Search

Chronic kidney disease (CKD) is a global public health problem accompanied by substantial comorbidities and reduced life expectancy. In this respect, progressive CKD leading to uraemia can be seen as a systemic disease with a critical impact on virtually all organ systems. Therefore, it is of particular importance to identify patients with ongoing CKD progression, which is challenging, because the individual course of CKD is difficult to predict. Patterns of progression in CKD patients include linear and non-linear trajectories of GFR loss, but kidney function can also remain stable for years. Moreover, a substantial GFR decline may occur in the absence of higher-grade albuminuria (non-proteinuric CKD), rendering the measurement of albuminuria less reliable for progression prediction in such individuals. In the present review, we focus on the recently identified glycoprotein Dickkopf-3 (DKK3) as a stress-induced, renal tubular epithelial cell-derived, pro-fibrotic molecule. In experimental CKD models, DKK3 promoted renal tubulointerstitial fibrosis through modulation of the canonical Wnt/β-catenin signalling pathway. In clinical studies, increased urinary DKK3 levels identified patients at high risk for short-term CKD progression, regardless of the cause of kidney disease, baseline kidney function and albuminuria. Moreover, increased urinary DKK3 levels are associated with a high risk for acute kidney injury and the subsequent loss of kidney function after cardiac surgery. These findings highlight DKK3 as a mediator of renal tubular cell damage in kidney injury and short-term progression of kidney disease, with potential therapeutic implications.

In anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) genetic predisposition, ANCA autoantibodies, neutrophil extracellular traps (NETs), complement activation, and toll-like receptor signaling are implicated in AAV pathogenesis. Heat shock proteins (HSPs), a highly conserved group of small-sized molecular chaperones, take part in protein folding during cellular stress. Although HSPs were initially observed intracellularly, it has been shown that they can be secreted in the extracellular space and modulate the immune response in various autoimmune diseases including AAV. The scope of the present study is to investigate the role of heat shock protein 60 (HSP60) and 70 (HSP70) in the long renal effects in an ANCA vasculitis cohort. In this cohort of ANCA-associated vasculitis, 29 patients were followed up over 20 years. At diagnosis, immunohistochemistry was performed for HSP60 and HSP70 within the various nephron compartments. Higher renal HSP60 expression was associated with increased interstitial inflammatory infiltrates at diagnosis, while HSP70 expression was associated with a greater extent of interstitial fibrosis at diagnosis. Notably, intense tissue expression of HSP70 at the time of biopsy was associated with a worsened kidney survival. Renal HSP70 expression was associated with poor renal outcomes during long-term follow-up. This finding may indicate a role of HSPs in renal disease progression in ANCA vasculitis. Further validating studies are needed to verify a causative association between HSP70 expression and renal outcomes in ANCA-associated vasculitis.

Background and Aims Heat shock proteins(HSP) present an evolving role in immune response. ANCA associated vasculitis(AAV) is often associated with kidney injury and progression to chronic kidney disease(CKD) Method Twenty nine patients with biopsy proven renal AAV were followed(1995-2015). Study end point was renal death. Renal tissue at diagnosis was stained with monoclonal antibodies against HSP60 and HSP70. Interstitial inflammatory cells and interstitial fibrosis graded were evaluated as mild(0-50%) or severe(≥50%). Healthy renal tissue served as control. Survival analysis(Kaplan-Meier), Fisher’s exact test, or Test Chi-Square and bivariate analysis were performed. Statistical significance was set at Results Mean age and mean eGFR at baseline was 57,8±19.2 years and 24,47 ml/min/1,73m2 BSA respectively. Interstitial inflammatory infiltrates were present in most patients. Interstitial fibrosis was present in 10,3% of patients. Control biopsies showed a weak HSP expression. AAV-patients presented significantly higher HSP expression within crescents, proximal tubule, distal tubule and renal interstitium. Renal fibrosis associated with intense interstitial HSP70 expression(Pearson´s-R=0.521 p=0,004). Interstitial inflammatory infiltrates associated with increased distal tubular HSP60 expression(Pearson´s-R=0.672 p Conclusion Interstitial HSP70 overexpression is associated with worse renal outcomes in renal AAV. To our knowledge this is the first study that shows an association of renal heat shock protein expression and renal outcomes in an AAV cohort.

Frailty in a surgical geriatric population may identify patients at increased risk of complications. However, the optimal method to diagnose it remains to be identified. This study aims to compare two common frailty models and assess their association with postoperative adverse outcomes in elderly patients undergoing general surgical procedures.Prospective study including 298 patients age 65 years or older undergoing elective general surgical operations in a tertiary hospital. Frailty phenotype (FP) was classified using a validated scale which included weight loss, weakness, exhaustion, slowed walking speed and low physical activity. A preoperative comprehensive geriatric assessment (CGA) was performed including managing daily activities (ADL), instrumental ADL, cognitive status, comorbidities, polypharmacy and nutritional status. Main outcomes measures were postoperative complications and length of stay.There were 135 (46%), 114 (38%) and 46 (15%) minor/intermediate, major and major + procedures, respectively. The agreement between the FP and CGA was moderate (kappa index: 0.45). FP was significantly associated with postoperative complications with an odds ratio (OR) of 2.3, (95% confidence interval 1.4-3.8, p 0.01). The association of CGA with postoperative complications did not reach statistical significance (p = 0.07). Postoperative hospital stay was significantly longer in both CGA frailty (p 0.001) and FP (p = 0.001) groups compared to the fit population. In the multivariate analysis adjusted for ASA and POSSUM category, FP retained its significance as a predictor of postoperative complications (OR: 1.9, 95% CI 1.03-3.3, p = 0.038).FP was associated more consistently than CGA with adverse postoperative outcomes in elderly patients undergoing general surgical procedures.

Background The individual course of CKD may vary, and improved methods for identifying which patients will experience short-term eGFR loss are needed. Assessing urinary Dickkopf-3 (DKK3), a stress-induced tubular epithelia–derived profibrotic glycoprotein, may provide information about ongoing tubulointerstitial fibrosis and short-term eGFR loss. Methods To investigate urinary DKK3’s potential as a biomarker of short-term eGFR loss (over 12 months), we prospectively assessed eGFR and urinary DKK3 levels in patients with CKD of various etiologies at baseline and annual follow-ups. We also measured urinary DKK3 in a general population sample and patients with diagnostic kidney biopsies or IgA nephropathy under treatment. Results Median urinary DKK3-to-creatinine concentration at baseline was significantly higher in patients with CKD than the general population sample (431 versus 33 pg/mg). In the CKD cohort, having a urinary DKK3-to-creatinine level >4000 pg/mg was independently and significantly associated after multiple adjustments with mean annual decline in eGFR of 7.6% over 12 months. Urinary DKK3 significantly improved prediction of kidney function decline compared with eGFR or albuminuria alone. Urinary DKK3-to-creatinine levels were related to the extent of tubulointerstitial fibrosis in kidney biopsies. In patients with IgA nephropathy, a rise in urinary DKK3 was associated with significant eGFR decline within 6 months, whereas stable or decreasing urinary DKK3 indicated a more favorable course. Conclusions Urinary DKK3 levels identify patients at high risk for eGFR decline over the next 12 months regardless of the cause of kidney injury and beyond established biomarkers, potentially providing a tool to monitor CKD progression and assess effects of interventions.

Background: Podocyte injury plays a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). We investigated whether patients with diabetes mellitus (DM) without overt DN present podocyte markers in urine suggestive of early podocyte injury. Methods: We studied 71 patients with DM type 2 and normal urine albumin excretion (UAE) and 39 non-diabetic controls. The mRNA abundance of 3 podocyte-specific markers in urinary sediment (nephrin, podocin and synaptopodin) was measured with real-time quantitative PCR. All the subjects were categorized according to their urinary podocyte marker profile into 2 groups, those with only synaptopodin mRNA presence (synaptopodin only group) and those with nephrin and/or podocin mRNA presence in addition to synaptopodin in their urine (nephrin and/or podocin group). Results: Synaptopodin mRNA was detected in the urine of all the diabetics and controls. The presence of nephrin and/or podocin mRNA in urine was more frequent among DM patients compared to controls (53.5 vs. 30.8%, respectively; p = 0.022). Binary logistic regression analysis revealed that the only significant predictor of the presence of nephrin and/or podocin mRNA in urine was the presence of DM (OR 2.59, 95% CI 1.14-5.91, p = 0.024, adjusted for all risk factors). A strong correlation between nephrin and podocin urinary mRNA levels was noted (r = +0.796, p < 0.001). Conclusion: This study demonstrated that urinary podocyte markers are more prevalent in diabetic patients with normal UAE compared to controls, and this may reflect early podocyte injury. DM is the only significant determinant of the presence of nephrin and/or podocin mRNA in urine in this population. Therefore, urinary podocyte markers may emerge as a valuable tool in the early diagnosis of DN.

Residual Renal function (RRF) has an important role in the overall morbidity and mortality in hemodialysis patients. The role of angiotensin-converting enzyme inhibitor (ACEi) in preserving renal function in chronic proteinuric nephropathies is well documented. We test the hypothesis that enalapril (an ACEi) slows the rate of decline of RRF in patients starting hemodialysis. A prospective, randomized open-label study was carried out. 42 patients were randomized in two groups either in treatment with enalapril or no treatment at all. Our study has proven that enalapril has a significant effect on preserving residual renal function in patients starting dialysis at least during the first 12 months from the initiation of the hemodialysis. Further studies are necessary in order to investigate the potential long-term effect of ACEi on residual renal function and on morbidity and mortality in patients starting hemodialysis.

Background: \ud \ud Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.\ud \ud Methods: \ud \ud We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.\ud \ud Findings: \ud \ud The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies.\ud \ud Interpretation: \ud \ud In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.\ud \ud Funding: \ud \ud Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.

Aims The vascular effects of high-density lipoproteins (HDL) differ under certain clinical conditions. The composition of HDL is modified in patients with chronic kidney disease (CKD). As a consequence, uremic HDL induces endothelial dysfunction. We have previously shown that accumulation of symmetric dimethylarginine (SDMA) in HDL causes these adverse effects of HDL in CKD. The aim of the study is to determine the impact of the accumulation of SDMA on the association between HDL and mortality. Methods and results Mortality, renal function, serum SDMA and HDL-cholesterol (HDL-C) were assessed in the LURIC study including 3310 subjects undergoing coronary angiography. All-cause mortality was 30.0% during median follow-up of 9.9 years. Serum SDMA levels significantly predicted all-cause and cardiovascular mortality, and were significantly correlated with SDMA accumulation in HDL. Notably, higher serum SDMA was independently associated with lower cholesterol efflux (P = 0.004) as a measure of HDL functionality. In subjects with low SDMA levels, higher HDL-C was associated with significantly lower mortality. In contrast, in subjects with high SDMA, HDL-C was associated with higher mortality. These findings were confirmed in 1424 participants of the MONICA/KORA S3 cohort. Of note, we derived an algorithm allowing for calculation of biologically effective HDL-C’ based on measured HDL-C and SDMA. We corroborated these clinical findings with in vitro evidence showing that SDMA accumulation abolishes the anti-inflammatory and regenerative properties of HDL. Conclusion The data identify SDMA as a marker of HDL dysfunction. These findings highlight on the pivotal role of SDMA accumulation in HDL as a mediator of pre-mature cardiovascular disease in patients with CKD.

The exclusion of cancer in endemic goiter is often difficult mainly because of the high number of nodules and the as-yet unclear natural history of diagnosed cancer in endemic goiter patients. In a large number of consecutive patients who were to undergo total thyroidectomy for endemic multinodular goiter, we assessed indications for surgery and thyroid cancer outcome.All patients who were to undergo total thyroidectomy for diffuse multinodular goiter on histological examination between January 1990 and October 2008 were evaluated.Of the 1,161 patients included in the study, 252 were cases of thyroid cancer (21.7%). Sensitivity of thyroid ultrasound (US) and fine-needle aspiration cytology (FNAC) for cancer detection was 30.3 and 64.1%, respectively. Differentiated thyroid carcinoma accounted for most of the tumors (96%), with 54.8% of them being papillary microcarcinomas, while bilateral-multicentric cancer occurred in 20.3%. In multivariate analysis, younger age (p = 0.06), sonographic findings (p = 0.03), and presence of histological thyroiditis (p = 0.09) were independently associated with the occurrence of tumors with diameter greater than 2 cm. The percentage of transient and permanent postoperative complications were approximately 25 and below 2%, respectively. After a median follow-up time of 78.5 months, overall recurrence rate was 6.7% and disease-specific mortality was 1.2%.As US and FNAC did not consistently detect cancer in patients with diffuse multinodular goiter in our endemic area, evidence-based indications for surgery in this group of patients is needed, although radical surgery and favorable tumor histology offer favorable outcomes in commonly diagnosed thyroid cancer after total thyroidectomy for endemic multinodular goiter.

Light-chain deposition disease (LCDD) is caused by an underlying clonal plasma cell dyscrasia in which monoclonal immunoglobulin light chains (LCs) are deposited in tissues, resulting in varying degrees of organ dysfunction. Autologous stem cell transplantation (ASCT) has been reported to stabilize renal function in patients with LCDD, but currently, no evidence of histopathologic resolution of LC deposition after ASCT exists. We present a patient, with severe renal dysfunction due to LCDD, who was treated with high-dose melphalan and ASCT that resulted in a significant and extended period of improved renal function. Four years after the initial improvement, the patient developed nephrotic range proteinuria, without any evidence of relapse of the plasma cell dyscrasia. At that time, a repeat renal biopsy showed complete resolution of LC depositions and development of extensive glomerulosclerosis, thus explaining proteinuria. To the best of our knowledge, this is the first report of a biopsy-proven resolution of renal LCDD following ASCT. A timely application of ASCT should be considered in LCDD to prevent deterioration of renal function in the long run.

Major liver involvement at the time of diagnosis is a rare event in patients with ovarian cancer, and the issue of major hepatectomy at the time of primary cytoreductive surgery is controversial. A 61-year-old woman was admitted to our hospital with nonspecific abdominal pain of 2-month duration and weight loss of 5 kg during the last semester. A computed tomography scan demonstrated bilateral ovarian masses, extending to the right iliac fossa, pressing the cecum-ascending colon. In the liver parenchyma, three cystic lesions were found of about 6-cm maximum diameter each, along with pelvic lymphadenopathy. There was no ascites. The diagnosis of advanced ovarian cancer was clinically suspected; the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, right hemicolectomy, omentectomy, left lobectomy, deroofing, and draining of the cystic formation of the right liver lobe along with systematic pelvic and para-aortic lymphadenectomy. Systemic chemotherapy (six cycles of paclitaxel/carboplatin) was subsequently administered, and after 15 months of follow-up period, the patient is still in first remission and alive. Ovarian cancer with concomitant extensive right colon infiltration and hematogenous liver metastases can be successfully managed with aggressive surgical resection and postoperative chemotherapy in carefully selected patients.

IntroductionProlapse of abdominal viscera into the thoracic subcutis through the chest wall is known as transdiaphragmatic intercostal hernia (TIH). Herein, we present the first case of spontaneous TIH presenting as a thoracoabdominal emergency.Presentation of caseA 78-year-old male presented with acute left thoracoabdominal pain following a sudden bulge at the left posterolateral chest wall corresponding to a partially reducible soft tissue mass with ecchymosis at the overlying skin. Paroxysmal cough during the last four days was also reported along with a prolonged daily application of a special tight abdominal belt that used while milking sheep. CT-scan of the abdomen showed intrathoracic proptosis of the splenic flexure through a defect of the left hemidiaphragm and subcutaneous prolapse of the herniated colon through the 7th intercostal space. On laparotomy, the herniated colon showed signs of ischemic necrosis leading to segmental colectomy followed by repair of the diaphragmatic defect.DiscussionThe clinical diagnosis of spontaneous TIH demands very high index of suspicion and thorough patient's history. In this case the daily elevation of the intraabdominal pressure due to an abdominal milking belt might have caused gradual slimming and loosening of the diaphragm and the intercostals muscles rendering them vulnerable to sudden increases of the thoracoabdominal pressure due to violent coughing. Such a hypothesis is reasonable in the absence of traumatic injury in this patient.ConclusionSpontaneous TIH should be suspected in patients presenting with a sudden palpable chest wall bulge and associated thoracoabdominal symptoms in the absence of preceding injury.

A solid pseudopapillary neoplasm (SPN) is an extremely rare tumour of the pancreas that frequently occurs in young females and is mostly benign. SPN is a low-grade malignant tumour that may evolve years before symptoms start. However, the pathogenesis of this tumour remains unclear and there are no adequate reports of long-term results to evaluate the management and the long-term surgical control. We describe a new case of SPN with a 10-year follow-up, and review the world literature that accounts for approximately 322 cases. Moreover, a review of the current management and surgical tendencies in the treatment of SPN is considered. An SPN pancreatic tumour occurred in a 24-year-old female who complained of episodic mild abdominal pain sustained by a palpable epigastric mass. The tumour mass was detected by ultrasound and computer tomography and was localised at the tail of the pancreas adherent to the spleen. The preoperative diagnosis was uncertain and en-block distal pancreatectomy and splenectomy were performed. The size of the mass which weighed 300 g was 11 x 12 x 8 cm, and the tumour was strictly adherent and invaded the splenic hilum. Histologic examination confirmed a complete resection of the primary SPN that locally invaded spleen. The postoperative period was uneventful and after a 10-year follow-up the patient is free of symptoms. SPN should be considered in the differential diagnosis of large pancreatic masses, especially in young females. Radical resection, where technically feasible, should be considered the therapy of choice as it is a safe and effective control of the disease.

Background: Recently, gastric stapling with posterior truncal vagotomy has been performed, either by conventional or laparoscopic surgery, as an alternative to highly selective vagotomy and the Taylor procedure for the treatment of chronic duodenal ulcer. Our aim was to investigate the longterm effects after a stapling-modified Taylor procedure, conventional and laparoscopic, on gastric secretion and emptying and on clinical indices and recurrence rates in patients treated for duodenal ulcer before 1994. Study Design: Thirty-one patients, aged 40 to 76 years (mean 53 years), were treated between 1986 and 1993, 21 by conventional and 10 by a laparoscopic stapling-modified Taylor procedure. Outcomes were studied for gastric acid secretion, solid and liquid gastric emptying, euterogastric reflux, endoscopic findings, and clinical indices using the Visick grading. Results: Endoscopy revealed a healing ulcer in 29 patients. Two patients showed signs of chronic ulcerative disease with mild symptoms, without gastritis or pyloric stenosis indicative of progressive ulcerative diathesis, and were classified as Visick III. Twenty-four patients were classified as Visick I and 5 as Visick II. The enterogastric reflux index ranged from 0% to 27%, and basal and peak acid output were 1.5 ± 0.6 mmol H + /h and 12.2 ± 6.4 mmol H + /h, respectively. The half-emptying time of solid and liquid meals was 78 ± 9 minutes and 18 ± 6 minutes, respectively. These results are likely to be similar to those obtained from the series of patients who underwent highly selective vagotomy or Taylor procedure and are close to those achieved in healthy controls. Conclusions: This modification of the original Taylor operation (conventional and laparoscopic) allows a more rapid, technically easier, and radical performance of the operation with excellent longterm results and should be considered an effective alternative for the treatment of duodenal ulcer.

Your article is protected by copyright and allrights are held exclusively by Springer Science+Business Media Dordrecht. This e-offprintis for personal use only and shall not be self-archived in electronic repositories. If you wishto self-archive your article, please use theaccepted manuscript version for posting onyour own website. You may further depositthe accepted manuscript version in anyrepository, provided it is only made publiclyavailable 12 months after official publicationor later and provided acknowledgement isgiven to the original source of publicationand a link is inserted to the published articleon Springer's website. The link must beaccompanied by the following text: "The finalpublication is available at link.springer.com”.

In this study, we evaluated the diagnostic utility of pulse wave velocity (PWV) alone or in combination with other diagnostic markers in predicting pre-eclampsia (PE) in high-risk women. Pregnant women at high risk for PE were recruited between 22 and 26 weeks of gestation and were assessed for (a) PWV, (b) serum levels of the placental soluble fms-like tyrosine kinase 1 (sFlt-1) protein and uric acid and (c) 24-h urinary protein and calcium excretion. Sensitivities and specificities were derived from receiver operating characteristic curves. Of 118 women recruited, 11 and 10 women developed early-onset PE (

Objective. Recent studies have shown a beneficial effect of rapamycin in passive and active Heymann Nephritis (HN). However, the mechanisms underlying this beneficial effect have not been elucidated.Methods. Passive Heymann Nephritis (PHN) was induced by a single intravenous infusion of anti-Fx1 in 12 Sprague-Dawley male rats. One week later, six of these rats were commenced on daily treatment with subcutaneous rapamycin 0.5 mgr/kg (PHN-Rapa). The remaining six rats were used as the proteinuric control group (PHN) while six more rats without PHN were given the rapamycin solvent and served as the healthy control group (HC). All rats were sacrificed at the end of the 7th week.Results. Rapamycin significantly reduced proteinuria during the autologous phase of PHN. Histological lesions were markedly improved by rapamycin. Immunofluorescence revealed attenuated deposits of autologous alloantibodies in treated rats. Untreated rats showed decreased glomerular content of both nephrin and podocin whereas rapamycin restored their expression.Conclusions. Rapamycin monotherapy significantly improves proteinuria and histological lesions in experimental membranous nephropathy. This beneficial effect may be mediated by inhibition of the alloimmune response during the autologous phase of PHN and by restoration of the normal expression of the podocyte proteins nephrin and podocin.

The study's aim was to assess the functional results of laparoscopically performed Heller's myotomy and Dor's fundoplication in our first few cases of esophageal achalasia. Four male patients (mean age: 61 years) with long-standing symptoms of achalasia (documented on esophagogram and esophageal manometry) and not responding to several sessions of pneumatic dilatation, had laparoscopic Heller's myotomy and Dor's fundoplication. Myotomy was facilitated by distending the esophagus. The mean duration of the operation was 99 min. The third patient developed a leak from the exposed esophageal mucosa on the 5th postoperative day while at home. The leak was attributed to late desloughing of a mucosal burn, and was sealed spontaneously 15 days later after drainage. The remaining three patients were discharged after resuming diet within the first 2 postoperative days. By 1 year postoperatively, dysphagia was abolished in all cases, and there were no gastroesophageal reflux symptoms. The esophagogram showed no reflux, which was also confirmed on ambulatory 24-h esophageal pH measurement. On manometry, lower esophageal sphincter (LES) pressure dropped significantly postoperatively (preop: 56 +/- 7 SD mm Hg, postop: 5 +/- 1 SD mm Hg, p0.001). In conclusion, laparoscopic Heller's myotomy with Dor's fundoplication for esophageal achalasia is a feasible procedure, offering clinical and laboratory results similar to the open approach, but with better patient tolerance.

BACKGROUND Acute coagulopathy associated with trauma has been recognized for decades and is a constituent of the "triad of death" together with hypothermia and acidosis. STUDY OBJECTIVE The aim of this study was to determine to what extent coagulopathy is already established upon emergency department (ED) admission and the association with the severity of injury, impaired outcome, and mortality. METHODS Ninety-one injured children were admitted to the ED in our hospital. Pediatric Trauma Score (PTS), Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) score were used to estimate injury severity, and organ function was assessed by the Sequential Organ Failure Assessment (SOFA) score. RESULTS Coagulopathy upon pediatric intensive care unit admission was present in 33 children (39.3%): 21 males and 12 females. PTS ranged from 1 to 12 (mean 8.2) in 51 children without coagulopathy and from -1 to +11 (mean 6.8) in 33 children with coagulopathy (p = 0.087). ISS and GCS ranged from 4 to 57 (mean 28) and from 3 to 11 (mean 7.3), respectively, in the coagulopathy group, whereas in the group without coagulopathy, ISS score ranged from 4 to 41 (mean 20.5; p = 0.08) and GCS from 8 to 15 (mean 12.8; p = 0.01). SOFA ranged from 0 to 10 (mean 3.4) in children without coagulopathy and from 0 to 15 (mean 5.4) in the coagulopathy group (p = 0.002). Among 33 children with coagulopathy, 7 did not survive (21%), all with parenchymal brain damage, whereas all trauma patients without coagulopathy survived (p < 0.001). CONCLUSION Acute coagulopathy is present on admission to the ED and is associated with injury severity and significantly higher mortality.

The AKT-mTOR pathway is activated in diabetic nephropathy. Renin-angiotensin system modulators exert beneficial effects on the diabetic kidney. We explored the action of losartan on AKT-mTOR phosphorylation in glomeruli and podocytes. Diabetes mellitus was induced to Sprague-Dawley rats by streptozotocin. Five months later, the rats were commenced on losartan and euthanized 2 months later. Kidneys were processed for immunofluorescence studies. Glomeruli were isolated for Western blot analysis. Diabetes increased activated forms of AKT and mTOR both in glomeruli and podocytes. In diabetic rats, losartan decreased phosphorylated/activated forms of AKT (Thr308) and mTOR (Ser2448) in glomeruli but decreased only activated mTOR in podocytes. However, in both glomeruli and podocytes of healthy animals, an inverse pattern was evident. In conclusion, a new body of evidence indicates the differential activation of AKT-mTOR in glomeruli and podocytes of healthy and diabetic animals in response to losartan.

Familial amyloid polyneuropathy is characterized by transthyretin (TTR) deposition in various tissues, including the kidneys. While deposition induces organ dysfunction, renal involvement in TTR-related amyloidosis could manifest from proteinuria to end-stage kidney failure. As proteinuria is considered result of glomerular filtration barrier injury we investigated whether TTR deposition affects either glomerular basement membrane (GBM) or podocytes.Immunohistochemistry, immunoblot and gene expression studies for nephrin, podocin and WT1 were run on renal tissue from human-TTRV30M transgenic mice hemizygous or homozygous for heat shock factor one (Hsf-1). Transmission electron microscopy was used for evaluation of podocyte foot process width (PFW) and GBM thickness in Hsf-1 hemizygous mice with or without TTRV30M or amyloid deposition.Glomeruli of hsf-1 hemizygous transgenic mice showed lower nephrin and podocin protein levels but an increased podocyte number when compared to Hsf-1 homozygous transgenic mice. Nephrin, podocin and WT1 gene expression levels were unaffected by the Hsf-1 carrier status. TTRV30M deposition was associated with increased PFW and GBM thickness.Under the effect of Hsf-1 hemizygosity, TTRV30M deposition has deleterious effects on GBM thickness, PFW and slit diaphragm composition, without affecting nephrin and podocin gene expression.

Background. In the normal kidney, rapamycin is considered to be non-nephrotoxic. In the present study, we investigated whether rapamycin is indeed non-nephrotoxic by examining the ultrastructural and molecular alterations of podocytes in healthy mice. Methods. Balb/c mice were given three different intraperitoneal doses of rapamycin for 1 week (dose model)— low-dose group: 1 mg/kg/day, intermediate-dose (ID) group: 1.5 mg/kg/day and high-dose (HD) group: 3 mg/kg/day; four mice in each group. An ID of rapamycin was also given for three different periods (time model): 1, 4 and 8 weeks; four mice were in each group. Mice treated with dimethyl sulphoxide served as controls. Body weight was measured weekly. Renal function was assessed by serum creatinine at the time of sacrifice. For estimation of albuminuria, 24h urine collections were performed before treatment and weekly thereafter. Glomerular content of nephrin, podocin, Akt and Ser473-phospho-Akt was estimated by western blot and immunofluorescence. Nephrin and podocin messenger RNA (mRNA) were measured by real-time polymerase chain reaction. Mean podocyte foot process width (FPW) was measured by electron microscopy. Results. Urine albumin levels increased in the HD and 4-week groups. Renal function was modestly deteriorated in the HD group. The mean FPW increased in a dose-dependant manner at Week 1, further deteriorated at Week 4 and finally improved at Week 8. Nephrin and podocin mRNA levels showed a significant decrease at Week 1 and were restored at Week 4 and 8. Nephrin and podocin protein levels were reduced at Week 4 and recovered at Week 8. Ser473phospho-Akt significantly increased in all rapamycintreated groups. Conclusions. Rapamycin induced significant ultrastructural and molecular alterations in podocytes in association with albuminuria. These alterations happened early during treatment and they tended to improve over an 8-week treatment period.

Introduction The kidney is increasingly recognised as a target organ of chronic graft-versus-host disease after hematopoietic cell transplantation in the context of the development of the nephrotic syndrome. Chronic graft-versus-host disease is associated with autoimmune phenomena similar, but not identical, to those observed in various rheumatologic disorders, implicating autoimmunity as an important component of the disease. Case presentation We report the case of a 57-year-old Caucasian man who developed the nephrotic syndrome due to membranous nephropathy in association with recurrent chronic graft-versus-host disease, along with a lupus-like syndrome manifested with pancytopenia, hair loss, positive anti-DNA antibodies and sub-epithelial and mesangial immune deposits. To the best of our knowledge, this is the first case reported in the literature. The nephrotic syndrome subsided soon after he was treated with a short course of cyclosporin with steroids. Unfortunately he died seven months later due to a relapse of leukemia. Conclusions Our case report confirms the notion that chronic graft-versus-host disease is characterized by the appearance of autoimmune phenomena similar, but not identical, to those seen in autoimmune diseases. The decision for more immunosuppression has to be weighed against the need for preservation of the graft versus leukemia phenomenon.

Background The mammalian target of rapamycin (mTOR) inhibitor, rapamycin, has been shown to inhibit the progression of murine lupus nephritis by virtue of its potent immunosuppressive properties. The phosphoinositol-3-kinase (PI3K)/Akt pathway is a major upstream activator of mTOR and has been implicated in the propagation of cancer and autoimmunity. However, the activation status of the PI3K/Akt/mTOR pathway in lupus nephritis has not been studied so far. Methods In NZBW/F1 female mice, we examined the glomerular expression of Akt and mTOR by immunofluorescence and western blot. We also searched for specific phosphorylations of these kinases known to ensue during activation of the PI3K/Akt/mTOR pathway. In parallel, we examined the therapeutic role of rapamycin either before or after the development of overt lupus nephritis. Results We found that in untreated mice, as opposed to healthy controls, Akt and mTOR were over-expressed and phosphorylated at key activating residues. Rapamycin prolonged survival, maintained normal renal function, normalized proteinuria, restored nephrin and podocin levels, reduced anti-dsDNA titres, ameliorated histological lesions, and reduced Akt and mTOR glomerular expression activation. Conclusions These results suggest that: (i) the PI3K/Akt/mTOR pathway is upregulated in murine lupus nephritis, thus justifying treatment with rapamycin; (ii) rapamycin not only blocks mTOR but also negatively regulates the PI3K/Akt/mTOR pathway; and (iii) rapamycin is an effective treatment of murine lupus nephritis. Examination of the PI3K/Akt/mTOR pathway may offer new insights into the pathogenesis of lupus nephritis in humans and may lead to more individualized and less toxic treatment.

Considerable controversy currently exists in the literature concerning the mode of catheter placement and its impact on the technical success of peritoneal dialysis (PD). We decided to compare the impact of the surgical versus the percutaneous insertion technique on peritoneal dialysis catheter (PDCs) complications and survival. Our study population comprised 152 patients in whom 170 PDCs were inserted between January 1990 and December 2007 at the main PD unit on the island of Crete. Eighty four catheters were surgically placed (S group) and 86 were placed percutaneously by nephrologists (N group). The total experience accumulated was 4997 patient-months. The overall complications did not differ between the two groups. Only early leakage was more frequent in N group than S group (10.3 versus 1.9 episodes per 1000 patient-months; p < 0.001). However, it was easily treated and did not constitute a cause of early catheter removal. Catheter survival was 91.1%, 80.7%, and 73.2%, in the S group versus 89.5%, 83.7%, and 83.7% for the N group at 1, 2, and 3 years, respectively (p = 0.2). Catheter survival has significantly increased over the last decade. Factors positively affecting PDC survival appeared to be the use of mupirocin for exit site care and the utilization of the coiled type of catheter, practices implemented mainly after 1999. Peritonitis-free survival and patient survival were not associated with the mode of placement, while in Cox regression analysis, were longer in patients treated with automated PD. The placement mode did not affect PD outcomes. Percutaneous implantation proved a safe, simple, low cost, immediately available method for PDC placement and helped to expand our PD program.

Background: Approximately 10% of patients treated with intrapleural instillation of fibrinolytics fail to respond and therefore need more invasive techniques, such as video-assisted thoracoscopic surgery (VATS). Methods: During the period 1994-99, we treated 20 consecutive patients with complicated parapneumonic effusion (CPE) and pleural empyema (PE) that did not resolve with urokinase instillation given through the chest tube in a dose of 100,000 IU diluted in 100 ml of normal saline/daily for 3-5 days. The patients' ages ranged from 21 to 68 years (median, 46); 14 were male and six female. All patients had pleural fluid pH 1000, glucose

The aim of this report is to present our experience with new techniques for extraanatomic lower limb arterial reconstruction. Two techniques are described here of construction of an extraanatomical bypass for lower limb revascularization either through the wing of the iliac bone or underneath the iliopsoas fascia through the muscular lacuna close to the anterior superior spine of the iliac crest. Both techniques are recommended for the treatment of a severely injured groin, such as in patients with pelvic malignancy and/or an acute groin bleeding due to postirradiation femoral artery erosion or an infected femoropopliteal bypass graft with severe upper medial thigh sepsis. These techniques were used in nine patients (five with malignancy and four with an infected femoropopliteal bypass graft). Our results showed that the transosseous route through the wing of the iliac bone or underneath the iliopsoas fascia through the muscular lacuna may be considered effective alternate routes for lower limb arterial extraanatomic reconstruction when the common femoral cannot be used for arterial inflow.

The risk of wound contamination in diabetic patients after abdominal operations is well known. Preincisional intraparietal injection of antibiotics is used for the prophylaxis of postoperative surgical infections. Whether topically injected antibiotics remain primarily in the surgical wound or are systematically absorbed is uncertain, however. The pharmacokinetics of a preincisional, intraparietal injection of 2 g ceftriaxone was studied in 50 consecutive diabetic (type I and II) patients undergoing abdominal surgery, with determination of serum, wound tissue, and wound fluid antibiotic concentrations. Preincisional intraparietal injection of ceftriaxone resulted in high antibiotic concentrations in the wound fluid. The highest plasma concentrations were achieved at 1.5 h (98.45 microg/ml, SD = 14.54). Plasma concentrations exceeded the minimal inhibitory concentrations of most aerobic gram positive and gram negative organisms with the exception of Pseudomonas aeruginosa, Acinetobacter species, and Streptococcus faecalis for 24 h (10.35 microg/ml, SD = 4.10). No long-lasting or general complications arose in any of the diabetic patients. Our results suggest that preincisional intraparietal administration of ceftriaxone for prophylaxis of wound sepsis in diabetic patients with high risk of infection is effective.

Internal hernia is a rare condition. These hernias are classified in different categories, depending on the location of its orifice. It should be considered in cases of acute intestinal obstruction, particularly in the absence of an external hernia or in the absence of history of previous abdominal surgery. The authors report a unique case of obstruction of the small bowel, that was almost entirely wrapped in a separate peritoneal sac.

RATIONALE AND OBJECTIVES Reports on the effect of the ovulatory cycle on gallbladder motility are inconsistent. The authors investigated the gallbladder motor function at both phases of the menstrual cycle in humans. METHODS Seventeen young, healthy, nulliparous women participated in the study. Gallbladder fasting volume and postprandial emptying were measured twice in each subject using real-time ultrasonography: one at the follicular (12th-13th day) and another at the luteal (21st-22nd day) phases. From the emptying curves, the duration of the lag phase and the ejection fraction of emptying were calculated. RESULTS Fasting volume was significantly greater (P = 0.025) at the luteal (14.8 +/- 8 mL standard deviation [SD]) than at the follicular (11.2 +/- 4.7 mL SD) phase. Although the lag phase duration was longer (P = 0.009) at the follicular (5.2 +/- 6.4 SD minutes) than the luteal (1.6 +/- 3.6 minutes SD) phase, the ejection fraction was significantly greater at the latter one (follicular phase: 62 +/- 13.2% SD; luteal phase: 73.4 +/- 14% SD; P = 0.0085). CONCLUSIONS Female sex hormones seem to biologically affect the gallbladder motor function.

Video-assisted thoracoscopic surgery (VATS) has been used recently in the diagnosis and management of thoracic diseases. In this report, VATS experience with 95 cases, focusing on indications, surgical procedures, complications, and failure rates, are reviewed. Over the past 5 years, 95 VATS procedures for diagnostic and therapeutic purposes were performed in 59 men and 36 women. The specific indications for VATS were lung biopsy for undiagnosed diffuse lung disease (48), mediastinal biopsy (12) and cyst (2), pleural effusion (10), empyema (5), pneumothorax and bullous lung disease (6), pericardial effusion (2) and cyst (2), paravertebral abscess (2), solitary pulmonary nodules (3), and thoracic trauma (3). In all patients, postoperative pain was controlled with non-narcotic analgesics and was measured according to the visual analogue scale (VAS). There was no surgical mortality. Postoperative nonfatal complications were seen in seven cases (7.5%). The overall median duration of chest tube drainage was 2.7 days and the mean postoperative hospital stay was 3 days. For diffuse lung disease, a tissue diagnosis was obtained in all the cases. Definitive diagnosis in the patients with undiagnosed pleural effusion was obtained in 90% of cases, and the overall diagnostic rate was 98.5%. The success rate of the therapeutic procedures was 100% after a mean follow-up of 12 months (range, 6-30 months). Conversion to thoracotomy was needed in six cases (6.6%). All patients scored postoperative pain

Highlights • Excessive drooping belly may lead to severe issues majorly affecting the person’s health as well as the quality of life. • Abdominoplasty could be used not only for cosmetic purposes but also for therapeutic purposes by eliminating morbidity and improving the quality of life., Background Abdominoplasty is a surgical procedure which is commonly used for cosmetic purposes. However, there are very few reports in the world literature describing the abdominoplasty procedure for therapeutic purposes rather than for cosmetic reasons. Methods A 58 year old female presented with an excessive drooping belly and a concomitant minor umbilical stoma hernia, who suffered from chronic back pain, urinary incontinence, nerve atrophy of the low extremes, central-type obesity, gastric disorders, and spinal osteophytes who underwent abdominoplasty and umbilical hernia repair. Result On discharge from the hospital after 11 days, the patient mentioned satisfactory elimination of the back pain as well as amelioration of the urinary incontinence. Within 14 months after the operation, the patient noticed extreme improvement of ambulation and postural stability as well as complete disappearance of the neuro-myodystrophy. Conclusion Wide abdominal rectus plication abdominoplasty should be considered to be performed for therapeutic purposes when major health problems occur.