Esophageal carcinoma cell line with high EGFR polysomy is responsive to gefitinib

Purpose

It has previously been shown that gefitinib-treated patients with epidermal growth factor receptor (EGFR) gene amplification or high polysomy had a statistically significant improvement in response, time to progression, and survival in non-small cell lung cancer (NSCLC). Only few studies utilizing anti-EGFR treatment in advanced esophageal adenocarcinomas have been performed and the results have been heterogeneous. The aim of this study was to evaluate EGFR-targeted therapy with gefitinib in esophageal adenocarcinoma with a high EGFR polysomy.

Methods

Novel esophageal cell lines PT6216 and LN6216c were established from primary tumor and lymph node metastasis of a patient with highly aggressive and metastatic adenocarcinoma. Pathological examination including tumor differentiation and prognostic marker analysis, immunohistochemical EGFR expression analysis, EGFR fluorescence in situ hybridization, and mutation analysis were performed. Response of novel cell lines to gefitinib treatment was evaluated by cell proliferation and vitality assays. Fifty-four esophageal adenocarcinoma specimens were evaluated for EGFR gene copy gain.

Results

The primary tumor cell line PT6216 and the lymph node cell line LN6216c show a homogenously high polysomy for EGFR determined by FISH analysis. Cell proliferation and vitality are highly sensitive to the tyrosine kinase inhibitor gefitinib compared to esophageal control cells without a high polysomy for EGFR. High polysomy for EGFR was found in 35 % of patients.

Conclusion

We show for the first time a significant treatment response to the EGFR tyrosine kinase inhibitor gefitinib in esophageal tumor cells with a high polysomy for EGFR, suggesting a future role of anti-EGFR therapy for esophageal adenocarcinoma patients with a high EGFR polysomy.     

Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy

Background

The primary abnormal manifestation in immunoglobulin A nephropathy (IgAN) is recurring bouts of hematuria with or without proteinuria. Although immunohistochemical analysis of renal biopsy tissue remains the gold standard not only for diagnosis but also for evaluating the activity of IgAN, new sensitive and reasonably specific noninvasive tests are emerging to guide therapeutic strategy applicable to all stages of IgAN. The present study examined serum levels of galactose-deficient IgA1 (Gd-IgA1) and its immune complex (IgA/IgG-IC) as noninvasive markers for the disease activity.

Methods

We enrolled 50 IgAN patients (male 40 %, median age 37 years) showing complete or partial clinical remission after steroid pulse therapy with tonsillectomy (TSP) whose clinical data and serum could be followed up for 3–5 years.

Results

Cross-sectional analysis revealed that the degree of hematuria and proteinuria were significantly associated with levels of Gd-IgA1 and levels of IgA/IgG-IC. Longitudinal analysis further showed that from the group of 44 patients with heavy hematuria before TSP, 31 patients showed complete disappearance of hematuria (group A), but the remaining patients did not (group B). Although the levels of Gd-IgA1 and IgA/IgG-IC in the two groups before TSP were similar, percentage decrease of Gd-IgA1 and IgA/IgG-IC levels in group A was significantly higher than in group B.

Conclusion

Disease activity of IgAN assessed by hematuria and proteinuria correlated with serum levels and changes of Gd-IgA1 and IgA/IgG-IC. These new noninvasive disease activity markers can be useful for future activity scoring system and guiding therapeutic approaches.     

Toll-like receptors,immunoproteasome and regulatory T cells in children with Henoch–Schönlein purpura and primary IgA nephropathy

Background

Henoch–Schönlein purpura (HSP) nephritis and primary IgA nephropathy (pIgAN) present with glomerular IgA deposits, but differ with regard to clinical features. The suspected involvement of different immune system pathways is largely unknown.

Methods

This study was aimed at investigating some of the immunological features including Toll-like receptors (TLR), proteasome (PS)/immunoproteasome (iPS) switch, and the regulatory T cell system (Treg/Th17 cells) in 63 children with HSP with/without renal involvement and in 25 with pIgAN. Real-time PRC (Taqman) was used to quantify mRNA levels in peripheral blood mononuclear cells (PBMC).

Results

The expression of mRNAs encoding for TLR4 in both HSP and pIgAN was higher than in controls (HC) and in both diseases FoxP3mRNA and TGF-β1mRNA expression was significantly lower than in HC. A switch from PS to iPS (LMP2/β1) was detected only in PBMC of HSP and it correlated with the level of TLR2mRNA, which was selectively increased only in children with HSP.

Conclusion

Children with HSP and pIgAN present with similar signs of engagement of the innate immunity and regulatory T cell depression. The increased immunoproteasome switch, which correlated with TLR2 activation, may suggest an innate immunity pathway peculiar to HSP vasculitic presentation. This research area also deserves further investigation for possible therapeutic applications.     

Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK,AKT and NF-kappa B pathways in murine RAW264.7 cells

The bone protective effects of the hydrogen molecule (H₂) have been demonstrated in several osteoporosis models while the underlying molecular mechanism has remained unclear. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. In this work, we evaluated the effects of incubation with H₂ on receptor activator of NFκB ligand (RANKL)-induced osteoclast differentiation. We found that treatment with H₂ prevented RANKL-induced osteoclast differentiation in RAW264.7 cells and BMMs. Treatment with H₂ inhibits the ability to form resorption pits of BMMs stimulated by RANKL. Treatment with H₂ reduced mRNA levels of osteoclast-specific markers including tartrate resistant acid phosphatase, calcitonin receptor, cathepsin K, metalloproteinase-9, carbonic anhydrase typeII, and vacuolar-type H⁺-ATPase. Treatment with H₂ decreased intracellular reactive oxygen species (ROS) formation, suppressed NADPH oxidase activity, down-regulated Rac1 activity and Nox1 expression, reduced mitochondrial ROS formation, and enhanced nuclear factor E2-related factor 2 nuclear translocation and heme oxygenase-1 activity. In addition, treatment with H₂ suppressed RANKL-induced expression of nuclear factor of activated T cells c1 and c-Fos. Furthermore, treatment with H₂ suppressed NF-κB activation and reduced phosphorylation of p38, extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and protein kinases B (AKT) stimulated with RANKL. In conclusion, hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-κB, mitogen-activated protein kinase and AKT pathways.     

Development of a novel marking system for laparoscopic gastrectomy using endoclips with radio frequency identification tags: feasibility study in a canine model

Background

Intraoperative identification of early gastric cancer is difficult to conduct during laparoscopic procedures. In this study, we investigated the feasibility and accuracy of a newly developed marking system using endoclips with radio frequency identification (RFID) tags in a canine model.

Methods

RFID is a wireless near field communication technology. Among the open frequency bands available for medical use, 13.56 MHz is suitable for a surgical marking system because of the similar and linear signal decay both in air and in biological tissues. The proposed system consists of four parts: (a) endoclips with RFID tags, (b) endoclip applier equipment, (c) laparoscopic locating probe, and (d) signal processing units with audio interface. In the experimental setting using canine models, RFID-tagged endoclips were applied to the mucosa of each dog’s stomach. During the subsequent operation, the clips with RFID tags placed in five dogs were located by the detection of the RFID signal from the tag (RFID group), and the conventional clips in the other six dogs were located by finger palpation (FP group). The detected sites were marked by ablation on the serosal surface. Distance between the clips and the metal pin needles indicating ablated sites were measured with X-ray radiographs of the resected specimen.

Results

All clips were successfully detected by the marking system in the RFID group (10/10) and by finger palpation in the FP group (17/17). The medians of detection times were 31.5 and 25.0 s, respectively; the distances were 5.63 and 7.62 mm, respectively. The differences were not statistically significant. No adverse event related to the procedures was observed.

Conclusions

Endoclips with RFID tags were located by our novel marking system in an experimental laparoscopic setting using canine stomachs with substantial accuracy comparable to conventional endoclips located by finger palpation through an open approach.     

Mechanisms of graft versus host disease produced by small bowel transplantation

Mechanisms of graft versus host disease have been studied in Lew x BN animals transplanted with a Lew small bowel. Grafted mesenteric lymph nodes but not host mesenteric lymph nodes or host spleen, in small bowel transplanted rats undergoing lethal GVHD, provide a source of CTL with specific anti-recipient cytotoxic activity. Host MLN and host spleen display anti-recipient CTL activity only when GVHD is provoked by intraperitoneal lymphocyte injection. These data demonstrate that lethal GVHD after SBTx may occur in the absence of detectable cytotoxic activity in host lymphoid tissues, suggesting that other mechanisms are involved in the pathogenesis of GVHD after SBTx. GVHD after SBTx or lymphocyte transfer is associated with the appearance of TNF in the serum. The intensity and reversibility of this phenomenon correlate with both the clinical severity and the lethality of GVHD. Taken together these data highly suggest that TNF is directly involved in the pathogenesis of GVHD after SBTx.     

Chemosensitivity Predicted by BluePrint 80-Gene Functional Subtype and MammaPrint in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST)

Purpose

The purpose of the NBRST study is to compare a multigene classifier to conventional immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) subtyping to predict chemosensitivity as defined by pathological complete response (pCR) or endocrine sensitivity as defined by partial response.

Methods

The study includes women with histologically proven breast cancer, who will receive neoadjuvant chemotherapy (NCT) or neoadjuvant endocrine therapy. BluePrint in combination with MammaPrint classifies patients into four molecular subgroups: Luminal A, Luminal B, HER2, and Basal.

Results

A total of 426 patients had definitive surgery. Thirty-seven of 211 (18 %) IHC/FISH hormone receptor (HR)+/HER2? patients were reclassified by Blueprint as Basal (n = 35) or HER2 (n = 2). Fifty-three of 123 (43 %) IHC/FISH HER2+ patients were reclassified as Luminal (n = 36) or Basal (n = 17). Four of 92 (4 %) IHC/FISH triple-negative (TN) patients were reclassified as Luminal (n = 2) or HER2 (n = 2). NCT pCR rates were 2 % in Luminal A and 7 % Luminal B patients versus 10 % pCR in IHC/FISH HR+/HER2? patients. The NCT pCR rate was 53 % in BluePrint HER2 patients. This is significantly superior (p = 0.047) to the pCR rate in IHC/FISH HER2+ patients (38 %). The pCR rate of 36 of 75 IHC/FISH HER2+/HR+ patients reclassified as BPLuminal is 3 %. NCT pCR for BluePrint Basal patients was 49 of 140 (35 %), comparable to the 34 of 92 pCR rate (37 %) in IHC/FISH TN patients.

Conclusions

BluePrint molecular subtyping reclassifies 22 % (94/426) of tumors, reassigning more responsive patients to the HER2 and Basal categories while reassigning less responsive patients to the Luminal category. These findings suggest that compared with IHC/FISH, BluePrint more accurately identifies patients likely to respond (or not respond) to NCT.     

Transcystic or Transductal Stone Extraction during Single-Stage Treatment of Choledochocystolithiasis: A Systematic Review

Background

Choledochocystolithiasis can be managed by endoscopic retrograde cholangiopancreaticography (ERCP) or laparoscopically by transcystic (TC) or transductal (TD) stone extraction.

Objective

The aim of this study was to systematically review safety and effectiveness of combined endoscopic/laparoscopic management versus total laparoscopic management for choledochocystolithiasis with specific emphasis on TC versus TD stone extraction.

Methods

MEDLINE/PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched systematically to identify trials on combined endoscopic/laparoscopic and total laparoscopic management for choledochocystolithiasis. Laparoscopic common bile duct (CBD) exploration was divided into TD and TC approach. Primary outcomes were successful stone clearance from CBD, postoperative/procedural morbidity, and mortality.

Results

Eight randomized trials with 965 patients were included. Successful bile duct clearance varied between 52.6 and 97 % in the ERCP groups, 80.4 and 100 % in the TC groups, and 58.3 and 100 % in the TD groups. There were more bile leaks after TD stone extraction (11 %) than after ERCP (1 %) and TC stone extraction (1.7 %). Total morbidity varied between 9.1 and 38.3 % in the ERCP groups, 7 and 10.5 % in the TC groups, and 18.4 and 26.7 % in the TD groups. Methodological and statistical heterogeneity among the trials precluded a meaningful meta-analysis.

Conclusion

Stone clearance rates are comparable between the three modalities, but TD stone extraction is associated with a higher risk of bile leaks and should only be performed by highly experienced surgeons. TC stone extraction seems a more accessible technique with lower complication rates. If unsuccessful, per- or postoperative endoscopic stone extraction is a viable option.     

Neurocognition in children with autosomal recessive polycystic kidney disease in the CKiD cohort study

Background

Autosomal recessive polycystic kidney disease (ARPKD) is an inherited disorder characterized by enlarged, cystic kidneys with progressive chronic kidney disease (CKD), systemic hypertension, and congenital hepatic fibrosis. Children with ARPKD can have early onset CKD and severe hypertension, both of which are known to have adverse neurocognitive effects. The objectives of this study were (1) to determine whether ARPKD patients have greater neurocognitive deficits compared to that of children with other causes of CKD, and (2) to examine the relative prevalence of hypertension in ARPKD, a known risk factor for neurocognitive dysfunction.

Methods

We performed a cross-sectional, control-matched analysis of 22 ARPKD patients with mild-to-moderate CKD in the Chronic Kidney Disease in Children (CKiD) cohort study, compared with a control group of 44 children with other causes of CKD, matched based on glomerular filtration rate, age at study entry, and age at diagnosis.

Results

Children with ARPKD in this cohort had neurocognitive functioning comparable to children with other causes of CKD in domains of intellectual functioning, academic achievement, attention regulation, executive functioning, and behavior. Blood pressure parameters were similar between the two groups; however, ARPKD patients required a significantly greater number of antihypertensive medications to achieve similar BP levels.

Conclusions

ARPKD patients are potentially at risk for neurocognitive dysfunction due to early onset CKD and more severe hypertension. However, this study of children with mild-to-moderate CKD in the CKiD cohort did not demonstrate increased risk in children with ARPKD compared to children with other causes of CKD. Further studies are needed to determine if these findings are applicable to children with more severe manifestations of ARPKD.     

Collagen type III alpha 1 polymorphism (rs1800255, COL3A1 2209 G>A) assessed with high-resolution melting analysis is not associated with pelvic organ prolapse in the Dutch population

Introduction and hypothesis

The rs1800255, COL3A1 2209 G>A polymorphism in the alpha 1 chain of collagen type III has been associated with an increased risk of pelvic organ prolapse (POP). In one of our previous studies however, polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) misdiagnosed rs1800255, COL3A1 2209 G>A in 6 % of cases. The high-resolution melting (HRM) analysis on the contrary obtained a 100 % accordance for this specific polymorphism and was used in the present study to validate this risk factor for POP.

Methods

In this case–control study, women with and without symptoms of POP were included and compared. DNA was extracted from blood samples. HRM analysis was used to assess for the presence of the homozygous rs1800255. Groups were compared using the Pearson chi-square, Mann–Whitney, and t tests. The discrepancy between HRM and PCR-RFLP results was investigated using PCR-RFLP results available from our previous study.

Results

The study included 354 women: 272 patients with POP and 82 controls; 18 (7 %) cases versus 3 (4 %) controls had a homozygous rs1800255, COL3A1 2209 G>A polymorphism (odds ratio 1.9, 95 % confidence interval 0.5–6.9, compared to the wild type), and thus no association between POP and the homozygous polymorphism could be demonstrated. A discrepancy between HRM and PCR-RFLP results was found in 8 % of the samples.

Conclusions

The previously found statistically significant association between the rs1800255, COL3A1 2209 G>A polymorphism as measured with PCR-RFLP and POP could no longer be demonstrated. This raises concerns regarding the results of other association studies using PCR-RFLP.     

Comparison of Nodal Metastasis Between BRCA Mutation Carriers and Non-BRCA Mutation Carriers with Breast Cancer

Objective

This study evaluates whether nodal status differs between breast cancer patients with BRCA mutations and those confirmed not to harbor mutations.

Methods

A prospective database identified patients with breast cancer who underwent genetic testing and axillary staging. Comparative variables included age, as well as tumor characteristics such as size, grade, lymphovascular invasion (LVI), estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2-neu), and nodal status.

Results

Overall, 235 patients with breast cancer underwent genetic testing for BRCA mutations from June 2000 to May 2012. Of these patients, 74 (31.4 %) were found to express BRCA 1 and/or 2 mutations, and 161 (68.5 %) patients were verified to have no detectable BRCA mutation. Among the entire 235 patients tested, 92 (39.1 %) were found to have nodal disease. In univariable analysis, only LVI and tumor size correlated with presence of nodal metastasis. Of the 74 BRCA mutation carriers, 34 (45.9 %) had nodal metastasis compared with 58 of the 161 (36 %; p = 0.15) patients without a BRCA mutation. BRCA mutation carriers with nodal disease were more likely to have poorly differentiated tumors than those without mutations who had nodal disease (24/33 [72.7 %] vs. 27/57 [47.4 %]; p = 0.027).

Conclusion

BRCA mutations are not themselves predictive of nodal metastasis. Patients with BRCA mutations did not have a statistically significant higher prevalence of nodal metastasis than those without mutations.     

The effects of fatigue on robotic surgical skill training in Urology residents

This study reports on the effect of fatigue on Urology residents using the daVinci surgical skills simulator (dVSS). Seven Urology residents performed a series of selected exercises on the dVSS while pre-call and post-call. Prior to dVSS performance a survey of subjective fatigue was taken and residents were tested with the Epworth Sleepiness Scale (ESS). Using the metrics available in the dVSS software, the performance of each resident was evaluated. The Urology residents slept an average of 4.07 h (range 2.5–6 h) while on call compared to an average of 5.43 h while not on call (range 3–7 h, p = 0.08). Post-call residents were significantly more likely to be identified as fatigued by the Epworth Sleepiness Score than pre-call residents (p = 0.01). Significant differences were observed in fatigued residents performing the exercises, Tubes and Match Board 2 (p = 0.05, 0.02). Additionally, there were significant differences in the total number of critical errors during the training session (9.29 vs. 3.14, p = 0.04). Fatigue in post-call Urology residents leads to poorer performance on the dVSS simulator. The dVSS may become a useful instrument in the education of fatigued residents and a tool to identify fatigue in trainees.     

Correlation study of chronic nonbacterial prostatitis with the levels of COX-2 and PGE2 in prostatic secretion

Objective

The prostatitis syndrome is a multifactorial condition of largely unknown etiology. This study is to analyze the relationship between cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) with the chronic nonbacterial prostatitis (CNBP).

Methods

A total of 172 CNBP patients and 151 healthy males were recruited as CNBP and control group, respectively. The prostatic fluid was collected and tested by pre- and post-massage test. White blood cell (WBC) number was counted, and the contents of COX-2 and PGE2 were determined by double antibody-based sandwich enzyme-linked immuno-sorbent assay. The pain and discomfort of each patient were scored according to the National Institutes of Health chronic prostatitis symptom index.

Results

Compared with the control group, CNBP group displayed significantly higher WBC count, COX-2 level, and PGE2 level. Contents of COX-2 and PGE2 in prostatic secretion of CNBP group were positively correlated with pain scores (r = 0.855 and 0.675, respectively, P < 0.01) and total symptom scores (r = 0.674 and 0.566, respectively, P < 0.01). A significantly positive correlation between COX-2 and PGE2 levels was also discovered (r = 0.493, P < 0.05). The WBC number was not obviously correlated with the accumulations of COX-2 and PGE2 or the clinic symptoms of CNBP.

Conclusion

Increase in PGE2 concentration caused by activated COX-2 pathway may contribute to the pain or discomfort symptom of the CNBP patients. Our results indicate that selective COX-2 inhibitors have application prospect in CNBP treatment.     

Expression and regulation of toll-like receptors (TLRs) in human intervertebral disc cells

Purpose

Although inflammatory processes play an essential role in painful intervertebral disc (IVD) degeneration, the underlying regulatory mechanisms are not well understood. This study was designed to investigate the expression, regulation and importance of specific toll-like receptors (TLRs)—which have been shown to play an essential role e.g. in osteoarthritis—during degenerative disc disease.

Methods

The expression of TLRs in human IVDs was measured in isolated cells as well as in normal or degenerated IVD tissue. The role of IL-1β or TNF-α in regulating TLRs (expression/activation) as well as in regulating activity of down-stream pathways (NF-κB) and expression of inflammation-related genes (IL-6, IL-8, HSP60, HSP70, HMGB1) was analyzed.

Results

Expression of TLR1/2/3/4/5/6/9/10 was detected in isolated human IVD cells, with TLR1/2/4/6 being dependent on the degree of IVD degeneration. Stimulation with IL-1β or TNF-α moderately increased TLR1/TLR4 mRNA expression (TNF-α only), and strongly increased TLR2 mRNA expression (IL-1β/TNF-α), with the latter being confirmed on the protein level. Stimulation with IL-1β, TNF-α or Pam3CSK4 (a TLR2-ligand) stimulated IL-6 and IL-8, which was inhibited by a TLR2 neutralizing antibody for Pam3CSK4; IL-1β and TNF-α caused NF-κB activation. HSP60, HSP70 and HMGB1 did not increase IL-6 or IL-8 and were not regulated by IL-1β/TNF-α.

Conclusion

We provide evidence that several TLRs are expressed in human IVD cells, with TLR2 possibly playing the most crucial role. As TLRs mediate catabolic and inflammatory processes, increased levels of TLRs may lead to aggravated disc degeneration, chronic inflammation and pain development. Especially with the identification of more endogenous TLR ligands, targeting these receptors may hold therapeutic promise.     

Characterization and Treatment of Local Recurrence Following Breast Conservation for Ductal Carcinoma In Situ

Purpose

The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences.

Methods

We conducted a retrospective cohort study using two data sources of patients who experienced a recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS) for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88) and patients with an index DCIS diagnosed from 1990 to 2001 at community-based integrated healthcare delivery sites of the Health Maintenance Organization Cancer Research Network (CRN) (N = 182).

Results

Just under half of local recurrences in both cohorts were invasive cancer. While 40 % of patients in both cohorts underwent mastectomy alone at recurrence, treatment of the remaining patients varied. In the earlier CRN cohort, most other patients underwent repeat BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only 16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN cohort. Compared with patients not treated with radiation, those who received radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37 %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17; CRN: 40 vs. 25 %, p = 0.09).

Conclusion

We found that treatment of recurrences after BCS and subsequent complications may be affected by the use of radiotherapy for the index DCIS. Initial treatment of DCIS may have long-term implications that should be considered.     

Dynamic regulation and dysregulation of the water channel aquaporin-2: a common cause of and promising therapeutic target for water balance disorders

The human body is two-thirds water. The ability of ensuring the proper amount of water inside the body is essential for the survival of mammals. The key event for maintenance of body water balance is water reabsorption in the kidney collecting ducts, which is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and never allows permeation of ions or other small molecules. Under normal conditions, AQP2 is restricted within the cytoplasm of the collecting duct cells. However, when the body is dehydrated and needs to retain water, AQP2 relocates to the apical membrane, allowing water reabsorption from the urinary tubule into the cell. Its impairments result in various water balance disorders including diabetes insipidus, which is a disease characterized by a massive loss of water through the kidney, leading to severe dehydration in the body. Dysregulation of AQP2 is also a common cause of water retention and hyponatremia that exacerbate the prognosis of congestive heart failure and hepatic cirrhosis. Many studies have uncovered the regulation mechanisms of AQP2 at the single-molecule level, the whole-body level, and the clinical level. In clinical practice, urinary AQP2 is a useful marker for body water balance (hydration status). Moreover, AQP2 is now attracting considerable attention as a potential therapeutic target for water balance disorders which commonly occur in many diseases.     

Association between non-alcoholic fatty liver disease and chronic kidney disease in population with prediabetes or diabetes

Purpose

The relationship between chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in population with diabetes remains controversial. Our current study aimed to explore the association between NAFLD and CKD in population with prediabetes or diabetes.

Methods

A cross-sectional study was conducted in Zhuhai city from June to October 2012. A total of 190 out of 334 participants with prediabetes or diabetes were enrolled in this study. CKD was defined as estimated GFR <60 ml/min per 1.73 m² and/or albumin-to-creatinine ratio ≥30 mg/g. NAFLD was diagnosed on the basis of ultrasonographic and excluded fatty liver disease caused by other reasons such as drinking. The association between NAFLD and CKD was then analyzed using SPSS (version 19.0).

Results

Subjects with NAFLD were more likely with a higher urinary albumin-to-creatinine ratio (P < 0.001). CKD were common among patients with NAFLD than those without NAFLD (P < 0.05). NAFLD was significantly associated with CKD (P < 0.05) in the unadjusted analyses as well as after adjustment for potential confounders. The unadjusted odd ratio and adjusted odd ratio for CKD were 2.25 (95 % CI 1.07–4.77, P = 0.034) and 2.68 (95 % CI 1.12–6.01, P = 0.016). When further adjusted for hypertension, serum high-density lipoprotein and serum fasting glucose, the association of NAFLD with CKD was still significant (OR 2.78, 95 % CI 1.03–7.52, P = 0.044).

Conclusions

Our current study suggests that ultrasound-diagnosed NAFLD is associated with CKD among population with prediabetes or diabetes.     

Resistance exercise: a strategy to attenuate inflammation and protein-energy wasting in hemodialysis patients?

Purpose

Patients undergoing hemodialysis (HD) present persistent inflammation and protein-energy wasting (PEW), which contributes to high rates of mortality. This study aimed to assess the effects of a resistance exercise training program (RETP) on inflammation and PEW in HD patients.

Methods

Thirty-seven patients (56.7 % men, 45.9 ± 14.1 years, 23.5 ± 3.9 kg/m²) performed 6 months of intradialytic RETP. Plasma adhesion molecules levels (ICAM-1 and VCAM-1) were measured using the enzyme immunometric assay, and interleukin-6 (IL-6), C-reactive protein, and tumor necrosis factor-alpha by ELISA. Anthropometric, physical capacity, and PEW (simultaneously presence of: BMI <23 kg/m², serum albumin <3.8 g/dL, and reduced arm muscle area) were analyzed.

Results

There was a reduction of ICAM-1 [(1,934.1 pg/mL (1,031.8–2,875.0) vs. 1,571.1 pg/mL (447.1–2,985.5), p < 0.05], VCAM-1 [5,259.51 pg/mL (3,967.4–6,682.4) vs. 3,062.11 pg/mL (2,034.0–5,034.4), p < 0.05], and CRP levels (2.3 ± 0.9 to 1.6 ± 0.6 pg/mL, p < 0.001) after 6 months of RETP. Body composition improved, albumin increased (3.7 ± 0.3 to 3.9 ± 0.2, p < 0.05), and the number of patients presenting PEW was decreased (p = 0.005).

Conclusions

Resistance exercise program for 6 months seems to be effective in reducing inflammation and PEW of HD patients. The universal trial number of this study is U1111-1139-1326.     

Locoregional Recurrence and Survival Outcomes by Type of Local Therapy and Trastuzumab Use Among Women with Node-Negative,HER2-Positive Breast Cancer

Background

While human epidermal growth factor receptor 2 (HER2) overexpression is an adverse breast cancer prognostic factor, it is unclear whether there are differences in outcomes between types of local treatment in this population. This retrospective study examined locoregional recurrence and survival in women with node-negative, HER2+ breast cancer treated with breast-conserving therapy (BCT) versus mastectomy.

Methods

Subjects were 748 patients with pT1–2, N0, M0 HER2+ breast cancer, treated with BCT (n = 422) or mastectomy (n = 326). Trastuzumab was used in 54 % of subjects. The 5-year Kaplan–Meier locoregional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), and overall survival (OS) were compared between cohorts treated with BCT versus mastectomy. Subgroup analyses of LRR and survival were performed separately among patients treated with BCT or mastectomy to examine the effect of trastuzumab on outcomes in each group.

Results

Median follow-up was 4.4 years. Patients treated with mastectomy had higher proportions of grade 3 histology (69 vs 60 %, p = 0.004) and lower rates of hormone therapy (51 vs 64 %, p < 0.001) and trastuzumab therapy (50 vs 57 %, p = 0.04). The 5-year outcomes in women treated with BCT compared with mastectomy were: LRRFS 98.0 versus 98.3 % (p = 0.88), BCSS 97.2 versus 96.1 % (p = 0.70), and OS 95.5 versus 93.4 % (p = 0.19). Trastuzumab was associated with similar LRRFS and improved OS in both local treatment groups.

Conclusions

BCT is safe in the population of women with pT1–2, N0, HER2+ breast cancer, providing high rates of locoregional control and survival equivalent to mastectomy. Trastuzumab was associated with improved survival in both groups.