IGAxBSA composite for assessing disease severity and response in patients with atopic dermatitis.

BACKGROUND: Accurate assessment of atopic dermatitis (AD) severity is critical when initiating and monitoring therapy. Use of existing research tools such as the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD) is complex and time-consuming in clinical practice. A previous analysis found the product of validated Investigator's Global Assessment (vIGA) and affected body surface area (BSA) to be an accurate and practical tool for routine assessment of paediatric AD. OBJECTIVE: To evaluate the IGAxBSA composite as an alternative to EASI or SCORAD for assessment of AD disease severity and disease responsiveness. METHODS: The relationship between IGAxBSA, EASI and SCORAD was assessed in a post hoc analysis of pooled data from the dupilumab clinical trial programme in adult and paediatric patients with moderate-to-severe AD who had received dupilumab or placebo, with or without topical corticosteroids (TCS). The trials are registered at ClinicalTrials.gov and EudraCT: LIBERTY AD SOLO 1 (NCT02277743, 2014-001198-15), LIBERTY AD SOLO 2 (NCT02277769, 2014-002619-40), LIBERTY AD SOLO-CONTINUE (NCT02395133, 2014-003384-38), LIBERTY AD CHRONOS (NCT02260986, 2013-003254-24), LIBERTY AD CAFÉ (NCT02755649, 2015-002653-35), LIBERTY AD ADOL (NCT03054428, 2015-004458-16), LIBERTY AD PEDS (NCT03345914, 2016-004997-16), LIBERTY AD OLE (NCT01949311, 2013-001449-15) and LIBERTY AD PEDS OLE (NCT02612454, 2015-001396-40). RESULTS: Using datapoints from pooled dupilumab randomized controlled trials (n = 3473) and open-label extension trials (n = 3045), we found that IGAxBSA correlated well with EASI and SCORAD, irrespective of treatment group and race (white, Asian, black). IGAxBSA correlated better with objective measures (EASI, SCORAD) than with patient- or caregiver-reported subjective measures. IGAxBSA correlated strongly with EASI and SCORAD in assessing disease change over time (r = 0·90, r = 0·76, respectively; P < 0·0001), and concordance between IGAxBSA-50/75/90 and EASI-50/75/90 was excellent (88-94%). CONCLUSIONS: IGAxBSA is a valid alternative for assessment of AD disease severity and response over time, compared with EASI or SCORAD in patients with AD, irrespective of race.

Intra-pleural Instillation of Autologous Blood - Fine-tuning Techniques for Better Success Rate: Two Case Reports.

In the past, many case series have reported the effectiveness of autologous blood patch pleurodesis (ABPP) in recurrent secondary spontaneous pneumothorax (SSP), particularly in those who were unfit for surgery. We describe two cases of persistent air leak in pneumoconiosis and pulmonary fibrosis with bronchiectasis, whereby the techniques employed had improved the success rate of ABPP. The determining factors that lead to the success of ABPP were determined by the volume of autologous blood instilled, Trendelenburg position post instillation, and early chest physiotherapy with mobilisation by application of pneumostat.

Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1·0% for persistent erythema of rosacea in a phase IV study.

BACKGROUND: Once-daily topical oxymetazoline cream 1·0% significantly reduced persistent facial erythema of rosacea in trials requiring live, static patient assessments. OBJECTIVES: To evaluate critically the methodology of clinical trials that require live, static patient assessments by determining whether assessment of erythema is different when reference to the baseline photograph is allowed. METHODS: In two identically designed, randomized, phase III trials, adults with persistent facial erythema of rosacea applied oxymetazoline or vehicle once daily. This phase IV study evaluated standardized digital facial photographs from the phase III trials to record ≥ 1-grade Clinician Erythema Assessment (CEA) improvement at 1, 3, 6, 9 and 12 h postdose. RESULTS: Among 835 patients (oxymetazoline n = 415, vehicle n = 420), significantly greater proportions of patients treated with oxymetazoline vs. vehicle achieved ≥ 1-grade CEA improvement. For the comparison between phase IV study results and the original phase III analysis, when reference to baseline photographs was allowed while evaluating post-treatment photographs, the results for oxymetazoline were similar to results of the phase III trials (up to 85.7%), but a significantly lower proportion of vehicle recipients achieved ≥ 1-grade CEA improvement (up to 29.7% [phase 4] vs. 52.3% [phase 3]; P<0.001). In the phase IV study, up to 80·2% of patients treated with oxymetazoline achieved at least moderate erythema improvement vs. up to 22·9% of patients treated with vehicle. The association between patients' satisfaction with facial skin redness and percentage of erythema improvement was statistically significant. CONCLUSIONS: Assessment of study photographs, with comparison to baseline, confirmed significant erythema reduction with oxymetazoline on the first day of application. Compared with the phase III trial results, significantly fewer vehicle recipients attained ≥ 1-grade CEA improvement, suggesting a mitigated vehicle effect. This methodology may improve the accuracy of clinical trials evaluating erythema severity.

Identification of ABCG2 as an Exporter of Uremic Toxin Indoxyl Sulfate in Mice and as a Crucial Factor Influencing CKD Progression.

Chronic kidney disease (CKD) patients accumulate uremic toxins in the body, potentially require dialysis, and can eventually develop cardiovascular disease. CKD incidence has increased worldwide, and preventing CKD progression is one of the most important goals in clinical treatment. In this study, we conducted a series of in vitro and in vivo experiments and employed a metabolomics approach to investigate CKD. Our results demonstrated that ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a major transporter of the uremic toxin indoxyl sulfate. ABCG2 regulates the pathophysiological excretion of indoxyl sulfate and strongly affects CKD survival rates. Our study is the first to report ABCG2 as a physiological exporter of indoxyl sulfate and identify ABCG2 as a crucial factor influencing CKD progression, consistent with the observed association between ABCG2 function and age of dialysis onset in humans. The above findings provided valuable knowledge on the complex regulatory mechanisms that regulate the transport of uremic toxins in our body and serve as a basis for preventive and individualized treatment of CKD.

A global perspective on the epidemiology of acne.

Acne is estimated to affect 9.4% of the global population, making it the eighth most prevalent disease worldwide. Epidemiological studies have demonstrated that acne is most common in postpubescent teens, with boys most frequently affected, particularly with more severe forms of the disease. This paper aims to provide an update on the epidemiology of acne worldwide. Recent general and institutional studies from around the world have shown that the prevalence of acne is broadly consistent globally (with the exception of specific populations, which are discussed). However, this review highlights that there is a wide range of disparate outcome measures being applied in epidemiology studies, and we emphasize the need to develop a widely accepted, credible, standard assessment scale to address this in the future. In addition we discuss special populations, such as those devoid of acne, as well as the impact of potential determinants of acne on disease epidemiology.

Targeting genes in insulin-associated signalling pathway, DNA damage, cell proliferation and cell differentiation pathways by tocotrienol-rich fraction in preventing cellular senescence of human diploid fibroblasts.

BACKGROUND AND OBJECTIVES: Tocotrienols have been known for their antioxidant properties besides their roles in cellular signalling, gene expression, immune response and apoptosis. This study aimed to determine the molecular mechanism of tocotrienol-rich fraction (TRF) in preventing cellular senescence of human diploid fibroblasts (HDFs) by targeting the genes in senescence-associated signalling pathways. MATERIALS AND METHODS: Real time quantitative PCR (qRT-PCR) was utilized to evaluate the expression of genes involved in these pathways. RESULTS: Our findings showed that SOD1 and CCS-1 were significantly down-regulated in pre-senescent cells while CCS-1 and PRDX6 were up-regulated in senescent cells (p<0.05). Treatment with TRF significantly down-regulated SOD1 in pre-senescent and senescent HDFs, up-regulated SOD2 in senescent cells, CAT in young HDFs, GPX1 in young and pre-senescent HDFs, and CCS-1 in young, pre-senescent and senescent HDFs (p<0.05). TRF treatment also caused up-regulation of FOXO3A in all age groups of cells (p<0.05). The expression of TP53, PAK2 and CDKN2A was significantly increased in senescent HDFs and treatment with TRF significantly down-regulated TP53 in senescent cells (p<0.05). MAPK14 was significantly up-regulated (p<0.05) in senescent HDFs while no changes was observed on the expression of JUN. TRF treatment, however, down-regulated MAPK14 in young and senescent cells and up-regulated JUN in young and pre-senescent HDFs (p<0.05). CONCLUSIONS: TRF modulated the expression of genes involved in senescence-associated signalling pathways during replicative senescence of HDFs.

Elucidating the roles of miR-372 in cell proliferation and apoptosis of nasopharyngeal carcinoma TW01 cells.

AIM: Deregulation of microRNA has been associated with cancer progression and the modification of cancer phenotypes could be achieved by targeting microRNA expression. This study aimed to determine the effects of miR-372 on cell progression and gene expression in nasopharyngeal carcinoma cell line, TW01. MATERIALS AND METHODS: NPC TW01 cells were transfected with the miR-372 precursor molecules. Gene expression studies were conducted using RT-PCR assays for nine cancer related genes. The effects of miR-372 on cell proliferation, cell cycle arrest and apoptosis were also investigated. RESULTS: Expression of -miR-372 caused cell cycle arrest at the S phase that was accompanied by an overall decrease of cells entering the G2/M phase. miR-372 did not have any significant effect on apoptosis. Of the nine genes studied, four were up-regulated, namely CDKN1A, INCA1, LATS2 and BIRC5. The other five genes - CDK2, CCNA1, TP53, BAX and BCL2 were down-regulated by miR-372. CONCLUSION: This preliminary study indicated the tumor suppressing roles of miR-372 in cell cycle progression of TW01 cells, possibly via the down-regulation of CDK2 and CCNA1 as well as the up-regulation of CDKN1A and INCA1.Key Words: apoptosis, microRNA, nasopharyngeal carcinoma, miR-372, CDK2, CCNA1.

Correlation of photographic images from the Leeds revised acne grading system with a six-category global acne severity scale.

BACKGROUND: Few global acne grading systems include individualized assessments of chest and back as well as face. The Leeds revised acne grading system is based on photographic images while the Comprehensive Acne Severity Scale (CASS) is based on textual descriptions. There exists an unmet need for a global scale based on both text and photos. PURPOSE: Our objective was to evaluate the correspondence of severity grades from descriptive text (CASS grades) for each Leeds image. METHODS: Twenty-three dermatologists independently graded 56 photos of face, chest and back of varying acne severity using CASS. Photographs were randomly presented from the The Leeds revised acne grading system (n = 31) and from acne patients of the corresponding author (n = 25). For each Leeds photo, rater responses for CASS grades were transformed into median, coefficient of variation and percentiles. RESULTS: High rater agreement (≥75%) was observed for Leeds facial inflammatory 2 (CASS 3), 4 (CASS 4), 6 (CASS 4), 9-12 (all CASS 5); Leeds facial comedonal A (CASS 2); Leeds chest 7 and 8 (both CASS 5); and Leeds back 7 and 8 (both CASS 5). Lowest coefficients of variance were observed in Leeds facial inflammatory 4, 9, 10, 11; Leeds facial comedonal A; Leeds chest 7 and 8; and Leeds back 8. Conclusions Leeds photos, by inadequately portraying facial acne grades 1 (almost clear) and 2 (mild) and back and chest grades 1-4 (almost clear to severe), cannot accurately represent the spectrum of severity in a six-category global acne scale. Accordingly, there is a current need for images that correspond to a categorical acne scale.

Palpitations and narrow-complex tachycardia.

A 56-year-old patient with a history of Parkinson's disease presented with palpitations and an apparently irregular narrow-complex tachycardia on electrocardiogram. The discrepancy in ventricular rate between the limb and precordial leads was the result of myopotentials from his tremors mimicking the QRS complexes in the limb leads. These myopotentials can be differentiated from true QRS complexes by the fact that they are usually variable in amplitude and occur at a frequency similar to that of limb tremors.

Adapalene 0.1% and benzoyl peroxide 2.5%: a novel combination for treatment of acne vulgaris.

Topical products commonly used to treat acne include retinoids and antimicrobials, due to their effects on different components of pathogenesis. Accordingly, a fixed combination of adapalene 0.1% and benzoyl peroxide (BPO) 2.5% was developed (Epiduo, Galderma) and was approved by the US FDA in December 2008 for the treatment of acne. The superior efficacy of this combination was demonstrated in 2 large randomized controlled trials. This paper reviews the evidence for efficacy and tolerability of the combination of the retinoid adapalene 0.1% and BPO 2.5%, a once-daily gel formulation for the treatment of acne.

New developments in hormonal therapy for acne.

Oral contraceptives (OCs) are a valuable option for the treatment of women with acne. The use of OCs can be considered across the spectrum of acne disease severity in women. In Canada, three preparations are approved for mild-to-moderate acne, and a fourth is indicated for severe acne. These formulations contain estrogen in the form of ethinyl estradiol and a progestin. In Canada, the most recently approved OC is ethinyl estradiol 0.03 mg and drospirenone 3mg (Yasmin, Bayer). With the accumulating evidence on the efficacy and safety of drospirenone-containing hormonal preparations, this formulation provides dermatologists with a new treatment option for acne and other hyperandrogenic disorders.

Clinics in diagnostic imaging (109). Nocardial adrenal abscess.

A 34-year-old man presented with a two-month history of intermittent fever and left loin pain. A large left suprarenal mass was detected on computed tomography and magnetic resonance imaging. Blood pressure, serum electrolytes, serum cortisol and urinary catecholamines were normal. Laparoscopic adrenalectomy was planned but the mass was found to be an isolated adrenal abscess due to Nocardiosis. He was later found to have AIDS. The clinical utility of various imaging modalities and management of adrenal cysts are reviewed.

Artificial urinary sphincter in adult male with neurogenic stress urinary incontinence: a rare indication.

INTRODUCTION: The artificial urinary sphincter (AUS) is a rare indication for stress urinary incontinence secondary to spinal cord injury. CLINICAL PICTURE: A 48-year-old male sustained spinal cord injury, resulting in detrusor acontractility and urinary stress incontinence. TREATMENT AND OUTCOME: An AUS was implanted and the patient achieved complete urinary continence. CONCLUSION: The AUS is an appropriate and durable device for management of patients with neurogenic stress incontinence.

Psychosocial impact of acne vulgaris: evaluating the evidence.

This paper reviews current evidence presented by recent studies on the impact of acne on psychosocial health. Study methodologies, including case-control and cross-sectional surveys, have demonstrated psychological abnormalities including depression, suicidal ideation, anxiety, psychosomatic symptoms, including pain and discomfort, embarrassment and social inhibition. Effective treatment of acne was accompanied by improvement in self-esteem, affect, obsessive-compulsiveness, shame, embarrassment, body image, social assertiveness and self-confidence. Acne is associated with a greater psychological burden than a variety of other disparate chronic disorders. Future studies with a longitudinal cohort design may provide further validation of the causal inference between acne and psychosocial disability provided by the current literature.

Erectile dysfunction in Singapore: prevalence and its associated factors--a population-based study.

PURPOSE: To study the prevalence of erectile dysfunction (ED) in Singapore males aged 30 and above and its association with demographic, medical and other risk factors. METHODOLOGY: A population based cross sectional study of 729 men aged 30 and above in Singapore was conducted using the abridged, five-item version of the International Index of Erectile Function (IIEF-5). Presence of erectile dysfunction was defined as IIEF-5 score of less than 21. Erectile dysfunction was further categorised into mild (IIEF-5: 16-20), moderate (IIEF-5: 11-15) and severe (IIEF-5: <11). A logistic regression model was used to identify significant independent risk factors for ED. RESULTS: Overall, 51.3% of respondents (n=374) reported some degree of erectile dysfunction. Of these, 23.2% have mild ED, 8.8% have moderate ED and 19.3% had severe ED. The prevalence of ED increased from 42.8% for men in their forties to 77.4% in their sixties. The prevalence of severe ED increased from 9.1% in men in their forties to 43.5% in their sixties and 77.0% in those aged 70 and above. Age above 50 years is the single most significant risk factor on multivariate analysis when adjusted for all confounding factors. Other important risk factors include Indian ethnic group, lower household income, physical inactivity, diabetes mellitus and cardiac diseases. CONCLUSION: Erectile dysfunction is common amongst Singaporean men. Age is the single most important physiologic factor affecting erectile function. The prevalence and severity increased significantly with age after 50 years old. With an ageing population, erectile dysfunction may become a significant health problem. Health care providers should plan their resources accordingly.