Cyclophosphamide plus granulocyte‐colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma

We retrospectively reviewed the results of cyclophosphamide (3 g/m²), doxorubicin and dexamethasone plus granulocyte‐colony stimulating factor (G‐CSF) (ID‐CY/DOX group), low‐dose cyclophosphamide (2 g/m²) plus G‐CSF (LD‐CY group) and G‐CSF alone (G‐CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10⁹/L for ID‐CY/DOX and LD‐CY groups and after eight doses of G‐CSF (5 μg/kg twice daily) for G‐CSF group. For five mobilizations in ID‐CY/DOX group, the rate of successful mobilization (≥4.0 × 10⁶/kg CD34+ cells) was 80%. For 78 mobilizations in LD‐CY group, the successful rate was 80.8%. For 10 mobilizations in the G‐CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID‐CY/DOX and LD‐CY groups as compared with that in G‐CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID‐CY/DOX and LD‐CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID‐CY/DOX and LD‐CY plus G‐CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G‐CSF alone and their engraftment time were similar. Total WBC count >10 × 10⁹/L can be used as a guide to start apheresis in CY‐based stem cell mobilization. J. Clin. Apheresis 31:423–428, 2016. © 2015 Wiley Periodicals, Inc.     

New frontiers in applied veterinary point‐of‐capture diagnostics: Toward early detection and control of zoonotic influenza

Among the chief limitations in achieving early detection and control of animal‐origin influenza of pandemic potential in high‐risk livestock populations is the existing lag time between sample collection and diagnostic result. Advances in molecular diagnostics are permitting deployment of affordable, rapid, highly sensitive, and specific point‐of‐capture assays, providing opportunities for targeted surveillance driving containment strategies with potentially compelling returns on investment. Interrupting disease transmission at source holds promise of disrupting cycles of animal‐origin influenza incursion to endemicity and limiting impact on animal production, food security, and public health. Adoption of new point‐of‐capture diagnostics should be undertaken in the context of promoting robust veterinary services systems and parallel support for operationalizing pre‐authorized plans and communication strategies that will ensure that the full potential of these new platforms is realized.     

Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: Incidence, associated factors and prognosis

Abstract Background and Aims: Interferon (IFN) plus ribavirin therapy for chronic hepatitis C (CHC) virus infection has been associated with thyroid dysfunction. The goal of our current study was to elucidate predictive factors of: (i) thyroid dysfunction associated with combination therapy; and (ii) long‐term reversibility of thyroid dysfunction. Methods: In total, 461 patients with CHC and normal baseline thyroid functions were enrolled. All patients received IFN‐α‐2b, 3 or 5 million units thrice weekly, or pegylated (PEG)‐IFN‐α‐2b 80 or 100 µg weekly combined with ribavirin 1–1.2 g daily for 24–48 weeks. Assays for serum thyroid stimulating hormone (TSH) and free thyroxine were performed. Results: By the end of the treatment, thyroid dysfunction (TSH <0.1 or >5 mU/L) had developed in 58 patients (12.6%). Female gender was significantly associated with thyroid dysfunction (P < 0.001 odds ratio (OR) = 2.85; 95% confidence interval (CI) = 1.6–5.1). The incidence of thyroid dysfunction was similar for standard IFN and PEG‐IFN‐treated patients (49/391 vs 9/70; P = 1.00). Under a nested case‐control design, detailed laboratory assessment was carried out on frozen serum samples from patients and age‐ (± 5 years) and sex‐matched controls (n = 58). Multivariate analysis revealed significant association between higher positive rates of pretreatment TMA and patients who developed thyroid dysfunction (OR = 5.8, 95% CI = 1.2–27.9). Ten patients (～2%) remained thyroid dysfunctional at the end of follow up (median, 26.5 months). For these patients, no risk factor can predict the reversibility of thyroid function. Conclusions: Female gender and pretreatment TMA positivity are associated with thyroid dysfunction. Long‐term thyroid dysfunction may persist in a small group of patients (～2%).     

The value of 2-D Doppler echocardiography in the evaluation of asymptomatic patients with Mustard operation for transposition of the great arteries

2-D Doppler echocardiography was used to assess the occurrenceof haemodynamic abnormalities in 45 asymptomatic patients, aged4 to 16 years (median 7·4) after a Mustard operationfor transposition of the great arteries. The findings were comparedwith those derived from cardiac catheterization. Thirty-fivecardiac lesions were correctly diagnosed by 2-D Doppler echocardiographyin 23 patients, but on six occasions, minor abnormalities weremissed. 2-D Doppler echocardiography demonstrated systemic venouspathway obstruction of more than 3 mmHg at cardiac catheterizationin nine patients, and in five of the six patients with pulmonaryvenous channel obstruction. A left ventricular outflow tractobstruction (pressure difference > 15 mmHg) was diagnosedcorrectly by Doppler echocardiography in seven patients. Baffleleakage was found in two patients with a left to right shuntof 25% or more of pulmonary bloodflow, but was missed in fiveout of nine patients with small shunts. Tricuspid regurgitationwas well defined in eight patients, The absence of symptomsand a routine examination after a Mustard operation do not ruleout haemodynamic abnormalities. However, these, with the possibleexception of minor baffle leakage, can be detected by 2-D Dopplerechocardiography.     

Early Postinterventional Stent Stenosis of a Ductus Stent Implanted for Palliation in a Newborn with Pulmonary Atresia with Intact Ventricular Septum: Successful Management with Bailout Stenting

A newborn with pulmonary atresia with intact ventricular septum (PA-IVS) was treated with radiofrequency current perforation of the atretic pulmonary valve. As the right ventricle was hypoplastic (z-value of the tricuspid valve: —4) the arterial duct was stented with a Gianturco-Roubin GR II stent. Early postinterventionally, the patient became cyunotic and compromised blood flow across the stented ductus arteriosus despite adequate stent position was detected echographically. The newborn was treated successfully with the implantation of a Palmaz stent (Johnson & Johnson Interventional Systems, Warren, NJ, USA) into the obstructed Gianturco-Roubin GR II stent. The Gianturco-Roubin GR II stents might be associated with the risk of early stent stenosis after implantation in actively contracting tissues like the ductus arteriosus. In patients with early stent stenosis after ductal stenting, bailout implantation of a subsequent stent can be performed. Transcatheter procedures can be effective means for therapy of PA-IVS . (J Interven Cardiol 2000;13:39–44)     

Photoinduced transformations of stiff-stilbene-based discrete metallacycles to metallosupramolecular polymers

Control over structural transformations in supramolecular entities by external stimuli is critical for the development of adaptable and functional soft materials. Herein, we have designed and synthesized a dipyridyl donor containing a central Z-configured stiff-stilbene unit that self-assembles in the presence of two 180° di-Pt(II) acceptors to produce size-controllable discrete organoplatinum(II) metallacycles with high efficiency by means of the directional-bonding approach. These discrete metallacycles undergo transformation into extended metallosupramolecular polymers upon the conformational switching of the dipyridyl ligand from Z-configured (0°) to E-configured (180°) when photoirradiated. This transformation is accompanied by interesting morphological changes at nanoscopic length scales. The discrete metallacycles aggregate to spherical nanoparticles that evolve into long nanofibers upon polymer formation. These fibers can be reversibly converted to cyclic oligomers by changing the wavelength of irradiation, which reintroduces Z-configured building blocks owing to the reversible nature of stiff-stilbene photoisomerization. The design strategy defined here represents a novel self-assembly pathway to deliver advanced supramolecular assemblies by means of photocontrol.Natural systems provide many examples of self-assembled biosupramolecules that respond to external stimuli through conformational changes that ultimately play a role in carrying out their various biological functions. Mimicking this stimuli-responsive behavior in artificial systems is a promising route toward obtaining sophisticated molecular-based architectures with functional and structural tunability (1–3). Using the absorption of photons as a trigger is particularly attractive in that light-induced transformations maintain high spatial and temporal resolution without producing waste products even during multiple reversible switching sequences (4). In materials science, one of the most appealing characteristics of photochromic molecules is the direct conversion of light into mechanical energy based on their photo-reversible structural transformations (5). Among such chromophores, a stiff-stilbene moiety (1,1′-biindane) is useful owing to its unique characteristics (6). First, stiff stilbene can adopt either a cis or trans configuration with respect to its central double bond. Second, the high activation barrier between the two isomers (∼43 kcal⋅mol⁻¹, corresponding to a half-life of ∼10⁹ y at 300 K) makes thermal E/Z isomerization negligible at temperatures of 420 K and lower. Third, the quantum yield for the photoisomerization of either isomer is high (50%). Fourth, the stiff-stilbene core is readily substituted using well-established synthetic methods. Owing to these promising characteristics, Boulatov and coworkers (7) constructed a molecular force probe by integrating the moiety into a stretched polymer to mimic the strain generated in diverse functional groups. Yang and coworkers (8) reported hydrogen-bonded supramolecular polymers and studied their polymerization mechanisms and physical properties based on the photoisomerization of the stiff-stilbene units. Nevertheless, stiff-stilbene-based supramolecular entities are underexplored despite exhibiting properties that make the functionality potentially useful in the construction of photoresponsive supramolecular materials.Coordination-driven self-assembly is a powerful method of constructing supramolecular coordination complexes (SCCs) by the spontaneous formation of metal–ligand bonds that draws inspiration from the design principles of natural systems (9–20). This approach organizes metal acceptors and organic donors to prepare well-defined cavity-cored 2D metallacycles and 3D metallacages, which can be functionalized on their interior or exterior vertices for applications in host–guest chemistry (21, 22), catalysis (23), molecular flasks (24), bioengineering (25), amphiphilic self-assembly (26), and so on. The versatility of coordination-driven self-assembly can be enhanced by designs that allow for post-self-assembly modifications that in some cases result in complete structural transformations. For example, the Stang group previously demonstrated the transformation of self-assembled polygons by changing the angle between the bonding sites of a ligand from 180° to 120° upon treatment of Co₂(CO)₆ with an acetylene moiety (27). Yang and coworkers (28) reported the construction of multibisthienylethene hexagons capable of reversible supramolecule-to-supramolecule conversions induced by ring-open and ring-closed conformational changes of the bisthienylethene units. Herein we expand upon the transformations established by the systems described above designing SCCs capable of evolving from discrete metallacycles into infinite constructs using external stimuli.Supramolecular polymers can be defined as dynamically reversible polymeric arrays (29–37) that form from the explicit manipulation of noncovalent forces between monomeric units (38–43). Supramolecular polymer chemistry can readily complement coordination-driven self-assembly, as exemplified by our efforts to design hierarchical supramolecular polymerizations of discrete organoplatinum(II) metallacycles, thus accessing novel supramolecular polymeric materials, such as macroscopic hexagonal supramolecular polymer fibers (44), dendronized organoplatinum(II) metallacyclic polymers (45), and a responsive, cavity-cored supramolecular polymer network metallogel (46). Herein, we report photoresponsive supramolecular transformations between discrete organoplatinum(II) metallacycles and infinite metallosupramolecular polymers induced by a cis/trans conformational transition of a stiff-stilbene-based dipyridyl ligand. The self-assembly behaviors, physical properties, topologies, and morphologies of these SCCs can be regulated by photoisomerization, demonstrating this powerful approach to prepare advanced supramolecular coordination complexes.