Parathyroidectomy slows renal function decline in patients with primary hyperparathyroidism.

PURPOSE: Primary hyperparathyroidism has deleterious effects on health and causes nephrolithiasis and osteoporosis. However, it remains unclear whether parathyroidectomy benefits kidney function among patients with primary hyperparathyroidism. METHODS: In this retrospective study, patients with primary hyperparathyroidism receiving parathyroidectomy in a tertiary medical center between 2003 and 2017 were followed up until December 31 2017, death, or requiring renal replacement therapy. Impact of parathyroidectomy on kidney function was examined using longitudinal estimated glomerular filtration rate (eGFR) change scales: single, average, absolute difference, percent change, annual decline rate, and slope. We applied linear mixed-effect model to determine the effect of parathyroidectomy on kidney function. RESULTS: During study period, 167 patients with primary hyperparathyroidism were identified from 498 parathyroidectomized patients, and finally, 27 patients fulfilled our stringent criteria. Median follow-up duration was 1.50 years (interquartile range 1.05-1.81) before surgery and 2.47 years (1.37-6.43) after surgery. Although parathyroidectomy did not affect amount of proteinuria and distribution of eGFR, parathyroidectomy significantly slowed decline rate of eGFR compared with that before surgery (- 1.67 versus - 2.73 mL/min/1.73 m2/year, p < 0.001). More importantly, parathyroidectomy made more beneficial effects on kidney function in patients with age < 65 years and those without chronic kidney disease or hypertension. CONCLUSIONS: Our study showed that parathyroidectomy slows renal function decline irrespective of age or comorbidities, which offers novel insight into the revision of guidelines for surgical indications in primary hyperparathyroidism. Given small sample size, further large-scale controlled studies are warranted to confirm our findings.

Design, evaluation and initial imaging results of a PET insert based on strip-line readout for simultaneous PET/MRI.

We present the development of a PET insert system for potential simultaneous PET/MR imaging using a 9.4 T small animal MRI scanner to test our system. The detectors of the system adopt a strip-line based multiplexing readout method for SiPM signals. In this readout, multiple SiPM outputs in a row share a common strip-line. The position information about a hit SiPM is encoded in the propagation time difference of the signals arriving at the two ends of the strip-line. The use of strip-lines allows us to place the data acquisition electronics remotely from the detector module to greatly simplify the design of the detector module and minimize the mutual electromagnetic interference. The prototype is comprised of 14 detector modules, each of which consists of an 8x4 LYSO scintillator array (each LYSO crystal is 3x3x10 mm3) coupled to two units of Hamamatsu MPPC arrays (4x4, 3.2 mm pitch) that are mounted on a strip-line board. On the strip-line board, outputs of the 32 SiPMs are routed to 2 strip-lines so that 16 SiPM signals share a strip-line. The detector modules are installed inside a plastic cylindrical supporting structure with an inner and outer diameter of 60 mm and 115 mm, respectively, to fit inside a Bruker BioSpec 9.4 Tesla MR scanner. The axial field of view of the prototype is 25.4 mm. The strip-lines were extended by using 5-meter cables to a sampling data acquisition (DAQ) board placed outside the magnet. The detectors were not shielded in the interest of investigating how they may affect and be affected by the MRI. Experimental tests were conducted to evaluate detection performance, and phantom and animal imaging were carried out to assess the spatial resolution and the MR compatibility of the PET insert. Initial results are encouraging and demonstrate that the prototype insert PET can potentially be used for PET/MR imaging if appropriate shielding will be implemented for minimizing the mutual interference between the PET and MRI systems.

Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer.

BACKGROUND: RNA-binding proteins have an important role in messenger RNA (mRNA) regulation during tumour development and carcinogenesis. In the present study, we examined the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; hereafter refered to as IMPs) and Lin28 family expressions in epithelial ovarian carcinoma (EOC) patients and correlated their expression levels with the response to chemotherapy, hCTR1 expression and patient survival. METHODS: Patients clinical information, real-time RT-PCR, immunohistochemistry, western blot, Transwell migration invasion assays, and cytotoxicity assays were used. RESULTS: From 140 EOC patients, high expression of IMP3 or Lin28B was associated with poor survival, and women diagnosed at advanced stages with elevated IMP3 and Lin28B were at higher risk of developing chemoresistance. High IMP3 levels combined with high Lin28B levels significantly correlated with the poorest 5-year survival rates. Knockdown of IMP3 or Lin28B decreased cell proliferation, migration, and invasion, and increased the platinum sensitivity, but not taxol sensitivity, of ovarian cancer cells through increased expression of hCTR1, a copper transporter involved in platinum uptake. High expression of hCTR1 correlated with low expression of IMP3/Lin28B and better progression-free survival in advanced-stage EOC patients. CONCLUSION: Testing for a combination of elevated IMP3 and Lin28B levels could further facilitate the identification of a patient subgroup with the worst prognosis.

Angiotensin II receptor blocker prevents upper gastrointestinal bleeding in hypertensive patients with chronic kidney disease not on dialysis.

AIMS: Investigate if angiotensin II receptor blocker (ARB) decreases risk of upper gastrointestinal bleeding (UGIB) in hypertensive patients with chronic kidney disease (CKD) not on dialysis. METHODS: All hypertensive patients with CKD not on dialysis in outpatient department of China Medical University Hospital from 2003 to May 2013 were enrolled. The risk of UGIB was analysed using Cox proportional hazard regression. RESULTS: A total of 2744 hypertensive CKD patients including 1515 male and 1229 female, aged 64.9 ± 13.8 years old in a median of 1.9 (0.9-3.9) years were analysed. The incidence of UGIB was 4.5 per 100 patient-years. ARB was associated with a decreased risk of UGIB (p < 0.001) with an adjusted hazard ratio (HR) of 0.533 [95% confidence interval (CI) 0.404-0.703]. A history of UGIB, Helicobacter pylori infection, diabetes, lower estimated glomerular filtration rate, elevated blood urea nitrogen and decreased serum albumin were independently associated with an increased risk of UGIB. CONCLUSIONS: Angiotensin II receptor blocker is associated with a decreased risk of UGIB in hypertensive CKD patients not on dialysis, independent of their renal function, history of gastrointestinal bleeding and nutrition status.

Subdural hematoma in diabetic patients.

BACKGROUND AND PURPOSE: Subdural hematoma (SDH) is associated with a high mortality rate. However, the risk of SDH in diabetic patients has not been well studied. The aim of the study was to examine the risk of SDH in incident diabetic patients. METHODS: From a universal insurance claims database of Taiwan, a cohort of 28,045 incident diabetic patients from 2000 to 2005 and a control cohort of 56,090 subjects without diabetes were identified. The incidence and hazard ratio of SDH were measured by the end of 2010. RESULTS: The mean follow-up years were 7.24 years in the diabetes cohort and 7.44 years in the non-diabetes cohort. The incidence of SDH was 1.57-fold higher in the diabetes cohort than in the non-diabetes cohort (2.04 vs. 1.30 per 1000 person-years), with an adjusted hazard ratio of 1.63 [95% confidence interval (CI) 1.43-1.85]. The stratified data showed that adjusted hazard ratios were 1.51 (95% CI 1.28-1.77) for traumatic SDH and 1.89 (95% CI 1.52-2.36) for non-traumatic SDH. The 30-day mortality rate for those who developed SDH in the diabetes cohort was 8.94%. CONCLUSIONS: This study demonstrates that incident diabetic patients are at higher risk of SDH than individuals without diabetes. Proper intervention for diabetic patients is necessary for preventing the devastating disorder.

COL11A1 promotes tumor progression and predicts poor clinical outcome in ovarian cancer.

Biomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovarian cancer. Microarray analysis suggested that COL11A1 is a disease progression-associated gene that is linked to ovarian cancer recurrence and poor survival. Small interference RNA-mediated specific reduction in COL11A1 protein levels suppressed the invasive ability and oncogenic potential of ovarian cancer cells and decreased tumor formation and lung colonization in mouse xenografts. A combination of experimental approaches, including real-time RT-PCR, casein zymography and chromatin immunoprecipitation (ChIP) assays, showed that COL11A1 knockdown attenuated MMP3 expression and suppressed binding of Ets-1 to its putative MMP3 promoter-binding site, suggesting that the Ets-1-MMP3 axis is upregulated by COL11A1. Transforming growth factor (TGF)-beta (TGF-ß1) treatment triggers the activation of smad2 signaling cascades, leading to activation of COL11A1 and MMP3. Pharmacological inhibition of MMP3 abrogated the TGF-ß1-triggered, COL11A1-dependent cell invasiveness. Furthermore, the NF-YA-binding site on the COL11A1 promoter was identified as the major determinant of TGF-ß1-dependent COL11A1 activation. Analysis of 88 ovarian cancer patients indicated that high COL11A1 mRNA levels are associated with advanced disease stage. The 5-year recurrence-free and overall survival rates were significantly lower (P=0.006 and P=0.018, respectively) among patients with high expression levels of tissue COL11A1 mRNA compared with those with low expression. We conclude that COL11A1 may promote tumor aggressiveness via the TGF-ß1-MMP3 axis and that COL11A1 expression can predict clinical outcome in ovarian cancer patients.

A bacteria injection scheme for in situ bioaugmentation.

This article presents an innovative design for inoculating the desired organisms to stratified geological layers at desired rates during in-situ bioaugmentation. The new delivery system consists of intermittent porous tubes connected in series with impermeable polyethylene tubes that run horizontally in each stratified layer of a contaminated aquifer. A bioaugmentation test using the new delivery system was conducted to inject an enriched culture of Escherichia coli (E. coli). Results of the test indicated that the distribution of E. coli through each porous tube was fairly uniform. A mathematical model previously developed to calculate the distribution of water flow through each porous tube was modified to calculate the distribution of E. coli. Geological layers often have different hydraulic conductivities. By controlling the permeability and the length of porous tubes placed in stratified layers, the new design provides a means to selectively deliver aqueous bacteria to various layers at desired rates according to aquifer heterogeneity.

Three-dimensional power Doppler ultrasound in cervical carcinoma: monitoring treatment response to radiotherapy.

OBJECTIVES: To investigate, using three-dimensional power Doppler ultrasound (3D-PDU), alterations in cervical intratumoral vascularization during and after radiotherapy. METHODS: Between 2004 and 2009 we enrolled into the study 37 patients with FIGO Stages IB1-IIB cervical carcinoma who were undergoing radiotherapy. Serial 3D-PDU scans were performed during treatment, providing ultrasonographic measurement of tumor size, vascularization index, flow index and vascularization flow index, as well as monthly for 3 months post-treatment and tri-monthly thereafter, until vascularity was undetectable on two consecutive occasions. Physical examination, cervical cytology and serum marker evaluation were performed every 3-6 months for the first 5 years following treatment. Patients evaluated after a 2-year tumor-free interval and those with clinically assessed positive findings at follow-up underwent 3D-PDU to detect possible local disease. RESULTS: A total of 329 3D-PDU scans were performed in the 37 women. Cervical tumors and intratumoral vascularization disappeared within 3 months following radiotherapy, except in one patient with persistent disease. Nine patients had disease relapse, in four of whom the recurrence was local. In three of these four, there was recurrence of tumor and vascularization after a complete response. At follow-up, 3D-PDU detected local disease with 75.0% sensitivity and 98.5% specificity, while serum markers detected local disease among 34 patients with squamous cell carcinoma with 20.0% sensitivity and 77.3% specificity. CONCLUSIONS: Compared with serum markers in cervical squamous cell carcinoma, 3D-PDU has higher sensitivity and specificity for detecting local recurrence or persistence in cervical carcinoma. Thus, 3D-PDU combined with clinical assessment may be a new and safe method for monitoring radiotherapy treatment response and detecting local recurrence.

An initial evaluation of analyser-based phase-contrast X-ray imaging of carotid plaque microstructure.

Carotid artery plaque instability can result in rupture and lead to ischaemic stroke. Stability of plaques appears to be a function of composition. Current non-invasive imaging techniques are limited in their ability to classify distinct histological regions within plaques. Phase-contrast (PC) X-ray imaging methods are an emerging class of techniques that have shown promise for identifying soft-tissue features without use of exogenous contrast agents. This is the first study to apply analyser-based X-ray PC imaging in CT mode to provide three-dimensional (3D) images of excised atherosclerotic plaques. The results provide proof of principle for this technique as a promising method for analysis of carotid plaque microstructure. Multiple image radiography CT (MIR-CT), a tomographic implementation of X-ray PC imaging that employs crystal optics, was employed to image excised carotid plaques. MIR-CT imaging yields three complementary images of the plaque's 3D X-ray absorption, refraction and scatter properties. These images were compared with histological sections of the tissue. X-ray PC images were able to identify the interface between the plaque and the medial wall. In addition, lipid-rich and highly vascularized regions were visible in the images as well as features depicting inflammation. This preliminary research shows MIR-CT imaging can reveal details about plaque structure not provided by traditional absorption-based X-ray imaging and appears to identify specific histological regions within plaques. This is the first study to apply analyser-based X-ray PC imaging to human carotid artery plaques to identify distinct soft-tissue regions.

Comparison of the GlideScope® videolaryngoscope and the Macintosh laryngoscope for double-lumen tube intubation.

Intubation with a double-lumen tube is important for achieving one-lung ventilation and facilitating thoracic surgery. The GlideScope(®) videolaryngoscope (Verathon Inc., Bothell, WA, USA) is designed to assist tracheal intubation for patients with a difficult airway. We wished to compare the GlideScope and direct laryngoscopy for double-lumen tube intubation. Sixty adult patients requiring a double-lumen tube for thoracic surgery and predicted uncomplicated laryngoscopy were randomly assigned to a direct Macintosh laryngoscopy group (n = 30) or a GlideScope group (n = 30). The mean (SD) duration of intubation was longer in the Macintosh group (62.5 (29.7) s) than in the GlideScope group (45.6 (10.7) s; p = 0.007). There was no difference in the success of the first attempt at intubation (26/30 (87%) and 30/30 (100%) for Macintosh and GlideScope groups, respectively; p = 0.112). The incidence of sore throat and hoarseness was higher in the Macintosh group (18 (60%) and 14 (47%), respectively) than in the GlideScope group (6 (20%) and 4 (13%), respectively; p = 0.003 and 0.004). We conclude that double-lumen tube intubation in patients with predicted normal laryngoscopy is easier using the GlideScope videolaryngoscope than the Macintosh laryngoscope.

Identifying LRRC16B as an oncofetal gene with transforming enhancing capability using a combined bioinformatics and experimental approach.

Oncofetal genes are expressed in embryos or fetuses, are downregulated or undetectable in adult tissues, and then re-expressed in tumors. Known oncofetal genes, such as AFP, GCB, FGF18, IMP-1 and SOX1, often have important clinical applications or pivotal biological functions. To find new oncofetal-like genes, we used the public information of expressed sequence tags to systematically analyze gene expression patterns and identified a novel oncofetal-like gene, LRRC16B. It increased the proliferation, anchorage-independent growth and tumorigenesis of transformed cells in xenografts, possibly through its effects on cyclin B1 protein levels. These findings exemplify the feasibility of using bioinformatics to find new oncofetal-like genes and suggest that more genes with important functional roles will be uncovered in the candidate gene list.

The relationship between chronic hepatitis B infection and bone mineral, metabolism in peritoneal dialysis patients.

OBJECTIVE: Abnormality of bone mineral metabolism is a common complication in chronic liver disease and/or chronic renal disease patients. We designed this study to evaluate the relationship between chronic hepatitis B infection and bone mineral metabolism in peritoneal dialysis patients. PATIENTS AND METHODS: Serum calcium[adj], phosphorus, calcium and phosphorus product (Ca x P), along with intact parathyroid hormone (iPTH) levels were compared in peritoneal dialysis patients with and without chronic hepatitis B infection. RESULTS: A total of 220 patients (142 female, 78 male) with a mean age of 56.30 +/- 14.28 (range 19 - 86) years old were recruited, 23 showed chronic hepatitis B infection and 197 showed none. No statistically significant difference in serum calcium[adj] levels (9.90 +/- 0.85 mg/dl vs. 10.08 +/- 0.80 mg/dl, p = 0.354), phosphorus levels (5.26 +/- 1.58 mg/dl vs. 5.21 +/- 1.35 mg/dl, p = 0.879) and calcium and phosphorus product (Ca x P) (52.23 +/- 17.54 mg(2)/dl(2) vs. 52.42 +/- 14.16 mg(2)/dl(2), p = 0.960) between groups with and without chronic hepatitis B infection was observed. Serum iPTH levels were significantly lower in chronic hepatitis B patients (median 143 pg/ml, range 3.42 - 889) than in the control group (median 235 pg/ml, range 3 - 2381) (p = 0.035). As analyzed by multi-variable linear regression, chronic hepatitis B was a predictor of lower serum iPTH levels (beta = -0.271; p = 0.030) after adjustments for age, gender, serum calcium and phosphorus levels and diabetes. CONCLUSION: No significant difference in serum calcium[adj]), phosphorus and calcium and phosphorus product (Ca x P) levels appeared between peritoneal dialysis patients with and without chronic hepatitis B infection. Serum iPTH levels proved to be definitely lower in chronic hepatitis B infection patients.

Hyponatraemia in patients with normal pressure hydrocephalus.

BACKGROUND: In clinical practice, hyponatraemia was frequently found in patients with hydrocephalus. We conducted this study to determine the prevalence and risk factors for hyponatraemia in patients with normal pressure hydrocephalus (NPH). METHODS: We retrospectively reviewed all patients with NPH who were admitted to China Medical University Hospital between 1998 and 2006. Hyponatraemia was defined as a plasma sodium concentration < 135 mEq/l on admission. Possible risk factors between patients with and without hyponatraemia were analysed using Student's t-test or chi2 test. The association between hyponatraemia and possible factors was analysed using multivariate logistic regression. The odds ratio was calculated to determine the effect of possible risk factors. RESULTS: A total of 146 patients (84 men and 62 women) who had NPH with a mean age of 66.1 +/- 15.9 years old were reviewed and 33 (22.6%) patients were found having hyponatraemia. Patients who developed hyponatraemia had a significantly higher prevalence of hypertension, use of nasogastric tube (NG), bed-ridden status and fever. In multivariate logistic regression, the presence of hypertension and the use of NG were two important risk factors for hyponatraemia. The odds ratio (95% CI) for hypertension and NG were 2.604 (95% CI: 1.136-5.967, p = 0.024) and 7.179 (95% CI: 2.3-22.409, p = 0.001) respectively. CONCLUSION: Hyponatraemia is not uncommon in patients with NPH. Physicians should be aware of this complication and obtain necessary laboratory examination for early detection of hyponatraemia.

C-reactive protein predicts ischaemic stroke in haemodialysis patients.

Dialysis patients have a higher incidence of cerebrovascular events compared with the general population. However, the value of C-reactive protein (CRP) in predicting stroke in chronic haemodialysis patients is unknown. The aim of this study was to determine the association between serum CRP levels and ischaemic stoke in chronic haemodialysis patients. We retrospectively reviewed 391 chronic haemodialysis patients between November 2001 and November 2004. Patients who developed acute ischaemic stroke within 36-month were recorded. Patients who had lacunar infarction discovered accidentally during brain computed tomography or magnetic resonance imaging scans were recorded for subgroup analysis. The relation of predialysis serum CRP levels, measured via the nephelometric method, to the development of acute ischaemic stroke was analysed using Kaplan-Meier analysis. Factors related to lacunar infarctions were analysed by multivariate logistic regression. Of the 391 patients, 21 developed acute stroke and 24 had lacunar infarction. Kaplan-Meier analysis showed that patients with a serum CRP > 0.8 mg/dl were at risk of developing acute infarction (p = 0.002). In the Cox regression model adjusted for age, cardiovascular disease, hypertension and diabetes, patients with serum CRP > 0.8 mg/dl are at risk of developing acute ischaemic stroke (p = 0.03). In multivariate logistic regression with adjusted for age, hypertension and diabetes, serum CRP levels significantly associated with lacunar infarction (p = 0.05). Serum CRP levels, independent of cardiovascular disease, age, hypertension and diabetes, are associated with the development of acute ischaemic stroke and lacunar infarct in chronic haemodialysis patients.

Clinical implications of insulin-like growth factor 1 system in early-stage cervical cancer.

This study was aimed to identify the expression and the correlation of insulin-like growth factor-1 (IGF-1) system and their prognostic impacts in cervical cancer. Seventy-two patients with early-stage cervical cancer were eligible. We obtained the serum levels of total IGF-1 and IGF binding protein-3 (IGFBP-3) by enzyme-linked immunosorbent assay and the expression of IGF-1 receptor (IGF-1R) in cancerous tissue by immuno-fluorescent (IF) stains. The 5-year recurrence-free and overall survival rates were significantly lower (P=0.003 and P=0.01, respectively) among patients with high-grade expression of tissue IGF-1R, compared with those with low-grade expression. After adjustment for other factors, preoperative serum total IGF-1 or IGFBP-3 levels failed to predict cancer death and recurrence. High-grade expression of IGF-1R and elevated preoperative squamous cell carcinoma antigen level were independent predictors of both death and recurrence, and combination of both factors could further help identify the subgroup of patients at higher death risk. The IF staining indicates the colocalisation of IGF-1 and IGF-1R in the cancerous tissues, whereas the IGF-1R expression is not correlated with circulating levels of IGF-1 or IGFBP-3. In early-stage cervical cancer, IGF-1 system may have a paracrine or autocrine function and the adverse impacts on prognosis by IGF-1R overexpression are implicated.