Poor agreement between the automated risk assessment of a smartphone application for skin cancer detection and the rating by dermatologists.

BACKGROUND: Several smartphone applications (app) with an automated risk assessment claim to be able to detect skin cancer at an early stage. Various studies that have evaluated these apps showed mainly poor performance. However, all studies were done in patients and lesions were mainly selected by a specialist. OBJECTIVES: To investigate the performance of the automated risk assessment of an app by comparing its assessment to that of a dermatologist in lesions selected by the participants. METHODS: Participants of a National Skin Cancer Day were enrolled in a multicentre study. Skin lesions indicated by the participants were analysed by the automated risk assessment of the app prior to blinded rating by the dermatologist. The ratings of the automated risk assessment were compared to the assessment and diagnosis of the dermatologist. Due to the setting of the Skin Cancer Day, lesions were not verified by histopathology. RESULTS: We included 125 participants (199 lesions). The app was not able to analyse 90 cases (45%) of which nine BCC, four atypical naevi and one lentigo maligna. Thirty lesions (67%) with a high and 21 with a medium risk (70%) rating by the app were diagnosed as benign naevi or seborrhoeic keratoses. The interobserver agreement between the ratings of the automated risk assessment and the dermatologist was poor (weighted kappa = 0.02; 95% CI -0.08-0.12; P = 0.74). CONCLUSIONS: The rating of the automated risk assessment was poor. Further investigations about the diagnostic accuracy in real-life situations are needed to provide consumers with reliable information about this healthcare application.

Needs and preferences of patients regarding basal cell carcinoma and cutaneous squamous cell carcinoma care: a qualitative focus group study.

BACKGROUND: Despite the high and rising incidence rate of keratinocyte cancer (KC) and the importance of incorporating patient values into evidence-based care, few studies have focused on the perspectives of patients with KC. OBJECTIVES: To identify the needs and preferences of patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) regarding care. METHODS: A qualitative study was conducted consisting of three focus groups with patients with BCC and three focus groups with patients with SCC. In total 42 patients participated. In each focus group, the patients' needs and preferences regarding treatment and follow-up were discussed, using a predefined topic list. All sessions were transcribed verbatim and analysed by two researchers. RESULTS: The following needs and preferences were identified: (i) the need to receive all relevant, tailored information; (ii) a physician who takes you seriously and communicates well; (iii) a short waiting period and the best treatment with direct results; (iv) to be seen by the same physician; a preference for a dermatologist during (v) treatment and (vi) follow-up; (vii) a general need for structured follow-up care and (viii) a full-body skin examination during follow-up. Patients with BCC additionally expressed the need for openness and transparency and wanting to participate in shared decision making. CONCLUSIONS: It is advocated to organize skin cancer care that is better tailored to the needs of patients with KC, providing patient-centred care. This should include investing in the patient-physician relationship, and personalizing the type and form of information and the follow-up schedules. Adding the patient's perspective to current guidelines could facilitate this process.

[Guideline on 'The treatment of recurrent varicose veins'Supplement to the Dutch Guideline on Venous disease]. / Richtlijn 'Behandeling bij neo-varices'.

The Dutch Guideline on Venous disease was lacking a section on recurrent varicose veins. The newly issued supplement on recurrent varicose veins fills this gap and provides clinicians with solutions concerning the management of patients with recurrent varicose veins following earlier treatment. Because venous disease is nowadays considered to be an ongoing disease, patients with this disorder will often require life-long care and different treatment than patients who have never been treated before.

Randomized clinical trial of endovenous laser ablation versus steam ablation (LAST trial) for great saphenous varicose veins.

BACKGROUND: The aim was to compare endovenous laser ablation (EVLA) and endovenous steam ablation (EVSA) for great saphenous varicose veins in a non-inferiority study. METHODS: Patients with primary great saphenous vein reflux were randomized to EVLA (940 nm) or EVSA (SVS™). Primary outcomes were treatment success (vein obliteration or abolition of reflux) [corrected] at 52 weeks, and Venous Clinical Severity Score (VCSS) at 12 weeks. Secondary outcomes were pain, satisfaction with treatment, duration of analgesia use and days lost from daily activities, changes in Aberdeen Varicose Vein Questionnaire (AVVQ) and EQ-5D™ scores after 12 weeks, and complications at 2 and 12 weeks. RESULTS: A total of 227 legs were treated (EVSA, 117; EVLA, 110); 36 legs treated with EVSA received a low dose and the remaining 81 a higher dose. At 1 year, the treatment success rate after high-dose EVSA was not inferior to that of EVLA: 92 (95 per cent confidence interval (c.i.) 86 to 98) versus 96 (92 to 100) per cent respectively. Changes in VCSS after 12 weeks were similar: -2·69 (95 per cent c.i. -2·34 to -3·04) and -2·51 (-2·10 to -2·93). AVVQ, EQ-5D™ and EQ VAS scores improved equally 12 weeks after both treatments. Patients treated with EVSA reported less postprocedural pain, fewer days of analgesia use, were more satisfied with therapy, and had a shorter convalescence. Complication rates were comparable. CONCLUSION: The 1-year treatment success of high-dose EVSA was not inferior to that of EVLA. Several secondary outcomes were in favour of EVSA. Registration number NCT02046967 (http://www.clinicaltrials.gov).

Long-term administration of the TNF blocking drug Remicade (cV1q) to mdx mice reduces skeletal and cardiac muscle fibrosis, but negatively impacts cardiac function.

Duchenne muscular dystrophy (DMD) is a degenerative skeletal muscle disease caused by mutations in the gene encoding dystrophin (DYS). Tumor necrosis factor (TNF) has been implicated in the pathogenesis since short-term treatment of mdx mice with TNF blocking drugs proved beneficial; however, it is not clear whether long-term treatment will also improve long-term outcomes of fibrosis and cardiac health. In this investigation, short and long-term dosing studies were carried out using the TNF blocking drug Remicade and a variety of outcome measures were assessed. Here we show no demonstrable benefit to muscle strength or morphology with 10mg/kg or 20mg/kg Remicade; however, 3mg/kg produced positive strength benefits. Remicade treatment correlated with reductions in myostatin mRNA in the heart, and concomitant reductions in cardiac and skeletal fibrosis. Surprisingly, although Remicade treated mdx hearts were less fibrotic, reductions in LV mass and ejection fraction were also observed, and these changes coincided with reductions in AKT phosphorylation on threonine 308. Thus, TNF blockade benefits mdx skeletal muscle strength and fibrosis, but negatively impacts AKT activation, leading to deleterious changes to dystrophic heart function. These studies uncover a previously unknown relationship between TNF blockade and alteration of muscle growth signaling pathways.

[Universal Dutch guideline on 'Venous disease']. / Overkoepelende richtlijn 'Veneuze pathologie'.

- The Dutch guideline on 'Venous disease' comprises four parts: two revised guidelines ('Varicose veins' and 'Venous leg ulcer') and two new guidelines ('Deep venous disease' and 'Compression therapy').- These guidelines were drawn up by a working party made up of representatives from the Dutch Association of Surgeons, the Dutch Society of Vascular Surgery and the Dutch Society of Dermatology and Venereology.- We will discuss the most important parts of the guideline here.

Ulcer recurrence after in-hospital treatment for recalcitrant venous leg ulceration.

BACKGROUND: Leg ulceration caused by chronic venous disease occurs in 1% of the adult Western population. A majority of these patients is successfully treated in the outpatient setting. A minority of patients is hospitalized, most frequently because of the lack of healing tendency. The literature provides recurrence rates for ulcer disease, but lacks specific data on recurrence rates after in-hospital treatment of recalcitrant venous leg ulcers. OBJECTIVES: To investigate time to ulcer recurrence after in-hospital treatment of venous leg ulceration. METHODS: A multicentre, retrospective cohort study of patients admitted for leg ulceration between 1996 and 2007 was conducted. RESULTS: Data could be collected for 107 of the patients. Of these, 27 had conservative treatment (bed rest, local wound care, pain management) and 48 patients underwent surgical ulcer treatment with (n = 19) or without (n = 29) initial vacuum-assisted closure (VAC) treatment. The treatment method was 'miscellaneous' in the remaining 32 patients. Median admission time was 30 days, median percentage of closure at discharge was 95%, and median time to ulcer recurrence 60 days. The Mann-Whitney U-test showed significant differences between the conservative group and the surgery group, the latter having a longer length of hospital stay (P < 0.0001) and a higher percentage of ulcer closure (P < 0.0001), but there was no difference in time to ulcer recurrence (P = 0.273). Comparable differences were demonstrated between the conservative group and the VAC plus surgery group. No significant differences could be demonstrated between the surgically treated patients and those treated by VAC and surgery. CONCLUSIONS: Hospital stay is significantly shorter in cases of surgical treatment of recalcitrant venous leg ulcers. Most ulcers recur within 2 months after hospital discharge. Recurrence of venous leg ulcers after hospital admission is independent of the method of treatment and cause of ulceration.

Evidence of a role for insulin-like growth factor binding protein (IGFBP)-3 in metabolic regulation.

IGF-binding protein (IGFBP)-3 is a metabolic regulator that has been shown to inhibit insulin-stimulated glucose uptake in murine models. This finding contrasts with epidemiological evidence of decreased serum IGFBP-3 in patients with type 2 diabetes. The purpose of this study was to clarify the role of IGFBP-3 in metabolism. Four-week-old male IGFBP-3(-/-) and control mice were subjected to a high-fat diet (HFD) for 12 wk. IGFBP-3(-/-) mice were heavier before the initiation of HFD and at the end of the study period. Resting metabolic rate was significantly decreased in knockout mice; however, respiratory exchange ratio was not significantly different. Fasting blood glucose and insulin levels were significantly elevated in IGFBP-3(-/-) mice. However, IGFBP-3(-/-) mice had relatively normal glucose tolerance because the relative glucose excursion over time was not different between the groups. During hyperinsulinemic clamps, IGFBP-3(-/-) mice had increased basal hepatic glucose production, but after insulin stimulation, no differences in hepatic glucose production were observed. A second cohort of older IGFBP-3(-/-) mice on HFD displayed unexpected evidence of hepatic steatosis. In summary, glucose tolerance and clamp testing indicate that IGFBP-3(-/-) mice preserve insulin sensitivity despite evidence of increased basal glucose turnover and hepatic steatosis. We provide evidence that genetic deletion of IGFBP-3 modulates hepatic carbohydrate and lipid metabolism.

[Echo-guided compression sclerotherapy using foam: an improvement in the treatment of varicose veins]. / Echogeleide sclerocompressietherapie met schuim: een aanwinst bij de behandeling van varices.

Recently, echo-guided compression sclerotherapy (ECST) using foam was introduced as an efficient and patient-friendly therapy for the treatment of varicose veins. ECST enables operation under either spinal or general anaesthetic to be avoided. Foam for phlebological use is a volatile mixture of a gas, usually air, and a small quantity of liquid with the characteristics of a detergent or soap, such as polidocanol. The product that is injected has deterging properties. It reduces the surface tension of endothelial cells resulting in the destruction of the vascular wall. The treated vessel is subsequently reduced to a fibrous cord. For small calibre varicose veins, sclerosing fluids are used. In The Netherlands, until relatively recently branch varicosities of the long and short saphenous veins were treated surgically, but ECST using foam can be successfully used to treat wide calibre varicosities. Caution is advised in treating patients who are known to have a history of open foramen ovale because of the higher risk of the occurrence of scotoma and transient cerebral ischaemia.

Overlapping roles of pocket proteins in the myocardium are unmasked by germ line deletion of p130 plus heart-specific deletion of Rb.

The pocket protein family of tumor suppressors, and Rb specifically, have been implicated as controlling terminal differentiation in many tissues, including the heart. To establish the biological functions of Rb in the heart and overcome the early lethality caused by germ line deletion of Rb, we used a Cre/loxP system to create conditional, heart-specific Rb-deficient mice. Mice that are deficient in Rb exclusively in cardiac myocytes (CRbL/L) are born with the expected Mendelian distribution, and the adult mice displayed no change in heart size, myocyte cell cycle distribution, myocyte apoptosis, or mechanical function. Since both Rb and p130 are expressed in the adult myocardium, we created double-knockout mice (CRbL/L p130-/-) to determine it these proteins have a shared role in regulating cardiac myocyte cell cycle progression. Adult CRbL/L p130-/- mice demonstrated a threefold increase in the heart weight-to-body weight ratio and showed increased numbers of bromodeoxyuridine- and phosphorylated histone H3-positive nuclei, consistent with persistent myocyte cycling. Likewise, the combined deletion of Rb plus p130 up-regulated myocardial expression of Myc, E2F-1, and G1 cyclin-dependent kinase activities, synergistically. Thus, Rb and p130 have overlapping functional roles in vivo to suppress cell cycle activators, including Myc, and maintain quiescence in postnatal cardiac muscle.

Increased baroreceptor response in mice deficient in monoamine oxidase A and B.

The recent development of mice doubly deficient for monoamine oxidase A and B (MAO-A/B, respectively) has raised questions about the impact of these mutations on cardiovascular function, in so far as these animals demonstrate increased tissue levels of the vasoactive amines serotonin, norepinephrine, dopamine, and phenylethylamine. We recorded femoral arterial pressures and electrocardiograms in adult MAO-A/B-deficient mice during halothane-nitrous oxide anesthesia as well as 30 min postoperatively. During both anesthesia and recovery, systolic, diastolic, and mean arterial pressures were 10-15 mmHg lower in MAO-A/B-deficient mice compared with normal controls (P < 0.01). Mutants also showed a greater baroreceptor-mediated reduction in heart rate in response to hypertension after intravenous pulses of phenylephrine or angiotensin II. Tachycardia elicited in response to hypotension after nitroprusside was greater in mutants than in controls. Heart rate responsiveness to changes in arterial pressure was abolished after administration of glycopyrrolate, with no differences in this phenomenon noted between genotypes. These data suggest that prevention of hypertension may occur in chronic states of catecholaminergic/indoleaminergic excess by increased gain of the baroreflex.

Inducible activation of c-Myc in adult myocardium in vivo provokes cardiac myocyte hypertrophy and reactivation of DNA synthesis.

c-Myc, a protooncogene, mediates both proliferative and cellular growth in many cell types. Although not expressed in the adult heart under normal physiological conditions, Myc expression is rapidly upregulated in response to hypertrophic stimuli. Although Myc is capable of sustaining hyperplastic growth in fetal myocytes, the effects of its re-expression in adult postmitotic myocardium and its role in mediating cardiac hypertrophy are unknown. To determine the effects of de novo Myc activity in adult postmitotic myocardium in vivo, we created a novel transgenic model in which Myc is expressed and inducibly activated specifically in cardiac myocytes. Activation of Myc in adult myocardium was sufficient to reproduce the characteristic changes in myocyte size, protein synthesis, and cardiac-specific gene expression seen in cardiac hypertrophy. Despite the increased cardiac mass, left ventricular function remained normal. Activation of Myc also provoked cell cycle reentry in postmitotic myocytes, which led to increased nuclei per myocyte and DNA content per nuclei.

Miniature heart cell force transducer system implemented in MEMS technology.

A fully submersible force transducer system for use with isolated heart cells has been implemented using microelectromechanical systems (MEMS) technology. By using integrated circuit fabrication techniques to make mechanical as well as electrical components, the entire low-mass transducer is only a few cubic millimeters in size and is of higher fidelity (approximately 100 nN and 13.3 kHz in solution) than previously available. When chemically activated, demembranated single cells attached to the device contract and slightly deform a strain gauge whose signal is converted to an amplified electrical output. When integrated with a video microscope, the system is capable of optical determination of contractile protein striation periodicity and simultaneous measurement of heart cell forces in the 100-nN to 50-microN range. The average measured maximal force was Fmax = 5.77 +/- 2.38 microN. Normalizing for the cell's cross-sectional area, Fmax/area was 14.7 +/- 7.7 mN/mm2. Oscillatory stiffness data at frequencies up to 1 kHz has also been recorded from relaxed and contracted cells. This novel MEMS force transducer system permits higher fidelity measurements from cardiac myocytes than available from standard macro-sized transducers.

Hypertension in beta-adducin-deficient mice.

Polymorphic variants of the cytoskeletal protein adducin have been associated with hypertension in humans and rats. However, the direct role of this protein in modulating arterial blood pressure has never been demonstrated. To assess the effect of beta-adducin on blood pressure, a beta-adducin-deficient mouse strain (-/-) was studied and compared with wild-type controls (+/+). Aortic blood pressure was measured in nonanesthetized, freely moving animals with the use of telemetry implants. It is important to note that these mice have at least 98% of C57Bl/6 genetic background, with the only difference from wild-type animals being the beta-adducin mutation. We found statistically significant higher levels of systolic blood pressure (mm Hg) (mean+/-SE values: -/-: 126.94+/-1.14, n=5; +/+: 108.06+/-2. 34, n=6; P:

A multiple-capillary electrophoresis system for small-scale DNA sequencing and analysis.

A five-capillary system has been developed for DNA sequencing and analysis. The post-column fluorescence detector is based on a sheath-flow cuvette. The instrument provides uniform and continuous illumination of the samples. The cuvette virtually eliminates cross-talk in the fluorescence signal between capillaries. Discrete single-photon counting avalanche photodiodes provide high efficiency light detection. The instrument has detection limits (3sigma) of 130 +/- 30 fluorescein molecules injected onto each capillary. Over 650 bases of sequence at 98.8% accuracy were generated in 100 min at 50 degrees C from M13mp18. Separation and detection of short tandem repeats proved efficient and accurate with the use of internal standards for direct comparison of migration times between capillaries.

Long cotton wool rolls as compression enhancers in macrosclerotherapy for varicose veins.

BACKGROUND: Macrosclerotherapy in combination with compression has proven to be safe and effective in the treatment of varicose veins. Local compression is increased by pads, according to Laplace law. Firm rolls of cotton wool are fixed over the course of the entire vein to increase local compression and to reduce complications. Additional compression is given by a combination of a class I (daytime and nighttime) and class II (daytime only) medical compression hosiery. PURPOSE: To evaluate the effectiveness and side effects of sclerocompression therapy with cotton wool rolls in combination with medical compression hosiery. METHOD: Prospective study with 100 patients (120 legs) with primary varicose veins, which are treated with polidocanol as sclerosant with the empty vein technique. Immediately after the injection, a long cotton wool roll is placed over the entire vein and fixed. Additional compression is obtained with class I and class II medical compression hosiery. The interface pressure on the skin, just under the cotton wool roll, is measured on 12 legs with the aid of an interface pressure measuring instrument (Oxford Pressure Monitor). RESULTS: Good sclerosing results are obtained in all patients. Side effects are classified as early and late. In 16 patients, minor side effects which needed no treatment are observed. In only 3 cases (2.5%), intravascular blood clots (2) and phlebitis (1) needed incision and expression. The mean interface pressure of all measuring sensors under the cotton wool roll is 84 mm/Hg (68 to 122 mm/Hg). CONCLUSION: This study proves the high effectiveness of a cotton wool roll compression right at the place of treatment. By using these long cotton wool compression rolls, the compression part of sclerocompression therapy becomes more effective and much easier to perform.