Clearance Rate Research Articles

Biodegradable coating constructed from carboxycellulose nanofibers for high photocatalytic decomposition of ethylene and synergistic antibacterial what of perishable fruits

Postharvest fruits, especially climacteric fruits, are prone to ethylene ripening, browning and aging, microbial growth accelerated decay and other problems in natural environment. Herein, a carboxylated cellulose nanofibers/phytic acid‑titanium dioxide nanoparticles (CPT) biodegradable coating with “photocatalytic antibacterial barrier” structure，was developed by homogeneous dispersion of phytic acid(PA) complexed titanium dioxide nanoparticles (TNPs) in carboxylated cellulose nanofibers(CCNF). The CPT coating achieves effective dispersion and efficient utilization of TNPs through the complexation of PA. The coating ethylene clearance rate of CPT up to 70.89 %. Meanwhile, the coating exhibits excellent antibacterial (99.67 %), UV resistance, gas barrier. It was found that the CPT coating delays fruit ripening caused by ethylene, which effectively maintaining the quality of respiratory climacteric fruits and non- climacteric fruits, extending the shelf life of perishable fruit by up to 9 days. In particular, the coating is virtually biodegradable in soil after 21 days, which offers the possibility of replacing non-biodegradable multifunctional coatings in food packaging.

Mass transfer of bilirubin and bovine serum albumin in hollow fiber membrane module of artificial liver

Understanding the mass transfer behaviors in hollow fiber membrane module of artificial liver is important for improving toxin removal efficiency. A three-dimensional numerical model was established to study the mass transfer of small molecule bilirubin and macromolecule bovine serum albumin (BSA) in the hollow fiber membrane module. Effects of tube-side flow rate, shell-side flow rate, and hollow fiber length on the mass transfer of bilirubin and BSA were discussed. The simulation results showed that the clearance of bilirubin was significantly affected by both convective and diffusive solute transport, while the clearance of macromolecule BSA was dominated by convective solute transport. The clearance rates of bilirubin and BSA increasd with the increase of tube-side flow rate and hollow fiber length. With the increase of shell-side flow rate, the clearance rate of bilirubin first rose rapidly, then slowly rose to an asymptotic value, while the clearance rate of BSA gradually decreased. The results can provide help for designing structures of hollow fiber membrane module and operation parameters of clinical treatment.

Safety and feasibility of same-day discharge for per-oral endoscopic myotomy.

Per-oral endoscopic myotomy (POEM) is a recognised treatment for achalasia, with the accepted approach involving admission for imaging and dietary progression. However, recent publications suggest same-day discharge (SDD) may be possible, which could be time and cost-saving. We sought to investigate the safety of SDD following POEM. Fifty consecutive POEMs at two referral centres in New Zealand were performed between 2020-2023. All patients were planned for early dietary introduction and were eligible for SDD if symptoms were managed. Analgesia was available in recovery and supplied at discharge. Imaging and endoscopy were performed only if there were clinical concerns. Rates of discharge clearance, discharge, complications and re-admission were analysed. All 50 POEMs were technically successful. A total of 41/50 (82%) received clearance for SDD. Additionally, 35/50 (70%) achieved discharge and 6/50 (12%) were observed overnight for social reasons, including lack of transport to the referring domicile. Of the patients not cleared for SDD, 7/9 (78%) were discharged within 24 hours, and the others after 48 and 72 hours. Procedural complications were recorded in three patients (6%), with one requiring endoscopic assessment and clipping. There were two re-admissions (4%), both lt;24-hour hospital stays, and managed medically. The majority of patients achieved same-day discharge clearance (82%) and 96% required less than 24 hours hospital stay. Complication and re-admission rates were low overall. We have demonstrated that POEM can be an SDD procedure facilitated by early dietary introduction and liberal analgesia, without the need for routine imaging or endoscopy.

Efficacy and safety of deferoxamine in moderately ill COVID-19 patients: An open label, randomized controlled trial.

Deferoxamine is a potent iron chelator that could remove iron from the virus, and severe acute respiratory syndrome coronavirus 2 requires iron to replication. Also, deferoxamine has antioxidant and cytokine-modulating effects. Therefore, we evaluated the efficacy and safety of deferoxamine in patients with moderate coronavirus disease 2019 (COVID-19). In this randomized controlled trial, patients with moderate COVID-19 were randomly assigned in a 1:1 ratio to the deferoxamine group (received a solution of 500 mg deferoxamine divided into 4 doses a day through a nebulizer for 7 days) and the control group. The main outcomes were viral clearance, oxygen saturation (SPO2), body temperature, and respiratory rate (RR). Intensive care unit admission, hospital length of stay, and hospital mortality were also assessed. A total of 62 patients, with 30 in the deferoxamine group and 32 in the control group, were randomly assigned. There was no statistically significant improvement in viral clearance after the intervention ended in the deferoxamine group (36.7%) compared to the control group (34.4%). The results showed there was no significant difference between the analyzed groups in terms of SPO2, body temperature, RR, and the number of patients with a worse prognosis (SPO2 < 96%, temperature ≥ 37.5 °C, or RR ≥ 16/min) at the end of the study. There were no significant differences seen between the groups in terms of intensive care unit admission, hospital length of stay, hospital mortality, and the occurrence of adverse medication events during the follow-up period. Deferoxamine had no significant impact on improving moderately ill patients with COVID-19. However, it was well-tolerated in the patients, and this intervention demonstrated a safe profile of adverse events.

Emulsion electrospun epigallocatechin gallate-loaded silk fibroin/polycaprolactone nanofibrous membranes for enhancing guided bone regeneration

Guided bone regeneration (GBR) membranes play an important role in oral bone regeneration. However, enhancing their bone regeneration potential and antibacterial properties is crucial. Herein, silk fibroin (SF)/polycaprolactone (PCL) core-shell nanofibers loaded with epigallocatechin gallate (EGCG) were prepared using emulsion electrospinning. The nanofibrous membranes were characterized via scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, water contact angle (CA) measurement, mechanical properties testing, drug release kinetics, and 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) free radical scavenging assay. Mouse pre-osteoblast MC3T3-E1 cells were used to assess the biological characteristics, cytocompatibility, and osteogenic differentiation potential of the nanofibrous membrane. Additionally, the antibacterial properties againstStaphylococcus aureus (S. aureus)andEscherichia coli (E. coli)were evaluated. The nanofibers prepared by emulsion electrospinning exhibited a stable core-shell structure with a smooth and continuous surface. The tensile strength of the SF/PCL membrane loaded with EGCG was 3.88 ± 0.15 Mpa, the water CA was 50°, and the DPPH clearance rate at 24 h was 81.73% ± 0.07%. The EGCG release rate of membranes prepared by emulsion electrospinning was reduced by 12% within 72 h compared to that of membranes prepared via traditional electrospinning.In vitroexperiments indicate that the core-shell membranes loaded with EGCG demonstrated good cell compatibility and promoted adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. Furthermore, the EGCG-loaded membranes exhibited inhibitory effects onE. coliandS. aureus. These findings indicate that core-shell nanofibrous membranes encapsulated with EGCG prepared using emulsion electrospinning possess good antioxidant, osteogenic, and antibacterial properties, making them potential candidates for research in GBR materials.

Chlorhexidine gluconate versus povidone-iodine for nasal bacteria decolonization before transsphenoidal surgery in patients with pituitary neuroendocrine tumors: A prospective, randomized, double-blind, non-inferiority trial.

This study aimed to compare the nasal decolonization efficacy and comfort between chlorhexidine gluconate (CHG) and povidone-iodine (PVP) to provide an evidence basis for clinical guidance. A prospective, randomized, single-blinded, noninferior clinical trial was conducted in 174 patients with pituitary neuroendocrine tumors (PitNETs) who were scheduled to undergo transsphenoidal surgery. The noninferiority margin was δ=-0.1. The primary outcome was the effective rate of disinfection. The secondary outcomes included post-operative inflammatory indicators, the intracranial infection rate, and the proportion of intracranial infection. The effective clearance rate of post-operative nasal bacteria was nonsignificantly different between the CHG and PVP groups (88.64% vs. 82.56%; between-group difference 6.10%; 95% CI [-5.30 to 17.50]). There was no significant difference in the incidence of post-operative central nervous system infections or serum inflammation-related indications between the two groups, but sterilization tended to occur quicker and last longer in the CHG group. CHG seemed to have advantages in terms of comfort, including less nasal irritation, less pungency, and better intranasal coloration. CHG and PVP have equal efficacy in nasal decolonization before transsphenoidal surgery, but CHG seems to have comfort-related advantages in terms of less nasal irritation, less pungency, and better intranasal coloration.

Long-term clinical outcomes of extracorporeal shockwave lithotripsy and endoscopic retrograde cholangiopancreatography for pancreatic duct stone treatment in patients with chronic pancreatitis.

Extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferred therapeutic approaches for painful chronic pancreatitis (CP) with pancreatic stones. This study aimed to report the short- and long-term outcomes following P-ESWL and ERCP in a large cohort with CP. Patients with painful CP and pancreatic stones >5 mm in size, who underwent P-ESWL and subsequent ERCP between March 2011 and June 2018, were included in this retrospective-prospective mixed observational study. The total stone clearance rates were recorded. All patients were followed up until the end of March 2024, with the visual analogue scale (VAS) for pain, pain type, quality-of-life scores and other relevant information recorded. A total of 2071 patients underwent P-ESWL, and 93.1% of them subsequently underwent ERCP during the study period. Patients were followed up for an average of 11.8 years from the onset of CP and 6.7 years from the first P-ESWL procedure. Complete stone clearance was achieved in 73.7% of the patients. At the end of the follow-up period, 70.1% of the patients achieved complete pain remission. Significant pain type conversion and lower VAS scores were observed in the patients after treatment. Quality-of-life scores and body mass indices increased after P-ESWL and ERCP. P-ESWL and ERCP are effective and minimally invasive treatments for pancreatic stones in patients with painful CP. Most patients achieved complete pain relief, and pain-type conversion was common after treatment. (ClinicalTrials.gov: NCT05916547).

Radioimmunotheragnosis in Cancer Research.

The combination of immunoPET-where an antibody (Ab) is labeled with an isotope for PET imaging-and radioimmunotherapy (RIT), using the same antibody with a therapeutic isotope, offers significant advantages in cancer management. ImmunoPET allows non-invasive imaging of antigen expression, which aids in patient selection for subsequent radioimmunotherapy. It also facilitates the assessment of tumor response to therapy, allowing for treatment adjustments if necessary. In addition, immunoPET provides critical pharmacokinetic data, including antibody biodistribution and clearance rates, which are essential for dosimetry calculations and treatment protocol optimization. There are still challenges to overcome. Identifying appropriate target antigens that are selectively expressed on cancer cells while minimally expressed on normal tissues remains a major hurdle to reduce off-target toxicity. In addition, it is critical to optimize the pharmacokinetics of radiolabeled antibodies to maximize tumor uptake and minimize normal tissue uptake, particularly in vital organs such as the liver and kidney. This approach offers the potential for targeted and personalized cancer therapy with reduced systemic toxicity by exploiting the specificity of monoclonal antibodies and the cytotoxic effects of radiation. However, further research is needed to address remaining challenges and to optimize these technologies for clinical use.

Clearance rate of contrast extravasation after endovascular therapy is associated with functional outcome and mediated by cerebral edema.

The brain's function of clearance and transport is closely related to the prognosis of acute ischemic stroke (AIS). In this study, we proposed a novel method, clearance rate of contrast extravasation (CROCE), to measure brain clearance and transport function in AIS patients undergoing endovascular therapy (EVT), and examined its association with cerebral edema and functional outcome. We conducted a pooled analysis of AIS patients of anterior circulation large vessel occlusion who underwent EVT in two academic hospitals. Patients who experienced contrast extravasation but not intracerebral hemorrhage following EVT were included. CROCE was defined as the mass of contrast agent cleared per hour on non-contrast CT (NCCT). Among the 215 patients finally included, we found that high CROCE was significantly associated with 90-day favorable functional outcome, and the association retained after adjustment for potential confounders. Different correlation analysis demonstrated a significant correlation between CROCE, cerebral edema, and functional outcome. Further mediation analysis revealed that cerebral edema mediated the effect of CROCE on functional outcome. These results revealed that CROCE may be a promising indicator of brain clearance function for patients who received EVT and had contrast extravasation.

Analysis of 5 patients with acute glyphosate poisoning clinical characteristics and metabolic concentration

Objective: To analyze the correlation between changes in the concentration of glyphosate (GLY) and its metabolites (AMPA) in patients with acute glyphosate poisoning and clinical symptoms, and to provide reference for the study of glyphosate toxicity. Methods: Urine samples from 5 patients with oral glyphosate poisoning admitted to the Emergency Department of Yangzhou Third Class A General Hospital from February to July 2021 were collected. Urine concentrations of GLY and AMPA were measured using derivatization gas chromatography-mass spectrometry, and analyzed based on the patient's clinical manifestations and treatment process. Results: The main symptoms of the patient after poisoning were acute gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, etc. The concentration of GLY in the patient's urine reached its maximum on the first day and gradually decreased over time. On the day of discharge, the final concentration of GLY was 10% lower than the initial concentration. At discharge, the clearance rates of GLY in cases 1, 2, 3, and 4 were 96.97%, 95.91%, 96.87% and 92.87%, respectively. Conclusion: The glyphosate has a shorter maintenance time after entering the human body; There is no correlation between the concentration of glyphosate and its metabolites admitted to the hospital, the dose of poisoning, and clinical symptoms in poisoned patients.

Modeling Metformin and Dapagliflozin Pharmacokinetics in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a complication of diabetes that affects circulating drug concentrations and elimination of drugs from the body. Multiple drugs may be prescribed for treatment of diabetes and co-morbidities, and CKD complicates the pharmacotherapy selection and dosing regimen. Characterizing variations in renal drug clearance using models requires large clinical datasets that are costly and time-consuming to collect. We propose a flexible approach to incorporate impaired renal clearance in pharmacokinetic (PK) models using descriptive statistics and secondary data with mechanistic models and PK first principles. Probability density functions were generated for various drug clearance mechanisms based on the degree of renal impairment and used to estimate the total clearance starting from glomerular filtration for metformin (MET) and dapagliflozin (DAPA). These estimates were integrated with PK models of MET and DAPA for simulations. MET renal clearance decreased proportionally with a reduction in estimated glomerular filtration rate (eGFR) and estimated net tubular transport rates. DAPA total clearance varied little with renal impairment and decreased proportionally to reported non-renal clearance rates. Net tubular transport rates were negative to partially account for low renal clearance compared with eGFR. The estimated clearance values and trends were consistent with MET and DAPA PK characteristics in the literature. Dose adjustment based on reduced clearance levels estimated correspondingly lower doses for MET and DAPA while maintaining desired dose exposure. Estimation of drug clearance rates using descriptive statistics and secondary data with mechanistic models and PK first principles improves modeling of CKD in diabetes and can guide treatment selection.

Biosafe, rapid, and ultrahigh‐capacity endotoxin purification in blood by a sustainable and recyclable MOF‐functionalized chitin microsphere adsorbent

AbstractSepsis is responsible for approximately 5.3 million deaths globally each year. Here, we constructed hierarchical chitin microspheres loaded with MOF‐919 (Ch/metal–organic frameworks [MOFs]) for the rapid and efficient removal of lipopolysaccharide (LPS) in complex blood environments. Furthermore, abundant active sites on MOF‐919(Sc) also enable a record‐high adsorption capacity of 9.56 mg/g in biomass‐based adsorbents due to the coordination interactions between endotoxin and MOF‐919(Sc). The LPS level of sepsis rabbits was less than 2 EU/mL (clearance rate &gt;95%) after 90‐min hemoperfusion, showing no adverse effect on the rabbit organs. Additionally, compared to the commonly used LPS scrubber Toraymyxin (polymethyl methacrylate), the chitin adsorbent is significantly more cost‐effective and environmentally friendly. The preparation strategy for hierarchical porous microspheres offers notable advantages in designability, recyclability, and renewability, providing a new approach to sepsis treatment and promising prospects for the biomedical application of sustainable biomass materials.

In vivo fluorescence flow cytometry reveals that the nanoparticle tumor vaccine OVA@HA-PEI effectively clears circulating tumor cells

Tumor vaccine therapy offers significant advantages over conventional treatments, including reduced toxic side effects. However, it currently functions primarily as an adjuvant treatment modality in clinical oncology due to limitations in tumor antigen selection and delivery methods. Tumor vaccines often fail to elicit a sufficiently robust immune response against progressive tumors, thereby limiting their clinical efficacy. In this study, we developed a nanoparticle-based tumor vaccine, OVA@HA-PEI, utilizing ovalbumin (OVA) as the presenting antigen and hyaluronic acid (HA) and polyethyleneimine (PEI) as adjuvants and carriers. This formulation significantly enhanced the proliferation of immune cells and cytokines, such as CD3, CD8, interferon-[Formula: see text], and tumor necrosis factor-[Formula: see text], in vivo, effectively activating an immune response against B16–F10 tumors. In vivo fluorescence flow cytometry (IVFC) has already become an effective method for monitoring circulating tumor cells (CTCs) due to its direct, noninvasive, and long-term detection capabilities. Our study utilized a laboratory-constructed IVFC system to monitor the immune processes induced by the OVA@HA-PEI tumor vaccine and an anti-programmed death-1 (PD-1) antibody. The results demonstrated that the combined treatment of OVA@HA-PEI and anti-PD-1 antibody significantly improved the survival time of mice compared to anti-PD-1 antibody treatment alone. Additionally, this combination therapy substantially reduced the number of CTCs in vivo, increased the clearance rate of CTCs by the immune system, and slowed tumor progression. These findings greatly enhance the clinical application prospects of IVFC and tumor vaccines.

Oil uptake via marine snow: Effects on blue mussels (Mytilus sp.)

Accidental oil spills into the ocean can lead to downward transport and settling of oil onto the seafloor as part of marine snow, as seen during the Deepwater Horizon incident in 2010 in the Gulf of Mexico. The arctic and subarctic regions may favor conditions leading to this benthic oil deposition, prompting questions about the potential impacts on benthic communities. This study investigated the effects of oil-contaminated marine snow uptake on the blue mussel (Mytilus sp.). We exposed mussels for four days to 1) oil-contaminated marine snow (MOS treatment), or to 2) chemically-enhanced water-accommodated fraction (CEWAF) of oil plus unaggregated food particles (CEWAF treatment). Both oil treatments received the same nominal concentration of oil and food. Two controls were included: 1) Clean seawater plus unaggregated food (agg-free control) and 2) clean seawater plus marine snow (marine snow control). After the exposure, mussels were allowed to recover for ten days under clean, running seawater. Samples were taken right before and after the exposure period, and after the recovery phase for the following endpoints: distribution (partitioning) of oil compounds between seawater and MOS, and between seawater and mussel tissue; DNA damage (assessed via the comet assay); clearance rate; and condition index [tissue dry weight (g) divided by shell length (mm)]. Some discernable patterns were found in the partitioning of oil compounds between seawater and MOS. However, these patterns did not translate to any significant differences in the partitioning of oil compounds into mussel tissue between the two oil treatments. DNA damage did not exceed background levels (10% tail DNA or less; to be expected in healthy, viable cells) at any sampling time point, but significantly higher DNA damage was observed in CEWAF-T compared to MOS-T mussels after the recovery phase. After the exposure, a significant difference emerged in the clearance rate between the CEWAF treatment and the agg-free control, but not between the MOS treatment and the marine snow control. All mussels except those from the CEWAF treatment exhibited an increased condition index after the exposure time. Together, these results suggest that aggregates could moderate the effects of oil exposure on blue mussels, possibly by providing better, more concentrated nutrition than unaggregated food particles.

Efficacy of interventions for cutaneous squamous cell carcinoma insitu (Bowen's disease): A systematic review and meta-analysis of proportions.

Cutaneous squamous cell carcinoma insitu (Bowen's disease) is a precancerous condition confined to the epidermis of the skin. Despite the critical need for effective interventions to halt its progression, there remains a notable shortage of comprehensive data comparing the efficacy of various therapeutic approaches. This systematic review and meta-analysis endeavour to compare the different efficacies of interventions by investigating and synthesizing data from numerous trials. A pre-defined protocol was registered in PROSPERO (CRD42021242224, registration date: 16 April 2021). Systematic searches in Medline, Embase and Central, along with manual trial register searches, identified studies reporting lesion clearance rates (LCR), participant clearance rates (PCR) or recurrence rates (date of last search: 12 June 2024). Quality assessment followed guidelines from the National Heart, Lung, and Blood Institute (NHLBI). After the study arms were categorized into treatment groups and groups of study quality, the proportions were pooled using the generalized linear mixed model (GLMM) as meta-analytical method. A comprehensive inclusion of 71 studies facilitated an evaluation of 3783 lesions for LCR, 1225 patients for PCR, 4073 lesions for lesion recurrence rates (LRR) and 740 patients for participant recurrence rates (PRR). Surgery demonstrated the highest LCR and PCR (0.97, 95% confidence interval (CI): 0.90-0.99) and the lowest LRR (0.04, 95% CI: 0.02-0.07). This study provides a thorough overview of reported efficacy outcomes for practice-relevant interventions for Bowen's disease. Surgery outperformed other treatments for Bowen's disease. For the other intervention groups, it was not possible to show clear differences in effectiveness: LCR, PCR, LRR and PRR showed various treatment rankings, and the comparability was restricted by different numbers of studies between treatment groups and outcome measures, methodical and clinical heterogeneity. Further high-quality studies are needed to investigate practice-relevant interventions for Bowen's disease.

Ocular and Systemic Pharmacokinetics of Lotilaner Ophthalmic Solution, 0.25%, Following a Single Dose or Repeated Doses in Dutch-Belted Rabbits.

Purpose: To evaluate the ocular and systemic pharmacokinetics of lotilaner ophthalmic solution, 0.25%, following bilateral topical ocular administration of single and repeated doses in rabbits. Methods: Dutch-belted rabbits (n = 34) were administered lotilaner ophthalmic solution, 0.25%, eye drops, either in a single bilateral dose (Group 1) or twice a day bilaterally for 7 days and once on Day 8 (Group 2). The pharmacokinetics and tissue distribution levels of lotilaner were assessed following the single dose in Group 1 and the last dose in Group 2. The drug levels were examined in various ocular tissues and whole blood. The maximal concentration of the drug (Cmax), time to maximal concentration, the terminal phase elimination half-life, the area under the concentration-time curve (AUC), and total clearance of the drug were determined. Results: In the eyelid margins, lotilaner exhibited the highest observed concentrations at 0.25 hour (h), presenting a mean Cmax of 14,600 ng/mL in Group 1 and 20,100 ng/mL in Group 2. The highest AUC was in the eyelid margin at 242,000 h×ng/mL in Group 1 and 535,000 h×ng/mL in Group 2. In the eyelid margin, the observed clearance rate (0.634 mL/h in single dose, 0.288 mL/h in repeat dose) was the slowest among all ocular tissues in both groups, with the longest half-life of 152 h (∼6.3 days) observed in the repeat dose group. Conclusions: Lotilaner ophthalmic solution, 0.25%, demonstrated rapid ocular tissue absorption into the eyelid margin tissue with a long half-life of almost a week. No adverse effects were observed following topical ocular administration in Dutch-belted rabbits.

Multi-institutional Analysis of Choledocholithiasis in Pediatric vs Adult Patients

BackgroundIn adults, upfront intraoperative cholangiogram with laparoscopic common bile duct exploration (LCBDE) is well accepted for management of choledocholithiasis. Despite recent evidence supporting LCBDE utility in children, there has been hesitation to adopt this surgery first (SF) approach over ERCP first (EF) due to perceived technical challenges. We compared rates of successful stone clearance during LCBDE between adult and pediatric patients to evaluate if pediatric surgeons could anticipate similar rates of successful clearance. MethodsA multicenter, retrospective review of pediatric (<18 years) and adult patients with choledocholithiasis managed from 2018 to 2024 was performed. Demographic and clinical data were obtained. Rate of successful duct clearance with LCBDE was compared. Surgical and endoscopic complications (infections, bleeding, pancreatitis, bile leak) were also compared. Results724 patients, 333 (45.9%) pediatric and 391 (54.0%) adults, were included. The median age of pediatric vs adult patients was 15.2 years [13.1, 16.6] vs 55.5 years [34.1, 70.5], respectively. Of these, 201 (60.4%) pediatric vs 169 (43.2%) adult patients underwent SF, p < 0.001. LCBDE was attempted in 84 (41.7%) pediatric vs 140 (82.8%) adults, p = 0.002. LCBDE success was higher in pediatric vs adult patients (82.1% vs 71.4%, p = 0.004). Complications rates were similar however, pediatric patients who underwent EF had higher endoscopic complications (9.1% vs 3.6%, p = 0.03). ConclusionLCBDE is highly successful in children vs adults with no increased surgical complications. This data, coupled with the limited ERCP access for children, supports that LCBDE is an equally effective tool for managing choledocholithiasis in children as is accepted in adults. Level of EvidenceLevel III.

Fetal sex effects on maternal health can now be tested via randomization: A first-in-class illustration in cows on glucoregulatory outcomes

BackgroundThe maternal-offspring relationship, such as whether fetal sex influences maternal health, is essential to explore to advance prenatal and maternal health. While associations exist between fetal sex and maternal health outcomes, it is unclear whether these reflect a causal relationship. ObjectiveTo demonstrate that fetal sex can be randomly assigned to test the causal effect of fetal sex on maternal outcomes. MethodsHolstein dairy cows were stratified and randomized using sealed opaque envelopes to be artificially inseminated with either X- or Y-sorted bull semen until 40 cows became pregnant. Monthly body weight measurements were recorded, and an intravenous glucose tolerance test was performed 30 days before the expected calving day. The primary outcome was insulin area under the curve (AUC), and secondary outcomes were clearance rate, half-life, and AUC for glucose, insulin, and non-esterified fatty acid concentrations. An intention-to-treat (ITT) approach using multiple imputation was employed for primary analysis, and an as-treated (AT) approach was used for secondary analysis. ResultsWe demonstrated that we could successfully randomize the assignment of fetal sex to dams and test for causal effects of fetal sex on glucoregulatory outcomes using dairy cows as a model. Insulin AUC was not statistically different between groups (ITT p = 0.857, AT p = 0.874), and other outcomes were also not statistically different (p > 0.05). ConclusionWe demonstrated that causal effects of fetal sex on maternal outcomes can be causally tested in dairy cows. Our study did not provide statistical evidence to support an effect of fetal sex on maternal glucose-related outcomes.

Value of Renal Artery Resistive Index in Nonazotaemic Cirrhotic Patients with Ascites

Background: Renal dysfunction is a common complication in patients with liver cirrhosis, with hepatorenal syndrome (HRS) being the most severe form. HRS is characterized by disturbances in both circulatory and kidney functions and is diagnosed by excluding other causes of renal failure. Objective: This study aimed to measure the renal artery resistive index (RI) in non-azotaemic cirrhotic patients with ascites to predict early renal haemodynamic dysfunction. Methodology: A prospective study was conducted involving 30 cirrhotic patients with ascites and 15 healthy controls. Renal artery RI was measured using Duplex Doppler ultrasonography. Inclusion criteria for patients included normal renal function, as indicated by serum creatinine ≤ 1.2 mg/dl and creatinine clearance rate ≥ 50 ml/min. Results: The mean renal artery RI was significantly higher in cirrhotic patients with ascites (70% had RI ≥ 0.70) compared to controls (all had RI &lt; 0.70). Significant differences were observed in serum bilirubin, SGPT, SGOT, and prothrombin time between cases and controls (p &lt; 0.05). Conclusion: Renal Doppler ultrasonography is a valuable noninvasive method for detecting early renal haemodynamic dysfunction in cirrhotic patients with ascites. Elevated renal artery RI can serve as an indicator of renal dysfunction, aiding in early diagnosis and management.

Croconaine-based NIR-II fluorescence imaging-guided tumor photothermal therapy induces long-term antitumor immune memory

Photothermal therapy (PTT) for cancers guided by optical imaging has recently shown great potential for precise diagnosis and efficient therapy. The second near-infrared window (NIR-II, 1000–1700 nm) fluorescence imaging (FLI) is highly desirable owing to its good spatial and temporal resolution, deep tissue penetration, and negligible tissue toxicity. Organic small molecules are attractive as imaging and treatment agents in biomedical research because of their low toxicity, fast clearance rate, diverse structures, ease of modification, and excellent biocompatibility. Various organic small molecules have been investigated for biomedical applications. However, there are few reports on the use of croconaine dyes (CRs), especially NIR-II emission CRs. To our knowledge, there have been no prior reports of NIR-II emissive small organic photothermal agents (SOPTAs) based on CRs. Herein, we report a croconaine dye (CR-TPE-T)-based nanoparticle (CR NP) with absorption and fluorescence emission in the NIR-I and NIR-II windows, respectively. The CR NPs exhibited intense NIR absorption, outstanding photothermal properties, and good biological compatibility. In vivo studies showed that CR NPs not only achieved real-time, noninvasive NIR-II FLI of tumors, but also induced significant tumor ablation with laser irradiation guided by imaging, without apparent side effects, and promoted the formation of antitumor immune memory in a colorectal cancer model. In addition, the CR NPs displayed efficient inhibition of breast tumor growth, improved longevity of mice and triggered efficient systemic immune responses, which further inhibited tumor metastasis to the lungs. Our study demonstrates the great potential of CRs as therapeutic agents in the NIR-II region for cancer diagnosis.