Successful therapy using high-dose furmonertinib for non-small cell lung cancer with leptomeningeal metastasis: a case report and literature review.

Background: Lung cancer is the second most common form of malignant tumor and has the highest mortality rate worldwide. Among its subtypes, lung adenocarcinoma is the most prevalent. Leptomeningeal metastasis (LM) is rare and is characterized by a dismal prognosis, with overall survival periods typically spanning 4 to 6 weeks without treatment. However, in specific cases, survival can be extended to 4 to 6 months with appropriate therapy. The recent approval of third-generation tyrosine kinase inhibitors (TKIs), such as osimertinib, aumolertinib, and furmonertinib, has introduced promising treatment options for individuals with non-small cell lung cancer (NSCLC) who develop LM after developing resistance to first- and second-generation TKIs. These third-generation TKIs exhibit an enhanced ability to penetrate the blood-brain barrier (BBB), opening up new avenues for managing this challenging condition. Case summary: We report the case of a 48-year-old Chinese man diagnosed with advanced NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. Following a pulmonary lobectomy and postoperative adjuvant therapy with gefitinib, the patient was diagnosed with LM, which was confirmed by his neurologic symptoms, cerebrospinal fluid cytologic analysis, and cranial enhancement magnetic resonance imaging. Subsequently, he received oral treatment in the form of 160 mg of furmonertinib daily. After 5 days of furmonertinib therapy, the patient recovered from lethargy, with an obvious improvement in cognitive function. Follow-up visits revealed a 6-month survival period following the LM diagnosis. Patients with NSCLC and LM typically present with severe symptoms, and the efficacy of systemic treatment, intrathecal chemotherapy, and radiotherapy remains unsatisfactory. We hope that this specific case provide valuable insights into the management of patients with EGFR mutation-associated NSCLC with LM. Conclusion: Furmonertinib, a third-generation EGFR TKI with notable BBB penetration, shows promise in LM control and the rapid alleviation of intracranial symptoms. Further investigations into appropriate dosage and toxicity management are imperative.

Cadmium exposure is associated with decreased muscle strength in middle-aged and older adults.

Cadmium, a toxic heavy metal, is ubiquitous in the environment. No previous research has evaluated the relationship of blood and urine cadmium levels with muscle strength measured by isokinetic knee extensor strength. This analysis included participants who were aged 50 years or older and had measurements of cadmium in blood (n = 2052) and urine (n = 811) from the National Health and Nutrition Examination Survey. Blood and urine cadmium levels were assessed by atomic absorption spectrometry and inductively coupled plasma-mass spectrometry, respectively. Isokinetic dynamometry was used to assess knee extensor strength (peak force). Linear regression models were used to examine the association between cadmium exposure and peak force, with adjustment for potential confounders. The median values (25-75th percentiles) of blood cadmium and creatinine-corrected urine cadmium were 0.50 µg/L (0.40-0.70) and 0.43 µg/g (0.27-0.71), respectively. After adjusting for potential confounders, linear dose-response relationships of peak force with blood and urine cadmium concentrations were observed in the present study. Compared to participants in the highest quartile of blood cadmium and urine cadmium, the peak force decreased by 6.99 Newton (95% CI: -21.96, 7.98) and 26.84 Newton (95% CI: -44.34, -9.34) in participants in the lowest quartiles, respectively. The observed associations were more evident among men participants. Our findings suggest that the cadmium levels have a dose response relationship with decreased muscle strength measured by isokinetic knee extensor strength in middle aged and older adults. Further longitudinal investigations are required to disentangle these complexities on this issue.

Exposure to mixture of heavy metals and muscle strength in children and adolescents: a population-based study.

Human beings are exposed to heavy metals through various ways in daily life. However, the effect of heavy metal mixtures on muscle strength in children and adolescents remains unclear. We aimed to investigate the relationship of exposure to heavy metal mixtures (barium, cadmium, cobalt, manganese, molybdenum, lead, antimony, strontium, tin, thallium, tungsten, uranium, and cesium) with muscle strength in children and adolescents. A total of 1357 (boys, 50.8%) participants aged between 8 and 17 were extracted from the National Health and Nutrition Examination Surveys 2011-2014. Urine metals were measured by inductively coupled plasma-mass spectrometry. Muscle strength was measured through a grip test using a handgrip dynamometer. Weighted quantile sum regression was performed to estimate the mixture effect of urinary metals on muscle strength. After adjusting for potential confounders, comparing participants in the highest versus lowest quartiles of cobalt, molybdenum, lead, antimony, strontium, thallium, and cesium, the handgrip strength decreased by - 4.48 kg (95% CI: - 6.93, - 2.03), - 6.13 kg (- 8.76, - 3.51), - 2.26 kg (- 4.22, - 0.30), - 2.38 kg (- 4.68, - 0.08), - 2.29 kg (- 4.45, - 0.13), - 4.78 kg (- 7.13, - 2.44), and - 5.68 kg (- 9.20, - 2.17), respectively. Furthermore, exposure to a mixture of metals were also significantly associated with decreased muscle strength (ß: - 2.62 kg; 95% CI: - 3.71, - 1.54). Findings from the present study suggest that higher heavy metal exposure and the exposure levels of a mixture of metals in urine are inversely related to handgrip strength, implying that children's grip strength is not entirely explained by energy intake or lack of exercise, but may be related to environmental pollutants.

Associations of Dietary Inflammatory Index With Prediabetes and Insulin Resistance.

BACKGROUND AND AIMS: Previous studies suggested that dietary inflammatory index (DII) was associated with a variety of adverse health conditions. However, less is known about the role of DII in prediabetes and insulin resistance (IR). Therefore, this study aimed to investigate whether DII is associated with prediabetes and IR in American adults. METHOD AND RESULTS: DII scores were calculated using the average of two 24-hour dietary recalls. Linear regression models were performed to evaluate the associations of DII with markers of Type 2 diabetes (T2D) risk, and the associations of DII with prediabetes and IR were estimated using logistic regression model. The diet of the participants showed an anti-inflammatory potential, with a mean DII score of -0.14 (range: -5.83 to +5.32). After controlling for multiple potential confounders, DII scores were positively associated with fasting plasma glucose (FPG) (ß: 0.009; 95%CI: 0.005 to 0.012), fasting serum insulin (FSI) (ß: 0.083; 95%CI: 0.067 to 0.099) and homeostatic model assessment of insulin resistance (HOMA-IR) (ß: 0.092; 95%CI: 0.075 to 0.109). Participants in the highest tertile of DII score have increased odds of prediabetes (OR: 1.40; 95%CI: 1.17 to 1.69; P for trend <0.001) and IR (OR: 1.79; 95%CI: 1.49 to 2.14; P for trend <0.001) compared with those in the first tertile of DII score. CONCLUSIONS: This study indicates that DII was positively associated with FPG, FSI, and HOMA-IR, and a more pro-inflammatory diet was related to increased odds of insulin resistant and prediabetes.

Metabolic syndrome severity score and the progression of CKD.

BACKGROUND: Metabolic syndrome severity, expressed by the continuous metabolic syndrome risk score (MetS score), has been demonstrated to be able to predict future health conditions. However, little is known about the association between MetS score and renal function. METHODS: A total of 22,719 participants with normal renal function abstracted from the Kailuan Study were followed from 2006 to 2016. The new onset of chronic kidney disease (CKD) was defined as eGFR <60 ml/min per 1.73 m2 and/or proteinuria >300 mg/dl. Progressive decline in renal function was defined as an annual change rate of eGFR below the 10th percentile of the whole population. RESULTS: In the multivariate-adjusted model, we found that the risk of progressive decline in renal function increased consistently with the MetS score, with an odds ratio of 1.49 (95% CI, 1.28, 1.73) for those subjects>75th percentile compared with those <25th percentile. Additionally, a high MetS score was found to be associated with an increased risk of CKD, with a hazard ratio of 1.53 (95% CI, 1.33, 1.78) for subjects >75th percentile compared with those <25th percentile. CONCLUSIONS: Our findings suggested that the MetS score was associated with an increased risk of a progressive decline in renal function and was also a strong and independent risk factor for the development of CKD. These findings provide evidence of the potential clinical utility of the MetS score for assessing metabolic syndrome severity to detect the risk of decreased renal function and CKD.

Visit-to-visit variability in the measurements of metabolic syndrome components and the risk of all-cause mortality, cardiovascular disease, and arterial stiffness.

BACKGROUND AND AIMS: The risk of adverse health conditions varied according to the number of metabolic syndrome components. We aimed to evaluate the risk of mortality and incident cardiovascular events according to the number of components with high variability. METHODS AND RESULTS: A total of 43,737 Kailuan Study participants with ≥3 examinations of waist circumference, fasting blood glucose, systolic blood pressure, triglyceride, and high-density lipoprotein during 2006-2013 were included in the present study. Visit-to-visit variability in each parameter was defined by the intraindividual standard deviation across visits. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability components (e.g., a score of 0 indicated no high-variability component). There were 1551 deaths during a median follow-up of 5.9 years, and 950 incident cardiovascular disease (CVD) cases during a median follow-up of 4.9 years. In the multivariable adjusted model, compared with participants with low variability for all components, participants with ≥3 high-variability components had significantly higher risks for all-cause mortality (hazards ratio [HR], 1.61; 95 % confidence interval [CI], 1.35-1.91) and incident CVD event (HR, 1.45; 95 % CI, 1.16-1.82). Additionally, participants with ≥3 high-variability components had increased odds of arterial stiffness, as measured by brachia-ankle pulse wave velocity (odds ratio [OR], 1.39; 95 % CI, 1.19-1.63). CONCLUSIONS: Our findings suggest that participants with at least three metabolic parameters with high variability experienced increased risk of CVD and all-cause mortality.

Epidemiological and clinical characteristics of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare workers in Hubei Province, China.

OBJECTIVE: To evaluate the epidemiological and clinical characteristics of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare workers (HCWs) in Hubei Province, China. DESIGN: Retrospective cohort study. SETTING: Hubei Provincial Center for Disease Control and Prevention. PARTICIPANTS: The participants in this study are cases identified by epidemiological investigation in Hubei Province, as of February 27, 2020, and were followed until March 7, 2020. In total, 1,989 HCWs and 41,137 other occupational cases were included for analysis. METHODS: We used descriptive statistics to summarize patient characteristics. RESULTS: Of 1,989 laboratory-confirmed HCWs, 297 (14.93%) had severe or critical cases, 73 (3.67%) had asymptomatic infections, and 18 died of coronavirus disease 2019 (COVID-19). The case fatality rate was 0.9%. The proportion of severe or critical cases decreased from the beginning to the end of the outbreak (from 21.29% to 3.52%), and the proportion of asymptomatic cases increased from 0.0% to 47.18%. Nearly half of HCWs with confirmed COVID-19 reported no known contact with COVID-19 patients (969, 48.72%). Fever and cough were the most common symptoms at disease onset in both HCWs and other occupational cases; however, HCWs had higher rates of fatigue (30.90% vs 25.02%; P < .001) and myalgia (19.15% vs 13.43%; P < .001). Additionally, compared with other occupational groups, HCWs were associated with a lower risk of death after adjustment for potential confounders (odd ratio [OR], 0.50; 95% confidence interval [CI], 0.30-0.79). CONCLUSIONS: Compared with COVID-19 cases in other occupational groups, HCWs with COVID-19 have half the risk of death, although they have been shown to have higher rates of fatigue and myalgia.

Arsenic concentrations, diversity and co-occurrence patterns of bacterial and fungal communities in the feces of mice under sub-chronic arsenic exposure through food.

BACKGROUND: Arsenic, a global pollutant and a threshold-free primary carcinogen, can accumulate in rice. Previous studies have focused on arsenic poisoning in drinking water and the effects on gut microbes. The research on arseniasis through food, which involves the bio-transformation of arsenic, and the related changes in gut microbiome is insufficient. METHOD: Mice were exposed from animal feed prepared with four arsenic species (iAsIII, iAsV, MMA, and DMA) at a dose of 30 mg/kg according to the arsenic species proportion in rice for 30 days and 60 days. The levels of total arsenic (tAs) and arsenic species in mice feces and urine samples were determined using ICP-MS and HPLC-ICP-MS, respectively. 16S rRNA and ITS gene sequencing were conducted on microbial DNA extracted from the feces samples. RESULTS: At 30 days and 60 days exposure, the tAs levels excreted from urine were 0.0092 and 0.0093 mg/day, and tAs levels in feces were 0.0441 and 0.0409 mg/day, respectively. We found significant differences in arsenic species distribution in urine and feces (p < 0.05). In urine, the predominant arsenic species were iAsIII (23% and 14%, respectively), DMA (55% and 70%, respectively), and uAs (unknown arsenic, 14% and 10%, respectively). In feces, the proportion of major arsenic species (iAsV, 26% and 21%; iAsIII, 16% and 15%; MMA, 14% and 14%; DMA, 19% and 19%; and uAs, 22% and 29%, respectively) were evenly distributed. Microbiological analysis (MRPP test, α- and ß-diversities) showed that diversity of gut bacteria was significantly related to arsenic exposure through food, but diversity of gut fungi is less affected. Manhattan plot and LEfSe analysis showed that arsenic exposure significantly changes microbial taxa, which might be directly associated with arsenic metabolism and diseases mediated by arsenic exposure, such as Deltaproteobacteria, Polynucleobacter, Saccharomyces, Candida, Amanitaceae, and Fusarium. Network analysis was used to identify the changing hub taxa in feces along with arsenic exposure. Function predicting analysis indicated that arsenic exposure might also significantly increase differential metabolic pathways and would disturb carbohydrates, lipid, and amino acids metabolism of gut bacteria. CONCLUSIONS: The results demonstrate that subchronic arsenic exposure via food significantly changes the gut microbiome, and the toxicity of arsenic in food, especially in staples, should be comprehensively evaluated in terms of the disturbance of microbiome, and feces might be the main pathway through which arsenic from food exposure is excreted and bio-transformed, providing a new insight into the investigation of bio-detoxification for arseniasis.

Association of dietary selenium intake with telomere length in middle-aged and older adults.

BACKGROUND: Growing evidence suggested that lifestyle factors including dietary habits may influence the telomere length which is a reliable marker of biological aging and predictor for chronic diseases. However, the role of dietary selenium intake in telomere length maintenance is rarely examined. OBJECTIVE: We aimed to test the relationship between dietary selenium intake and telomere length among middle-aged and older adults in America. METHODS: A total of 3194 United States adults older than 45 years old were extracted from the National Health and Nutrition Examination Survey (NHANES) in 1999-2000 and 2001-2002. Leukocyte telomere length was measured using the quantitative real-time polymerase chain reaction (qPCR). Dietary selenium intake was assessed by a trained interviewer using 24-h dietary recall method. Generalized linear models were performed to evaluate the association of dietary selenium intake with telomere length. The restricted cubic spline analysis was used to further explore the nonlinear dose-response relationship between dietary selenium intake and telomere length. RESULTS: After adjusting potential confounders, every 20 µg increase in dietary selenium intake was associated with 0.42% (95% CI: 0.02%, 0.82%) longer telomere length in all participants. In the subgroup analyses, dietary selenium intake was related to longer telomere length in females (Percentage change: 0.87%; 95% CI: 0.26%, 1.49%) and non-obese participants (Percentage change: 0.53%; 95% CI: 0.04%, 1.02%), but not in males (Percentage change: 0.04%; 95% CI: -0.49%, 0.57%) and obese participants (Percentage change: 0.21%; 95% CI: -0.47%, 0.91%). The restricted cubic spline analysis showed a linear association between dietary selenium intake and telomere length. CONCLUSIONS: This study indicated that the increased dietary selenium intake was associated with longer telomere length among middle-aged and older adults in America. These findings require further corroboration from future prospective studies.

Prenatal exposure to thallium is associated with decreased mitochondrial DNA copy number in newborns: Evidence from a birth cohort study.

BACKGROUND: Prenatal exposure to thallium is related to adverse birth outcomes. However, little is known about the effects of prenatal exposure to thallium on the mitochondrial DNA copy number (mtDNAcn) in newborns; such knowledge might reveal a potential mechanism linking maternal thallium exposure and adverse birth outcomes. OBJECTIVE: To investigate the trimester-specific associations of maternal thallium exposure with cord blood leukocyte mtDNAcn. METHODS: A total of 746 pregnant women with trimester-specific urinary samples and cord blood samples were recruited from Wuhan Children Hospital between November 2013 and March 2015 in Wuhan City, China. The concentration of thallium in maternal urine was quantified using inductively coupled plasma mass spectrometry (ICP-MS). Cord blood leukocyte mtDNAcn was measured by real-time quantitative polymerase chain reaction (qPCR). Trimester-specific associations of specific gravity (SG)-adjusted urinary thallium concentrations with mtDNAcn were estimated using a multiple informant model. RESULTS: The geometric mean value of maternal urinary thallium was 0.34 µg/L, 0.36 µg/L, and 0.34 µg/L for the first, second, and third trimesters, respectively. Prenatal exposure to thallium during the first trimester, rather than during the second or the third trimester, was identified as negatively related to mtDNAcn. The multiple informant model showed a 10.4% lower level of mtDNAcn with each doubling increase of thallium levels (95% CI, -16.4%, -3.9%; P = 0.002). The observed associations were stronger among female newborns and among newborns born to older mothers. CONCLUSIONS: The present study revealed a significant negative association between maternal thallium exposure during early pregnancy and cord blood leukocyte mtDNAcn in Chinese newborns, pointing to the important role of mitochondria as a target of thallium toxicity in early pregnancy.