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Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Apr 2024The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May...
The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.
Topics: Humans; Leukemia, Myeloid, Acute; Sulfonamides; Bridged Bicyclo Compounds, Heterocyclic; Antineoplastic Combined Chemotherapy Protocols; Induction Chemotherapy; Female; Male; Middle Aged; Adult
PubMed: 38951068
DOI: 10.3760/cma.j.cn121090-20231208-00298 -
BMJ Open Jul 2024Novel antidiabetes medications with proven cardiovascular or renal benefit, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1...
OBJECTIVES
Novel antidiabetes medications with proven cardiovascular or renal benefit, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA), have been introduced to the market. This study explored the 4-year trends of antidiabetes medication use among medical hospitalisations with type 2 diabetes (T2D).
DESIGN
Retrospective cohort study.
SETTING
Tertiary care hospital in Switzerland.
PARTICIPANTS
4695 adult hospitalisations with T2D and prevalent or incident use of one of the following antidiabetes medications (metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), sulfonylureas, GLP-1 RA, SGLT-2i, short-acting insulin or long-acting insulin), identified using electronic health record data. Quarterly trends in use of antidiabetes medications were plotted overall and stratified by cardiovascular disease (CVD) and chronic kidney disease (CKD).
RESULTS
We observed a stable trend in the proportion of hospitalisations with T2D who received any antidiabetes medication (from 77.6% during 2019 to 78% in 2022; p for trend=0.97). In prevalent users, the largest increase in use was found for SGLT-2i (from 7.4% in 2019 to 21.8% in 2022; p for trend <0.01), the strongest decrease was observed for sulfonylureas (from 11.4% in 2019 to 7.2% in 2022; p for trend <0.01). Among incident users, SGLT-2i were the most frequently newly prescribed antidiabetes medication with an increase from 26% in 2019 to 56.1% in 2022 (p for trend <0.01). Between hospital admission and discharge, SGLT-2i also accounted for the largest increase in prescriptions (+5.1%; p<0.01).
CONCLUSIONS
These real-world data from 2019 to 2022 demonstrate a significant shift in antidiabetes medications within the in-hospital setting, with decreased use of sulfonylureas and increased prescriptions of SGLT-2i, especially in hospitalisations with CVD or CKD. This trend aligns with international guidelines and indicates swift adaptation by healthcare providers, signalling a move towards more effective diabetes management.
Topics: Humans; Diabetes Mellitus, Type 2; Retrospective Studies; Hypoglycemic Agents; Male; Female; Hospitalization; Aged; Middle Aged; Switzerland; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Renal Insufficiency, Chronic; Sulfonylurea Compounds; Cardiovascular Diseases; Adult; Metformin
PubMed: 38950998
DOI: 10.1136/bmjopen-2024-084526 -
Environmental Pollution (Barking, Essex... Jun 2024Urban aquifers are at risk of contamination from persistent and mobile organic compounds (PMOCs), especially per- and polyfluoroalkyl substances (PFAS), which are...
Urban aquifers are at risk of contamination from persistent and mobile organic compounds (PMOCs), especially per- and polyfluoroalkyl substances (PFAS), which are artificial organic substances widely used across various industrial sectors. PFAS are considered toxic, mobile and persistent, and have therefore gained significant attention in environmental chemistry. Moreover, precursors could transform into more recalcitrant products under natural conditions. However, there is limited information about the processes which affect their behaviour in groundwater at the field-scale. In this context, the aim of this study is to assess the presence of PFAS in an urban aquifer in Barcelona, and identify processes that control their evolution along the groundwater flow. 21 groundwater and 6 river samples were collected revealing the presence of 16 PFAS products and 3 novel PFAS. Short and ultra-short chain PFAS were found to be ubiquitous, with the highest concentrations detected for perfluorobutanesulfonic acid (PFBS), trifluoroacetic acid (TFA) and trifluoromethanesulfonic acid (TFSA). Long chain PFAS and novel PFAS were found to be present in very low concentrations (< 50 ng/L). It was observed that redox conditions influence the behaviour of a number of PFAS controlling their attenuation or recalcitrant behaviour. Most substances showed accumulation, possibly explained by sorption/desorption processes or transformation processes, highlighting the challenges associated with PFAS remediation. In addition, the removal processes of different intensities for three PFAS were revealed. Our results help to establish the principles of the evolution of PFAS along the groundwater flow, which are important for the development of conceptual models used to plan and adopt site specific groundwater management activities (e.g., Managed Aquifer Recharge).
PubMed: 38950847
DOI: 10.1016/j.envpol.2024.124468 -
Future Medicinal Chemistry Jul 2024This study aimed to enhance the aqueous dissolution of SRPK inhibitor -(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340). A complex with...
This study aimed to enhance the aqueous dissolution of SRPK inhibitor -(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340). A complex with -sulfonic calix[6]arene (Host) and SRPIN340 (Guest) was prepared, studied via H nuclear magnetic resonance (NMR) and theoretical calculations and biologically evaluated on cancer cell lines. The 1:1 host (H)/guest (G) complex significantly enhanced the aqueous dissolution of SRPIN340, achieving 64.8% water solubility as determined by H NMR quantification analysis. The H/G complex reduced cell viability by 75% for HL60, ∼50% for Nalm6 and Jurkat, and ∼30% for B16F10 cells. It exhibited greater cytotoxicity than free SRPIN340 against Jurkat and B16F10 cells. Theoretical studies indicated hydrogen bond stabilization of the complex, suggesting broader applicability of SRPIN340 across diverse biological systems.
PubMed: 38949866
DOI: 10.1080/17568919.2024.2366690 -
ACS Omega Jun 2024Imbalance of potassium-ion levels in the body can lead to physiological dysfunctions, which can adversely impact cardiovascular, neurological, and ocular health. Thus,...
Imbalance of potassium-ion levels in the body can lead to physiological dysfunctions, which can adversely impact cardiovascular, neurological, and ocular health. Thus, quantitative measurement of potassium ions in a biological system is crucial for personal health monitoring. Nanomaterials can be used to aid in disease diagnosis and monitoring therapies. Optical detection technologies along with molecular probes emitting within the near-infrared (NIR) spectral range are advantageous for biological measurements due to minimal interference from light scattering and autofluorescence within this spectral window. Herein, we report the development of NIR fluorescent nanosensors, which can quantitatively detect potassium ions under biologically relevant conditions. The optical nanosensors were developed by using photoluminescent single-walled carbon nanotubes (SWCNTs) encapsulated in polymers that contain potassium chelating moieties. The nanosensors, polystyrene sulfonate [PSS-SWCNTs, nanosensor 1 (NS1)] or polystyrene--polystyrene sulfonate [PS--PSS-SWCNTs, nanosensor 2 (NS2)], exhibited dose-dependent optical responses to potassium ion level. The nanosensors demonstrated their biocompatibility via the evaluation of cellular viability, proliferation assays, and expression of cytokeratin 12 in corneal epithelial cells (CEpiCs). Interestingly, the nanosensors' optical characteristics and their responses toward CEpiCs were influenced by encapsulating polymers. NS2 exhibited a 10 times higher fluorescence intensity along with a higher signal-to-noise ratio as compared to NS1. NS2 showed an optical response to potassium ion level in solution within 5 min of addition and a limit of detection of 0.39 mM. Thus, NS2 was used for detailed investigations including potassium ion level detection in serum. NS2 showed a consistent response to potassium ions at the lower millimolar range in serum. These results on optical sensing along with biocompatibility show a great potential for nanotube sensors in biomedical research.
PubMed: 38947780
DOI: 10.1021/acsomega.4c01867 -
Microsystems & Nanoengineering 2024Targeted delivery of neurochemicals and biomolecules for neuromodulation of brain activity is a powerful technique that, in addition to electrical recording and...
Targeted delivery of neurochemicals and biomolecules for neuromodulation of brain activity is a powerful technique that, in addition to electrical recording and stimulation, enables a more thorough investigation of neural circuit dynamics. We have designed a novel, flexible, implantable neural probe capable of controlled, localized chemical stimulation and electrophysiology recording. The neural probe was implemented using planar micromachining processes on Parylene C, a mechanically flexible, biocompatible substrate. The probe shank features two large microelectrodes (chemical sites) for drug loading and sixteen small microelectrodes for electrophysiology recording to monitor neuronal response to drug release. To reduce the impedance while keeping the size of the microelectrodes small, poly(3,4-ethylenedioxythiophene) (PEDOT) was electrochemically coated on recording microelectrodes. In addition, PEDOT doped with mesoporous sulfonated silica nanoparticles (SNPs) was used on chemical sites to achieve controlled, electrically-actuated drug loading and releasing. Different neurotransmitters, including glutamate (Glu) and gamma-aminobutyric acid (GABA), were incorporated into the SNPs and electrically triggered to release repeatedly. An in vitro experiment was conducted to quantify the stimulated release profile by applying a sinusoidal voltage (0.5 V, 2 Hz). The flexible neural probe was implanted in the barrel cortex of the wild-type Sprague Dawley rats. As expected, due to their excitatory and inhibitory effects, Glu and GABA release caused a significant increase and decrease in neural activity, respectively, which was recorded by the recording microelectrodes. This novel flexible neural probe technology, combining on-demand chemical release and high-resolution electrophysiology recording, is an important addition to the neuroscience toolset used to dissect neural circuitry and investigate neural network connectivity.
PubMed: 38947533
DOI: 10.1038/s41378-024-00685-6 -
ACS Central Science Jun 2024Protein-based therapeutics comprise a rapidly growing subset of pharmaceuticals, but enabling their delivery into cells for intracellular applications has been a...
Protein-based therapeutics comprise a rapidly growing subset of pharmaceuticals, but enabling their delivery into cells for intracellular applications has been a longstanding challenge. To overcome the delivery barrier, we explored a reversible, bioconjugation-based approach to modify the surface charge of protein cargos with an anionic "cloak" to facilitate electrostatic complexation and delivery with lipid nanoparticle (LNP) formulations. We demonstrate that the conjugation of lysine-reactive sulfonated compounds can allow for the delivery of various protein cargos using FDA-approved LNP formulations of the ionizable cationic lipid DLin-MC3-DMA (MC3). We apply this strategy to functionally deliver RNase A for cancer cell killing as well as a full-length antibody to inhibit oncogenic β-catenin signaling. Further, we show that LNPs encapsulating cloaked fluorescent proteins distribute to major organs in mice following systemic administration. Overall, our results point toward a generalizable platform that can be employed for intracellular delivery of a wide range of protein cargos.
PubMed: 38947210
DOI: 10.1021/acscentsci.4c00071 -
Materials Horizons Jul 2024Electrochemical deionization (ECDI) has emerged as a promising technology for water treatment, with faradaic ECDI systems garnering significant attention due to their...
Electrochemical deionization (ECDI) has emerged as a promising technology for water treatment, with faradaic ECDI systems garnering significant attention due to their enhanced performance potential. This study focuses on the development of a highly stable and efficient, full-polymer (polypyrrole, PPy) ECDI system based on two key strategies. Firstly, dopant engineering, involving the design of dopants with a high charge/molecular weight () ratio and structural complexity, facilitating their effective integration into the polymer backbone. This ensures sustained contribution of strong negative charges, enhancing system performance, while the bulky dopant structure promotes stability during extended operation cycles. Secondly, operating the system with well-balanced charges between deionization and concentration processes significantly reduces irreversible reactions on the polymer, thereby mitigating dopant leakage. Implementing these strategies, the PPy(PSS)//PPy(ClO) (PSS: polystyrene sulfonate) system achieves a high salt removal capacity (SRC) of 48 mg g, an ultra-low energy consumption (EC) of 0.167 kW h kg, and remarkable stability, with 96% SRC retention after 104 cycles of operation. Additionally, this study provides a detailed degradation mechanism based on pre- and post-cycling analyses, offering valuable insights for the construction of highly stable ECDI systems with superior performance in water treatment applications.
PubMed: 38946305
DOI: 10.1039/d4mh00494a -
Journal of Immunotoxicology Dec 2024Per- and polyfluoroalkyl substances (PFAS) are anthropogenic organofluorine compounds that persist indefinitely in the environment and bioaccumulate throughout all...
Per- and polyfluoroalkyl substances (PFAS) are anthropogenic organofluorine compounds that persist indefinitely in the environment and bioaccumulate throughout all trophic levels. Biomonitoring efforts have detected multiple PFAS in the serum of most people. Immune suppression has been among the most consistent effects of exposure to PFAS. PFAS often co-occur as mixtures in the environment, however, few studies have examined immunosuppression of PFAS mixtures or determined whether PFAS exposure affects immune function in the context of infection. In this study, mixtures containing two or four different PFAS and a mouse model of infection with influenza A virus (IAV) were used to assess immunotoxicity of PFAS mixtures. PFAS were administered the drinking water as either a binary mixture of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) or quaternary mixture of PFOS, PFOA, perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). The results indicated that the binary mixture affected the T-cell response, while the quaternary mixture affected the B-cell response to infection. These findings indicate that the immunomodulatory effects of PFAS mixtures are not simply additive, and that the sensitivity of immune responses to PFAS varies by cell type and mixture. The study also demonstrates the importance of studying adverse health effects of PFAS mixtures.
Topics: Fluorocarbons; Animals; Mice; Influenza A virus; Alkanesulfonic Acids; Orthomyxoviridae Infections; Caprylates; Humans; Female; Mice, Inbred C57BL; Influenza, Human; Disease Models, Animal; T-Lymphocytes
PubMed: 38946256
DOI: 10.1080/1547691X.2024.2340495 -
Yakugaku Zasshi : Journal of the... 2024Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and is primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients with AML...
Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and is primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients with AML simultaneously administered VEN and CYP3A4 inhibitors require a more appropriate management of drug-drug interactions (DDIs). Here, we report two cases of patients with AML (54-year-old man and 22-year-old woman) administrated VEN and CYP3A4 inhibitors, such as posaconazole, cyclosporine, or danazol. In the first case, we evaluated the appropriateness of timing for adjusting VEN dosage subsequent to the cessation of posaconazole. Consequently, modifying the VEN dosage in conjunction with the cessation of Posaconazole simultaneously may result in elevated plasma VEN levels. In the second case, plasma VEN concentrations were markedly elevated when co-administered with several CYP3A4 inhibitors. Additionally, in vitro assays were conducted for reverse translational studies to analyze CYP3A4 inhibition. CYP3A4 inhibition by combinatorial administration of cyclosporine A and danazol was demonstrated in vitro, which potentially explains the increasing plasma VEN concentrations observed in clinical settings. Although the acquisition of therapeutic effects is a major priority for patients, frequent therapeutic drug monitoring and dosage adjustments considering DDIs would be important factors in chemotherapy.
Topics: Humans; Sulfonamides; Leukemia, Myeloid, Acute; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Male; Young Adult; Middle Aged; Bridged Bicyclo Compounds, Heterocyclic; Female; Drug Monitoring; Cytochrome P-450 CYP3A; Cyclosporine; Triazoles; Antineoplastic Agents
PubMed: 38945852
DOI: 10.1248/yakushi.24-00018