Generic Method Research Articles

Multi‐Material Gradient Printing Using Meniscus‐enabled Projection Stereolithography (MAPS)

AbstractLight‐based additive manufacturing methods are widely used to print high‐resolution 3D structures for applications in tissue engineering, soft robotics, photonics, and microfluidics, among others. Despite this progress, multi‐material printing with these methods remains challenging due to constraints associated with hardware modifications, control systems, cross‐contamination, waste, and resin properties. Here, a new printing platform coined Meniscus‐enabled Projection Stereolithography (MAPS) is reported, a vat‐free method that relies on generating and maintaining a resin meniscus between a crosslinked structure and bottom window to print lateral, vertical, discrete, or gradient multi‐material 3D structures with no waste and user‐defined mixing between layers. MAPS is compatible with a wide range of resins shown and can print complex multi‐material 3D structures without requiring specialized hardware, software, or complex washing protocols. MAPS's ability to print structures with microscale variations in mechanical stiffness, opacity, surface energy, cell densities, and magnetic properties provides a generic method to make advanced materials for a broad range of applications.

Highly Sensitive and Robust LC-MS/MS Method for Determination up to 15 Small Molecule Nitrosamine Impurities in Pharmaceutical Drug Substances.

Nitrosamine impurities have been classified as probable human carcinogens for decades. These impurities were reported in water, food, tobacco, pesticides, and plastics but received attention in mid-2018 when N-nitrosodimethylamine (NDMA) was reported in valsartan drug products. Subsequently, it was revealed that several small molecule and complex nitrosamine impurities can form in any active pharmaceutical ingredient (API) or drug product in which secondary or tertiary amines are present (as API or as impurities) along with a nitrosating agent. Consequently, regulators have provided several guidelines for the risk assessment of nitrosamine formation during manufacturing, storage, or from contaminated supply chains. This has led to a demand for validated analytical methods that quantify N-nitrosamine impurities in pharmaceutical products. In this study, a highly sensitive and robust analytical method was developed and validated for quantitatively determining up to 15 small nitrosamines at low levels (0.01 ppm) in sartan drug substances. The study also suggests that this method can be extended not only to corresponding sartan drug products but could also be used as a generic screening method to test a variety of drug substances, and drug products with the minimum required optimization of method conditions.

Abstract 4148096: Discrimination Abilities of Euroscore and SYNTAX score for Prognostic Outcomes in patients with Stable Coronary Artery Disease: A Systematic Review and Meta-analysis

Introduction: There is a lack of good risk prediction models in patients with stable coronary artery disease (SCAD). We conducted a meta-analysis of validation studies to compare and determine the discrimination abilities of Euroscore (ES) and Syntax score (SS) for prognostic outcomes in patients with SCAD. Methods: A comprehensive literature search was conducted across MEDLINE, Cochrane and Embase from inception till May 2024. All studies that reported C-statistic/AUC for predicting all cause mortality, cardiac death or Major adverse cardiovascular events (MACE) for patients with stable coronary artery disease (SCAD) were included in the analysis. Studies lacking confidence intervals (CI) for C-statistic or those which reported C-statistics in patients with acute coronary syndromes or mixed SCAD and ACS patients were excluded. A generic inverse variance method was used to pool C-statistics and their corresponding standard errors (SEs). The SEs were calculated from CI wherever needed. A pooled C statistic of >0.8 was considered to be a good discrimination ability. Results: A total of 5 studies with a patient population of 5903 were included in the meta-analysis. For ES, the pooled C-statistic for all cause mortality (n=2666) was 0.69[0.51-0.87] while for cardiac death (n=2666) it was 0.77[0.60-0.71]. The discrimination ability of ES for MACE as reported by one study (n=305) was 0.54[0.49-0.60]. For SS, the summary AUC for all cause mortality (n=2936) was 0.77[0.69-0.85] while for cardiac death (n=305) it was 0.52[0.46-0.57]. The pooled AUC of SS for occurrence of MACE(n=2666) was 0.56[0.45-0.66]. Conclusion: None of the two scores have a a good discrimination ability for risk stratification in SCAD patients. The predictive accuracy of SS is comparatively better than ES for all cause mortality. However, ES performs better for predicting cardiac death. Better risk prediction models with large scale external validations are needed.

Abstract 4137175: Functional Mitral Regurgitation as a Predictor of Atrial Fibrillation Recurrence Following Catheter Ablation: A Systematic Review and Meta-Analysis

Background: Recent studies showed that functional mitral valve regurgitation (FMR) was associated with higher long-term mortality in chronic heart failure patients and poorer outcomes in those with atrial fibrillation (AF), including a higher risk of atrial cardiomyopathy. However, the effect of baseline FMR on outcomes post-AF catheter ablation remains unclear due to inconsistent evidence. Methods: We systematically reviewed studies from Medline and EMBASE databases from inception to April 2024. Eligible studies must report the association between baseline FMR and risk of AF recurrence post-AF catheter ablation compared to individuals without FMR. Relative Risk (RR) or hazard ratio (HR) and 95% CIs were retrieved from each study and combined using the generic inverse variance method. Results: Our meta-analysis included 7 cohort studies and found that baseline FMR was associated with a higher risk of AF recurrence compared to those without FMR. The pooled risk ratios (RR) were 1.40 (95% CI 1.11-1.78, I2 = 31%, p = 0.005). No publication bias was identified on the funnel plot. Conclusions: Our pooled analysis found that patients with FMR who underwent AF catheter ablation had a higher risk of AF recurrence compared to those without FMR. Further research is needed to explore the underlying mechanisms and their clinical implications. Keyword: Functional mitral regurgitation, Atrial fibrillation, Catheter ablation, Atrial fibrillation recurrence, Systematic review, Meta-analysis

A generic novel HPLC method for the determination of nitrite ion by direct derivatization

BackgroundThis research introduces a novel, simplified method to quantify carcinogenicity generating nitrite in Key Starting Materials (KSMs) and specific drugs. Since no straightforward approach exists in the literature, this method aimed to fill the lacunae and fulfill safety assessments in pharmaceutical applications. MethodThe developed method employs a direct and simple derivatization procedure using High-Performance Liquid Chromatography (HPLC). The conditions include Zorbax SB C8 column (stationary phase), trifluoroacetic acid (TFA): water: acetonitrile at 0.05:55:45 % v/v as mobile phase A, and TFA: acetonitrile at 0.05:100 % v/v as mobile phase B in a gradient elution at 0.8 mL/minute flow rate. The gradient program is time/%A, 0/100, 10/100, 15/0, 19/0, 20/100, 25/100. Significant findingsA simple method was established to regulate the nitrite ion levels in KSMs and certain medications. By making a fine-tuning to chromatographic conditions, this method can quantify nitrite content in any pharmaceutical materials, thus, demonstrating its generic applicability. The developed method was validated according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. It is linear and accurate from the limit of quantitation (LOQ) to 150 % (i.e., 0.5 to 1.5 ppm) of the specified limit (1.0 ppm). The LOQ and limit of detection (LOD) for this method are 0.5 and 0.1 ppm, respectively.

An autoencoder-based confederated clustering leveraging a robust model fusion strategy for federated unsupervised learning

Concerns related to data privacy, security, and ethical considerations become more prominent as data volumes continue to grow. In contrast to centralized setups, where all data is accessible at a single location, model-based clustering approaches can be successfully employed in federated settings. However, this approach to clustering in federated settings is still relatively unexplored and requires further attention. As federated clustering deals with remote data and requires privacy and security to be maintained, it poses particular challenges as well as possibilities. While model-based clustering offers promise in federated environments, a robust model aggregation method is essential for clustering rather than the generic model aggregation method like Federated Averaging (FedAvg). In this research, we proposed an autoencoder-based clustering method by introducing a novel model aggregation method FednadamN, which is a fusion of Adam and Nadam optimization approaches in a federated learning setting. Therefore, the proposed FednadamN adopted the adaptive learning rates based on the first and second moments of gradients from Adam which offered fast convergence and robustness to noisy data. Furthermore, FednadamN also incorporated the Nesterov-accelerated gradients from Nadam to further enhance the convergence speed and stability. We have studied the performance of the proposed Autoencoder-based clustering methods on benchmark datasets and using the novel FednadamN model aggregation strategy. It shows remarkable performance gain in federated clustering in comparison to the state-of-the-art.

Prevalence and Risk Factors of Heart Failure in Patients Diagnosed with Hyperthyroidism: A Systematic Review and Meta-analysis.

Objectives: Hyperthyroidism has a significant impact on the cardiovascular system, causing thyrotoxic cardiomyopathy, which is characterized by atrial fibrillation, left ventricular hypertrophy and diastolic dysfunction, and may lead to heart failure. This study aimed to investigate the prevalence and associated risk factors for heart failure in patients with hyperthyroidism. Methods: A systematic literature search was conducted on PubMed, SCOPUS and Ovid SP up until April 2023. Pooled prevalence and pooled odds ratio for risk factors were calculated using the generic inverse variance method. Results: Studies involving 30,889 patients were included in this meta-analysis. The overall prevalence of heart failure in patients with hyperthyroidism was 8% (95% confidence interval [CI]: 6-11%). Further analyses revealed that the prevalence of heart failure in patients who underwent treatment with radioactive iodine ablation, antithyroid medication and thyroidectomy was 8% (95% CI: -1 to 16%), 6% (95% CI: 2 to 11%) and 4% (95% CI: -2 to 10%), respectively. The risk factors of heart failure in hyperthyroidism include atrial fibrillation, chronic kidney disease, anaemia, hypertension, history of stroke or transient ischaemic attack, history of coronary artery disease and diabetes mellitus. Conclusion: Heart failure occurs in 8% of patients with hyperthyroidism, with the most common risk factor being atrial fibrillation.

Prognostic Value of Neutrophil-to-Eosinophil Ratio (NER) in Cancer: A Systematic Review and Meta-Analysis.

The identification of reliable prognostic biomarkers is crucial for optimizing cancer treatment strategies, especially in the era of personalized medicine. This systematic review and meta-analysis evaluate the prognostic significance of the neutrophil-to-eosinophil ratio (NER) in various cancer types, with a focus on its association with overall survival (OS) and progression-free survival (PFS). We conducted a systematic literature search across PubMed, Scopus, and Web of Science databases for studies published up to 28 July 2024. We performed the meta-analyses with the generic inverse variance method with a random effects model and reported hazard ratios (HR) with 95% confidence intervals (CI). The comprehensive literature search identified 10 studies comprising 2351 patients. Pooled analyses demonstrated that elevated pretreatment NER levels were significantly correlated with poorer OS (HR: 1.74, 95% CI: 1.28-2.36, p < 0.001) and PFS (HR: 1.53, 95% CI: 1.21-1.95, p < 0.001). Subgroup analyses confirmed a consistent adverse association between high NER and OS across various tumor types and geographic locations, although results from studies conducted in the Far East did not reach statistical significance. This meta-analysis demonstrates that elevated NER is associated with poorer OS and PFS in cancer patients, suggesting its potential utility as a non-invasive prognostic marker. Further validation in large, prospective studies is warranted to establish NER's role in guiding personalized treatment strategies across diverse oncologic contexts.

Triple-oxygen isotopes of stony micrometeorites by secondary ion mass spectrometry (SIMS): Olivine, basaltic glass and iron oxide matrix effects for sensitive high-mass resolution ion microprobe-stable isotope (SHRIMP-SI).

Micrometeorites are extraterrestrial particles smaller than ~2mm in diameter, most of which melted during atmospheric entry and crystallised or quenched to form 'cosmic spherules'. Their parentage among meteorite groups can be inferred from triple-oxygen isotope compositions, for example, by secondary ion mass spectrometry (SIMS). This method uses sample efficiently, preserving spherules for other investigations. While SIMS precisions are improving steadily, application requires assumptions about instrumental mass fractionation, which is controlled by sample chemistry and mineralogy (matrix effects). We have developed a generic SIMS method using sensitive high-mass resolution ion micro probe-stable isotope (SHRIMP-SI) that can be applied to finely crystalline igneous textures as in cosmic spherules. We correct for oxygen isotope matrix effects using the bulk chemistry of samples obtained by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and model bulk chemical compositions as three-component mixtures of olivine, basaltic glass and Fe-oxide (magnetite), finding a unique matrix correction for each target. Our first results for cosmic spherules from East Antarctica compare favourably with established micrometeorite groups defined by precise and accurate but consumptive bulk oxygen isotope methods. The Fe-oxide content of each spherule is the main control on magnitude of oxygen isotope ratio bias, with effects on δ18O up to ~6‰. Our main peak in compositions closely coincides with so-called 'Group 1' objects identified by consumptive methods. The magnitude of SIMS matrix effects we find is similar to the previous intraspherule variations, which are now the limiting factor in understanding their compositions. The matrix effect for each spherule should be assessed quantitatively and individually, especially addressing Fe-oxide content. We expect micrometeorite triple-oxygen isotope compositions obtained by SIMS to converge on the main clusters (Groups 1 to 4) after correction firstly for magnetite content and secondarily for other phases (e.g., basaltic glass) in each target.

Red blood cell distribution width to albumin ratio as novel prognostic biomarker in cardiovascular disease

Abstract Background The red blood cell distribution width-to-albumin ratio (RAR) is a novel, cost-effective, and accessible biomarker for inflammation. Although numerous studies have investigated the relationship between RAR values and mortality in cardiovascular diseases (CVD), the generalizability and robustness of these individual studies' results remain uncertain, underscoring the necessity for a meta-analysis. Purpose To explore the pooled association between RAR and all-cause mortality in several CVDs. Methods A systematic search for eligible studies was conducted across scientific databases, including Scopus, Web of Science, PubMed, and ProQuest, up to February 1, 2024. Mortality hazard ratios (HRs) for the highest versus lowest RAR categories were pooled using the Generic Inverse Variance method. A dose-response meta-analysis was performed using generalized least-squares regression to estimate trends of HRs across dose categories. Publication bias was assessed by inspecting funnel plots and performing Egger's test. Subgroup analyses were based on the underlying CVDs. Statistical analyses were executed in RStudio software, with the significance threshold set at p &amp;lt; 0.05. Results This systematic review and meta-analysis reviewed 16 high-quality studies published between 2021 and 2024 with 30,933 participants. The underlying diseases in the included studies were Acute Myocardial Infarction (AMI), Heart Failure (HF), Atrial Fibrillation (AF), aortic valvular disease, stroke and pulmonary embolism. The lowest quartile range for RAR was 0.80–1.20 ml/g, while the highest quartile ranged from 6.09 to 15.45 ml/g. Pooled results with a random-effect model showed that patients with higher RAR had significantly increased risk of all-cause mortality (HR 1.88, 95%CI 1.59–2.23, p&amp;lt;0.0001, I² = 91%). Non-linearity was observed in the dose-response relationship; thus, it was primarily illustrated using the restricted cubic spline model, with the linear model provided for comparison. A 1 ml/g increase in RAR corresponded to a 27% rise in the predicted HR for all-cause mortality (HR 1.27, 95%CI 1.16–1.39; p &amp;lt; 0.0001). Subgroup analyses based on the primary CVD diagnoses in the included studies confirmed a significant association between RAR values and all-cause mortality across all subgroups (AMI: HR 2.43, 95%CI 1.52–3.87, I² = 45%; HF: HR 1.78, 95%CI 1.13–2.81, I² = 94%; Stroke: HR 1.58, 95%CI 0.94–2.67, I² = 90%; Other CVD: HR 1.97, 95%CI 1.34–2.89, I² = 57%; p for interaction 0.24). Conclusion This is the first meta-analysis demonstrating the positive dose-response association between RAR values and all-cause mortality in CVD. Thus, RAR may be considered as a simple and practical prognostic biomarker in CVD.Forest plot based on CVD diagnosisDose-response RAR value to HR

CTARR: A fast and robust method for identifying anatomical regions on CT images via atlas registration

Medical image analysis tasks often focus on regions or structures located in a particular location within the patient’s body. Often large parts of the image may not be of interest for the image analysis task. When using deep-learning based approaches, this causes an unnecessary increases the computational burden during inference and raises the chance of errors. In this paper, we introduce CTARR, a novel generic method for CT Anatomical Re- gion Recognition. The method serves as a pre-processing step for any deep learning-based CT image analysis pipeline by automatically identifying the pre-defined anatomical region that is relevant for the follow-up task and removing the rest. It can be used in (i) image segmentation to prevent false positives in anatomically implausible regions and speeding up the inference, (ii) image classification to produce image crops that are consistent in their anatomical context, and (iii) image registration by serving as a fast pre-registration step. Our proposed method is based on atlas registration and provides a fast and robust way to crop any anatomical region encoded as one or multiple bounding box(es) from any unlabeled CT scan of the brain, chest, abdomen and/or pelvis. We demonstrate the utility and robustness of the proposed method in the context of medical image segmentation by evaluating it on six datasets of public segmentation challenges. The foreground voxels in the regions of interest are preserved in the vast majority of cases and tasks (97.45-100%) while taking only fractions of a seconds to compute (0.1-0.21s) on a deep learning worksta- tion and greatly reducing the segmentation runtime (2.0-12.7x). Our code is available at &lt;a href='https://github.com/ThomasBudd/ctarr'&gt;https://github.com/ThomasBudd/ctarr&lt;/a&gt;

Suppression of quantum dissipation: a cooperative effect of quantum squeezing and quantum measurement.

The ability to isolate a quantum system from its environment is of fundamental interest and importance in optical quantum science and technology. Here we propose an experimentally feasible scheme for beating environment-induced dissipation in an open two-level system coupled to a parametrically driven cavity. The mechanism relies on a novel, to the best of our knowledge, cooperation between light-matter coupling enhancement and frequent measurements. We demonstrate that, in the presence of the cooperation, the system dynamics can be completely dominated by the effective system-cavity interaction, and the dissipative effects from the system-environment coupling can be surprisingly ignored. This work provides a generic method of dissipation suppression in a variety of quantum mechanical platforms, including natural atoms and superconducting circuits.

Comparison of central precocious puberty frequency before and during COVID-19: a systematic review and meta-analysis

ObjectiveThe current systematic review and meta-analysis assessed the prevalence of central precocious puberty (CPP) throughout the novel coronavirus disease 2019 (COVID-19) pandemic.DesignA systematic review and meta-analysis were carried out following the principles outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA, 2020).Data sourcesPubMed, Embase, Web of Science, and WANFANG databases were searched from January 1, 2019, to March 30, 2023.Eligibility criteria for selecting studies(1) children and adolescents ≤ 15 years; (2) studies with the outcome of frequency of central precocious puberty, measured prior to and throughout the COVID-19 pandemic; (3) a novel CPP diagnosis was created depending on all of the following criteria: girls with a chronological age < 8 years and boys with a chronological age < 9 years at the onset of symptoms, basal luteinizing hormone (LH) levels > 0.3 UI/L, and/or GnRH-stimulated peak LH levels > 5 IU/L.Data extraction and synthesisThe process of extracting data and evaluating the likelihood of bias was carried out by two independent reviewers. The data were pooled employing the generic inverse-variance method and presented as mean differences (MDs) with 95% CIs. The evaluation of heterogeneity was conducted employing the Cochran Q statistic, and the degree of heterogeneity was measured employing the I2 statistic.ResultsThis meta-analysis included 17 studies. In contrast to the same period prior to the COVID-19 pandemic, the occurrence of CPP elevated (OR = 2.57; 95% CI, 1.85–3.56). Moreover, body mass index standard deviation score (BMI SDS) differences between CPP patients prior to COVID-19 and throughout the pandemic follow-up was 0.12 (95% CI − 0.01 to 0.25 P = 0.06).ConclusionOverall, CPP frequency significantly elevated throughout the COVID-19 pandemic. Given the restricted number of cohort investigations in this meta-analysis, additional research may be conducted on larger groups of children in order to establish a correlation between the observed rise in precocious puberty and specific pathogenic factors.

Development, validation, and application of a generic image-based noise addition method for simulating reduced dose computed tomography images.

Major efforts in computed tomography (CT) have been focused on reducing radiation dose to patients while maintaining adequate diagnostic quality. To that end, research tools have been developed to simulate reduced-dose images via either image-based or projection-based methods. The former is limited to fully capturing realistic texture, streak, and non-stationary characteristics of reduced dose, while the latter is impractical clinically. To develop and validate an image-based noise addition method that accounts for such attributes while being practical in clinical settings. A noise addition method was developed to add realistic noise in the image domain. The method first estimates the noise power spectrum (NPS) of CT images, which are also forward-projected to form synthetic projections. The projection data are supplemented with random white noise proportional to their attenuation values. The noise sinogram is then back-projected onto the image, filtered by the NPS, and scaled according to the desired dose reduction level. The tool was evaluated using both phantom images and patient data. The phantom images were acquired using a multi-sized image quality phantom (Mercury Phantom 3.0, Duke University), and a thorax anthropomorphic phantom (Lungman Phantom, Kyoto Kagaku) at different dose levels and reconstruction settings. The patient images consisted of two dose levels of various CT examinations and reconstruction settings. The simulated and real reduced-dose images were compared in terms of the noise magnitude and texture (i.e., NPS average frequency, NPS-fav). The utility of this methodology was also assessed for routine clinical use for CT protocol review. For the phantom images, the percent errors in the noise magnitude between the simulated images and the actual images of the Mercury Phantom and anthropomorphic phantom images were 3.34% and 3.50%, respectively. The difference in fav was 0.07mm-1 for the Mercury Phantom and 0.06mm-1 for the anthropomorphic phantom between the simulated and actual images. The average noise magnitude percent error between the simulated and actual patient images was 4.61% with noise texture judged to be visually comparable with some kernel dependencies. When implemented clinically, the tool proved practical to simplify the process of estimating radiation dose reduction for CT protocols, resulting in a 50% dose reduction of our multiple myeloma protocol. The method generated simulated CT images with realistic noise properties similar to images acquired at the same radiation exposure without needing access to raw projection data.

Association Between P-Wave Duration, Dispersion, and Interatrial Block and Atrial High-Rate Episodes in CIED Patients.

Atrial high-rate episodes (AHRE) have been linked to increased thromboembolic risk and all-cause mortality in patients with cardiac implantable electronic devices (CIEDs). Various predictors of AHRE development have been identified, emphasizing the need for close monitoring and the potential transition to clinical atrial fibrillation (AF). However, the predictive value of P wave characteristics on AHRE development remains conflicting. This meta-analysis aims to summarize existing data to investigate this association. We examined studies from MEDLINE and EMBASE databases up to May 2024 to investigate the association of baseline P-wave duration (PWD), P-wave dispersion (PWDIS), and interatrial block (IAB) with the risk of developing AHRE. We extracted the mean and standard deviations of PWD and PWDIS to calculate the pooled mean difference (MD). Risk ratios (RR) and 95% confidence intervals (CIs) were used to assess the association between IAB and AHRE risk, using the generic inverse variance method for combination. The meta-analysis included nine studies. Patients with AHRE had longer PWD and PWDIS compared to those without AHRE, with a pooled MD for PWD of 9.17ms (95% CI: 4.74-13.60; I2 = 47%, p < 0.001) and a pooled MD for PWDIS of 20.56ms (95% CI: 11.57-29.56; I2 = 57%, p < 0.001). Additionally, patients with IAB had a higher risk of developing AHRE, with a pooled RR of 3.33 (95% CI: 2.53-4.38; I2 = 0%, p < 0.001), compared to those without IAB. Our meta-analysis found that patients with AHRE had higher PWD and PWDIS than those without AHRE. Additionally, IAB was associated with a higher risk of developing AHRE. These findings emphasize the importance of close monitoring and risk stratification, particularly for patients with P wave abnormalities.

12455 Bone Mineral Density Improvement After Resolution Of Endogenous Cushing Syndrome

Abstract Disclosure: C. Plessias: None. N. Charoenngam: None. T. Rittiphairoj: None. T. Suenghataiphorn: None. T. Srikulmontri: None. P. Wattanachayakul: None. M. Kurt: None. Bone Mineral Density Improvement After Resolution of Endogenous Cushing Syndrome: a Meta-analysis and meta-regression Patients with endogenous Cushing syndrome (eCS) are known to have decreased bone mineral density (BMD) and are prone to fragility fractures. Treatment of eCS have been shown in multiple studies to result in improvement in BMD. However, the degree of BMD improvement after resolution of eCS remains inadequately explored due to limited sample sizes in existing studies. Through systematic review, meta-analysis, and meta-regression techniques, we aimed to identify all available evidence to evaluate BMD improvement after resolution of eCS. Potentially eligible studies were identified from the PubMed and EMBASE databases from inception to February 2024, utilizing a search strategy incorporating terms related to "Bone mineral density" and "Cushing syndrome". Eligible studies must include adult or pediatric patients diagnosed with any form of eCS, encompassing Cushing disease (CD), adrenal adenoma, mild autonomous cortisol secretion or ectopic ACTH-secreting tumors, who received treatment resulting in CS resolution. These studies must either present lumbar spine (LS) or femoral neck (FN) BMD measurements in the form of T-score, Z-score or actual BMD values before and after CS resolution, or report mean differences (MD) of BMD, or provide individual BMD data. Point estimates with corresponding standard errors were extracted from each study and combined using the generic inverse variance method. Meta-regression analysis was utilized to explore the impact of time after resolution of eCS on BMD improvement.A total of 5,085 records were identified from the databases. After systematic review, 14 studies, including a total of 386 patients, were deemed eligible for analysis. The meta-analysis demonstrated that resolution of eCS resulted in statistically significantly improvement of LS BMD (pooled MD: Z-score: +0.76, 95%CI 0.50 – 1.02, I2 76%; T-score: +0.87, 95%CI 0.55 – 1.19, I2 78%; actual BMD: +0.092 g/cm2, 95%CI 0.060 – 0.124, I2 74%) and FN BMD (pooled MD: Z-score: +0.54, 95%CI 0.32 – 0.76, I2 75%; T-score: +0.38, 95%CI 0.25 – 0.51, I2 0%; actual BMD: +0.041 g/cm2, 95%CI 0.021 – 0.062, I2 0%). The meta-regression analysis revealed a statistically significant association between follow-up time and improvements in LS T-score BMD (predicted LS T-score improvement = 0.42 + 0.062 × year, p = 0.027) and FN Z-score BMD (predicted FN Z-score improvement = 0.35 + 0.037 × year, p = 0.003), but not with LS Z-score and FN T-score.In summary, our study presents the extent of improvement in LS and FN BMD following the resolution of eCS based on all available data in the literature. These findings have clinical significance as they offer guidance for management of osteoporosis following the resolution of eCS. Presentation: 6/3/2024

Twin pregnancy and postpartum haemorrhage: a systematic review and meta-analysis

BackgroundPostpartum haemorrhage (PPH) continues to stand as the primary cause of maternal morbidity and mortality post-delivery, with twin pregnancies carrying a heightened risk of PPH compared to singleton deliveries.ObjectivesTo investigate the incidence of primary PPH among twin pregnancies and report on maternal and peripartum characteristics within this population.MethodsA literature search was conducted using data from PubMed, EMBASE, Cochrane, Scopus, and Web of Science. The search aimed to identify studies concerning mothers with twin pregnancies and postpartum haemorrhage (PPH) from the inception of each respective database to June 8th, 2023. Pooled means and proportions were analyzed using the generic inverse variance method. This review was registered prospectively with PROSPERO (CRD42023427192).ResultsA total of 21 studies involving 23,330 twin pregnant patients were included. Incidence of PPH for vaginal delivery and Caesarean delivery (CS) was found to be 10.9% (95% CI: -0.017, 0.235, I2 = 96%) and 27.0% (95% CI: 0.180, 0.359, I2 = 99%) respectively. In vitro fertilization (IVF) was the most common conception method at 62.0% (95% CI: 0.448, 0.792, I2 = 100%) with 81.1% (95% CI: 0.708, 0.915, I2 = 100%) of twins being dichorionic diamniotic.ConclusionThis meta-analysis demonstrated more than one in ten vaginal deliveries and over one in four cesarean sections result in PPH for twin pregnancies. IVF is the predominant method of conception in this patient group and seems to contribute to subsequent PPH risk in specific mothers. While preliminary, these findings underscore the necessity for further well-designed and high-quality studies to validate these results.

Development of an accelerometer age- and sex-specific approach based on population-standardized values for physical activity surveillance: A proof of concept

BackgroundA shift from self-reports to wearable sensors for global physical activity (PA) surveillance has been recommended. The conventional use of a generic cut-point to assess moderate-to-vigorous PA (MVPA) is problematic as these cut-points are often derived from non-representative samples under non-ecological laboratory conditions. This study aimed to develop age- and sex-specific (age-sex) cut-points for MVPA based on population-standardized values as a feasible approach to assess the adherence to PA guidelines and to investigate its associations with all-cause mortality. MethodsA total of 7601 participants (20–85+ years) were drawn from the 2003–2004 and 2005–2006 National Health and Nutrition Examination Surveys (NHANES). Minutes per week of MVPA were assessed with a hip-worn accelerometer. Counts per minute (CPM) were used to define an age- and sex-specific target intensity, representing the intensity each person should be able to reach based on their age and sex. Age- and sex-specific MVPA cut-points were defined as any activity above 40% of the target intensity. These population- and free-living-based age-sex specific cut-points overcome many of the limitations of the standard generic cut-point approach. For comparison, we also calculated MVPA with a generic cut-point of 1952 CPM. Both approaches were compared for assessing adherence to PA guidelines and association of MVPA with all-cause mortality (ascertained through December 2015). ResultsBoth approaches indicated that 37% of the sample met the 150+ min/week guideline. The generic cut-point approach showed a trend to inactivity with age, which was less pronounced using the age-sex cut-points. Overall mortality rates were comparable using generic cut-point (hazard ratio (HR) = 0.61, 95% confidence interval (95%CI): 0.50‒0.73) or age-sex cut-points (HR = 0.57, 95%CI: 0.50‒0.66) for the entire sample. The generic cut-point method revealed an age- and sex-related gap in the benefits of achieving 150+ min/week of MVPA, with older adults showing an 18% greater reduction in mortality rates than younger adults, and a larger difference in women than in men. This disparity disappeared when using age-sex-specific cut-points. ConclusionOur findings underscore the value of age-sex cut-points for global PA surveillance. MVPA defined with age-sex thresholds was associated with all-cause mortality and the dose‒response was similar for all ages and sexes. This aligns with the single recommendation of accumulating 150+ min/week MVPA for all adults, irrespective of age and sex. This study serves as a proof of concept to develop this methodology for PA surveillance over more advanced open-source acceleration metrics and other national and international cohorts.

Risk of renal impairment in atypical antipsychotics: a systematic review and meta-analysis.

Atypical antipsychotics are associated with several adverse effects including metabolic syndrome, weight gain, QTc interval prolongation, and extrapyramidal effects. This study aims to investigate the risk of renal impairment in patients receiving atypical antipsychotics. A systematic literature search was conducted via PubMed and Ovid SP and Web of Science to retrieve studies reporting the risk of renal impairment in patients receiving atypical antipsychotic treatment. The pooled risk ratio (RR) of renal impairment and the subgroup analysis was calculated using the random-effects generic inverse variance method in Cochrane Review Manager. A total of 4 studies involving 514,710 patients (221, 873 patients on atypical antipsychotics/CKD and 292, 837 controls) were included in this meta-analysis. Patients on atypical antipsychotics exhibited an increased risk of renal impairment, with a pooled risk ratio of 1.34 (95%CI 1.23-1.47). Subgroup analysis demonstrated that atypical antipsychotic use was associated with an increased risk of both acute kidney injury (AKI) (RR 1.51, 95%CI 1.34-1.71) and chronic kidney disease (CKD) (RR: 1.23, 95%CI 1.12-1.35). Patients receiving atypical antipsychotics have an increased risk of renal impairment. Quetiapine carries the highest risk of renal impairment encompassing both AKI and CKD.

Functional and radiological sinonasal outcomes of CFTR modulators for sinus disease in cystic fibrosis: A meta-analysis.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in cystic fibrosis (CF) by stabilizing the CFTR protein on respiratory epithelial surfaces. To determine the efficacy of CFTR modulators on sinonasal outcomes in patients with CF, we performed a meta-analysis of clinical trials to date that include functional and radiographic evidence of sinus disease. English full-text articles were searched in PubMed, Embase, and Scopus databases. Two reviewers screened articles and a third reviewer resolved disagreements. Articles were included if they reported functional or radiological sinonasal outcomes in patients with CF before and after CFTR modulator therapies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the risk of bias in non-randomized studies of interventions tool was used for quality assessment. The generic inverse variance method with random effects model was used for meta-analysis. Standardized mean difference (SMD) and mean difference (MD) were used as effect measurements. Seven prospective and two retrospective studies representing 248 patients were included in this analysis. There was a significant improvement in sinonasal outcome test-22 scores on elexacaftor‒tezacaftor‒ivacaftor (MD=12.80, [95% confidence interval, CI: 10.46‒15.13], p<0.001, n=222), with no heterogeneity detected (I2=0%, p=0.820). There was also a significant improvement in Lund‒Mackay scores (SMD=1.25, [95% CI: 0.58‒1.91], p<0.001, n=88), with heterogeneity detected (I2=67%, p=0.030). CFTR modulators improve functional and radiologic sinonasal outcomes. Given the utility of CFTR modulators, the treatment paradigm for CF-related chronic rhinosinusitis promises to evolve.