Anxiety and depression are associated with heightened risk of incident deep vein thrombosis: Mediation through stress-related neural mechanisms.

Controversy exists as to whether anxiety and depression increase deep vein thrombosis (DVT) risk, and the mechanisms mediating potential links remain unknown. We aimed to evaluate the association between anxiety and depression and DVT risk and determine whether upregulated stress-related neural activity (SNA), which promotes chronic inflammation, contributes to this link. Our retrospective study included adults (N = 118 871) enrolled in Mass General Brigham Biobank. A subset (N = 1520) underwent clinical 18F-FDG-PET/CT imaging. SNA was measured as the ratio of amygdalar to cortical activity (AmygAC). High-sensitivity C-reactive protein (hs-CRP) and heart rate variability (HRV) were also obtained. Median age was 58 [interquartile range (IQR) 42-70] years with 57% female participants. DVT occurred in 1781 participants (1.5%) over median follow-up of 3.6 years [IQR 2.1-5.2]. Both anxiety and depression independently predicted incident DVT risk after robust adjustment (HR [95% CI]: 1.53 [1.38-1.71], p < .001; and 1.48 [1.33-1.65], p < .001, respectively). Additionally, both anxiety and depression associated with increased AmygAC (standardized beta [95% CI]: 0.16 [0.04-0.27], p = .007, and 0.17 [0.05-0.29], p = .006, respectively). Furthermore, AmygAC associated with incident DVT (HR [95% CI]: 1.30 [1.07-1.59], p = .009). Mediation analysis demonstrated that the link between anxiety/depression and DVT was mediated by: (1) higher AmygAC, (2) higher hs-CRP, and (3) lower HRV ( < .05 for each). Anxiety and depression confer an attributable risk of DVT similar to other traditional DVT risk factors. Mechanisms appear to involve increased SNA, autonomic system activity, and inflammation. Future studies are needed to determine whether treatment of anxiety and depression can reduce DVT risk.

Impact of pelvic floor muscle training on sexual function in women affected by stress urinary incontinence.

Background: Pelvic floor muscle training can effectively improve pelvic floor muscle strength and activities; however, its impact on sexual function in women with stress urinary incontinence remains unclear. Aim: The study sought to investigate the impact of pelvic floor muscle training on pelvic floor muscle and sexual function in women with stress urinary incontinence. Methods: This was a retrospective observational study involving women who visited a urogynecologic clinic at a tertiary medical center. Patients with stress urinary incontinence without pelvic organ prolapse underwent pelvic floor muscle training programs that included biofeedback and intravaginal electrostimulation. Other evaluations included pelvic floor manometry, electromyography, and quality-of-life questionnaires, including the short forms of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, Urogenital Distress Inventory, and Incontinence Impact Questionnaire. Outcomes: Clinical characteristics, vaginal squeezing and resting pressure, maximal pelvic floor contraction, duration of sustained contraction, quality-of-life scores, and sexual function were compared between baseline and after the pelvic floor muscle training programs. Results: There were 61 women included in the study. The mean number of treatment sessions was 12.9 ± 6.3, and the mean treatment duration was 66.7 ± 32.1 days. The short forms of the Urogenital Distress Inventory (7.7 ± 3.8 vs 1.8 ± 2.1; P < .001) and Incontinence Impact Questionnaire (5.9 ± 4.3 vs 1.8 ± 2.0; P < .001) scores significantly improved after the pelvic floor muscle training program. In addition, all pelvic floor muscle activities significantly improved, including maximal vaginal squeezing pressure (58.7 ± 20.1 cmH2O vs 66.0 ± 24.7 cmH2O; P = .022), difference in vaginal resting and maximal squeezing pressure (25.3 ± 14.6 cmH2O vs 35.5 ± 16.0 cmH2O; P < .001), maximal pelvic muscle voluntary contraction (24.9 ± 13.8 µV vs 44.5 ± 18.9 µV; P < .001), and duration of contraction (6.2 ± 5.7 s vs 24.9 ± 14.6 s; P < .001). Nevertheless, the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire score demonstrated no significant improvement (28.8 ± 9.7 vs 29.2 ± 12.3; P = .752). Clinical Implications: Pelvic floor muscle training programs may not improve sexual function in women with stress urinary incontinence. Strengths and Limitations: The strength of this study is that we evaluated sexual function with validated questionnaires. The small sample size and lack of long-term data are the major limitations. Conclusion: Pelvic floor muscle training can improve pelvic floor muscle activities and effectively treat stress urinary incontinence; however, it may not improve sexual function.

Heart-brain axis: Pushing the boundaries of cardiovascular molecular imaging.

Despite decades of research, the heart-brain axis continues to challenge investigators seeking to unravel its complex pathobiology. Strong epidemiologic evidence supports a link by which insult or injury to one of the organs increases the risk of pathology in the other. The putative pathways have important differences between sexes and include alterations in autonomic function, metabolism, inflammation, and neurohormonal mechanisms that participate in crosstalk between the heart and brain and contribute to vascular changes, the development of shared risk factors, and oxidative stress. Recently, given its unique ability to characterize biological processes in multiple tissues simultaneously, molecular imaging has yielded important insights into the interplay of these organ systems under conditions of stress and disease. Yet, additional research is needed to probe further into the mechanisms underlying the heart-brain axis and to evaluate the impact of targeted interventions.

Integrative methylome and transcriptome analysis reveals epigenetic regulation of Fusobacterium nucleatum in laryngeal cancer.

The aetiological mechanisms of Fusobacterium nucleatum in laryngeal cancer remain unclear. This study aimed to reveal the epigenetic signature induced by F. nucleatum in laryngeal squamous cell carcinoma (LSCC). Combined analysis of methylome and transcriptome data was performed to address the functional role of F. nucleatum in laryngeal cancer. Twenty-nine differentially expressed methylation-driven genes were identified by mapping the methylation levels of significant differential methylation sites to the expression levels of related genes. The combined analysis revealed that F. nucleatum promoted Janus kinase 3 (JAK3) gene expression in LSCC. Further validation found decreased methylation and elevated expression of JAK3 in the F. nucleatum-treated LSCC cell group; F. nucleatum abundance and JAK3 gene expression had a positive correlation in tumour tissues. This analysis provides a novel understanding of the impact of F. nucleatum in the methylome and transcriptome of laryngeal cancer. Identification of these epigenetic regulatory mechanisms opens up new avenues for mechanistic studies to explore novel therapeutic strategies.

A machine-learning exploration of the exposome from preconception in early childhood atopic eczema, rhinitis and wheeze development.

BACKGROUND: Most previous research on the environmental epidemiology of childhood atopic eczema, rhinitis and wheeze is limited in the scope of risk factors studied. Our study adopted a machine learning approach to explore the role of the exposome starting already in the preconception phase. METHODS: We performed a combined analysis of two multi-ethnic Asian birth cohorts, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) and the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohorts. Interviewer-administered questionnaires were used to collect information on demography, lifestyle and childhood atopic eczema, rhinitis and wheeze development. Data training was performed using XGBoost, genetic algorithm and logistic regression models, and the top variables with the highest importance were identified. Additive explanation values were identified and inputted into a final multiple logistic regression model. Generalised structural equation modelling with maternal and child blood micronutrients, metabolites and cytokines was performed to explain possible mechanisms. RESULTS: The final study population included 1151 mother-child pairs. Our findings suggest that these childhood diseases are likely programmed in utero by the preconception and pregnancy exposomes through inflammatory pathways. We identified preconception alcohol consumption and maternal depressive symptoms during pregnancy as key modifiable maternal environmental exposures that increased eczema and rhinitis risk. Our mechanistic model suggested that higher maternal blood neopterin and child blood dimethylglycine protected against early childhood wheeze. After birth, early infection was a key driver of atopic eczema and rhinitis development. CONCLUSION: Preconception and antenatal exposomes can programme atopic eczema, rhinitis and wheeze development in utero. Reducing maternal alcohol consumption during preconception and supporting maternal mental health during pregnancy may prevent atopic eczema and rhinitis by promoting an optimal antenatal environment. Our findings suggest a need to include preconception environmental exposures in future research to counter the earliest precursors of disease development in children.

Metagenomic shotgun sequencing reveals the enrichment of Salmonella and Mycobacterium in larynx due to prolonged ethanol exposure.

The exposure of ethanol increases the risk of head and neck inflammation and tumor progression. However, limited studies have investigated the composition and functionality of laryngeal microbiota under ethanol exposure. We established an ethanol-exposed mouse model to investigate the changes in composition and function of laryngeal microbiota using Metagenomic shotgun sequencing. In the middle and late stages of the experiment, the laryngeal microbiota of mice exposed to ethanol exhibited obvious distinguished from that of the control group on principal-coordinate analysis (PCoA) plots. Among the highly abundant species, Salmonella enterica and Mycobacterium marinum were likely to be most impacted. Our findings indicated that the exposure to ethanol significantly increased their abundance in larynxes in mice of the same age, which has been confirmed through FISH experiments. Among the species-related functions and genes, metabolism is most severely affected by ethanol. The difference was most obvious in the second month of the experiment, which may be alleviated later because the animal established tolerance. Notable enrichments concerning energy, amino acid, and carbohydrate metabolic pathways occurred during the second month under ethanol exposure. Finally, based on the correlation between species and functional variations, a network was established to investigate relationships among microbiota, functional pathways, and related genes affected by ethanol. Our data first demonstrated the continuous changes of abundance, function and their interrelationship of laryngeal microbiota under ethanol exposure by Metagenomic shotgun sequencing. Importance: Ethanol may participate in the inflammation and tumor progression by affecting the composition of the laryngeal microbiota. Here, we applied the metagenomic shotgun sequencing instead of 16 S rRNA sequencing method to identify the laryngeal microbiota under ethanol exposure. Salmonella enterica and Mycobacterium marinum are two dominant species that may play a role in the reconstruction of the laryngeal microenvironment, as their local abundance increases following exposure to ethanol. The metabolic function is most evidently impacted, and several potential metabolic pathways could be associated with alterations in microbiota composition. These findings could help us better understand the impact of prolonged ethanol exposure on the microbial composition and functionality in the larynx.

The changes in bladder function and symptoms after robot-assisted sacrocolpopexy and transvaginal mesh surgery for pelvic organ prolapse.

OBJECTIVE: This study is aimed to compare the impact on bladder function and symptoms between robotic sacrocolpopexy (RSC) and transvaginal mesh surgery (TVM) in women with pelvic organ prolapse. MATERIALS AND METHODS: This prospective controlled study enrolled patients who received RSC or TVM at our hospital between March 2020 and June 2022. We compared preoperative and postoperative bladder function between two groups by using a questionnaire of lower urinary tract symptom (LUTs) for subjective assessment and urodynamic study for objective assessment. RESULTS: A total of 60 patients were enrolled, of whom 30 received RSC and 30 received TVM. In LUTs analysis, the RSC group had a higher risk of de novo stress urinary incontinence than the TVM group (33.3% vs. 3.3%, p = .007). Urodynamic studies showed that both groups had a deterioration in maximal urethral closure pressure postoperatively (RSC: 56.9 ± 17.1 vs. 44.2 ± 15.5 cmH2O; and TVM: 61.2 ± 29.4 vs. 47.6 ± 19.7 cmH2O, p < .01 and p = .03, respectively). The incidence of urodynamic stress incontinence was also significantly increased after RSC (33.3% vs. 76.7%, p = .01). The de novo urodynamic stress incontinence rate was 46.7% after RSC, which was not significantly different to the TVM group (26.7%, p = .16). In the TVM group, the incidence of voiding difficulty decreased after surgery (43.3% vs. 10.0%, p < .01), and urodynamic measurements revealed that the prevalence of urine retention decreased (43.3% vs. 16.7%, p < .01). In the RSC group, the incidence of incomplete emptying sensation decreased (36.7% vs. 13.3%, p = .04), and urodynamic measurements showed that none of the patients had bladder outlet obstruction, underactive detrusor, or urine retention after surgery. CONCLUSION: RSC and TVM are both beneficial to improve voiding function in women with pelvic organ prolapse. However, a deterioration in urethral function was observed and the de novo SUI rate was higher in the RSC group than in the TVM group.

Unraveling the surface marker signature of cell-derived vesicles via proteome analysis and nanoparticle flow cytometry.

The cell-derived vesicles (CDVs) obtained using a proprietary extrusion process are the foundation of BioDrone platform technology. With superior productivity and versatility, this technology has garnered increasing attention in broad applications, particularly as a drug delivery vehicle. Previously, we showed that CDVs exhibited varying levels of expression for tetraspanin and organelle membrane markers while revealing no discernible differences in physical characteristics compared to naturally produced extracellular vesicles (EVs). To further understand and utilize the therapeutic potentials of CDVs, a more comprehensive study of membrane protein profiles is necessary. In addition, it is crucial to validate that the CDVs produced from extrusion are indeed intact lipid vesicles rather than other impurities. Here, we produced multiple batches of CDVs and EVs from HEK293 cells. CDVs and EVs were subjected to the same purification processes for subsequent proteome and particle analyses. The proteome analyses revealed unique proteome signatures between CDVs, EVs, and parental cells. Extensive proteome analyses identified the nine most prominent membrane markers that are abundant in CDVs compared to cells and EVs. Subsequent western blotting and nanoparticle flow cytometry analyses confirmed that CD63, lysosome-associated membrane glycoprotein 1 (LAMP1), and nicastrin (NCSTN) are highly enriched in CDVs, whereas CD81, CD9, and prostaglandin F2 receptor negative regulator (PTGFRN) are more abundant in EVs. This highlights the unique membrane composition and marker signature of CDVs that are distinct from EVs. Lastly, we demonstrated that more than 90% of the CDVs are genuine lipid vesicles by combining two different classes of vesicle labeling dyes and detergents to disrupt lipid membranes. This indicates that our proprietary extrusion technology is highly compatible with other well-characterized EV production methods. The robust CDV markers identified in this study will also facilitate the engineering of CDVs to achieve enhanced therapeutic effects or tissue-selective cargo delivery.

Fusobacterium nucleatum facilitates proliferation and autophagy by activating miR-361-3p/NUDT1 axis through oxidative stress in hypopharyngeal squamous cell carcinoma.

BACKGROUND: To investigate how Fusobacterium nucleatum (Fn) promotes oxidative stress and mediates proliferation and autophagy in hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: The prognosis for 82 HPSCC cases was retrospectively analyzed. HPSCC cell line FaDu was co-cultured with Fn. Knockdown of NUDT1 (shNUDT1 group) was done after observing DNA damage response. CCK8 and tumorigenesis assays for proliferation observation, mitochondria ROS (MitoROS) measurement to examine intracellular oxidative stress, and ELISA to analyze concentration of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in cells. Dual-luciferase reporter assays clarified miR-361-3p connection with NUDT1. Autophagy flow was observed using electron microscopy and related proteins. RESULTS: Fn was highly associated with NUDT1. The shNUDT1 group experienced lower proliferation compared with normal FaDu (NC group) in vivo and in vitro. The shNUDT1 group showed 8-oxo-dG and γH2AX to be elevated. Intracellular ROS decreased in shNUDT1Fn group when compared to Fn group. Upregulating miR-361-3p could suppress NUDT1 expression and downstream proliferation and autophagy. Fn modulated miR-361-3p via OH-, which could be proven by H2O2 assay and N-acetylcysteine. CONCLUSIONS: Higher Fn in HPSCC patients suggests poorer prognosis. NUDT1 might affect cell proliferation and autophagy and modulate DNA damage response. The oxidative stress induced miR-361-3p/NUDT1 axis is first introduced in microbiome-carcinoma research.

Smoke exposure and childhood atopic eczema and food allergy: A systematic review and meta-analysis.

BACKGROUND: There is no consensus on the effect of timing and type of smoke exposure on early allergy development. This study aimed to determine the relationship between early eczema or food allergy/hypersensitivity development in children by firstly investigating the effect of smoke exposure across critical development periods and secondly by analyzing effects of parental atcive or passive smoking. METHODS: Four databases (PubMed, Web of Science, Scopus and Embase) were searched in May 2022 and assessed by two independent reviewers. Case-control, cross-sectional or cohort studies reporting on smoke exposure from preconception to postnatal periods and atopic eczema, food allergy and/or hypersensitivity outcomes by age 3 years were included. The Newcastle-Ottawa Scale was used to assess study quality. Random effects model was used to estimate the pooled risk ratios. RESULTS: From 1689 identified records, 32 studies with nearly 190,000 subjects were included. Parental smoking during preconception, pregnancy and postnatal periods was generally not associated with the risk of eczema, food allergy and food sensitisation development by age 3 years. Maternal active smoking during pregnancy was negatively associated with self-reported doctor diagnosis of eczema (RR = 0.87, 95% CI 0.77-0.98; I2 = 50.56) and maternal passive smoking during pregnancy was positively associated with clinician assessment of eczema in one study (RR = 1.38; 95% CI 1.06-1.79). CONCLUSION: Our findings highlighted the importance of in utero programming in early-life allergy development. Despite the weak evidence, our results suggest pregnant women should minimise their contact with second-hand smoke to prevent offspring eczema development. There is a need for greater utilisation of objective allergy assessments in future studies.

Early minimally invasive intracerebral hemorrhage evacuation: a phase 2a feasibility, safety, and promise of surgical efficacy study.

BACKGROUND: Surgical treatment of intracerebral hemorrhage (ICH) is unproven, although meta-analyses suggest that both early conventional surgery with craniotomy and minimally invasive surgery (MIS) may be beneficial. We aimed to demonstrate the safety, feasibility, and promise of efficacy of early MIS for ICH using the Aurora Surgiscope and Evacuator. METHODS: We performed a prospective, single arm, phase IIa Simon's two stage design study at two stroke centers (10 patients with supratentorial ICH volumes ≥20 mL and National Institutes of Health Stroke Scale (NIHSS) score of ≥6, and surgery commencing <12 hours after onset). Positive outcome was defined as ≥50% 24 hour ICH volume reduction, with the safety outcome lack of significant ICH reaccumulation. RESULTS: From December 2019 to July 2020, we enrolled 10 patients at two Australian Comprehensive Stroke Centers, median age 70 years (IQR 65-74), NIHSS score 19 (IQR 19-29), ICH volume 59 mL (IQR 25-77), at a median of 227 min (IQR 175-377) post-onset. MIS was commenced at a median time of 531 min (IQR 437-628) post-onset, had a median duration of 98 min (IQR 77-110), with a median immediate postoperative hematoma evacuation of 70% (IQR 67-80%). A positive outcome was achieved in 5/5 first stage patients and in 4/5 second stage patients. One patient developed significant 24 hour ICH reaccumulation; otherwise, 24 hour stability was observed (median reduction 71% (IQR 61-80), 5/9 patients <15 mL residual). Three patients died, unrelated to surgery. There were no surgical safety concerns. At 6 months, the median modified Rankin Scale score was 4 (IQR 3-6) with 30% achieving a score of 0-3. CONCLUSION: In this study, early ICH MIS using the Aurora Surgiscope and Evacuator appeared to be feasible and safe, warranting further exploration. TRIAL REGISTRATION NUMBER: ACTRN12619001748101.

Pressure-Volume Loop Analysis of Voiding Workload: An Application in Trans-Vaginal Mesh-Repaired Pelvic Organ Prolapse Patients.

Although trans-vaginal mesh (TVM) offers a successful anatomical reconstruction and can subjectively relieve symptoms/signs in pelvic organ prolapse (POP) patients, its objective benefits to the voiding function of the bladder have not been well established. In this study, we investigated the therapeutic advantage of TVM on bladder function by focusing on the thermodynamic workload of voiding. The histories of 31 POP patients who underwent TVM repair were retrospectively reviewed. Cystometry and pressure volume analysis (PVA) of the patients performed before and after the operation were analyzed. TVM postoperatively decreased the mean voiding resistance (mRv, p < 0.05, N = 31), reduced the mean and peak voiding pressure (mPv, p < 0.05 and pPv, p < 0.01, both N = 31), and elevated the mean flow rate (mFv, p < 0.05, N = 31) of voiding. While displaying an insignificant effect on the voided volume (Vv, p < 0.05, N = 31), TVM significantly shortened the voiding time (Tv, p < 0.05, N = 31). TVM postoperatively decreased the loop-enclosed area (Apv, p < 0.05, N = 31) in the PVA, indicating that TVM lessened the workload of voiding. Moreover, in 21 patients who displayed postvoiding urine retention before the operation, TVM decreased the residual volume (Vr, p < 0.01, N = 21). Collectively, our results reveal that TVM postoperatively lessened the workload of bladder voiding by diminishing voiding resistance, which reduced the pressure gradient required for driving urine flow.

Clinical predictors of wheeze trajectories and associations with allergy in Asian children.

BACKGROUND: Childhood wheezing is a highly heterogeneous condition with an incomplete understanding of the characteristics of wheeze trajectories, particularly for persistent wheeze. OBJECTIVE: To characterize predictors and allergic comorbidities of distinct wheeze trajectories in a multiethnic Asian cohort. METHODS: A total of 974 mother-child pairs from the prospective Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort were included in this study. Wheeze and allergic comorbidities in the first 8 years of life were assessed using the modified International Study of Asthma and Allergies in Childhood questionnaires and skin prick tests. Group-based trajectory modeling was used to derive wheeze trajectories and regression was used to assess associations with predictive risk factors and allergic comorbidities. RESULTS: There were 4 wheeze trajectories derived, including the following: (1) early-onset with rapid remission from age 3 years (4.5%); (2) late-onset peaking at age 3 years and rapidly remitting from 4 years (8.1%); (3) persistent with a steady increase to age 5 years and high wheeze occurrence until 8 years (4.0%); and (4) no or low wheeze (83.4%). Early-onset wheezing was associated with respiratory infections during infancy and linked to subsequent nonallergic rhinitis throughout childhood. Late-onset and persistent wheeze shared similar origins characterized by parent-reported viral infections in later childhood. However, persistent wheezing was generally more strongly associated with a family history of allergy, parent-reported viral infections in later childhood, and allergic comorbidities as compared with late-onset wheezing. CONCLUSION: The timing of viral infection occurrence may determine the type of wheeze trajectory development in children. Children with a family history of allergy and viral infections in early life may be predisposed to persistent wheeze development and the associated comorbidities of early allergic sensitization and eczema.

An integrated life cycle assessment and techno-economic analysis: Evaluation on the production of polymers of intrinsic microporosity (PIM-1) and UiO-66-NH2 as membrane materials.

Material synthesis requires an enormous amount of organic solvents which leads to huge environmental burdens. Being so, the necessity to utilize non-toxic chemicals is of growing interest in the global market. Harnessing a green fabrication strategy could be a sustainable remedy. Herein, life cycle assessment (LCA) and techno-economic assessment (TEA) using a cradle-to-gate approach to select the green synthesis route for the production of main components in mixed matrix membranes such as polymer and fillers were studied. Five representative synthesis routes of polymers of intrinsic microporosity (PIM-1) and fillers such as UiO-66-NH2 (UiO: University of Oslo) were conducted. Our findings revealed that the tetrachloroterephthalonitrile (TCTPN) synthesized PIM-1 using a novel approach (e.g., P5-Novel synthesis) and solvent-free synthesized UiO-66-NH2 (e.g., U5-Solvent-free) demonstrated the least environmental impact and are most economically feasible. The environmental burden and cost of PIM-1 synthesized by P5-Novel synthesis route decreased by 50 % and 15 %, respectively, while that of UiO-66-NH2 produced via U5-Solvent-free route reduced by 89 % and 52 %, respectively. Additionally, solvent reduction was found to have an apparent effect on cost-saving, whereby the production cost declined 13 % with a 30 % solvent reduction. Alleviation of environmental burdens could also be found through recovering solvents or substituting with a greener alternative (e.g., water). The fundamentals gained on the environmental impacts and economic feasibility of PIM-1 and UiO-66-NH2 production from this LCA-TEA study may provide a preliminary evaluation for the development of green and sustainable materials.

Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes in Malaysia: Results from a Prospective, Non-interventional Real-World Study.

Objectives: Insulin degludec (IDeg)/insulin aspart (IAsp; IDegAsp) is a co-formulation of 70% IDeg and 30% IAsp. According to several randomized controlled trials, IDegAsp is effective and safe for patients with type 2 diabetes mellitus (T2DM). A subgroup analysis of the ARISE study was conducted to explore the safety and efficacy of IDegAsp among Malaysian patients with T2DM in real-world settings. Methodology: ARISE, an open-label, multicenter, non-interventional, prospective study was conducted between August 2019 and December 2020. Adult Malaysian patients with T2DM who were enrolled from 14 sites received IDegAsp as per the local label for 26 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) levels from baseline to end of study (EOS). Results: Of the 182 patients included in the full analysis set, 159 (87.4%) completed the study. From baseline to EOS, HbA1c (estimated difference [ED]: -1.3% [95% CI: -1.61 to -0.90]) and fasting plasma glucose levels (ED: -1.8 mmol/L [95% CI: -2.49 to -1.13]) were significantly reduced (p<0.0001). The patient-reported reduced hypoglycemic episodes (overall and nocturnal) during treatment. Overall, 37 adverse events were observed in 23 (12.6%) patients. Conclusion: Switching or initiating IDegAsp treatment resulted in significant improvements in glycemic control and a reduction in hypoglycemic episodes.

FIGO recommendations: Use of midurethral slings for the treatment of stress urinary incontinence.

BACKGROUND: Stress urinary incontinence (SUI) is a global problem. It can significantly adversely impact a woman's quality of life. The use of synthetic mesh in vaginal surgery is controversial, especially when used for pelvic organ prolapse surgery. Although negative effects have been reported, the synthetic mesh midurethral sling (MUS) is considered to be safe and effective in the surgical treatment of SUI. OBJECTIVES: To provide evidence-based data and recommendations for the obstetrician/gynecologist who treats women with SUI and performs or plans to perform MUS procedures. METHODS: Academic searches of MEDLINE, the Cochrane Library, Embase, and Google Scholar articles published between 1987 and March 2020 were performed by a subgroup of the Urogynecology and Pelvic Floor Committee, International Federation of Gynecology and Obstetrics (FIGO). SELECTION CRITERIA: The obtained scientific data were associated with a level of evidence according to the Oxford University Centre for Evidence-Based Medicine and GRADE Working Group system. In the absence of concrete scientific evidence, the recommendations were made via professional consensus. RESULTS: The FIGO Urogynecology and Pelvic Floor Committee reviewed the literature and prepared this evidence-based recommendations document for the use of MUS for women with SUI. CONCLUSIONS: Despite the extensive literature, there is a lack of consensus in the optimal surgical treatment of SUI. These recommendations provide a direction for surgeons to make appropriate decisions regarding management of SUI. The MUS is considered safe and effective in the treatment of SUI, based on many high-quality scientific publications and professional society recommendations. Comprehensive long-term data and systemic reviews are still needed, and these data will become increasingly important as women live longer. These recommendations will be continuously updated through future literature reviews.

Emerging PET Tracers in Cardiac Molecular Imaging.

18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) represent emerging PET tracers used to assess atherosclerosis-related inflammation and molecular calcification, respectively. By localizing to sites with high glucose utilization, FDG has been used to assess myocardial viability for decades, and its role in evaluating cardiac sarcoidosis has come to represent a major application. In addition to determining late-stage changes such as loss of perfusion or viability, by targeting mechanisms present in atherosclerosis, PET-based techniques have the ability to characterize atherogenesis in the early stages to guide intervention. Although it was once thought that FDG would be a reliable indicator of ongoing plaque formation, micro-calcification as portrayed by NaF-PET/CT appears to be a superior method of monitoring disease progression. PET imaging with NaF has the additional advantage of being able to determine abnormal uptake due to coronary artery disease, which is obscured by physiologic myocardial activity on FDG-PET/CT. In this review, we discuss the evolving roles of FDG, NaF, and other PET tracers in cardiac molecular imaging.

Tumour microbiota structure predicts hypopharyngeal carcinoma recurrence and metastasis.

Objectives: The relationship between microbiota and HPSCC recurrence and metastasis remains uncertain. This study aimed to investigate the role of the tumour microbiota in the disease-free survival (DFS) of HPSCC patients. Materials and methods: Formalin-fixed paraffin-embedded (FFPE) tumour tissues were collected from 103 patients with HPSCC for 16S rRNA sequencing. We analysed the tumour microbiota in HPSCC patients with recurrence/metastasis and nonrecurrence/metastasis. The linear predictor score (LPS) was calculated based on the Cox regression model to assess the risk of recurrence and metastasis. Then, a time-dependent ROC curve was used to evaluate the prognostic power of the LPS. Results: The phyla Bacteroidota, Firmicutes and Proteobacteria were the most abundant bacterial taxa in the tumour tissues. Eubacterium_coprostanoligenes_group (hazard ratio [HR] = 0.289, 95% confidence interval [CI] 0.137-0.608, p= 0.001) and Prevotella (HR = 3.744, 95% CI 1.439-9.738, p= 0.007) were independent predictors of DFS. The predicting classifier for recurrence and metastasis risk yielded an area under the curve (AUC) of 0.838 at 3 years and 0.860 at 5 years. Conclusion: Our study demonstrated the relationship between tumour microbiota and recurrence and metastasis in patients with HPSCC.

Impact of Weight Gain on Surgical Outcomes and Quality of Life among Women after Sling Surgeries.

STUDY OBJECTIVE: To investigate the impact of body weight gain after sling surgeries on outcomes in women with stress urinary incontinence. DESIGN: A single-center, retrospective study. SETTING: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taiwan. PATIENTS: A total of 248 women who underwent sling surgeries from 2010 to 2015 were reviewed. Patients who gained more than 10% body weight were compared with those with stable body weight. INTERVENTIONS: Midurethral sling surgery with single-incision, transobturator, or retropubic slings. MEASUREMENTS AND MAIN RESULTS: Objective success was defined as no urine leakage during the stress test in the filling phase of urodynamic studies. De novo overactive bladder (OAB) was defined as the appearance of urgency, frequency, and/or nocturia, with or without urinary incontinence after midurethral sling surgery persisting after 6 months. Quality of life evaluations included the short forms of the Urogenital Distress Inventory-6 and Incontinence Impact Questionnaire-7. A total of 248 women who underwent sling surgeries and had complete weight measurement and evaluation data before and after the surgeries were included, of whom 47 gained body weight, and 201 had a stable body weight. The median follow-up duration was 18 months (range, 6-47 months). There were no significant differences in surgical outcomes between the 2 groups regarding objective cure rate (86% vs 87%, p = .834), 1-hour pad test (4.5 ± 17.8 vs 3.6 ± 18.6 g, p = .770), or postoperative quality of life (Urogenital Distress Inventory-6: 1.9 ± 2.8 vs 2.8 ± 3.2, p = .122; Incontinence Impact Questionnaire-7: 1.8 ± 3.9 vs 2.6 ± 4.3, p = .307). A trend toward increased de novo OAB rate was observed, although this finding was not adequately powered. CONCLUSION: Weight gain after sling surgeries did not influence surgical outcomes, but there was a nonsignificant trend toward increased OAB in the weight gain group. It may be beneficial to counsel patients with regard to body weight maintenance after sling surgeries.

Atherosclerosis Imaging: Positron Emission Tomography.

Assessment of molecular changes by PET has introduced a new paradigm in atherosclerosis imaging, which has traditionally relied on anatomic changes visualized by conventional angiography or computed tomography. The use of 18F-fluorodeoxyglucose (FDG) to identify atherosclerotic changes in the vessel wall was first described more than 2 decades ago. Since then, PET tracers targeting macrophage activity, neoangiogenesis, smooth muscle activity, and other aspects of atherogenic changes have been proposed. The evolving roles of PET tracers including frontrunners FDG and 18F-sodium fluoride, which show arterial wall inflammation and microcalcification, respectively, are discussed.