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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]

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]

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]

Background Cardiac hypertrophy is associated with abnormal electrophysiology and increased arrhythmia risk. This study assessed whether candesartan cilexetil, an angiotensin II type 1 receptor blocker, could suppress arrhythmogenecity by attenuating cardiac electrical remodeling and calcium mishandling in rats with pressure-overload hypertrophy. Methods and Results Male Sprague-Dawley rats were randomly subjected to abdominal aorta banding or sham procedure and received either candesartan cilexetil (3.0 mg/kg per day) or vehicle by gavage for 5 weeks. Pressure overload was characterized by compensated left ventricular (LV) hypertrophy and fibrosis, increased LV pressure and its decay time, and prolonged corrected QT interval, all of which were attenuated by candesartan cilexetil treatment. Candesartan cilexetil-treated banded rat hearts displayed shorter QT intervals and lower vulnerability to atrial and ventricular tachyarrhythmias than vehicle-treated banded hearts. Candesartan cilexetil prevented banding-induced prolonged action potential duration and reduced the occurrence of triggered activity in LV papillary muscles. In addition, the prolonged time to 50% cell relengthening and calcium transient decay time were normalized in LV myocytes from candesartan cilexetil-treated banded rats, along with a normalization of decreased SERCA2a (sarco[endo]plasmic reticulum calcium-ATPase) expression in LV tissues. Furthermore, candesartan cilexetil normalized depressed transient outward potassium current densities and protein and mRNA levels of both voltage-gated potassium 4.2 and 4.3 channel subunits (Kv4.2 and Kv4.3) in banded rats. Conclusions Candesartan cilexetil protects the heart from pressure overload-induced adverse electrical remodeling by preserving potassium channel densities. In addition, calcium handling and its molecular regulation also improved after treatment. These beneficial effects may contribute to a lower susceptibility to arrhythmias in hearts from candesartan cilexetil-treated pressure-overloaded rats.