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Journal of Clinical and Experimental... 2024Limited data exist on the safety of early nasogastric (NG) feeding in patients with cirrhosis after endotherapy for variceal bleeding (VB). We studied the impact of...
BACKGROUND AND AIMS
Limited data exist on the safety of early nasogastric (NG) feeding in patients with cirrhosis after endotherapy for variceal bleeding (VB). We studied the impact of early NG tube feeding in these patients in this proof-of-concept open-label randomized controlled trial.
METHODS
Eligible patients with cirrhosis undergoing endotherapy for VB were randomized to receive either a liquid diet through a 14 Fr NG tube (commencing 1 h after endotherapy) (early feeding [EF] group) or sips of water and lemon water orally (standard-of-care [SOC] group) for total duration of 48 h. The primary outcome was 5-day rebleeding in both arms. Other outcomes included 5-day infection rate, hepatic encephalopathy during hospitalization, and 6-week mortality.
RESULTS
Eighty patients (Mean age: 41 ± 11.5 years; males [82.5%]; alcohol etiology [55%]) were included. Baseline median Child-Pugh and MELD scores were similar (CTP: 8 [IQR: 8-9] vs 9 [8-9.25]; = 0.47 and MELDNa: 13 [10.75-16.25] vs 15 [12-18.25]; = 0.16). The 5-day rebleeding rates in EF and SOC groups were 2.5% and 5%, respectively ( = 0.55), and non-inferiority or superiority of either could not be demonstrated. The incidence of infection (2.5% [EF] vs 2.5% [SOC]; = 1.00) and development of HE (5% [EF] vs 2.5% [SOC]; = 0.36) during hospitalization were comparable. The average daily calorie and protein intake in the EF group during the 48 h was 1318 ± 240 Kcals and 43.4 ± 9.2 g of proteins. No patient in the EF group had feed intolerance.
CONCLUSION
Early initiation of NG tube-based feeding after endotherapy in VB appears safe and well tolerated without the additional risk of rebleeding or encephalopathy.
PubMed: 38076376
DOI: 10.1016/j.jceh.2023.07.413 -
PloS One 2024The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US... (Observational Study)
Observational Study
Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study.
The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181-0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [-5.49-4.12]; LVDd, -0.55 [-3.24-2.15]; LVDd index, -0.25 [-1.92-1.43]; LVDs, -0.03 [-3.84-3.90]; LVDs index, -0.04 [-2.38-2.30]; heart rate, 1.62 [-3.07-6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol.
Topics: Humans; Adrenergic beta-Antagonists; Carvedilol; Heart Failure; Japan; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left
PubMed: 38452137
DOI: 10.1371/journal.pone.0299510 -
Journal of Materials Science. Materials... Jan 2024Extramedullary multiple myeloma (EMM) is defined as the presence of plasma cells outside the bone marrow of multiple myeloma patients, and its prognosis is poor....
Extramedullary multiple myeloma (EMM) is defined as the presence of plasma cells outside the bone marrow of multiple myeloma patients, and its prognosis is poor. High-dose chemotherapy with autologous stem cell transplantation, as a good option on early lines of therapy, has retained the survival benefit of youny EMM patients, but is intolerant for the majority of old patients because of drug cytotoxicity. To essentially address the intolerance above, we designed a CXCR4-PEG-CdTe-DOX (where CXCR4: chemokine receptor 4; PEG-CdTe: polyethylene glycol-modified cadmium telluride; DOX:doxorubicin) nanoplatform. First, CXCR4 is highly expressed in extramedullary plasma cells. Second, PEG-CdTe a drug carrier that controls drug release, can reduce adverse reactions, prolong drug (e.g, DOX) circulation time in the body, and form a targeting carrier after connecting antibodies. In vitro experiments showed CXCR4-PEG-CdTe-DOX facilitated intracellular drug accumulation through active CXCR4 targeting and released DOX into the microenvironment in a pH-controlled manner, enhancing the therapeutic efficacy and apoptosis rate of myeloma cells (U266). Therefore, targeted chemotherapy mediated by CXCR4-PEG-CdTe-DOX is a promising option for EMM treatment.
Topics: Humans; Cadmium Compounds; Multiple Myeloma; Tellurium; Hematopoietic Stem Cell Transplantation; Quantum Dots; Transplantation, Autologous; Doxorubicin; Drug Carriers; Polyethylene Glycols; Cell Line, Tumor; Drug Delivery Systems; Tumor Microenvironment; Receptors, CXCR4
PubMed: 38244066
DOI: 10.1007/s10856-023-06772-w -
Nutrients Apr 2024Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether...
Prenatal Choline Supplementation Improves Glucose Tolerance and Reduces Liver Fat Accumulation in Mouse Offspring Exposed to Ethanol during the Prenatal and Postnatal Periods.
Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether postnatal AE exacerbates metabolic deterioration resulting from prenatal AE. Choline is a semi-essential nutrient that has been demonstrated to mitigate the cognitive impairment of prenatal AE. This study investigated how maternal choline supplementation (CS) may modify the metabolic health of offspring with prenatal and postnatal AE (AE/AE). C57BL/6J female mice were fed either a Lieber-DeCarli diet with 1.4% ethanol between embryonic day (E) 9.5 and E17.5 or a control diet. Choline was supplemented with 4 × concentrations versus the control throughout pregnancy. At postnatal week 7, offspring mice were exposed to 1.4% ethanol for females and 3.9% ethanol for males for 4 weeks. AE/AE increased hepatic triglyceride accumulation in male offspring only, which was normalized by prenatal CS. Prenatal CS also improved glucose tolerance compared to AE/AE animals. AE/AE suppressed hepatic gene expression of peroxisome proliferator activated receptor alpha () and low-density lipoprotein receptor (), which regulate fatty acid catabolism and cholesterol reuptake, respectively, in male offspring. However, these changes were not rectified by prenatal CS. In conclusion, AE/AE led to an increased risk of steatosis and was partially prevented by prenatal CS in male mice.
Topics: Animals; Female; Pregnancy; Choline; Ethanol; Male; Dietary Supplements; Liver; Prenatal Exposure Delayed Effects; Mice, Inbred C57BL; Mice; Fatty Liver; Triglycerides; PPAR alpha; Receptors, LDL; Glucose Intolerance; Lipid Metabolism
PubMed: 38732511
DOI: 10.3390/nu16091264 -
Molecular Pharmaceutics Jun 2024With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have...
With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have shown that dibenzazepine (DBZ), a Notch inhibitor, could alleviate NASH development in a mouse model. However, low bioavailability, poor water solubility, and extrahepatic side effects restrict its clinical application. To overcome these barriers, we developed a reactive oxygen species (ROS)-sensitive nanoparticle based on the conjugation of bilirubin to poly(ethylene glycol) (PEG) chains, taking into account the overaccumulation of hepatic ROS in the pathologic state of nonalcoholic steatohepatitis (NASH). The PEGylated bilirubin can self-assemble into nanoparticles in an aqueous solution and encapsulate insoluble DBZ into its hydrophobic cavity. DBZ nanoparticles (DBZ Nps) had good stability, rapidly released DBZ in response to HO, and effectively scavenged intracellular ROS of hepatocytes. After systemic administration, DBZ Nps could accumulate in the liver of the NASH mice, extend persistence in circulation, and improve the bioavailability of DBZ. Furthermore, DBZ Nps significantly improved glucose intolerance, relieved hepatic lipid accumulation and inflammation, and ameliorated NASH-induced liver fibrosis. Additionally, DBZ Nps had no significant extrahepatic side effects. Taken together, our results highlight the potential of the ROS-sensitive DBZ nanoparticle as a promising therapeutic strategy for NASH.
Topics: Animals; Non-alcoholic Fatty Liver Disease; Reactive Oxygen Species; Mice; Nanoparticles; Lipogenesis; Mice, Inbred C57BL; Male; Liver; Receptors, Notch; Humans; Inflammation; Bilirubin; Polyethylene Glycols; Disease Models, Animal; Hepatocytes; Dibenzazepines
PubMed: 38751169
DOI: 10.1021/acs.molpharmaceut.4c00070 -
Zhonghua Jie He He Hu Xi Za Zhi =... Jun 2024Obstructive sleep apnea (OSA) shows sex differences in the pathophysiology, epidemiology, and clinical presentation. Women have different characteristics of OSA at...
Obstructive sleep apnea (OSA) shows sex differences in the pathophysiology, epidemiology, and clinical presentation. Women have different characteristics of OSA at different life stages. Based on 26 guidelines and consensus, 121 English literatures, and 24 Chinese literatures, the Sleep Disorder Group of Chinese Thoracic Society has drafted a consensus with multidisciplinary experts to summarize the epidemiology, clinical characteristics, diagnosis, treatment, and follow-up of OSA in women at different life stages, particularly issues related to OSA during pregnancy. The consensus is divided into four parts: epidemiology, diagnosis, treatment, and issues for pregnant women with OSA, with 34 recommendations covering 13 clinical issues. The aim was to improve the understanding and managements of OSA in women. What is the prevalence of OSA in women at different life stages?The prevalence of OSA varies among women at different life stages. Sex differences are not significant in childhood and adolescence. The prevalence of OSA in women of childbearing age is significantly lower than that in men. The prevalence of OSA increases during pregnancy due to changes in hormone levels and the influence of pregnancy physiology, as well as with gestational weeks. In postmenopausal women, the prevalence of OSA increases significantly, and the sex differences are no longer significant. What are the risk factors for OSA in women at different life stages?The risk factors for OSA in women at different life stages are not identical. (1) Childhood and adolescence: Tonsillar and adenoid hypertrophy, obesity, and craniofacial structural anomalies increase the risk of OSA; (2) Childbearing age: The prevalence of OSA in women is lower than in men. However, obesity, hypothyroidism, acromegaly, and polycystic ovary syndrome increase the risk of OSA, and these patients should be screened for OSA; (3) Pregnancy: hormonal effects, uterine enlargement, and weight changes increase the risk of OSA, especially in those with a history of snoring or OSA before pregnancy; (4) Perimenopausal and post-menopausal periods: Decreased levels of estrogen/progesterone reduce the protective effects on the upper airways, and increase the risk of OSA. Menopause is an important risk factor for OSA in women. What are the harms of OSA in women?OSA is an independent risk factor for diseases such as hypertension, cardiovascular and cerebrovascular diseases, metabolic disorders, emotional and cognitive impairments, and malignant tumors in women. OSA during pregnancy has several adverse effects on maternal and infant health, and is associated with increased risks of preeclampsia, hypertensive disorders complicating pregnancy (HDP), gestational diabetes mellitus (HDM), premature birth, neonatal asphyxia, fetal growth restriction, . What are the clinical symptoms and physical signs of OSA in women?The symptoms of OSA in women are different from those in men. Attention should be paid to whether women snore and the frequency of snoring, especially among postmenopausal and obese women. The atypical symptoms of OSA, including insomnia, daytime fatigue, morning headache, anxiety and nightmares, should not be ignored, especially in postmenopausal, obese, and pregnant women. When should women be screened for OSA?(1) Postmenopausal and pregnant women, as well as women with a first-degree relative with OSA. It should be noted that the clinical symptoms of OSA in women are not typical; (2) Women with polycystic ovary syndrome, hypothyroidism, and acromegaly; (3) Women engaged in various occupations, including driving and working at heights. How to screen OSA in women?Many screening tools and questionnaires can be used to screen for OSA, but should not be used to diagnose OSA in the absence of objective sleep tests. (1) Questionnaires and screening tools: The STOP-Bang questionnaire targeting the general population has higher sensitivity than Berlin Questionnaire (BQ), Epworth Sleepiness Scale (ESS), and others. STOP Bang≥3 points combined with ESS can further improve its specificity and can be used for OSA screening in women. However, the questionnaire has poor sensitivity for female OSA. Type Ⅳ monitoring devices can be used for OSA screening in women with a weak recommendation; (2) PSG is the gold standard for diagnosis. Type Ⅱ or Ⅲ portable monitoring (PM) devices are recommended for the diagnosis of OSA in women in the following conditions: 1) Diagnosis of high-risk OSA patients without complex comorbidities; 2) OSA patients who are immobile or critically ill and unable to undergo PSG monitoring in a sleep center; 3) Diagnosis of perioperative OSA patients; 4) Pregnant women with high suspicion of OSA. How to diagnose OSA in women?The diagnostic and grading criteria for adult non-pregnant women with OSA are the same as the diagnostic criteria for adult OSA; for diagnosis and grading of OSA in pregnant women, see "Section 4: OSA in Pregnancy". How to treat OSA in women?For all the OSA patients with varying degrees of severity in women, the general treatment can be applied: weight loss, dietary control, exercise, position therapy, reduction of alcohol intake, and cautious use of sedative and hypnotic drugs. Medical costs and the risk of comorbidities with OSA in women are higher than those in men. Therefore, OSA patients in women should be promptly evaluated and treated. How to optimize non-invasive positive pressure ventilation (NPPV) treatment and improve compliance for OSA patients in women?(1) NPPV is the first-line treatment for moderate to severe OSA in women. It can relieve upper airway obstruction, eliminate sleep hypoxia, improve sleep quality and quality of life, and reduce the incidence of related complications and mortality; (2) To improve compliance with NPPV treatment, behavioral interventions and patient education are recommended. Selecting an appropriate human-machine interface, improving the humidification effect, promptly handling adverse reactions, and applying remote medical models may improve the compliance. What are the other options for OSA treatment in women?Other treatment methods include oral appliances, upper airway surgery, and sublingual nerve stimulation therapy, which have moderate therapeutic effects in women. Postmenopausal hormone therapy (MHT) in women has a certain therapeutic effect on OSA, but its safety needs further evaluation. What is follow-up evaluation for OSA in women?(1) Follow-up every 6 months or 1 year after receiving NPPV treatment; (2) PSG should be rechecked at the 3rd and 6th months after surgical treatment to evaluate the therapeutic effects. For patients with poor therapeutic effects after surgery, it is recommended to use treatments such as NPPV; (3) PSG should be rechecked at the 3rd and 6th months after oral appliance treatment. Oral appliances should be adjusted as needed to consolidate long-term efficacy, or switched to a treatment such as NPPV; (4) During follow-up, attention should be paid to the improvement of apnea hypopnea index(AHI), symptoms, and side effects; (5) It is recommended that NPPV treatment be remotely managed via the internet, which can provide high-quality and comprehensive sleep care; (6) Follow-up of OSA during pregnancy can be found in "Section 4: OSA in Pregnancy ". How to diagnose and evaluate OSA during pregnancy?OSA during pregnancy has adverse effects on maternal and infant outcomes. It is recommended that high-risk pregnant women be screened and diagnosed for OSA during pregnancy management and healthcare.(1) Screening of the high-risk population: Individuals who meet any of the following criteria are considered at high risk for OSA during pregnancy. 1) Symptoms: snoring during sleep, arousal, headache in the morning, insomnia, depression, excessive daytime sleepiness, and fatigue; 2) Pregnant women over 35 years old; 3) Physical signs: weight exceeding standard body weight by 20% or more, BMI≥28 kg/m, and neck circumference>40 cm; anatomical abnormalities of the upper airways, such as nasal obstruction, tonsil hypertrophy, and mandibular retrognathia, .; 4) Combined internal medicine diseases, such as refractory hypertension, unknown arrhythmia, chronic congestive heart failure, refractory diabetes and insulin resistance, refractory asthma, hypothyroidism, primary aldosteronism; 5) Those with obstetric related diseases, such as preeclampsia, HDP, GDM, and intrauterine growth restriction of the fetus, and with symptoms of chest tightness and apnea that cannot be explained by other factors, and with previous history of gestational OSA or family history.(2) Screening time: There is currently no strong evidence to support the recommendation for optimal screening time. Given the adverse effects of OSA on mothers and infants, it is recommended that high-risk individuals of OSA be screened for OSA between12 and 18 weeks of pregnancy.(3) Screening tools: The main manifestations of OSA in pregnant women are insomnia and poor sleep quality, whereas daytime drowsiness is often not severe. Various sleep questionnaires and models for OSA in pregnancy have poor sensitivity and specificity. Type Ⅳ and consumer-level monitoring devices are lack of sufficient clinical validation. It is recommended that the results of the above screening tools should only have an indicative role in the diagnosis of OSA during pregnancy.(4) Diagnostic tools: PSG is the gold standard for the diagnosis of OSA in pregnancy. PM may be the first choice diagnostic technique for OSA in pregnancy, and Type Ⅲ monitoring devices are the most commonly used devices.(5) Diagnostic criteria: Diagnosis of OSA during pregnancy should be based on symptoms, signs, and PSG or PM monitoring results. Diagnostic criteria for OSA during pregnancy are as follows: 1) PSG or PM monitoring shows AHI≥5 times/h with symptoms or signs of OSA in women, or with related complications (such as diagnosed hypertension, emotional disorders, unexplained arrhythmias, chronic congestive heart failure, HDP, HDM, intrauterine growth restriction that cannot be explained by other factors, chest tightness and apnea excluding other reasons), or with previous history of OSA or family history of OSA; 2) PSG or PM monitoring shows AHI≥10 times/h in those with less daytime drowsiness (ESS≤9 points). How to manage OSA during pregnancy?(1) Once OSA is diagnosed during pregnancy, personalized treatment plans from pregnancy to birth should be developed through collaborative discussions between sleep center professionals, obstetricians, pregnant women, and their families. Multidisciplinary collaboration among anaesthesia, neonatology, and critical care medicine may be required in some cases. A comprehensive management approach should be adopted based on the patient's condition, which includes strengthening weight management, positioning treatment, NPPV treatment, oral appliances, and management of maternal and infant complications; (2) Considering the Regarding continuous weight gain during pregnancy, APAP treatment is more appropriate mode for pregnant women with OSA; (3) Oral appliances are suitable for patients with snoring or mild to moderate OSA, especially those with combined mandibular retraction or NPPV intolerance. However, oral appliances are not recommended as the first-line treatment; (4) It is not recommended to use surgical methods to treat OSA during pregnancy; (5) Follow-up and evaluation: Patients' conditions should be re-evaluated and treatment plans should be adjusted at around 24 weeks of pregnancy. Postpartum PSG or PM monitoring should be repeated to assess the need for continued treatment after delivery.
Topics: Humans; Sleep Apnea, Obstructive; Female; Pregnancy; Pregnancy Complications; Consensus
PubMed: 38858201
DOI: 10.3760/cma.j.cn112147-20240206-00072