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Purpose: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR‐TKI‐induced skin toxicities. Experimental Design: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR‐TKI‐treated cancer patients were analysed and compared with those of 43 non‐EGFR‐TKI‐treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib‐induced skin eruptions was established in a 14‐day‐murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR‐TKI‐treated cancer patients. Results: EGFR‐TKI‐treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR‐TKI‐induced skin toxicities showed a significant negative correlation (r = −0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR‐TKI treatment. Zinc supplementation to the EGFR‐TKI‐treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks. Conclusions: Skin impairment following EGFR‐TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR‐TKI therapy. [ABSTRACT FROM AUTHOR]

Byline: Chi-Jen Chang, Nye-Jan Cheng, Yu-Shien Ko, Yu-Lin Ko, Cheng-Wen Chiang Author Affiliation: Taipei, Taiwan Article Note: (footnote) [star] Reprint requests: Chi-Jen Chang, MD, the First Cardiovascular Division, Chang Gung Memorial Hospital, 199, Tung Hwa North Road, Taipei, 105 Taiwan., [star][star] Am Heart J 1997;133:598-601, a 0002-8703/97/$5.00 + 0 4/4/77022

Abstract Background Long-term heavy alcohol drinkers are prone to the development of cardiac arrhythmia. To understand the mechanisms, we evaluated the cardiac structural and electrophysiological changes in mice chronically drinking excessive alcohol. Results Male C57BL/6J mice were given 36% alcohol in the drinking water. Those given blank water were used as control. Twelve weeks later, the phenotypic characteristics of the heart, including gap junctions and electrical properties were examined. In the alcohol group the ventricles contained a smaller size of cardiomyocytes and a higher density of capillary networks, compared to the control. Western blots showed that, after drinking alcohol, the content of connexin43 (Cx43) protein in the left ventricle was increased by 18% (p < 0.05). Consistently, immunoconfocal microscopy demonstrated that Cx43 gap junctions were up-regulated in the alcohol group with a disorganized distribution, compared to the control. Optical mapping showed that the alcohol group had a reduced conduction velocity (40 ± 18 vs 60 ± 7 cm/sec, p < 0.05) and a higher incidence of ventricular tachyarrhythmia (62% vs 30%, p < 0.05). Conclusion Long-term excessive alcohol intake resulted in extensive cardiac remodeling, including changes in expression and distribution of gap junctions, growth of capillary network, reduction of cardiomyocyte size, and decrease of myocardial conduction.

Background: High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal growth factor receptor tyrosine kinase inhibitor(EGFR‐TKI)‐induced paronychia, which may even interrupt the course of treatment for EGFR‐TKI therapy. Thus, we conducted this study to determine how effectively a topical β‐blocker, betaxolol, prevents EGFR‐TKI‐induced paronychia. Methods: This case–control cohort study included a total of 131 non‐small‐cell lung cancer patients. The prevention group comprised 40 patients treated with topical betaxolol 0.25% solution to prevent paronychia while they received EGFR‐TKI therapy. The control group comprised 91 patients who did not preventively use topical betaxolol 0.25% solution while receiving EGFR‐TKI therapy. The patients' age, gender, antineoplastic regimen, duration of antineoplastic treatment before the appearance of lesions, number of involved digits (fingernails or toenails) with lesions, grading of paronychia, and pain score were recorded. Results: In terms of the cumulative incidence of paronychia, significant differences (P < 0.01) were noted at both the 2nd and 3rd months after starting EGFR‐TKIs. Furthermore, the average visual analogue scale scores were 3.125 and 6.29 in the prevention group and control group, respectively (P < 0.01). The average grades of paronychia were 1.5 and 2.12 in the prevention group and control group, respectively (P < 0.01). The average numbers of involved digits were 2.25 (range: 1–5 digits) in the prevention group and 3.03 (range: 1–7) in the control group (P = 0.07). Conclusions: Preventively using topical betaxolol can significantly decrease the incidence, VAS score, and grading of EGFR‐TKI‐induced paronychia. [ABSTRACT FROM AUTHOR]

Background: Paronychia is a common adverse event caused by epidermal growth factor receptor (EGFR) inhibitors. However, high rates of post‐treatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion for EGFR inhibitor‐induced paronychia. Furthermore, poor wound healing and malnutrition were common conditions found in cancer patients. The aim of this study is to find an effective, pain‐relieving, and noninvasive treatment for patients with severe paronychia induced by EGFR inhibitors. Methods: Data from a series of 35 non‐small cell lung cancer cases suffering from EGFR inhibitor‐induced paronychia with pyogenic granuloma‐like lesions of digits treated with betaxolol 0.25% ophthalmic solution once daily were collected and analyzed. Results: Of the 35 patients suffering from grade 2 or 3 paronychia with pyogenic granuloma‐like lesions induced by EGFR inhibitors, 34 (97.1%) demonstrated complete resolution and only one (2.9%) had partial resolution after 12 weeks of topical betaxolol treatment. The grading of paronychia according to the Common Terminology Criteria for Adverse Events decreased from an average of 2.29 to 0.63 after 4 weeks of treatment (P = 5.55 × 10−16). All the patients had significant improvement (50% pain reduction), as their pain visual analogue scale scores decreased from an average of 7.06 to 2.26 after one week of treatment (P = 6.11 × 10−25). Conclusion: Betaxolol 0.25% ophthalmic solution is an effective, safe, and pain‐relieving treatment for patients suffering from EGFR inhibitor‐induced paronychia with pyogenic granuloma‐like lesions and deep fissures. [ABSTRACT FROM AUTHOR]

Background: Cirrhotic cardiomyopathy (CCM) refers to cardiac dysfunction in patients with liver cirrhosis, in the absence of other known cardiac disease. Methods: Control group and patients diagnosed of liver cirrhosis without known cardiac disease or hepatocellular carcinoma were enrolled for this clinical observation study. Patients with diabetes mellitus, hypertension were excluded. Absolute global longitudinal strain, one-point carotid pulse wave velocity (one-point PWV) and various parameters were measured in resting status. Results: There were 29 participants in the control group and 80 patients in the liver cirrhosis group. 27.8% of cirrhotic patients presented with normal systolic but abnormal diastolic functions and QTc prolongation that were compatible with CCM. 34.2% of cirrhotic patients presented with diastolic dysfunction in resting state comparing to 24.1% in control group. Systolic functions did not show conspicuous difference between cirrhosis and control group nor between compensated and decompensated cirrhosis, neither. Furthermore, one-point PWV was significantly higher in liver cirrhosis than in control group and higher in CCM than in non-CCM patients. One-point PWV predicted CCM and diastolic dysfunction in cirrhosis. Most importantly, its value > 1370cm/s predicted overall mortalities in decompensated cirrhosis (multivariable Cox analysis OR = 6.941) in addition to CTP score specifically in HCV related cirrhotic patients (AUC = 0.817). Conclusions: In patients with cirrhosis, 27.8% were diagnosed with CCM by resting cardiovascular parameters. One-point PWV increased in CCM, correlated with diastolic dysfunction. It also correlated with overall mortality in patients with hepatitis C virus (HCV) related decompensated cirrhosis. Further study may be needed to confirm its capability for assessing CV and mortality risks in HCV related decompensated cirrhotic patients. [ABSTRACT FROM AUTHOR]

Objectives: Our study aimed to correlate pulse wave parameters such as augmentation index (AI) and heart rate variability with traditional Chinese medicine (TCM) constitution for evaluating health status.Design: Out of 177 subjects, 69 healthy subjects were enrolled in the present study, and others were excluded because of cardiovascular, liver, kidney, or other diseases. Each subject was invited to complete pulse wave examination and the Constitution in Chinese Medicine Questionnaire. Independent Student's t-tests, Mann-Whitney tests, and binary logistic regression analysis were used to analyse the correlation between pulse wave parameters and TCM constitution.Results: Qi-deficient individuals had higher AI (p=0.006) and lower diastolic blood pressure (p=0.011); yang-deficient individuals had lower dP/dt max (p=0.030), systolic blood pressure (p=0.020), and pulse pressure (p=0.048); and damp-heat individuals had higher subendocardial viability index (SEVI) scores (p=0.011). We then categorized the phlegm dampness and yang-deficiency individuals into the cold group and those with damp-heat and yin-deficiency into the heat group. A comparison of the two constitution groups showed higher AI in the cold group (p=0.026). Binary logistic regression analysis demonstrated that only AI was a determinant, as evidenced by the finding that an increase of one unit in AI corresponded to an increase of 5% in the odds ratio for individuals to have a cold constitution (p=0.026).Conclusions: Individuals with qi-deficient and cold constitutions had higher AI and lower SEVI, potentially reflecting an increase in arterial stiffness. This study can provide a basis for further investigation of the physiological indicators of TCM constitutions in modern medicine. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to estimate the risk of hyperuricaemia and gout in people with hypothyroid or hyperthyroid status. Methods: This study analyzed data from individuals who participated in health screening programs at Chang Gung Memorial Hospital in northern Taiwan (2000–2010). Participants were categorized as having euthyroid, hypothyroid, or hyperthyroid status according to their thyroid-stimulating hormone (TSH) levels. Multinomial logistic regression models were used to calculate the odds ratios (95% CI) for hyperuricaemia and gout in participants with thyroid dysfunction compared to euthyroid participants. Results: A total of 87,813 (euthyroid, 83,502; hypothyroid, 1,460; hyperthyroid, 2,851) participants were included. The prevalence of hyperuricaemia was higher in hyperthyroid subjects (19.4%) than in euthyroid subjects (17.8%) but not in hypothyroid subjects (19.3%). The prevalence of gout was significantly higher in both hypothyroid (6.0%) and hyperthyroid (5.3%) subjects than in euthyroid subjects (4.3%). In men, hypothyroid or hyperthyroid status was not associated with hyperuricaemia. However, hypothyroid or hyperthyroid status was associated with ORs (95% CI) of 1.47 (1.10–1.97) and 1.37 (1.10–1.69), respectively, for gout. In women, hypothyroid status was not associated with hyperuricaemia or gout. However, hyperthyroid status was associated with ORs (95% CI) of 1.42 (1.24–1.62) for hyperuricaemia and 2.13 (1.58–2.87) for gout. Conclusions: Both hyperthyroid and hypothyroid status were significantly associated with gout and weakly associated with hyperuricaemia. A thyroid function test for gout patients may by warranted. [ABSTRACT FROM AUTHOR]

Abstract: Percutaneous transluminal angioplasty (PTA) for thrombosed dialysis graft is both difficult and time-consuming that may increase radiation exposure. A predictor of PTA success and procedure time has not been identified yet. Sonography data and the PTA results of 88 grafts were reviewed retrospectively. The echogenicity of the majority of the intra-graft thrombus and the presence/absence of thrombus free space in the grafts were examined. The association between the sonography findings and PTA procedure success and procedure time was analyzed. The echogenicity of the intra-graft thrombus and presence/absence of thrombus free space were the major determinants of procedure success and procedure time. Higher intra-graft echogenicity and lack of thrombus free space were associated with more procedure failures (p < 0.01 vs. p = 0.04) and longer procedure times (p = 0.03 vs. p < 0.01). Thrombi from occluded dialysis grafts may differ in resistance to mechanical/pharmacological thrombolysis. Sonography characteristics of the intra-graft thrombus may help to differentiate them. [Copyright &y& Elsevier]

Aims The bladder contractile dysfunction resulting from acute ischemia may be attributed to nerve growth factor (NGF) overexpression. This study was conducted to evaluate the acute and mid-term effects of bladder ischemia on the temporal expression of NGF immunoreactivity and mRNA. Materials and Methods Bladder ischemia was induced by ligation of bilateral vesical arteries in female rats. We examined the NGF content of bladder detrusor muscle at 1 day, 1 week and 4 weeks after artery ligation. Immunoreactivity of NGF was studied by immunofluorescent staining and Western blot. The NGF mRNA was analyzed by real-time polymerase chain reaction. Results The immunofluorescence of NGF at 1 week and 4 weeks was significantly reduced when compared to sham-operated group ( P < 0.05). This decreased tendency was also found in Western blot test. An increased expression of NGF mRNA was noted at 1 day, 1 week and 4 weeks, but had no significant change when compared to sham-operated group ( P > 0.05). Conclusions Our study showed bilateral vesical artery ligation may cause damage of detrusor muscle and there is decreased NGF immunofluorescence and elevated NGF mRNA in bladder suggesting an expression disparity following ischemia. Neurourol. Urodynam. 29:512-516, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Coronary computed tomography angiography (CCTA) is a widely used imaging modality for diagnosing coronary artery disease (CAD) but is limited by a high false positive rate when evaluating coronary arteries with stents and heavy calcifications. Virtual intravascular endoscopy (VIE) images generated from CCTA can be used to qualitatively assess the vascular lumen and might be helpful for overcoming this challenge. In this study, one hundred subjects with coronary stents underwent both CCTA and invasive coronary angiography (ICA). A total of 902 vessel segments were analyzed using CCTA and VIE. The vessel segments were first analyzed on CCTA alone. Then, using VIE, the segments were classified qualitatively as either negative or positive for in-stent restenosis (ISR) or CAD. These results were compared, using ICA as the reference, to determine the added diagnostic value of VIE. Of the 902 analyzed vessel segments, CCTA/VIE had sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (shown in %) of 93.9/90.2, 96.2/98.2, 96.0/97.7, 70.0/83.1, and 99.4/99.0, respectively, in diagnosing ISR or CAD, with significantly improved specificity (p = 0.025), accuracy (p = 0.046), and positive predictive value (p = 0.047). VIE can be a helpful addition to CCTA when evaluating coronary arteries. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to clarify the response of endothelial connexins to hypertension and antihypertensive drugs. Methods: Rats remained normotensive (group 1, N = 10) or were made hypertensive using Nω -nitro-l-arginine methyl ester (L-NAME) (groups 2 to 4, N = 10/group). Seven weeks later groups 3 and 4 were respectively fed atenolol or carvedilol daily for 7 days and the aortic endothelial gap junctions were analyzed. In parallel the effects of atenolol, carvedilol, labetalol, vitamin C, and vitamin E on connexin43 (C×43) in human umbilical vein endothelial cells (HUVEC) were compared. Results: Endothelial C×43 was reduced by 35% and C×37 by 59% in hypertensive rats (P < .001). The reduction was recovered fully by carvedilol but only partially by atenolol (P < .05), although both drugs lowered the blood pressure to similar levels. C×40 remained stationary in all groups. In HUVEC, carvedilol (10 μg/mL) increased C×43 protein expression by >70% (P < .01), whereas other drugs had minimal effects. The upregulation by carvedilol was associated with increased transcripts and decreased proteolysis of C×43. Conclusions: The study showed that L-NAME–induced hypertension has differential effects on endothelial connexins, which respond variously to carvedilol and atenolol. In HUVEC carvedilol directly upregulates endothelial C×43 and the effect is independent of its antioxidant activity. [Copyright &y& Elsevier]