Increased risk of lung cancer in patients with eczema: a nationwide cohort study in Taiwan.

BACKGROUND: The association between lung cancer and eczema remains controversial. Previous studies have yielded conflicting results. This retrospective population-based cohort study is aimed at clarifying the risk of lung cancer associated with eczema. PATIENTS AND METHODS: By using the Taiwan National Health Insurance Research Database, we identified 43,719 patients who had been newly diagnosed with eczema in the years 2000 to 2010. The comparison cohort included 87,438 randomly selected, age-matched patients without eczema. The cases of these two cohorts were followed until 2011. The Cox proportional hazard regression model was used to calculate the risk of lung cancer in eczema patients. The database did not contain any information regarding smoking, alcohol consumption, socioeconomic status, or family history. RESULTS: After adjusting for age and comorbidity, the population with eczema had a 2.80-fold greater risk of developing lung cancer compared with the population in the comparison cohort (adjusted hazard ratio 2.80, 95 % confidence interval 2.59-3.03). Eczema patients with comorbid diseases including asthma, chronic obstructive -pulmonary disease, alcoholic liver damage, or diabetes were at a higher risk of lung cancer compared with the non-eczema patients without comorbidity. CONCLUSIONS: Eczema is associated with a greater risk for the development of lung cancer. Further studies with more comprehensive information on potential confounders are warranted.

Erhöhtes Lungenkrebs-Risiko bei Ekzempatienten: eine landesweite Kohortenstudie in Taiwan.

HINTERGRUND: Der Zusammenhang zwischen Lungenkrebs und Ekzemen bleibt umstritten. Frühere Studien haben zu widersprüchlichen Ergebnissen geführt. Diese retrospektive populationsbasierte Kohortenstudie zielt darauf ab, das Risiko von Lungenkrebs im Zusammenhang mit Ekzemen abzuklären. PATIENTEN UND METHODEN: In der Forschungsdatenbank der taiwanesischen nationalen Krankenversicherung identifizierten wir 43719 Patienten, bei denen in den Jahren 2000 bis 2010 ein Ekzem neu diagnostiziert wurde. Die Vergleichskohorte bildeten 87438 zufällig ausgewählte, altersangepasste Patienten ohne Ekzem. Die Fälle aus diesen beiden Kohorten wurden bis 2011 verfolgt. Zur Kalkulation des Lungenkrebsrisikos bei Ekzempatienten wurde die Cox-Regression verwendet. Die Datenbank enthielt keine Informationen über Raucherstatus, Alkoholkonsum, sozioökonomischen Status oder Familienanamnese. ERGEBNISSE: Nach der Bereinigung um Alter und Komorbidität hatte die Population mit Ekzemen ein um 2,80 erhöhtes Risiko für die Entwicklung von Lungenkrebs gegenüber der Vergleichskohorte (bereinigte Hazard-Ratio 2,80, 95 % Konfidenzinterval 2,59-3,03). Ekzempatienten mit Begleiterkrankungen, darunter Asthma, chronisch obstruktive Lungenerkrankungen, alkoholbedingten Leberschäden oder Diabetes, hatten ein höheres Lungenkrebsrisiko als Patienten ohne Ekzeme oder Komorbidität. SCHLUSSFOLGERUNGEN: Ekzeme gehen mit einem höheren Risiko für die Entwicklung von Lungenkrebs einher. Weitere Studien mit umfassenderen Informationen über weitere potentielle Einflussfaktoren sind sinnvoll.

Association between antidiabetic drugs and psoriasis risk in diabetic patients: results from a nationwide nested case-control study in Taiwan.

BACKGROUND: The risk of psoriasis in diabetic patients has rarely been explored. OBJECTIVES: We sought to investigate the association between antidiabetic therapies and psoriasis. METHODS: The incidence of psoriasis was compared between a representative diabetic cohort and a matched nondiabetic cohort. We next conducted a nationwide cohort study with 1,659,727 diabetic patients using the National Health Insurance Research Database of Taiwan 1997 through 2011. Multivariate conditional logistic regression was used for nested case-control analyses. RESULTS: Incidence rates of psoriasis among diabetic patients and nondiabetic matched control subjects were 70.2 (95% confidence interval [CI] 59.5-80.9) and 42.3 (95% CI 39.5-45.5) per 100,000 person-years, respectively (P < .0001). Frequent insulin use was associated with higher risk of incident psoriasis (adjusted odds ratio 1.29, 95% CI 1.18-1.42) after adjusting for comorbidities, disease duration, and number of hospital visits. Among diabetic patients without history of insulin use, frequent use of thiazolidinedione was associated with lower risk of psoriasis (adjusted odds ratio 0.87, 95% CI 0.77-0.99). LIMITATIONS: The National Health Insurance Research Database did not contain information regarding disease severity, diet, body mass index, lifestyle, or family history. CONCLUSION: Among diabetic patients, regular insulin use is associated with psoriasis development. Frequent use of thiazolidinedione may be associated with modest reduction in psoriasis risk.

Bullous systemic lupus erythematosus in a child responding to dapsone.

Bullous systemic lupus erythematosus is a subepidermal blistering disorder that primarily affects young women and only rarely occurs in children. We report a case of bullous systemic lupus erythematosus refractory to corticosteroid therapy in a 12-year-old boy who was successfully treated with oral dapsone.

Antipruritic effect of cold stimulation at the Quchi acupoint (LI11) in mice.

BACKGROUND: Acupuncture and moxibustion are used to treat pruritus and atopic dermatitis. However, whether cold stimulation (defined as that the temperature conducted under skin temperature) of acupoints affects itching in experimental murine models remains unclear. METHODS: The present study was designed to determine the therapeutic effects of different thermal stimulations at the Quchi acupoint (LI11) in a murine model in which scratching behaviour was elicited by subcutaneous injection with a pruritogenic agent (compound 48/80). Male ICR mice were divided into several groups as follows: control (saline), those receiving compound 48/80 and compound 48/80 with various thermal stimulations (5°C-45°C) at LI11 (n = 6 per group). The scratch response of each animal to these stimulations was recorded for 30 min. The antipruritic effect of the acupoint was further evaluated in LI11 and sham (non-acupoint) groups (n = 6 per group). RESULTS: Treatment with lower temperature (20°C) at the LI11 acupoint significantly attenuated compound 48/80-induced scratching; however, this antipruritic effect was not observed with stimulation at the sham point. The expression of c-fos in the neuron of the cervical spine induced by compound 48/80 was suppressed by cold stimulation at LI11. The antipruritic effect of cold stimulation was blocked by ruthium red (RR), a non-selective transient receptor potential (TRP) channel blocker, suggesting that TRP channels may play an important role in the antipruritic effect of cold stimulation at LI11 in mice. CONCLUSIONS: This study demonstrated that cold stimulation at LI11 attenuated compound 48/80-induced scratching behaviour in mice, possibly by a TRP-related pathway.

Association between traditional systemic antipsoriatic drugs and tuberculosis risk in patients with psoriasis with or without psoriatic arthritis: results of a nationwide cohort study from Taiwan.

BACKGROUND: Although the link between tuberculosis (TB) and biologics use is well established, the risk of TB among patients with psoriasis exposed to traditional systemic therapies remains elusive. OBJECTIVES: The aim is to investigate the association between traditional systemic therapies and TB among patients with psoriasis. METHODS: We conducted a retrospective cohort study on the risk of active TB among patients with psoriasis and psoriatic arthritis, using the National Health Insurance Research Database of Taiwan, 1996 through 2008. Standardized incidence ratios of TB were analyzed in comparison with age- and gender-matched general population. Logistic regression was used in a nested case-control analysis to estimate the odds ratios of TB related to exposure to traditional systemic agents during the year before TB development. RESULTS: Among the 81,266 patients in the psoriasis cohort, 497 new active TB cases were identified. The incidence rate of TB was 102 cases per 100,000 person-years among patients with psoriasis (standardized incidence ratio 1.22, 95% confidence interval 1.18-1.33). The risk of TB was higher in patients with severe disease (standardized incidence ratio 1.52, 95% confidence interval 1.46-1.74). To facilitate comparisons with the 497 active TB cases, a total of 1988 matched control subjects were selected for a nested case-control study. Patients taking systemic corticosteroids and nonsteroidal anti-inflammatory drugs were associated with higher incidence of TB, especially frequent users, after adjustment for multiple TB risk factors, drug exposures, hospital visits, and level of urbanization. Stratified analyses of current users and new users of these drugs revealed similar results. Finally, traditional systemic antipsoriatic treatment was not associated with TB on any of the analyses. LIMITATION: The National Health Insurance Research Database did not contain information regarding severity of psoriasis, smoking status, alcohol use, diet, laboratory parameters, chest radiograph, or history of recent contact with an individual with TB. Misclassification of disease cannot be ruled out in a registry-based database. The accessibility of health care may be associated with the level of urbanization, which could confound the effect of drugs in multivariate analyses. CONCLUSIONS: Severe psoriasis may be associated with an elevated TB risk. Traditional systemic therapies do not seem to be strongly associated with TB occurrence.

Association between systemic antipsoriatic drugs and cardiovascular risk in patients with psoriasis with or without psoriatic arthritis: a nationwide cohort study.

OBJECTIVE: Psoriasis is associated with ischemic heart disease (IHD). Results of prior studies have suggested that methotrexate (MTX) may improve vascular disease in patients with psoriasis and rheumatoid arthritis. The aim of this study was to assess the risk of new-onset IHDs in psoriasis patients, comparing those taking MTX with those taking other nonbiologic antipsoriatic drugs. METHODS: In this retrospective cohort study, we utilized claims data from the National Health Insurance Research Database of Taiwan to identify 179,200 subjects who had received a diagnosis of psoriasis, with or without psoriatic arthritis, on at least 3 visits. The risk of hospitalization for new-onset IHD was compared between psoriasis patients taking MTX monotherapy (n = 6,578; MTX case cohort) and psoriasis patients taking other nonbiologic antipsoriatic drugs (n = 5,471; reference control cohort) between January 1996 and December 2008. Additional adjustments were made for cardiovascular risk factors, number of hospital visits, Charlson comorbidity score, and use of other antiinflammatory drugs. RESULTS: The incidence rates of IHD were 666 cases per 100,000 person-years in the MTX case cohort and 830 cases per 100,000 person-years in the reference control cohort (unadjusted P = 0.027). Increasing age, male sex, presence of hypertension, presence of diabetes, Charlson comorbidity score, and use of phototherapies were independent risk factors for hospitalization related to a new IHD in the study cohorts. However, the multivariate-adjusted hazard ratio for IHD-related hospitalizations among patients receiving MTX, in comparison with those receiving other nonbiologic antipsoriatic drugs, was 0.97 (95% confidence interval 0.79-1.19), after adjustment for age, sex, comorbidity score, number of hospital visits, and other antiinflammatory treatments for psoriasis. CONCLUSION: In patients with psoriasis with or without coexisting psoriatic arthritis, the adjusted risk of hospitalization for an IHD among individuals receiving MTX was comparable with that among individuals receiving other nonbiologic antipsoriatic drugs.

Protective effect of Flos carthami extract against ethylene glycol-induced urolithiasis in rats.

Flos carthami (FC), also known as Carthamus tinctorius, is a traditional Chinese herbal plant that has been prescribed since centuries for treating various symptoms related to blood circulation improvement. This study aimed to investigate the effects of FC on calcium oxalate (CaOx) formation in ethylene glycol (EG)-fed rats. A total of 50 male Sprague-Dawley rats were divided into the following 6 groups: group 1, as the normal control (n = 5); group 2 received gastric gavages of starch and 0.75% EG (placebo, n = 5) as a stone inducer; group 3 (n = 10) received EG and potassium citrate as positive controls; group 4 (n = 10) received 0.75% EG and 300 mg/day FC; group 5 (n = 10) was treated with EG and 600 mg/day FC; group 6 (n = 10) received with EG and 1,200 mg/day FC. For all experimental animals, 24-h urine and blood samples were analyzed at the beginning and end of the experiment. Kidney tissue was histopathologically examined using a polarized light microscope, and crystal deposits were evaluated by a semi-quantitative scoring method; these scores were significantly lower in the FC groups (600 and 1,200 mg/day) than in the placebo group. Thus, FC administration appeared to inhibit the deposition of CaOx crystal EG-fed rats. We, therefore, consider that FC may be effective for preventing stone disease, albeit with certain side effects, such as a bleeding tendency. Further clinical trials are needed for evaluating its benefits and possible side effects.

The risk of cancer in patients with psoriasis: a population-based cohort study in Taiwan.

BACKGROUND: An association between psoriasis and malignancy has been explored. However, no studies have been reported regarding cancer risk in Asian psoriasis populations. OBJECTIVES: The aim of this study was to investigate the risk of cancer development in association with psoriasis. The effects of age at diagnosis, treatment modalities, and observation time were also evaluated. METHODS: Data for this retrospective population-based cohort study were obtained from the Taiwan National Health Insurance Research Database (NHIRD). This study included 3,686 patients with first-time diagnosis of psoriasis between 1996 and 2000. Another 200,000 patients without psoriasis served as the comparison group. All enrolled subjects were followed-up until the end of 2007. Cumulative incidences and hazard ratios (HRs) of cancer development were determined. RESULTS: Among the 3,686 psoriasis patients, 116 had incident cancers. The 7-year cumulative incidence of cancer among psoriasis patients was 4.8%. The adjusted HR for developing a cancer in association with psoriasis was 1.66 (95% confidence interval [CI], 1.38-2.00). Cancer risk was higher in male patients than in female patients (adjusted HR 1.86 vs.1.14, respectively). Certain cancers were significantly associated with psoriasis, including those of the urinary bladder and skin, followed by oropharynx/larynx, liver/gallbladder, and colon/rectum. Patients with psoriasis had an increased adjusted HR for cancer that varied by age. Younger patients with psoriasis tended to have the greatest risk of cancer. Finally, systemic phototherapy and oral medication did not significantly increase the risk of cancer. Phototherapy with UVB appeared to reduce the risk of cancer in psoriasis (adjusted HR, 0.52; 95% CI, 0.29-0.95; P = .03). LIMITATIONS: NHIRD did not contain information regarding severity of psoriasis, status of smoking, alcohol use, family history of cancer, or diet. Misclassification of disease cannot be ruled out in a registry-based database. CONCLUSIONS: Psoriasis carries an elevated risk of malignancies, especially in younger and in male patients. This effect is independent of systemic treatment for psoriasis. Finally, phototherapy with UVB did not increase, but rather reduced, the risk of cancer in psoriasis.

Impact of shock wave lithotripsy on heart rate variability in patients with urolithiasis.

The physiological response of the cardiac autonomic nervous system during shock wave lithotripsy (SWL) remains unclear. Heart rate variability (HRV) is an index of cardiac autonomic balance. This study aimed to analyze HRV during SWL in patients with urolithiasis. Electrocardiograms of patients who underwent SWL were obtained. Recordings were obtained before and after SWL. For each time point, the recordings were obtained continuously for 6 min, after which R wave-to-R wave (RR) intervals were extracted. The time digital sequence derived from RR intervals was the HRV signal. Time-domain analysis revealed that the mean of RR intervals (MRR) and standard deviation of normal beat-to-normal beat (NN) intervals (SDNN), but not the square root of the mean squared difference of successive NNs (RMSSD) or triangular interpolation of NN intervals (TINN), significantly increased during SWL. The increase in SDNN persisted after SWL but MRR returned to the initial level. Frequency-domain analysis revealed that very low frequency (VLF), low frequency (LF), and LF/high frequency (HF) ratio significantly increased after SWL, while there was no statistically significant difference in HF. Thus, the patients had significantly high MRR and SDNN during SWL and significantly high SDNN, VLF, LF, and LF/HF ratio after SWL. SWL could alter the functioning of the cardiac autonomic nervous system, resulting in reduction in sympathetic activity and increase in parasympathetic activity. Further studies with larger samples are required to confirm these findings and understand the underlying mechanisms.

Neuron Regeneration and Proliferation Effects of Danshen and Tanshinone IIA.

This study evaluates the proliferative effects of danshen and its monomer extract, tanshinone IIA, on Schwann cell proliferation. A piece of silicone rubber was guided across a 15-mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of danshen (0-100 mg/mL). The results showed that danshen increased the expressions of uPA, cyclin D1, E and ERK, JNK, and P38 MAP kinases via the FGF-2 signaling pathway in a dose-dependent manner. RSC96, Schwann cells were also administered with danshen (0, 20, 40, 60, 80, and 100 µg/mL) and tanshinone IIA (0, 2, 4, 6, 8, and 10 µg/mL). In lower concentrations, danshen and tanshinone IIA exhibited an apparent effect on Schwann cells. Similar effects were also demonstrated in the FGF-2-uPA regulating cascade and cell cycle proliferative protein results. Schwann cell migration was elevated as well. We used MAPK-signaling chemical inhibitors and identified the proliferative effects of danshen and tanshinone IIA as MAPK-signaling dependent. The results from the in vitro systems indicate that danshen and tanshinone IIA can be used to induce Schwann cell proliferation, and in vivo results potentially suggest that danshen and tanshinone IIA might enhance neuron regeneration.

Transcutaneous electrical nerve stimulation on ST36 and SP6 acupoints prevents hyperglycaemic response during anaesthesia: a randomised controlled trial.

BACKGROUND AND OBJECTIVE: Hyperglycaemia is a common result of stress signals caused by pain and surgical procedure. Volatile anaesthetics also directly manipulate glucose homeostasis by affecting pancreatic insulin release and induce hyperglycaemia without surgical stress. We determined the preoperative application of transcutaneous electrical nerve stimulation (TENS) to the Chinese acupoints ST36 (Zusanli) and SP6 (Sanyinjiao) as a complementary therapy for controlling plasma glucose and improving insulin resistance during anaesthesia. METHODS: We designed a single-blind, randomised controlled clinical study of female patients, scheduled for elective hysterectomy. The 52 patients consented to enrolment and were assigned to receive either TENS (n = 26) on bilateral ST36 and SP6 acupoints with continuous mode at a frequency of 15 Hz and the intensity of 10 mA synchronously for 30 min or non-stimulation (placebo group, n = 26) preoperatively. Haemodynamics, blood glucose and plasma insulin were measured during general anaesthesia. RESULTS: At baseline, there was no significant difference between the TENS group and the placebo group in plasma glucose and insulin levels as well as homeostasis model assessment (HOMA) index. In the placebo group, plasma glucose, insulin and HOMA index increased during induction of general anaesthesia, surgical incision, and throughout the operation. Plasma glucose and insulin levels as well as HOMA index were significantly lower in the TENS group as compared to the placebo group at different time points after discontinuation of TENS application. These results indicate the positive effect of prevention of hyperglycaemia and the increased sensitivity of plasma insulin in the TENS group. CONCLUSION: We found TENS at bilateral ST36 and SP6 acupoints to be an alternative means of managing the plasma glucose level and improving insulin resistance perioperatively.

Association of interleukin-18 gene polymorphisms with calcium oxalate kidney stone disease.

OBJECTIVE: The interleukin-18 (IL-18) encoding gene has three common single-nucleotide polymorphisms at -607C/A, -137G/C and +105A/C, which have been reported to be associated with several diseases. The aim of this study is to test whether IL-18 polymorphisms could act as genetic markers for renal stone disease. MATERIAL AND METHODS: A control group of 104 healthy subjects, and 272 patients with recurrent calcium oxalate stones were examined. Polymerase chain reaction-based restriction endonuclease analysis was used to detect IL-18 polymorphisms. RESULTS: The patient and control groups differed significantly in genotypic expression of the IL-18 +105A/C polymorphism. The prevalence of the A/C + C/C genotypes in the patients was higher than that in the controls. The allelic frequency of IL-18 +105A/C differed significantly between the patients and the controls. The odds ratio (OR) of the A/C heterozygote of IL-18 +105A/C associated with urolithiasis was 2.772. The OR of the A/C + C/C genotypes of IL-18 +105A/C associated with urolithiasis was 3.097. The OR per copy of the C allele of IL-18 +105A/C associated with urolithiasis was 4.143. There were also significant differences in the prevalence of genotype IL-18 -137G/C polymorphisms between the patients and controls. The distribution of the G/G homozygote in the patients was higher than that in the controls. There was no significant difference in genotype and allelic frequency at the IL-18 -607C/A polymorphism between patients and control subjects. CONCLUSION: The results indicate that IL-18 +105A/C polymorphisms may play a role in the development of urolithiasis.

Identification of melamine/cyanuric acid-containing nephrolithiasis by infrared spectroscopy.

Melamine-contaminated milk formula caused infant nephrolithiasis in some areas of China. Its combination with cyanuric acid causes crystallization in renal tubules. Following this renal damage and even renal failure that require long-term hemodialysis has been reported. Therefore, correct and timely diagnosis of these complex diseases is critical. Melamine containing stone is a combination of equal molar ratios of common stone compositions that has been reported from previous animal studies. We have previously identified the compositions of urinary tract stones with infrared (IR) spectroscopy. We hypothesized that the absorbance of wavelength of IR can identify melamine/cyanuric acid in the presence of mixing human stone compositions. In this study, we made an artificial stone composition and examine under IR absorbance by mixing equal molar ratios of melamine/cyanuric acid with different types of human urinary stones, and established a reference of IR analysis for the identification of melamine/cyanuric acid-containing human urinary tract stones. Knowledge of the precise stone composition allowed institution of appropriate prophylactic dietary and medical therapy and this may help in the prevention of urinary stone recurrence. The results are promising that melamine and cyanuric acid can be identified clearly in a low percentile (approximately 1%) of stone mixture pellet. Therefore, IR seems to be an ideal tool for the identification of melamine/cyanuric acid-containing stones.

Lack of association between transient receptor potential cation channel 6 polymorphisms and primary membranous glomerulonephritis.

Membranous glomerulonephritis (MGN) is one common cause of idiopathic nephrotic syndrome. Transient receptor potential cation channel 6 (TRPC6) has been identified as causing a familial form of progressive focal and segmental glomerulosclerosis. The objective was to clarify the relationship between TRPC6 polymorphisms and MGN. We recruited a cohort of 134 biopsy-diagnosed MGN patients and 265 healthy subjects. Genotyping of TRPC6 polymorphisms was performed using allele-specific polymerase chain reaction methods. We then analyzed associations between TRPC6 gene polymorphisms and clinical manifestations and pathogenesis of MGN. There was no statistically significant difference of TRPC6 gene rs3824935 C/T, rs17096918 C/T, and rs4326755 A/G polymorphisms between controls and patients with MGN. There was no statistical significance of allele frequencies in these two groups. The characteristics of clinical parameters in TRPC6 gene (rs3284935) C/T polymorphism revealed no difference except proteinuria (p < 0.0005) between CC and non-CC genotype in MGN patients. Besides, no apparent statistically significant differences of rs17096918 C/T (TT and non-TT) and rs4326755 A/G (AA and non-AA) polymorphisms between genotypes were found in the clinical parameters. There is no different genotype distribution between normal controls and patients with MGN of TRPC6 gene. The data also show that TRPC6 gene may not be associated with disease clinical course of MGN.

Honokiol and magnolol as multifunctional antioxidative molecules for dermatologic disorders.

Chinese herbs have been and still are widely used as important remedies in Oriental medicine. Over the recent years, a variety of biologically active constituents have been isolated from these sources and confirmed to have multifunctional activity in experimental studies. Honokiol is a small-molecule polyphenol isolated from the genus Magnolia. It is accompanied by other related polyphenols, including magnolol, with which it shares certain biological properties. Recently, honokiol and magnolol have been found to have anti-oxidative, anti-inflammatory, anti-tumor, and anti-microbial properties in preclinical models, without appreciable toxicity. These findings have increased interest in bringing honokiol and magnolol to the clinic as novel therapeutic agents in dermatology. In this review, the findings concerning the major mechanisms of action of honokiol and magnolol are described. Knowledge of the multiple activities of honokiol and magnolol can assist with the development of honokiol and magnolol derivatives and the design of clinical trials that will maximize the potential benefit of honokiol and magnolol in the patient setting for dermatologic disorders.