[Diabetic neuropathy and diabetic foot syndrome (update 2023)]. / Diabetische Neuropathie und diabetischer Fuß (Update 2023).

These are the guidelines for diagnosis and treatment of diabetic neuropathy and diabetic foot.The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy, including the complex situation of the diabetic foot syndrome. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided. The needs to prevent and treat diabetic foot syndrome are summarized.

Bariatric surgery prevents carotid wall thickness progression.

BACKGROUND: Bariatric surgery is a treatment option for patients with severe obesity and improves parameters of cardiovascular and/or metabolic disease. Carotid intima media thickness (C-IMT) is a surrogate measure of subclinical atherosclerosis. Previous studies showed short to mid-term arrest and even regression of C­IMT progression following bariatric surgery. We aimed to investigate the long-term effect of weight loss on C­IMT progression 10 years after bariatric surgery in comparison to a population-based control cohort. METHODS: In total, 21 eligible patients were examined preoperatively, at 5 and 10 years after bariatric surgery. Anthropometric parameters, plasma triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), insulin, and glucose were assessed at all three study visits. C­IMT was measured via B­mode scans of the common carotid artery. C­IMT progression was measured in an age-matched and BMI-matched cohort selected from the population-based Bruneck study to compare with changes in C­IMT progression after bariatric surgery. RESULTS: C­IMT remained stable over the 10-year observation period after bariatric surgery. The control cohort showed a significant C­IMT progression over 10 years. The difference in C­IMT progression over 10 years was significant (p < 0.01) between both cohorts. CONCLUSION: Weight loss induced by bariatric surgery halts the natural progression of C­IMT over a 10-year observation period.

Stereotactic Radiofrequency Ablation of an Unresectable Intrahepatic Cholangiocarcinoma (ICC): Transforming an Aggressive Disease into a Chronic Condition.

In 2010, we reported on a 72-year-old patient with a large, unresectable cholangiocarcinoma with intrahepatic metastases, which was treated by stereotactic radiofrequency ablation (SRFA) in three consecutive sessions. Within the last nine years, the same patient has received seven additional ablation sessions for a total of ten recurrent intrahepatic lesions. One year after the last SRFA, the patient's liver function is still within the physiological range, suggesting that this approach is not only sufficient for locally controlling tumor disease, but also for sparing healthy tissue. Moreover, periods of hospitalization were relatively short, while procedure-related pain was generally mild. In summary, SRFA has turned an aggressive disease with a devastating prognosis into a chronic condition while improving the patient's quality of life.

[Diabetic neuropathy and diabetic foot syndrome (Update 2019)]. / Diabetische Neuropathie und diabetischer Fuß (Update 2019).

These are the guidelines for diagnosis and treatment of diabetic neuropathy and diabetic foot. Diabetic neuropathy comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy.The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy, including the complex situation of the diabetic foot syndrome. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided. The needs to prevent and treat diabetic foot syndrome are summarized.

[The diabetic foot]. / Diabetischer Fuß.

These are the guidelines for preventive care, diagnosis and treatment of the diabetic foot syndrome. Diabetic periphery neuropathy, peripheral vascular disease, bone deformity and altered biomechanics are foot-related risk conditions. The position statement is focused on screening methods and recommendations for clinical care for diabetics, who currently have no foot ulcers. A decision pathway is offered with respect to diagnosis and management of diabetic patients at an increased risk or manifest injuries.

Incidence of Gallstone Formation and Cholecystectomy 10 Years After Bariatric Surgery.

PURPOSE: Rapid weight loss is a risk factor for gallstone formation, and postoperative treatment options for gallstone formation are still part of scientific discussion. No prospective studies monitored the incidence for gallstone formation and subsequent cholecystectomy after bariatric surgery longer than 5 years. The aim of the study was to determine the incidence of gallstone formation and cholecystectomy in bariatric patients over 10 years. MATERIALS AND METHODS: One hundred nine patients were observed over 10 years after laparoscopic gastric banding or gastric bypass/gastric sleeve. The incidence of gallstone formation and cholecystectomy was correlated to longitudinal changes in anthropometric parameters. RESULTS: In total, 91 female and 18 male patients were examined. Nineteen patients had postoperative gallstone formation, and 12 female patients required cholecystectomy. The number needed to harm for gallstone formation was 7.1 and 2.3 cases in the banding group and gastric bypass/gastric sleeve group, respectively. The number needed to harm for cholecystectomy was 11.6 and 2.5 cases in the banding group and the gastric bypass/gastric sleeve group, respectively. Weight loss was higher in patients requiring subsequent cholecystectomy. Mean follow-up to cholecystectomy was 21.5 months with the latest operation after 51 months. CONCLUSION: Female gender and rapid weight loss were major risk factors for postoperative cholelithiasis. Ultrasound examinations within 2 to 5 years are recommended in every patient, independent of bariatric procedure. Pharmacologic treatment should be considered in high risk patients within 2 to 5 years to prevent postoperative cholelithiasis. This helps to optimize patient care and lowers postoperative morbidity.

Effect of weight loss on serum pigment epithelium-derived factor levels.

BACKGROUND: Cumulating evidence suggests that the broadly acting neurotrophic pigment epithelium-derived factor is associated with visceral adiposity, the metabolic syndrome, diabetes and exerts beneficial effects on atherosclerosis. To further elucidate the relationship between pigment epithelium-derived factor and metabolic perturbations characteristic of obesity, we examined the effect of pronounced weight loss on serum levels of pigment epithelium-derived factor. MATERIALS AND METHODS: Thirty-six severely obese adults were examined before and 18 months after bariatric surgery. Abdominal fat distribution was determined by ultrasound, metabolic parameters by standard methods, pro-inflammatory biomarkers and serum pigment epithelium-derived factor levels by enzyme-linked immunosorbent assay. RESULTS: Bariatric surgery resulted in a mean body mass index (BMI) reduction of 9·0 ± 5·0 kg m(-2) and concomitant improvements in glucose homoeostasis and lipid profile. Pigment epithelium-derived factor serum levels decreased from a median 11·0 µg mL(-1) (interquartile range: 3·8) to 9·2 µg mL(-1) (interquartile range: 4·5) (P < 0·0001). In univariate analysis, relative change in pigment epithelium-derived factor levels was significantly associated with change in weight, BMI, fat mass, visceral fat diameter, insulin, homoeostasis model for insulin resistance, triglyceride and leptin levels (all r > 0·370, P < 0·05). No associations were observed for C-reactive protein, interleukin-6 or tumour necrosis factor alpha. After adjustment for age, sex and smoking status, associations remained significant. CONCLUSIONS: The beneficial effects of bariatric surgery-induced pronounced weight loss on glucose homoeostasis may partially be attributable to visceral adipose tissue reduction and concomitantly decreasing pigment epithelium-derived factor concentrations.

Influence of significant weight loss on serum matrix metalloproteinase (MMP)-7 levels.

BACKGROUND: Matrix metalloproteinases (MMPs) and their specific inhibitors (tissue inhibitor of metalloproteinases [TIMPs]), are involved in adipogenesis, angiogenesis and remodeling of extracellular matrix. MMPs and TIMPs have been shown to be associated with various diseases such as neurological disorders, malignancies and cardiovascular disease. MMPs and TIMPs are thought to play a major role in extensive reorganization of the adipose tissue in obesity. METHODS AND MATERIALS: To test whether significant weight loss alters circulating MMPs and TIMPs, 18 morbidly obese women, who underwent bariatric surgery for weight loss, were investigated before and one year after surgery in a prospective design study. Body composition, glucose and lipid metabolism parameters were determined in all study subjects before and after weight loss. Circulating MMP-2, -3, -7 and TIMP-1, -2 and -4 serum levels were measured using commercially available, enzyme-linked immunoassays. RESULTS: Pronounced weight loss was accompanied by improvements in glucose homeostasis and lipid parameters. In the mean time MMP-2 and MMP-3, as well as TIMP-1, -2 and TIMP-4 concentrations were not affected by significant weight loss, and circulating MMP-7 increased significantly after bariatric surgery, although without reaching the standard levels as determined in 18, lean, healthy women. CONCLUSION: Our data indicate that reduced MMP-7 levels in obesity might be restored by significant weight loss, suggesting that the reorganization of adipose tissue in obesity might be partially reversible by weight reduction. We hypothesize that increased circulating MMP-7 might indicate enhanced adipocyte differentiation in subjects who had undergone bariatric surgery.

Effect of bariatric surgery on both functional and structural measures of premature atherosclerosis.

AIMS: To bridge the beneficial metabolic effects of pronounced weight loss on one side and the data on morbidity and mortality on the other side, we investigated the impact of profound weight loss on structural and functional markers of early atherosclerosis. METHODS AND RESULTS: Thirty-seven obese adults were examined before and 18 months after bariatric surgery. Carotid intima-media thickness (CIMT), brachial flow-mediated dilation (FMD), nitroglycerine-mediated dilation, and abdominal fat distribution were assessed by high-resolution ultrasound. Surgery resulted in a body mass index decrease of 9.1 +/- 4.9 kg/m(2) with concomitant improvements in glucose and lipid metabolism. Carotid intima-media thickness diminished from 0.56 +/- 0.09 to 0.53 +/- 0.08 mm (n = 37; P = 0.004). Flow-mediated dilation improved from 5.81 +/- 3.25 to 9.01 +/- 2.93% (n = 25; P < 0.001). Both CIMT and FMD were associated with intra-abdominal fat diameter. CONCLUSION: The present results demonstrate that bariatric surgery-induced diminution of visceral fat improves both functional and structural markers of early atherosclerosis, providing a link between the weight loss-associated improvements of traditional and non-traditional risk factors and the reduced long-term morbidity and mortality after bariatric surgery.

Influence of visceral obesity and liver fat on vascular structure and function in obese subjects.

Endothelial dysfunction and increased intima-media thickness (IMT) have been found in obese patients. Both regional fat distribution and liver steatosis may influence these markers of subclinical atherosclerosis. We sought to determine the interrelationships of endothelial function, carotid IMT, visceral and subcutaneous adipose tissue accumulation, and liver steatosis in severely obese subjects. In 64 severely obese patients (BMI 42.3 +/- 4.3 kg/m(2)), we determined (i) endothelial function as flow-mediated dilation (FMD) of the brachial artery, (ii) carotid IMT, (iii) visceral fat diameter, and (iv) degree of liver steatosis using ultrasound. FMD was associated inversely with visceral fat diameter and degree of steatosis (r = -0.577, P < 0.0001 and r = -0.523, P < 0.0001, respectively). Carotid IMT correlated with visceral fat mass (r = 0.343, P = 0.007) but not with liver steatosis. After adjustment for conventional cardiovascular risk factors, FMD was predicted independently by the visceral fat diameter, age, and sex (r(2) = 0.48, P < 0.0001), but not by the degree of liver steatosis or plasma adiponectin levels. In contrast, age and sex were the only predictors of IMT (r(2) = 0.33, P < 0.001). In obese patients, visceral fat diameter is a major determinant of endothelial dysfunction, independent of traditional risk factors or the degree of liver steatosis and plasma adiponectin. Measurement of visceral fat diameter by ultrasound is a novel and simple method to identify subjects with an increased risk for atherosclerosis within an obese population.

Retinol-binding protein 4, visceral fat, and the metabolic syndrome: effects of weight loss.

Retinol-binding protein 4 (RBP-4) has been reported to be associated with visceral-fat accumulation and parameters of the metabolic syndrome (MetS). In this study, we investigated the relationship between RBP-4, visceral fat, and the MetS during pronounced weight loss after bariatric surgery. Thirty-six subjects were examined before and 2 years after surgery. Abdominal-fat distribution was determined by ultrasound, metabolic parameters, and serum RBP-4 levels by standard methods. After surgery BMI decreased by 9.07 kg/m(2), visceral-fat diameter (VFD) decreased by 60.6%, and RBP-4 serum levels by 16.6%. Change of RBP-4 levels was associated with reductions of waist (r = 0.364, P = 0.037), waist-to-hip ratio (WHR) (r = 0.415, P = 0.016), and VFD (r = 0.425, P = 0.010). MetS, as defined by International Diabetes Federation (IDF), was present in 19 patients at baseline and in nine patients at follow-up. Change in RBP-4 levels was the best predictor for the diagnosis of MetS at follow-up. In the subgroup without MetS at baseline, the decrease in RBP-4 levels (-28.1% vs. -6.3%, P = 0.020) and reduction in VFD (-66.9% vs. -55.0%, P = 0.038) were significantly greater compared to the subgroup with MetS. We demonstrate a marked decrease of RBP-4 levels after bariatric surgery, which correlates with reduction in visceral-fat mass. Furthermore, the extent of changes in RBP-4 levels differs according to the severity of the MetS.

Post-chemotherapy laparoscopic retroperitoneal lymph-node dissection in testis cancer patients.

BACKGROUND AND PURPOSE: Retroperitoneal lymph node dissection (RPLND) is still the most sensitive and specific method for the detection of malignant tumor and mature teratoma in stage II nonseminomatous testicular carcinoma after chemotherapy. Acceptance of this operation, however, has decreased because of the morbidity associated with the open approach. To reduce the morbidity and to improve the acceptance of RPLND, laparoscopy has been introduced. In this study, we describe our experiences with laparoscopic RPLND for stage II testicular carcinoma after chemotherapy. METHODS: Sixteen patients underwent 17 laparoscopic RPLND after chemotherapy for clinical stage IIA-III nonseminomatous testicular cancer. Patients with post-chemotherapy residual masses >1 cm and normalization of tumor markers were considered for the procedure. Our dissection field included the resection of the residual tumor as well as the ipsilateral template. RESULTS: Laparoscopic RPLND was completed in all patients. Operative time ranged from 125 to 370 minutes (mean 240 +/- 56 min). No transfusions were required, and no intra- or postoperative complications occurred because of the procedure. A bleomycin-induced interstitial pneumonia developed in one patient. After a mean follow-up period of 26 +/- 11 months (range 4 to 38), two disease recurrences were observed. CONCLUSION: Laparoscopic RPLND after chemotherapy is a feasible and oncologically safe procedure. However, the technique is challenging and should only be performed in selected patients with low residual tumor volume.

Carotid plaques and their predictive value for cardiovascular disease and all-cause mortality in hemodialysis patients considering renal transplantation: a decade follow-up.

BACKGROUND: Carotid plaque formation is very common in dialysis patients. The prognostic value of plaques, both calcified and noncalcified, rarely was investigated prospectively in these patients. By using a carotid plaque score, this study aims to determine the risk for combined cardiovascular disease (CVD) events and all-cause mortality in 165 hemodialysis patients in a long-term follow-up considering phases of renal transplantation. METHODS: Baseline carotid ultrasonography was performed in 165 hemodialysis patients to screen for carotid plaques. Patients subsequently were followed up for a period up to 13 years (average, 86 months). Because of biases associated with renal transplantation, 3 methods of multivariate analysis were compared by using Cox proportional hazards regression models. RESULTS: Plaques were present in 107 of 165 patients (65%). During the observation period, 50 patients (30%) experienced a combined CVD event, 95 patients (58%) died, and 79 patients (48%) underwent at least 1 renal transplantation. Mean plaque score differed significantly between patients who reached an end point and those who did not (CVD events, 3.1 +/- 2.7 versus 2.0 +/- 2.4; P = 0.01; all-cause mortality, 3.5 +/- 2.6 versus 0.9 +/- 1.3; P < 0.001). Plaque score entered all 3 tested Cox regression models for CVD events and all-cause mortality. The lowest statistical power was associated with censoring at the time of renal transplantation. Not considering transplantation at all neglected a major change in risk. CONCLUSION: We identified carotid plaque score and treatment modality as highly significant predictors for CVD events and all-cause mortality.

Laparoscopic management of the adult nonpalpable testicle.

OBJECTIVES: This report describes own experiences with laparoscopic management of adult men with cryptorchidism. PATIENTS AND METHODS: 8 men with nonpalpable testes were referred to our department. Laparoscopy was used to assess the presence and location of the gonad and perform an orchiectomy or orchidopexy, respectively. RESULTS: A uni-/bilateral atrophic testicle was palpable in 2 patients under general anesthesia and removed after inguinal exploration. In 4 individuals the testicular vessels and vas deferens were found laparoscopically entering the internal inguinal ring. Two vanishing testicles and 2 atrophic gonads were removed during subsequent inguinal exploration. In 1 patient with a solitary testis, a morphologically intact abdominal testicle was presented. In this patient, endocrine function was lost completely after stage 1 of a Fowler-Stephens orchidopexy. In 1 patient an atrophic abdominal testicle was removed laparoscopically. CONCLUSIONS: These results demonstrate the suitability of laparoscopy for the treatment of cryptorchidism in the adult population. In most cases, atrophic inguinal gonads or vanishing testicles are found and should be removed. Our results suggest that in cases of intact abdominal testicles, Fowler-Stephens orchidopexy with transection of the spermatic vessels should be avoided to preserve endocrine function of the gonad.

Laparoscopic retroperitoneal lymph-node dissection with the waterjet is technically feasible and safe in testis-cancer patient.

BACKGROUND AND PURPOSE: The acceptance of open retroperitoneal lymph node dissection (RPLND) for stage I and II nonseminomatous testicular cancer has decreased because of the intraoperative and postoperative morbidity of the procedure. Laparoscopic RPLND is a minimally invasive and safe alternative for low-stage germ-cell tumors. It is, however, technically demanding and should therefore be performed only in experienced centers. The purpose of the present study was to evaluate the waterjet technique for laparoscopic RPLND. PATIENTS AND METHODS: A series of 18 patients with clinical stage I testis cancer (group A) and 7 patients who had received chemotherapy for stage II disease (group B) underwent laparoscopic RPLND at our institution. The procedure was performed identically to the open approach using the modified template according to Weissbach and associates. The waterjet was used for removal of lymphatic tissue from the aorta and the vena cava, as well as from the sympathetic trunk. RESULTS: The operation was completed in all patients without conversion to open surgery. The mean operating time was 232 +/- 48 minutes. The waterjet was able to remove lymphatic tissue easily and atraumatically. At pressures of 20 bar, the lymph-node capsule remained completely intact, thus avoiding tumor-cell spread. Antegrade ejaculation could be preserved in all patients, who, to date, show no evidence of disease. CONCLUSIONS: The waterjet allows the safe and complete removal of lymphatic tissue, leaving vulnerable anatomic structures intact. It can decrease the learning curve of laparoscopic RPLND and contribute to better acceptance of this procedure.

Secretoneurin, an angiogenic neuropeptide, induces postnatal vasculogenesis.

BACKGROUND: Induction of postnatal vasculogenesis, the mobilization of bone marrow-derived endothelial progenitor cells and incorporation of these cells into sites of blood vessel formation, is a well-known feature of angiogenic cytokines such as vascular endothelial growth factor. We hypothesized that the angiogenic neuropeptide secretoneurin induces this kind of neovascularization. METHODS AND RESULTS: Secretoneurin induced mobilization of endothelial progenitor cells to sites of vasculogenesis in vivo in the cornea neovascularization assay. Progenitor cells were incorporated into vascular structures or were located adjacent to them. Systemic injection of secretoneurin led to increase of circulating stem cells and endothelial progenitor cells. In vitro secretoneurin induced migration, exerted antiapoptotic effects, and increased the number of these cells. Furthermore, secretoneurin stimulated the mitogen-activated protein kinase system, as shown by phosphorylation of extracellular signal-regulated kinase, and activated the protein kinase B/Akt pathway. Activation of mitogen-activated protein kinase was necessary for increase of cell number and migration, whereas Akt seemed to play a role in migration of endothelial progenitor cells. CONCLUSIONS: These data show that the angiogenic neuropeptide secretoneurin stimulates postnatal vasculogenesis by mobilization, migration, and incorporation of endothelial progenitor cells.

Valproate therapy and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease was defined recently as another symptom of insulin resistance. Continuous therapy with valproate can result in increased body weight and insulin resistance, but no data are yet available on a possible relationship between valproate and nonalcoholic fatty liver disease. We here demonstrate in abdominal ultrasound investigations that characteristics of fatty liver disease were present in 61% of valproate-treated patients as compared with 23% receiving carbamazepine therapy.