Summary
Background Dermatoscopy is a noninvasive technique that can be helpful in the diagnosis of pigmented and nonpigmented skin tumours. The dermatoscopic evaluation of Bowen disease (BD) ...improves diagnostic accuracy.
Objective To evaluate the usefulness of dermatoscopy as a tool for assessing responses to therapy and recurrence of BD.
Methods Patients with histopathologically diagnosed BD were prospectively enrolled. In all lesions, 3 months after the end of treatment (photodynamic therapy or 5% imiquimod cream), dermatoscopic and histopathological examinations were repeated to evaluate and correlate changes in dermatoscopic features and histopathological results. Cured lesions were monitored using dermatoscopy during the follow‐up period.
Results A total of 23 patients with 29 histopathologically diagnosed BD lesions were included in this study. After treatment, dermatoscopic examination revealed the disappearance of pre‐existing vascular structures in 16 lesions, and remaining vascular structures in 13 lesions. Histopathological evaluation of the treated lesions showed remnant intraepithelial neoplasms and increased dermal vascularity in lesions with persistent dermatoscopic vascular structures. However, normal epidermis and decreased dermal vascularity were observed in all but one of the lesions without previous dermatoscopic vascular structures. During the follow‐up period, one lesion showed reappearance of previous vascular structures on dermatoscopy 9 months after treatment. Histopathological examination confirmed the recurrence of BD.
Conclusions Our study demonstrates that the persistence of dermatoscopic vascular structures of BD appears to be associated with residual disease, and disappearance of vascular structures suggests that the disease has been cured. In addition, reappearance of previous dermatoscopic vascular structures indicates the recurrence of BD. Therefore, we suggest that dermatoscopy can be a useful, reliable and noninvasive tool in the therapeutic follow‐up of BD.
There are only a few reports on the feasibility and safety of stents used in the PICA, and clinical and angiographic follow-up results have not been fully addressed. We report our experiences of ...treating PICA origin or vertebral artery-PICA lesions by using self-expanding stents as adjuvant or rescue therapy with angiographic and clinical follow-up results.
Six patients were treated with self-expanding stent placements from the vertebral artery to the PICA. Two patients had a vertebral artery dissecting aneurysm involving the PICA origin, 3 had vertebral artery-PICA aneurysms, and 1 had segmental stenosis of the vertebral artery harboring the origin of the PICA. The safety, feasibility, and follow-up angiographic results were retrospectively evaluated.
All procedures were successfully performed without any procedure-related complications. None of the patients showed PICA territorial infarction on DWI posttreatment. All patients were neurologically intact during the clinical follow-up of 3-24 months following the procedure. Follow-up angiography was performed at between 6 and 12 months in 5 of the 6 patients and was scheduled for the sixth patient but was not performed. The PICA showed good patency without in-stent stenosis in all 5 patients.
In patients with lesions of the PICA origin or vertebral artery-PICA lesions, vertebral artery-to-PICA stent placement may be an option for preserving PICA patency in selected cases.
Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to ...evaluate the efficacy of bococizumab in patients at high cardiovascular risk.
In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months.
At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter 1.8 mmol per liter and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval CI, 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter 2.6 mmol per liter and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001).
In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389 .).
Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously ...shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression.
We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point.
The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period.
The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.
A very high Chern number
Topologically nontrivial electronic structure can often be characterized by the Chern number, the value of which is related to the magnitude of some of the exotic effects ...predicted to occur in such systems. Many topological phases discovered so far have a Chern number of 1 or 2, but higher values are also theoretically possible. Schröter
et al.
predicted that the chiral material palladium gallium (PdGa) would have a Chern number of 4, and they confirmed that prediction using photoemission experiments. Interestingly, the sign of the Chern number was opposite for the two enantiomers of PdGa.
Science
, this issue p.
179
Angle-resolved photoemission indicates that chiral crystalline PdGa has a Chern number of 4.
Topological semimetals feature protected nodal band degeneracies characterized by a topological invariant known as the Chern number (
C
). Nodal band crossings with linear dispersion are expected to have at most
|
C
|
=
4
, which sets an upper limit to the magnitude of many topological phenomena in these materials. Here, we show that the chiral crystal palladium gallium (PdGa) displays multifold band crossings, which are connected by exactly four surface Fermi arcs, thus proving that they carry the maximal Chern number magnitude of 4. By comparing two enantiomers, we observe a reversal of their Fermi-arc velocities, which demonstrates that the handedness of chiral crystals can be used to control the sign of their Chern numbers.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF family, is a type II transmembrane cytokine molecule. Soluble TRAIL has been shown to induce apoptosis in a ...wide variety of cancer cells in vitro and to suppress tumor growth specifically without damaging normal cells and tissues in vivo. In our previous report, we have demonstrated that an artificial gene encoding the polypeptide composed of the three functional elements (a secretion signal, a trimerization domain and an apoptosis-inducing moiety of TRAIL gene sequence) expresses and secretes highly apoptotic trimeric TRAIL into the culture supernatant. Here, as an approach to TRAIL-based cancer gene therapy, we developed an adenoviral vector delivering the gene that encodes our secretable trimeric TRAIL (stTRAIL). This adenovirus (Ad-stTRAIL) potently induced apoptosis in vitro in cancer cell lines such as HeLa, MDA-MB-231, A549, HCT116 and U-87MG. In an animal xenograft tumor model bearing a human glioma cell line U-87MG, intratumoral delivery of Ad-stTRAIL dramatically suppressed tumor growth without showing detectable adverse side effects. Histological analysis revealed that Ad-stTRAIL suppresses tumor growth by inducing apoptotic cell death. Contrary to the known rapid clearance of systemically delivered TRAIL protein from the blood circulation, stTRAIL expressed by Ad-stTRAIL in tumor tissues persisted for more than 4 days. In a comparison of tumor suppressor activity between Ad-stTRAIL and Ad-flTRAIL (delivering the full-length TRAIL gene) after mixing infected cells with uninfected cells and implanting these mixed cells in nude mice, Ad-stTRAIL showed higher tumor suppressor activity than that of Ad-flTRAIL. Our data reveal that a gene therapy using Ad-stTRAIL has a promising potential to treat human cancers including gliomas.
Despite recent advances in the chemotherapy of chronic hepatitis B (CHB), an effective viral suppression after cessation of therapy has not yet been achieved. To investigate whether hepatitis B virus ...(HBV)-specific T-cell responses are inducible and can contribute to the viral suppression after cessation of the therapy, we conducted a proof-of-concept study with a DNA vaccine comprising of most HBV genes plus genetically engineered interleukin-12 DNA (IL-12N222L) in 12 CHB carriers being treated with lamivudine (LAM). When the ex vivo and/or cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN-gamma secreting T-cell responses were observed at the end of treatment and during a follow-up. These type 1T-cell responses, particularly CD4(+) memory T-cell responses could be maintained for at least 40 weeks after the therapy and correlated with virological responses, but not with alanine aminotransferase elevation. Moreover, DNA vaccination under LAM treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Thus, a combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB.
Little has been known about the clinical and angiographic follow-up results of stent-only therapy for intracranial vertebrobasilar dissecting aneurysms (VBDA). The purpose of this study was to ...evaluate the feasibility, safety, clinical, and angiographic follow-up of stent-only therapy for VBDA.
Twenty-seven patients with 29 VBDAs (11 ruptured, 18 unruptured), not suitable for deconstructive treatment, underwent stent-only therapy. Feasibility, safety, clinical, and angiographic follow-up were retrospectively evaluated. Angiographic outcomes were compared between single-stent and multiple-stent groups.
All attempted stent placements were successfully accomplished without any treatment-related complication. Of the 11 ruptured VBDAs, 4 were treated by single stents, 6 by double overlapping stents, and 1 by triple overlapping stents. Of the 18 unruptured VBDAs, 6 were treated by stents, and 12 by double overlapping stents. One patient with a ruptured VBDA, treated by single stent, had rebleeding and died. None of the remaining patients had posttreatment bleeding during follow-up (mean, 28 months; range, 7-50 months). Eight patients with ruptured VBDA and all patients with unruptured VBDA had excellent outcomes (modified Rankin Scale, 0-1). The remaining 2 patients with ruptured VBDA were moderately disabled because of the initial damage. Angiographic follow-up was available in 27 VBDAs, 4 to 42 months (mean, 12 months) after treatment. Follow-up angiograms revealed complete obliteration of the dissecting aneurysm in 12, partial obliteration in 12, stable in 1, enlargement in 1, and in-stent occlusion in 1. Angiographic improvement (complete or partial obliteration) was more frequent in the multiple-stent group (17/17) than in the single-stent group (7/9; P < .05).
In this small series, stent-only therapy was safe and effective in the treatment of VBDAs that were not deemed suitable for treatment with parent-artery occlusion.
Background
Trachyonychia can be refractory to conventional treatments including topical, intralesional or systemic corticosteroids, as well as cyclosporine and retinoids. Therefore, new treatment ...options are needed for recalcitrant trachyonychia.
Objective
To evaluate the efficacy and safety of oral alitretinoin for idiopathic recalcitrant trachyonychia.
Methods
A total of 21 adult patients with 210 nails affected by idiopathic recalcitrant trachyonychia were evaluated in this open‐label prospective study. All patients took 30 mg of alitretinoin daily for at least 3 months. Clinical outcomes were assessed using the Physician Global Assessment (PGA) scale proposed by Park et al. (degree of roughness: 0, clear; 1, mild; 2, moderate; 3, marked; 4, severe) at baseline and 1, 3 and 6 months after treatment.
Results
After 1, 3 and 6 months of treatment, 74.3% (123/210), 98.1% (206/210) and 99.2% (119/120) of nails showed clinical improvement, respectively; 0% (0/210), 22.9% (48/210) and 69.2% (83/120) were completely free from nail abnormalities. The mean PGA score at baseline was 3.4, decreasing significantly to 2.7, 1.3 and 0.7 at 1, 3 and 6 months following treatment, respectively.
Limitations
A small number of participants and lack of a control group were limitations.
Conclusions
For the first time, this study evaluated the efficacy and safety of oral alitretinoin for idiopathic recalcitrant trachyonychia in adults. The results suggest that oral alitretinoin can be a good treatment option for adult patients with recalcitrant trachyonychia.
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