Characteristic multimodal imaging of medication-related osteonecrosis of the jaw : comparison between oral and parenteral routes of medication administration

Background: To assess multimodal imaging features of medication-related osteonecrosis of the jaw (MRONJ) and to analyze the differences between oral and parenteral routes of medication administration. We retrospectively reviewed panoramic radiographs, CT, MRI, and bone scintigraphy of patients with MRONJ. Material/Methods: A retrospective study was conducted in 16 patients with MRONJ who underwent panoramic radiography, CT, MRI, and bone scintigraphy. Statistical analysis for the comparison between routes of medication administration and multimodal imaging features was performed with the Pearson's c2 test. Results: The percentage of cases with sequestrum separation was 25.0% (4/16 cases) on panoramic radiography and 81.3% (13/16 cases) on CT. The percentage of cases with periosteal bone proliferation on CT was 41.7% (5/12 cases) in the oral route of administration vs. 100% (4/4 cases) in the parenteral route of administration (p=0.042). The percentage of cases with spread of soft tissue inflammation to buccal and other spaces on CT and MRI was 33.3% (4/12 cases) in the oral route of administration vs. 100% (4/4 cases) in the parenteral route of administration (p=0.021). Conclusions: The sequestrum separation on panoramic radiography in patients with MRONJ was unclear in comparison to CT. Furthermore, characteristic CT findings of patients with MRONJ in the parenteral administration group were periosteal bone proliferation and spread of soft tissue inflammation to buccal and other spaces

Comparison between squamous cell carcinoma and inflammatory diseases of the oral and maxillofacial region using gallium-67 scintigraphy with computed tomography and magnetic resonance imaging

Purpose: This study aimed to compare squamous cell carcinoma (SCC) with inflammatory diseases of the oral and maxillofacial region using gallium 67 (67Ga) scintigraphy with computed tomography (CT) and magnetic resonance imaging (MRI). Material and methods: Seventy patients with SCC and 15 patients with inflammatory diseases of the oral and maxillofacial region underwent 67Ga scintigraphy with CT and MRI. A comparison between imaging features of 67Ga scintigraphy, CT, and MRI and lesions was performed with the Pearson's chi-squared test. Results: 67Ga scintigraphy was positive for 25 of 39 patients with SCC positive on CT and/or MRI (64.1%) and for 13 of 15 patients with inflammatory diseases positive on CT and/or MRI (86.7%). The detection of inflammatory diseases with 67Ga scintigraphy was higher than that of SCC (p = 0.104). Conclusions: This study compared SCC with inflammatory diseases of the oral and maxillofacial region using 67Ga scintigraphy with CT and MRI. 67Ga scintigraphy is an effective technique for detection of inflammatory diseases of the oral and maxillofacial region

Comparative Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Classes of Glucose-Lowering Medications on Renal Outcome in Type 2 Diabetes

Objective: To assess whether sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy is associated with a favorable renal prognosis for patients with type 2 diabetes melllitus (T2DM) outside the clinical trials setting. Participants and Methods: This retrospective study analyzed routinely collected health care records of ∼160 medical institutions in Japan from April 1, 2014, to December 31, 2017/2018 (varying at the institutional level). Adults with T2DM but without end-stage renal disease who initiated either SGLT2i or other classes of glucose-lowering medications (o-GLM) were matched using propensity score. The primary outcome was the time course of estimated glomerular filtration rate (eGFR) displayed in spline curve. The composite of renal worsening (>40% decline in eGFR) and the development of eGFR<30 mL/1.73 m2 per minute was evaluated as a secondary outcome. Two sensitivity analyses were conducted to determine the robustness of results. Results: We compared a matched cohort of 1433 SGLT2i users and 2739 o-GLM users (mean age: 61 years). The eGFR declined over time in both groups during the observation period (median: 17 months; maximum: 54 months), with a slower eGFR slope observed in SGLT2i users. This slower decline was consistently observed across different SGLT2i agents and different baseline eGFR groups. The cumulative incidence of composite renal endpoints was lower in the SGLT2i group with a hazard ratio of 0.70 (95% CI, 0.50-0.98; P=.039). Those findings were consistent in sensitivity analyses limited to the period adherent to the initial drug regimen and with a different approach for propensity score calculation. Conclusion: In a matched cohort of T2DM patients, SGLT2i use was associated with preserved renal function relative to o-GLM use over 2 to 4 years

Diffusion-weighted imaging in the oral and maxillofacial region : usefulness of apparent diffusion coefficient maps and maximum intensity projection for characterization of normal structures and lesions

Background: The aim of this study was to investigate diffusion-weighted imaging (DWI) in the oral and maxillofacial region, with a special focus on the usefulness of apparent diffusion coefficient (ADC) maps and maximum intensity projection (MIP) for characterization of normal structures and lesions. Material/Methods: Thirty-five patients who underwent magnetic resonance imaging (MRI) for diagnosis of oral and maxillofacial lesions were included in this prospective study. DWI was performed on a 1.5 T unit, with b factor of 0 and 800 s/mm2; moreover, ADC maps were generated. ADC values were measured for normal structures, odontogenic infections, squamous cell carcinomas (SCC), and hemangiomas. Results: As regards the normal structures, the mean ADC value of the cerebrospinal fluid (3.65±0.60×10-3 mm2/s) in the upper neck area was higher than that of the spinal cord (0.74±0.15×10-3 mm2/s, P=0.000), lymph nodes (0.87±0.17×10-3 mm2/s, P=0.000), and Waldeyer’s ring (0.92±0.29×10-3 mm2/s, P=0.000). The mean ADC value of hemangiomas (1.52±0.31×10-3 mm2/s) was higher than that of odontogenic infections (0.85±0.36×10-3 mm2/s, P=0.034) and SCC (1.38±0.22×10-3 mm2/s, P=0.840). Furthermore, MIP (DWI) showed the normal structures and lesions in the oral and maxillofacial region in an improved way. Conclusions: DWI, ADC maps, and MIP can be used to characterize and differentiate normal structures and lesions in the oral and maxillofacial region

Clinical Practice Changes After Post-Market Safety Reports on Desmopressin Orally Disintegrating Tablet in Japan: A Single-Center Retrospective Study

Background: Desmopressin orally disintegrating tablet (ODT) was approved in March 2012 in Japan; the post-market safety reports, which warned about adequate initial dose of desmopressin ODT, were published in 2014. However, it is unclear how the warning affected physician and patient behavior. Methods: We performed a retrospective single-center study to compare the clinical situation of Japanese central diabetes insipidus patients before and after the report. Results: Thirty-four patients before October 2014 and 16 patients after November 2014 switched from intranasal desmopressin to desmopressin ODT. The mean follow-up period after the switch to desmopressin ODT was 38 ± 3 months. Patients switching after November 2014 tended to have lower ratios of oral to nasal desmopressin dose at switching and 3 months after the switch (at switching; P = 0.20, 3 months; P = 0.42, respectively), and higher ratios from 6 to 12 months than before October 2014 (6 months; P = 0.93, 9 months; P = 0.52, 12 months; P = 0.80, respectively). Relative doses per initial desmopressin ODT at 9 and 12 months were significantly higher in patients switching after November 2014 than in patients switching before October 2014 (9 months; P = 0.02, 12 months; P = 0.04, respectively). Moreover, logistic regression analysis revealed that the incidence of hyponatremia was dependent on the ratio of nasal to oral desmopressin dose (P = 0.02). In addition, in four out of six patients who had serum sodium level reduced below 130 mEq/L, hyponatremia occurred within 1 month after the switch. Conclusions: A more gradual dose titration after the safety reports was performed, which involved the long-term safety of desmopressin ODT use. Vigilance of hyponatremia in early phase of desmopressin ODT use should be noted

Structural variations in parotid glands induced by radiation therapy in patients with oral carcinoma observed on contrast-enhanced computed tomography

Background: Xerostomia is one of the commonest radiation-induced complications in patients with head and neck carcinoma. The aim of this study was to assess structural variations in parotid glands induced by radiation therapy in patients with oral carcinoma with contras-enhanced computed tomography (CECT). Material/Methods: A retrospective study was performed in 41 patients with oral carcinoma who underwent CECT for head and neck malignancies before and after radiotherapy. We analyzed the relationship between parotid density variations, parotid volume change, as seen on CECT, and the mean radiation dose applied to the parotid glands in patients with oral carcinoma immediately after radiotherapy, and 2 and 3 years later. Results: Immediately after radiotherapy, high-density changes on contrast-enhanced CT were observed in 70.5% of the irradiated parotids. Low-density changes due to fat degeneration were seen in 46.2% and 72.2% of the irradiated parotids 2 and 3 years after radiotherapy, respectively. The mean dose applied to the parotids with the low-density changes and without such changes 3 years after radiotherapy was 46.0 Gy and 27.7 Gy, respectively (p=0.049). Furthermore, parotid shrinkage was observed in 63.6% of the irradiated parotids. Conclusions: This study suggests that the structural variations in parotid glands induced by radiotherapy included high-density changes that were observed immediately after radiotherapy and low-density changes that were seen at late follow-up. This study should be useful for clinicians in the assessment of radiation-induced injuries in the parotids with respect to early prediction of xerostomia

Voxel‐based specific regional analysis system for Alzheimer’s disease utility as a screening tool for unrecognized cognitive dysfunction of elderly patients in diabetes outpatient clinics: Multicenter retrospective exploratory study

AIMS/INTRODUCTION: An efficient screening strategy for identification of cognitive dysfunction remains a clinical issue in the management of elderly adults with diabetes. A magnetic resonance imaging voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) has been developed as an automated brain morphometry system that includes the hippocampus. We carried out a multicenter retrospective study to evaluate the utility of VSRAD for screening cognitive dysfunction in diabetes outpatient clinics. MATERIALS AND METHODS: We enrolled patients with diabetes aged >65 years who underwent brain magnetic resonance imaging scans for the purpose of a medical checkup between November 2018 and May 2019. Patients who were already suspected or diagnosed with mild cognitive impairment and/or dementia as well as those with a history of cerebrovascular disease were excluded. RESULTS: A total of 67 patients were enrolled. Five patients were diagnosed with mild cognitive impairment or dementia (clinical cognitive dysfunction). Patients with clinical cognitive dysfunction showed a significantly higher z-score in VSRAD analysis (2.57 ± 0.47 vs 1.15 ± 0.55, P < 0.01). The sensitivities and specificities for diagnosis of clinical cognitive dysfunction were 80 and 48% for the Mini-Mental State Examination, 100 and 89% for the z-score, and 100 and 90% for the combination of the Mini-Mental State Examination score and z-score, respectively. CONCLUSIONS: VSRAD analysis can distinguish patients with clinical cognitive dysfunction in the elderly with diabetes, and also shows reasonable sensitivity and specificity compared with the Mini-Mental State Examination alone. Thus, VSRAD analysis can be useful for early identification of clinical cognitive dysfunction in the elderly with diabetes

Changes in expression level of OsHKT1;5 alters activity of membrane transporters involved in K+ and Ca2+ acquisition and homeostasis in salinized rice roots

In rice, the OsHKT1;5 gene has been reported to be a critical determinant of salt tolerance. This gene is harbored by the SKC1 locus, and its role was attributed to Na+ unloading from the xylem. No direct evidence, however, was provided in previous studies. Also, the reported function of SKC1 on the loading and delivery of K+ to the shoot remains to be explained. In this work, we used an electrophysiological approach to compare the kinetics of Na+ uptake by root xylem parenchyma cells using wild type (WT) and NIL(SKC1) plants. Our data showed that Na+ reabsorption was observed in WT, but not NIL(SKC1) plants, thus questioning the functional role of HKT1;5 as a transporter operating in the direct Na+ removal from the xylem. Instead, changes in the expression level of HKT1;5 altered the activity of membrane transporters involved in K+ and Ca2+ acquisition and homeostasis in the rice epidermis and stele, explaining the observed phenotype. We conclude that the role of HKT1;5 in plant salinity tolerance cannot be attributed to merely reducing Na+ concentration in the xylem sap but triggers a complex feedback regulation of activities of other transporters involved in the maintenance of plant ionic homeostasis and signaling under stress conditions

Big insulin-like growth factor 2-producing multiple solitary fibrous tumors treated with debulking surgery: A case report

BackgroundNon-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by a tumor-producing high molecular weight form of insulin-like growth factor 2 (IGF2) known as big IGF2. The only curative treatment for this condition is surgical resection of the responsible tumors. However, this may not be feasible in cases with multiple metastases at diagnosis of NICTH, and no standard treatment strategy for multiple tumors has been established. The effects of pharmacological therapies including somatostatin analogs are often inefficient and remain difficult to predict.Case descriptionA 68-year-old man was admitted to our hospital due to impaired consciousness and severe hypoglycemia. His medical history included diagnosis of a left temporal solitary fibrous tumor (SFT) at the age of 48 years, after which local recurrent and metastatic tumors were repeatedly resected. Four years before admission, multiple intraabdominal and subcutaneous tumors were detected and, being asymptomatic, were managed conservatively. Laboratory exam on admission demonstrated hypoglycemia accompanied with low serum insulin and IGF1 levels. Computed tomography (CT) scan revealed multiple intraabdominal and subcutaneous tumors increasing in size. Serum big IGF2 was detected on immunoblot analysis, and he was diagnosed as NICTH. In addition, tumor uptake was observed on 68Ga-labelled 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid-d-Phe1-Tyr3-octreotide positron emission tomography/CT (DOTATOC-PET/CT). Since larger tumor is more suspicious about responsible producibility of big IGF2, we planned to resect large ones preferentially and reduce the amounts of residual tumors. Debulking surgery was performed by removing eleven intraabdominal tumors; the hypoglycemia was then completely corrected. Histological analyses revealed the resected tumors to be metastases of SFT having somatostatin receptor 2 expression. In immunoblot analysis, the resected tumors were found to be positive for big IGF2; serum big IGF2 was undetectable after surgery.ConclusionWe present a case of NICTH with multiple metastatic SFTs. We strategically performed debulking surgery, which led to remission of hypoglycemia. This result demonstrates a pioneering practical solution for NICTH cases with multiple tumors. In addition, in cases of SFTs presenting with NICTH, positivity of DOTATOC-PET/CT as well as single-dose administration of octreotide may be predictive of the efficacy of somatostatin-based therapy