Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

[The beginnings and evolution of a pancreatic surgeon: a technical morphological analysis in first 5 years].

Objective: To explore the development of the pancreatic surgeon technique in a high-volume center. Methods: A total of 284 cases receiving pancreatic surgery by a single surgeon from June 2015 to December 2020 were retrospectively included in this study. The clinical characteristics and perioperative medical history were extracted from the medical record system of Zhongshan Hospital,Fudan University. Among these patients,there were 140 males and 144 females with an age (M (IQR)) of 61.0 (16.8) years(range: 15 to 85 years). The "back-to-back" pancreatic- jejunal anastomosis procedure was used to anastomose the end of the pancreas stump and the jejunal wall. Thirty days after discharge,the patients were followed by outpatient follow-up or telephone interviews. The difference between categorical variables was analyzed by the Chi-square test or the CMH chi-square test. The statistical differences for the quantitative data were analyzed using one-way analysis of variance or Kruskal-Wallis H test and further analyzed using the LSD test or the Nemenyi test,respectively. Results: Intraoperative blood loss in pancreaticoduodenectomy between 2015 and 2020 were 300,100(100),100(100),100(0),100(200) and 150 (200) ml,respectively. Intraoperative blood loss in distal pancreatectomy was 250 (375),100 (50),50 (65), 50 (80),50 (50),and 50 (100) ml,respectively. Intraoperative blood loss did not show statistical differences in the same operative procedure between each year. The operative time for pancreaticoduodenectomy was respectively 4.5,5.0(2.0),5.5(0.8),5.0(1.3),5.0(3.3) and 5.0(1.0) hours in each year from 2015 to 2020,no statistical differences were found between each group. The operating time of the distal pancreatectomy was 3.8 (0.9),3.0 (1.5),3.0 (1.8),2.0 (1.1),2.0 (1.5) and 3.0(2.0) hours in each year,the operating time was obviously shorter in 2018 compared to 2015 (P=0.026) and 2020 (P=0.041). The median hospital stay in 2020 for distal pancreatectomy was 3 days shorter than that in 2019. The overall incidence of postoperative pancreatic fistula gradually decreased,with a incident rate of 50.0%,36.8%,31.0%,25.9%,21.1% and 14.8% in each year. During this period,in a total of 3,6,4,2,0 and 20 cases received laparoscopic operations in each year. The incidence of clinically relevant pancreatic fistula (grade B and C) gradually decreased,the incident rates were 0,4.8%,7.1%,3.4%,4.3% and 1.4%,respectively. Two cases had postoperative abdominal bleeding and received unscheduled reoperation. The overall rate of unscheduled reoperation was 0.7%. A patient died within 30 days after the operation and the overall perioperative mortality was 0.4%. Conclusion: The surgical training of a high-volume center can ensure a high starting point in the initial stage and steady progress of pancreatic surgeons,to ensure the safety of pancreatic surgery.

[Pancreas multidisciplinary team optimizes the diagnosis and treatment of pancreas-related diseases and improves the prognosis of pancreatic cancer patients].

Objectives: To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer. Methods: The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ2 test. Results: Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months,P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%,P<0.05;32.9% vs. 21.9%,P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%,P>0.05). Conclusions: The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients' compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

[Advances on the management of renal lesion in glycogen storage disease type I].

Glycogen storage disease (GSD) is a group of congenital defects involved in the synthesis and decomposition of glycogen. As the most common type, GSD I is caused by mutations in glucose-6-phophate catalytic subunit (type Ia), or glucose-6-phosphate transporter (type Ib). Both defects can lead to hypoglycemia and accumulation of glycogen in the liver and kidney. So renal lesion is one of the main complications, which may manifest as increased glomerular filtration rate in the early stage, followed by microalbuminuria and decreased glomerular filtration rate and proteinuria. Subsequently it may progress into renal interstitial fibrosis, glomerulosclerosis, and eventually renal failure. Early detection and timely intervention of renal impairment are very important. Here we mainly describe the progress of diagnosis and treatment on the kidney disease of glycogen storage disease type I.

[Clinical analysis and prognosis factors of malignancy in the patients with mucinous cystic neoplasms of the pancreas].

Objective: To examine clinic pathological features of mucinous cystic neoplasms (MCN) of the pancreas and explore the prognosis factors associated with malignant transformation of MCN of the pancreas. Methods: This multicenter retrospective study included all patients with pancreatic MCN underwent surgery at Department of Pancreatic Surgery, Zhongshan Hospital of Fudan University between January 2008 and December 2018 and patients with MCN who confirmed by postoperative pathology from Multicenter Pancreatic Cystic Tumor Database. There were 50 males (14.4%) and 297 females (85.6%) and the mean age was 48.6 years (range: 24-77 years). According to the pathological results, all patients were divided into benign lesion group (including MCN and which associated with low/medium grade dysplasia) and malignant lesion group (including MCN with high-grade dysplasia or invasive carcinoma) . The preoperative clinical pathology and imaging features of the two groups were analyzed, and the risk factors associated with malignant transformation of MCN were statistically analyzed. Results: This multicenter retrospective study included 347 patients. Twenty-four of the 347 patients were malignant, including 7 males and 17 females. Univariate analysis showed that age, gender, carcino-embryonic antigen (CEA) , CA19-9, CA125, tumor maximum diameter, and tumor location were remarkably different in the two groups (P<0.05) . Logistic regression analysis found that the preoperative tumor maximum diameter (OR=1.023, 95% CI: 1.002-1.045, P=0.035) was an independent risk factor for MCN malignant transformation. Conclusions: Age, gender, CEA, CA19-9, CA125, tumor maximum diameter, and tumor location are important features of MCN malignant lesions.The maximum diameter of the preoperative tumor is an independent risk factor for MCN malignant transformation.

[The value of preoperative CA19-9 combined with platelet-to-lymphocyte ratio in predicting invasive malignancy in intraductal papillary mucinous neoplasms].

Objective: To explore preoperative predictive markers for invasive malignancy in intraductal papillary mucinous neoplasm(IPMN). Methods: The retrospective case-controlled study was adopted.Seventy-nine patients who underwent surgery and with pathologically confirmed IPMN from January 2005 to December 2014 at Department of Pancreatic Surgery, Zhongshan Hospital Fudan University were enrolled.Forty-six patients were male and 33 were female,with an average age of (62.9±8.9)years (range:37-82 years).Tumor sites:56 tumors were located at the head of the pancreas,22 were located at the body and tail of the pancreas,and 1 was located across the whole pancreas.Surgical procedures: 51 patients underwent pancreaticoduodenectomy, 22 patients underwent distal pancreatectomy, 4 patients underwent segmental pancreatectomy and 2 patients underwent total pancreatectomy.IPMNs were classified into non-invasive lesions and invasive carcinomas according to the histopathological findings of the tumor.Thirty-two tumors were non-invasive lesions and 47 were invasive carcinomas.The preoperative findings were compared between patients with non-invasive IPMN and patients with invasive carcinoma by univariate analysis using t test and χ(2) test accordingly,and factors with statistically significance were subsequently submitted to multivariate analysis. Results: Univariate analysis showed that tumor size(P=0.022), carcinoembryonic antigen(P=0.012), CA19-9(P=0.011), lymphocytes(P=0.034), neutrophil-to-lymphocyte ratio(P=0.010)and platelet-to-lymphocyte ratio(PLR)(P=0.004)were predictive markers with statistical significance.Multivariate analysis showed that CA19-9(P=0.012)and PLR(P=0.025) were independent predictive markers for invasive malignancy in IPMN.The area under curve of the combination factor of CA19-9 and PLR(0.864) was larger than that of CA19-9(0.806) or PLR(0.685) alone, and all the authentic indicators of the combination factor were better than those of each alone. Conclusions: CA19-9 and PLR are independent predictive markers for invasive malignancy in IPMN.The combination of CA19-9 and PLR has improved efficacy than each alone.

[Diagnostic value and patient compliance of a pancreas-oriented multidisciplinary clinic: a retrospective analysis from a Chinese pancreatic disease center].

Objective: To evaluate the role of multidisciplinary team (MDT) clinic in the diagnosis of pancreatic diseases and patient compliance with MDT advice in the current medical system. Methods: The study included 512 patients that had visited the pancreas-oriented MDT clinic of Zhongshan Hospital between May 2015 and May 2019.The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. Compliance was determined according to whether a patient received corresponding therapies or undergoing further checks or follow-ups. Results: Among the 512 patients that had visited the MDT clinic, 121 patients were referred due to undetermined diagnosis. Classified according to the final diagnosis, the rate of undetermined diagnosis in different disease categories from high to low in order was inflammatory diseases of the pancreas (75.0%, 24/32), other lesions of the pancreas (56.1%,23/41), pancreatic cystic lesions (19.1%,17/89), pancreatic carcinomas (18.3%,48/262) and pancreatic neuroendocrine neoplasms (pNEN)(10.2%,9/88). The MDT clinic made diagnosis to 68 patients directly with an accuracy of 89.7%. The rate of compliance in the entire cohort was 63.4%. The rate of compliance of patients from June 2017 to May 2019 (68.4%) was higher than that of patients from May 2015 to May 2017(59.6%). The compliance rate of patients in different disease categories from high to low in order was inflammatory diseases of the pancreas(84.4%, 27/32), pancreatic carcinomas (67.9%, 178/262), pNEN(60.2%,53/88), other lesions of the pancreas (56.1%,23/41), and pancreatic cystic lesions(49.4%, 44/89). The compliance rate of patients with different MDT advice from high to low in order was best supportive care(78.6%,22/28), antitumor approaches beyond surgery(71.6%,159/222), further tests(62.6%, 77/123), surgery(53.7%, 65/121) and follow-up(49.2%, 31/63). In patients suggested for surgery, the compliance rate of patients with carcinomas(67.4%, 33/49) was higher than patients with other kinds of neoplasms. Conclusions: MDT clinic could facilitate the diagnosis of pancreatic diseases conveniently and inexpensively. The overall compliance rate of MDT clinic patients is rather low, and patients with carcinomas have a relative high rate of compliance with the suggestion of surgery.

Association between leukoaraiosis and cerebral blood flow territory alteration in asymptomatic internal carotid artery stenosis.

AIM: To test the hypothesis that leukoaraiosis (also known as white matter lesion) is associated with cerebral blood flow territory change as revealed by territorial arterial spin-labeling (TASL) magnetic resonance imaging (MRI) in patients with asymptomatic internal carotid artery stenosis (aICAS). MATERIALS AND METHODS: The institutional review board approved this study. Thirty-three patients with aICAS were included prospectively and divided into high-grade (ultrasonographic stenosis ≥70%, n=17) and low-grade (n=16) groups; 16 healthy subjects were also included. Cerebral flow territory was delineated for left ICA, right ICA, and vertebral arteries using TASL MRI and fuzzy clustering. Two licensed neuroradiologists independently and dichotomously rated the hemispherical asymmetry of flow territories. Flow territories were finalised by consensus, and when asymmetry was present, these were divided into normal and abnormal areas where the raters separately assessed leukoaraiosis based on fluid-attenuated inversion recovery images and the Fazekas scale. RESULTS: The inter-rater agreement in the evaluation of flow territory asymmetry with TASL imaging in conjunction with time-of-flight angiogram is substantial (Cohen's kappa=0.82). Multinomial logistic regression (reference group=healthy subjects) indicates that global leukoaraiosis is not a predictor of aICAS after controlling for age, whereas in high-grade patients, the deep white matter lesion is more severe in the area receiving collateral circulation than in the area with normal flow territory (Wilcoxon signed-rank test, p=0.03). CONCLUSION: TASL MRI is clinically feasible in aICAS and shows that more severe deep white matter lesions are associated with collateral circulation in high-grade patients.

Body mass index and depressive symptoms in adolescents in Taiwan: testing mediation effects of peer victimization and sleep problems.

BACKGROUND: Despite recognition of the link between body mass index (BMI) and depression in adolescence, the underlying mechanisms behind this association remain understudied. This study aims to examine three mediational pathways from BMI to depressive symptoms through peer victimization and sleep problems. Sex differences in the mediating effects were also explored. METHODS: Data came from 1893 adolescents participating in a multi-wave longitudinal study from grade 9 to 12 in northern Taiwan were analyzed. Measures included BMI in 2009, peer victimization in 2010, sleep problems in 2011, depressive symptoms in 2012 and other covariates (sex, age, parental education, family structure, family economic stress, stressful life events, pubertal development and previous scores of focal study variables). A series of multiple regression models were conducted to test mediation hypotheses. A bootstrapping approach was applied to obtain confidence intervals for determining the significance of indirect effects. RESULTS: The association between BMI and depressive symptoms was significantly mediated by peer victimization and sleep problems. Higher BMI predicted more peer victimization and sleep problems, each of which led to higher levels of depressive symptoms. Our results further showed that higher BMI was associated with more peer victimization, which led to greater sleep problems and in turn resulted in increased depressive symptoms. No sex differences was found for the indirect effects of BMI on depressive symptoms through either peer victimization or sleep problems. CONCLUSIONS: Peer victimization and sleep problems partly explain the link between BMI and depressive symptoms. Interventions to prevent or manage depressive symptoms may yield better results if they consider the effects of these two psychosocial factors rather than targeting BMI alone.

Increased expression of triggering receptor expressed on myeloid cells 1 and 2 in inflamed human gingiva.

BACKGROUND AND OBJECTIVE: Periodontitis is an infectious disease in which the host immune and inflammatory responses play essential roles in resistance to bacterial infection, as well as the induction of tissue destruction if the immune response is dysregulated. The triggering receptor expressed on myeloid cells (TREMs) modulates inflammatory and innate immune signaling. TREM-1 is considered as an amplifier of the immune response, while TREM-2 is a negative regulator that has yet to be explored in periodontal disease before. We hypothesized that TREMs participated in the innate immune responses during the pathogenesis of periodontitis. Therefore, the aim of this study was to evaluate TREM-1 and TREM-2 expression in the gingival tissues from patients with chronic periodontitis and healthy subjects as well as their correlation with clinical periodontal parameters. This study is the first to identify TREM-2 in periodontal tissue, as well as the protein expression changes of TREM-1 and TREM-2 in periodontal tissues. MATERIAL AND METHODS: Gingival tissue sections were collected from 31 healthy subjects and 53 patients with chronic periodontitis. Immunohistochemistry and quantitative real-time polymerase chain reaction were employed to evaluate the protein and mRNA expression of these receptors in gingival tissues. The recorded clinical parameters were probing depth, clinical attachment loss, plaque index and bleeding on probing. RESULTS: In addition to myeloid cells in gingival connective tissues, TREM-1 and TREM-2 were also found expressed in gingival epithelial cells. In particular, TREM-1 was detected in almost all gingival epithelium from both healthy and inflamed biopsies. The expression levels of TREM-1 and TREM-2 were significantly increased in the periodontitis group compared to the healthy group. Increased levels of these receptors are to be positively correlated with site-specific periodontal parameters. CONCLUSION: The increased expression of TREM-1 and TREM-2 levels in periodontitis may confer diagnostic and potential therapeutic targets as well as indicating their association with the clinical severity of the disease.

Electroacupuncture ameliorates spatial learning and memory impairment via attenuating NOX2-related oxidative stress in a rat model of Alzheimer's disease induced by Aß1-42.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive deterioration of cognition and memory, in which oxidative stress has been played a crucial role in the pathology of AD. Electroacupuncture (EA) is a widely used therapy based on traditional acupuncture combined with modern electrotherapy in Asia. The present study aimed to determine the effects of EA treatment on spatial learning and memory impairment, and to elucidate the status of NOX2-related oxidative stress in a rat model of Alzheimer's disease induced by Beta-amyloid1-42 (Aß1-42). Fifty-six adult female Sprague-Dawley (SD) rats were randomly divided into four groups: sham, sham+EA, AD and AD+EA. The rats in Sham+EA and AD+EA groups were respectively administrated EA treatment at Baihui and yongquan acupoints, once a day for 30 min, lasting for 28 days. The spatial learning and memory functions were assessed by Morris water maze (MWM) test. The activities of total antioxidant capacity (T-AOC), reactive oxygen species (ROS), malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) were evaluated. Moreover, the neuronal injury was detected by Nissl staining. Meanwhile, the NeuN expression was examined in the hippocampus, the expression levels of Nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase2(NOX2) was detected by immunofluorescence staining and western blot. The results showed that EA treatment significantly improved spatial learning and memory impairment in rats induced by Aß1-42. Concomitantly, EA treatment markedly restored T-AOC and attenuated the abnormal increase in levels of ROS, MDA and 8-OH-dG in the hippocampus of the AD rats. More notably, EA treatment also effectively ameliorated neuronal injury and counteracted the aberrant increase of NOX2 levels in the hippocampus of AD rats. Our findings suggested that EA is a potential strategy for the treatment of AD, and the possible mechanism is associated with the alleviation of neuronal injury and inhibition of NOX2-related oxidative stress.

Genetic variability in copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with Alzheimer's disease in a Chinese population.

Previous experiments demonstrated that transgenic mice carrying both amyloid precursor protein and mutant ATP7B transgenes reduce amyloid plaques and diminish plasma Abeta levels. These experiments showed that a structural change of ATP7B may affect Alzheimer’s disease (AD) susceptibility. In this study three missense SNPs in ATP7B gene (rs1801243, rs1801244, and rs1801249) were chosen to test whether they were associated with AD. We tested this hypothesis using a case control design. The experimental data showed that there was a significant deviation from Hardy-Weinberg equilibrium (HWE) for SNP rs1801249 (c.3419 T greater than C, Val1140Ala) in the case group (p = 0.014) but not in the control group and that there was an association between SNP rs1801249 and AD under a recessive model (p = 0.003). The data also showed that the genotype frequency distribution of the ATP7B c.1366 G greater than C polymorphism (rs1801244, Val456Leu) differed significantly between the AD patients and the normal subjects (p = 0.012). In addition, the frequency of the TGC haplotype of SNPs rs1801243, rs1801244, and rs1801249 was significantly higher in the AD patients compared with the normal subjects (p = 8.49×10-7). These observations suggested that genetic variations in the copper transporter gene ATP7B might contribute to AD pathogenesis in the Taiwanese population.

Role of mechanical strain and estrogen in modulating osteogenic differentiation of mesenchymal stem cells (MSCs) from normal and ovariectomized rats.

Bone's adaptability to loading depends upon the process of bone remodeling. This adaptive mechanism is restricted in postmenopausal osteoporosis. Differentiation of mesenchymal stem cells (MSCs) is crucial to bone remodeling and regeneration. It is well accepted that mechanical loading influences the fate of MSC differentiation. The aim of this study was to explore the possible restricted mechanism in osteoporotic condition, through investigating response of MSCs from both sham-operated and ovariectomized rats. MSCs were exposed to estrogen and mechanical strain (2%, 1Hz, 6h/day) for 3 days. Osteogenic differentiation and ß-catenin protein in MSCs were examined. Exposure to estrogen and mechanical strain alone enhanced expression of Runx2 (Cbfα1), type I collagen (ColI) and activated ß-catenin protein in MSCs from both sham-operated and OVX rats. MSCs from both sham-operated and OVX rats stimulated with both mechanical strain and estrogen had higher expression of osteogenic genes and activated ß-catenin protein than these cells exposed to estrogen and mechanical strain alone. Osteoporotic MSCs had lower expression of osteogenic genes and protein in the absence and presence of stimulation than did MSCs from sham-operated rats. Cumulatively, our results indicate that mechanical strain and estrogen in vitro enhance osteogenic potential and activation of ß-catenin in MSCs from both sham-operated and OVX rats. Estrogen augments strain-induced osteogenic potential and activity of ß-catenin in MSCs.

Association between red blood cell distribution width and macrovascular and microvascular complications in diabetes.

AIMS/HYPOTHESIS: Red blood cell distribution width (RDW) has been reported to be a risk marker of morbidity and mortality for cardiovascular disease in various study populations. However, no studies have investigated the relationship between RDW and diabetes complications. We therefore evaluated RDW as a marker of macrovascular and microvascular complications in a nationally representative sample of the adult diabetes population in the USA. METHODS: A cross-sectional study was performed using the nationwide 1988 to 1994 data set from the Third National Health and Nutrition Examination Survey. The association between RDW quartiles and macrovascular and microvascular complications was evaluated in 2,497 non-pregnant adults aged 20 years and older and affected by diabetes. Logistic regression modelling was used to adjust for potential confounding. RESULTS: Compared with the lowest RDW quartile, higher RDW values (3rd and 4th quartiles) were associated with increased adjusted odds of any vascular complication (OR 4th quartile 2.06 [95% CI 1.11, 3.83]), myocardial infarction (OR 4th quartile 2.45 [95% CI 1.13, 5.28]), heart failure (OR 4th quartile 4.40 [95% CI 1.99, 9.72]), stroke (OR 4th quartile 2.56 [95% CI 1.21, 5.42]) and nephropathy (OR 4th quartile 2.33 [95% CI 1.42, 3.82]). The odds of developing diabetic retinopathy were not significantly increased across RDW quartiles. CONCLUSIONS/INTERPRETATION: Higher RDW values are associated with increased odds of developing cardiovascular disease and nephropathy in a nationally representative sample of USA adults with diabetes. RDW may be an important clinical marker of vascular complications in diabetes and one that is independent of traditional risk factors and disease duration.

Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy.

AIMS: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). MATERIALS AND METHODS: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of ≥100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. RESULTS: After a median follow-up of 26.7 ± 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and ≥100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of ≥100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count ≤10(5)/mm(3) (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. CONCLUSIONS: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

20-MHz phased array ultrasound transducer for in vivo ultrasound imaging of small animals.

In vivo ultrasound imaging with phased array transducers is of great importance for both clinical application and biomedical research. In this work, relaxor ferroelectric PMN-0.28PT single crystal with very high piezoelectric constant d33 ≥ 2000 pC/N and electromechanical coupling coefficient k33 âˆ¼ 0.92 is used to fabricate high-frequency phased array transducers. A 128-element 20-MHz phased array transducer is successfully fabricated, and the optimized performance of -6 dB average bandwidth of âˆ¼ 84 % and insertion loss of -43 dB are achieved. The axial and lateral imaging resolutions of the transducer are determined to be 81 µm and 243 µm, respectively. With Verasonics image platform, in vivo fisheye images are acquired, demonstrating the potential application of our developed high-frequency phased array transducer for biomedical research on small animals.

Psychosocial problems in children with allergic diseases: a population study in Taiwan.

BACKGROUND: A few studies had pointed out the relationship between a single allergic disease and children's psychosocial problems; however, all of these researchers considered the allergic diseases separately. Therefore, this study aimed to investigate the relationship between collective allergic diseases and psychosocial problems among 4- to 12-year-old children in Taiwan. METHODS: The data were generated from the 2005 Taiwan National Health Interview Survey. A total of 2955 parents or guardians completed the answers for their 4- to 12-year-old children. We used logistic regressions to investigate the association of allergic diseases and the psychosocial problems. RESULTS: About 40.62% children had at least one allergic disease in the past year, and 17.75% children had a score of psychosocial problems higher than or equal to the 75th percentile. After controlling for demographic factors, the risk of having high-level psychosocial problem for children with any allergic disease was 1.84 times of those without allergy. For those who had one, two or more than two allergic diseases, the risks of having psychosocial problems were 1.56, 2.20 and 3.39 times of those had no allergy disease respectively. Children with asthma, dermatitis and rhinitis simultaneously had the highest psychosocial impact (odds ratio = 5.10). CONCLUSIONS: Collective allergic diseases were associated with psychosocial problems in children, and the effect was gradient. Parents and paediatricians should pay attention to psychosocial problems in children with allergic diseases and vice versa.

Normal-sized ovarian papillary serous carcinoma: a case report.

A normal-sized ovarian papillary serous carcinoma is rare. We present the case of a 46-year-old woman with progressive abdominal fullness of one week's duration. The medical evaluation revealed abdominal carcinomatosis with normal-sized ovaries and an elevated serum CA-125 level of 147,365.8 U/ml. Cytoreductive surgery (hysterectomy, bilateral salpingo-oophorectomy, omentectomy, lymphadenectomy, infracolic omentectomy, peritoneal biopsy, washing cytology, and appendectomy) was performed. The histologic examination revealed an ovarian serous papillary carcinoma. Adjuvant chemotherapy was administered. The serum CA-125 level decreased after completion of treatment. Normal-sized ovarian serous surface papillary carcinomas should be kept in mind as an origin of disease in patients who have peritoneal carcinomatosis, which sometimes is a diagnostic dilemma of the disease source. We report this case to emphasize the clinical symptoms and importance of the early and accurate diagnosis of a normal-sized ovarian papillary serous carcinoma.

Current status in cervical carotid artery stent placement.

Based upon recent and old medical literature, with the exception of high surgical risk symptomatic patients, there remains much debate on how to manage extracranial carotid arterial disease, whether by surgical or endovascular intervention or by medical therapy alone. A review of the various global current carotid artery stent and endarterectomy registries and trials was performed incorporating more than 14,000 patients who have received carotid stents. There is substantial evidence supporting the benefit of carotid artery stenting (CAS) for the high anatomic risk population. Complication rates with symptomatic patients, including octogenarians, continue to show trend towards improvement as operators gain experience. The results are limited for standard risk carotid stenting for symptomatic patients though results with recent trials are pending but will probably show equivalence with endarterectomy. The asymptomatic patient population remains controversial: there is a small but reproducible benefit for revascularization. Long term (1-3 years) neurological results are now being reported for the major registries and trials. Analysis of target lesion revascularization, stroke and death rates of carotid stenting is comparable or better than rates for endarterectomy. Carotid artery stent placement has met the CMS targets 3% for MAE for asymptomatic patients and 6% for symptomatic patients with numerous registries and trials. CAS has also proven outcomes at 3 years with restenosis rates and stroke-free rates comparable or better than CEA. CAS provides an option for patients not suited for medical therapy and who were high-risk for CEA, especially for those symptomatic patients. It is still controversial with the role of stenting asymptomatic patients as well as for octogenarians. However, forthcoming trials will be helpful in providing more insight. Despite questionable studies and bad press, carotid stenting in the right hands with good patient selection is an excellent procedure. Finally, it is important to remember, carotid stenting is still in its early development and will only get better.

Malignant transformation of extragonadal endometriosis: a case report.

Though malignant transformation of endometriosis has been documented, malignancy arising from extragonadal endometriosis is rare. We present the case of a 39-year-old woman with abdominal pain and fullness after menstruation. Evaluation revealed a cul-de-sac mass and CA-125 level of 1048 U/ml. A hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. Endometrioid adenocarcinoma with a clearly defined transition zone from endometriosis to adenocarcinoma was noted histologically. Adjuvant chemotherapy and GnRH agonist treatment was administered. Serum CA-125 level was 1.51 U/ml 19 months after completion of treatment. Patients with endometriosis and elevated CA-125 levels should be managed aggressively and CA-125 levels monitored until they have normalized.