Development of an umbilical cord blood transplantation-specific nonrelapse mortality risk assessment score.

ABSTRACT: Higher rate of nonrelapse mortality (NRM) remains yet to be resolved in umbilical cord blood transplantation (UCBT). Considering that UCBT has some unique features compared with allogeneic hematopoietic cell transplantation from other graft sources, a UCBT-specific NRM risk assessment system is required. Thus, in this study, we sought to develop a UCBT-specific NRM Risk Assessment (CoBRA) score. Using a nationwide registry database, we retrospectively analyzed 4437 recipients who had received their first single-unit UCBT. Using the backward elimination method, we constructed the CoBRA score in a training cohort (n = 2687), which consisted of recipients age ≥55 years (score 2), hematopoietic cell transplantation-specific comorbidity index ≥3 (score 2), male recipient, graft-versus-host disease prophylaxis other than tacrolimus in combination with methotrexate, performance status (PS) 2 to 4, HLA allele mismatch ≥ 2, refined Disease Risk Index high risk, myeloablative conditioning, and CD34+ cell doses < 0.82 × 105/kg (score 1 in each). The recipients were categorized into 3 groups: low (0-4 points), intermediate (5-7 points), and high (8-11 points) groups according to the CoBRA score. In the validation cohort (n = 1750), the cumulative incidence of NRM at 2 years was 14.9%, 25.5%, and 47.1% (P < .001), and 2-year overall survival (OS) was 74.2%, 52.7%, and 26.3% (P < .001) in the low, intermediate, and high groups, respectively. In summary, the CoBRA score could predict the NRM risk as well as OS after UCBT. Further external validation will be needed to confirm the significance of the CoBRA score.

Convergent synthesis of oligomannose-type glycans via step-economical construction of branch structures.

Oligomannose-type glycans on glycoproteins are important signaling molecules in the glycoprotein quality control system in the endoplasmic reticulum. Recently, free oligomannose-type glycans generated by the hydrolysis of glycoproteins or dolichol pyrophosphate-linked oligosaccharides were recognized as important signals for immunogenicity. Hence, there is a high demand for pure oligomannose-type glycans for biochemical experiments; however, the chemical synthesis of glycans to achieve high-concentration products is laborious. In this study, we demonstrate a simple and efficient synthetic strategy for oligomannose-type glycans. Sequential regioselective α-mannosylation at the C-3 and C-6 positions of 2,3,4,6-unprotected galactose residues in galactosylchitobiose derivatives was demonstrated. Subsequently, the inversion of the configuration of the two hydroxy groups at the C-2 and C-4 positions of the galactose moiety was successfully carried out. This synthetic route reduces the number of the protection-deprotection reactions and is suitable for constructing different branching patterns of oligomannose-type glycans, such as M9, M5A, and M5B.

Stochasticity of individual competition and local matchup inequality for saplings in a niche-structured forest.

Ecologists have recently accepted the notion that species coexistence involves both niche and neutral processes, but few studies have explained how both of these opposite views can explain coexistence in the same community. Here we focus on competition among sessile organisms and explored first the extent to which species-based niche reflects local "matchups" between nearby individuals, using 726 saplings of 10 temperate tree species, and second the members engaging in the matchups, which have rarely been quantified despite the importance in mixed-species forests. Growth responses to light showed considerable species-level differences, suggesting commonly seen regeneration niches. Outcomes of the individual matchups were basically predictable from the species mean response, but also with substantial contribution of within-species variation. We found strong imbalance in matchup frequencies, such that some individuals meet more individuals of differing species but others meet fewer, as well as many isolated, competition-free ones. The niche and neutral processes appear to reflect, respectively, between- and within-species differences, and our findings suggest that even when niche segregation is discernible, the role of stochasticity for the frequency of local competition, as well as its outcomes, cannot be discounted in species coexistence.

Cone-Beam Computed Tomography Fusion Technique for Vascular Assessment of Skull Base Meningiomas.

OBJECTIVE: Cone-beam computed tomography (CBCT) images for skull base tumors provide detailed vascular information and localization in regard to surrounding bony structures. We report use of the CBCT fusion technique for skull base meningiomas. METHODS: Six patients with petroclival or petrotentorial meningiomas supplied by multiple arterial systems were preoperatively evaluated using CBCT fusion imaging. Fusion images were reconstructed from three-dimensional rotational angiography with contrast agent injections from the internal carotid artery (ICA) and external carotid artery in 4 cases, vertebral artery and external carotid artery in 1 case, and ICA and vertebral artery in 1 case. RESULTS: The feeding pedicles and tumor stains from 2 arterial systems were differentiated by separate colors. The courses and territories of the ICA dural feeders or ICA/vertebral artery pial feeders were easily distinguished from the external carotid artery dural feeders. Anastomoses between thin feeders from different arterial systems could be detected. Mixed stain (stain with both colors) was observed in some tumor compartments, suggesting dual supply from 2 arterial systems and the presence of peritumoral anastomoses. All patients underwent preoperative embolization without complications. CONCLUSIONS: CBCT fusion images clearly visualized the feeders from each arterial system, the vascular compartments within the tumor, and possible peritumoral anastomoses. This technique provides a substantial contribution to both preoperative embolization and surgical resection of skull base meningiomas.

Preoperative Assessment of Pathologic Subtypes of Meningioma and Solitary Fibrous Tumor/Hemangiopericytoma Using Dynamic Computed Tomography: A Clinical Research Study.

BACKGROUND: Solitary fibrous tumors (SFTs)/hemangiopericytomas (HPCs) are highly vascularized tumors well known for malignant, invasive, and highly vascular features. To date, several studies have reported the preoperative imaging findings of SFTs/HPCs. In this study, computed tomography (CT) tumor values acquired from dynamic CT scan were selected to determine the tumor pathology of highly vascular tumors, such as SFTs/HPCs. METHODS: We conducted a retrospective study on patients with pathologically diagnosed meningiomas and SFTs/HPCs who had undergone a dynamic contrast CT scan. We assessed and compared the CT values of these tumors according to the pathology. RESULTS: From a total of 34 patients, 30 patients with meningiomas and 4 patients with HPCs were included. The mean CT values of SFTs/HPCs and angiomatous meningioma were statistically significantly higher than those of the other meningioma subtypes (P = 0.003). We also performed receiver operating characteristic curve analyses to detect an appropriate cutoff point for the CT value to differentiate tumor pathology, and the calculated threshold was 161 Hounsfield units (HU) (sensitivity, 100%; specificity, 75%; area under the curve, 0.87; 95%, CI 0.75-0.99). CONCLUSIONS: This study showed that obtaining a CT value is useful in determining highly vascular tumor pathology preoperatively. When considering neurosurgical extra-axial tumor removal, and when the CT value of tumors is >161 HU, then highly vascular tumors such as SFTs/HPCs or angiomatous meningiomas are likely, and this should be considered prior to surgical intervention and for risk assessment.

Gemcitabine in patients previously treated with platinum-containing chemotherapy for refractory thymic carcinoma: radiographic assessment using the RECIST criteria and the ITMIG recommendations.

BACKGROUND: The key drugs for chemotherapy of thymic carcinoma are gradually being revealed in phase II and conventional retrospective studies. Gemcitabine is regarded as one of these key drugs according to the findings of clinical trials in which it was combined with capecitabine. However, the activity of single-agent gemcitabine concerning refractory thymic carcinoma remains unclear. PATIENTS AND METHODS: We conducted a retrospective review of the medical records of refractory thymic carcinoma patients previously treated with platinum-containing chemotherapy between 1980 and 2014. RESULTS: Of all 11 patients in this study, the objective response rate regarding gemcitabine was 36.4 % [95 % confidence interval (CI) 15.2-64.6] using the RECIST criteria and the response criteria proposed by the ITMIG. The median progression-free survival time was 4.3 months (95 % CI 0.7-11.0). The survival time from the start of gemcitabine treatment was 28.5 months (95 % CI 5.5-47.8), and from the start of first-line chemotherapy was 46.5 months (95 % CI 7.3-47.8). CONCLUSIONS: Gemcitabine achieved a moderate response and has the potential to be used as a key drug for thymic carcinoma. Some patients treated with gemcitabine demonstrated prolonged cancer control even in later lines of chemotherapy.

Growth differentiation factor-5 promotes brown adipogenesis in systemic energy expenditure.

Although growth differentiation factor-5 (GDF5) has been implicated in skeletal development and joint morphogenesis in mammals, little is known about its functionality in adipogenesis and energy homeostasis. Here, we show a critical role of GDF5 in regulating brown adipogenesis for systemic energy expenditure in mice. GDF5 expression was preferentially upregulated in brown adipose tissues from inborn and acquired obesity mice. Transgenic overexpression of GDF5 in adipose tissues led to a lean phenotype and reduced susceptibility to diet-induced obesity through increased systemic energy expenditure. Overexpression of GDF5 facilitated the development of brown fat-like cells, called brite or beige cells, along with the expression of uncoupling protein-1 in inguinal subcutaneous white adipose tissue. In mutant mice harboring the dominant-negative GDF5, marked impairment in energy expenditure and thermogenesis was seen under obesogenic conditions. Recombinant GDF5 promoted brown adipogenesis through the mothers against decapentaplegic homolog (Smad) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathways after activation of bone morphogenetic protein receptor (BMPR). These results suggest that brown adipogenesis and energy homeostasis are both positively regulated by the GDF5/BMPR/Smad/PGC-1α signaling pathway in adipose tissues. Modulation of these pathways might be an effective therapeutic strategy for obesity and type 2 diabetes.

Image fusion of thallium-201 SPECT and MR imaging for the assessment of recurrent head and neck tumors following flap reconstructive surgery.

The aim of this study was to assess the value of fused MR and Tl-201 single photon emission computed tomography (SPECT) images in the diagnosis of recurrent head and neck tumors in patients after flap reconstruction surgery. Twenty-four patients after resection of primary head and neck tumors with flap reconstruction were suspected of having recurrent tumor by follow-up MR examination. Both MR examination and Tl-201 SPECT were prospectively performed to produce fused images. For qualitative analysis, two independent readers separately evaluated the existence of tumor recurrence in the fused images. The Tl-201 uptake of the lesion (Tl index) was also quantitatively compared with that of the normal nuchal muscles. Eighteen patients were histologically proved as having recurrence. The remaining 6 patients, false positive on MRI alone, had non-recurrence. Using the fused images, false positive was found in 1 case for one reader and 2 cases for the other reader. The Tl index of recurrent tumors was significantly higher (p < 0.001) than that of non-recurrent mass lesions. In the assessment of recurrent tumors following flap reconstruction surgery in the head and neck, the use of fused MRI and Tl-201 SPECT images can reduce the number of false positives.