Laparoscopic distal gastric and D1 resection for large perforated duodenal bulb peptic ulcer, with intracorporeal antecolic gastrojejunal anastomosis.

BACKGROUND: Peptic ulcer perforation is a common surgical emergency and a major cause of death especially in elderly patients, despite the fact of the presence of effective drug treatments and an increased understanding of its etiology. Giant duodenal perforations, in particular, pose a significant challenge and there is scarce data regarding their optimal management. Laparoscopic surgery is advocated in the surgical treatment of perforated duodenal ulcer disease, in experienced hands. METHODS: Herein we present an 84-year-old man with past medical history of type II diabetes mellitus and hypertension who was admitted to our Department due to epigastric pain and diffuse peritonitis. CT scan revealed the presence of a significant amount of free air and fluid in the upper abdomen secondary to a duodenal perforation. RESULTS: The patient was taken immediately to the theater for an urgent laparoscopy. Methylene blue via the NG tube better defined the extent of the duodenal perforation which was not amenable to a primary repair. Consequently, a decision was made for a laparoscopic pancreas-sparing, ampulla preserving gastroduodenectomy with intracorporeal Billroth II gastrojejunal anastomosis. The postoperative period was uneventful and the patient was discharged on the 13th postoperative day. Histopathology revealed a large benign duodenal ulcer. CONCLUSIONS: Although the incidence of peptic ulcer disease is decreasing, it appears that the incidence of complications is rising. Laparoscopic approach, especially when performed by laparoscopic surgery experts, could be a treatment option for difficult duodenal ulcer perforations with less pain, shorter hospital stay and reduced morbidity.

Angiography-based estimation of coronary physiology: A frame is worth a thousand words.

Cumulative evidence has shown that coronary revascularization should be guided by functional significance of coronary lesions. Fractional flow reserve (FFR) is the gold standard for assessment of hemodynamic significance of coronary stenosis and FFR-guided percutaneous coronary intervention has improved clinical outcomes in patients with coronary artery disease. However, limitations of FFR such as increased operational time and cost, requirement of pressure wire and adenosine and technical difficulties have led to significant underutilization of the method in clinical practice. In the last few years, several methods of FFR estimation based on coronary angiography images have emerged to overcome invasive FFR limitations. The common elements of the novel indices include a 3D anatomical reconstruction of coronary vessels by angiographic projections and various approaches to fluid dynamics computation. Angiography-derived FFR methods have shown high diagnostic accuracy compared to invasive FFR. Although there are promising results regarding their prognostic role, large randomized trials evaluating clinical outcomes are lacking. The aim of this review is to present currently available angiography-derived FFR indices and highlight their differences, advantages, disadvantages and potential clinical implications.

Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC).

OBJECTIVES: Locally advanced pancreatic cancer (LAPC) is found in about 40% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a nonthermal ablative technique that provides an alternative in patients with LAPC and can be safely combined with chemotherapy. MATERIALS AND METHODS: From 2015 until October of 2019, we performed laparotomic IRE in a total of 40 patients with stage III LAPC. The median age of these patients was 65.2 years (range: 46 to 81 y), and the median tumor size was 3.8 cm (range: 2 to 5.2 cm). 33 of 40 patients were treated preoperatively with FOLFIRINOX or nab-paclitaxel plus gemcitabine and in case of disease control, IRE was performed, whereas in 7 patients, IRE was performed without previous chemotherapy. RESULTS: All patients were treated successfully with IRE as the tumor evaluation showed no disease progression after the completion of induction chemotherapy. No IRE-related deaths occurred. Two major grade III complications were reported: pancreatic fistula grade A in 8 patients and 3 patients diagnosed with delayed gastric emptying. Up to October 31, 2019, the median overall survival (OS) of all patients was 24.2 months (range: 6 to 36 mo), and the median progression-free survival was 10.3 months (range: 3 to 24 mo). After the completion of IRE, 30 patients (75%) continued with adjuvant chemotherapy. Fifteen patients (37%) have >24 months OS and 3 patients (8%) have reached 36 months OS and are still alive. CONCLUSION: The combination of chemotherapy with IRE, which is a safe and effective procedure, may result in a survival benefit for patients with LAPC.

A Bayesian meta-analysis on early tobacco exposure and vascular health: From childhood to early adulthood.

BACKGROUND: Smoking has been consistently associated with increased cardiovascular risk in adults. Although exposure to tobacco products often starts in early life, evidence for the possible adverse effects on the cardiovascular system of the young is scarce. We sought to derive pooled estimates of smoking effects on indices of early vascular damage in children and adolescents. DESIGN AND METHODS: We performed a systematic review and meta-analysis of clinical studies involving young individuals up to 21 years old that provided data on smoking exposure (active or passive) and flow-mediated dilatation, carotid to femoral pulse wave velocity and maximum carotid intima-media thickness. We employed three distinct methodologies of random-effects data synthesis, including the Sidik-Jonkman estimator, the Hartung and Knapp correction and a Bayesian method with a well-informed prior on the level of between-study variance. RESULTS: In 12 studies and 5279 individuals in total, smoking exposure was related to deterioration in all three outcomes (mean adjusted flow-mediated dilatation decrease: -0.77%, 95% confidence interval -1.38--0.15, mean adjusted pulse wave velocity increase: 0.1 m/s, 95% confidence interval 0.02-0.17 and mean adjusted carotid intima-media thickness increase: 0.35 mm, 95% confidence interval 0.16-0.55, for the Sidik-Jonkman estimator). No difference was established between active and passive smoking on associations with arterial damage. CONCLUSIONS: Exposure to tobacco products is associated with subclinical vascular damage early in life, even from childhood. Public health initiatives should target these very young age groups to prevent early smoking exposure and associated arterial damage and its sequelae.

Impaired dexamethasone resorption in two patients with pseudo-Cushing after bariatric surgery: Implications for immunosuppressive treatment.

Two cases of middle-aged female patients treated by gastric bypass surgery for weight loss presented to our clinic for a follow-up examination 3-6 months after the surgical procedure (a mini gastric bypass and a modified single anastomosis sleeve-ileostomy). In both patients increased ACTH levels and either high serum cortisol or an increased urinary cortisol excretion was apparent and triggered further endocrine testing. Serum cortisol could not be suppressed adequately by 2 and 4 mg dexamethasone in the standardized oral overnight suppression test while midnight salivary cortisol dropped well below the desired cut-off. This led to the hypothesis of an impaired dexamethasone resorption and could be further substantiated by suppression of serum cortisol below the cut-off by an intravenous dexamethasone application. The data presented point to an impairment of enteral synthetic corticosteroid resorption in patients after gastric bypass surgery and could be of importance for individuals in need for immunosuppressive treatment. In view of the growing number of bariatric procedures, pharmacokinetics of corticosteroids and other drugs should be tested in clinical trials.

The efficacy and safety of the open approach irreversible electroporation in the treatment of pancreatic cancer: A systematic review.

BACKGROUND: Irreversible Electroporation (IRE) is a novel non-thermal ablation technique used in patients with locally advanced pancreatic cancer (LAPC), in the proximity of sensitive structures such as vessels, intestinal wall and the bile duct. Currently, it is only used in the setting of clinical trials. This systematic review aimed to tackle the knowledge gap in the literature, in relation to the safety and efficacy of the open approach IRE. METHODS: MEDLINE, EMBASE and Cochrane libraries were searched for English language articles published from January 2000 to December 2019. Data related to safety and efficacy were extracted. RESULTS: Nine studies involving 460 patients with LAPC were included. Open approach IRE was associated with high morbidity (29.4%) but with a survival benefit compared to traditional treatment. Median overall survival (OS) was at 17.15 months. Major morbidity was at 10.2% and mortality at 3.4%. CONCLUSIONS: Despite the paucity of literature and the low quality of evidence, the results regarding safety and efficacy appear to be encouraging. The high morbidity seems to be mitigated by a demonstrated improvement in OS. The potential of this technique is more evident when mortality and major morbidity are considered, since they are at acceptable levels. The limitations of this review have made it difficult to extract definitive conclusions. Higher quality evidence is needed in the form of large-scale multicentre randomized controlled trials. It remains to be elucidated whether the rate of adverse events decreases as our experience with this technique increases.

Open Interphalangeal Dislocation of the Great Toe in an Amateur Football Player: A Rare Case Report.

INTRODUCTION: Open interphalangeal (IP) dislocations are completely uncommon. Up to now, different patterns of dislocation have been described. The combination of axial loading and hyperdorsiflexion forces, leading to plantar dislocation of the distal phalanx, is a rare type of injury, which has yet not been reported. CASE REPORT: A rare case of traumatic open dislocation of the left great toe IP joint in a highly active, overweighted, male, amateur football player is presented. The possible underlying mechanism was impact of the left great toe against the ground and subsequent hyperdorsiflexion. The distal phalanx was dislocated plantarly, whereas the proximal phalanx was protruding out the dorsal skin of the toe. Open exploration and reduction led to excellent clinical results 6 months after surgery. CONCLUSION: Open traumatic IP dislocation of the great toe due to low force activity is a very rare mode of injury, which requires adequate treatment including immediate purification of the exposed joint, control of the sesamoids' position, exclusion of intra-articular fractures, joint's reduction, soft-tissue repair, and proper stabilization.

Snare Technique for Transcatheter Aortic Valve Implantation in a Difficult Anatomy With Calcified Aortic Valve.

Crossing the aortic annulus with a prosthetic valve was impossible due to severe calcification. A snare catheter technique was used to centralize the entire system with the aortic orifice.

Laparoscopic Versus Open Adrenalectomy for Localized/Locally Advanced Primary Adrenocortical Carcinoma (ENSAT I-III) in Adults: Is Margin-Free Resection the Key Surgical Factor that Dictates Outcome? A Review of the Literature.

BACKGROUND: The aim of this study was to review the current literature on the role of laparoscopic adrenalectomy (LA) in the treatment of primary adrenocortical carcinoma (ACC; European Network for the Study of Adrenal Tumors [ENSAT] I-III) in adults. MATERIALS AND METHODS: Nonrandomized controlled trials published between January 1999 and February 2017 were identified by searching the Pubmed, EMBASE, Cochrane Library, and Google Scholar databases. Primary and secondary endpoints included surgical and pathological parameters (patients age, tumor size, ENSAT stage, type of surgical approach, and period of follow-up), surgical outcomes (operative time, estimated blood loss, length of hospital stay, conversion rate to laparotomy, R0 resection, and surgical margin's status), and oncological outcomes (rate of recurrence, disease-free survival [DFS], and overall survival [OS] rates). RESULTS: A total of 13 studies encompassing data on 1171 patients were included in the review. Compared with open approach, LA demonstrated lower tumor size, shorter operative time, lower intraoperative blood loss, shorter postoperative hospital stay, and equivalent local recurrence rates. No significant differences were observed between groups treated with an open or laparoscopic approach for the following criteria: R0 surgical resection status, tumor overall recurrence, and postoperative DFS and OS rates. CONCLUSIONS: LA appears to be equivalent to open method for localized/locally advanced primary ACC (ENSAT I-III) in terms of R0 resection rate, overall recurrence, DFS, and OS, therefore suggesting that the extent of surgery with adequate tumor resection is the predominant endpoint, rather than the surgical approach itself. Multicenter randomized controlled trials with long follow-up time periods exploring the long-term oncological outcomes are required to determine the benefits of the laparoscopic over the open approach in adrenocortical carcinoma.

Electrical Muscle Stimulation Induces an Increase of VEGFR2 on Circulating Hematopoietic Stem Cells in Patients With Diabetes.

PURPOSE: External electric muscle stimulation (EMS) of the thigh muscles was found to reduce pain resulting from diabetic neuropathy (DN), a vascular complication of diabetes. This study investigated circulating hematopoietic stem cells (HSCs) after EMS treatment. Impaired function of HSCs and the subpopulation endothelial progenitor cells (EPCs), important for neovascularization and endothelial repair, has been associated with DN. METHODS: Twenty-four patients with painful DN were treated 3 times with EMS over a period of 1 week. Blood samples were collected before and after the first EMS treatment. Before a fourth treatment, neuropathic pain was evaluated and a third blood sample was collected. Cells were used for flow cytometry. FINDINGS: Patients with painful DN reported that the pain decreased after 3 times of 1-hour treatments with EMS (Neuropathy Symptom Score: from 8 to 6, P = 0.001; Neuropathy Disability Score: from 5.5 to 5, P = 0.027, n = 24). At the end of the study, diastolic blood pressure had decreased from 80 to 70 mm Hg (P = 0.043), and plasma adrenaline and noradrenaline metabolites metanephrine and normetanephrine were reduced (both P ≤ 0.01; n = 21). A single EMS treatment caused an immediate and transient decrease in the frequency of CD34+ HSCs in circulation (-20%; P < 0.001; n = 27). In 9 of the patients with DN, the proportion of HSCs expressing vascular endothelial growth factor receptor 2 (VEGFR2; defining the HSCs as EPCs) increased by 36% (P = 0.011) after EMS treatment. Proteins required for binding to endothelium (junctional adhesion molecule A and CD31), homing toward hypoxic tissue (C-X-C chemokine receptor type 4), and endothelial differentiation (CD31) were increased on HSCs immediately after EMS treatment. An increased frequency of VEGFR2 expression was also observed on HSCs of 6 healthy control volunteers (34%; P = 0.046) after EMS treatment, but not after sham treatment. IMPLICATIONS: Three EMS treatments decreased symptoms of pain caused by DN and reduced diastolic blood pressure and biomarkers of stress. A single EMS treatment increased molecules mediating attachment and differentiation on the surface of HSCs in circulation. We hypothesize that the EMS-induced increase in surface attachment molecules on the HSCs caused the HSCs to leave circulation and that EMS treatment improves the function of HSCs and EPCs in vivo.

E-cadherin in gastric carcinomas: Relations with histological parameters and its prognostic value.

PURPOSE: Gastric cancer (GC) is still one of the most common malignancies with the majority of the tumors being diagnosed at advanced stage. The need for identification of prognostic and early detection biomarkers is thus compulsory. E-cadherin is one of the emerging biomarkers that is currently evaluated in the literature in the frame of epithelial-mesenchymal transition (EMT). Our aim was to study the expression of E-cadherin in the various histological subtypes of GC and to evaluate its prognostic value. METHODS: This historical cohort survey was performed on gastric tumors obtained from 66 (46 men and 20 women) patients with documented gastric adenocarcinoma who underwent total or partial gastrectomy and regional lymphadenectomy from 2003 till 2011. Features such as tumor size, depth of invasion, grade and histological subtype, lymphovascular space invasion and regional lymph nodes involvement were also evaluated. Immunohistochemistry (IHC) was used for assessing the expression of E-cadherin with a semi-quantitative model. RESULTS: The correlation of E-cadherin tissue expression with patient overall survival (OS) or disease-free survival (DFS) was not statistically significant, as well as with gender, T stage, N stage, TNM stage, grade, positive lymph nodes ratio or lymphovascular invasion. CONCLUSIONS: 73.0% of the evaluated tumors showed abnormal E-cadherin expression in IHC, but the correlation of E-cadherin tissue expression with patient OS or DFS was not statistically significant. Literature stands equivocal about the association between E-cadherin gene mutation, and histopathology and tumor invasiveness. Our results further strengthen the need of larger studies to fully elucidate the predictive role of E-cadherin in the natural history of GC.

Intracholecystic papillary-tubular neoplasm in a patient with choledochal cyst: a link between choledochal cyst and gallbladder cancer?

BACKGROUND: Intracholecystic papillary-tubular neoplasms are rare precursor lesions of gallbladder cancer. They were proposed as a separate pathologic entity in 2012 by Adsay et al. for the unification of a variety of mass-forming precursor lesions including papillary adenomas, tubulopapillary adenomas, intestinal adenomas, and others. They are considered homologous to intrapapillary mucinous neoplasms of the pancreas and intrabiliary papillary neoplasms of the common bile duct. In contrast with the commoner flat-type precursor gallbladder cancer lesions, they follow a more indolent clinical course and probably different genetic pathways to carcinogenesis. They are largely uninvestigated with only a handful of studies providing biological and clinical information. Choledochal cysts are dilation of the common bile duct. Diagnosis is usually established during childhood, and only a minority of patients are diagnosed at adulthood. They are of major clinical importance as they are known predisposing factors for biliary carcinogenesis. CASE PRESENTATION: The current report describes a patient with a simultaneous diagnosis of choledochal cyst and intracholecystic papillary-tubular neoplasm. The patient underwent excision of the extrahepatic biliary tree for a Todani I choledochal cyst, and histological examination of the specimen revealed an intracholecystic papillary-tubular neoplasm of the gallbladder. Authors describe diagnostic and clinical course of the patient alongside clinical and biological characteristics of these rare lesions. CONCLUSIONS: To the best of our knowledge, this is the first report of a patient with a simultaneous diagnosis of choledochal cyst and intracholecystic papillary-tubular neoplasm. Those rare lesions shed light on different forms of gallbladder cancer carcinogenesis and its relationship with choledochal cysts and cholestasis.

Circulating periostin levels in patients with AS: association with clinical and radiographic variables, inflammatory markers and molecules involved in bone formation.

OBJECTIVE: The aim of this study was to evaluate serum periostin levels in patients with AS in comparison with healthy controls as well as their association with clinical, inflammatory and radiographic parameters and molecules involved in bone formation. METHODS: Serum samples for periostin, total Dickkopf-1 (Dkk-1), sclerostin, VEGF and inflammatory markers were obtained from 65 TNF inhibitor-naive patients with AS. The BASDAI, BASFI, modified Stoke AS Spine Score and BASRI for the spine (BASRI-s) were assessed for each patient. Serum periostin levels were also measured in 36 sex-, age- and BMI-matched controls. RESULTS: Serum periostin levels were significantly lower in AS patients compared with controls [234.4 pg/ml (s.e.m. 7.5) vs 291.4 (s.e.m. 8.3), respectively; P < 0.001]. Periostin levels were higher in AS patients with elevated CRP (P = 0.005), high BASDAI (P = 0.014) and low BASRI-s (P = 0.033) and were correlated with BMI (r = -0.304, P = 0.014), ESR (r = 0.395, P = 0.001), CRP (r = 0.413, P = 0.001), BASRI-s (r = -0.242, P = 0.047) and sclerostin (r = -0.280, P = 0.024). In multiple regression analysis, periostin levels were an independent variable of CRP (ß = 0.160, P = 0.009) and sclerostin levels (ß = -0.311, P = 0.012). CONCLUSION: Our data suggest that periostin levels are low in patients with AS. Among AS patients, periostin levels are higher in those with higher disease activity, higher systemic inflammation and less extensive radiographic damage. Periostin is independently associated with CRP and sclerostin levels.

Perforation of the cecum by a toothpick: report of a case and review of the literature.

BACKGROUND: Ingesting a foreign body (FB) is not an uncommon occurrence. Most pass through the gastrointestinal (GI) tract uneventfully and rarely cause complications. However, long, sharp, slender, and hard objects such as fish bones, chicken bones, and toothpicks may lead to perforation of the GI tract, which is a potentially life-threatening complication. CASE REPORT: We report the case of a 50-year-old woman who presented to the Emergency Department of our hospital complaining of right lower quadrant abdominal pain of 2 days' duration. Ultrasound imaging and computed tomography scan demonstrated the presence of a foreign body protruding from the lateral cecal wall and surrounded by an area of inflammation. The patient was taken to the operating room, where a toothpick was found to have perforated the cecum. The FB was removed and the defect of the intestinal wall was closed using a TA linear stapler (Covidien, Mansfield, MA). The patient was discharged on the 8(th) postoperative day. We also conducted a literature search for reports on injuries caused by ingested FBs. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Perforation of the GI tract by an ingested FB in the adult population is most commonly secondary to accidental ingestion. Patients rarely recall the episode of the ingestion, or may remember the incident only after a diagnosis is made. We present this case to increase awareness of the diagnosis.

CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity.

Promiscuity of pattern recognition receptors, such as receptor for advanced glycation end products (RAGE), allows for a complex regulatory network controlling inflammation. Scavenging of RAGE ligands by soluble RAGE treatment is effective in reducing delayed-type hypersensitivity (DTH), even in RAGE(-/-) mice by 50% (p < 0.001). This has led to the hypothesis that molecules scavenged by soluble RAGE bind to receptors other than RAGE. This study identifies CD166/ALCAM (ALCAM) as a close structural and functional homolog of RAGE, and it shows that binding of S100B to CD166/ALCAM induces dose- and time-dependent expression of members of the NF-κB family in wild type (WT) and RAGE(-/-) mouse endothelial cells. Blocking CD166/ALCAM expression using small interfering RNA completely inhibited S100B-induced NF-κB activation in RAGE(-/-), but not in WT cells. The in vivo significance of these observations was demonstrated by attenuation of DTH in WT and RAGE(-/-) animals pretreated with CD166/ALCAM small interfering RNA by 50% and 40%, respectively (p < 0.001). Experiments in ALCAM(-/-) animals displayed an only slight reduction of 16% in DTH, explained by compensatory reciprocal upregulation of RAGE in animals devoid of CD166/ALCAM, and vice versa. Consistently, ALCAM(-/-) mice, but not WT mice treated with RAGE small interfering RNA show a 35% reduction in DTH, and ALCAM(-/-) RAGE(-/-) double-knockout mice show a 27% reduction in DTH reaction. Thus, S100B is a proinflammatory cytokine bridging RAGE and CD166/ALCAM downstream effector mechanisms, both being compensatory upregulated after genetic deletion of its counterpart.

Acute phase response following intravenous zoledronate in postmenopausal women with low bone mass.

An acute phase response (APR) is frequently observed in patients treated with intravenous (i.v.) zoledronate (ZOL). We aimed to define clinical and laboratory parameters that may predict ZOL-induced APR in women with low bone mass. Fifty-one postmenopausal women with low bone mass were given a single i.v. infusion of ZOL 5mg. APR was clinically defined by the visual analog pain scale (VAS) for the musculoskeletal symptoms and body temperature. White blood cell count (WBC), leucocyte subpopulations, C-reactive protein (CRP), parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], interleukins (IL)-1b and -6, tumor necrosis factor (TNF)α and interferon (IFN)γ were measured before and 48 h following the infusion. Subsequently, patients were divided into those experiencing APR (APR+) or not (APR-). WBC, granulocytes, CRP, IL-1b and IL-6 were significantly increased, whereas lymphocytes, eosinophils, calcium, phosphate and 25(OH)D decreased 48h after ZOL infusion. Twenty-eight of the 51 patients (54.9%) experienced an APR. APR+ patients were younger and had higher baseline lymphocytes compared to APR- patients. There was no difference (p=0.405) in the development of APR between treatment-naive patients (19/32, 59.4%) and patients previously treated with another oral nitrogen-containing bisphosphonate (9/19, 47.4%). In conclusion, our data suggest that pre-treatment higher lymphocyte number increases the risk of APR while previous treatment with another nitrogen-containing bisphosphonate does not significantly reduce the risk. Serum 25(OH)D concentrations decrease significantly after the infusion, possibly as part of the inflammatory response to ZOL.

The combination of fibrin glue and quilting reduces drainage in the extended latissimus dorsi flap donor site.

BACKGROUND: The use of quilting sutures in the extended latissimus dorsi flap donor site significantly reduces the incidence of donor-site seroma. However, the donor site has a drain inserted, and the duration of use of this drain often dictates when a patient is discharged to home from the hospital. Fibrin glue has been shown to reduce the need for drainage at other operative sites. The authors therefore evaluated the use of fibrin glue (Tisseel Lyo; Baxter Healthcare, Norfolk, United Kingdom) in addition to quilting in reducing the total volume and duration of drainage following extended latissimus dorsi flap breast reconstruction. METHODS: The authors compared a group of 11 consecutive, prospective patients who underwent extended latissimus dorsi donor-site closure with fibrin glue and quilting with a control group of 24 consecutive, retrospective patients who underwent extended latissimus dorsi donor-site closed with quilting alone. RESULTS: The results show that the combination of fibrin glue and quilting in the extended latissimus dorsi flap donor site significantly reduces average drainage in the immediate postoperative period: 13 ml compared with 170 ml (p

Urinary adiponectin excretion: a novel marker for vascular damage in type 2 diabetes.

OBJECTIVE: Markers reliably identifying vascular damage and risk in diabetic patients are rare, and reports on associations of serum adiponectin with macrovascular disease have been inconsistent. In contrast to existing data on serum adiponectin, this study assesses whether urinary adiponectin excretion might represent a more consistent vascular damage marker in type 2 diabetes. RESEARCH DESIGN AND METHODS: Adiponectin distribution in human kidney biopsies was assessed by immunohistochemistry, and urinary adiponectin isoforms were characterized by Western blot analysis. Total urinary adiponectin excretion rate was measured in 156 patients with type 2 diabetes who had a history of diabetic nephropathy and 40 healthy control subjects using enzyme-linked immunosorbent assay. Atherosclerotic burden was assessed by common carotid artery intima-media-thickness (IMT). RESULTS: A homogenous staining of adiponectin was found on the endothelial surface of glomerular capillaries and intrarenal arterioles in nondiabetic kidneys, whereas staining was decreased in diabetic nephropathy. Low-molecular adiponectin isoforms ( approximately 30-70 kDa) were detected in urine by Western blot analysis. Urinary adiponectin was significantly increased in type 2 diabetes (7.68 +/- 14.26 vs. control subjects: 2.91 +/- 3.85 microg/g creatinine, P = 0.008). Among type 2 diabetic patients, adiponectinuria was associated with IMT (r = 0.479, P < 0.001) and proved to be a powerful independent predictor of IMT (beta = 0.360, P < 0.001) in multivariable regression analyses. In a risk prediction model including variables of the UK Prospective Diabetes Study coronary heart disease risk engine urinary adiponectin, but not the albumin excretion rate, added significant value for the prediction of increased IMT (P = 0.007). CONCLUSIONS: Quantification of urinary adiponectin excretion appears to be an independent indicator of vascular damage potentially identifying an increased risk for vascular events.