Two-year follow-up of a dose reduction strategy trial of biologics adalimumab, etanercept, and ustekinumab in psoriasis patients in daily practice.

BACKGROUND/OBJECTIVES: Tightly-controlled dose reduction was possible during 1 year in psoriasis patients on adalimumab, etanercept or ustekinumab with low disease activity (CONDOR trial). Extended observation is needed to ensure long-term effectiveness and safety of the strategy. With prolonged follow-up, we investigated the clinical effects and safety of the strategy, the proportion of patients with successful dose reduction, and assessed if patients with a disease flare regained remission. METHODS: Two-year follow up of a subgroup of patients previously included in a randomized pragmatic study comparing usual care (UC) with stepwise dose reduction (DR). Effectiveness (Psoriasis Area and Severity Index, PASI), Dermatology Life Quality Index (DLQI), adverse events, proportion of patients with successful DR and proportion of persistent disease flares were analyzed. RESULTS: DR leads temporarily to a slightly increased PASI groupwise, but on the long-term patients regained low PASI. DLQI scores remained stable during follow-up. No serious adverse events due to DR were reported. Forty-one percent of patients remained on a low dose up to 2 years. The number of persistent flares was low in DR and UC. CONCLUSIONS: The proposed dose reduction strategy is effective for a significant part of patients and remains safe up to 2 years of follow-up.

Unmet Personal Patient Needs in Psoriasis Patients with Low Disease Activity on Adalimumab, Etanercept or Ustekinumab.

BACKGROUND: Personal treatment goals have been systematically investigated in psoriasis patients with active but not in controlled disease. OBJECTIVES: To explore patient needs in psoriasis patients with controlled disease due to biologic therapy with adalimumab, etanercept or ustekinumab. METHODS: Treatment needs in patients on adalimumab, etanercept or ustekinumab with a stable low disease activity for ≥ 6 months and preferably a Psoriasis Area and Severity Index (PASI) < 5, were explored with the Patient Needs Questionnaire (PNQ). Goal importance was expressed as overall mean importance score, percentage of patients that reported a goal to be quite/very important, and per PNQ subscale. Data were analysed separately for treatment, gender, age group (< 50 vs. ≥ 50 years), biologic naivety and willingness to participate in a pragmatic dose-reduction strategy. RESULTS: Sixty-five patients were included. 'To be free of itching', 'to be healed of all skin defects' and 'to have confidence in the therapy' were rated quite/very important in 78.5% of the patients, followed by 'to have no fear the disease will progress' (75.4%) and 'to get better skin quickly' (75.4%). Goals related to the subscale 'confidence in healing' were still of high importance in controlled disease. Least importance was attributed towards social goals. For female patients, it was significantly more important than for males to 'feel less depressed' and 'be comfortable showing yourself more in public'. CONCLUSIONS: Psoriasis patients with controlled disease still report substantial treatment needs, with high importance ascribed to confidence in healing. To apply personalized medicine, treatment needs should be explored on an individual level.

In psoriasis patients, a large reduction in disease severity can lead to a significant improvement in health-related quality of life. In addition to quality-of-life measurements, individual treatment goals can be assessed to evaluate patients' preferences regarding their psoriasis treatment. As opposed to patients with more severe psoriasis, unmet treatment needs in psoriasis patients with stable, low disease activity have barely been reported. In this study, the personal treatment aims of patients with controlled disease due to treatment with adalimumab, etanercept or ustekinumab were explored using the Patient Needs Questionnaire. Sixty-five patients with sustained low disease activity for ≥ 6 months were included. We found that despite low disease activity, these patients still have substantial patient needs. Patients attributed the highest importance to goals on confidence in healing, in contrast to social goals, which were valued of least importance. For female patients, it was significantly more important to 'feel less depressed' and 'be comfortable showing yourself more in public' compared to male patients. Previous treatment with biologic therapy was not associated with an altered attitude towards specific treatment goals. Our population with low disease activity seemed to award a lower level of importance to all treatment goals compared to groups of patients with more severe psoriasis that have been described in literature. Since treatment goals differ per patient, individual treatment could be optimized by actively inquiring about the patient's personal treatment goals. Clinicians should be aware that even in patients with controlled disease, substantial personal treatment needs remain.

Cannabidiol protects keratinocyte cell membranes following exposure to UVB and hydrogen peroxide.

Keratinocytes, the major cell type of the epidermis, are particularly sensitive to environmental factors including exposure to sunlight and chemical agents. Since oxidative stress may arise as a result of these factors, compounds are actively sought that can act as protective agents. Recently, cannabidiol (CBD), a phytocannabinoid found in Cannabis Sativa L., has gained increased interest due to its anti-inflammatory and antioxidant properties, and absence of psychoactive effects. This prompted us to analyze the protective effects of CBD on keratinocytes exposed to UVB irradiation and hydrogen peroxide. Here we show, using liquid chromatography mass spectrometry, that CBD was able to penetrate keratinocytes, and accumulated within the cellular membrane. CBD reduced redox balance shift, towards oxidative stress, caused by exposure UVB/hydrogen peroxide, estimated by superoxide anion radical generation and total antioxidant status and consequently lipid peroxidation level. CBD was found to protect keratinocytes by preventing changes in the composition of the cellular membrane, associated with UVB/hydrogen peroxide damages which included reduced polyunsaturated fatty acid levels, increased sialic acid and lipid peroxidation products (malondialdehyde and 8-isoprostanes) levels. This maintains cell membranes integrity and prevents the release of lactate dehydrogenase. In addition, CBD prevented UVB/hydrogen peroxide-induced reduction of keratinocyte size and zeta potential, and also decreased activity of ATP-binding cassette membrane transporters. Together, these findings suggest that CBD could be a potential protective agent for keratinocytes against the harmful effects of irradiation and chemical environmental factors that cause oxidative stress.

Frequency and predictors of a high clinical response in patients with psoriasis on biological therapy in daily practice: results from the prospective, multicenter BioCAPTURE cohort.

BACKGROUND: It is important to assess which patients with psoriasis are more likely to achieve high clinical responses on biologics. OBJECTIVES: To assess the number of treatment episodes (TEs) that achieve a 100% improvement in Psoriasis Area and Severity Index (PASI 100), PASI 90 or PASI ≤ 5 at week 24 of biological treatment, and which baseline patient characteristics predict treatment response. METHODS: Data from patients with psoriasis treated with adalimumab, etanercept, infliximab or ustekinumab were extracted from a prospective cohort. TEs with high clinical responses were described. Uni- and multivariate regression analyses were performed with the generalized estimating equation method to elucidate which baseline patient characteristics were predictors for PASI 90 and PASI ≤ 5 at week 24. RESULTS: In total, 454 TEs were extracted (159 adalimumab; 193 etanercept; 19 infliximab; 83 ustekinumab) from 326 patients. At week 24, in 3%, 15% and 59% of TEs, respectively, PASI 100, PASI 90 and PASI ≤ 5 was reached. In TEs without a PASI 100 or PASI 90 response, PASI ≤ 5 was still achieved in 58% and 52%, respectively. Baseline PASI ≥ 10 was a strong predictor for achieving PASI 90; baseline PASI < 10 and a lower baseline body mass index (BMI) were significant predictors for PASI ≤ 5 at week 24. CONCLUSIONS: A limited number of patients achieved PASI 100 or PASI 90 at 24 weeks of biological treatment. Including an absolute PASI score in the assessment of psoriasis severity is important. Baseline BMI was an important, modifiable predictor for a high response.

Modified Limberg transposition flap in the treatment of pilonidal sinus disease.

BACKGROUND: Pilonidal sinus disease (PSD) is a common problem in surgical practice. Different non-surgical and surgical methods have been used for treating PSD. Flap techniques including the Limberg flap have become more popular in recent years. A modified Limberg flap was used to reduce the problems of skin maceration and recurrence associated with the conventional Limberg flap technique. The aim of this retrospective study was to assess the effectiveness of the modified Limberg flap technique for PSD. METHODS: Medical records of 94 patients with PSD who had been treated with a modified Limberg flap between December 2006 and 2009 were evaluated. The patients' age, sex, duration of preoperative symptoms, operative time, mean hospital stay, postoperative complications, wound infection rate, maceration rate and recurrence rate, time until return to work, time until sitting on the toilet without pain, hypoesthesia in the gluteal region, and satisfaction score were recorded during follow-up or at the last interview. Clinical data were obtained at the end of the 5th postoperative day and at 1, 3, 6, and 12 months following surgery. RESULTS: There were 83 male and 11 female patients. The mean operative time was 38.95 ± 6.77 min (range 30-67 min). All patients were followed up longer than 12 months, and the mean follow-up period was 30.97 ± 12.7 months (range 12-54 months). While wound dehiscence was observed in only one patient, we did not detect any case of flap necrosis. Two cases of seroma were observed. Wound infection was detected in 5 patients (5.3%). Surgical drainage was performed in 2 cases. Another 3 patients were treated with oral antibiotics. Maceration of the surgical incision site was detected in 8 patients (8.5%) who were all successfully treated with conservative measures. There were 4 patients (4.2%) with recurrence in this series. CONCLUSIONS: When compared with the available data on use of the conventional Limberg flap for PSD, our results suggest that use of the modified Limberg flap is associated with a lower maceration and recurrence rate, and greater patient satisfaction.

The effect of p.Arg25Cys alteration in NKX2-5 on conotruncal heart anomalies: mutation or polymorphism?

Heterozygous mutations in the NKX2-5 gene of patients with various congenital heart defects have been reported. Most of the congenital heart defects associated with the mutations in the NKX2-5 gene are conotruncal heart anomalies, primarily the tetralogy of Fallot. In this study, the authors screened 72 Turkish children with conotruncal heart anomalies and 185 healthy control subjects to find the NKX2-5 alterations. They found one previously documented NKX2-5 missense alteration, heterozygous c.73C>T (p.Arg25Cys), in a 10-year-old boy with tetralogy of Fallot. The same heterozygous alteration was found also in the patient's healthy father and in two unrelated persons in the healthy control group. The current study shows for the first time the presence of p.Arg25Cys in healthy control subjects other than African Americans. These results show that no genetic support exists for the pathogenecity of this alteration, although a previous in vitro study and theoretical predictions suggest a structural/functional difference in the altered protein region.

First pulmonary valve replacement with Freedom Solo stentless valve in an adolescent. A case report.

Tetralogy of Fallot (TOF) is a common form of cyanotic heart disease. Complete surgical correction in younger age group offers good long-term results with reasonable morbidity and improved prognosis in patients with TOF. However, following corrective surgery pulmonary valve replacement (PVR) might be required for residual pulmonary regurgitation in order to avoid irreversible right ventricular remodeling. Otherwise, residual uncorrected pulmonary regurgitation may lead to right ventricular dilatation, impaired biventricular function, ventricular arrhythmias and limited exercise capacity. We report the first case of Freedom Solo stentless valve (Sorin Group, Saluggia, Italy) implantation in the pulmonary position in an adolescent with severe pulmonary insufficiency 12 years after the repair of TOF. Pericardial stentless valves may be an alternative choice for pulmonary valve replacement to improve right ventricular contractile recovery and remodeling after PVR and may have impact on long-term survival.

The value of the levels of acute phase reactants for the prediction of familial Mediterranean fever associated amyloidosis: a case control study.

In order to determine the role of levels of acute phase proteins (APPs) for the development of amyloidosis in familial Mediterranean fever (FMF) patients, the levels of serum amyloid A (SAA), C reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate were measured in paired sera of 36 FMF patients during and in between acute attacks, 39 of their healthy parents (obligate heterozgotes), and 15 patients with FMF associated amyloidosis. To compare the levels of APPs, 39 patients with chronic infections or inflammatory diseases who may develop secondary amyloidosis, 20 patients with acute infections who are known to have elevated acute phase response but will never develop amyloidosis and 19 healthy controls were included. The median levels of all APPs are increased in the patients with FMF during attacks and a significant decrease was observed after the attack was over. The level of SAA was above reference range in all FMF patients during the attack free period and the level of at least one other APP was also above normal in 64% of the patients. Both CRP and SAA levels were found to be higher in obligate heterozygotes compared to controls. The levels of SAA in patients with FMF during the attack-free period, obligate heterozygotes and patients with FMF-amyloidosis were found to be similar. The levels in each group were found to be higher than SAA levels found in healthy controls yet lower than the levels measured in the patients with acute infections and patients with chronic inflammation or chronic infections. In conclusion, our results show that SAA level reflects subclinical inflammation with high sensitivity but its value for the prediction of amyloid formation process seems to be low.

Prevalence of interatrial septal aneurysm in newborns and their natural course.

The objective of this study was to evaluate the prevalence of atrial septal aneurysm (ASA) in newborns, to define the natural course of ASA, and to investigate its role on closure of associated interatrial septal opening (IASO). A total of 1072 consecutive neonates were examined with echocardiography in the early postnatal period. The length of the interatrial septum, the diameter of IASO, the excursion and base of aneurysm, and the width of the related atrium were measured and the excursion ratio and the basal ratio were calculated for each neonate. Aneurysms with an excursion ratio > or = 25% were diagnosed as ASA. There were 81 neonates (7.6%) with ASA. The prevalence of ASA was 11.1% in preterm (14 of 126) and 7.1% in full-term newborns (67 of 946). All of the ASAs disappeared at the end of the first year of life, and there were no complications related to the lesion during the follow-up period. Although overall IASO prevalence was 78.6% (843 of 1072), it was 72.8% (59 of 81) among the cases with ASA. Although the disappearance time of interatrial septal shunt was not significantly different between the cases with and without ASA, spontaneous closure was less frequent in the cases with ASA than in those without ASA 77.7 and 96.1%), respectively (p < 0.001). The prevalence of ASA is high among newborns, with a high resolution rate. Therefore, it can be considered that it is benign and transient observation. Less frequent spontaneous closure of IASO in cases with ASA indicates that ASA may have a deleterious effect on spontaneous closure.

Bilateral coronary artery dilatation and supravalvular pulmonary stenosis in a child with noonan syndrome.

Noonan syndrome is the second most frequent congenital malformation syndrome, after Down syndrome, associated with cardiovascular abnormalities. The most prevalent cardiovascular abnormalities in Noonan syndrome are pulmonary stenosis and hypertrophic cardiomyopathy. We report the case of a 12-year-old girl with Noonan syndrome who had multiple cardiovascular abnormalities, including extensive bilateral coronary artery dilatation, valvular and supravalvular pulmonary stenosis, atrial septal defect, and mitral valve prolapse. Both coronary artery dilatation and supravalvular pulmonary stenosis, although rarely reported, are abnormalities of the cardiovascular system that may occur in Noonan syndrome.

Microleakage and SEM evaluation of fissure sealants placed by use of self-etching priming agents.

OBJECTIVES: This study evaluated the microleakage and internal seal of fissure sealants placed by use of self-etching priming agents in comparison to phosphoric acid etching of enamel. METHODS: Seventy-two caries-free extracted human molars were divided into six groups with 12 teeth each. Occlusal surfaces were cleansed by either pumicing (Groups I, III, V) or by 15-s air-abrasion treatment with 25 microm aluminum oxide particles (Groups II, IV, VI). Fissures were sealed with the self-etching priming systems, Clearfil Liner Bond 2 (Groups I, II) or Resulcin AquaPrime (Groups III, IV). In Groups V and VI, sealants were placed after phosphoric acid etching. Half of the teeth in each group were thermocycled. After staining with 0.5% methylene blue, the teeth were sectioned for evaluation of microleakage. Internal adaptation of the fissure sealants was analyzed by SEM on replicas of cross sections. RESULTS: Independent of the methods used for cleansing of the occlusal surfaces, fissure sealants in Groups I and II showed significantly more microleakage and less sufficient internal seal as compared to sealants placed in Groups III to VI. Sealants placed by Resulcin AquaPrime (Groups III, IV) leaked significantly more than sealants applied after phosphoric acid etching (Groups V, VI) of the enamel. However, statistical analysis (H-test) did not reveal significant differences concerning the internal adaptation of sealants placed in Groups III, IV, V and VI. CONCLUSIONS: Concerning the microleakage data, use of the self-etching bonding systems, Clearfil Liner Bond 2 and Resulcin AquaPrime, cannot be recommended for fissure sealing, since the sealing ability is less effective as compared to the conventional acid-etching technique.

Factor V 1691 G-A mutation in children with intracardiac thrombosis: a prospective study.

UNLABELLED: The objective of this study was to determine the association between intracardiac thrombosis and hereditary causes of thrombophilia, including factor V 1691 G-A (factor V Leiden, FVL) and prothrombin 20210 G-A mutations. Over a period of 3 y, genetic risk factors were evaluated in 13 consecutive children (mean age 6.27 +/- 5.44 y) with intracardiac thrombosis, diagnosed by cross-sectional echocardiography. Thrombi were localized in the left heart in four patients and the right heart in nine patients. All children had predisposing factors for thrombus formation: ventriculoatrial shunt for hydrocephalus (n = 3), indwelling catheter for chemotherapy (n = 5), cardiomyopathy (n = 2), sepsis (n = 1), homocystinuria (n = 1) and tetralogy of Fallot (n = 1). Six of the 13 children with intracardiac thrombosis were heterozygotes for FVL mutation. Three of these six children with FVL mutation had ventriculoatrial shunt for hydrocephalus, two children had cardiomyopathy and one had sepsis. None of the patients carried the prothrombin 20210 G-A mutation. CONCLUSION: It is recommended that FVL mutations should be investigated in all cases of intracardiac thrombosis irrespective of whether or not a predisposing factor is identified. When a predisposing factor is found antithrombotic prophylaxis may be considered in patients carrying the FVL mutation.

Impact of dialysis adequacy on cardiac function in pediatric CAPD patients.

BACKGROUND: Left ventricular hypertrophy is a major cause of morbidity and mortality among patients with chronic renal failure. Uremia-related risk factors play a fundamental role in its occurrence, thus better prognosis and prolonged survival can be attained by successful dialytic therapies. OBJECTIVE: To investigate whether dialysis adequacy has a beneficial effect on cardiac structure and function in children receiving continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Cross-sectional study in the Pediatric Peritoneal Dialysis Unit of a university hospital. PATIENTS: Eighteen children, aged 13.3 +/- 2.8 years, being treated with CAPD, and 20 healthy age- and sex-matched control subjects were enrolled in this study. MAIN OUTCOME MEASURES: Echocardiographic evaluation was performed in all subjects. Dialysis adequacy indices [weekly urea (Kt/V) and creatinine clearance (TCCr)] were calculated in the dialysis group. RESULTS: Interventricular septal thickness, left ventricular (LV) posterior wall thickness, LV mass index (LVMI), and LV end systolic and diastolic dimensions were all found to be significantly higher in the CAPD group compared to the control subjects (p < 0.01). Ejection fraction and fractional shortening of the LV were not significantly different between the two groups. Mean Kt/V was 2.02 +/- 0.71 and mean TCCr was 58 +/- 33 L/wk/1.73 m2. There were significant negative correlations between dialysis adequacy indices and LV end systolic and diastolic dimensions (p < 0.05 and p < 0.001). Ejection fraction and fractional shortening were positively correlated with Kt/V (p < 0.01). Systolic and diastolic blood pressures were positively correlated with LVMI (r= 0.501 and r = 0.523). Significant inverse correlations between mean arterial pressure and both Kt/V and TCCr (r = -0.555 and r = -0.520) were detected. CONCLUSION: These data clearly document that cardiac structure and function are remarkably influenced by the uremic state and dialysis therapy in pediatric CAPD patients. The close relationships between echocardiographic findings and dialysis adequacy indices suggest that adequate dialysis has a beneficial effect on cardiac function via effective removal of toxic substances.

QRS axis in isolated perimembranous ventricular septal defect and influences of morphological factors on QRS axis.

To detect the frequency of left axis deviation (LAD) in isolated perimembranous ventricular septal defects (VSD) we retrospectively analyzed electrocardiograms of 59 patients, aged 8 months to 15 years. Patients were grouped into those having ventricular septal aneurysm (VSA) formation (n:20) and those who did not have VSA (n:39). Patients with VSA were then stratified into 2 groups according to the presence of left ventricular-to-right atrial (LV-RA) shunt. Four hundred healthy children served as the control group. We found that 12 (20.3%) of 59 patients with isolated perimembranous VSD had a LAD. Five of 6 patients with perimembranous outlet VSD and 6 with perimembranous inlet VSD had abnormal LAD with a qR pattern in I and aVL and rS in aVF. Abnormal LAD was more prevalent in patients with VSA (40%) than without VSA (7.7%) (P <.01). We also found that mild right ventricular hypertrophy (RVH) with the rsR' or rSR' pattern in V1 was more frequent in patients with VSA, especially those who had LV-RA shunt. However, we could not find significant difference between patients with or without LV-RA shunt for the incidence of abnormal LAD and mild RVH. Localization of perimembranous VSD was not found to have an effect on frequency of abnormal LAD and mild RVH in this patient group. In patients with clinical findings of VSD, the existence of abnormal LAD especially if it is associated with mild RVH, should raise the possibility of perimembranous VSD with VSA formation.