Impact of Tumor Size on Survival Outcome in Esophageal Squamous Cell Carcinoma After Esophagectomy Following Neoadjuvant Chemotherapy.

BACKGROUND: Large tumor size is a prognostic factor in esophageal squamous cell carcinoma (ESCC). However, the effect of tumor size on outcomes following neoadjuvant chemotherapy (NAC) has not been evaluated. This study aimed to assess the influence of tumor size on prognosis of patients undergoing esophagectomy after NAC. PATIENTS AND METHODS: This study was made up of 272 patients who underwent esophagectomy after NAC at Kobe University Hospital. We evaluated the pathological tumor size and determined the cutoff level for tumor size using receiver operating characteristics analysis to the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS: The patients were categorized into two groups: patients with tumor sizes ≥ 36 mm and < 36 mm. Deep pathological tumor invasion and worse histological response to NAC were associated with tumor size ≥ 36 mm. In patients with pT0-1, pT2, and pT4 ESCC, no significant differences in overall survival (OS) rates were observed between the two groups. In patients with pT3, OS of the tumor size ≥ 36 mm group was significantly worse than that of the tumor size < 36 mm group (p < 0.0001). Multivariate analysis in pT3 patients revealed tumor size ≥ 36 mm was an independent risk factor for OS. The 5-year OS rate was 10% in patients with tumor size ≥ 36 mm pT3 ESCC with pathological lymph node metastasis (p < 0.0001). CONCLUSIONS: Tumor size ≥ 36 mm is an independent risk factor for poorer survival in pT3 patients. Furthermore, tumor size ≥ 36 mm with pathological lymph node metastasis in pT3 patients was associated with very poor survival.

Canonical and Non-Canonical Functions of Erythropoietin and Its Receptor in Mature Nucleated Erythrocytes of Western Clawed Frog, Xenopus tropicalis.

Enucleated erythrocytes are characteristic of adult mammals. In contrast, fish, amphibians, reptiles, birds, and fetal mammals possess nucleated erythrocytes in their circulation. Erythroid maturation is regulated by erythropoietin (EPO) and its receptor (EPOR), which are conserved among vertebrates. In mammals, EPOR on the erythroid progenitor membrane disappears after terminal differentiation. However, in western clawed frog, Xenopus tropicalis, mature erythrocytes maintain EPOR expression, suggesting that they have non-canonical functions of the EPO-EPOR axis rather than proliferation and differentiation. In this study, we investigated the non-canonical functions of EPOR in Xenopus mature erythrocytes. EPO stimulation of peripheral erythrocytes did not induce proliferation but induced phosphorylation of intracellular proteins, including signal transducer and activator of transcription 5 (STAT5). RNA-Seq analysis of EPO-stimulated peripheral erythrocytes identified 45 differentially expressed genes (DEGs), including cytokine inducible SH2 containing protein gene (cish) and suppressor of cytokine signaling 3 gene (socs3), negative regulators of the EPOR-Janus kinase (JAK)-STAT pathway. These phosphorylation studies and pathway analysis demonstrated the activation of the JAK-STAT pathway through EPO-EPOR signaling in erythrocytes. Through comparison with EPO-responsive genes in mouse erythroid progenitors obtained from a public database, we identified 31 novel EPO-responsive genes indicating non-canonical functions. Among these, we focused on ornithine decarboxylase 1 gene (odc1), which is the rate-limiting enzyme in polyamine synthesis and affects hematopoietic progenitor differentiation and the endothelial cell response to hypoxic stress. An EPO-supplemented culture of erythrocytes showed increased odc1 expression followed by a decrease in polyamine-rich erythrocytes, suggesting EPO-responsive polyamine excretion. These findings will advance our knowledge of the unknown regulatory systems under the EPO-EPOR axis and functional differences between vertebrates' nucleated and enucleated erythrocytes.

The number of resected lymph nodes from the upper mediastinal area predicts long-term outcomes of esophageal squamous cell carcinoma after minimally invasive esophagectomy.

BACKGROUND: The total number of resected lymph nodes (LNs) is an important determinant of longer survival after esophagectomy for esophageal squamous cell carcinoma (ESCC). However, the resected LN counts from areas that affect long-term outcomes remain unclear. METHODS: This study included 406 patients who underwent minimally invasive esophagectomies (MIEs) at Kobe University Hospital. Resected LN counts were evaluated in the following areas: upper mediastinal (UM), middle mediastinal (MM), lower mediastinal (LM), and abdominal (Abd). Cut-off values for LN counts from each area were determined using receiver operating characteristics analysis of the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS: The cut-off values for large or small numbers of resected LN counts in the UM, MM, LM, and Abd areas were 4, 8, 5, and 18, respectively, in patients with upper and middle thoracic (Ut/Mt) ESCC and 7, 6, 5, and 24, respectively, in patients with lower thoracic (Lt) ESCC. Multivariate analysis in patients with Ut/Mt ESCC revealed that tumor invasion depth, LN metastasis, and the resected LN count from the UM area were independent risk factors for overall survival [hazard ratio (HR), 7.04; 95% confidence interval (CI) 4.47-11.1; HR, 4.01; 95% CI 1.96-8.21; HR, 2.18; 95% CI 1.24-3.82, respectively]. In patients with Lt ESCC, tumor invasion depth, LN metastasis, and pulmonary complications were independent risk factors for overall survival (HR, 4.23; 95% CI 2.14-8.35; HR, 3.83; 95% CI 1.75-8.38; HR, 2.80; 95% CI 1.38-5.65, respectively). Resected LN counts from no areas were prognostic factors. CONCLUSION: The number of resected LNs from the UM area influenced the survival outcomes of patients with Ut/Mt ESCC after MIE.

Associations of dietary patterns and longitudinal brain-volume change in Japanese community-dwelling adults: results from the national institute for longevity sciences-longitudinal study of aging.

BACKGROUND: The association of dietary patterns and longitudinal changes in brain volume has rarely been investigated in Japanese individuals. We prospectively investigated this association in middle-aged and older Japanese community-dwelling adults. METHODS: Data with a 2-year follow-up from the sixth wave (July 2008 to July 2010; baseline) to the seventh (July 2010 to July 2012; follow-up) of the National Institute for Longevity Sciences-Longitudinal Study of Aging project were analyzed. Dietary intake was assessed using a 3-day dietary record, and longitudinal volume changes (%) in the total gray matter (TGM), total white matter, and frontal, parietal, occipital, temporal, and insular lobes were assessed using 3-dimensional T1 magnetic resonance imaging scans. Multiple factor analysis and hierarchical clustering revealed sex-specific dietary patterns. Associations between dietary patterns and annual brain-volume changes (%) were evaluated using general linear models adjusted for age, apoprotein E genotype, body mass index, medical history, lifestyle behaviors, socioeconomic factors, and energy intake. RESULTS: Among the 1636 participants (age: 40.3-89.2 years), three dietary patterns were determined for men (n = 815; Western; Vegetable-Fruit-Dairy; and Traditional Japanese diets) and women (n = 821; Western; Grain-Vegetable-Fruit; and Traditional Japanese diets). Compared to women following the Western diet, those on the Traditional Japanese diet had less TGM atrophy. Multivariable-adjusted ß (95% confidence interval) of the annual change (%) of TGM was - 0.145 (-0.287 to -0.002; P = 0.047), which correlated with reduced parietal lobe atrophy. No association between dietary pattern and brain atrophy was observed in men. CONCLUSIONS: Adherence to healthy dietary patterns, with higher consumption of whole grains, seafood, vegetables, fruits, mushrooms, soybean products, and green tea, potentially confers a protective effect against brain atrophy in middle-aged and older Japanese women but not in men. Further research to confirm these results and ascertain the underlying mechanisms is required. This study highlights the importance of sex-specific effects on the relationship between dietary patterns and brain health in diverse populations.

Autoinflammatory Diseases Due to Defects in Degradation or Transport of Intracellular Proteins.

The number of human inborn errors of immunity has now gone beyond 430. The responsible gene variants themselves are apparently the cause for the disorders, but the underlying molecular or cellular mechanisms for the pathogenesis are often unclear. In order to clarify the pathogenesis, the mutant mice carrying the gene variants are apparently useful and important. Extensive analysis of those mice should contribute to the clarification of novel immunoregulatory mechanisms or development of novel therapeutic maneuvers critical not only for the rare monogenic diseases themselves but also for related common polygenic diseases. We have recently generated novel model mice in which complicated manifestations of human inborn errors of immunity affecting degradation or transport of intracellular proteins were recapitulated. Here, we review outline of these disorders, mainly based on the phenotype of the mutant mice we have generated.

Effectiveness of long-term tube feeding intervention in preventing skeletal muscle loss after minimally invasive esophagectomy.

PURPOSE: Esophageal cancer is a lethal tumor typically treated by neoadjuvant chemotherapy and surgery. For patients undergoing esophagectomy, postoperative enteral nutrition is important in preventing complications. Sarcopenia is associated with poor postoperative outcomes in esophageal cancer. In this study, we evaluated the benefits of tube feeding intervention and compared its short- and long-term outcomes in patients who underwent esophagectomy. METHODS: Propensity score matching was performed in 303 patients who underwent esophagectomy at Kobe University Hospital between 2010 and 2020. Patients were divided into feeding and nonfeeding jejunostomy tube groups (n = 70 each). The feeding jejunostomy tube group was further divided into long-term (≥ 60 days) and short-term (< 60 days) subgroups. The groups were then retrospectively compared regarding postoperative albumin levels, body weight, and psoas muscle area and volume. RESULTS: In the long-term feeding jejunostomy tube group, anastomotic leakage (p = 0.013) and left laryngeal nerve palsy (p = 0.004) occurred frequently. There were no significant between-group differences in postoperative albumin levels, body weight, or psoas muscle area. However, significant psoas muscle volume recovery was confirmed in the long-term jejunostomy tube group at 6 months postoperatively (p = 0.041). CONCLUSIONS: Tube feeding intervention after minimally invasive esophagectomy may attenuate skeletal muscle mass loss and help prevent sarcopenia.

Association of Plasma Claudin-5 with Age and Alzheimer Disease.

The blood-brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5-but not pTau181-decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of AD.

[Analysis of Nuclear ß-Catenin before Starting Treatment Could Potentially Predict the Therapeutic Response to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer].

Although a therapeutic response to neoadjuvant chemoradiotherapy(NACRT)is important to improve oncological outcomes after surgery in patients with locally advanced rectal cancer, there is no reliable predictor for this. The Wnt/ß-catenin signal is known to be crucial for the tumorigenesis of colorectal cancer. This study aimed to investigate the association between Wnt/ß-catenin signal activation and the response to NACRT in patients with locally advanced rectal cancer. We analyzed the expression of nuclear and membranous ß-catenin in biopsy samples obtained from 60 patients who underwent curative surgery following NACRT. We found that patients with low nuclear ß-catenin expression had a higher rate of good histological responses compared to those with high nuclear ß-catenin expression. Additionally, patients with low nuclear/high membranous ß-catenin expression tended to have better relapse-free survival. The activation of the Wnt/ß- catenin signal pathway, represented by nuclear ß-catenin accumulation, was significantly associated with a poor response to NACRT in patients with rectal cancer. The analysis of nuclear ß-catenin accumulation before starting treatment could potentially predict the therapeutic response to NACRT.

2D Photonic Colloidal Liquid Crystals Composed of Self-Assembled Rod-Shaped Particles.

Photonic crystals, characterized by their periodic structures, have been extensively studied for their ability to manipulate light. Typically, the development of 2D photonic crystals requires either sophisticated equipment or precise orientation of spherical nanoparticles. However, liquid-crystalline (LC) materials offer a promising alternative, facilitating the formation of periodic structures without the need for complex manipulation. Despite this advantage, the development of 2D photonic periodic structures using LC materials is limited to a few colloidal nanodisk liquid crystals. Herein, 2D photonic colloidal liquid crystals composed of biomineral-based nanorods and water is reported. The soft photonic materials with 2D structure by self-assembled LC colloidal nanorods are unique and a new class of photonic materials different from conventional solid 2D photonic materials. These colloids exhibit bright structural colors with high reflectance (>50%) and significant angular dependency. The structural colors are adjusted by controlling the concentration and size of the LC colloidal nanorods. Furthermore, mechanochromic hydrogel thin films with 2D photonic structure are developed. The hydrogels exhibit reversible mechanochromic properties with angular dependency, which can be used for an advanced stimuli responsible sensor.

Aquatic Functional Liquid Crystals: Design, Functionalization, and Molecular Simulation.

Aquatic functional liquid crystals, which are ordered molecular assemblies that work in water environment, are described in this review. Aquatic functional liquid crystals are liquid-crystalline (LC) materials interacting water molecules or aquatic environment. They include aquatic lyotropic liquid crystals and LC based materials that have aquatic interfaces, for example, nanoporous water treatment membranes that are solids preserving LC order. They can remove ions and viruses with nano- and subnano-porous structures. Columnar, smectic, bicontinuous LC structures are used for fabrication of these 1D, 2D, 3D materials. Design and functionalization of aquatic LC sensors based on aqueous/LC interfaces are also described. The ordering transitions of liquid crystals induced by molecular recognition at the aqueous interfaces provide distinct optical responses. Molecular orientation and dynamic behavior of these aquatic functional LC materials are studied by molecular dynamics simulations. The molecular interactions of LC materials and water are key of these investigations. New insights into aquatic functional LC materials contribute to the fields of environment, healthcare, and biotechnology.

Acceptance and Preference of Computed Tomographic Colonography and Colonoscopy: Results of a Nationwide Multicenter Comparative Questionnaire Survey in Japan.

Objectives: To investigate patient acceptance and preference for computed tomographic colonography (CTC) over colonoscopy. Methods: Participants were recruited from a nationwide multicenter trial in Japan to assess the accuracy of CTC detection. They were scheduled to undergo colonoscopy after CTC with common bowel preparation on the same day. Some were administered sedative drugs during colonoscopy, depending on the referring clinician and participant's preferences. The participants were requested to complete a questionnaire to evaluate the acceptability of bowel preparation, examinations, and preference for future examinations. Results: Of the 1,257 enrolled participants, 1,180 (mean age: 60.6 years; women: 43.3%) completed the questionnaire. Sedative drugs were not administered in 687 participants (unsedated colonoscopy group) and were administered intravenously during colonoscopy in 493 participants (sedated colonoscopy group). Before propensity score matching, the mean participants' age, percentages of asymptomatic participants, insufflation of gas during colonoscopy, and number of participants with a history of abdominal/pelvic operation significantly differed between the groups. After propensity score matching, 912 participants from each group were included in the analysis. In the unsedated colonoscopy group, CTC was answered as significantly easier than colonoscopy (p<0.001). Conversely, CTC was significantly more difficult than colonoscopy in the sedated colonoscopy group (p<0.001). In the unsedated colonoscopy group, 48% preferred CTC and 22% preferred colonoscopy for future examinations, whereas in the sedated colonoscopy group, 26% preferred CTC and 38% preferred colonoscopy (p<0.001). Conclusions: CTC has superior participant acceptability compared with unsedated colonoscopy. However, our study did not observe the advantages of CTC acceptance over sedative colonoscopy.

Identification and characterization of myeloid cells localized in the tadpole liver cortex in Xenopus laevis.

In the present study, using transgenic frogs that express GFP specifically in myeloid cells under the myeloperoxidase enhancer sequence, we found that myeloperoxidase-positive cells are localized in the liver cortex at the late tadpole stages. Immunohistochemical analysis revealed that myelopoiesis in the liver cortex became evident after st. 50 and reached its peak by st. 56. Transplantation experiments indicated that cells with a high density at the liver cortex were derived from the dorso-lateral plate tissue in the neurula embryo. Analysis of smear samples of the cells isolated from collagenase-treated liver tissues of the transgenic tadpoles indicated that myeloid cells were the major population of blood cells in the larval liver and that, in addition to myeloid colonies, erythroid colonies expanded in entire liver after metamorphosis. Cells that were purified from the livers of transgenic tadpoles according to the GFP expression exhibited the multi-lobed nuclei. The results of present study provide evidence that the liver cortex of the Xenopus tadpole is a major site of granulopoiesis.

Electrochemical Detection of Selective Anion Transport through Subnanopores in Liquid-Crystalline Water Treatment Membranes.

The anion-selective transport through subnanoporous liquid-crystalline (LC) water treatment membranes was quantitatively detected by the deposition and electrochemical analysis of the LC membrane on the GaN electrode. The time course of the capacitance and Warburg resistance of the LC membrane suggest that the interaction of the LC membrane with monovalent Cl- ions is distinctly different from that with SO42- ions. A continuous decay in capacitance suggests the condensation of Cl- ions in subnanopores, whereas the interaction between SO42- ions and the inner wall of subnanopores is much weaker. The chronoamperometry data further suggest that SO42- ions are transported through subnanoporous channels 10 times faster than Cl- ions. These results, together with the previous X-ray emission spectroscopy, suggest that SO42- ions, which possess similar hydrogen-bonded structures to the hydrogen-bonded networks inside the subnanopores, can exchange the associated water molecules and hop along the network of water molecules, but Cl- ions bind and accumulate inside subnanopores. The well-controlled supramolecular self-assembly of LC building blocks opens a large potential toward the fine adjustment of hydrogen-bonding networks in nanospace providing materials new functions, which cannot be realized by bulk water.

Monodisperse nanosheet mesophases.

Self-assemblies of anisotropic colloidal particles into colloidal liquid crystals and well-defined superlattices are of great interest for hierarchical nanofabrications that are applicable for various functional materials. Inorganic nanosheets obtained by exfoliation of layered crystals have been highlighted as the intriguing colloidal units; however, the size polydispersity of the nanosheets has been preventing precise design of the assembled structures and their functions. Here, we demonstrate that the anionic titanate nanosheets with monodisperse size reversibly form very unusual superstructured mesophases through finely tunable weak attractive interactions between the nanosheets. Transmission electron microscopy, polarizing optical microscopy, small-angle x-ray scattering, and confocal laser scanning microscopy clarified the reversible formation of the mesophases (columnar nanofibers, columnar nematic liquid crystals, and columnar nanofiber bundles) as controlled by counter cations, nanosheet concentration, solvent, and temperature.

Hydrogen-Bonded Structures of Water Molecules in Hydroxy-Functionalized Nanochannels of Columnar Liquid Crystalline Nanostructured Membranes Studied by Soft X-ray Emission Spectroscopy.

Here, we report a synchrotron-based high-resolution soft X-ray emission spectroscopy study on hydrogen-bonded structures of water molecules in the self-organized, hydroxy-group-functionalized one-dimensional nanochannels of liquid crystalline nanostructured membranes. The water molecules confined in the uncharged hydroxy-functionalized nanochannels (which have a diameter of about 1.5 nm) exhibit hydrogen-bonded structures close to those of bulk liquid water, even directly interacting with diol groups. These hydrogen-bonded structures contrast with the more distorted hydrogen bonding of water molecules confined in self-organized channels with a diameter of 0.6 nm formed by an analogous nanostructured membrane with a cationic moiety, which was explained by the ability of the channel functional groups to donate and accept hydrogen bonds in a confined space and the nanochannel diameter.

Influence of facetectomy, cross-link augmentation, and interbody procedure on progression of bone fusion in single-level posterior lumbar interbody fusion using the long cortical bone trajectory technique.

OBJECTIVE: When using the cortical bone trajectory (CBT) technique, two technical countermeasures are recommended to promote bone fusion: taking a long CBT screw path directed more anteriorly and improving the stability of the spinal construct by facet joint preservation, cross-link augmentation, and rigid anterior interbody reconstruction. However, there has been no report on how these surgical procedures, which are heavily dependent on the surgeon's preference, contribute to successful bone fusion. The aim of the present study was to investigate the progression of lumbar spinal fusion using the long CBT technique and identify factors contributing to the time taken to achieve bone fusion, with a particular focus on the involvement of surgical procedures. METHODS: A total of 167 consecutive patients with L4 degenerative spondylolisthesis who underwent single-level posterior lumbar interbody fusion at L4-5 using the long CBT technique were included (mean follow-up 42.8 months). Bone fusion was assessed to identify factors contributing to the time to achieve bone fusion. Investigated factors were 1) age, 2) sex, 3) BMI, 4) bone mineral density, 5) intervertebral mobility, 6) screw depth in the vertebra, 7) extent of facetectomy, 8) cross-link augmentation, 9) cage material, 10) cage design, 11) number of cages, and 12) contact area of cages with the vertebral endplate. RESULTS: The bone fusion rate was 89.2% at 2 years postoperatively and 95.8% at the last follow-up, with a mean period to bone fusion of 16.6 ± 9.6 months. Multivariate regression analysis revealed that age (standardized regression coefficient [ß] = 0.25, p = 0.002), female sex (ß = -0.22, p = 0.004), and BMI (ß = 0.15, p = 0.045) were significant independent factors affecting the time to achieve bone fusion. There was no significant effect of surgical procedures (p ≥ 0.364). CONCLUSIONS: This is the first study to investigate the progression of lumbar spinal fusion using the long CBT technique and identify factors contributing to the time taken to achieve bone fusion. Patient factors such as age, sex, and BMI affected the progression of bone fusion, and surgical factors had only weak effects.

Blood levels of glial fibrillary acidic protein for predicting clinical progression to Alzheimer's disease in adults without dementia: a systematic review and meta-analysis protocol.

BACKGROUND: There is urgent clinical need to identify reliable prognostic biomarkers that predict the progression of dementia symptoms in individuals with early-phase Alzheimer's disease (AD) especially given the research on and predicted applications of amyloid-beta (Aß)-directed immunotherapies to remove Aß from the brain. Cross-sectional studies have reported higher levels of cerebrospinal fluid and blood glial fibrillary acidic protein (GFAP) in individuals with AD-associated dementia than in cognitively unimpaired individuals. Further, recent longitudinal studies have assessed the prognostic potential of baseline blood GFAP levels as a predictor of future cognitive decline in cognitively unimpaired individuals and in those with mild cognitive impairment (MCI) due to AD. In this systematic review and meta-analysis, we propose analyzing longitudinal studies on blood GFAP levels to predict future cognitive decline. METHODS: This study will include prospective and retrospective cohort studies that assessed blood GFAP levels as a prognostic factor and any prediction models that incorporated blood GFAP levels in cognitively unimpaired individuals or those with MCI. The primary outcome will be conversion to MCI or AD in cognitively unimpaired individuals or conversion to AD in individuals with MCI. Articles from PubMed and Embase will be extracted up to December 31, 2023, without language restrictions. An independent dual screening of abstracts and potentially eligible full-text reports will be conducted. Data will be dual-extracted using the CHeck list for critical appraisal, data extraction for systematic Reviews of prediction Modeling Studies (CHARMS)-prognostic factor, and CHARMS checklists, and we will dual-rate the risk of bias and applicability using the Quality In Prognosis Studies and Prediction Study Risk-of-Bias Assessment tools. We will qualitatively synthesize the study data, participants, index biomarkers, predictive model characteristics, and clinical outcomes. If appropriate, random-effects meta-analyses will be performed to obtain summary estimates. Finally, we will assess the body of evidence using the Grading of Recommendation, Assessment, Development, and Evaluation Approach. DISCUSSION: This systematic review and meta-analysis will comprehensively evaluate and synthesize existing evidence on blood GFAP levels for prognosticating presymptomatic individuals and those with MCI to help advance risk-stratified treatment strategies for early-phase AD. TRIAL REGISTRATION: PROSPERO CRD42023481200.

Comparison of consistency in centiloid scale among different analytical methods in amyloid PET: the CapAIBL, VIZCalc, and Amyquant methods.

OBJECTIVE: The Centiloid (CL) scale is a standardized measure for quantifying amyloid deposition in amyloid positron emission tomography (PET) imaging. We aimed to assess the agreement among 3 CL calculation methods: CapAIBL, VIZCalc, and Amyquant. METHODS: This study included 192 participants (mean age: 71.5 years, range: 50-87 years), comprising 55 with Alzheimer's disease, 65 with mild cognitive impairment, 13 with non-Alzheimer's dementia, and 59 cognitively normal participants. All the participants were assessed using the three CL calculation methods. Spearman's rank correlation, linear regression, Friedman tests, Wilcoxon signed-rank tests, and Bland-Altman analysis were employed to assess data correlations, linear associations, method differences, and systematic bias, respectively. RESULTS: Strong correlations (rho = 0.99, p < .001) were observed among the CL values calculated using the three methods. Scatter plots and regression lines visually confirmed these strong correlations and met the validation criteria. Despite the robust correlations, a significant difference in CL value between CapAIBL and Amyquant was observed (36.1 ± 39.7 vs. 34.9 ± 39.4; p < .001). In contrast, no significant differences were found between CapAIBL and VIZCalc or between VIZCalc and Amyquant. The Bland-Altman analysis showed no observable systematic bias between the methods. CONCLUSIONS: The study demonstrated strong agreement among the three methods for calculating CL values. Despite minor variations in the absolute values of the Centiloid scores obtained using these methods, the overall agreement suggests that they are interchangeable.

Tumor-induced Osteomalacia Successfully Treated by En Bloc Tumor Excision and Reconstruction Using a Tumor-bearing Frozen Autograft: A Case Report.

BACKGROUND/AIM: Tumor-induced osteomalacia (TIO) is a rare pathology caused by overproduction of fibroblast growth factor 23 (FGF23). Its common clinical features include generalized muscle weakness, bone pain, and fractures. Complete resection of the offending tumor is the mainstay treatment. In this report, we present the first case of TIO by an FGF23 producing tumor treated using a tumor-bearing autograft treated with liquid nitrogen. CASE REPORT: A 63-year old female presented with generalized body pain, particularly in the left arm. The patient was diagnosed with a FGF23 producing tumor of the left humerus. Wide resection of the involved tumor was performed using a tumor-bearing autograft that was treated with liquid nitrogen. Postoperatively, the FGF23 and alkaline phosphatase (ALP) levels significantly decreased and inorganic phosphate normalized. There was also subsequent relief of generalized body pain. Immediately after the operation, range of motion of the left shoulder and elbow was initiated. The patient was instructed to perform forward flexion and abduction up to 90° with a rotational restraint. Almost complete bone union was observed at 12 months post procedure. Postoperative functional results were as follows: Musculoskeletal Tumor Society (MSTS) score of 27/30, 90% and International Society of Limb Salvage (ISOLS) score of 26/30, 87%. Ten years after the surgery, osteotomy line was completely obscured based on radiographs. The patient was disease free and without activity limitation. CONCLUSION: This is the first case report of wide excision of a FGF23 producing tumor and reconstruction using a tumor-bearing frozen autograft performed with excellent outcomes.

A novel PET probe to selectively image heat shock protein 90α/ß isoforms in the brain.

BACKGROUND: Heat shock proteins (HSPs) are present throughout the brain. They function as molecular chaperones, meaning they help with the folding and unfolding of large protein complexes. These chaperones are vital in the development of neuropathological conditions such as Alzheimer's disease and Lewy body disease, with HSP90, a specific subtype of HSP, playing a key role. Many studies have shown that drugs that inhibit HSP90 activity have beneficial effects in the neurodegenerative diseases. Therefore, HSP90 PET imaging ligand can be used effectively to study HSP90 in neurodegenerative diseases. Among four HSP90 isoforms, two cytosolic isoforms (HSP90α and HSP90ß) thought to be involved in the structural homeostasis of the proteins related to the neurodegenerative diseases. Currently, no useful PET imaging ligands selectively targeting the two cytosolic isoforms of HSP90 have been available yet. RESULTS: In this study, we developed a novel positron emission tomography (PET) imaging ligand, [11C]BIIB021, by 11C-radiolabeling (a positron emitter with a half-life of 20.4 min) 6-Chloro-9-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine (BIIB021), an inhibitor with a high affinity for and selectivity to HSP90α and HSP90ß. [11C]BIIB021 was synthesized with a high yield, molar activity and radiochemical purity. [11C]BIIB021 showed a high binding affinity for rat brain homogenate as well as human recombinant HSP90α and HSP90ß proteins. Radioactivity was well detected in the rat brain (SUV 1.4). It showed clear specific binding in PET imaging of healthy rats and autoradiography of healthy rat and human brain sections. Radiometabolite was detected in the brain, however, total distribution volume was well quantified using dual-input graphical model. Inhibition of p-glycoprotein increased brain radioactivity concentrations. However, total distribution volume values with and without p-glycoprotein inhibition were nearly the same. CONCLUSIONS: We have developed a new PET imaging agent, [11C]BIIB021, specifically targeting HSP90α/ß. We have been successful in synthesizing [11C]BIIB021 and in vitro and in vivo imaging HSP90α/ß. However, the quantification of HSP90α/ß is complicated by the presence of radiometabolites in the brain and the potential to be a substrate for p-glycoprotein. Further efforts are needed to develop radioligand suitable for imaging of HSP90α/ß.