Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

Background

Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with ^99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation.

Methods

Ten adult sleepwalkers and twelve controls with normal sleep were scanned using ^99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers.

Results

During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls.

Conclusions

Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness.     

Neuropsychological Correlates of Brain Perfusion SPECT in Patients with Macrophagic Myofasciitis

Background

Patients with aluminum hydroxide adjuvant-induced macrophagic myofasciitis (MMF) complain of arthromyalgias, chronic fatigue and cognitive deficits. This study aimed to characterize brain perfusion in these patients.

Methods

Brain perfusion SPECT was performed in 76 consecutive patients (aged 49±10 y) followed in the Garches-Necker-Mondor-Hendaye reference center for rare neuromuscular diseases. Images were acquired 30 min after intravenous injection of 925 MBq ^99mTc-ethylcysteinate dimer (ECD) at rest. All patients also underwent a comprehensive battery of neuropsychological tests, within 1.3±5.5 mo from SPECT. Statistical parametric maps (SPM12) were obtained for each test using linear regressions between each performance score and brain perfusion, with adjustment for age, sex, socio-cultural level and time delay between brain SPECT and neuropsychological testing.

Results

SPM analysis revealed positive correlation between neuropsychological scores (mostly exploring executive functions) and brain perfusion in the posterior associative cortex, including cuneus/precuneus/occipital lingual areas, the periventricular white matter/corpus callosum, and the cerebellum, while negative correlation was found with amygdalo-hippocampal/entorhinal complexes. A positive correlation was also observed between brain perfusion and the posterior associative cortex when the time elapsed since last vaccine injection was investigated.

Conclusions

Brain perfusion SPECT showed a pattern of cortical and subcortical changes in accordance with the MMF-associated cognitive disorder previously described. These results provide a neurobiological substrate for brain dysfunction in aluminum hydroxide adjuvant-induced MMF patients.     

Images de soustraction TEMP, en double isotope, Tc-sestamibi/I fusionnées au scanner : intérêt chez des patients présentant une hyperparathyroïdie

Purpose

To assess dual-tracer imaging of hybrid SPECT/CT (S/CT) compared to planar scintigraphy (S/PL) and ultrasounds (US), in preoperative localization hyperparathyroidism.

Methods

Dual tracer S/CT, S/PL and US for preoperative localization were performed in 99 patients with hyperparathyroidism. Patients with single-gland and multiple gland disease (MGD) were evaluated. For S/PL and S/CT, 15 MBq of ¹²³I were given and 2 hours later, 555 MBq/kg of ^99mTc-MIBI was injected. Images were acquired simultaneously using appropriate windows in S/PL and S/CT, then compared to US. Thus, the predicted positions were compared to the intraoperative findings and abnormal parathyroid glands were measured.

Results

Seventy-five patients underwent invasive surgery, which served as standard. Sixty-seven adenomas and 17 MGD were found on 70 patients. Sensitivity for US, S/PL and S/CT was respectively 69, 82 and 83%; and specificity was 96, 91 and 93% with an overall kappa-coefficient of 0.64, 0.73 and 0.76. US, S/PL and S/CT were correlated with the size of abnormal glands even if US remains the most accurate measuring technique. S/CT was able to predict the true position of the abnormal gland in 80% of cases.

Conclusion

Dual-isotope planar imaging and S/CT were statistically significantly superior to US imaging in sensitivity. The addition of CT to SPECT further improves parathyroid adenoma localization and predicts the size, which can help for mini-invasive surgery.     

Radioembolization with Y-90 Glass Microspheres: Do We Really Need SPECT-CT to Identify Extrahepatic Shunts?

Purpose

Selective Internal Radiation Therapy (SIRT) with ⁹⁰yttrium (Y-90) is an increasingly used therapeutic option for unresectable liver malignancies. Nontarget embolization of extrahepatic tissue secondary to vascular shunting can lead to SIRT associated complications. Our aim was to assess whether extrahepatic shunts can reliably be diagnosed based on hepatic digital subtraction angiography (DSA) or whether subsequent SPECT/CT data can provide additional information.

Materials and Methods

825 patients with hepatocellular carcinoma (n = 636), hepatic metastases (n = 158) or cholangiocellular carcinoma (n = 31) were retrospectively analyzed. During hepatic DSA 128 arteries causing shunt flow to gastrointestinal tissue were coilembolized (right gastric artery n = 63, gastroduodenal artery n = 29; branches to duodenum / pancreas n = 36). Technectium-99m-labeled human serum albumin (HSA) was injected in all 825 patients. SPECT/CT data was used to identify additional or remaining shunts to extrahepatic tissue.

Results

An unexpected uptake of HSA in extrahepatic tissue was found by SPECT/CT in 54/825 (6.5%) patients (located in stomach n = 13, duodenum n = 26, distal bowel segments n = 12, kidney n = 1, diaphragm n = 2). These patients underwent repeated DSA and newly identified shunt vessels were coilembolized in 22/54 patients, while in 12/54 patients a more distal catheter position for repeat injection of HSA was chosen. In 20/54 patients the repeated SPECT/CT data still revealed an extrahepatic HSA uptake. These patients did not receive SIRT.

Conclusion

Most extrahepatic shunts can be identified on DSA prior to Y-90 therapy. However, SPECT-CT data helps to identify additional shunts that were initially not seen on DSA.     

An Exploratory Study on 99mTc-RGD-BBN Peptide Scintimammography in the Assessment of Breast Malignant Lesions Compared to 99mTc-3P4-RGD2

Purpose

This study aimed to explore the diagnostic performance of single photon emission computed tomography / computerized tomography (SPECT/CT) using a new radiotracer ^99mTc-RGD-BBN for breast malignant tumor compared with ^99mTc-3P4-RGD₂.

Methods

6 female patients with breast malignant tumors diagnosed by fine needle aspiration cytology biopsy (FNAB) who were scheduled to undergo surgery were included in the study. ^99mTc-3P4-RGD₂ and ^99mTc-RGD-BBN were performed with single photon emission computed tomography (SPECT) at 1 hour after intravenous injection of 299 ± 30 MBq and 293 ± 32 MBq of radiotracers respectively at separate day. The results were evaluated by the Tumor to non-Tumor ratios (T/NT). ^99mTc-RGD-BBN and ^99mTc-3P4-RGD₂ SPECT/CT images were interpreted independently by 3 experienced nuclear medicine physicians using a 3-point scale system. All of the samples were analyzed immunohistochemically to evaluate the integrin αvβ3 and gastrin-releasing peptide receptor (GRPR) expression. The safety, biodistribution and radiation dosimetry of ^99mTc-RGD-BBN were also evaluated in the healthy volunteers.

Results

No serious adverse events were reported in any of the patients during the study. The effective radiation dose entirely conformed to the relevant standards. A total of 6 palpable malignant lesions were detected using ^99mTc-RGD-BBN SPECT/CT with clear uptake. All malignant lesions were also detected using ^99mTc-3P4-RGD₂ SPECT/CT. The results showed that five malignant lesions were with clear uptake and the other one with barely an uptake. 4 malignant cases were found with both αvβ3 and GRPR expression, 1 case with only GRPR positive expression (integrin αvβ3 negative) and 1 case with only integrin αvβ3 positive expression (GRPR negative).

Conclusion

^99mTc-RGD-BBN is a safe agent for detecting breast cancer. ^99mTc-RGD-BBN may have the potential to make up for the deficiency of ^99mTc-3P4-RGD₂ in the detection of breast cancer with only GRPR positive expression (integrin α_vβ₃ negative). The preliminary application of ^99mTc-RGD-BBN has demonstrated its powerful potential in breast cancer diagnosis and therapy.     

Comparison of 99mTc-3PRGD2 Integrin Receptor Imaging with 99mTc-MDP Bone Scan in Diagnosis of Bone Metastasis in Patients with Lung Cancer: A Multicenter Study

Purpose

^99mTc-3PRGD2, a promising tracer targeting integrin receptor, may serve as a novel tumor-specific agent for single photon emission computed tomography (SPECT). A multi-center study was prospectively designed to evaluate the diagnostic accuracy of ^99mTc-3PRGD2 imaging for bone metastasis in patients with lung cancer in comparison with the conventional ^99mTc-MDP bone scan.

Methods

The patients underwent whole-body scan and chest tomography successively at both 1 h and 4 h after intravenous injection of 11.1 MBq/Kg ^99mTc-3PRGD2. ^99mTc-MDP whole-body bone scan was routinely performed within 1 week for comparison. Three experienced nuclear medicine physicians blindly read the ^99mTc-3PRGD2 and ^99mTc-MDP images. The final diagnosis was established based on the comprehensive assessment of all available data.

Results

A total of 44 patients (29 male, 59±10 years old) with suspected lung cancer were recruited from 4 centers. Eighty-nine bone lesions in 18 patients were diagnosed as metastases and 23 bone lesions in 9 patients were benign. In a lesion-based analysis, ^99mTc-3PRGD2 imaging demonstrated a sensitivity, specificity, and accuracy of 92.1%, 91.3%, and 92.0%, respectively. The corresponding diagnostic values for ^99mTc-MDP bone scan were 87.6%, 60.9%, and 82.1%, respectively in the same patients. ^99mTc-MDP bone scan had better contrast in most lesions, whereas the ^99mTc-3PRGD2 imaging seemed to be more effective to exclude pseudo-positive lesions and detect bone metastases without osteogenesis.

Conclusion

^99mTc-3PRGD2 is a novel tumor-specific agent based on SPECT technology with a promising value in diagnosis of bone metastasis in patients with lung cancer.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01737112","term_id":"NCT01737112"}}NCT01737112     

Mortality Prediction in the Oldest Old with Five Different Equations to Estimate Glomerular Filtration Rate: The Health and Anemia Population-based Study

Background

Kidney function declines considerably with age, but little is known about its clinical significance in the oldest-old.

Objectives

To study the association between reduced glomerular filtration rate (GFR) estimated according to five equations with mortality in the oldest-old.

Design

Prospective population-based study.

Setting

Municipality of Biella, Piedmont, Italy.

Participants

700 subjects aged 85 and older participating in the “Health and Anemia” Study in 2007–2008.

Measurements

GFR was estimated using five creatinine-based equations: the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD), MAYO Clinic, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study-1 (BIS-1). Survival analysis was used to study mortality in subjects with reduced eGFR (<60 mL/min/1.73m²) compared to subjects with eGFR ≥60 mL/min/1.73m².

Results

Prevalence of reduced GFR was 90.7% with the C-G, 48.1% with MDRD, 23.3% with MAYO, 53.6% with CKD-EPI and 84.4% with BIS-1. After adjustment for confounders, two-year mortality was significantly increased in subjects with reduced eGFR using BIS-1 and C-G equations (adjusted HRs: 2.88 and 3.30, respectively). Five-year mortality was significantly increased in subjects with eGFR <60 mL/min/1.73m² using MAYO, CKD-EPI and, in a graduated fashion in reduced eGFR categories, MDRD. After 5 years, oldest old with an eGFR <30 mL/min/1.73m² showed a significantly higher risk of death whichever equation was used (adjusted HRs between 2.04 and 2.70).

Conclusion

In the oldest old, prevalence of reduced eGFR varies noticeably depending on the equation used. In this population, risk of mortality was significantly higher for reduced GFR estimated with the BIS-1 and C-G equations over the short term. Though after five years the MDRD appeared on the whole a more consistent predictor, differences in mortality prediction among equations over the long term were less apparent. Noteworthy, subjects with a severely reduced GFR were consistently at higher risk of death regardless of the equation used to estimate GFR.     

Subcutaneous Progesterone Is Effective and Safe for Luteal Phase Support in IVF: An Individual Patient Data Meta-Analysis of the Phase III Trials

Objective

To summarize efficacy and safety data on a new progesterone compound which is available for subcutaneous administration as compared to vaginally administered progesterone for luteal phase support in patients undergoing IVF treatment.

Design

Data from two randomized phase III trials (07EU/Prg06 and 07USA/Prg05) performed according to GCP standards with a total sample size of 1435 per-protocol patients were meta-analyzed on an individual patient data level.

Setting

University affiliated reproductive medicine unit.

Patients

Subcutaneous progesterone was administered to a total of 714 subjects and vaginal progesterone was administered to a total of 721 subjects who underwent fresh embryo transfer after ovarian stimulation followed by IVF or ICSI. The subjects were between 18 and 42 years old and had a BMI <30kg/m².

Interventions

Subcutaneous progesterone 25 mg daily vs. either progesterone vaginal gel 90 mg daily (07EU/Prg06) or 100 mg intravaginal twice a day (07USA/Prg05) for luteal phase support in IVF patients.

Main outcome measures

Ongoing pregnancy rate beyond 10 gestational weeks, live birth rate and OHSS risk.

Results

The administration of subcutaneous progesterone versus intra-vaginal progesterone had no impact on ongoing pregnancy likelihood (OR = 0.865, 95% CI 0.694 to 1.077; P = n.s.), live birth likelihood (OR = 0.889, 95% CI 0.714 to 1.106; P = n.s.) or OHSS risk (OR = 0.995, 95% CI 0.565 to 1.754; P = n.s.) in regression analyses accounting for clustering of patients within trials, while adjusting for important confounders. Only female age and number of oocytes retrieved were significant predictors of live birth likelihood and OHSS risk.

Conclusion

No statistical significant or clinical significant differences exist between subcutaneous and vaginal progesterone for luteal phase support.     

Longitudinal Cerebral Perfusion Change in Transient Global Amnesia Related to Left Posterior Medial Network Disruption

Background

The pathophysiology of transient global amnesia (TGA) is not fully understood. Previous studies using single photon emission computed tomography (SPECT) have reported inconclusive results regarding cerebral perfusion. This study was conducted to identify the patterns of regional cerebral blood flow (rCBF) in TGA patients via longitudinal SPECT analysis. An association between the observed SPECT patterns and a pathophysiological mechanism was considered.

Methods

Based on the TGA registry database of Seoul National University Bundang Hospital, 22 TGA patients were retrospectively identified. The subjects underwent initial Tc-99m-ethyl cysteinate dimer (ECD) SPECT within 4 days of an amnestic event and underwent follow-up scans approximately 6 months later. The difference in ECD uptake between the two scans was measured via voxel-based whole brain analysis, and the quantified ECD uptake was tested using a paired t-test.

Results

The TGA patients had significantly decreased cerebral perfusion at the left precuneus (P<0.001, uncorrected) and at the left superior parietal and inferior temporal gyrus according to the voxel-based whole brain analysis (P<0.005, uncorrected). A difference in the quantified ECD uptake between the 2 scans was also found at the left precuneus among the 62 cortical volumes of interest (P = 0.018, Cohen’s d = -0.25).

Conclusion

We identified left hemispheric lateralized hypoperfusion that may be related to posterior medial network disruption. These findings may be a contributing factor to the pathophysiology of TGA.     

Long-Term Follow-Up of Proteinuria and Estimated Glomerular Filtration Rate in HIV-Infected Patients with Tubular Proteinuria

Objective

The objective of this prospective observational study was to describe the evolution of tubular proteinuria detected in HIV-infected patients, and to evaluate the impact of tenofovir disoproxil fumarate (TDF) discontinuation.

Methods

Proteinuria and estimated glomerular filtration rate (eGFR) were followed during a median duration of 32 months, in 81 HIV-infected patients with tubular proteinuria and eGFR ≥ 60 ml/min/1.73 m² (determined using the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation). Tubular proteinuria was defined by urine protein to creatinine ratio (uPCR) ≥200 mg/g and albumin to protein ratio (uAPR) <0.4.

Results

Twenty per cent of patients had persistence of tubular proteinuria: TDF continuation was the main factor associated with this persistence [OR 9.0; 95%CI: 1.9–41.4; p = 0.01]. Among the 23 patients who discontinued TDF, uPCR returned below the threshold of 200 mg/g in 11 patients. Overall, eGFR decreased with a mean rate of decline of 3.8 ml/min/1.73m²/year. The decline in eGFR was lesser after discontinuation of TDF (5.8 ml/min/1.73m²/year during TDF exposure versus 3 ml/min/1.73m²/year after TDF discontinuation; p = 0.01).

Conclusions

The continuation of TDF was the main factor associated with the persistence of proteinuria. Moreover, proteinuria was normalized in only half of the patients who discontinued TDF. The clinical significance of TDF-related low level of proteinuria as a factor associated with renal disease progression and bone loss remains poorly understood.     

Body Mass Index,Mortality, and Gender Difference in Advanced Chronic Kidney Disease

Background and Aim

A higher body mass index (BMI) appears to be reversely associated with mortality in dialysis patients. Moreover, although women have better survival in chronic kidney disease (CKD), this survival advantage is cancelled in dialysis. The association between BMI and mortality and the gender difference remain controversial in advanced CKD.

Methods

This study enrolled 3,320 patients (1,938 men and 1,382 women) from southern Taiwan who had CKD stages 3–5 with a BMI of 15.0–35.0 kg/m².

Results

During a median 2.9-year follow-up, there were 328 (16.9%) all-cause mortality and 319 (16.5%) cardiovascular (CV) events and death in male patients, 213 (15.4%) all-cause mortality and 224 (16.2%) CV events and death in female patients. Compared with the reference BMI of 27.6–30.0 kg/m² in an adjusted Cox model, lower-BMI groups in men, BMI 15.0–20.0 kg/m² and 20.1–22.5 kg/m², were associated with higher risks of all-cause mortality: hazard ratios (HRs) 3.19 (95% confidence interval [CI], 1.97–5.18) and 2.01 (95% CI, 1.29–3.14), respectively. Higher-BMI group in men, BMI 30.1–35.0 kg/m², was associated with a higher risk of all-cause mortality: HR 1.72 (95% CI, 1.02–2.96). Likewise, lower- and higher-BMI groups in men were associated with a higher risk of CV events and death. In women, these associations between BMI and poor outcomes were not observed.

Conclusions

In advanced CKD, there was a reverse J-shaped association between BMI and all-cause mortality, and a U-shaped association between BMI and CV outcomes in men. Neutral associations between BMI and poor outcomes were detected in women. Gender could modify the effect of BMI on mortality in patients with CKD.     

Efficacy of a Community-Based Physical Activity Program KM2H2 for Stroke and Heart Attack Prevention among Senior Hypertensive Patients: A Cluster Randomized Controlled Phase-II Trial

Objective

To evaluate the efficacy of the program Keep Moving toward Healthy Heart and Healthy Brain (KM2H²) in encouraging physical activities for the prevention of heart attack and stroke among hypertensive patients enrolled in the Community-Based Hypertension Control Program (CBHCP).

Design

Cluster randomized controlled trial with three waves of longitudinal assessments at baseline, 3 and 6 months post intervention.

Setting

Community-based and patient-centered self-care for behavioral intervention in urban settings of China.

Participants

A total of 450 participants diagnosed with hypertension from 12 community health centers in Wuhan, China were recruited, and were randomly assigned by center to receive either KM2H² plus standard CBHCP care (6 centers and 232 patients) or the standard care only (6 centers and 218 patients).

Intervention

KM2H² is a behavioral intervention guided by the Transtheoretical Model, the Model of Personalized Medicine and Social Capital Theory. It consists of six intervention sessions and two booster sessions engineered in a progressive manner. The purpose is to motivate and maintain physical activities for the prevention of heart attack and stroke.

Outcome Measures

Heart attack and stroke (clinically diagnosed, primary outcome), blood pressure (measured, secondary outcome), and physical activity (self-report, tertiary outcome) were assessed at the individual level during the baseline, 3- and 6-month post-intervention.

Results

Relative to the standard care, receiving KM2H² was associated with significant reductions in the incidence of heart attack (3.60% vs. 7.03%, p < .05) and stroke (5.11% vs. 9.90%, p<0.05), and moderate reduction in blood pressure (-3.72mmHg in DBP and -2.92 mmHg in DBP) at 6-month post-intervention; and significant increases in physical activity at 3- (d = 0.53, 95% CI: 0.21, 0.85) and 6-month (d = 0.45, 95% CI: 0.04, 0.85) post-intervention, respectively.

Conclusion

The program KM2H² is efficacious to reduce the risk of heart attack and stroke among senior patients who are on anti-hypertensive medication. Findings of this study provide solid data supporting a formal phase-III trial to establish the effectiveness of KM2H² for use in community settings for prevention.

Trial Registration

ISRCTN Register ISRCTN12608966     

Preoperative Diagnostic Strategy for Parotid Gland Tumors Using Diffusion-Weighted MRI and Technetium-99m Pertechnetate Scintigraphy: A Prospective Study

Objective

Fine needle aspiration cytology (FNAC) for diagnosis of a parotid gland tumor is widely used but its sensitivity is low and non-diagnostic rate is relatively high. In contrast, core needle biopsy (CNB) has a higher sensitivity and lower rate of sampling errors but has a higher risk of injury to adjacent organs such as facial nerve than FNAC. Screening of patients with parotid gland tumors to identify cases of pleomorphic adenoma (PA) and Warthin tumor (WT) may allow CNB to be confined to patients without PA and WT. We established an algorithm for preoperative diagnosis and management of parotid gland tumor using diffusion-weighted MRI and ^99mTc pertechnetate scintigraphy. This algorithm was developed with the goal of maximal reduction of the number of patients in whom CNB is required. The purpose of the study is to validate our algorithm prospectively.

Methods

A prospective study was conducted in 71 cases who were newly diagnosed with parotid gland tumor and 53 cases were enrolled in the study. In the algorithm, PA (high apparent diffusion coefficient (ADC) _mean≥1.5×10⁻³ mm²/s) and non-PA (low ADC_mean<1.5×10⁻³ mm²/s) cases are first distinguished based on the ADC_mean on diffusion-weighed MRI. Second, among suspected non-PA cases, WT and non-WT are distinguished using technetium-99m pertechnetate scintigraphy. CNB is then performed only in probable non-PA and non-WT cases.

Results

Although CNB was only required in 40% (21/53) of all cases, we made a preoperative histopathological diagnosis with an accuracy of 87% (46/53) and we correctly diagnosed whether a tumor was benign or malignant with an accuracy of 96% (51/53). Preoperative surgical planning had to be changed during surgery in only one case (2%)

Conclusions

Our algorithm is valuable in terms of clinical practice with highly potential for preoperative diagnosis and with less risk of CNB procedure.     

Chronic Kidney Disease and Diabetic Retinopathy in Patients with Type 2 Diabetes

Purpose

To explore the relationship between chronic kidney disease (CKD) and diabetic retinopathy (DR) in a representative population of type 2 diabetes mellitus (DM2) patients in Catalonia (Spain).

Methods

This was a population-based, cross-sectional study. A total of 28,344 patients diagnosed with DM2 who had recorded ophthalmologic and renal functional examinations were evaluated. Data were obtained from a primary healthcare electronic database of medical records. CKD was defined as an estimated glomerular filtration ratio (eGFR) of <60 ml/min/1.73m² and/or urine albumin to creatinine ratio (UACR) ≥30 mg/g. DR was categorized as non-vision threatening diabetic retinopathy and vision threatening diabetic retinopathy.

Results

CKD was associated with a higher rate of DR [OR], 95% confidence interval [CI], 1.5 (1.4–1.7). When we analyzed the association between different levels of UACR and DR prevalence observed that DR prevalence rose with the increase of UACR levels, and this association was significant from UACR values ≥10 mg/g, and increased considerably with UACR values ≥300mg/g (Odds ratio [OR], 95% confidence interval [CI], 2.0 (1.6–2.5). This association was lower in patients with eGFR levels 44 to 30 mL/min/1.73m² [OR], 95% confidence interval [CI], 1.3 (1.1–1.6).

Conclusions

These results show that CKD, high UACR and/or low eGFR, appear to be associated with DR in this DM2 population.     

99mTc-3P4-RGD2 Scintimammography in the Assessment of Breast Lesions: Comparative Study with 99mTc-MIBI

Purpose

To compare the potential application of ^99mTc-3P-Arg-Gly-Asp (^99mTc-3P₄-RGD₂) scintimammography (SMM) and ^99mTc-methoxyisobutylisonitrile (^99mTc-MIBI) SMM for the differentiation of malignant from benign breast lesions.

Method

Thirty-six patients with breast masses on physical examination and/or suspicious mammography results that required fine needle aspiration cytology biopsy (FNAB) were included in the study. ^99mTc-3P₄-RGD₂ and ^99mTc-MIBI SMM were performed with single photon emission computed tomography (SPECT) at 60 min and 20 min respectively after intravenous injection of 738±86 MBq radiotracers on a separate day. Images were evaluated by the tumor to non-tumor localization ratios (T/NT). Receiver operating characteristic (ROC) curve analysis was performed on each radiotracer to calculate the cut-off values of quantitative indices and to compare the diagnostic performance for the ability to differentiate malignant from benign diseases.

Results

The mean T/NT ratio of ^99mTc-3P₄-RGD₂ in malignant lesions was significantly higher than that in benign lesions (3.54±1.51 vs. 1.83±0.98, p<0.001). The sensitivity, specificity, and accuracy of ^99mTc-3P₄-RGD₂ SMM were 89.3%, 90.9% and 89.7%, respectively, with a T/NT cut-off value of 2.40. The mean T/NT ratio of ^99mTc-MIBI in malignant lesions was also significantly higher than that in benign lesions (2.86±0.99 vs. 1.51±0.61, p<0.001). The sensitivity, specificity and accuracy of ^99mTc-MIBI SMM were 87.5%, 72.7% and 82.1%, respectively, with a T/NT cut-off value of 1.45. According to the ROC analysis, the area under the curve for ^99mTc-3P₄-RGD₂ SMM (area = 0.851) was higher than that for ^99mTc-MIBI SMM (area = 0.781), but the statistical difference was not significant.

Conclusion

^99mTc-3P₄-RGD₂ SMM does not provide any significant advantage over the established ^99mTc-MIBI SMM for the detection of primary breast cancer. The T/NT ratio of ^99mTc-3P₄-RGD₂ SMM was significantly higher than that of ^99mTc-MIBI SMM. Both tracers could offer an alternative method for elucidating non-diagnostic mammograms.     

Body Mass Index,High-Sensitivity C-Reactive Protein and Mortality in Chinese with Coronary Artery Disease

Background

To investigate single and joint associations of body mass index (BMI) and serum high-sensitivity C-reactive protein (hsCRP) with death.

Methods

The study included 1871 coronary artery disease (CAD) patients aged 40–85 year-old recruited from 2008 to 2011. Cox regression models were used to estimate the association of BMI and hsCRP with mortality. The data was analyzed in 2014.

Results

During 3.1 years follow-up, 141 deaths were recorded, 110 died of cardiovascular disease (CVD). After adjustment of major CVD risk factors, there was a J-shaped association between BMI and all-cause and CVD mortality, and a positive association between hsCRP and mortality. The J-shaped association of BMI with mortality was present among patients who never smoked or with elevated hsCRP (≥3.0 mg/L). Compared with overweight (BMI 24–27.9 kg/m²) patients with normal hsCRP (<3.0 mg/L), obese patients (BMI≥28 kg/m²) with elevated hsCRP had a 3.41-fold risk of all-cause mortality (95% CI 1.49–7.80) and a 3.50-fold risk of CVD mortality (1.40–8.75), lean patients (BMI<24 kg/m²) with elevated hsCRP concentration had a 2.54-fold risk of all-cause mortality (1.36–4.74) and a 2.36-fold risk of CVD mortality (1.19–4.70).

Conclusions

The association pattern between baseline BMI and mortality changed among different baseline hsCRP concentrations, indicating that low-grade inflammation may be related to BMI and secondary prognosis of CAD.     

Postoperative Capecitabine with Concurrent Intensity-Modulated Radiotherapy or Three-Dimensional Conformal Radiotherapy for Patients with Stage II and III Rectal Cancer

Background

The aim of this study was to evaluate the survival outcomes and toxicity of postoperative chemoradiotherapy with capecitabine and concurrent intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) in patients with stage II and III rectal cancer.

Patients

We recruited 184 patients with pathologically proven, stage II or III rectal cancer. Following total mesorectal excision (TME), the patients were treated with capecitabine and concurrent IMRT/3D-CRT. The treatment regimen consisted of two cycles of oral capecitabine (1600 mg/m²/day), administered twice daily from day 1–14 of radiotherapy, followed by a 7-day rest. The median pelvic dose was 50 Gy in 25 fractions. Oxaliplatin-based adjuvant chemotherapy was administered after the chemoradiotherapy.

Results

The 5-year overall survival, disease-free survival and locoregional control (LRC) rates were 85.1%, 80% and 95.4%, respectively. Grade 3 and 4 toxicities were observed in 28.3% of patients during treatment. Grade 3 or 4 late toxicity, including neurotoxicity or gastrointestinal toxicity, was only observed in nine patients (4.9%).

Conclusions

This study demonstrated that capecitabine chemotherapy with concurrent IMRT/3D-CRT following TME is safe, is well tolerated and achieves superior LRC and favorable survival rates, with acceptable toxicity.     

Adherence with Dosing Guideline in Patients with Impaired Renal Function at Hospital Discharge

Objectives

To determine the prevalence, determinants, and potential clinical relevance of adherence with the Dutch dosing guideline in patients with impaired renal function at hospital discharge.

Design

Retrospective cohort study between January 2007 and July 2011.

Setting

Academic teaching hospital in the Netherlands.

Subjects

Patients with an estimated glomerular filtration rate (eGFR) between 10-50 ml/min/1.73m² at discharge and prescribed one or more medicines of which the dose is renal function dependent.

Main Outcome Measures

The prevalence of adherence with the Dutch renal dosing guideline was investigated, and the influence of possible determinants, such as reporting the eGFR and severity of renal impairment (severe: eGFR<30 and moderate: eGFR 30-50 ml/min/1.73m²). Furthermore, the potential clinical relevance of non-adherence was assessed.

Results

1327 patients were included, mean age 67 years, mean eGFR 38 ml/min/1.73m². Adherence with the guideline was present in 53.9% (n=715) of patients. Reporting the eGFR, which was incorporated since April 2009, resulted in more adherence with the guideline: 50.7% vs. 57.0%, RR 1.12 (95% CI 1.02-1.25). Adherence was less in patients with severe renal impairment (46.0%), compared to patients with moderate renal impairment (58.1%, RR 0.79; 95% CI 0.70-0.89). 71.4% of the cases of non-adherence had the potential to cause moderate to severe harm.

Conclusion

Required dosage adjustments in case of impaired renal function are often not performed at hospital discharge, which may cause harm to the majority of patients. Reporting the eGFR can be a small and simple first step to improve adherence with dosing guidelines.     

The Cascade of Care for an Australian Community-Based Hepatitis C Treatment Service

Background

Hepatitis C treatment uptake in Australia is low. To increase access to hepatitis C virus treatment for people who inject drugs, we developed a community-based, nurse-led service that linked a viral hepatitis service in a tertiary hospital to primary care clinics, and resulted in hepatitis C treatment provision in the community.

Methods

A retrospective cohort study of patients referred to the community hepatitis service was undertaken to determine the cascade of care. Logistic regression analyses were used to identify predictors of hepatitis C treatment uptake.

Results

Four hundred and sixty-two patients were referred to the community hepatitis service; 344 attended. Among the 279 attendees with confirmed chronic hepatitis C, 257 (99%) reported ever injecting drugs, and 124 (48%) injected in the last month. Of 201 (72%) patients who had their fibrosis staged, 63 (31%) had F3-F4 fibrosis. Fifty-five patients commenced hepatitis C treatment; 26 (47%) were current injectors and 25 (45%) had F3-F4 fibrosis. Nineteen of the 27 (70%) genotype 1 patients and 14 of the 26 (54%) genotype 3 patients eligible for assessment achieved a sustained virologic response. Advanced fibrosis was a significant predictor of treatment uptake in adjusted analysis (AOR 2.56, CI 1.30–5.00, p = 0.006).

Conclusions

Our community hepatitis service produced relatively high rates of fibrosis assessment, hepatitis C treatment uptake and cure, among people who inject drugs. These findings highlight the potential benefits of providing community-based hepatitis C care to people who inject drugs in Australia–benefits that should be realised as direct-acting antiviral agents become available.     

Patient-Related Risk Factors for Periprosthetic Joint Infection after Total Joint Arthroplasty: A Systematic Review and Meta-Analysis

Background

Periprosthetic joint infections (PJIs) are dreaded complications of total joint arthroplasties. The risk of developing PJIs is likely to be influenced by several patient factors such as sociodemographic characteristics, body mass index (BMI), and medical and surgical histories. However, the nature and magnitude of the long-term longitudinal associations between these patient-related factors and risk of developing PJIs are uncertain.

Objective

To conduct a systematic review and meta-analysis to assess the associations between several patient-related factors and PJI.

Data Sources

MEDLINE, EMBASE, Web of Science, Cochrane Library, and reference lists of relevant studies from inception to September 2015.

Study Selection

Longitudinal studies with at least one-year of follow-up for PJIs after total joint arthroplasty.

Data Extraction and Synthesis

Two investigators extracted data on study characteristics, methods, and outcomes. A consensus was reached with involvement of a third. The relative risk (RR) with 95% confidence intervals was used as the summary measure of association across studies. Study-specific RRs with 95% confidence intervals were meta-analysed using random effect models and were grouped by study-level characteristics.

Results

Sixty-six observational (23 prospective cohort and 43 retrospective cohort or case-control) studies with data on 512,508 participants were included. Comparing males to females and smokers to non-smokers, the pooled RRs for PJI were 1.36 (1.18–1.57) and 1.83 (1.24–2.70) respectively. There was no evidence of any significant associations of PJI with age and high alcohol intake. Comparing BMI ≥ 30 versus < 30 kg/m²; ≥ 35 versus < 35 kg/m²; and ≥ 40 versus < 40 kg/m²; the pooled RRs were 1.60 (1.29–1.99); 1.53 (1.22–1.92); and 3.68 (2.25–6.01) respectively. Histories of diabetes, rheumatoid arthritis, depression, steroid use, and previous joint surgery were also associated with increased risk of PJI. The results remained similar when grouped by relevant study level characteristics.

Conclusions

Several potentially modifiable patient-related factors are associated with the risk of developing PJIs. Identifying patients with these risk factors who are due to have arthroplasty surgery and modulating these risk factors might be essential in reducing the incidence of PJI. Further research is however warranted to assess the potential clinical utility of these risk factors as risk assessment tools for PJI.

Systematic Review Registration

PROSPERO 2015: CRD42015023485