Serum adiponectin predicts fracture risk in individuals with type 2 diabetes: the Fukuoka Diabetes Registry.

AIMS/HYPOTHESIS: Serum adiponectin has been reported to impact upon fracture risk in the general population. Although type 2 diabetes is associated with increased fracture risk, it is unclear whether serum adiponectin predicts fractures in individuals with type 2 diabetes. The aim of the study was to prospectively investigate the relationship between serum adiponectin and fracture risk in individuals with type 2 diabetes. METHODS: In this study, data was obtained from The Fukuoka Diabetes Registry, a multicentre prospective study designed to investigate the influence of modern treatments on the prognoses of patients with diabetes mellitus. We followed 4869 participants with type 2 diabetes (mean age, 65 years), including 1951 postmenopausal women (defined as self-reported amenorrhea for >1 year) and 2754 men, for a median of 5.3 years. The primary outcomes were fractures at any site and major osteoporotic fractures (MOFs). RESULTS: During the follow-up period, fractures at any site occurred in 682 participants, while MOFs occurred in 277 participants. Age-adjusted HRs (95% CIs) of any fracture and MOFs for 1 SD increment in log e -transformed serum adiponectin were 1.27 (1.15, 1.40) and 1.35 (1.17, 1.55) in postmenopausal women and 1.22 (1.08, 1.38) and 1.40 (1.15, 1.71) in men, respectively. HRs (95% CIs) of MOFs for hyperadiponectinaemia (≥ 20 µg/ml) were 1.72 (1.19, 2.50) in postmenopausal women and 2.19 (1.23, 3.90) in men. The per cent attributable risk of hyperadiponectinaemia for MOFs was as high as being age ≥70 years or female sex. CONCLUSIONS/INTERPRETATION: Higher serum adiponectin levels were significantly associated with an increased risk of fractures at any site and with an increased risk of MOFs in individuals with type 2 diabetes, including postmenopausal women.

The gene-treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes: Fukuoka diabetes registry.

BACKGROUND: Although statins deteriorate glucose metabolism, their glucose-lowering effects have emerged in some situations. Here, we assessed whether these effects are a consequence of statins' interaction with paraoxonase (PON)1 enzyme polymorphism. METHODS: Adult Japanese type 2 diabetes patients (n = 3798) were enrolled in a cross-sectional study. We used Q192R polymorphism of the PON1 gene as a representative single-nucleotide polymorphism and focused on the effects of the wild-type Q allele, in an additive manner. For patients with and without statin therapy, the associations of this allele with fasting plasma glucose (FPG), HbA1c, C-peptide, HOMA2-%ß, and HOMA2-IR were investigated separately using a linear regression model, and were compared between groups by testing interactions. Sensitivity analyses were performed using propensity score to further control the imbalance of characteristics between groups. RESULTS: Among patients with statin therapy, there were linear associations of the number of Q alleles with decreased FPG and HbA1c, and with increased serum C peptide and HOMA2-%ß (all P < 0.01 for trends), while such associations were not observed among those without statin therapy. These differences were statistically significant only for serum C peptide and HOMA2-%ß (P < 0.01 for interactions). These associations remained significant after multiple explanatory variable adjustment. Sensitivity analyses using propensity score showed broad consistency of these associations. CONCLUSIONS: Patients with the Q allele of the PON1 Q192R polymorphism who were treated with statins exhibited improvement in glucose metabolism, especially in insulin secretion, suggesting the importance of genotyping PON1 Q192R to identify those who could benefit from statin therapy.

Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma.

Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated. Ours is the first report that the expression level of COX-2 in brain tissue samples from patients with LGG and in LGG cell lines is higher than in the non-neoplastic region and in normal brain cells. We found that celecoxib attenuated LGG cell proliferation in a dose-dependent manner. It inhibited the generation of prostaglandin E2 and induced apoptosis and cell-cycle arrest. We also show that celecoxib hampered the activation of the Akt/survivin- and the Akt/ID3 pathway in LGGs. These findings suggest that celecoxib may have a promising therapeutic potential and that the early treatment of LGG patients with the drug may be beneficial.

Comparison of cystatin C- and creatinine-based estimated glomerular filtration rates for predicting all-cause mortality in Japanese patients with type 2 diabetes: the Fukuoka Diabetes Registry.

BACKGROUND: There is little information about the predictive ability of cystatin C-based estimated glomerular filtration rates (eGFRCys) for all-cause mortality in Asian populations. We compared the discriminatory ability of eGFRCys for all-cause mortality with that of creatinine-based estimated glomerular filtration rates (eGFRCr) in Japanese patients with type 2 diabetes. METHODS: A total of 4869 participants were classified into four categories (eGFR ≤29, 30-59, 60-89, and ≥90 ml/min/1.73 m2) by eGFRCr and eGFRCys, and followed up for a median of 3.3 years. RESULTS: 150 deaths were identified. The multivariable-adjusted risk of all-cause mortality was significantly increased in eGFRCr ≤29 ml/min/1.73 m2 compared with eGFRCr ≥90 ml/min/1.73 m2 [hazard ratio (HR) 2.4 (95 % confidence interval (95 % CI) 1.2-5.0)], whereas it was significantly increased in eGFRCys 59 ml/min/1.73 m2 or lower [30-59 ml/min/1.73 m2, HR 1.9 (95 % CI 1.1-3.5); ≤29 ml/min/1.73 m2, HR 5.8 (95 % CI 2.8-12.0)]. Comparing eGFRCys with eGFRCr, the proportions of participants reclassified to lower and higher eGFR stages were 6.3 and 28.8 %, respectively. The multivariable-adjusted HRs for all-cause mortality were 1.8 (95 % CI 1.1-2.9) and 0.7 (95 % CI 0.4-1.1), respectively. The C statistic of the model including eGFRCys and other risk factors was significantly increased compared with the model including eGFRCr. The net reclassification improvement and the integrated discrimination improvement were significantly positive. CONCLUSIONS: Our findings suggest that eGFRCys has a stronger association with all-cause mortality and is superior to eGFRCr for predicting all-cause mortality in Japanese patients with type 2 diabetes.

Fetal Hepatic Hemangioma Diagnosed in Utero Using Doppler Microvascular Imaging.

A 35-year-old pregnant woman was referred to our institution at 33 weeks' gestation for evaluation of a fetal abdominal tumor. B-mode ultrasonography demonstrated a massive lesion. Bidirectional power Doppler mode showed abundant blood flow surrounding the tumor. On superb micro-vascular imaging, various Doppler signal patterns were observed within the tumor, including diffuse fine dotted-like signals, linear flow, and internal shunt flow. Sequential observations of the tumor and cardiac cycles also revealed pulsatile flow beneath the edges of the tumor and continuous fine flow in the central area, resembling a 'centripetal fill-in' appearance on contrast computed tomography. Therefore, we assumed the fetal tumor to be a hepatic hemangioma. Fetal heart failure was detected at 37 weeks' gestation, and a 2,484-g female infant was delivered with 1- and 5-min Apgar scores of 7 and 8, respectively. A postnatal contrast computed tomography examination showed a progressive centripetal fill-in appearance, leading to a diagnosis of hepatic hemangioma. Kasabach-Merritt syndrome was also noted. Intensive treatment was performed, and the infant was discharged at 3 months after birth. In summary, we experienced a case of hepatic hemangioma diagnosed in utero using superb micro-vascular imaging. And basing seamless postnatal treatments on prenatal imaging findings may help to reduce the perinatal mortality.

18F-FDG PET/CT imaging of IgG4-producing MALT lymphoma with multiple site involvement.

18F-FDG PET/CT is regarded as a modality utilized for the purpose of lesion localization, staging and assessment of treatment response in patients with lymphoma. However, it is difficult that we diagnose among multifocal lymphoma, IgG4-related disease (IgG4-RD), or a combination of both conditions when confronted with multiple sites of 18F-FDG uptake with heightened serum IgG4 levels. We present a case of a 72-year-old male who was suspected of Sjögren's syndrome based on symptoms of xerostomia accompanied by swelling of the bilateral upper eyelid and salivary glands. Following a diagnostic biopsy that revealed mucosa-associated lymphoid tissue (MALT) lymphoma as a possible finding, 18F-FDG PET/CT was conducted, which demonstrated multiple sites of 18F-FDG accumulation. While multifocal MALT lymphoma was initially suspected, the coexistence of IgG4-RD could not be definitively ruled out due to the elevated serum IgG4 levels. Subsequent histopathological and immunohistochemical examinations confirmed the diagnosis of IgG4-producing MALT lymphoma. After receiving systemic therapy with rituximab, the swelling of the bilateral upper eyelid and parotid glands resolved upon visual examination, and the serum IgG4 levels returned to within the normal range in a few months. No new lesions were detected during the subsequent follow-up examinations conducted over a period of 3 years.

Effectiveness of 18F-FDG PET/CT in finding lung metastasis from a retroperitoneal paraganglioma.

A 50-year-old woman was diagnosed with iron deficiency anemia on general medical examination. Further, contrast-enhanced abdominal CT and magnetic resonance imaging revealed a large hypervascular mass with internal degeneration and necrosis in the retroperitoneal space. She was referred to our hospital for further evaluation and treatment. Because the paraganglioma was most likely as the imaging diagnosis, 123I-MIBG scintigraphy was performed. It revealed the marked abnormal accumulation in the retroperitoneal lesion indicating the paraganglioma and no other abnormal accumulation was noted. Several plasma catecholamines and their urinary metabolites were normal. On the subsequent 18F-FDG PET/CT, high FDG uptake was found in the retroperitoneal lesion (SUVmax=38). FDG uptake was also found in a small nodule at the base of the lower lobe of the right lung (SUVmax= 9.8). Contrast-enhanced imaging revealed a hypervascular nodule at the base of the right lung, suggesting pulmonary metastasis of a paraganglioma. The abdominal lesion and right lung nodule were excised, and retroperitoneal paraganglioma and pulmonary metastasis were diagnosed based on the pathology findings. In this case, 18F-FDG PET/CT was useful in the search for paraganglioma metastasis. We report a relationship between 123I-MIBG accumulation and 18F-FDG uptake in paraganglioma and review the relevant literature.

Parental Accompaniment in Operating Rooms Reduces Child Anxiety.

BACKGROUND: We believe that parental presence before the induction of anesthesia for surgery among children with a cleft palate/lip would be effective in mitigating their preoperative anxiety. OBJECTIVE: We assessed the states of patients with a cleft palate/lip when their parents accompanied them into operating rooms and clarified their and their parents' cognition using a questionnaire. METHODS: Data were collected via nursing observation when patients and their parents entered the operating room. Furthermore, an anonymous questionnaire was administered to patients and parents after the operation regarding their feelings about parental presence in the operating room. RESULTS: In total, nine patients cried when they entered the surgical room. Furthermore, six patients and three parents reported preoperative anxiety. In addition, eight patients agreed that they were satisfied with the presence of their parents before induction. CONCLUSION: Approximately half of the patients cried. However, the presence of parents before the induction of anesthesia was effective in reducing anxiety among most patients and their parents.

Combination of Prednisolone and Calcineurin Inhibitors Prevents Lung Function Decline in Patients with Anti-aminoacyl-tRNA Synthetase Antibody-Positive Polymyositis/Dermatomyositis.

OBJECTIVE: Anti-aminoacyl-tRNA synthetase antibody-positive polymyositis/dermatomyositis-associ ated interstitial lung disease (ARS-ILD) has a good prognosis, with few cases progressing to respiratory failure. This study aimed to determine factors predictive of lung function changes in patients with ARS-ILD. METHODS: We retrospectively studied 49 patients with ARS-ILD treated at Kurume University Hospital Hospital between 2000 and 2018. We followed 30 patients for more than 2 years after prednisolone (PSL) therapy, with or without calcineurin inhibitors (CNIs), evaluating clinical, physiological, computed tomography, pulmonary func tion, and serological data. RESULTS: After treatment for 24 months, no significant differences were noted between clinical parameters and improvement in forced vital capacity (FVC), %FVC, % carbon monoxide diffusing capacity/alveolar volume (%DLCO), and %DLCO/alveolar volume. Conversely, the annual change of %FVC significantly correlated with the Medical Research Council dyspnea scale grade and %FVC at the first visit and treatment. Furthermore, the annual change of %DLCO/VA significantly correlated with the duration from the first visit to treatment initiation. CONCLUSION: Compared with PSL monotherapy, combining PSL and CNI showed greater mitigation of %FVC decline. The time from onset of ARS-ILD to the first visit is critical for preventing a decline in lung function, and as such, patients should be monitored carefully.

Utility of non-contrast-enhanced magnetic resonance imaging in predicting preoperative clinical stage and prognosis in patients with thymic epithelial tumor.

PURPOSE: The purpose of this study was to find useful imaging features on non-contrast-enhanced magnetic resonance imaging (MRI) that can divide patients with thymic epithelial tumor (TET) into clinical stage I-II and III-IV groups under assumption that contrast media are contraindicated. MATERIALS AND METHODS: This retrospective study included 106 patients (median age, 60 years; range, 27-82 years; 62 women) with surgically resected TET who underwent MRI between August 1986 and July 2015. All cases were classified according to the 2015 WHO classification and staged using the eighth edition of the TNM system. Two radiologists independently evaluated 14 categories of MRI findings; the findings in patients with stage I-II were compared with those of patients with stage III-IV using a logistic regression model. Disease-specific survival associated with significant findings was calculated using the Kaplan-Meier method. RESULTS: Univariate analysis showed that stage III-IV patients were more likely to have tumors with an irregular contour, heterogeneity on T1WI, low-signal intensity on T2WI, irregular border with lung, findings of great vessel invasion (GVI) (hereafter, GVI sign), pericardial thickening/nodule, and lymphadenopathy (all, P < 0.01). On multivariable analysis, only two findings, irregular border between tumor and lung (odds ratio [OR], 272.8; 95% CI 26.6-2794.1; P < 0.001) and positive GVI sign (OR, 49.3; 95% CI 4.5-539.8; P = 0.001) remained statistically significant. Patients with one or both features had significantly worse survival (log-rank test, P < 0.001). CONCLUSION: For patients with TET who are unable to receive contrast for preoperative staging, the two image findings of an irregular border between tumor and lung and the positive GVI sign on non-contrast-enhanced MRI could be helpful in determining stage III-IV disease which is associated with a worse survival.

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated bronchioloalveolar disorder required differentiation from fibrotic chronic hypersensitivity pneumonitis.

We encountered a case of HTLV-1-associated bronchioloalveolar disorder (HABA) that was difficult to distinguish from fibrotic chronic hypersensitivity pneumonitis (CHP). Chest thin-section computed tomography (CT) showed diffuse micronodules and revealed peribronchovascular and perilobular distribution. Further, thickening of the interlobular septa, areas of ground-glass attenuation, traction bronchiectasis/bronchiolectasis, and air trapping were observed. Based on these findings, diseases that cause lymphatic tract abnormalities and fibrotic CHP were considered differential diseases. A surgical lung biopsy was performed, and an HTLV-1 antibody was detected using the Western blot analysis of bronchoalveolar lavage fluid. The final diagnosis of HABA was made through a multidisciplinary discussion.

Unilateral axillary lymph node fluorodeoxyglucose uptakes after coronavirus disease 2019 vaccination.

Vaccination against coronavirus disease 2019 (COVID-19) started in early December 2020 worldwide, and healthcare workers in Japan were vaccinated in February 2021. We encountered three patients who underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for cancer screening at our institution, showing FDG uptakes in the axillary lymph nodes, which seemed to be reactive changes. Two of them were males in their 40s and one was a female in her 50s; all of them were healthcare workers. The medical history revealed that they received the Pfizer-BioNTech COVID-19 vaccination twice at their left shoulders before the FDG PET/CT examination. The degree of FDG uptakes were maximum standardized uptake value (SUVmax)=3.2-9.9, SUVmax=5.9-10.3, and SUVmax=2.8-7.9, respectively. They were diagnosed with reactive lymph nodes because of vaccination owing to the absence of abnormal FDG PET/CT findings at other sites. As COVID-19 vaccination becomes more widespread in Japan, radiologists should be aware of these findings to avoid misdiagnosis of FDG uptakes in pathological lymph nodes and to prevent unnecessary additional examinations. Recently, similar FDG PET/CT findings have been reported after receiving the COVID-19 vaccination, and we will report it with a literature review.

Positive Autoantibody Is Associated with Malignancies in Patients with Idiopathic Interstitial Pneumonias.

Various autoantibodies are associated with clinical outcomes in patients with idiopathic interstitial pneumonias (IIPs). We retrospectively analyzed the association between autoantibodies and malignancies in IIP patients. Comprehensive analyses of autoantibodies were performed using immunoprecipitation and enzyme-linked immunosorbent assays in 193 consecutive IIP patients. Cancer-related factors were analyzed using logistic regression analysis. In total, 22 of 193 patients (11.4%) with IIP had malignant disease. In univariate analysis, positivity for any autoantibody (odds ratio (OR), 3.1; 95% confidence interval (CI), 1.2-7.7; p = 0.017) and antinuclear antibody titer ≥1:320 (OR, 3.4; CI, 1.2-9.8; p = 0.024) were significantly associated with malignancies. Positive anti-aminoacyl tRNA synthetase (ARS) (OR, 3.7; CI, 0.88-15.5; p = 0.074) and anti-Ro52 antibody (OR, 3.2; CI, 0.93-11.2; p = 0.065) tended to be associated with malignancies. In multivariate analysis, independent risk factors were male sex (OR, 3.7; CI, 1.0-13.5; p = 0.029) and positivity for any autoantibody (OR, 3.9; CI, 1.5-10.1; p = 0.004) in model 1, and male sex (OR, 3.9; CI, 1.0-15.3; p = 0.049), antinuclear antibody titer ≥1:320 (OR, 4.2; CI, 1.4-13.3; p = 0.013), and positivity for anti-ARS antibody (OR, 6.5; CI, 1.2-34.1; p = 0.026) in model 2. Positivity for any autoantibody, antinuclear and anti-ARS antibodies, and male sex were independent risk factors for malignancies in IIP patients. Testing autoantibodies in IIP patients might help the early diagnosis of malignancies.

T1 invasive lung adenocarcinoma: Thin-section CT solid score and histological periostin expression predict tumor recurrence.

Adenocarcinoma is the most common histological type of non-small cell lung cancer (NSCLC), and various biomarkers for predicting its prognosis after surgical resection have been suggested, particularly in early-stage lung adenocarcinoma. Periostin (also referred to as POSTN, PN or osteoblast-specific factor) is an extracellular matrix protein, the expression of which is associated with tumor invasiveness in patients with NSCLC. In the present study, the novel approach, in which the thin-section CT findings prior to surgical resection and periostin expression of resected specimens were analyzed in combination, was undertaken to assess whether the findings could be a biomarker for predicting the outcomes following resection of T1 invasive lung adenocarcinoma. A total of 73 patients who underwent surgical resection between January 2000 and December 2009 were enrolled. A total of seven parameters were assessed in the thin-section CT scans: i) Contour; ii) part-solid ground-glass nodule or solid nodule; iii) percentage of solid component (the CT solid score); iv) presence of air-bronchogram and/or bubble-like lucencies; v) number of involved vessels; vi) shape linear strands between the nodule and the visceral pleura; and vii) number of linear strands between the nodule and the visceral pleura. Two chest radiologists independently assessed the parameters. Periostin expression was evaluated on the basis of the strength and extent of staining. Univariate and multivariate analyses were subsequently performed using the Cox proportional hazards model. There was a substantial to almost perfect agreement between the two observers with regard to classification of the seven thin-section CT parameters (κ=0.64-0.85). In the univariate analysis, a CT solid score >80%, pathological lymphatic invasion, tumor and lymph node status and high periostin expression were significantly associated with recurrence (all P<0.05). Multivariate analysis demonstrated that a CT solid score >80% and high periostin expression were risk factors for recurrence (P=0.002 and P=0.011, respectively). The cumulative recurrence rates among the three groups (both negative, CT solid score >80% or high periostin expression, or both positive) were significantly different (log-rank test, P<0.001). Although the solid component is already known to be a major predictor of outcome in lung adenocarcinomas according to previous studies, the combined analysis of CT solid score and periostin expression might predict the likelihood of tumor recurrence more precisely.

Imaging features in patients with SAPHO/CRMO: a pictorial review.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and chronic recurrent multifocal osteomyelitis (CRMO) have been described as disorders of chronic osteoarthritic inflammation frequently associated with skin manifestations, and SAPHO and CRMO (SAPHO/CRMO) are rare autoinflammatory disorders of unknown etiology. SAPHO tends to occur in adults and CRMO predominantly occurs in children and adolescents. SAPHO/CRMO can affect any skeletal region (e.g., anterior chest wall, spine, or long bones). As SAPHO/CRMO are diagnoses of exclusion, the diagnoses might be difficult if skin manifestations are not clearly evident. However, knowledge of the imaging findings of skeletal disorders is helpful for correcting the diagnosis and avoiding unnecessary invasive procedures, as well as in facilitating early diagnosis and adequate treatment. This pictorial review describes the appearance of increased skeletal uptake for SAPHO/CRMO on bone scintigraphy along with findings from radiography, computed tomography, and magnetic resonance imaging.

Downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes contributes to antitumor effects in a mouse model of malignant glioma.

Glioblastoma multiforme involves glioma stem cells (GSCs) that are resistant to various therapeutic approaches. Here, we studied the importance of paracrine signaling in the glioma microenvironment by focusing on the celecoxib-mediated role of chemokines C-C motif ligand 2 (CCL2), C-X-C ligand 10 (CXCL10), and their receptors, CCR2 and CXCR3, in GSCs and a GSC-bearing malignant glioma model. C57BL/6 mice were injected with orthotopic GSCs intracranially and divided into groups administered either 10 or 30 mg/kg celecoxib, or saline to examine the antitumor effects associated with chemokine expression. In GSCs, we analyzed cell viability and expression of chemokines and their receptors in the presence/absence of celecoxib. In the malignant glioma model, celecoxib exhibited antitumor effects in a dose dependent manner and decreased protein and mRNA levels of Ccl2 and CxcL10 and Cxcr3 but not of Ccr2. CCL2 and CXCL10 co-localized with Nestin+ stem cells, CD16+ or CD163+ macrophages and Iba-1+ microglia. In GSCs, celecoxib inhibited Ccl2 and Cxcr3 expression in a nuclear factor-kappa B-dependent manner but not Ccr2 and CxcL10. Moreover, Ccl2 silencing resulted in decreased GSC viability. These results suggest that celecoxib-mediated regulation of the CCL2/CCR2 and CXCL10/ CXCR3 axes may partially contribute to glioma-specific antitumor effects.

Clinical significance of patterns of increased [18F]-FDG uptake in the thyroid gland: a pictorial review.

In the diagnosis and staging of oncologic patients, [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) is well recognized as an important functional imaging modality. FDG-PET also has been used for cancer screening in healthy individuals. In general, the normal thyroid gland shows absent or low uptake on FDG-PET, which is often identified as an incidental finding on PET. Today, thyroid FDG uptake can be seen in three patterns: diffuse; focal; and diffuse-plus-focal. Diffuse thyroid uptake is mainly considered an indicator of chronic thyroiditis. Focal thyroid uptake has been associated with malignancy (range 25-50%). Diffuse-plus-focal uptake is not well recognized and might also indicate a risk of malignancy. Understanding the patterns of thyroid FDG uptake is thus important for nuclear medicine physicians or radiologists when giving recommendations to the referring physician. In this pictorial review, we show the clinical significance of different patterns of thyroid uptake on FDG-PET [PET/computed tomography (CT)], including ultrasonography (US) findings.

Large cell neuroendocrine carcinoma of the maxillary sinus on fine needle aspiration cytology: Report of a rare case with a focus on pitfalls in diagnosis.

Head and neck large cell neuroendocrine carcinoma (LCNEC) is a rare high-grade malignant tumor with neuroendocrine differentiation. We report a case of LCNEC causing difficulty in cytological diagnosis. A 60-year-old man with right-sided face pain presented with a swelling at the right cheek, and he complained of right nasal obstruction and lacrimation. Preoperative fine-needle aspiration cytology (FNAC) showed high cellularity, with a moderate number of clusters of tumor cells on an abundant necrotic background. The clusters were arranged in sheet structures with palisading, and were cohesive with overlapping. The tumor cells had comparatively abundant cytoplasm, with conspicuous large, irregular nucleoli with a fine granular chromatin pattern. Mitotic figures were observed easily. On immunocytochemistry using LBC smear, tumor cells were negative for p40. High-grade carcinoma other than non-keratinizing squamous cell carcinoma was suggested from these findings on FNAC. The pretreatment histological biopsy sample revealed tumor cells with solid growth pattern, necrotic materials and large polygonal cells with abundant cytoplasm, fine granular chromatin, and conspicuous nucleoli. Head and neck LCNEC with abundant cytoplasm, fine granular chromatin patterns, prominent nucleoli, and necrotic background were very characteristic of LCNEC. If considered carefully, these findings can enable us to exclude the majority of non-keratinizing squamous cell carcinomas, and FNAC using ancillary technique can be very useful for proper diagnosis.

The serum creatinine to cystatin C ratio predicts bone fracture in patients with type 2 diabetes: The Fukuoka Diabetes Registry.

AIMS: Sarcopenia is involved in the pathogenesis of increased fracture risk associated with diabetes. The serum creatinine to cystatin C (Cr/CysC) ratio has been reported as a surrogate marker for muscle mass. We aimed to prospectively investigate the relationship between the Cr/CysC ratio and fracture risk. METHODS: We followed 1911 postmenopausal women and 2689 men with type 2 diabetes (mean age, 66 years) for a median of 5.3 years, and divided into Cr/CysC ratio quartiles by sex. The primary outcome was fragility fractures and the secondary outcome was any fracture. RESULTS: Fragility fractures occurred in 192 participants, and any fracture occurred in 645 participants. Multivariate-adjusted hazard ratios (95% CI) for fragility fractures were 2.15 (1.19-3.88) (Q1), 1.63 (0.89-2.98) (Q2), 1.34 (0.72-2.51) (Q3) and 1.0 (ref.) (Q4) in postmenopausal women, and 1.75 (0.64-4.50) (Q1), 2.09 (0.83-5.26) (Q2), 1.56 (0.58-4.18) (Q3) and 1.0 (ref.) (Q4) in men. Those for any fracture were 1.46 (1.07-1.98) (Q1), 1.33 (0.98-1.81) (Q2), 1.40 (1.03-1.88) (Q3) and 1.0 (ref.) (Q4) in postmenopausal women, and 2.33 (1.54-3.54) (Q1), 2.02 (1.54-3.04) (Q2), 1.13 (0.71-1.78) (Q3) and 1.0 (ref.) (Q4) in men. CONCLUSIONS: A lower Cr/CysC ratio is a significant risk factor for fractures in patients with type 2 diabetes.

Impact of Body Weight Loss From Maximum Weight on Fragility Bone Fractures in Japanese Patients With Type 2 Diabetes: The Fukuoka Diabetes Registry.

OBJECTIVE: There is growing evidence that weight loss is associated with increased fracture risk in the general population. As patients with diabetes often lose weight intentionally or unintentionally, we aimed to investigate prospectively the relationship between weight loss from maximum body weight and fracture risk. RESEARCH DESIGN AND METHODS: A total of 4,706 Japanese participants with type 2 diabetes (mean age 66 years), including 2,755 men and 1,951 postmenopausal women, were followed for a median of 5.3 years and were divided according to weight loss from maximum weight: <10%, 10% to <20%, 20% to <30%, and ≥30%. The primary outcomes were fragility fractures defined as fractures at sites of hip and spine. RESULTS: During the follow-up period, fragility fractures occurred in 198 participants. The age- and sex-adjusted incidence rates per 1,000 person-years in all participants were 6.4 (<10% weight loss from maximum body weight), 7.8 (10% to <20%), 11.7 (20% to <30%), and 19.2 (≥30%) (P for trend <0.001). Multivariate-adjusted hazard ratios for fragility fractures compared with reference (<10% weight loss) were 1.48 (95% CI 0.79-2.77) in the 10% to <20% group, 2.23 (1.08-4.64) in 20% to <30%, and 5.20 (2.15-12.57) in ≥30% in men, and 1.19 (0.78-1.82) in 10% to <20%, 1.62 (0.96-2.73) in 20% to <30%, and 1.97 (0.84-4.62) in ≥30% in postmenopausal women. CONCLUSIONS: The current study demonstrates that ≥20% body weight loss from maximum weight is a significant risk factor for fragility fractures in patients with type 2 diabetes, especially in men.