordable (e.g. the anti-IL-36 receptor antibody). AMP-activated protein kinase (AMPK), a regulator of cellular energy and metabolism, is known to participate in inflammatory diseases. However, its role in IL-36-induced skin inflammation remains unclear. Therefore, we sought to investigate the role of AMPK signals in regulating IL-36-induced responses in the skin. EXPERIMENTAL APPROACH: IL-36-stimulated primary normal human epidermal keratinocytes (NHEKs) and IL-36-injected (intradermally) BALB/c mice served as the cell and animal models, respectively. Additionally, 5-aminoimidazole-4-carboxamide riboside (AICAR) and A769662 served as AMPK activators. KEY RESULTS: AICAR and A769662 significantly suppressed the IL-36-induced IL-8 (CXCL8) and CCL20 production from NHEKs. IL-36-induced IκBζ protein expression was prominently reduced and IKK/IκBα phosphorylation was attenuated by AICAR and A769662. Conversely, AMPKα knockdown increased IκBζ protein expression and IKK/IκBα phosphorylation in IL-36-treated NHEKs. Furthermore, AICAR and A769662 enhanced IL-36-induced-IκBζ protein degradation via the proteasome-dependent but not the lysosome-dependent pathway. Pretreatment of NHEKs with IL-36 slightly suppressed the AICAR- and A769662-triggered phosphorylation of AMPK and acetyl-CoA carboxylase. In the mouse model, topical application of AICAR significantly reduced ear swelling, redness, epidermal thickening, neutrophil infiltration and inflammatory and antimicrobial peptide gene expression. CONCLUSION AND IMPLICATIONS: AMPK activation suppresses IL-36-induced IL-8 and CCL20 release by regulating IκBζ expression in keratinocytes and reduces IL-36-induced skin inflammation in mice, suggesting that AMPK activation is a potential strategy for treating patients with IL-36-mediated inflammatory skin disorders.

Downregulated antisense lncRNA ENTPD3-AS1 contributes to the development of lung adenocarcinoma.

The poor outcome of patients with lung adenocarcinoma (LUAD) highlights the importance to identify novel effective prognostic markers and therapeutic targets. Long noncoding RNAs (lncRNAs) have generally been considered to serve important roles in tumorigenesis and the development of various types of cancer, including LUAD. Here, we aimed to investigate the role of ENTPD3-AS1 (ENTPD3 Antisense RNA 1) in LUAD and to explore its potential mechanisms by performing comprehensive bioinformatic analyses. The regulatory effect of ENTPD3-AS1 on the expression of NR3C1 was validated by siRNA-based silencing. The effect of miR-421 on the modulation of NR3C1 was determined by miRNA mimics and inhibitors transfection. ENTPD3-AS1 was expressed at lower levels in tumor parts and negatively correlated with unfavorable prognosis in LUAD patients. It exerted functions as a tumor suppressor gene by competitively binding to oncomir, miR-421, thereby attenuating NR3C1 expression. Transfection of lung cancer A549 cells with miR-421 mimics decreased the expression of NR3C1. Transfection of lung cancer A549 cells with miR-421 inhibitors increased the expression of NR3C1 with lower cellular functions as proliferation and migration via epithelial-mesenchymal transition. In addition, inhibition of ENTPD3-AS1 by siRNA transfection decreased the levels of NR3C1, supporting the ENTPD3-AS1/miR-421/NR3C1 cascade. Moreover, the bioinformatic analysis also showed that ENTPD3-AS1 could interact with the RNA-binding proteins (RBPs), CELF2 and QKI, consequently regulating RNA expression and processing. Taken together, we identified that ENTPD3-AS1 and its indirect target NR3C1 can act as novel biomarkers for determining the prognosis of patients with LUAD, and further study is required.

Impact of obesity on outcomes after surgical stabilization of multiple rib fractures: Evidence from the US nationwide inpatient sample.

BACKGROUND: Obesity is a global health issue with increasing prevalence. Surgical procedures, such as surgical stabilization of rib fractures (SSRF), may be affected by obesity-related complications. The objective of the study is to investigate the effects of obesity on SSRF outcomes in multiple rib fractures. METHODS: This retrospective study analyzed data from adults aged ≥ 20 years in the Nationwide Inpatient Sample (NIS) database diagnosed with multiple rib fractures who underwent SSRF between 2005 and 2018. It investigated the relationship between obesity and in-patient outcomes, such as discharge status, length of stay (LOS), in-hospital mortality, hospital costs, and adverse events using logistic and linear regression analyses. RESULTS: Analysis of data from 1,754 patients (morbidly obese: 87; obese: 106; normal weight: 1,561) revealed that morbid obesity was associated with longer LOS (aBeta = 0.07, 95% CI: 0.06, 0.07), higher hospital costs (aBeta = 47.35, 95% CI: 38.55, 56.14), increased risks of adverse events (aOR = 1.63, 95% CI: 1.02, 2.61), hemorrhage/need for transfusion (aOR = 1.77, 95% CI: 1.12, 2.79) and mechanical ventilation ≥ 96 hours (aOR = 2.14, 95% CI: 1.28, 3.58) compared to normal weight patients. Among patients with flail chest, morbid obesity was significantly associated with tracheostomy (aOR = 2.13, 95% CI: 1.05, 4.32), ARDS/respiratory failure (aOR = 2.01, 95% CI: 1.09, 3.70), and mechanical ventilation ≥ 96 hours (aOR = 2.80, 95% CI: 1.47, 5.32). In contrast, morbid obesity had no significant associations with these adverse respiratory outcomes among patients without a flail chest (p > 0.05). CONCLUSIONS: Morbid obesity is associated with adverse outcomes following SSRF for multiple rib fractures, especially for flail chest patients.

Predictive factors for severe outcomes in substance abuse-related emergency visits: A 5-year retrospective analysis at a medical center in Taiwan.

BACKGROUND: Substance abuse is a considerable medical issue worldwide, yet current surveillance systems in Taiwan offer limited insights into the clinical characteristics and outcomes of substance abuse patients. This study aimed to delineate the epidemiology of emergency department visits related to substance abuse at a hospital in Taiwan and to identify factors predictive of severe complications or mortality. METHODS: A retrospective analysis was conducted on substance abuse-related emergency department visits at a medical center in Taiwan between 2009 and 2013. Eligible participants were individuals aged 20 or older who had confirmed substance abuse through urinalysis. Variables such as patient demographics, substances abused, clinical characteristics, and outcomes were collected. Severe outcomes were defined as admission to the intensive care unit, requirement for endotracheal intubation, or in-hospital death. Logistic regression models were employed to identify factors contributing to severe outcomes. RESULTS: The cohort consisted of 623 patients, of whom 64.0% were female and 67.1% were aged between 20 and 49 years. Benzodiazepines were detected in 75.3% of patients, while z-drugs (specifically zopiclone, zolpidem, or zaleplon) were found in 27.8%. Depressants, stimulants, and hallucinogens were present in 14.9%, 10.6%, and 0.6% of the cases, respectively. Of the patient, 121 (19.4%) experienced severe outcomes, including 116 (18.6%) intensive care unit admissions, 73 (11.7%) intubations, and 11 (1.8%) in-hospital deaths. Multivariable logistic regression analysis revealed multiple predictors of severe outcomes, such as emergency department triage level, aspiration pneumonia, leukocytosis, abnormal hepatic function, abnormal renal function, hypernatremia, and hypocalcemia. CONCLUSION: In Taiwan, benzodiazepines emerged as the most prevalent substance of abuse among emergency department visitors, and a significant proportion of these patients experienced severe outcomes. Continuous monitoring of severe outcome predictors is essential for enhanced understanding and management.

Weight and metabolic changes among virally suppressed people with HIV who switched to co-formulated bictegravir/emtricitabine/tenofovir alafenamide.

OBJECTIVES: We aimed to investigate the evolution of weight, lipid profiles, and glucose homeostasis among virally suppressed people with HIV (PWH) who switched to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). METHODS: PWH with viral suppression who switched to BIC/FTC/TAF in Taiwan between October 2019 and May 2021 were followed for 96 weeks to examine changes in weight, lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG)), and glycated hemoglobin (HbA1c) levels. RESULTS: 889 PWH with an average weight of 72.1 kg at baseline were included. At week 96, more than 95% of PWH consistently maintained plasma HIV RNA load <50 copies/mL at each 24-week interval of follow-up, while the weight change was small (+0.7 kg, P < 0.0001), although statistically significant. Baseline levels of TC, LDL-C, HDL-C, TG, and HbA1c were 191.8 mg/dL, 114.2 mg/dL, 48.9 mg/dL, 174.3 mg/dL, and 5.31%, respectively. After 96 weeks, changes were observed in TC (-11.6 mg/dL, P < 0.0001), LDL-C (-3.4 mg/dL, P = 0.0084), HDL-C (+0.6 mg/dL, P = 0.1089), TG (-30.2, P < 0.0001), and HbA1c (+0.12%, P < 0.0001). A 5% or more weight gain was associated with age of 30-40 years, normal weight at baseline, and prior use of non-integrase inhibitors or tenofovir disoproxil fumarate. Obesity was associated with development of both dyslipidaemia and diabetes mellitus after switch. CONCLUSIONS: Stable switch to BIC/FTC/TAF maintained high rates of viral suppression and had a small effect on weight and metabolic changes in virally suppressed PWH. Follow-up of the weight and metabolic changes is warranted in PWH on long-term antiretroviral therapy.

The impact of serum estradiol and progesterone levels during implantation on obstetrical complications and perinatal outcomes in frozen embryo transfer.

BACKGROUND: This study sought to evaluate obstetric complications and perinatal outcomes in frozen embryo transfer (FET) using either a natural cycle (NC-FET) or a hormone therapy cycle (HT-FET). Furthermore, we investigated how serum levels of estradiol (E2) and progesterone (P4) on the day of and 3 days after embryo transfer (ET) correlated with clinical outcomes in the two groups. METHODS: We conducted a retrospective, single-center study from January 1, 2015, to December 31, 2019. The study included couples who underwent NC-FET or HT-FET resulting in a singleton live birth. Serum levels of E2 and P4 were measured on the day of and 3 days after ET. The primary outcomes assessed were preterm birth rate, low birth weight, macrosomia, hypertensive disorders in pregnancy, gestational diabetes mellitus, postpartum hemorrhage, and placenta-related complications. RESULTS: A total of 229 singletons were included, with 49 in the NC-FET group and 180 in the HT-FET group. There were no significant differences in obstetric complications and perinatal outcomes between the two groups. The NC-FET group had significantly higher serum levels of P4 (17.2 ng/mL vs 8.85 ng/mL; p < 0.0001) but not E2 (144 pg/mL vs 147 pg/mL; p = 0.69) on the day of ET. Additionally, 3 days after ET, the NC-FET group had significantly higher levels of both E2 (171 pg/mL vs 140.5 pg/mL; p = 0.0037) and P4 (27.3 ng/mL vs 11.7 ng/mL; p < 0.0001) compared with the HT-FET group. CONCLUSION: Our study revealed that although there were significant differences in E2 and P4 levels around implantation between the two groups, there were no significant differences in obstetric complications and perinatal outcomes. Therefore, the hormonal environment around implantation did not appear to be the primary cause of differences in obstetric and perinatal outcomes between the two EM preparation methods used in FET.

Upregulated enhancer of rudimentary homolog promotes epithelial­mesenchymal transition and cancer cell migration in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the deadliest cancers regarding both mortality rate and number of deaths and warrants greater effort in the development of potential therapeutic targets. The enhancer of rudimentary homolog (ERH) has been implicated in the promotion and progression of certain types of cancer. In the present study, ERH was assessed for its expression pattern and survival association with LUAD in public transcriptomic and proteomic databases. Bioinformatic methods and data from websites, including University of Alabama at Birmingham CANcer data analysis Portal and The Cancer Genome Atlas, were utilized to demonstrate the functional behaviors and corresponding pathways of ERH in LUAD. Human A549 and CL1­0 cell lines were used to validate the findings via functional assays. It was demonstrated that the expression of ERH, at both the transcriptomic and proteomic levels, was higher in LUAD compared with in adjacent non­tumor lung tissue and was associated with worse survival prognosis. Moreover, high ERH expression was correlated with more aggressive functional states, such as cell cycle and invasion in LUAD, and the positive ERH­correlated gene set was associated with worse survival and an immunosuppressive tumor microenvironment. Small nuclear ribonucleoprotein polypeptide G was identified as a molecule that potentially interacted with ERH. Lastly, it was demonstrated that ERH promoted epithelial­mesenchymal transition and cell migration in vitro, but not proliferation. In conclusion, higher expression of ERH in LUAD may facilitate cancer progression and confer worse outcomes. Further deep investigation into the role of ERH in LUAD is needed.

Beyond 10-year lead-times in EQ-5D-5L: leveraging alternative lead-times in willingness-to-accept questions to capture preferences for worse-than-dead states and their implication.

BACKGROUND: A fixed 10-year lead-time in composite time-trade-off (C-TTO) tasks might compromise the precision of utility values below - 1. This study explored how alternative lead-times (ALTs) influence EQ-5D-5L value sets and their implications in economic evaluations. METHODS: Leveraging data from Taiwan's EQ-5D-5L valuation and capitalizing on its exploratory willingness-to-accept question, we explored participants' quantification of "worse-than-dead (WTD)" health states with ALTs up to 50 years. We then derived alternative value sets incorporating these ALTs through interval regression and compared them against those from conventional models. To evaluate their impact on health change valuation, we simulated utility differences for all possible EQ-5D-5L health-state-pairs using each value set. RESULTS: With a salient floor effect observed in the C-TTO values, the model with ALT led to a wider range of predicted utilities ( - 2.3897 ~ 1), compared with those of conventional models (generalized least squares (GLS): - 0.7773 ~ 1; Tobit-GLS: - 0.9583 ~ 1). Compared to the Tobit-GLS model, the model with ALT increased the numerical distance in 80% of health-state-pairs, with 11% decreasing and 9% altering direction (e.g., positive to negative) in utility differences. CONCLUSIONS: While ALTs offer insights into patient preferences, their integration into economic evaluations might require rescaling. Future research should prioritize advanced rescaling methods or enhanced elicitation strategies for populations with substantial censoring. This is pivotal for improving the elicitation of extreme WTD states and accurately discerning the relative distances between health states. Countries developing EQ-5D-5L value sets should consider pilot studies and incorporating region-specific questions on social determinants, especially where pronounced floor effects are suspected.

Effect of extra-low dose levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism undergoing in vitro fertilization and embryo transfer.

OBJECTIVE: This study was undertaken to test the therapeutic effect of extra-low dose of levothyroxine (LT4; 25 mcg/day) to preconception and pregnant women with subclinical hypothyroidism (SCH). MATERIALS AND METHODS: This is a retrospective study, SCH women who succeeded in their first in vitro fertilization (IVF) cycle between January 1, 2018, to December 31, 2020 were included. SCH is defined as normal serum free thyroxine (T4) level and an elevated serum thyroid stimulating hormone (TSH) level >4 mIU/L. Extra-low dose of levothyroxine (LT4; 25 mcg/day) was prescribed to the SCH women from the establish of diagnosis of SCH to the end of pregnancy. The pregnancy outcomes (miscarriage, live birth, preterm birth, and small for gestational age baby) were compared to the euthyroid pregnant women. RESULTS: Totally, 589 women were screened, and 317 cases received their first time IVF treatment. 167 women were clinically pregnant after IVF treatment, 155 of them were euthyroid and 12 of these women were diagnosed to have SCH. The average age of the participants was 35 years old. There were no significant differences in age, body mass index (BMI), anti-müllerian hormone (AMH), types of embryo transfer, number of embryos to transfer, or embryo stage during transfer between two groups. The live birth rate, miscarriage rate, and preterm birth rate in women with SCH supplemented with extra-low dose of LT4 were non-inferior to euthyroid patients (miscarriage rate: P = 0.7112; live birth rate: P = 0.7028; preterm delivery: P = 0.2419; small for gestational age: P = 0.2419). CONCLUSION: Our result demonstrated that supplementation with extra-low dose of levothyroxine at 25 mcg/day to SCH women can produce the comparable obstetrical and neonatal outcome as that in euthyroid pregnant women. Accordingly, we suggest extra-low-dose of levothyroxine may be considered as a safe and effective alternative for those SCH pregnant women who were not tolerated to the standard dose of levothyroxine.