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Introduction: This study aims to answer the question of whether adding mobile cone-beam computed tomography (mCBCT) imaging to shape-sensing robotic-assisted bronchoscopy (ssRAB) translates into a quantifiable improvement in the tool-lesion relationship. Methods: Data from 102 peripheral lung lesions with ≥2 sequential mCBCT orbital spins and from 436 lesions with 0-1 spins were prospectively captured and retrospectively analysed. The primary outcome was the tool-lesion relationship status across the first and the last mCBCT spins. Secondary outcomes included 1) the change in distance between the tip of the sampling tool and the centre of the lesion between the first and the last spins and 2) the per-lesion diagnostic yield. Results: Compared to lesions requiring 0-1 spins, lesions requiring ≥2 spins were smaller and had unfavourable bronchus sign and intra-operative sonographic view. On the first spin, 54 lesions (53%) were designated as non-tool-in-lesion (non-TIL) while 48 lesions (47%) were designated as TIL. Of the 54 initially non-TIL cases, 49 (90%) were converted to TIL status by the last spin. Overall, on the last spin, 96 out of 102 lesions (94%) were defined as TIL and six out of 102 lesions (6%) were defined as non-TIL (p<0.0001). The mean distance between the tool and the centre of the lesion decreased from 10.4 to 6.6â mm between the first and last spins (p<0.0001). The overall diagnostic yield was 77%. Conclusion: Targeting traditionally challenging lung lesions, intra-operative volumetric imaging allowed for the conversion of 90% of non-TIL status to TIL. Guidance with mCBCT resulted in a significant decrease in the distance between the tip of the needle to lesion centre.
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Objective: Uremic pruritus (UP) is a prevalent and troublesome condition affecting individuals with end-stage renal failure, which results in intense pruritus, depression, as well as poor quality of sleep, significantly impacting their quality of life. According to previous studies, acupuncture and acupoint stimulation have been shown to provide additional benefits in treating UP in dialysis patients. In addition, using acupoints combination may yield superior effectiveness compared to utilizing a singular acupoint. To investigate the potential correlations between acupoint combinations, an association-rule analysis was employed. Materials and Methods: Apriori algorithms stand out as highly potent techniques for identifying associations in databases; this study utilized an association rule mining to examine the association rules of key acupoint groupings that could be employed for treating UP. Results: The analysis utilized information derived from the meta-analysis encompassing 40 randomized controlled trials that used acupuncture to treat UP. In total, 64 acupoints were analyzed, and 71 association rules were found. The following acupoint combinations: Auricular shenmen (TF4), Quchi (LI11), and Geshu (BL17); Auricular heart (Extra14), Sanyinjiao (SP6), and Auricular lung (CO14); and Auricular heart (Extra14), Xuehai (SP10), and Auricular lung (CO14) showed the strongest associations. Conclusion: Acupoints involving Auricular shenmen (TF4), Quchi (LI11), Geshu (BL17), Auricular heart (Extra14), Sanyinjiao (SP6), Auricular lung (CO14), and Xuehai (SP10) can be regarded as the core combination of acupuncture points for managing UP.
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CONTEXT: Patients with Cushing's disease (CD) face challenges living with and receiving appropriate care for this rare, chronic condition. Even with successful treatment, many patients experience ongoing symptoms and impaired quality of life (QoL). Different perspectives and expectations between patients and healthcare providers (HCPs) may also impair well-being. OBJECTIVE: To examine differences in perspectives on living with CD between patients and HCPs, and to compare care goals and unmet needs. DESIGN: Memorial Sloan Kettering Pituitary Center established an annual pituitary symposium for pituitary patients and HCPs. Through anonymous pre-program surveys distributed at the 2020 and 2022 symposia, patients and HCPs answered questions related to their own sense, or perception of their patients' sense, of hope, choice, and loneliness in the context of living with CD. PARTICIPANTS: From 655 participants over two educational events, 46 patients with CD and 116 HCPs were included. Median age of both groups was 51 years. 78.3% of the patients were female vs. 53.0% of the HCPs. RESULTS: More patients than HCPs reported they had no choices in their treatment (21.7% vs. 0.9%, P < 0.001). More patients reported feeling alone living with CD than HCPs' perception of such (60.9% vs. 45.5%, P = 0.08). The most common personal care goal concern for patients was 'QoL/mental health,' vs. 'medical therapies/tumor control' for HCPs. The most common CD unmet need reported by patients was 'education/awareness' vs. 'medical therapies/tumor control' for HCPs. CONCLUSIONS: CD patients experience long term symptoms and impaired QoL which may in part be due to a perception of lack of effective treatment options and little hope for improvement. Communicating experiences and care goals may improve long term outcomes for CD patients.
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Neoplasias , Hipersecreção Hipofisária de ACTH , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Hipersecreção Hipofisária de ACTH/terapia , Hipersecreção Hipofisária de ACTH/diagnóstico , Qualidade de Vida/psicologia , Estudos Longitudinais , MotivaçãoRESUMO
Cardiovascular disease (CVD) and its risk factors seem to be linked with deteriorated graft function and persists as the major cause of mortality in kidney transplant recipients (KTRs). Diet quality is associated with CVD prevention in the healthy population, however, less study focuses on KTRs. The study aimed to determine the association between diet quality indices and lipid profile abnormalities as risk factors for CVD in KTRs. This prospective study enrolled 106 KTRs who had functioning allografts from September 2016. Lipid profiles included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) and were based on the National Cholesterol Education Program Adult Treatment Panel III recommendations. Three-day dietary data were collected by a well-trained registered dietitian. The Alternative Healthy Eating Index-Taiwan (AHEI-Taiwan), Alternative Healthy Eating Index-2010 (AHEI-2010), and Healthy Eating Index-2015 (HEI-2015) scores were calculated and divided into quartiles and compared accordingly. KTRs' mean LDL-C, HDL-C, TC, and TG levels were 119.8 ± 36.6 mg/dL, 52.0 ± 17.9 mg/dL, 205.8 ± 43.9 mg/dL, and 160.2 ± 121.6 mg/dL, respectively. Compared with the lowest quartile, only the highest quartile of AHEI-Taiwan had lower TC and LDL-C levels. After adjustment for age, gender, energy, Charlson comorbidity index, transplant duration, and dialysis duration, logistic regression analysis revealed that the highest quartile of AHEI-Taiwan had 82% (odds ratio [OR], 0.18; 95% confidence interval [CI] 0.04-0.72, p < 0.05) lower odds of high TC and 88% (OR 0.12; 95% CI 0.03-0.58, p < 0.05) lower odds of high LDL-C, and the highest quartile of HEI-2015 had 77% (OR 0.23; 95% CI 0.05-0.95, p < 0.05) lower odds of high LDL-C. Higher adherence to a healthy diet as per AHEI-Taiwan and HEI-2015 guidelines associated with lower risk of lipid profile abnormalities in KTRs.
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Doenças Cardiovasculares , Transplante de Rim , Adulto , Humanos , LDL-Colesterol , Estudos Prospectivos , Transplante de Rim/efeitos adversos , Diálise Renal , Dieta , Fatores de Risco , Triglicerídeos , Colesterol , HDL-Colesterol , Doenças Cardiovasculares/etiologiaRESUMO
Several dietary indices assess the impacts of the Dietary Approaches to Stop Hypertension (DASH) diet on health outcomes. We explored DASH adherence and renal function among 85 Taiwanese renal transplant recipients (RTRs) in a cross-sectional study. Data collection included demographics, routine laboratory data, and 3-day dietary records. Three separate DASH indices, that defined by Camões (based on nine nutrients), that defined by Fung (using seven food groups and sodium), and that modified by Fung (as above but separated for men and women) were used. Renal function was ascertained through the estimated glomerular filtration rate (eGFR) from patients' medical records. Participants' mean age was 49.7 ± 12.6 years and eGFR was 54.71 ± 21.48 mL/min/1.73 m2. The three established DASH diet indices displayed significant correlations (r = 0.50-0.91) and indicated the nutritional adequacy of the diet. Multiple linear regressions indicated a significant positive association between higher DASH scores for each index and increased eGFR. In addition, RTRs in the highest DASH score tertile had higher eGFR rates than those in the lowest tertile, regardless of confounding variables. Adherence to a DASH-style diet correlated with better renal function among RTRs. Educating RTRs about the DASH diet may prevent graft function deterioration.
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The phase of mild cognitive impairment (MCI) holds significant importance for postponing the onset of dementia. Therefore, MCI has become a central focus in research related to dementia prevention. The purpose of this study was to investigate the dietary intake and dietary patterns of MCI patients in Taiwan. In total, 40 subjects were enrolled in this cross-sectional study that was conducted from July 2019 to September 2021 at the Linkou Chang Gung Memorial Hospital. The results of the clinical dementia rating (CDR) and mini-mental state examination (MMSE) were obtained from medical records. Participants were divided into two groups: a healthy group (MMSE ≥ 26 points, CDR = 0) and an MCI group (MMSE ≥ 26 points, CDR = 0.5). Results indicated that the MCI group had significantly higher copper and lower low-fat meat intake compared to the healthy group. Furthermore, the high MIND (Mediterranean dietary approaches to stop hypertension intervention for neurodegenerative delay) diet score represented a lower risk of MCI. After adjusting for age, gender, diabetes mellitus, hypertension, and calorie intake in the multivariate regression analysis, calcium and fruit intake levels were positively associated with the MMSE, whereas low-fat meat intake was negatively associated with the CDR. In conclusion, the prevalence of MCI demonstrated a close correlation with nutrient intake, including copper and calcium. Furthermore, a MIND diet, particularly one high in n-3 polyunsaturated fatty acids, might be useful for preventing MCI. However, more extensive research with larger populations is needed to confirm this potential.
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Disfunção Cognitiva , Demência , Hipertensão , Humanos , Cálcio , Cobre , Estudos Transversais , Ingestão de Alimentos , Cálcio da Dieta , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/prevenção & controleRESUMO
BACKGROUND: Cancer therapy-related cardiac dysfunction (CTRCD) is an important treatment-limiting toxicity for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer that adversely affects cancer and cardiovascular outcomes. Easy-to-use tools that incorporate readily accessible clinical variables for individual estimation of CTRCD risk are needed. METHODS AND RESULTS: From 2004 to 2013, 1440 patients with stage I to III HER2-positive breast cancer treated with trastuzumab-based therapy were identified. A multivariable Cox proportional hazards model was constructed to identify risk factors for CTRCD and included the 1377 patients in whom data were complete. Nine clinical variables, including age, race, body mass index, left ventricular ejection fraction, systolic blood pressure, coronary artery disease, diabetes, arrhythmia, and anthracycline exposure were built into a nomogram estimating risk of CTRCD at 1 year. The nomogram was validated for calibration and discrimination using bootstrap resampling. A total of 177 CTRCD events occurred within 1 year of HER2-targeted treatment. The nomogram for prediction of 1-year CTRCD probability demonstrated good discrimination, with a concordance index of 0.687. The predicted and observed probabilities of CTRCD were similar, demonstrating good model calibration. CONCLUSIONS: A nomogram composed of 9 readily accessible clinical variables provides an individualized 1-year risk estimate of CTRCD among women with HER2-positive breast cancer receiving HER2-targeted therapy. This nomogram represents a simple-to-use tool for clinicians and patients that can inform clinical decision-making on breast cancer treatment options, optimal frequency of cardiac surveillance, and role of cardioprotective strategies.
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Neoplasias da Mama , Cardiopatias , Humanos , Feminino , Neoplasias da Mama/metabolismo , Nomogramas , Volume Sistólico , Função Ventricular Esquerda , Cardiotoxicidade/etiologiaRESUMO
BACKGROUND: Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI. PATIENTS AND METHODS: A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020. ICI-related EPI patients had steatorrhea with or without abdominal discomfort or weight loss, started pancrelipase after initiation of ICI, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, race, sex, cancer type, and year of ICI start. RESULTS: Of 12 905 ICI-treated patients, 23 patients developed ICI-related EPI and were matched to 46 controls. The incidence rate of EPI was 1.18 cases per 1000 person-years and the median onset of EPI was 390 days after the first dose of ICI. All 23 (100%) EPI cases had steatorrhea that improved with pancrelipase, 12 (52.2%) had weight loss, and 9 (39.1%) had abdominal discomfort; none had changes of chronic pancreatitis on imaging. Nine (39%) EPI patients had episodes of clinical acute pancreatitis preceding the onset of EPI, compared to 1 (2%) control (OR 18.0 (2.5-789.0), P < .001). Finally, the EPI group exhibited higher proportions of new or worsening hyperglycemia after ICI exposure compared with the control group (9 (39.1%) vs. 3 (6.5%), P < .01). CONCLUSION: ICI-related EPI is a rare but clinically significant event that should be considered in patients with late onset diarrhea after ICI treatment and often is associated with development of hyperglycemia and diabetes.
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Insuficiência Pancreática Exócrina , Hiperglicemia , Pancreatite , Esteatorreia , Humanos , Pancrelipase/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Esteatorreia/induzido quimicamente , Esteatorreia/complicações , Esteatorreia/tratamento farmacológico , Estudos Retrospectivos , Estudos de Casos e Controles , Doença Aguda , Pancreatite/induzido quimicamente , Pancreatite/complicações , Pancreatite/tratamento farmacológico , Insuficiência Pancreática Exócrina/induzido quimicamente , Insuficiência Pancreática Exócrina/epidemiologia , Insuficiência Pancreática Exócrina/tratamento farmacológico , Hiperglicemia/induzido quimicamente , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Redução de PesoRESUMO
BACKGROUND: Various dietary quality indices demonstrate that a higher dietary quality score is associated with a reduced risk of several chronic diseases. However, creating an index tailored to the national population is crucial. The study investigated the association between the Alternative Healthy Eating Index-Taiwan (AHEI-Taiwan) and graft dysfunction in Taiwanese renal transplant recipients (RTRs). METHODS: A prospective cohort study recruited 102 RTRs with a functioning allograft without acute rejection in the last 3 months from September 2016 to June 2018. Laboratory data were obtained from the medical records of patients. Graft dysfunction was indicated by an estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 in accordance with the Kidney Disease Outcomes Quality Initiative guideline. The dietary quality index AHEI-Taiwan was adapted from the AHEI based on Taiwanese dietary recommendations. RESULTS: Mean age, renal transplant time, and eGFR were 48.9 ± 12.8 years, 8.5 ± 5.8 years, and 54.9 ± 17.8 mL/min per 1.73 m2, respectively, in 102 RTRs. The RTRs with the highest quartile of AHEI-Taiwan scores were older and had a higher eGFR. Logistic regression analysis adjusted for age, sex, calories, Charlson comorbidity index, transplant time, and dialysis time showed that the highest quartile of the AHEI-Taiwan was associated with an 88% (odds ratio, 0.12; 95% CI, 0.03-0.59, P < .01) lower risk of graft dysfunction. CONCLUSION: A high AHEI-Taiwan score was associated with a reduced risk of graft dysfunction in Taiwanese RTRs.
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Transplante de Rim , Humanos , Adulto , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Dieta Saudável , Taiwan , Estudos Prospectivos , Diálise Renal , TransplantadosRESUMO
The scarcity of dietary guidance for renal transplant recipients (RTRs) raises concerns regarding obesity and associated comorbidities, including impaired renal function. This two-stage cross-sectional study examined longitudinal changes in dietary nutrient intake in the same individuals over a 5-year interval. This study involved two stages: T1 (September 2016 to June 2018) and T2 (July 2022 to August 2023). The average duration between the two data collection stages was 6.17 ± 0.42 (range 5.20-6.87) years. The study included 227 RTRs with an average age and time since transplant of 49.97 ± 12.39 and 9.22 ± 7.91 years, respectively. Of the 35 patients who participated in both phases, fewer than half met the recommended intakes for energy, dietary fiber, and most vitamins and minerals, as set in the Dietary Reference Intakes (DRIs) or by the Dietitian Association Australia (DAA). Over half exceeded the DRI recommended intake for total protein, and more than 80% of the protein consumed per kilogram of body weight exceeded the DAA's recommendations. In the T2 stage, the RTRs had a significantly higher blood urea nitrogen level, lower albumin level, and estimated glomerular filtration rate. These findings indicate that deteriorating dietary intake in RTRs can adversely affect their nutritional status and transplanted kidney function over a 5-year period.
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Transplante de Rim , Humanos , Taxa de Filtração Glomerular , Estudos Transversais , Ingestão de Alimentos , RimRESUMO
Background: Uremic pruritus causes sleep disturbances, poor quality of life, and increased morbidity in patients with chronic kidney disease. Acupuncture has been shown to improve uremic pruritus. There is limited evidence of the efficacy of traditional Chinese therapies. We conducted a systematic review and meta-analysis to evaluate the efficacy of acupoint stimulation therapy in patients with uremic pruritus. Methods: A systematic search of seven databases (up to Sep 2022) was conducted for randomized controlled trials that evaluated the clinical efficacy of acupuncture, acupressure, auricular acupressure, acupoint injection, acupoint thermal therapy, acupoint sticking therapy, or transcutaneous electrical acupoint stimulation in the treatment of patients with uremic pruritus. Two reviewers selected eligible articles for inclusion in the meta-analysis and evaluated the risk of bias via Cochrane Collaboration. The results of pruritus assessments and uremic pruritus-related laboratory parameters were analyzed. Results: Forty trials published between 2002 and 2022, including a total of 2,735 participants, were identified for inclusion in the meta-analysis. The effective rates for acupuncture, auricular acupressure, and the combination of acupoint injection and acupoint massage were significantly greater in patients with uremic pruritus compared to the control group. The levels of serum BUN, PTH, and histamine levels were significantly lower vs. control group. Conclusions: Acupuncture, auricular acupressure, and the combination of acupoint injection and acupoint massage seem to be effective in improving uremic pruritus in patients with chronic kidney disease. However, further investigation of these potential treatments is now warranted in larger patient populations and over a longer time frame. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022354585, identifier: PROSPERO CRD42022354585.
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Background: Candidemia is associated with morbidity and mortality in cancer patients. We analyzed adherence to the 2016 Infectious Diseases Society of America (IDSA) candidiasis guidelines and the reasons for guideline nonadherence. We also investigated whether matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) improved time to effective antifungal therapy compared with historical data (median, 43.2â hours). Methods: Cancer patients with candidemia between 1/1/17 and 12/31/19 were included. Adherence to 7 individual IDSA guideline components was assessed. Composite IDSA guideline adherence (defined as meeting ≥6 guideline components) was also assessed. Charts were reviewed to examine reasons for noncompliance. Results: Of 157 patients with candidemia, 150 (95.5%) had infectious disease (ID) consultation. The median total time from blood culture collection to antifungal initiation was 42.1â hours. Excluding 39 patients with short treatment due to death, there was 100% adherence with surveillance blood cultures, followed by antifungal susceptibility testing (117/118, 99.2%), initial appropriate therapy (117/118, 99.2%), antifungal duration (110/118, 93.2%), line removal (82/91, 90.1%), eye exams (93/118, 78.8%), and step-down therapy (69/94, 73.4%). A quarter (30/118) did not meet composite IDSA guideline adherence. Univariate logistic regression suggested a relationship between poor cancer prognosis and incomplete adherence to the 2016 IDSA candidiasis guidelines (odds ratio, 8.6; 95% CI, 1.6-47). Conclusions: The addition of MALDI-TOF did not shorten time to effective antifungal therapy. Nearly all patients were seen by ID for candidemia. Poor cancer prognosis was a common factor for incomplete composite adherence to the 2016 IDSA candidiasis guidelines.
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Uremic pruritus is a disturbing and refractory symptom in patients with advanced chronic kidney disease. Chinese herbal medicine has been reported to alleviate uremic pruritus. To investigate the effects of Chinese herbal medicine, we conducted a systematic review and meta-analysis on patients with uremic pruritus. We searched databases (prior to 3 May 2022) for randomized controlled trials on the effects of Chinese herbal medicine in treating uremic pruritus. Our meta-analysis included 3311 patients from 50 randomized controlled trials. In patients with uremic pruritus, adjunctive Chinese herbal medicine significantly improved overall effectiveness (risk ratio 1.29, 95% CI 1.23 to 1.35), quality of life, renal function, reduced pruritus score, and inflammatory biomarkers compared to control groups with hemodialysis alone or with anti-pruritic treatments. Chinese herbal medicine treatment showed a time-dependent tendency in improving the visual analog scale of dialysis patients. Compared to control groups, no significantly higher risk of adverse events in patients taking Chinese herbal medicine (risk ratio 0.60, 95% CI 0.22 to 1.63). Chinese herbal medicine appears to be effective and safe in complementing the treatment of patients with uremic pruritus.
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Acetaminophen is among the most widely used analgesics; however, the proportion and mechanism of transplacental transfer of unbound acetaminophen with actual pharmacological activity remain unknown. Our hypothesis is that acetaminophen gradually penetrates the blood-placenta barrier to reach the fetus. A multiple microdialysis coupled to liquid chromatography with photodiode array detection method was developed to monitor acetaminophen levels in the maternal blood, placenta, fetus, and amniotic fluid of a pregnant rat and investigate this hypothesis. The pharmacokinetic data indicates that acetaminophen exhibits a nonlinear behavior in the maternal blood within the dosage regimen of 100 and 300 mg/kg. In addition, acetaminophen penetrates the placenta, fetus, and amniotic fluid during treatment. The transplacental transfer ratio represented by the area under the concentration curve (AUC) ratio for the conceptus (the collective term for the fetus, placenta, and amniotic fluid) and maternal blood (AUCtissue/AUCblood) was approximately 11-23 % after acetaminophen (100 and 300 mg/kg) administration. However, the transporter of multidrug resistance-associated protein (MRP) inhibitor MK-571 did not significantly change the transplacental transfer ratio. This basic study provides constructive information for the clinical application of acetaminophen in pregnant women.
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Acetaminofen , Troca Materno-Fetal , Acetaminofen/metabolismo , Líquido Amniótico/metabolismo , Animais , Cromatografia Líquida , Feminino , Feto/metabolismo , Humanos , Placenta/metabolismo , Gravidez , RatosRESUMO
Background: The incidence of ischemic stroke (IS) is much higher among patients with chronic kidney disease (CKD) compared to the general population. Few studies have evaluated the association between the risk of IS and the use of Chinese herbal medicine (CHM) in patients with CKD. We aimed to investigate the risk of IS among patients with CKD using CHM as add-on therapy. Methods: We conducted a retrospective cohort study based on Taiwan's National Health Insurance Research Database to assess 21,641 patients with newly diagnosed CKD between 2003 and 2012. Patients were classified as either the CHM (n = 3,149) or the non-CHM group (n = 3,149) based on whether they used CHM after first diagnosis of CKD. We used the proportional subdistribution hazards model of Fine and Gray to examine the hazard ratio (HR) of IS in propensity-score matched samples at a ratio of 1:1 for two groups. Results: The risk of IS was significantly reduced in the CHM group (adjusted HR [aHR]: 0.58, 95% confidence interval [CI]: 0.48-0.70) compared with the non-CHM group. Those who used CHM for >180 days had an even lower risk of IS than those in the non-CHM group (aHR: 0.51, 95% CI: 0.41-0.63). Additionally, frequently prescribed formulae, such as Ji-Sheng-Shen-Qi-Wan, Liu-Wei-Di-Huang-Wan, and Zhen-Wu-Tang were associated with a 30%-50% reduced risk of IS. Conclusion: Our results suggest that patients with CKD who used CHM as add-on therapy had a lower hazard of IS than those in the non-CHM group, especially for patients taking CHM for >180 days. Further experimental studies are required to clarify the causal relationship.
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ETHNOPHARMACOLOGICAL RELEVANCE: Papaveris Pericarpium, which is the dried husk of Papaver somniferum L., has been used as a phytomedicine to relieve cough, diarrhea and pain. The alkaloid codeine contained therein via biotransformation converts to morphine and potentially produces addictive and toxic effects. Due to the healthy concern for a pregnant woman, our hypothesis is that codeine and its metabolites can penetrate the placental barrier to reach the foetus and amniotic fluid, and these processes may be modulated by the transporter. AIM OF THE STUDY: Because codeine is also considered a prodrug of morphine, it has a good analgesic effect. It is often used by pregnant women but may expose the foetus to the risk of morphine harm. The aim of this study is to investigate the metabolic rate, distribution and transplacental transfer mechanism of codeine and its metabolites morphine and morphine-3-glucuronide (M3G) in pregnant rats and to assess the risk of medication for pregnant women. MATERIALS AND METHODS: Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with a microdialysis system was developed to monitor codeine, morphine and M3G in multiple sites of maternal blood, placenta, foetus and amniotic fluid after codeine administration. A compartmental model was used to calculate the pharmacokinetic parameters of codeine in blood after codeine administration (10 mg/kg, i.v.). The area under the concentration (AUC) ratio of AUCmetabolite/AUCcodeine and AUCtissue/AUCblood was used to represent the metabolic biotransformation ratio and the drug from blood-to-tissue transfer ratio, respectively. RESULTS: The pharmacokinetic results demonstrated that codeine fit well with a two-compartment model and went through rapid metabolism to morphine and M3G in pregnant rats after codeine administration (10 mg/kg, i.v.). The biotransformation ratios of AUCmorphine/AUCcodeine, AUCM3G/AUCmorphine and AUCM3G/AUCcodeine were 0.12 ± 0.03, 54.45 ± 20.61 and 6.53 ± 2.47, respectively, after codeine administration (10 mg/kg, i.v.), which suggested that codeine was easily metabolized into M3G through morphine. The tissue distribution results demonstrated that all of the analytes penetrated into the foetus through the placenta; however, the blood-to-tissue transfer ratio (AUCtissue/AUCblood) of morphine and M3G was relatively lower than that of codeine after codeine administration (10 mg/kg, i.v.), which suggested that the blood-placenta barrier blocks the penetration of morphine and M3G into the foetus. Thus, the tissue transfer of morphine in the placenta and foetus was significantly enhanced by treatment with corticosterone, an inhibitor of organic cation transporter (OCT). CONCLUSION: Based on microdialysis coupled to a validated UHPLC-MS/MS system, the pharmacokinetics and metabolic biotransformation of codeine and its metabolites were analyzed and clarified. The potential mechanism of morphine placental transfer was modulated by OCT transporters.
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Codeína , Papaver , Animais , Codeína/análise , Feminino , Humanos , Morfina , Derivados da Morfina/análise , Derivados da Morfina/metabolismo , Placenta/química , Placenta/metabolismo , Gravidez , Ratos , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Remdesivir was the first prodrug approved to treat coronavirus disease 2019 (COVID-19) and has the potential to be used during pregnancy. However, it is not known whether remdesivir and its main metabolite, GS-441524 have the potential to cross the blood-placental barrier. We hypothesize that remdesivir and predominant metabolite GS-441524may cross the blood-placental barrier to reach the embryo tissues. METHODS: To test this hypothesis, ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) coupled with multisite microdialysis was used to monitor the levels of remdesivir and the nucleoside analogue GS-441524 in the maternal blood, fetus, placenta, and amniotic fluid of pregnant Sprague-Dawley rats. The transplacental transfer was evaluated using the pharmacokinetic parameters of AUC and mother-to-fetus transfer ratio (AUCfetus/AUCmother). FINDINGS: Our in-vivo results show that remdesivir is rapidly biotransformed into GS-441524 in the maternal blood, which then readily crossed the placenta with a mother-to-fetus transfer ratio of 0.51 ± 0.18. The Cmax and AUClast values of GS-441524 followed the order: maternal blood > amniotic fluid > fetus > placenta in rats. INTERPRETATION: While remdesivir does not directly cross into the fetus, however, its main metabolite, GS-441524 readily crosses the placenta and can reside there for at least 4 hours as shown in the pregnant Sprague-Dawley rat model. These findings suggest that careful consideration should be taken for the use of remdesivir in the treatment of COVID-19 in pregnancy. FUNDING: Ministry of Science and Technology of Taiwan.
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Tratamento Farmacológico da COVID-19 , Complicações Infecciosas na Gravidez , Adenosina/análogos & derivados , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Líquido Amniótico , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Biotransformação , Feminino , Feto/metabolismo , Furanos/metabolismo , Placenta/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Pirróis/metabolismo , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodosRESUMO
In tumor development, increased expression of DNA methyltransferase (DNMT) has been observed. In particular, cigarette smoke and tea polyphenols may influence DNMT3B mRNA expression by regulating microRNA (miR)-29b expression. Herein, we designed a case−control study to evaluate the joint effects of smoking and green tea consumption, with miR-29b and DNMT3B mRNA expression, in lung cancer development. A total of 132 lung cancer patients and 132 healthy controls were recruited to measure miR-29b and DNMT3B mRNA expression in whole blood. Results revealed that lung cancer patients had lower miR-29b expression (57.2 vs. 81.6; p = 0.02) and higher DNMT3B mRNA expression (37.2 vs. 25.8; p < 0.001) than healthy controls. Compared to non-smokers with both higher miR-29b and lower DNMT3B mRNA expression, smokers with both low miR-29b and higher DNMT3B mRNA expression had an elevated risk of lung cancer development (OR 5.12, 95% CI 2.64−9.91). Interactions of smoking with miR-29b or DNMT3B mRNA expression in lung cancer were significant. Interaction of green tea consumption with miR-29b expression and DNMT3B mRNA expression in lung cancer was also significant. Our study suggests that smokers and green tea nondrinkers with lower miR-29b expression and higher DNMT3B mRNA expression are more susceptible to lung cancer development.
Assuntos
Fumar Cigarros , Neoplasias Pulmonares , MicroRNAs , Estudos de Casos e Controles , Humanos , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , Fumar/efeitos adversos , Fumar/genética , CháRESUMO
This study aimed to assess evidence for the effect of movement-based mind-body interventions (MMBIs) for cardiac rehabilitation (CR). Six databases were searched from January 1995 to September 2020. All randomized controlled trials (RCTs) evaluated the effect of MMBIs on heart disease (HD) patients' physical and psychological outcomes. Two reviewers independently assessed the quality of all the included studies using the revised Cochrane risk-of-bias tool for RCTs. Sixteen RCTs (5160 participants) published between 1996 and 2020 met all inclusion criteria. In total, these studies investigated the effect of MMBIs for CR. Outcome measures that emerged in these studies included physical and psychological, and/or biochemical parameters to comprehensively evaluate the effects of MMBIs on HD patients. Overall, these studies suggest that MMBIs seem to be an alternative with the optimal CR option.