Sugar-Sweetened Beverages and Adverse Human Health Outcomes: An Umbrella Review of Meta-Analyses of Observational Studies.

Our aim was to conduct an umbrella review of evidence from meta-analyses of observational studies investigating the link between sugar-sweetened beverage consumption and human health outcomes. Using predefined evidence classification criteria, we evaluated evidence from 47 meta-analyses encompassing 22,055,269 individuals. Overall, 79% of these analyses indicated direct associations between greater sugar-sweetened beverage consumption and higher risks of adverse health outcomes. Convincing evidence (class I) supported direct associations between sugar-sweetened beverage consumption and risks of depression, cardiovascular disease, nephrolithiasis, type 2 diabetes mellitus, and higher uric acid concentrations. Highly suggestive evidence (class II) supported associations with risks of nonalcoholic fatty liver disease and dental caries. Out of the remaining 40 meta-analyses, 29 were graded as suggestive or weak in the strength of evidence (classes III and IV), and 11 showed no evidence (class V). These findings inform and provide support for population-based and public health strategies aimed at reducing sugary drink consumption for improved health.

Tracking neuroinflammatory biomarkers in Alzheimer's disease: a strategy for individualized therapeutic approaches?

BACKGROUND: Recent trials of anti-amyloid-ß (Aß) monoclonal antibodies, including lecanemab and donanemab, in early Alzheimer disease (AD) showed that these drugs have limited clinical benefits and their use comes with a significant risk of serious adverse events. Thus, it seems crucial to explore complementary therapeutic approaches. Genome-wide association studies identified robust associations between AD and several AD risk genes related to immune response, including but not restricted to CD33 and TREM2. Here, we critically reviewed the current knowledge on candidate neuroinflammatory biomarkers and their role in characterizing the pathophysiology of AD. MAIN BODY: Neuroinflammation is recognized to be a crucial and contributing component of AD pathogenesis. The fact that neuroinflammation is most likely present from earliest pre-stages of AD and co-occurs with the deposition of Aß reinforces the need to precisely define the sequence and nature of neuroinflammatory events. Numerous clinical trials involving anti-inflammatory drugs previously yielded unfavorable outcomes in early and mild-to-moderate AD. Although the reasons behind these failures remain unclear, these may include the time and the target selected for intervention. Indeed, in our review, we observed a stage-dependent neuroinflammatory process in the AD brain. While the initial activation of glial cells counteracts early brain Aß deposition, the downregulation in the functional state of microglia occurs at more advanced disease stages. To address this issue, personalized neuroinflammatory modulation therapy is required. The emergence of reliable blood-based neuroinflammatory biomarkers, particularly glial fibrillary acidic protein, a marker of reactive astrocytes, may facilitate the classification of AD patients based on the ATI(N) biomarker framework. This expands upon the traditional classification of Aß ("A"), tau ("T"), and neurodegeneration ("N"), by incorporating a novel inflammatory component ("I"). CONCLUSIONS: The present review outlines the current knowledge on potential neuroinflammatory biomarkers and, importantly, emphasizes the role of longitudinal analyses, which are needed to accurately monitor the dynamics of cerebral inflammation. Such a precise information on time and place will be required before anti-inflammatory therapeutic interventions can be considered for clinical evaluation. We propose that an effective anti-neuroinflammatory therapy should specifically target microglia and astrocytes, while considering the individual ATI(N) status of patients.

Novel Artificial Intelligence Combining Convolutional Neural Network and Support Vector Machine to Predict Colorectal Cancer Prognosis and Mutational Signatures From Hematoxylin and Eosin Images.

Reducing recurrence following radical resection of colon cancer without overtreatment or undertreatment remains a challenge. Postoperative adjuvant chemotherapy (Adj) is currently administered based solely on pathologic TNM stage. However, prognosis can vary significantly among patients with the same disease stage. Therefore, novel classification systems in addition to the TNM are necessary to inform decision-making regarding postoperative treatment strategies, especially stage II and III disease, and minimize overtreatment and undertreatment with Adj. We developed a prognostic prediction system for colorectal cancer using a combined convolutional neural network and support vector machine approach to extract features from hematoxylin and eosin staining images. We combined the TNM and our artificial intelligence (AI)-based classification system into a modified TNM-AI classification system with high discriminative power for recurrence-free survival. Furthermore, the cancer cell population recognized by this system as low risk of recurrence exhibited the mutational signature SBS87 as a genetic phenotype. The novel AI-based classification system developed here is expected to play an important role in prognostic prediction and personalized treatment selection in oncology.

Evaluation of Bayesian Point-Based System on the Variant Classification of Hereditary Cancer Predisposition Genes.

PURPOSE: To assess the differences in variant classifications using the ACMG/AMP 2015 guidelines and the Bayesian point-based classification system (here referred to as the point system) in 115 hereditary cancer predisposition genes and explore variant sub-tiering by the point system. METHODS: Germline variant classifications for 721 pediatric patients from an in-house panel were retrospectively evaluated using the two scoring systems. RESULTS: 2376 unique variants were identified, with ∼23.5% exhibiting discordant classifications. Unique variants classified by the point system demonstrated a lower rate of variants of uncertain significance (VUS; ∼15%) compared to ACMG/AMP 2015 (∼36%). This change is attributed to unique variants with one benign supporting evidence (∼12%) or one benign strong evidence (∼4%) being classified as likely benign by the point system. Additionally, variants with conflicting/modified evidence (∼5% of 2376) are also resolved by the point system. Sub-tiering unique variants classified by the point system as VUS (n=354) indicates ∼77.4% were VUS-Low (0-1 points), while the remaining ∼22.6% were VUS-Mid (2-3 points) and VUS-High (4-5 points). CONCLUSION: The point system reduces the VUS rate and facilitates their sub-tiering. Future large-scale studies are warranted to explore the impact of the point system on improving VUS reporting and/or VUS clinical management.

Cerebral Palsy and Motor Impairment After Extreme Prematurity: Prediction of Diagnoses at Ages 2 and 10 Years.

OBJECTIVE: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. STUDY DESIGN: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.

Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

iBCS: 3. A Biopharmaceutics Classification System for Orally Inhaled Drug Products.

In this article, we specify for the first time a quantitative biopharmaceutics classification system for orally inhaled drugs. To date, orally inhaled drug product developers have lacked a biopharmaceutics classification system like the one developed to navigate the development of immediate release of oral medicines. Guideposts for respiratory drug discovery chemists and inhalation product formulators have been elusive and difficult to identify due to the complexity of pulmonary physiology, the intricacies of drug deposition and disposition in the lungs, and the influence of the inhalation delivery device used to deliver the drug as a respirable aerosol. The development of an inhalation biopharmaceutics classification system (iBCS) was an initiative supported by the Product Quality Research Institute (PQRI). The goal of the PQRI iBCS working group was to generate a qualitative biopharmaceutics classification system that can be utilized by inhalation scientists as a "rule of thumb" to identify desirable molecular properties and recognize and manage CMC product development risks based on physicochemical properties of the drug and the deposited lung dose. Herein, we define the iBCS classes quantitatively according to the dose number and permeability. The proposed iBCS was evaluated for its ability to categorize marketed inhaled drugs using data from the literature. The appropriateness of the classification of each drug was assessed based on published development, clinical and nonclinical data, and mechanistic physiologically based biopharmaceutics modeling. The inhaled drug product development challenges for each iBCS classification are discussed and illustrated for different classes of marketed inhaled drugs. Finally, it is recognized that discriminatory laboratory methods to characterize regional lung deposition, dissolution, and permeability will be key to fully realizing the benefits of an iBCS to streamline and derisk inhaled drug development.

Transplant nephropathology: Wherefrom, wherein, and whereto.

Renal pathology is a relatively recent entry in nephrology. While diseases of the kidney are old, their study began in the 19th century with the report of Richard Bright of the lesions of end-stage kidney disease. Its easy diagnosis from albuminuria soon elevated Bright's nephritis into a leading cause of death. The transformative events in the care of these cases were renal replacement therapy that converted a fatal into a chronic disease, and kidney biopsy that allowed study of the course and pathogenesis of kidney disease. Apart from its fundamental contributions to clinical nephrology, biopsy of renal allografts became an integral component of the evaluation and care of kidney transplant recipients. The Banff transplant pathology conferences launched in 1991 led to developing the classification of allograft pathology into an essential element in the evaluation, treatment, and care of allograft recipients with spirit of discovery. That success came at the cost of increasing complexity leading to the recent realization that it may need the refinement of its consensus-based system into a more evidence-based system with graded statements that are easily accessible to the other disciplines involved in the care of transplanted patients. Collaboration with other medical disciplines, allowing public comment on meeting reports, and incorporation of generative artificial intelligence (AI) are important elements of a successful future. The increased pace of innovation brought about by AI will likely allow us to solve the organ shortage soon and require new classifications for xenotransplantation pathology, tissue engineering pathology, and bioartificial organ pathology.

Development of a health state classification system for the PedsQL™ 4.0 Generic Core Scales for preference-based valuation in Australia.

OBJECTIVES: Pediatric Quality of Life InventoryTM Version 4.0 Generic Core Scales (PedsQL GCS), comprising 23 items covering four sub-scales (physical, emotional, social, and school functioning), is a widely applied generic measure of childhood health-related quality of life, but does not provide health utilities for cost-effectiveness-based decision-making. This study aimed to develop a reduced item version of PedsQL GCS amenable to health utility derivation in Australia. METHODS: Data sources were two cohorts of the Longitudinal Study of Australian Children, including proxy responses for all PedsQL GCS versions (Toddlers, Young Children, Children, Teens), and the CheckPoint sample containing child self-report to the Children version. Three analytic samples were: CheckPoint sample (n=1,874); Mallinson sample containing one measurement per child from one of the Young Children, Children or Teens versions (n=7,855); and Toddlers sample (n=7,401). Exploratory and confirmatory factor analyses assessed dimensionality. Psychometric analyses used Rasch and classical criteria on three randomly selected subsamples (n=500) per sample. Item selection prioritised psychometric performance in CheckPoint sample, also considering performance in other samples and conceptual content. RESULTS: Dimensionality assessments did not generate an alternative empirical structure for the measure, and psychometric analyses were conducted on the original four sub-scales. The selected items were: 'Get aches and pains' for physical functioning; 'Feel sad/blue' for emotional functioning; 'Other kids not friends' for social functioning; and 'Keeping up with school work' for school functioning. CONCLUSIONS: The final four-item set, pending further psychometric validation and valuation, can generate health utilities from the widely used PedsQL GCS to inform cost-effectiveness-based decision-making.

Trends in caesarean section rates in Europe from 2015 to 2019 using Robson's Ten Group Classification System: A Euro-Peristat study.

OBJECTIVE: To assess changes in caesarean section (CS) rates in Europe from 2015 to 2019 and utilise the Robson Ten Group Classification System (TGCS) to evaluate the contribution of different obstetric populations to overall CS rates and trends. DESIGN: Observational study utilising routine birth registry data. SETTING: A total of 28 European countries. POPULATION: Births at ≥22 weeks of gestation in 2015 and 2019. METHODS: Using a federated model, individual-level data from routine sources in each country were formatted to a common data model and transformed into anonymised, aggregated data. MAIN OUTCOME MEASURES: By country: overall CS rate. For TGCS groups (by country): CS rate, relative size, relative and absolute contribution to overall CS rate. RESULTS: Among the 28 European countries, both the CS rates (2015, 16.0%-55.9%; 2019, 16.0%-52.2%) and the trends varied (from -3.7% to +4.7%, with decreased rates in nine countries, maintained rates in seven countries (≤ ± 0.2) and with increasing rates in 12 countries). Using the TGCS (for 17 countries), in most countries labour induction increased (groups 2a and 4a), whereas multiple pregnancies (group 8) decreased. In countries with decreasing overall CS rates, CS tended to decrease across all TGCS groups, whereas in countries with increasing rates, CS tended to increase in most groups. In countries with the greatest increase in CS rates (>1%), the absolute contributions of groups 1 (nulliparous term cephalic singletons, spontaneous labour), 2a and 4a (induction of labour), 2b and 4b (prelabour CS) and 10 (preterm cephalic singletons) to the overall CS rate tended to increase. CONCLUSIONS: The TGCS shows varying CS trends and rates among countries of Europe. Comparisons between European countries, particularly those with differing trends, could provide insight into strategies to reduce CS without clinical indication.

Stillbirth mortality by Robson ten-group classification system: A cross-sectional registry of 80 663 births from 16 hospital in sub-Saharan Africa.

OBJECTIVE: To assess stillbirth mortality by Robson ten-group classification and the usefulness of this approach for understanding trends. DESIGN: Cross-sectional study. SETTING: Prospectively collected perinatal e-registry data from 16 hospitals in Benin, Malawi, Tanzania and Uganda. POPULATION: All women aged 13-49 years who gave birth to a live or stillborn baby weighting >1000 g between July 2021 and December 2022. METHODS: We compared stillbirth risk by Robson ten-group classification, and across countries, and calculated proportional contributions to mortality. MAIN OUTCOME MEASURES: Stillbirth mortality, defined as antepartum and intrapartum stillbirths. RESULTS: We included 80 663 babies born to 78 085 women; 3107 were stillborn. Stillbirth mortality by country were: 7.3% (Benin), 1.9% (Malawi), 1.6% (Tanzania) and 4.9% (Uganda). The largest contributor to stillbirths was Robson group 10 (preterm birth, 28.2%) followed by Robson group 3 (multipara with cephalic term singleton in spontaneous labour, 25.0%). The risk of dying was highest in births complicated by malpresentations, such as nullipara breech (11.0%), multipara breech (16.7%) and transverse/oblique lie (17.9%). CONCLUSIONS: Our findings indicate that group 10 (preterm birth) and group 3 (multipara with cephalic term singleton in spontaneous labour) each contribute to a quarter of stillbirth mortality. High mortality risk was observed in births complicated by malpresentation, such as transverse lie or breech. The high mortality share of group 3 is unexpected, demanding case-by-case investigation. The high mortality rate observed for Robson groups 6-10 hints for a need to intensify actions to improve labour management, and the categorisation may support the regular review of labour progress.

Association between the consumption of ultra-processed foods and the incidence of peptic ulcer disease in the SUN project: a Spanish prospective cohort study.

PURPOSE: Consumption of ultra-processed foods (UPF) has increased despite potential adverse health effects. Recent studies showed an association between UPF consumption and some gastrointestinal disorders. We evaluated the association between UPF consumption and peptic ulcer disease (PUD) in a large Spanish cohort. METHODS: We conducted a prospective analysis of 18,066 participants in the SUN cohort, followed every two years. UPF was assessed at baseline and 10 years after. Cases of PUD were identified among participants reporting a physician-made diagnosis of PUD during follow-ups. Cases were only partially validated against medical records. Cox regression was used to assess the association between baseline UPF consumption and PUD risk. Based on previous findings and biological plausibility, socio-demographic and lifestyle variables, BMI, energy intake, Helicobacter pylori infection, gastrointestinal disorders, aspirin and analgesic use, and alcohol and coffee consumption were included as confounders.We fitted GEE with repeated dietary measurements at baseline and after 10 years of follow-up. Vanderweele's proposed E value was calculated to assess the sensitivity of observed associations to uncontrolled confounding. RESULTS: During a median follow-up of 12.2 years, we recorded 322 new PUD cases (1.56 cases/1000 person-years). Participants in the highest baseline tertile of UPF consumption had an increased PUD risk compared to participants in the lowest tertile (HR = 1.52, 95% CI: 1.15, 2.00, Ptrend=0.002). The E-values for the point estimate supported the observed association. The OR using repeated measurements of UPF intake was 1.39 (95% CI: 1.03, 1.87) when comparing extreme tertiles. CONCLUSION: The consumption of UPF is associated with an increased PUD risk.

Qualification of In Vitro Dissolution Absorption System 2 (IDAS2) with Caco-2 and MDCK Cell Monolayers: Dose Sensitivity Study Using BCS Class I and III Drugs.

This study aimed to validate the In vitro Dissolution Absorption System 2 (IDAS2) containing a biological barrier of Caco-2 or Madin-Darby canine kidney (MDCK) cell monolayer through dose sensitivity studies. Metoprolol and propranolol were selected as Biopharmaceutics Classification System (BCS) Class I model drugs, and atenolol as a Class III model drug. The IDAS2 is comprised of a dissolution vessel (500 mL) and two permeation chambers (2 × 8.0 mL) mounted with Caco-2 or MDCK cell monolayer. One or two immediate-release tablet(s) of the model drug were added to the dissolution vessel, and the time profiles of dissolution and permeation were observed. Greater than 85% of metoprolol and propranolol (tested at two dosing concentrations) were dissolved by 15 min, and all drugs were fully dissolved by 30 min. All three drugs were more permeable across Caco-2 cells than MDCK cells with a linear increase in permeation across both cells at both dose concentrations. Thus, the dose sensitivity of the IDAS2 was demonstrated using both cell barriers. These results indicate a successful qualification of IDAS2 for the development/optimization of oral formulations and that MDCK cells can be utilized as a surrogate for Caco-2 cells.

Prediction model for spontaneous preterm birth less than 32 weeks of gestation in low-risk women with mid-trimester short cervical length: a retrospective cohort study.

BACKGROUND: A short cervix in mid-trimester pregnancy is a risk factor for spontaneous preterm birth. However, there is currently a lack of predictive models and classification systems for predicting spontaneous preterm birth in these patients, especially those without additional risk factors for spontaneous preterm birth. METHODS: A retrospective observational cohort study of low-risk singleton pregnant women with a short cervix (≤ 25 mm) measured by transvaginal ultrasonography between 22 and 24 weeks was conducted. A multivariate logistic regression model for spontaneous preterm birth < 32 weeks in low-risk pregnant women with a short cervix was constructed. Moreover, we developed a nomogram to visualize the prediction model and stratified patients into three risk groups (low-, intermediate-, and high-risk groups) based on the total score obtained from the nomogram model. RESULTS: Between 2020 and 2022, 213 low-risk women with a short cervix in mid-trimester pregnancy were enrolled in the study. Univariate logistic analysis revealed that a high body mass index, a history of three or more miscarriages, multiparity, a short cervical length, leukocytosis, and an elevated C-reactive protein level were associated with spontaneous preterm birth < 32 weeks, but multivariate analysis revealed that multiparity (OR, 3.31; 95% CI, 1.13-9.68), leukocytosis (OR, 3.96; 95% CI, 1.24-12.61) and a short cervical length (OR, 0.88; 95% CI, 0.82-0.94) were independent predictors of sPTB < 32 weeks. The model incorporating these three predictors displayed good discrimination and calibration, and the area under the ROC curve of this model was as high as 0.815 (95% CI, 0.700-0.931). Patients were stratified into low- (195 patients), intermediate- (14 patients) and high-risk (4 patients) groups according to the model, corresponding to patients with scores ≤ 120, 121-146, and > 146, respectively. The predicted probabilities of spontaneous preterm birth < 32 weeks for these groups were 6.38, 40.62, and 71.88%, respectively. CONCLUSIONS: A noninvasive and efficient model to predict the occurrence of spontaneous preterm birth < 32 weeks in low-risk singleton pregnant women with a short cervix and a classification system were constructed in this study and can provide insight into the optimal management strategy for patients with different risk stratifications according to the score chart.

Caesarean section rates in a tertiary teaching hospital in northern Uganda: a retrospective analysis using the robson ten group classification system.

BACKGROUND: The Robson Ten Groups Classification System (RTGCS) is increasingly used to assess, monitor, and compare caesarean section (CS) rates within and between healthcare facilities. We evaluated the major contributing groups to the CS rate at Gulu Regional Referral Hospital (GRRH) in Northern Uganda using the RTGCS. METHODS: We conducted a retrospective analysis of all deliveries from June 2019 through July 2020 at GRRH, Gulu city, Uganda. We reviewed files of mothers and collected data on sociodemographic and obstetric variables. The outcome variables were Robson Ten Groups (1-10) based on parity, gestational age, foetal presentation, number of foetuses, the onset of labour, parity and lie, and history of CS. RESULTS: We reviewed medical records of 3,183 deliveries, with a mean age of 24.6 ± 5.7 years. The overall CS rate was 13.4% (n = 427). Most participants were in RTGCS groups 3 (43.3%, n = 185) and 1 (29.2%, n = 88). The most common indication for CS was prolonged labour (41.0%, n = 175), followed by foetal distress (19.9%, n = 85) and contracted pelvis (13.6%, n = 58). CONCLUSION: Our study showed that GRRH patients had a low-risk obstetric population dominated by mothers in groups 3 and 1, which could explain the low overall CS rate of 13.4%. However, the rates of CS among low-risk populations are alarmingly high, and this is likely to cause an increase in CS rates in the future. We recommend group-specific interventions through CS auditing to lower group-specific CS rates.

Effects of Rheopheresis in dialysis patients with peripheral artery disease and diabetic foot ulcers: A multicentric Italian study.

BACKGROUND: Peripheral artery disease (PAD) in hemodialysis (HD) patients has a significant social impact due to its prevalence, poor response to standard therapy and dismal prognosis. Rheopheresis is indicated by guidelines for PAD treatment. MATERIALS AND METHODS: Twenty-five HD patients affected by PAD stage IV Lerichè-Fontaine and ischemic ulcer 1C or 2C according to the University of Texas Wound Classification System (UTWCS), without amelioration after traditional medical therapy and/or revascularization, were selected and underwent 12 Rheopheresis sessions in 10 weeks. Improvements in pain symptoms using Numerical Rating Scale (NRS), healing ulcers and laboratory hemorheological parameters have been evaluated. RESULTS: A clinically and statistically significant mean value reduction and of relative percentage differences between estimated marginal means (Δ), calculated at each visits, of NRS was observed, with a maximum value (-48.5%) between the first and last visit. At the end of the treatment period 14.3% of ulcers were completely healed, 46.4% downgraded, 53.6% were stable. Overall, no ulcers upgraded. A statistically significant reduction of the Δ, between the first and last visit, for fibrinogen (-16%) was also observed. CONCLUSION: Rheopheresis reduced overall painful symptoms; data suggest that it could heal or improve ulcers and hemorheological laboratory parameters in HD patients with PAD and ischemic ulcers resistant to standard therapies.

Proposal for Diagnostic Criteria of Y-Shaped Dysmorphic Uterus Based on 3-Dimensional Transvaginal Ultrasound Measurements.

STUDY OBJECTIVE: To define objective and readily applied diagnostic criteria for Y-shaped uteri using 3-dimensional transvaginal ultrasound (3D-TVUS) volume recordings. DESIGN: A retrospective case-control diagnostic measurements study. SETTING: A tertiary university hospital's reproductive health and research center. PATIENTS: Two hundred thirteen patients who presented with infertility between January 2020 and December 2022. INTERVENTIONS: Two blinded physicians re-evaluated the 3D-TVUS images of all patients for the presence of a uterine abnormality. The images of patients with a Y-shaped uterus were re-evaluated, and descriptive measurements were done. MEASUREMENTS AND MAIN RESULTS: The most common uterine abnormality in this cohort was the Y-shaped uterus with a prevalence of 12.2%, followed by the arcuate, T-shaped, and septate uteri, respectively. Reviewers identified 26 and 28 Y-shaped uteri, respectively, and came to a consensus on 25 images. Diagnostic criteria for the Y-shaped uterus based on 3D-TVUS findings have been specified as: lateral indentation depths between 4 and 7 mm, fundal indentation depth between 5 and 9 mm, lateral indentation angles between 121° and 149°, fundal indentation angle between 121° and 145°, and Y-angles 25° to 46°. CONCLUSION: Some subtypes of dysmorphic uteri, such as the Y-shaped uterus, whose clinical significance is unknown and may be variants of the normal, may actually be more common than thought. Determining objective diagnostic criteria with 3D-TVUS will allow standard research on these anomalies and their clinical significance.

Prediction of physicochemical and pharmacokinetic properties of botanical constituents by computational models.

Botanicals contain complex mixtures of chemicals most of which lack pharmacokinetic data in humans. Since physicochemical and pharmacokinetic properties dictate the in vivo exposure of botanical constituents, these parameters greatly impact the pharmacological and toxicological effects of botanicals in consumer products. This study sought to use computational (i.e., in silico) models, including quantitative structure-activity relationships (QSAR) and physiologically based pharmacokinetic (PBPK) modeling, to predict properties of botanical constituents. One hundred and three major constituents (e.g., withanolides, mitragynine, and yohimbine) in 13 botanicals (e.g., ashwagandha, kratom, and yohimbe) were investigated. The predicted properties included biopharmaceutical classification system (BCS) classes based on aqueous solubility and permeability, oral absorption, liver microsomal clearance, oral bioavailability, and others. Over half of these constituents fell into BCS classes I and II at dose levels no greater than 100 mg per day, indicating high permeability and absorption (%Fa > 75%) in the gastrointestinal tract. However, some constituents such as glycosides in ashwagandha and Asian ginseng showed low bioavailability after oral administration due to poor absorption (BCS classes III and IV, %Fa < 40%). These in silico results fill data gaps for botanical constituents and could guide future safety studies. For example, the predicted human plasma concentrations may help select concentrations for in vitro toxicity testing. Additionally, the in silico data could be used in tiered or batteries of assays to assess the safety of botanical products. For example, highly absorbed botanical constituents indicate potential high exposure in the body, which could lead to toxic effects.

The Predictive Power of Bosniak 3 and 4 Cystic Renal Lesion Categorization Using Contrast-Enhanced Ultrasound.

OBJECTIVES: Contrast-enhanced ultrasound (CEUS) is increasingly utilized for the noninvasive assessment of renal cystic lesions, using the Bosniak grading system. Bosniak 3-4 lesions require surgical referral, which allows correlation with the histopathological outcome. METHODS: In this single-center, retrospective study we evaluated renal CEUS exams conducted with SonoVue® with a diagnosis of a Bosniak 3 or 4 lesion between 2019 and 2022. A total of 49 patients and 50 lesions met the inclusion criteria, 31 lesions had available histopathological results. Patient demographics, cyst morphology, and dominant imaging features were registered. The histopathological diagnosis was considered a reference standard. RESULTS: Positive predictive power (PPV) for neoplastic lesions was comparable in the Bosniak 3 and 4 categories (75 vs 93.3%, P = .33), while PPV for histopathologically malignant lesion was considerably higher in the latter group (25 vs 93.33%, P = .0002). None of the lesions which had vividly enhancing thin septa as their dominant CEUS feature were malignant. Oncocytoma, multilocular cystic renal neoplasm of low malignant potential, and cystic nephroma were the major benign entities among Bosniak 3 lesions. Localized cystic kidney disease and hemorrhagic cysts were found to be the primary mimickers leading to false positive imaging findings. CONCLUSIONS: CEUS has a high predictive power for malignancy in the Bosniak 4 category, which is not maintained in the Bosniak 3 group due to the large proportion of benign lesions. Adherence to rigorous rule-in criteria and active surveillance strategies need to be considered for equivocal CEUS Bosniak 3 lesions.

Are we ready to bridge classification systems? A comprehensive review of different reporting systems in thyroid cytology.

The evaluation of thyroid lesions is common in the daily practice of cytology. While the majority of thyroid nodules are benign, in recent decades, there has been increased detection of small and well-differentiated thyroid cancers. Combining ultrasound evaluation with fine-needle aspiration cytology (FNAC) is extremely useful in the management of thyroid nodules. Furthermore, the adoption of specific terminology, introduced by different thyroid reporting systems, has helped effectively communicate thyroid FNAC diagnoses in a clear and understandable way. In 1996, the Papanicolaou Society thyroid cytological classification was introduced. This was followed in 2005 by the first Japanese and then in 2007 by the Bethesda System for Reporting Thyroid Cytopathology, which subsequently underwent two revisions. Other international thyroid terminology classifications include the British, Italian, Australasian and other Japanese cytology systems. This review covers similarities and differences among these cytology classification systems and highlights key points that unify these varied approaches to reporting thyroid FNAC diagnoses.