The combination of soluble tumor necrosis factor receptor type 1 and fibroblast growth factor 21 exhibits better prediction of renal outcomes in patients with type 2 diabetes mellitus.

PURPOSE: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. METHODS: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. RESULTS: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. CONCLUSION: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.

Nutrition therapy in esophageal cancer-Consensus statement of the Gastroenterological Society of Taiwan.

A number of clinical guidelines on nutrition therapy in cancer patients have been published by national and international societies; however, most of the reviewed data focused on gastrointestinal cancer or non-cancerous abdominal surgery. To collate the corresponding data for esophageal cancer (EC), a consensus panel was convened to aid specialists from different disciplines, who are involved in the clinical nutrition care of EC patients. The literature was searched using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the ISI Web of Knowledge. We searched for the best evidence pertaining to nutrition therapy in the case of EC. The panel summarized the findings in 3 sections of this consensus statement, based on which, after the diagnosis of EC, an initial distinction is made between the patients, as follows: (1) Assessment; (2) Therapy in patients with resectable disease; patients receiving chemotherapy or chemoradiotherapy prior to resection, and patients with unresectable disease, requiring chemoradiotherapy or palliative therapy; and (3) Formula. The resulting consensus statement reflects the opinions of a multidisciplinary group of experts, and a review of the current literature, and outlines the essential aspects of nutrition therapy in the case of EC. The statements are: Patients with EC are among one of the highest risk to have malnutrition. Patient generated suggestive global assessment is correlated with performance status and prognosis. Nutrition assessment for patients with EC at the diagnosis, prior to definitive therapy and change of treatment strategy are suggested and the timing interval can be two weeks during the treatment period, and one month while the patient is stable. Patients identified as high risk of malnutrition should be considered for preoperative nutritional support (tube feeding) for at least 7-10 days. Various routes for tube feedings are available after esophagectomy with similar nutrition support benefits. Limited intrathoracic anastomotic leakage postesophagectomy can be managed with intravenous antibiotics and self-expanding metal stent (SEMS) or jejunal tube. Enteral nutrition in patients receiving preoperative chemotherapy or chemoradiation provides benefits of maintaining weight, decreasing toxicity, and preventing treatment interruption. Tube feeding or SEMS can offer nutrition support in patients with unresectable esophageal cancer, but SEMS is not recommended for those with neoadjuvant chemoradiation before surgery. Enteral immunonutrition may preserve lean body mass and attenuates stress response after esophagectomy. Administration of glutamine may decrease the severity of chemotherapy induced mucositis. Enteral immunonutrition achieves greater nutrition status or maintains immune functions during concurrent chemoradiation.

Survival outcome of weak estrogen/progesterone receptor expression in HER2 negative breast cancer is similar to triple negative breast cancer.

BACKGROUND: Recent publications have suggested that human epidermal growth factor receptor 2 (HER2)-negative breast cancers with "weak" estrogen receptor (ER)/progesterone receptor (PR) expression levels by immunohistochemical (IHC) analysis were considered as the triple-negative (TN) subtype. This study aimed to evaluate the overall survival (OS), disease-free survival rates (DFS), and disease-specific survival (DSS) based on ER and PR expression levels into one of three groups, ER and PR <1%, ER and PR 1%-20%, and ER or PR >20% by hormone therapy. METHODS: Medical records of 3353 breast cancer patients treated from 2006 to 2013 were retrospectively reviewed. Tumor characteristics, type of treatment, OS, DFS and DSS were evaluated among the three patient groups. RESULTS: Regarding OS, there were significant differences according to the received hormone therapy in the different groups: ER and PR <1% (P = 0.972), ER and PR 1%-20% (P = 0.264), and ER or PR >20% (P = 0.014). Regarding DFS and DSS, there were also significant differences in the different groups: ER and PR <1% (P = 0.611, 0.766), ER and PR 1%-20% (P = 0.847, 0.629), and ER or PR >20% (P = 0.031, 0.002). CONCLUSIONS: In HER2 negative breast cancer patient with hormone therapy, ER and PR expression level of 1%-20% has similar survival outcome to the ER and PR expression level of <1% by IHC analysis.

Inclined-incidence hard-X-ray resonator with ultrahigh efficiency and resolution.

We report a high-efficiency hard-X-ray resonator with inclined-incidence geometry. A beam incident at 36.87° with respect to [3 1 0] excites Bragg back diffraction along (12 4 0) at 14.4388 keV for resonance in a Si-based resonator to produce intense resonance fringes. The experimental results showed the visibility enhanced by nearly 30 times compared with normal incidence. Also numerical calculations of the inclined-incidence resonator demonstrate ultrahigh efficiency and extremely narrow resolving power (sub-meV) with low background. This geometry surpasses the intrinsic limits of normal-incidence crystal-based resonators and enables ultrahigh-resolution X-ray optics for X-ray diffraction, spectroscopy, and imaging applications.

ANG II promotes IGF-IIR expression and cardiomyocyte apoptosis by inhibiting HSF1 via JNK activation and SIRT1 degradation.

Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure. Our previous studies found that the activation of insulin-like growth factor receptor II (IGF-IIR) signaling was critical for hypertensive angiotensin II (ANG II)-induced cardiomyocyte apoptosis. However, the detailed mechanism by which ANG II regulates IGF-IIR in heart cells remains elusive. In this study, we found that ANG II activated its downstream kinase JNK to increase IGF-IIR expression through the ANG II receptor angiotensin type 1 receptor. JNK activation subsequently led to sirtuin 1 (SIRT1) degradation via the proteasome, thus preventing SIRT1 from deacetylating heat-shock transcription factor 1 (HSF1). The resulting increase in the acetylation of HSF1 impaired its ability to bind to the IGF-IIR promoter region (nt -748 to -585). HSF1 protected cardiomyocytes by acting as a repressor of IGF-IIR gene expression, and ANG II diminished this HSF1-mediated repression through enhanced acetylation, thus activating the IGF-IIR apoptosis pathway. Taken together, these results suggest that HSF1 represses IGF-IIR gene expression to protect cardiomyocytes. ANG II activates JNK to degrade SIRT1, resulting in HSF1 acetylation, which induces IGF-IIR expression and eventually results in cardiac hypertrophy and apoptosis. HSF1 could be a valuable target for developing treatments for cardiac diseases in hypertensive patients.

Impact of metabolic syndrome components on incident stroke subtypes: a Chinese cohort study.

Limited evidence is available on the risk differences in the development of stroke subtypes in relation to particular clustering patterns of the metabolic syndrome (MetS) components. A follow-up study of a Chinese cohort involving 10,292 individuals was performed to assess the roles of cluster patterns of the MetS components in the prediction of incident stroke subtypes. During follow-up, there were 161 incident cases of ischemic strokes and 41 incident cases of hemorrhagic strokes. Among MetS components, only the hypertensive trait was associated with significantly elevated risks of both ischemic and hemorrhagic strokes. Furthermore, MetS with hypertension as components was associated with increased risk of ischemic and hemorrhagic strokes (adjusted hazards ratio (95% confidence interval) was 2.96 (1.94-4.50) and 2.93 (1.25-6.90), respectively) as compared with those who had neither hypertension nor MetS. Notably, as the number of the MetS components increased, the risk of ischemic stroke significantly and dose-dependently increased. This implies a cumulative effect of MetS components in elevating the risk of ischemic stroke. These findings suggest that MetS comprises heterogenous clusters with respect to the risk of developing the subtype of stroke.

Advanced age is not a contraindication for liver resection in cases of large hepatocellular carcinoma.

BACKGROUND: The role of surgery in the management of large hepatocellular carcinomas (HCCs) is controversial. Advanced age and comorbidities are taken into account when major surgery is considered. PURPOSE: To compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) for resectable HCC in patients aged 70 years or older. PATIENTS AND MATERIALS: This study included 70 patients aged 70 years or older treated for large HCCs (≥5 cm) between January 2007 and December 2012: 37 underwent LR and 33 underwent TACE. The outcomes of these patients were retrospectively analyzed. Univariate and multivariate Cox proportional hazard models were established. Kaplan-Meier survival curves were generated, and survival data were compared using the log-rank test. RESULTS: Hospital stay was significantly longer in the LR group than in the TACE group (10 days vs 8.5 days; P = 0.003). Treatment-related complications were more frequent in the TACE group, but this difference was not statistically significant. LR was associated with a better disease-free survival rate, median survival rate and cumulative overall survival rate. CONCLUSION: Our results showed that LR could be a safe and effective treatment option for HCC tumors ≥5 cm in patiets aged 70 years or older.

Profiles of circulating endothelial cells and serum cytokines during adjuvant chemoradiation in rectal cancer patients

INTRODUCTION: This research aimed to demonstrate the correlation of circulating endothelial cells (CECs) count and serum cytokine levels with side effects and prognosis in rectal cancer patients receiving adjuvant chemoradiation. METHODS: Eleven patients received proctectomy, chemoradiotherapy and follow-up for 4 years. Fifty-five blood samples were taken before radiation and during the course. The quantities of CECs were estimated by flow cytometry, and serological factors were measured by ELISA. RESULTS: The CEC level in patients without tumor recurrence was significantly lower than in patients with tumor recurrence (p < 0.01). The IL-6 and TGF-β1 levels exhibited a similar profile (p < 0.01). For morbidity, the mean CEC level in patients with grade 3 diarrhea was significantly greater than patients with grades 1 (p < 0.001) and 2 diarrhea (p < 0.005). CONCLUSIONS: Levels of CECs, serum IL-6, TGF-β1 and TNF-α during post-operative chemoradiation in rectal cancer patients might be candidate biomarkers for prognosis and morbidity (NCT00325871) (AU)

Clinical application of total parenteral nutrition in patients with peritoneal carcinomatosis.

Cancer patients with terminal stage peritoneal carcinomatosis are often unable to eat, rendering total parenteral nutrition (TPN) as the only option to avoid starvation. In this retrospective study, we reviewed the medical records of 46 patients with peritoneal carcinomatosis and compared them to the records of 51 patients who had gastrointestinal malignancy without evidence of peritoneal carcinomatosis. The factors evaluated include demographic data, cause of primary malignancy, ascites formation, anthropometric measurements, laboratory tests, and outcome measurements as well as factors associated with greater than 90-day survival. In-hospital mortality was observed in 31 of the 46 patients with peritoneal carcinomatosis, with a median survival time of 40 days (4-148 days) for all 46 patients. The median duration of TPN administration in the peritoneal carcinomatosis group was 24.1 ± 27.4 days (3-68 days). Severe infection related to TPN application was seen in 5/46 (10.7%) patients with peritoneal carcinomatosis and 6/51 (9.8%) patients without peritoneal carcinomatosis. The length of survival varied widely among terminal patients with peritoneal carcinomatosis. The average survival time in peritoneal carcinomatosis patients receiving TPN was short, indicating that the nutrition support of TPN was relatively suboptimal. Ascites was not a prognostic factor for peritoneal carcinomatosis, while body mass index was a predictor for 90-day survival.

Profiles of circulating endothelial cells and serum cytokines during adjuvant chemoradiation in rectal cancer patients.

INTRODUCTION: This research aimed to demonstrate the correlation of circulating endothelial cells (CECs) count and serum cytokine levels with side effects and prognosis in rectal cancer patients receiving adjuvant chemoradiation. METHODS: Eleven patients received proctectomy, chemoradiotherapy and follow-up for 4 years. Fifty-five blood samples were taken before radiation and during the course. The quantities of CECs were estimated by flow cytometry, and serological factors were measured by ELISA. RESULTS: The CEC level in patients without tumor recurrence was significantly lower than in patients with tumor recurrence (p < 0.01). The IL-6 and TGF-ß1 levels exhibited a similar profile (p < 0.01). For morbidity, the mean CEC level in patients with grade 3 diarrhea was significantly greater than patients with grades 1 (p < 0.001) and 2 diarrhea (p < 0.005). CONCLUSIONS: Levels of CECs, serum IL-6, TGF-ß1 and TNF-α during post-operative chemoradiation in rectal cancer patients might be candidate biomarkers for prognosis and morbidity (NCT00325871).

Adverse effect on syngeneic islet transplantation by transgenic coexpression of decoy receptor 3 and heme oxygenase-1 in the islet of NOD mice.

Decoy receptor 3 (DcR3) blocks both Fas ligand- and LIGHT-induced pancreatic ß-cell damage in autoimmune diabetes. Heme oxygenase 1 (HO-1) possesses antiapoptotic, anti-inflammatory, and antioxidative effects that protect cells against various forms of attack by the immune system. Previously, we have demonstrated that transgenic islets overexpressing DcR3 or murine HO-1 (mHO-1) exhibit longer survival times than nontransgenic islets in syngeneic islet transplantation. In this study, we evaluated whether DcR3 and mHO-1 double-transgenic islets of NOD mice could provide better protective effects and achieve longer islet graft survival than DcR3 or mHO-1 single-transgenic islets after islet transplantation. We generated DcR3 and mHO-1 double-transgenic NOD mice that specifically overexpress DcR3 and HO-1 in islets. Seven hundred islets isolated from double-transgenic, single-transgenic, or nontransgenic NOD mice were syngeneically transplanted into the kidney capsules of newly diabetic female recipients. Unexpectedly, there was no significant difference in the survival time between double-transgenic or nontransgenic NOD islet grafts, and the survival times of double-transgenic NOD islet grafts were even shorter than those of DcR3 or mHO-1 single-transgenic islets. Our data indicate that transplantation of double-transgenic islets that coexpress HO-1 and DcR3 did not result in a better outcome. On the contrary, this strategy even caused an adverse effect in syngeneic islet transplantation.

Efficacy of double filtration plasmapheresis in removing xenoantibodies and prolonging xenograft survival in an ex vivo swine perfusion model.

INTRODUCTION: In xenotransplantation, antibodies mediate humoral rejection, resulting in organ dysfunction. Removal of xenoantibodies is likely a first step for successful transplantation. Double filtration plasmapheresis (DFPP) selectively removes large molecular weight pathogenic substances, such as immunoglobulins (Ig), without other plasma proteins. The antibodies fractions removed and the changes in blood biochemistry are unanswered questions after DFPP in addressed this ex vivo swine heart perfusion model. MATERIALS AND METHODS: Twelve swine hearts were perfused with human blood in a modified Langendorff's apparatus. The perfusate containing human blood was divided into 2 groups: controls (N = 6) and DFPP-treated group (N = 4). Blood counts, biochemistry data, and immunological profiles were compared at 3 time points: before and after DFPP and after heart perfusion. RESULT: Perfusion times of control and DFPP groups were 5.43 ± 1.81 vs 9.25 ± 3.00 hours, respectively. Only the values of albumin and total protein showed difference. The immunologic profile revealved complete removal of IgM and most IgG, IgA, C3, and C4, namely, 79.95%, 88.58%, 83.15%, and 87.97%, respectively. CONCLUSION: DFPP showed excellent efficacy to remove xenoantiboidies and prolong xenograft survival in an ex vivo perfusion model.

Prevalence of food allergy in Taiwan: a questionnaire-based survey.

AIM: Food allergy is common in children and adults, and could be potentially fatal in minor groups. It is important for physicians to identify the prevalence of food allergies and to recognise common food allergens to make precise diagnosis and choose correct therapeutic approaches. METHODS: We used a nationwide, cross-sectional, random questionnaire-based survey to estimate the self-reported and expert-screened prevalence of food allergies and to identify the common food allergens in Taiwan. In this study, the perceptional diagnosis of food allergies was screened by physicians according to descriptions of convincing symptoms and medical recordings; in the meantime, non-allergic adverse reactions to foods, including food intolerance or food avoidance, were clarified. RESULTS: A total of 30 018 individuals who met the inclusion criteria was evaluated, and 6.95% of them were diagnosed as victims of food allergies. The prevalence was 3.44% in children under 3 years of age, 7.65% in children aged 4-18 years and 6.40% in adults respectively. About 77.33% of the food allergy population had experienced recurrent allergic attacks. Systemic reactions happened about 4.89% in food allergies group. The most commonly reported food allergen in Taiwan is seafood, including shrimp, crab, fish and mollusc. In addition, mango, milk, peanuts and eggs were also important food allergens in the general population; while milk, shellfish, peanuts and eggs were common in children. CONCLUSIONS: Less than 10% of the Taiwan population suffers from food allergy with different allergic symptoms to variable food allergens in different age groups.

Carotid intima-media thickness in Chinese Type 2 diabetic subjects with or without microalbuminuria.

BACKGROUND: To examine the association of microalbuminuria (MAU) with the carotid intima-media thickness (CIMT) in Chinese Type 2 diabetic subjects. MATERIALS AND METHODS: Two hundred and thirty-nine patients (64±13 yr, 154 males) were divided into 2 groups: one with MAU (no.=119) or one without (no.=120). We recorded clinical and biochemical data as well as CIMT and ankle-brachial index (ABI). RESULTS: The patients with MAU had had diabetes mellitus (DM) longer, had higher blood pressure (BP). They also had lower estimated glomerular filtration rate (eGFR) and higher levels of circulating glucose, glycated hemoglobin, high sensitivity C-reactive protein than those without. Lower mean ABI was found in those with MAU, however, they did not have higher mean CIMT (0.72±0.15 vs 0.71±0.16 mm, p=0.525). In patients without MAU, CIMT correlated with age, DM duration, systolic BP, eGFR, albumin- to-creatinine ratio, and ABI. However, in those with MAU, CIMT correlated only with age and eGFR. Multivariate regression analysis revealed that mean CIMT correlated only with age for patients without MAU, but correlated with age and body mass index for those with MAU. Dividing the patients into 5 age groups, we found that the older the patient, the higher the mean CIMT with no group differences between those with and without MAU in both genders. However, patients with eGFR below 60 ml/min/1.73 m(2) had higher mean CIMT than those above (0.75±0.16 vs 0.69±0.14 mm, p=0.005). CONCLUSIONS: Type 2 diabetic patients with MAU were not associated with higher CIMT. Conversely, those with deterioration of renal function were more likely associated.

Factors predictive of breast cancer in open biopsy in cases with atypical ductal hyperplasia diagnosed by ultrasound-guided core needle biopsy.

AIMS: The purpose of the study was to explore factors predictive of breast cancer as diagnosed by excision biopsy in cases with a diagnosis of atypical ductal hyperplasia (ADH) on ultrasound-guided core needle biopsy (CNB). PATIENTS AND METHODS: We carried out diagnosis of breast lesions by ultrasound-guided CNB in a single hospital in Taiwan from November 2003 to October 2009. Patients who were diagnosed with ADH and subsequently underwent excision biopsy were included in this study (n = 124). RESULTS: Fifty-six of the 124 patients who were included (45.2%) had cancer, and the remaining 68 had benign lesions. By multivariate analysis of all clinical characteristics and on the basis of the imaging features in these cases, older patient age (≥50 y/o, OR: 3.910, p = 0.005), larger tumour size (≥15 mm, OR: 3.398, p = 0.013), and the presence of architectural distortion by mammography (OR: 10.7, p = 0.036) were found likely to be associated with breast cancer. CONCLUSIONS: Open biopsy is necessary in patients who were diagnosed with ADH on CNB. Older patients (≥50 y/o), with a larger tumour size (≥15 mm) and an abnormal mammography are especially likely to have breast cancer.

A progesterone-receptor-positive huge retroperitoneal tumour mimics metastasis in a breast cancer patient: sarcomatoid renal cell carcinoma.

We report a rare case of breast cancer concomitant with progesterone-receptor-positive renal cell carcinoma. A 48-year-old woman was diagnosed as having infiltrating ductal carcinoma of the breast and underwent modified radical mastectomy. A synchronous retroperitoneal tumour was detected by sonography of the abdomen in a routine cancer staging. Initially, the tumour was diagnosed as a synchronous retroperitoneal metastasis by needle biopsy; further tests revealed that it was progesterone receptor-positive. The retroperitoneal tumour showed poor response to full courses of adjuvant chemotherapy for breast cancer. Subsequently, the patient underwent a radical operation that included nephrectomy. The final pathology confirmed a sarcomatoid renal cell carcinoma. The post-operative course was uneventful. The patient had no recurrence at the 1-year follow-up. In this report, accurate diagnosis and adequate treatment were discussed. An intra-abdominal tumour with progesterone receptor- (PR) positive features is usually considered to be metastatic in breast cancer patients. For breast cancer patients with a PR-positive retroperitoneal tumour, renal cell carcinoma should be differentiated from a metastatic lesion of breast cancer, even if PR-expression is rare in renal cell carcinoma. To the best of our knowledge, this is the first case of PR-positive expression in breast cancer concomitant with renal carcinoma. In clinical settings, it is challenging for the surgeon to make an accurate diagnosis and to provide prompt treatment in such cases.

Influence of age on PPV of sonographic BI-RADS categories 3, 4, and 5.

PURPOSE: The purpose of this retrospective study was to calculate the positive predictive value (PPV) of sonographic Breast Imaging Reporting and Data System (BI-RADS) categories 3, 4, and 5 in different age groups to investigate whether age influences the PPV of the BI-RADS category in breast ultrasound. MATERIALS AND METHODS: From our sonography-guided core biopsy database of breasts between 2006 and 2008, we identified 2817 BI-RADS category 3, 4, and 5 lesions with known pathological diagnosis in 2587 women, all of whom underwent the earlier breast assessment via ultrasound with a sonographic BI-RADS lexicon and later sonography-guided core biopsy. All lesions were classified into three age groups (< 45, 45 - 59, and > 59 years). The age-related PPVs of each BI-RADS category among three age groups were calculated on the basis of pathological diagnoses and were compared using a χ(2)-test. RESULTS: The overall PPV of each BI-RADS category was 2.2 % in category 3, 6.5 % in category 4a, 35.2 % in category 4b, 79.6 % in category 4c, and 99.6 % in category 5. The age-related PPVs of category 3 varied significantly among the three age groups (0.9 % versus 3.9 % versus 2.0 % p = 0.048), and notably, the age-related PPV in group 2 was higher than the others. Additionally, there was a significant positive association between the age-related PPVs and increasing age in categories 4a and 4b (4a, p < 0.0001 and 4b, p = 0.0139), but not in categories 4c and 5 (4c, p = 0.1853 and 5, p = 0.2871). CONCLUSION: The incidence of female breast cancer differs not only in different sonographic BI-RADS categories, but also in different age groups. Therefore, more attention should be paid to the special age group that we found for sonographic BI-RADS categories 3, 4a, and 4b.

Diffraction-enhanced beam-focusing for X-rays in curved multi-plate crystal cavity.

Unusual x-ray focusing effect is reported for parabolic curved multi-plate x-ray crystal cavities of silicon consisting of compound refractive lenses (CRL). The transmitted beam of the (12 4 0) back reflection near 14.4388 keV from these monolithic silicon crystal devices exhibits extraordinary focusing enhancement, such that the focal length is reduced by as much as 18% for 2-beam and 56% for 24-beam diffraction from the curved crystal cavity. This effect is attributed to the presence of the involved Bragg diffractions, in which the wavevector of the transmitted beam is bent further when traversing several curved crystal surfaces.