Dlx5 Represses the Transcriptional Activity of PPARγ.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master transcription factor in adipocyte differentiation, while distal-less homeobox 5 (Dlx5) is essential for initiating osteoblast differentiation by driving Runt-related transcription factor 2 expression. Considering that adipocytes and osteoblasts share common progenitors, there is a reciprocal correlation between bone and fat formation. However, the mechanism by which Dlx5 controls PPARγ remains unclear. We elucidated that Dlx5 physically binds to PPARγ during immunoprecipitation; in particular, the ligand-binding and DNA-binding domains of PPARγ were involved in the interaction. Transcriptional activity of PPARγ was significantly decreased by Dlx5 overexpression, whereas the opposite results were detected with Dlx5 knockdown. Rosiglitazone, a PPARγ agonist, further enhanced the PPARγ-induced transcriptional activity; however, Dlx5 overexpression effectively repressed the rosiglitazone-mediated increase in activity. Finally, DNA-binding affinity assay revealed that Dlx5 interrupts the interaction of PPARγ with the PPARγ response element promoter. In conclusion, our findings indicate that Dlx5 impedes PPARγ-induced activity, and it may be useful for managing diabetes drug-mediated obesity.

Assessment of patient-reported outcomes (PROs): treatment satisfaction, medication adherence, and quality of life (QoL) and the associated factors in postmenopausal osteoporosis (PMO) patients in Korea.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

Irreversible Electroporation: Defining the MRI Appearance of the Ablation Zone With Histopathologic Correlation in a Porcine Liver Model.

OBJECTIVE: The purpose of this study is to evaluate the MRI appearance of the irreversible electroporation zone in porcine liver, with histopathologic correlation. MATERIALS AND METHODS: Nine irreversible electroporation ablations were percutaneously created in two Yorkshire pigs. Irreversible electroporation was performed with a bipolar 16-gauge electrode with 3-cm exposure tip and fixed 8-mm interpolar distance. Gadoxetate disodium-enhanced 3-T MRI was performed 50 hours after irreversible electroporation. Livers were harvested immediately after MRI for histopathologic analysis. Ablation zone size was measured on each pulse sequence and correlated with pathologic ablation zone size. Qualitative MRI features of the ablation zone were assessed, and contrast-to-noise ratios (CNRs) were calculated. Statistical analysis included Pearson correlation and t tests. RESULTS: Histopathologically, three distinct layers were present in the irreversible electroporation ablation zone: an inner layer of coagulative necrosis (hyperintense at T1- and T2-weighted imaging and nonenhancing), a middle layer of congestion and hemorrhage (hypointense at T1-weighted imaging, hyperintense at T2-weighted imaging and DWI, and progressively enhancing but hypointense at the hepatobiliary phase), and a peripheral layer of inflammation (hyperintense at the arterial phase but isointense at all other sequences). The hepatobiliary phase ablation zone size showed the highest correlation with the pathologic ablation zone size (r = 0.973). This correlation was significant (p < 0.001). T2-weighted imaging had the highest lesion-to-normal tissue CNR. CONCLUSION: The irreversible electroporation ablation zone contains three distinct histopathologic zones, each with unique MRI features. T2-weighted imaging had the highest CNR, and the hepatobiliary phase had the strongest correlation with ablation zone size.

Osterix plays a critical role in BMP4-induced promoter activity of connexin43.

Osterix is an essential transcription factor for osteogenesis and is expressed in osteoblasts. Although Osterix has been shown to be induced by bone morphogenetic protein 4, the molecular mechanism underlying Osterix function during osteoblast differentiation remains unclear. Connexin43 (Cx43) is the most abundant gap junction protein in bone cells and plays a critical role in osteoblast differentiation. However, little is known about the functional interactions between Osterix and the Cx43 promoter. In the present study, we investigated the relationship between Osterix and Cx43 in HEK293 and C2C12 cells. Cx43 expression was significantly repressed by the addition of shRNA against Osterix, whereas overexpression of Osterix resulted in enhanced Cx43 expression. Furthermore, Osterix directly occupied the promoter region of Cx43 and subsequently increased Cx43 promoter activity in a dose-dependent manner. In addition, phosphorylation of the Ser76 and Ser80 residues in Osterix were found to be critical for its activity on the Cx43 promoter. Our results suggest that Osterix plays an important role in increasing bone morphogenetic protein 4-induced Cx43 activity.

Contrast Enhancement Patterns after Irreversible Electroporation: Experimental Study of CT Perfusion Correlated to Histopathology in Normal Porcine Liver.

PURPOSE: To analyze ablated tissue zones after irreversible electroporation (IRE) of porcine liver using computed tomography (CT) perfusion imaging with histopathologic correlation. MATERIALS AND METHODS: Under ultrasound and CT guidance, 10 IRE ablations were performed percutaneously in three Yorkshire pigs using a single bipolar electrode. CT perfusion imaging was performed in all pigs immediately after ablation and on day 2. Pathologic sections were prepared for correlation with histopathology (hematoxylin-eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling stains, 5-mm-thick slices). The short diameter of different enhancing zones on CT was correlated with the gross specimen. RESULTS: CT perfusion images showed three differently enhancing zones: zone 1, inner nonenhancing zone; zone 2, middle well-defined progressive internal enhancement zone; and zone 3, outer ill-defined arterial enhancement zone with rapid washout. On histopathology, zone 1 showed a strong correlation with a pale zone, and zone 2 correlated with a red zone, together accounting for the extent of cell death. Zone 3 was outside of the ablation zone and contained inflammatory cells. Each enhancing zone had different perfusion parameters. CONCLUSIONS: CT perfusion imaging in the acute setting effectively demonstrates histopathologic tissue zones after IRE ablation. Zone 2 is unique to IRE not seen in thermal ablation, characterized by progressive intra-zonal enhancement, and its outer boundary defines the extent of cell death.

Pelvic floor musculature and bladder neck changes before and after continence recovery after radical prostatectomy in pelvic MRI.

PURPOSE: To evaluate the changes in pelvic floor anatomy using MRI before and after continence recovery after radical prostatectomy (RP). MATERIALS AND METHODS: Thirteen men with prostate cancer who underwent RP (mean age, 67.4 ± 8.8 years) volunteered for this study. Prostate MRIs were performed during the preoperative (i), incontinent (ii), and continent (iii) periods. The membranous urethra length (MUL), puborectalis muscle (PRM) thickness, and the position of the bladder neck in relation to the pubic bone (Dx) and the pubococcygeous line (Dy) were measured. We compared all parameters in the preoperative, incontinent, and continent periods. RESULTS: MUL2 and MUL3 was significantly longer compared with MUL1, although no difference was found between MUL2 and MUL3. PRM3 thickness was significantly increased compared with PRM2 thickness. The Dx of the continence period was shorter than that of the incontinence period. The Dy of the continence period was longer than that of the incontinence period. CONCLUSION: The PRM thickened and the bladder neck moved upward and forward during the continence period. The changes in PRM thickness and the position of bladder neck may play an important role in the recovery of continence after RP.

Risedronate increases osteoblastic differentiation and function through connexin43.

Bisphosphonates are potent antiresorptive drugs which have antifracture efficacy by reducing bone turnover rate and increasing bone mineral density. In addition to inhibiting osteoclast function, bisphosphonates have been reported to also promote survival of osteocyte and osteoblast via an anti-apoptotic effect, mediated by opening of hemi-gap junction channels formed by connexin43 (Cx43). In this study, we investigated the effect of risedronate, one amino-bisphosphonate, on osteoblast differentiation and Cx43 expression using the mesenchymal cell line C2C12. Risedronate dose-dependently increased the activity of osterix (OSE)-luciferase containing Runx2 response element with highest activity at 50µM. The activity of osteocalcin (OC)- and bone sialoprotein (BSP)-luciferase reporters, markers of osteoblast differentiation, were also increased by risedronate. When risedronate and BMP2 were used in combination, alkaline phosphatase (ALP) activity increased to a larger extent than when BMP2 was used alone. Risedronate as well as the pro-osteogenic transcription factors, Runx2, Osterix or Dlx5, increased transcriptional activity of the Cx43 promoter in a dose-dependent manner. In the presence of Runx2 or Dlx5, risedronate had an additive effect on Cx43 promoter activity. Accordingly, risedronate increased protein expression of Cx43, Runx2, Osterix, and Dlx5. These results suggest that risedronate promotes osteoblastic differentiation and positively regulates Cx43 gene transcription.

The prevalence and risk factors of vertebral fractures in Korean patients with type 2 diabetes.

Although type 2 diabetes mellitus (T2DM) has been associated with an increase in fracture risk, there is no data regarding the prevalence of vertebral fractures or its risk factors for patients with T2DM in Korea. In this cross-sectional study, we recruited postmenopausal women with T2DM from 24 tertiary hospital diabetes clinics in Korea. Prevalent vertebral fractures were identified on lateral spinal radiographs of thoracolumbar vertebrae by vertebral morphometry. Demographic and biochemical characteristics related to diabetes were obtained, and bone mineral density of the lumbar spine and femoral neck, which was available in 752 (33.6 %) and 675 (30.1 %) patients, respectively, was also analyzed. Of the 2239 subjects recruited (mean age 63.9 years), a total of 970 (43.3 %) subjects had vertebral fractures. In the bivariate analysis, history of fragility fractures after 50 years of age, microalbuminuria, presence of cardiovascular disease (myocardial infarction, angina, cerebrovascular complications of cardiovascular disease), and presence of osteoporosis at the total hip were significantly associated with the presence of vertebral fractures, after adjusting for age. In the multivariate analysis, the presence of cardiovascular diseases in addition to advancing age and history of fragility fractures was significantly associated with increased odds of vertebral fractures. Vertebral fractures were highly prevalent in postmenopausal women with T2DM in this study conducted in Korea, and the presence of cardiovascular disease, in addition to older age and history of fragility fractures, was significantly associated with the presence of vertebral fractures.

The usefulness of computed tomographic colonography for evaluation of deep infiltrating endometriosis: comparison with magnetic resonance imaging.

OBJECTIVE: We wanted to assess the diagnostic value and morphologic feature of deep infiltrating endometriosis (DIE), involving rectosigmoid colon, with computed tomography (CT) colonography in comparison with magnetic resonance (MR). METHODS: Fifty patients with DIE, who had undergone CT colonography and MR imaging (MRI) before surgery, were enrolled. Among these 50 patients who underwent laparoscopic surgery with DIE, 37 patients were diagnosed as rectosigmoid involvement of endometriosis (presence of rectal outer wall involvement, endometrial implantation in the rectouterine space, and complete obliteration of cul-de-sac with histologic confirmation). Image findings at CT colonography and MRI were reviewed by 2 radiologists to determine whether there are radiologic features that can help predict rectosigmoid endometriosis. Computed tomography images were analyzed for the luminal alteration of rectosigmoid colon, mural thickening, and mass formation in the rectosigmoid colon, whereas MR images were analyzed for the mass formation in the rectosigmoid colon, fat plane obliteration, between rectum and uterus or vagina, retroversion of uterus, retraction of uterus toward the colon, and detection of endometrial spot in rectovaginal or rectouterine space. Statistical analysis was performed with Pearson χ and receiver operating characteristic curve. RESULTS: With CT colonography, the luminal alteration of rectosigmoid colon was detected with sensitivity of 96.0% and specificity of 48.0% (P < 0.001) in the overall rectosigmoid endometriosis and with sensitivity of 84.0% and specificity of 80.0% (P = 0.005) in the case of DIE with cul-de-sac obliteration. With MR, the sensitivity and specificity for detection of endometriosis of rectosigmoid or rectouterine space were 94.4% and 37.5% (P = 0.013), respectively. Other variables had no statistical significance. The diagnostic accuracy of CT colonography is higher than that of MRI (area under the curve, 0.786 vs 0.691; P < 0.001), for the overall rectosigmoid endometriosis. In the evaluation of complete cul-de-sac obliteration, morphologic change of rectosigmoid colon is identified more accurately with CT colonography than that of MRI (area under the curve, 0.821 vs 0.686; P < 0.001). CONCLUSIONS: Both CT colonography and MRI are highly sensitive to the detection of rectosigmoid endometriosis, but lack specificity. However, the depiction rate of morphologic change in rectosigmoid colon is greater with CT colonography than that of MRI, in the case of cul-de-sac obliteration. The luminal alteration significantly correlates with morphologic change in rectosigmoid endometriosis.

68 Ga-FAPI PET/CT Imaging of the Pancreas in a Patient With Fulminant Type 1 Diabetes.

ABSTRACT: Fulminant type 1 diabetes is a recently recognized diabetes subtype characterized by extremely rapid destruction of the pancreatic beta cells, leading to an absolute deficiency in insulin secretion. Fulminant type 1 diabetes is clinically characterized by the drastic onset of hyperglycemia and ketoacidosis within a few days, as well as near-normal glycated hemoglobin (HbA 1c ) levels despite remarkable hyperglycemia at initial presentation. A 41-year-old woman diagnosed with fulminant type 1 diabetes underwent 68 Ga-FAPI PET/CT, which showed intense FAPI uptake throughout the pancreas, especially in the pancreatic tail. Contrast-enhanced abdominal CT failed to reveal any pancreatic abnormalities. This case indicated that 68 Ga-FAPI PET/CT might be useful for evaluating patients with fulminant type 1 diabetes.

Relationship between plasma leucine-rich α-2-glycoprotein 1 and urinary albumin excretion in patients with type 2 diabetes.

Aims: To explore the relationship between plasma leucine-rich α-2-glycoprotein 1 (LRG1) level and the degree of urinary albumin excretion in patients with type 2 diabetes. Methods: We evaluated 332 patients with type 2 diabetes in a cross-sectional study. Result: The plasma LRG1 level differed significantly according to the quartiles of urinary albumin excretion (Q1 [<7.7 mg/g], 17.1 µg/mL; Q2 [7.7-15.0 mg/g], 17.5 µg/mL; Q3 [15.1-61.4 mg/g], 18.6 µg/mL; Q4 [≥61.5 mg/g], 22.3 µg/mL; p for trend = 0.003) under adjustment with other covariates. A positive correlation was found between plasma LRG1 level and urinary albumin excretion (ρ = 0.256, p <0.001). According to a multivariate model, the association between LRG1 and urinary albumin excretion remained significant, under adjustment for confounding factors (ß = 0.285, p <0.001). Conclusion: Plasma LRG1 level was independently associated with urinary albumin excretion in patients with type 2 diabetes. This study suggests that LRG1 may be associated with increased excretion of urinary albumin in the early stages of diabetic nephropathy.

Predicting resection margin status of pancreatic neuroendocrine tumors on CT: performance of NCCN resectability criteria.

OBJECTIVE: To test the performance of the National Comprehensive Cancer Network (NCCN) CT resectability criteria for predicting the surgical margin status of pancreatic neuroendocrine tumor (PNET) and to identify factors associated with margin-positive resection. METHODS: Eighty patients with pre-operative CT and upfront surgery were retrospectively enrolled. Two radiologists assessed the CT resectability (resectable [R], borderline resectable [BR], unresectable [UR]) of the PNET according to NCCN criteria. Logistic regression was used to identify factors associated with resection margin status. κ statistics were used to evaluate interreader agreements. Kaplan-Meier method with log-rank test was used to estimate and compare recurrence-free survival (RFS). RESULTS: Forty-five patients (56.2%) received R0 resection and 35 (43.8%) received R1 or R2 resection. R0 resection rates were 63.6-64.2%, 20.0-33.3%, and 0% for R, BR, and UR diseases, respectively (all p ≤ 0.002), with a good interreader agreement (κ, 0.74). Tumor size (<2 cm, 2-4 cm, and >4 cm; odds ratio (OR), 9.042-18.110; all p ≤ 0.007) and NCCN BR/UR diseases (OR, 5.918; p = 0.032) were predictors for R1 or R2 resection. The R0 resection rate was 91.7% for R disease <2 cm and decreased for larger R disease. R0 resection and smaller tumor size in R disease improved RFS. CONCLUSION: NCCN resectability criteria can stratify patients with PNET into distinct groups of R0 resectability. Adding tumor size to R disease substantially improves the prediction of R0 resection, especially for PNETs <2 cm. ADVANCES IN KNOWLEDGE: Tumor size and radiologic resectability independently predicted margin status of PNETs.

Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance.

BACKGROUND: To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus. METHODS: This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed. RESULTS: The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by -0.68%±1.39% and -1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a "responder" to empagliflozin therapy. CONCLUSION: Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

Radiofrequency ablation using real-time ultrasonography-computed tomography fusion imaging improves treatment outcomes for T1a renal cell carcinoma: Comparison with laparoscopic partial nephrectomy.

PURPOSE: To determine whether real-time ultrasonography-computed tomography (US-CT) fusion imaging can improve technical feasibility versus B-mode US and provide comparable outcomes of radiofrequency ablation (RFA) for T1a renal cell carcinoma (RCC) compared with laparoscopic partial nephrectomy (LPN). MATERIALS AND METHODS: Between June 2013 and August 2016, biopsy- or pathologically confirmed stage T1a RCCs were retrospectively reviewed. Of these, 39 cases were included in the RFA group, and 46 cases were included in the LPN group. In the RFA group, we evaluated tumor visibility and technical feasibility before RFA on a four-point scale on B-mode US and US-CT fusion images. After RFA, hospital days, creatinine value, complications, and disease-free survival rate were compared between the two groups. All results were analyzed by use of the Mann-Whitney U-test and Kaplan-Meier method. RESULTS: Compared with B-mode US alone, real-time US-CT fusion significantly improved the tumor visibility score and overall mean technical feasibility grade (p<0.001). The 5-year disease-free survival rate was 97.4% and 97.8% in the RFA and LPN groups, respectively, and there was no statistically significant difference between groups (p=0.1). Mean periprocedural creatinine levels were significantly lower in the RFA group than in the LPN group. The number of hospital days was shorter in the RFA group. Minor complications were present in 5.1% of the RFA group and 13.0% of the LPN group, with no major complications. CONCLUSIONS: US-CT fusion-image-guided RFA improved tumor visibility scores and overall mean technical validity and resulted in a comparable disease-free survival rate to LPN.

A Real-World Comparative Study of Microwave and Radiofrequency Ablation in Treatment-Naïve and Recurrent Hepatocellular Carcinoma.

The efficacy and safety of microwave ablation (MWA) compared to radiofrequency ablation (RFA) for patients with treatment-naïve and recurrent hepatocellular carcinoma (HCC) has not been clarified in Korea. There were 150 HCC patients (100 in the RFA group and 50 in the MWA group) enrolled in our study. The primary outcome was one- and two-year disease-free survival (DFS). Secondary outcomes were complete response (CR) rate, two-year survival rate, risk factors for DFS and complication rate. Treatment outcomes were also assessed using propensity-score matching (PSM). The MWA group had better one- and two-year DFS than the RFA group (p = 0.035 and p = 0.032, respectively), whereas the CR rate, two-year survival rate, and complication rate were similar between the two groups with fewer major complications in the MWA group (p = 0.043). Patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. MWA was also an independent factor for favorable one- and two-year DFS. Finally, the MWA group still showed better one- and two-year DFS than the RFA group after PSM. In conclusion, MWA could be an alternative treatment to RFA especially in patients with a high risk of recurrence, perivascular tumors, and small tumor size.

Plasma galectin-3 concentration and estimated glomerular filtration rate in patients with type 2 diabetes with and without albuminuria.

This study aimed to investigate the association between galectin-3 concentration and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria. In this cross-sectional study, we examined 334 patients with T2DM. The eGFR was calculated using a creatinine-based formula (eGFRcrea) and a combined creatinine-cystatin C equation (eGFRcrea-cyst). The participants were categorized into two groups based on the urinary albumin-to-creatinine ratio (UACR): patients without albuminuria (UACR < 30 mg/g) and those with albuminuria (UACR ≥ 30 mg/g). Greater concentrations of plasma galectin-3 were associated with lower eGFRcrea-cyst and eGFRcrea levels in patients with and without albuminuria. Plasma galectin-3 concentrations were negatively correlated with eGFRcrea-cyst in patients with normoalbuminuria and albuminuria (γ = - 0.405, P < 0.001; γ = - 0.525, P < 0.001, respectively). Galectin-3 concentrations were significantly associated with eGFRcrea-cyst after adjusting for sex, age, and other confounding factors, including UACR as a categorical or continuous variable in multiple regression analyses (ß = - 0.294, 95% CI - 70.804 to - 41.768, P < 0.001; ß = - 0.265, 95% CI - 65.192 to - 36.550, P < 0.001, respectively). Likewise, when eGFRcrea-cyst was treated in place of eGFRcrea, this result was replicated in the correlation and regression analyses. Galectin-3 concentration was negatively associated with eGFR in patients with T2DM, independent of albuminuria status.

Retrospective study of two biochemical markers for the risk assessment of oral bisphosphonate-related osteonecrosis of the jaws: can they be utilized as risk markers?

PURPOSE: the purpose of this retrospective study was to examine the possibility of utilizing serum C-terminal telopeptide cross-link of type I collagen (s-CTX) and serum osteocalcin (s-OC) as risk markers for oral bisphosphonate-related osteonecrosis of the jaws (BRONJ). PATIENTS AND METHODS: the s-CTX values and the s-OC values were measured from 23 patients (one male, 22 females) diagnosed with BRONJ using clinical and radiographic examinations. The two biochemical markers were evaluated during a regular checkup for osteoporosis management. For the control group of s-CTX study, s-CTX values were obtained from 61 independently recruited postmenopausal women who have been on bisphosphonate therapy for >6 months. The s-CTX values of the ONJ group and the control group were compared. Because of retrospective nature of this study, the control group for s-OC study could not be established. A single sample t-test was performed for the s-OC value from the ONJ group. RESULT: twenty-three ONJ patients had taken alendronate for osteoporosis treatment, and the s-CTX testing results were low levels of 10-192 pg/ml (mean: 93.2 ± 49.4 pg/ml). Mean of s-CTX of the control (n=61) was 125 ± 85.7 pg/ml. The duration of BP therapy ranged between 1 and 10 years (4.82 ± 2.6). The s-OC level was estimated between 0.2 and 5.4 ng/ml (1.91 ± 1.51 ng/ml). The mean s-CTX value of the control group was higher but without significance (P=0.12). The s-OC values of the ONJ group were significantly lower than the lowest value of the reference range (P<0.001). CONCLUSION: as a result of the s-CTX and s-OC testings at the diagnosis of BRONJ, the values of the two markers were decreased. The decrease of the s-OC values implies a problem during the bone-formation process. Therefore, we can assume that in this patient group, invasive dental surgery contributes to an increase in the risk of BRONJ incidence. This result may imply that, during bisphosphonate therapy, simultaneous consideration of s-CTX showing inhibition of bone resorption and s-OC indicating the degree of bone formation might be a set of risk markers assessing risk prediction for BRONJ before invasive dental surgery.

High-intensity focused ultrasound treatment of abnormal vaginal bleeding secondary to uterine myoma.

We describe the use of high-intensity focused ultrasound for acute vaginal bleeding secondary to uterine myoma in 2 young female patients. Both patients had episodes of abnormal vaginal bleeding with severe dysmenorrhea that was not efficiently controlled by medical treatment. After high-intensity focused ultrasound ablation, both vaginal bleeding control and symptom relief were achieved without postinterventional complications. The patients remained free of symptoms during 2 months of follow-up and regained normal menstruation after high-intensity focused ultrasound therapy. High-intensity focused ultrasound treatment is one of the least invasive options for dysfunctional vaginal bleeding and may be an effective and safe alternative to other procedures in women of reproductive age with abnormal vaginal bleeding secondary to uterine myoma.

Relationship between plasma growth differentiation factor-15 level and estimated glomerular filtration rate in type 2 diabetes patients with and without albuminuria.

AIM: To assess the relationship between growth differentiation factor-15 (GDF-15) levels and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus (DM) patients with and without albuminuria. METHODS: We examined 324 patients with type 2 DM in a cross-sectional study. eGFR was determined using equations from creatinine (eGFRcr) and the combination of creatinine and cystatin C (eGFRcr-cys). The patients were classified into two groups based on urinary albumin: creatinine ratio (ACR): the normoalbuminuria group (urinary ACR < 30 mg/g) and the albuminuria group (urinary ACR ≥ 30 mg/g). RESULTS: In individuals both with and without albuminuria, higher GDF-15 levels were associated with lower eGFRcr and eGFRcr-cys. Plasma GDF-15 levels were inversely correlated with eGFRcr in individuals both with and without albuminuria (γ = -0.624, p < 0.001 and γ = -0.509, p < 0.001, respectively). A multiple regression analysis showed that GDF-15 levels were significantly associated with eGFRcr after adjusting for age, sex and other confounders, including urinary ACR as a continuous or categorical variable (ß = -0.309, p < 0.001 and ß = -0.318, p < 0.001, respectively). Similarly, these results were replicated when eGFRcr-cys was considered instead of eGFRcr in correlation and regression analyses. CONCLUSION: GDF-15 levels were inversely associated with eGFR in patients with type 2 DM. This relationship was independent of albuminuria status.