Association between atopic dermatitis and hypertension: a systematic review and meta-analysis.

BACKGROUND: Previous studies have found conflicting results about the association of atopic dermatitis (AD) with hypertension. OBJECTIVES: To determine whether AD and AD severity are associated with hypertension. METHODS: A systematic review was performed of published studies in Ovid MEDLINE, Embase, Scopus, Web of Science, and GREAT (Global Resource for EczemA Trials) databases. At least two reviewers conducted title/abstract, full-text review and data extraction. Quality of evidence was assessed using the Newcastle-Ottawa Scale. RESULTS: Fifty-one studies met the inclusion criteria and 19 had sufficient data for meta-analysis. AD was associated with higher odds of hypertension compared with healthy controls [increased in nine of 16 studies; pooled prevalence 16·4% vs. 13·8%; random-effects regression, pooled unadjusted odds ratio (OR) 1·16, 95% confidence interval (CI) 1·04-1·30], but lower odds of hypertension compared with psoriasis [decreased in five of eight studies; 15·4% vs. 24·8% (OR 0·53, 95% CI 0·37-0·76)]. In particular, moderate-to-severe AD was associated with hypertension compared with healthy controls [increased in four of six studies; 24·9% vs. 14·7% (OR 2·33, 95% CI 1·10-4·94)]. Hypertension was commonly reported as an adverse event secondary to AD treatments, particularly systemic ciclosporin A. Limitations include lack of longitudinal studies or individual-level data, and potential confounding. CONCLUSIONS: AD, particularly moderate-to-severe disease, was associated with increased hypertension compared with healthy controls, but with lower odds than for psoriasis.

What are the best endpoints for Eczema Area and Severity Index and Scoring Atopic Dermatitis in clinical practice? A prospective observational study.

BACKGROUND: Multiple strategies have been used to evaluate the minimal important change (MIC) of the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD). The meaningfulness of these MICs is not well established across all severities of atopic dermatitis (AD). OBJECTIVES: To determine the MIC of percentage and absolute improvement of EASI and SCORAD scores in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 826). An anchor-based approach was used to determine thresholds for the percentage and absolute MICs of EASI, SCORAD and objective SCORAD (O-SCORAD) at follow-up from baseline. RESULTS: One-grade improvements of Physician's Global Assessment (PGA) and validated Investigator Global Assessment scale for AD (vIGA-AD) were associated with 50%, 35% and 35% decreases of EASI, SCORAD and O-SCORAD, respectively. The thresholds for percentage MIC of EASI (Kruskal-Wallis test, P = 0·61), SCORAD (P = 0·07) and O-SCORAD (P = 0·09) were similar across baseline AD severities. One-grade improvements of PGA and vIGA-AD were associated with 14·0- and 14·9-point decreases of EASI, 19·9- and 14·9-point decreases of SCORAD, and 15·5- and 17·4-point decreases of O-SCORAD. The thresholds for the absolute MIC of EASI (P < 0·001), SCORAD (P < 0·001) and O-SCORAD (P < 0·001) significantly differed by baseline AD severity. Percentage and absolute MICs for EASI and SCORAD were associated with improvements of AD symptoms and quality of life. CONCLUSIONS: EASI 50, SCORAD 35 and O-SCORAD 35 were meaningful percentage MICs regardless of baseline AD severity. The absolute MICs for EASI, SCORAD and O-SCORAD varied by baseline AD severity.

Measurement properties of the Rajka-Langeland severity score in children and adults with atopic dermatitis.

BACKGROUND: Multiple atopic dermatitis (AD) severity scales exist, with no gold standard for use in clinical practice. OBJECTIVES: To determine the measurement properties of the Rajka-Langeland score and compare it with other clinician-reported outcomes in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 427). RESULTS: Rajka-Langeland had good concurrent validity with the Eczema Area and Severity Index (Spearman rho = 0·63), SCORing AD (SCORAD) (rho = 0·61), objective-SCORAD (rho = 0·52) and body surface area (rho = 0·51); good convergent validity with the numeric rating scale average-itch (rho = 0·60) and worst-itch (rho = 0·59), Patient-Oriented Eczema Measure (rho = 0·57), Dermatology Life Quality Index (rho = 0·53), Patient-Reported Outcomes Measurement Information System Itch Questionnaire (rho = 0·35-0·55) in adults and/or children; fair discriminant validity for patient- and physician-reported global AD severity; good responsiveness to change of severity of AD and itch; good reliability; internal consistency; with no floor or ceiling effects. Interpretability bands (3, clear/almost clear; 4-5, mild; 6-7, moderate; 8-9, severe) and minimal clinically important difference (1 point) were established. CONCLUSIONS: The Rajka-Langeland score showed good construct validity, reliability, internal consistency and responsiveness in adults and children with AD.

Measurement properties of the product of investigator's global assessment and body surface area in children and adults with atopic dermatitis.

BACKGROUND: Multiple clinician-reported outcome measures exist for atopic dermatitis (AD) severity. However, there is no gold standard for use in clinical practice. OBJECTIVES: To determine the measurement properties of the product of validated Investigator's Global Assessment for AD (vIGA) and body surface area (BSA) overall or divided into six categories (cBSA: 0%/0.1, <10%/10, <30%/30, <50%/50, <70%/70 and <90%/90-100%) and compare with other clinician-reported and patient-reported outcomes in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 653). RESULTS: vIGA*BSA and vIGA*cBSA had good convergent validity with BSA (Spearman's ρ = 0.97 and 0.93), eczema area and severity index (ρ = 0.94 and 0.92), and objective SCORAD (ρ = 0.88 and 0.89); and weak-to-good convergent validity with Numeric Rating Scale average itch (ρ = 0.22 and 0.22) and worst itch (ρ = 0.27 and 0.28), Patient-Oriented Eczema Measure (ρ = 0.44 and 0.43), Dermatology Life Quality Index (ρ = 0.48 and 0.49), ItchyQOL (ρ = 0.45 and 0.46), PROMIS Sleep Disturbance (ρ = 0.46 and 0.37) and sleep-related impairment (ρ = 0.31 and 0.31) in adults and/or children; very good discriminant validity for physician-reported global AD severity; good responsiveness to change of severity of AD and itch; and good reliability (intraclass correlation coefficient [95% confidence interval]: 0.72 [0.60-0.81] and 0.74 [0.62-0.82]) with no floor or ceiling effects. Thresholds for interpretability bands and clinically important difference were established. CONCLUSIONS: vIGA*BSA and vIGA*cBSA scores showed good convergent and discriminant validity, reliability, responsiveness and interpretability in adults and children with AD, and were feasible for use in clinical practice. vIGA*BSA and vIGA*cBSA had slightly lower convergent validity than EASI or objective SCORAD, but might be more efficient to collect and score.

Associations of cutaneous and extracutaneous infections with hidradenitis suppurativa in U.S. children and adults.

BACKGROUND: Hidradenitis suppurativa (HS) is associated with bacterial colonization, skin-barrier disruption, immune dysregulation and treatments that can increase infection risk. OBJECTIVES: To determine whether HS is associated with cutaneous and extracutaneous infections and related outcomes. METHODS: Data from the 2002-2012 National Inpatient Sample were analysed, including a 20% sample of U.S. hospitalizations (n = 87 053 155). RESULTS: The prevalence (with 95% confidence interval) of infections was higher in adults (34·0%, 33·2-34·7% vs. 23·4%, 23·2-23·6%) and children (31·8%, 28·7-34·9% vs. 12·6% (12·1-13·1%) with vs. without HS. Inpatients with HS had higher prevalences of infections overall (excluding cellulitis and erysipelas) than those with psoriasis, but lower than those with atopic dermatitis. In multivariable logistic regression models adjusting for sociodemographics, HS was associated with 18 of 45 infections examined (adults: 16 of 45; children: six of 45), including acute infections (herpes simplex virus, herpes zoster, necrotizing fasciitis, septicaemia, bone infection, Clostridium difficile, methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Streptococcus, Pseudomonas, mycobacterial, fungal, viral), chronic infections (HIV, hepatitis B) and antibiotic-resistant infections. HS alone was associated with increased infections. Patients with comorbid cancer; HIV; cardiometabolic, autoimmune or mental health diagnoses or acne had even higher odds of infections. Inpatients with HS with vs. without serious infection had increased inpatient mortality (0·71% vs. 0·16%), mean length of stay (7·3 vs. 4·8 days) and cost of care (US$13 578 vs. $9242), with a mean annual excess 41 050 days and $71 622 339 cost of hospitalization. CONCLUSIONS: Adults and children with HS had increased acute and chronic, cutaneous, extracutaneous and systemic infections, which were associated with increased mortality and cost. What's already known about this topic? Little is known about the risk of infection in patients with hidradenitis suppurativa (HS). What does this study add? Adults and children with HS had increased cutaneous, extracutaneous and systemic infections, at even higher rates than in patients with psoriasis and atopic dermatitis. These infections were associated with increased inpatient mortality and cost. Respond to this article.

Measurement properties of the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire: itch severity assessments in adults with atopic dermatitis.

BACKGROUND: Little is known about the validity of numeric rating scales (NRS) and verbal rating scales (VRS) for itch and itch frequency for assessing itch severity in atopic dermatitis (AD). We evaluated the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire (PIQ) - itch severity assessment, including multiple NRS, VRS and frequency of itch assessments, in adults with AD and compared their performance. METHODS: Self-administered questionnaires and skin examinations were performed in 410 patients with AD (aged 18-90 years) in a dermatology practice setting. RESULTS: PIQ NRS, VRS and frequency of itch had good content validity, strong correlations with one another (Spearman correlations P < 0·001) and weak-to-moderate correlations with patient-oriented eczema measure (POEM), Eczema Area and Severity Index (EASI), objective SCORing AD (SCORAD) and Dermatology Life Quality Index (DLQI) (P < 0·001) and very good discriminant validity. Changes from baseline in NRS, VRS and frequency of itch were moderately to strongly correlated with one another, and weakly to moderately correlated with other patient-reported (POEM, SCORAD itch, DLQI) and clinician-reported outcomes (EASI, objective SCORAD). NRS and VRS worst itch and average itch showed moderate-to-good test-retest reliability. There were no floor or ceiling effects for NRS or VRS itch, but there were ceiling effects for itch frequency. Each assessment was completed in < 1 min by all patients. CONCLUSIONS: NRS, VRS and frequency of itch items from PIQ - itch severity showed good content and construct validity, reliability, and/or responsiveness in adults with AD, and were feasible for use in clinical trials and practice. What is already known about this topic? Numeric rating scales (NRS), verbal rating scales (VRS) and frequency of itch have been used to assess the burden of itch. However, there have been limited results demonstrating their validity, responsiveness, interpretability and feasibility, particularly in atopic dermatitis (AD). What does this study add? This study demonstrated that NRS, VRS and frequency of itch items from the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire (PIQ) - itch severity assessments had good construct validity, responsiveness, reliability and feasibility in the assessment of adult AD. PIQ NRS, VRS and frequency of itch all appear to have sufficient validity, reliability and feasibility for use as assessments of itch in adults with AD in clinical practice and trials. What are the clinical implications of this work? PIQ NRS and VRS are all simple, valid, reliable and feasible for use in clinical practice and trials to assess itch in adults with AD. Linked Comment: Oosterhaven. Br J Dermatol 2020; 183:802-803.

Validation of Patient-Reported Outcomes Information System Sleep Disturbance and Sleep-Related Impairment in adults with atopic dermatitis.

BACKGROUND: Sleep disturbances are common in adults with atopic dermatitis (AD). Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) are validated questionnaires to assess sleep in adults. Little is known about their measurement properties in adults with AD. OBJECTIVES: To assess the measurement properties of the PROMIS SD and SRI eight-item short forms in AD. METHODS: We performed a prospective dermatology-practice-based study using questionnaires and evaluation by a dermatologist (n = 420). RESULTS: PROMIS SD and SRI showed moderate correlations to each other (ρ = 0·67), and weak correlations with Patient-Oriented Eczema Measure (ρ = 0·43 and 0·39, respectively); average (ρ = 0·31/0·30) and worst numerical rating scale for itch (ρ = 0·32/0·30); Eczema Area and Severity Index (ρ = 0·41/0·31); and Scoring Atopic Dermatitis (SCORAD) (ρ = 0·44/0·30) (Spearman correlations, P < 0·001). PROMIS SD and SRI increased significantly and stepwise with more frequent sleep disturbance, severe itch and self-reported global AD severity (ancova, P < 0·001). PROMIS SD and SRI showed good internal consistency (Cronbach alpha 0·84 and 0·91). Changes from baseline in PROMIS SD and SRI were weakly to moderately correlated with each other and with changes of multiple patient-reported and clinician-reported AD outcomes. There were no floor or ceiling effects for PROMIS SD or SRI. The median completion time for PROMIS SD and SRI was 2 min. CONCLUSIONS: PROMIS SD and SRI showed good construct validity, internal consistency, responsiveness and feasibility to assess sleep in adult patients with AD. What is already known about this topic? The Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) scales were found to be valid in adults with chronic disease. However, the validity and feasibility of PROMIS SD and SRI in atopic dermatitis remain unknown. What does this study add? This study demonstrated that PROMIS SD and SRI had good content, concurrent, convergent and discriminant validity; feasibility; and responsiveness, with no floor or ceiling effects observed. What are the clinical implications of this work? The PROMIS SD and SRI eight-item bank short forms appear to have sufficient validity and feasibility to be used as assessments for burden of sleep in adults with atopic dermatitis in clinical practice.

Association between hidradenitis suppurativa and hospitalization for psychiatric disorders: a cross-sectional analysis of the National Inpatient Sample.

BACKGROUND: Hidradenitis suppurativa (HS) is associated with pain, disfigurement, psychosocial distress and poor quality of life, all of which may lead to a higher likelihood of mental health (MH) disorders. However, little is known about the MH comorbidities of HS. OBJECTIVES: To determine the MH disorders and cost burden associated with HS. METHODS: Data were examined from the 2002-2012 National Inpatient Sample, comprising approximately a 20% sample of all U.S. paediatric and adult hospitalizations (87 053 155 admissions). RESULTS: MH disorders were much more common in inpatients with vs. without HS (34·27% vs. 20·05%). In multivariable logistic regression models controlling for sex, age, race/ethnicity and insurance status, HS was associated with significantly higher odds of an MH disorder (adjusted odds ratio 2·53, 95% confidence interval 2·42-2·63), including 10 of 15 MH disorders examined. In contrast, HS was not associated with primary hospitalization for an MH disorder overall (odds ratio 0·95, 95% confidence interval 0·84-1·07), but it was associated with primary hospitalization for eight of 15 MH disorders examined. Among inpatients with HS, primary admission for an MH disorder was associated with female sex, public or no insurance and more chronic diseases, but inversely associated with older age and nonwhite race/ethnicity. HS was associated with > $38 million (USD) of excess mean annual costs of hospitalization for MH disorders. CONCLUSIONS: Inpatients with HS had increased odds of comorbid MH disorders, overall, and multiple primary MH admissions, in particular, which were associated with considerable excess costs.

Measurement properties of three assessments of burden used in atopic dermatitis in adults.

BACKGROUND: Standardized quality-of-life (QoL) assessments can provide important and clinically relevant information. There is currently a lack of standardization in QoL assessments used in atopic dermatitis (AD). OBJECTIVES: To determine the content validity, construct validity, internal consistency, differential reporting, responsiveness, floor or ceiling effects and feasibility of the Dermatology Life Quality Index (DLQI), Itchy Quality of Life (ItchyQoL) and 5-dimensions (5-D) itch scales for assessing burden of AD in adults and to compare their performance. METHODS: Self-administered questionnaires and skin examination were performed in 340 adults with AD in a dermatology practice setting. RESULTS: DLQI, ItchyQoL and 5-D all had good content validity. DLQI, mean ItchyQoL and 5-D itch all had strong correlations with frequency of AD symptoms (Patient-Oriented Eczema Measure) and intensity of itch (numerical rating scale for itch), and moderate correlations with AD severity (Eczema Area and Severity Index and Scoring Atopic Dermatitis) (Spearman correlations, P < 0·001 for all). DLQI and 5-D itch showed good internal consistency (Cronbach's alpha = 0·89 and 0·84), although ItchyQoL appeared to have several redundant items (alpha = 0·96). Uniform and nonuniform differential item functioning by age, sex and/or race/ethnicity was found for multiple items in DLQI, ItchyQoL and 5-D itch. DLQI, ItchyQoL and 5-D itch scores all demonstrated responsiveness, although ItchyQoL demonstrated the greatest responsiveness. There were no floor or ceiling effects for total scores. The median times for completion of DLQI, ItchyQoL and 5-D itch were 2 min. CONCLUSIONS: The DLQI, ItchyQoL and 5-D itch scales all showed good content and construct validity, and responsiveness in the assessment of AD in adults, and were feasible for use in clinical trials and practice.

The mental health burden in acne vulgaris and rosacea: an analysis of the US National Inpatient Sample.

BACKGROUND: Little is known about the mental health (MH) hospitalization among patients with acne and rosacea. AIMS: To determine the MH disorders and cost burden associated with acne and rosacea. METHODS: Data were examined from the 2002-2012 US National Inpatient Sample, comprising a sample of ~20% of all US paediatric and adult hospitalizations (n = 87 053 155 admissions). RESULTS: A diagnosis of ≥ 1 MH disorder was much more common among all inpatients with vs. those without a diagnosis of acne (43.7% vs. 20.0%, respectively) and rosacea (35.1% vs. 20.0%, respectively). In multivariable logistic regression models controlling for sex, age, race/ethnicity and insurance status, acne (adjusted OR = 13.02; 95% CI 11.75-14.42) and rosacea (adjusted OR = 1.70; 95% CI 1.56-1.95) were associated with significantly higher odds of a primary admission for an MH disorder (13 and 8, respectively, of 15 MH disorders examined). Both acne and rosacea were associated with higher risk of mood, anxiety, impulse control and personality disorders, and with > $2 million of excess mean annual costs of hospitalization for MH disorders in the USA. CONCLUSION: In this study, inpatients with acne or rosacea had increased odds of comorbid MH disorders. In particular, there was an increased number of hospital admissions secondary to a primary MH disorder with coexistent acne/rosacea. MH comorbidities were associated with considerable excess costs among inpatients with acne or rosacea.

Association of vitiligo with hospitalization for mental health disorders in US adults.

BACKGROUND: Vitiligo has a complex bidirectional relationship with mental health (MH) disturbances. However, little is known about the relationship between vitiligo and MH emergencies. OBJECTIVE: To examine the associations of vitiligo and MH hospitalizations in the United States. METHODS: Data from the 2002 to 2012 National Inpatient Sample were analysed, including a ~20% sample of all US hospitalizations (n = 87 053 155 children and adults). Prevalence of hospitalization for MH disorders, their length of stay (LOS) and cost of care were determined for those with vitiligo compared to those without vitiligo. RESULTS: Hospitalization for MH disorders occurred more commonly in those with vitiligo compared to those without vitiligo (4.17% vs. 2.18%). In multivariable logistic regression models, vitiligo was associated with higher odds of admission for any MH disorder [adjusted odds ratio (95% confidence interval): 1.69 (1.61-1.78)], including 14 of 15 MH disorders examined. Associated MH disorders included anxiety, schizophrenia, depression, suicidal risk, personality disorder, ADD/ADHD and conduct disorder, substance use disorder, childhood and adolescent psychiatric illnesses, alcohol-related disorders, adjustment disorders, developmental disorders, impulse control disorders, history of mental health disorders and miscellaneous mental health disorders. Vitiligo patients hospitalized with any MH disorder had higher geometric-mean (95% confidence interval) cost of inpatient care [$10 992 ($10 477-$11 507) vs. $10 082 ($9728-$10 435)] and LOS [5.6 (5.3-5.8) vs. 4.8 (4.6-4.9); P < 0.0001] compared to those without vitiligo, with $10.5 million excess annual costs from hospitalization with MH disorders in persons with vitiligo. CONCLUSIONS: Persons with vitiligo had increased hospitalization for multiple MH disorders, which were associated with a considerable cost burden.

Risk Factors for Sputum Positive Pulmonary Tuberculosis Retreatment Cases and Factors Responsible for Treatment Outcome.

BACKGROUND: Identification of the characteristics that confer higher risk of relapse, failure, or default and factors associate with treatment outcome in retreatment cases may help in planning country-specific prevention strategies. OBJECTIVE: To evaluate the risk factors for retreatment failure, default or relapse and factors responsible for the treatment outcome. METHODS: In this study sputum positive pulmonary TB retreatment cases were included. All patients were treated by eight months Revised National Tuberculosis Control Program (RNTCP) Cat II regimen. Outcome was recorded as Cured, Failure, Death or Defaulted. RESULTS: Patients having body weight > 45 kgs had higher cure rates (94.74%). Poor outcome was significantly higher in patient with cavitory lesions on Chest X ray (30.43% vs 7.14%) and in patient with bilateral lesions (28.57% vs 4.35%). Patients with initial sputum of 3 + grade was significantly associated with poor outcome than having sputum of scanty to 2 + grade (26.93% vs 8%). CONCLUSION: Patients presenting for TB retreatment have distinct demographic and clinical characteristics, important difference in retreatment outcomes in relation to different parameters. So, new country specific strategies are required to identify and address risk factor for retreatment cases and factors responsible for poor outcome of these cases.

A randomized phase IIa study of quantified bone scan response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride alone or in combination with abiraterone acetate/prednisone or enzalutamide.

BACKGROUND: In metastatic castration-resistant prostate cancer (mCRPC), assessing treatment response and bone lesions with technetium-99m is limited by image resolution and subjectivity. We evaluated bone scan lesion area (BSLA), a quantitative imaging assessment of response in patients with mCRPC receiving radium-223 alone or in combination with androgen receptor pathway inhibitors (abiraterone/prednisone or enzalutamide). PATIENTS AND METHODS: This randomized, non-comparative phase IIa three-arm trial (NCT02034552) evaluated technetium-99m-based BSLA response rate (RR), safety, radiologic progression-free survival (rPFS), and time to first symptomatic skeletal event (SSE) in men with mCRPC and bone metastases receiving radium-223 with/without abiraterone/prednisone or enzalutamide. The primary endpoint was week 24 BSLA RR. RESULTS: Overall, 63 patients received treatment (abiraterone/prednisone combination, n = 22; enzalutamide combination, n = 22; radium-223 monotherapy, n = 19). Median treatment duration (first to last dose of any study treatment) was 12 months (abiraterone/prednisone combination), 10 months (enzalutamide combination), and 3 months (radium-223 monotherapy). Week 24 BSLA RR was 58% [80% confidence interval (CI) 41% to 74%; one-sided P < 0.0001; 11/19 patients] with abiraterone/prednisone combination, 50% (32% to 68%; one-sided P < 0.0001; 8/16 patients) with enzalutamide combination, and 22% (10% to 40%; one-sided P = 0.0109; 4/18 patients) with radium-223 monotherapy. Median rPFS was not evaluable for combination arms and 4 months (80% CI 4 to 12) for monotherapy. SSEs were reported in 32% of patients; median time to first SSE was not estimable. Fatigue and back pain were the most commonly reported treatment-emergent adverse events (TEAEs); more patients receiving combination therapy than monotherapy had TEAEs. Fractures were reported in 18% receiving abiraterone/prednisone, 32% receiving enzalutamide, and 11% receiving radium-223 monotherapy. Fracture rates were lower in patients taking bone health agents versus not taking bone health agents at baseline. CONCLUSIONS: Technetium-99m imaging BSLA may offer objective, quantifiable assessment of isotope uptake changes, and potentially treatment response, in patients with mCRPC and bone metastases treated with radium-223 alone or in combination with abiraterone/prednisone or enzalutamide. In this largely treatment-naive population, BSLA RR was numerically lower with radium-223 monotherapy versus combination therapy, indicating a limited role as first-line treatment. Use of radium-223 should follow evidence-based treatment guidelines and the licensed indication.

Measurement of circulating tumor cells in squamous cell carcinoma of the head and neck and patient outcomes.

OBJECTIVES: We report the outcomes of patients with squamous cell carcinoma of the head and neck (HNSCC) whose circulating tumor cells (CTCs) were quantified using surface-enhanced Raman scattering (SERS) nanotechnology. METHODS: SERS tagged with EGF was used to directly measure targeted CTCs. Patient charts were retrospectively reviewed. An optimal cut point for CTCs in 7.5 ml of peripheral blood predictive of for distant metastasis-free survival (DMFS) was identified by maximizing the log-rank statistic. An ROC analysis was also performed. RESULTS: Of 82 patients, 13 experienced metastatic progression. The optimal cut point for DMFS was 675 CTCs (p = 0.047). For those with distant recurrence (n = 13) versus those without distant recurrence (n = 69), the CTC cut point which results in the largest combined sensitivity and specificity values is also 675 (sensitivity = 69%, specificity = 68%). CONCLUSION: Liquid biopsy techniques in HNSCC show promise as a means of identifying patients at greater risk of disease progression.

Clinical implications of p53 alterations in oral cancer progression: a review from India.

p53 plays a central role in prevention of normal cell from the development of the malignant phenotype. Somatic alterations (mutations, loss of heterozygosity, deletions) in p53 are a hallmark of most human cancers and cause defects in normal p53 function. However, in the tumors harboring wild-type p53, there are alterations in the regulation of the p53. Thus, understanding why p53 is unable to perform its role as a tumor suppressor in these wild-type tumors is very crucial. Germ-line polymorphisms in p53 are also anticipated to cause measurable disturbance in p53 function. Over-expression as well as polymorphic variants of MDM2 might have effects on cancer development. In addition, degradation of p53 by E6 protein of high risk human papillomavirus is also suggested as one of the mechanisms which attenuate p53 responses in oral carcinogenesis. p53 has also been demonstrated to mediate cellular responses upon various DNA damaging cancer therapies, importantly, apoptosis. These responses have been implicated in an individual's ability to respond to these cancer therapies. Thus, exploring mechanisms by which normal function of p53 is affected in the comprehensive way in oral cancer might aid in the identification of tumor characteristics, prognosis and thus in the development of a new approach to treat the oral cancer.

The adverse effects of an excessive folic acid intake.

Folate is a vital component of a healthy diet, being essential for numerous bodily functions. Deficiency of folate is common, with studies suggesting prevalence of deficiencyas high as 85.5% as was shown in women between the ages of 16 and 49, living in the UK. Causes of folate deficiency range from diet and lifestyle, to pathological and pharmacological processes. Because of the well-known role of folate in prevention of neural tube defects, numerous countries have implemented strategies to increase folate intake, with programs such as mandatory grain fortification. As a result, the intake of folate in these countries is often higher than the recommended dietary allowance for many groups of people. Although folate is believed to be non-toxic, the potential adverse effects of excessive intake of folic acid (synthetic form of folate) have not been highlighted well by authorities to people taking supplements; despite this, many studies have addressed this issue. However, the results of these studies provide discrepant results, leading to confusion as to whether mandatory folic acid fortification should be introduced in other countries. The purpose of this review was to provide a summary of evidence related to high folic acid ingestion and to look at the unwanted effects it may have on the certain groups within the general population.

Mast cell-derived neurotrophin 4 mediates allergen-induced airway hyperinnervation in early life.

Asthma often progresses from early episodes of insults. How early-life events connect to long-term airway dysfunction remains poorly understood. We demonstrated previously that increased neurotrophin 4 (NT4) levels following early-life allergen exposure cause persistent changes in airway smooth muscle (ASM) innervation and airway hyper-reactivity (AHR) in mice. Herein, we identify pulmonary mast cells as a key source of aberrant NT4 expression following early insults. NT4 is selectively expressed by ASM and mast cells in mice, nonhuman primates, and humans. We show in mice that mast cell-derived NT4 is dispensable for ASM innervation during development. However, upon insults, mast cells expand in number and degranulate to release NT4 and thus become the major source of NT4 under pathological condition. Adoptive transfer of wild-type mast cells, but not NT4-/- mast cells restores ASM hyperinnervation and AHR in KitW-sh/W-sh mice following early-life insults. Notably, an infant nonhuman primate model of asthma also exhibits ASM hyperinnervation associated with the expansion and degranulation of mast cells. Together, these findings identify an essential role of mast cells in mediating ASM hyperinnervation following early-life insults by producing NT4. This role may be evolutionarily conserved in linking early insults to long-term airway dysfunction.

Modification of vesicle surfaces with amphiphilic sterols. Effect on permeability and in vivo tissue distribution.

In this paper, we describe the permeability of vesicles prepared with various synthetic cholesterol derivatives. Cholesterol derivatives with side-chains ending in hydroxyl groups reduced the permeability of unilamellar vesicles. However, addition of cholesterol derivatives with terminal amino groups makes the vesicles more permeable. Vesicles prepared with a short-chain amino-cholesterol derivative were found to be less permeable in phosphate-buffered saline, but not in bovine serum, while long-chain amino-cholesterol-containing vesicles were very permeable in both media. Studies in vivo indicate a rapid clearance rate for intravenously administered amino-cholesterol-containing vesicles with a concomitant increase in liver uptake. However, no difference was found in either the clearance or tissue distribution of control vesicles and the less permeable hydroxyl-cholesterol-containing vesicles.

The pharmacological efficacy of a rigid non-phospholipid liposome drug delivery system.

Hydration of an ethoxylate derivative of cholesterol, triethoxycholesterol, results in the formation of stable, rigid, bilayer-like structures capable of encapsulating polar compounds. Studies on the stability and tissue distribution of these liposomes in mice indicate that they are suitable as a drug delivery system. Intraperitoneal injection of triethoxycholesterol encapsulated methotrexate into mice bearing hepatoma ascites tumor results in a doubling of the survival time, relative to untreated mice and those receiving unencaptulated drug. These studies show that fluid, acyl chains are not required for the formation of pharmacologically useful vesicles and that such formulations need not be limited to phospholipid-containing systems.