New-onset COPD and Decline in Lung Function Among Wood Dust-Exposed Workers: Re-analysis of a 6-year Follow-up Study

Abstract

Objectives

There is a lack of longitudinal studies exploring the association between organic wood dust exposure and new-onset chronic obstructive pulmonary disease (COPD) and change in lung function. We have re-investigated these associations in a 6-year follow-up cohort of furniture workers exposed to wood dust using improved outcome measures and methods.

Methods

A large follow-up study of 1112 woodworkers (63%) from the Danish furniture industry and 235 controls (57%) was conducted between 1998 and 2004. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and the ratio (FEV1/FVC) standardized for age, height, and sex using the Global Lung Function Initiative 2012 equations were assessed at baseline and follow-up. Questionnaires on respiratory symptoms, wood dust exposure, and smoking habits were collected. Exposure was assessed as exposure level at baseline and as cumulative exposure in the follow-up period from quantitative task specific job exposure matrix available at both baseline and follow-up based on personal dust sampling using passive dust monitors. The association between exposure to wood dust and new-onset COPD was assessed with logistic regression, whereas the association between wood dust and the longitudinal change in z-score for lung function was assessed with linear regression.

Results

Similar associations were seen for different exposure metrics. An exposure–response relation was seen for new-onset COPD for female smokers with an odds ratio (OR) (95% confidence interval [CI]) of 8.47 (0.9–82.4) in the highest exposed group compared to controls, and a significant test for trend P = 0.049. No such association was seen among males for whom only smoking was strongly associated to new-onset COPD. For change in lung function, a significant exposure–response was seen for females, confirming previous findings, with increasing levels of wood dust exposure showing larger decline in lung function (β [95% CI]: −0.32 ΔzFEV1 (−0.56 to −0.08, P = 0.009) for third quartile exposure compared to controls, test for trend, P = 0.005, equivalent to an excess loss of 125 ml in the 6 years of follow-up). An opposite association was seen for men.

Conclusion

In conclusion, we found that female woodworkers have a dose-dependent increased OR of new-onset COPD and an excess decline in lung function suggesting that female woodworkers may be more susceptible to wood dust exposure than male woodworkers. Among male woodworkers, only smoking and asthma were significant predictors for new-onset COPD and excess decline in lung function. These results emphasize that reduction in both smoking and wood dust exposure should continuously be an effort to prevent adverse pulmonary health effects.

Early‐onset neutropenia after rituximab therapy for bullous pemphigoid

Clinical and Experimental Dermatology, EarlyView.

Scarring alopecia with follicular papules in a father and his daughter

Clinical and Experimental Dermatology, EarlyView.

Concentrations and health risks of heavy metals in soils and crops around the Pingle manganese (Mn) mine area in Guangxi Province, China

Abstract

Heavy metal concentrations in agricultural fields and their ecological risks are a source of extensive concern worldwide. A field survey was conducted to investigate the present situation and health risks of heavy metals (Mn, Pb, Zn, Cu, and Cd) and crops (corn, green soybean, sweet potato, persimmon, cassava, and Chinese chestnut) around the Pingle manganese (Mn) mine site in Guangxi Province, China, which was abandoned 20 years ago. The results showed that the ranges of Mn, Pb, Zn, Cu, and Cd were 2706.54–6760.16, 229.37–275.84, 160.39–215.48, 58.11–75.30, and 5.78–6.98 mg kg⁻¹, respectively, which were approximately 15.38–38.41, 11.76–14.15, 2.12–2.85, 2.09–2.71, and 21.64–28.75 times greater than their respective background values. Most of these concentrations exceeded the national standard for soil quality (grade 2) developed by the Ministry of Environmental Protection of China (1995). Contamination assessments based on the single contamination index (P_i), Nemerow multi-factor index (P_com), and potential ecological risk index (RI) showed that the sampled soils were severely polluted with these heavy metals, especially Pb and Cd. Similarly, the crops were enriched with Pb and Cd, with concentrations of 10.22–41.78 and 2.33–5.37 mg kg⁻¹, respectively, which were much higher than the threshold values of the national food standards. Contamination assessments with P_i and P_com also showed that the crops were severely polluted with Pb and Cd. The bioaccumulation factor values for Cd were highest among the heavy metals, with an average mean of 0.66 in these six crops, demonstrating that Cd readily accumulates in these crops. An assessment showed that the health risk for adults living in the mining-impacted areas was significant. Our study strongly recommends that heavy metal contamination in agricultural soils and crops grown around the Pingle Mn mining-affected areas should be treated to mitigate the health risks.

“My clothes, pillowcases, and bedsheets have turned green-colored!”

Introduction: Chromhidrosis is a rare disorder in which there is pigmentation of sweat in a variety of colors. The condition can be categorized into apocrine, pseudoeccrine, and true eccrine chromhidrosis. Although it does not cause serious health problem, it may be associated with psychologic stress and social embarrassment. We report a rare case of idiopathic chromhidrosis in a healthy middle-aged female with no significant medical history. A 56-year-old woman with no significant medical history and no personal history of skin cancer presented with a chief complaint "my clothes, pillows, and bedsheets have turned green-colored from my sweats." The patient has noticed light green-colored stains on her pillow cases, bedsheets, and her underwear, shirts, and bras for the past 6 months without any identifiable precipitants or triggers.

Clinical assessment of the local tolerance and cosmetic efficacy of a topical skin care formulation used after 70% glycolic acid facial skin rejuvenation procedures in healthy female subjects: A randomized, controlled, evaluator-blind study

Background: Facial chemical peels are among the most widespread nonsurgical cosmetic procedures. Post-peeling guidelines recommend only the general use of topical emollients and the need for high factor broad spectrum sunscreens. However, clinical evidence on the use of specific emollients in this indication is limited.

Clinical complications of lepra reactions: An in-patient experience from Pakistan

Introduction: The World Health Organization stated the global prevalence of leprosy as 176,176 cases at the end of 2015. Leprosy is an incapacitating infectious disease primarily affecting the skin and peripheral nerves. Immunologic complications of leprosy occur as immune-mediated lepra reactions type 1 and 2. These reactions remain a diagnostic dilemma for many physicians, dermatologists and neurologists. Despite the success of multidrug therapy these reactions cause considerable morbidity and physical disabilities by nerve damage.

Clinical evaluation of 11 investigational allergens in TRUE Test panel 3.2 in children and adolescents

Background: Epicutaneous patch testing is the criterion standard method to confirm contact sensitization, the first step in making the diagnosis of allergic contact dermatitis (ACD) in both adult and pediatric populations. Eleven new investigational allergens of the Thin-Layer Rapid Use Epicutaneous (TRUE) Test panels had been Food and Drug Administration (FDA) approved for adults for diagnosis of ACD, but not in children at the time of this study.

Clinical evaluation of a comprehensive topical antioxidant system in mildly to moderately photodamaged skin

Background: Topical antioxidants are fundamental to skin health. A product containing water-soluble, enzymatic, and lipid-soluble antioxidants provides protection at all cellular levels of the skin against the visible effects of ultraviolet (UV) and environmental damaging free-radicals.

Sensitive skin compatibility of cleansing wipes

Background: Individuals with sensitive skin should use skin cleansing products that are efficacious, nonirritating, and help maintain a healthy skin barrier. Facial cleansing wipes are a popular format used for general cleansing and make-up removal. A facial wipe was developed with nonionic surfactants, which were selected to provide nonirritating and efficacious cleansing, due to the surfactants' low protein-binding affinity. The unique blend of spun-lace nonwoven fibers in this facial wipe offers gentle and effective cleansing.

The rates of herpes zoster, hepatitis c, and tuberculosis among patients with psoriasis treated with apremilast, biologics, conventional systemics, and corticosteroids in the U.S. MarketScan database

Background: Patients (pts) with psoriasis are at increased risk for infection. We compared rates of treated herpes zoster, hepatitis C (HepC), and tuberculosis (TB) by treatment in pts with psoriasis.

Point-of-care decision support for appropriate acne management

Background: Referral from primary care providers for acne is a costly process associated with high no-show rates and delayed treatment. We previously demonstrated that models of algorithm-based acne care may lead to reductions in the rate of dermatology referrals, missed appointments, and delayed treatment. In this retrospective chart analysis, we evaluate the impact of an electronic decision support tool on the management of patients referred for acne.

Superior even skin tone and antiaging benefit of combination of 4-hexyl resorcinol and niacinamide

Unevenness of skin tone is a pervasive problem that develops with aging and sun exposure. Skin color results from the action of multiple biologic pathways that primarily control melanin synthesis and distribution. In the present studies we explored the possibility of using a synergistic approach to enhance the efficacy of cosmetic products. We evaluated the in vitro and clinical efficacy of a combination of 4-hexyl resorcinol, a known tyrosinase inhibitor and niacinamide, a melanosome transfer inhibitor, both of which regulate two different process involved in the development of skin color.

Reasons for discontinuation of secukinumab between weeks 12 and 52 in psoriasis patients responsive to treatment at week 12

Background: Patients enrolled in RCTs are subject to strict study guidelines to ensure validity, thus limiting a patients' ability to manage their own treatment plan. As such, rates and reasons for treatment discontinuation reported in secukinumab RCTs may not correlate to outcomes seen in the real world. Therefore, we aimed to investigate reasons for discontinuation of secukinumab between weeks 12 and 52 in patients who achieved efficacious outcomes at week 12.

Noxious nocebos in dermatology

Importance: Negative expectations on the part of the patient or the dermatologist can negatively influence treatment responses resulting in the nocebo effect.

The burden of nail psoriasis: A real-world analysis from the Corrona Psoriasis Registry

Objective: Nail psoriasis (Pso) is often correlated with more severe psoriatic disease and is difficult to treat; only a few studies have shown its association with significant functional and psychosocial impairment. The objective of this study was to describe the impact of nail Pso on clinical and patient-reported outcomes (PROs) among patients enrolled in the Corrona Psoriasis Registry.

Sonidegib preplanned subgroup analyses of objective response rates: 30-month results from the BOLT study

Background: Sonidegib 200 mg once daily (qd) was approved in the United States for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy based on results of the phase 2 BOLT study (NCT01327053). The 30-month overall efficacy and safety data from the BOLT study have been presented; here we report the 30-month results from a preplanned subgroup analysis for the primary end point, the objective response rate (ORR), in patients with laBCC receiving 200 mg, data which have not been presented.

Staphylococcus aureus biofilm in atopic dermatitis (AD): In vitro model and in vivo early AD study

Introduction and objectives: Biofilm is one of the most important virulence factors in infectious diseases; biofilm-associated bacteria show an innate resistance to antibiotics and host innate immune defenses. The presence of S. aureus biofilms in AD lesions has been described recently. In AD, biofilm seems to play a role in pruritus, inflammation and in resistance to antimicrobial peptides (PAMs). We used in vitro models to study the role of S. aureus and its biofilm in AD and to evaluate a lipid-replenishing balm specifically formulated for baby and child with atopic skin.

Patient profile of nonresponders to ustekinumab in moderate-to-severe psoriasis patients enrolled in the Corrona Psoriasis Registry

Objective: Describe the baseline characteristics of moderate to severe psoriasis (Pso) patients enrolled in the Corrona Psoriasis Registry who respond/did not respond to ustekinumab.

The impact of dermatology lectures on internal medicine residents

Background: Most medical students receive an average of 10 hours of dermatology teaching before starting residency, and only 25% take dermatology elective in medical school. Internal medicine (IM) residents regularly encounter dermatologic complaints and diseases, yet 63% of primary care residents state that they are inadequately prepared to diagnose common skin disorders. A recent study showed that an isolated didactic curriculum is a sufficient teaching method for IM residents, as measured by a multiple-choice test.

Targeted phototherapy: An eight-year experience in a tertiary dermatologic center

Background: Targeted phototherapy is the localized delivery of ultraviolet (UV) light to affected areas of skin. The commonest indications for targeted UV therapy include localized psoriasis, vitiligo, atopic dermatitis, and lymphoproliferative skin disorders involving a limited area of the body or difficult-to-treat anatomic areas. In view of advancing treatment options in the field of phototherapy for common skin conditions, little has been published about targeted phototherapy in Asian patients, especially in big numbers.

Subcorneal pustular dermatosis (Sneddon-Wilkinson disease): A case report with good reponse to cyclosporine and dapsone treatment

Introduction: Subcorneal pustular dermatosis (SCPD), or Sneddon-Wilkinson disease, is a rare chronic-relapsing skin disorder that manifests as flaccid sterile pustules without systemic symptoms. It typically presents in women over the age of 40, affecting the trunk and intertriginous areas. The treatment of choice is dapsone, although other drugs have been used. We report a 65-year-old woman with SCPD with a good response to cyclosporine and dapsone treatment.

Skin cancer with history of actinic keratosis: A large, urban, single-center, midwestern U.S. population observational study

Introduction: Actinic keratosis (AK) may be considered by some to be an incipient form of squamous cell carcinoma (SCC) as the rate of SCC in individuals with AK has been estimated at 0.025%-16%. There is much less reported evidence for AK association with basal cell carcinoma (BCC) and melanoma (MM). The aim of this study is to determine if an association exists between AK and nonmelanoma skin cancer (NMSC; SCC and BCC) and between AK and MM in a large midwestern U.S. patient population.

Scrofuloderma: Beyond a cutaneus tuberculosis

Science: Tuberculosis (TB) is a major public health issue worldwide. It has various clinical presentations making the diagnosis a challenge. Skin involvement is uncommon and scrofuloderma is the most frequent type of cutaneous TB. It results from direct dissemination to the skin of an underlying structure, primarily lymph nodes, and in rare cases can occur as a manifestation of miliary TB. An adequate anamnesis along with clinical suspicion are fundamental for timely diagnosis and treatment.

Annual variation patterns of the effluent water quality from a green roof and the overall impacts of its structure

Abstract

To explore the optimal combination of vegetation type, substrate type, and substrate thickness in a green roof and the interannual variation patterns of the runoff quality, eight green roof units were constructed in Shenzhen, China. Runoff quality of the eight units was monitored for 3 years (24 rainfall events). The rainfall event mean concentrations (EMC) were used to evaluate runoff quality as well as annual pollutant load. An orthogonal L₈(2⁴) experiment was designed to verify the significance of different factors. An optimal level of significant factors was selected to determine the optimal design of green roof. The optimal vegetation was Ophiopogon japonicus. The optimal substrate was modified perlite, while optimal substrate thickness was 200 mm. A three-year interannual variation analysis was performed on the optimal green roof. It was found that the interannual variation of each runoff quality index is different. The concentrations of SS, COD, and NH₄⁺-N in the runoff decreased with years. The concentration of NO₃⁻-N increased over time, while TP remained stable. The concentration of TN had certain volatility with no significant interannual variation. Overall, the runoff quality of the green roof improves over time. The optimal green roof's runoff quality in the third year including 11 rainfall events was monitored. Results showed that the effluent quality from the green roof was lower than that of precipitation. The average concentrations of SS, COD, NH₄⁺-N, TN, and TP decreased respectively by 37.85%, 28.89%, 30.25%, 14.52%, and 12.93%, but NO₃⁻-N increased by 69.91% comparing to the traditional roof.

Formation of 1,3,8-tribromodibenzo- p -dioxin and 2,4,6,8-tetrabromodibenzofuran in the oxidation of synthetic hydroxylated polybrominated diphenyl ethers by iron and manganese oxides under dry conditions

Abstract

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are ubiquitous and highly toxic emerging endocrine disruptors found in surface and subsurface soils and clay deposits. Seriously, they could be easily transformed to the more toxic dioxins (PBDD/Fs) in photochemical processes and incineration, but the spontaneous formation of PBDD/Fs has rarely been reported. This study focused on the formation of 1,3,8-tribromodibenzo-p-dioxin (1,3,8-TrBDD) and 2,4,6,8-tetrabromodibenzofuran (2,4,6,8-TeBDF) from 2′-OH-BDE-68 and 2,2′-diOH-BB-80 under the oxidization of iron and manganese oxides (goethite and MnO_x). Approximately 0.09 μmol/kg (2.33%) and 0.17 μmol/kg (4.15%) were transformed to 1,3,8-TrBDD and 2,4,6,8-TeBDF by goethite in 8 days and a higher conversion 0.15 μmol/kg (3.77%) and 0.23 μmol/kg (5.74%) were observed for MnO_x in 4 days. However, the formation of PBDD/Fs, probably proceeding via Smiles rearrangements and bromine elimination processes, was greatly inhibited by the presence of water. Transformation of OH-PBDEs by goethite and MnO_x was accompanied by release of Fe and Mn ions and the possible pathways for the formation of reaction products were proposed. In view of the ubiquity of OH-PBDEs and metal oxides in the environment, oxidation of OH-PBDEs mediated by goethite and MnO_x is likely an abiotic route for the formation of PBDD/Fs.

Issue Information

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue S6, Page 1-2, September 2018.

Poster

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue S6, Page 23-84, September 2018.

Freie Vorträge

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, Volume 16, Issue S6, Page 3-22, September 2018.

Acute effects of air pollution on type II diabetes mellitus hospitalization in Shijiazhuang, China

Abstract

Air pollution has been considered as an important contributor to diabetes development. However, the evidence is fewer in developing countries where air pollution concentrations were much higher. In this study, we conduct a time-series study to investigate the acute adverse effect of six air pollutants on type II diabetes mellitus (T2DM) hospitalization in Shijiazhuang, China. An over-dispersed passion generalized addictive model adjusted for weather conditions, day of the week, and long-term and seasonal trends was used. Finally, a 10-μg/m³ increase of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and carbon monoxide (CO) corresponded to 0.53% (95% confidence interval = 0.22–0.83), 0.32% (95% CI = 0.10–0.55), 0.55% (95% CI = 0.04–1.07), 1.27% (95% CI = 0.33–2.22), and 0.04% (95% CI = 0.02–0.06) increment of T2DM hospitalization, respectively. The effects of PM_2.5, PM₁₀, and CO were robust when adjusted for co-pollutants. The associations appeared to be a little stronger in the cool season than in the warm season. And stronger associations were found in male and elderly (≥ 65 years) than in female and younger people (35–65 years). Our results contribute to the limited data in the scientific literature on acute effects of air pollution on type II diabetes mellitus in developing countries. Main findings: This is the first adverse effect evidence of air pollution on T2DM in Shijiazhuang, a severely polluted city in China. Males were more vulnerable than females in severe pollution.

Good vibrations: itch induction by whole body vibration exercise without the need of a pruritogen

Experimental Dermatology, Volume 0, Issue ja, -Not available-.

Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer-types

Abstract

Background

We hypothesized that the abundance of PD1 mRNA in tumor samples might explain the differences in overall response rates (ORR) observed following anti-PD1 monotherapy across cancer-types.

Patients and Methods

RNASeqv2 data from 10,078 tumor samples representing 34 different cancer-types was analyzed from TCGA. Eighteen immune-related gene signatures and 547 immune-related genes, including PD1, were explored. Correlations between each gene/signature and ORRs reported in the literature following anti-PD1 monotherapy were calculated. To translate the in-silico findings to the clinical setting, we analyzed the expression of PD1 mRNA using the nCounter platform in 773 formalin-fixed paraffin embedded (FFPE) tumor samples across 17 cancer-types. To test the direct relationship between PD1 mRNA, PDL1 immunohistochemistry (IHC), stromal tumor-infiltrating lymphocytes (sTILs) and ORR, we evaluated an independent FFPE-based dataset of 117 patients with advanced disease treated with anti-PD1 monotherapy.

Results

In pan-cancer TCGA, PD1 mRNA expression was found strongly correlated (r > 0.80) with CD8 T-cell genes and signatures and the proportion of PD1 mRNA-high tumors (80^th percentile) within a given cancer-type was variable (0-84%). Strikingly, the PD1-high proportions across cancer-types were found strongly correlated (r = 0.91) with the ORR following anti-PD1 monotherapy reported in the literature. Lower correlations were found with other immune-related genes/signatures, including PDL1. Using the same population-based cutoff (80^th percentile), similar proportions of PD1-high disease in a given cancer-type were identified in our in-house 773-tumor dataset as compared to TCGA. Finally, the pre-established PD1 mRNA FFPE-based cutoff was found significantly associated with anti-PD1 response in 117 patients with advanced disease (PD1-high 51.5%, PD1-intermediate 26.6% and PD1-low 15.0%; odds ratio between PD1-high and PD1-intermediate/low=8.31; P < 0.001). In this same dataset, PDL1 tumor expression by IHC or percentage of sTILs were not found associated with response.

Conclusions

Our study provides a clinically applicable assay that links PD1 mRNA abundance, activated CD8 T-cells and anti-PD1 efficacy.

PD-L1 Expression, Tumor Mutational Burden, and Response to Immunotherapy in Patients with MET exon 14 Altered Lung Cancers

Abstract

BackgroundMET exon 14 alterations are actionable oncogenic drivers. Durable responses to MET inhibitors are observed in patients with advanced MET exon 14-altered lung cancers in prospective trials. In contrast, the activity of immunotherapy, PD-L1 expression and tumor mutational burden (TMB) of these tumors and are not well characterized.Patients and Methods Patients with MET exon 14-altered lung cancers of any stage treated at two academic institutions were identified. A review of clinicopathologic and molecular features, and an analysis of response to single-agent or combination immune checkpoint inhibition were conducted. PD-L1 immunohistochemistry was performed and TMB was calculated by estimation from targeted next-generation sequencing panels.Results We identified 147 patients with MET exon 14-altered lung cancers. PD-L1 expression of 0%, 1-49%, and ≥50% was 37%, 22%, and 41%, respectively, in 111 evaluable tumor samples. The median TMB of MET exon 14-altered lung cancers were lower than that of unselected non-small cell lung cancers (NSCLCs) in both independently-evaluated cohorts: 3.8 vs 5.7 mutations/megabase (p < 0.001, n = 78 vs 1,769, Cohort A), and 7.3 vs 11.8 mutations/megabase (p < 0.001, n = 62 vs 1,100, Cohort B). There was no association between PD-L1 expression and TMB (Spearman rho = 0.18, P = 0.069). In response-evaluable patients (n = 24), the objective response rate was 17% (95% CI 6-36%) and the median progression free survival was 1.9 months (95% CI 1.7 – 2.7). Responses were not enriched in tumors with PD-L1 expression ≥ 50% nor high TMB.Conclusion A substantial proportion of MET exon 14-altered lung cancers express PD-L1, but the median TMB is lower compared with unselected NSCLCs. Occasional responses to PD-1 blockade can be achieved, but overall clinical efficacy is modest.

Associations between RAD51D germline mutations and breast cancer risk and survival in BRCA1/2-negative breast cancers

Abstract

Background

RAD51D is involved in DNA double-strand break repair by homologous recombination and plays an important role in the maintenance of genomic stability. The associations between RAD51D germline mutations and breast cancer risk and survival are not fully elucidated.

Patients and methods

RAD51D germline mutations were determined using a multi-gene panel in 7657 unselected breast cancer patients who were negative for BRCA1/2 germline mutations. The RAD51D recurrent mutation p.K91fs was screened in 7947 healthy controls by Sanger sequencing.

Results

A total of 29 cases (0.38%) carried deleterious RAD51D germline mutations among this cohort of 7657 unselected breast cancer patients. The RAD51D recurrent mutation p.K91fs was identified in 18 cases (0.24%) of these 7657 patients. In contrast, the p.K91fs mutation was found in 8 of 7947 healthy controls with a frequency of 0.10%. The RAD51D p.K91fs mutation was significantly associated with increased breast cancer risk in unselected breast cancer [odds ratio=2.34, 95% confidence interval (CI) 1.02-5.38; P=0.040]. RAD51D mutation carriers were diagnosed at a younger age (P=0.006) and were more likely to be triple-negative breast cancer (P=0.003), estrogen receptor negative (P=0.005) and high-grade cancers (P=0.023) than non-carriers. Furthermore, RAD51D mutation carriers had a significantly worse recurrence-free survival [unadjusted hazard ratio (HR)=3.00, 95% CI 1.56-5.80; P=0.001] and distant recurrence-free survival (unadjusted HR = 2.54, 95% CI 1.14-5.67; P=0.023) than non-carriers.

Conclusion

The RAD51D recurrent mutation, p.K91fs, confers a moderately increased breast cancer risk, and RAD51D mutation carriers have an unfavorable survival compared with non-carriers.

Small repeated boluses are unreliable to provide rapid analgesia with intravenous morphine titration and mislead conversion ratio to oral morphine

Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer

Abstract

Background

We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC).

Patients and Methods

ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing (NGS) and FISH analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were performed to exclude confounders.

Results

Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients median PFS and OS was significantly lower compared to TP53 wildtype patients (PFS 3.9 months [95% CI: 2.4-5.6] vs. 10.3 months [95% CI: 8.6-12.0], p<0.001; OS 15.0 months [95% CI: 5.0-24.9] vs. 50.0 months [95% CI: 22.9-77.1], p=0.002). This difference was confirmed in all treatment-related subgroups including chemotherapy only (PFS first line chemotherapy 2.6 months [95% CI: 1.3-4.1] vs. 6.2 months [95% CI: 1.8-10.5], p=0.021; OS 2.0 months [95% CI: 0.0-4.6] vs. 9.0 months [95% CI: 6.1-11.9], p=0.035), crizotinib plus chemotherapy (PFS crizotinib 5.0 months [95% CI: 2.9-7.2] vs. 14.0 months [95% CI: 8.0-20.1], p<0.001; OS 17.0 months [95% CI: 6.7-27.3] versus not reached, p=0.049) and crizotinib followed by next-generation ALK-inhibitor (PFS next-generation inhibitor 5.4 months [95% CI: 0.1-10.7] vs. 9.9 months [95% CI: 6.4-13.5], p=0.039; OS 7.0 months vs. 50.0 months [95% CI: not reached] (p=0.001).

Conclusions

In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.

CO 2 bio-fixation and biofuel production in an airlift photobioreactor by an isolated strain of microalgae Coelastrum sp. SM under high CO 2 concentrations

Abstract

Microalgae cultivation is a promising approach to remove ambient CO₂ via photosynthesis process. This paper investigates the impact of high CO₂ concentrations (6, 12, and 16%) on algae growth, CO₂ biofixation, lipid and carbohydrate contents, and nutrient removal of newly isolated microalgae, Coelastrum sp. SM. In addition, the ability of microalgae to produce biodiesel at optimal condition was studied. The microalgae were cultivated in wastewater using an airlift photobioreactor. Under 12% CO₂, the maximum biomass productivity and CO₂ fixation rate were 0.267 g L⁻¹ day⁻¹ and 0.302 g L⁻¹ h⁻¹, respectively. Total Kjeldahl nitrogen (TKN), total phosphorous (TP), nitrate, and sCOD removal efficiency were 84.01, 100, 86.811, and 73.084%, respectively. Under 12% CO₂ and at the same condition for cell growth, the highest lipid and carbohydrate contents were 3 7.91 and 58.45%, respectively. The composition of fatty acids methyl ester (FAME) of the microalga lipid was defined. Based on the obtained results and FAME profile, Coelastrum sp. SM was a suitable feedstock for biodiesel production and also, the organism had a great potential for CO₂ biofixation, which is also more suitable than any other reported strains in other related studies.

Stéphanie Ruphy: Scientific Pluralism Reconsidered. A New Approach to the (Dis)Unity of Science

Transforming growth factor-β1 gene polymorphism in psoriasis vulgaris

Widespread keratosis pilaris in a patient with Noonan syndrome with multiple lentigines

International Journal of Dermatology, EarlyView.

Case of histiocytosis with bone involvement of fingers successfully treated with peginterferon‐α

The Journal of Dermatology, EarlyView.

Congenital nail clubbing

The Journal of Dermatology, EarlyView.

Treatment of psoriasis and psoriatic arthritis with secukinumab after unsatisfactory response to ustekinumab in multiple sclerosis patient

The Journal of Dermatology, EarlyView.

Case of anaphylaxis caused by black ginger in a dietary supplement

The Journal of Dermatology, EarlyView.

Evaluation of epicardial adipose tissue volume and coronary artery calcification in Japanese patients with psoriasis vulgaris

The Journal of Dermatology, EarlyView.

Case of anaphylaxis to lansoprazole confirmed by histamine release test and oral provocation test

The Journal of Dermatology, EarlyView.

Rhinosinusitis symptoms, smoking and COPD: prevalence and associations

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.

Interactions between Helicobacter pylori and gastroesophageal reflux disease

Abstract

Interactions between Helicobacter Pylori (HP) and gastroesophageal reflux disease (GERD) are a complex issue. Several pathophysiological factors influence the development and the course of GERD, HP infection might be only one of these. Many studies emphasize the co-existence of these diseases. HP infection could contribute to GERD through both a protective and an aggressive role. Gastric acid secretion is a key factor in the pathophysiology of reflux esophagitis. Depending on the type of gastritis related to HP, acid secretion may either increase or decrease. Gastritis in corpus leads to hypoacidity, while antrum gastritis leads to hyperacidity. In cases of antral gastritis and duodenal ulcers which have hyperacidity, the expectation is an improvement in pre-existing reflux esophagitis after eradication of HP. In adults, HP infection is often associated with atrophic gastritis in the corpus. Atrophic gastritis may protect against GERD. Pangastritis which leads to gastric atrophy is commonly associated with CagA strains of HP and it causes more severe gastric inflammation. In case of HP-positive corpus gastritis in the stomach, pangastritis, and atrophic gastritis, reflux esophagitis occurs frequently after eradication of HP. Nonetheless, as a predisposing disease of gastric cancer, HP should be treated. In conclusion, as the determinative factors affecting GERD involving in HP, detailed data on the location of gastric inflammation and CagA positivity should be obtained by the studies at future.

Conjunctival Retention Cysts: Outcomes of Aspiration and Sclerotherapy With Sodium Tetradecyl Sulfate

Purpose: To assess the outcome of aspiration and sclerotherapy with sodium tetradecyl sulfate in the management of conjunctival inclusion cysts. Methods: Retrospective interventional case series of 6 patients with clinical diagnosis of conjunctival inclusion cysts treated with cyst aspiration and foam sclerotherapy with 3% sodium tetradecyl sulfate. The volume of the sclerosant was 20% of the aspirated cyst volume. Results: Four patients had an inclusion cyst in anophthalmic sockets and 2 patients in sighted eyes. Average time lag between primary surgery and cyst formation was 14.6 months (range 2–30 months). Average amount of fluid aspirated from cyst was 3.07 ml (range 1–9 ml). Average volume of sclerosant injected was (20% of the aspirated volume) 0.55 ml (range 0.2–1.1 ml). All 6 patients showed complete resolution of cyst at a mean follow-up period of 15.6 months (range 9–24 months). All but one showed complete resolution of cyst with single injection sclerosant. Only 1 patient required a second sclerosant injection. There was no ocular surface or implant-related complications in this cohort. Conclusions: Cyst aspiration and sodium tetradecyl sulfate foam sclerotherapy is a minimally invasive procedure for the management of conjunctival inclusion cysts in anophthalmic sockets and sighted eyes. The injection of sodium tetradecyl sulfate in a dose of 20% of the aspirate is effective in the management of conjunctival inclusion cysts over a follow-up period of 13 months. The procedure is safe, with insignificant inflammation and without ocular surface or implant complications. Accepted for publication June 22, 2018. This study is funded by the Hyderabad Eye Research Foundation. The authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Tarjani Vivek Dave, M.D., L V Prasad Eye Institute, Kallam Anji Reddy Campus, Road No. 2, Banjara Hills, Hyderabad 500034, Telangana, India. E-mail: tvdeye@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Intracytoplasmic eosinophilic inclusion bodies with embryonic folliculosebaceous‐apocrine unit differentiation in syringocystadenoma papilliferum

Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.