Cost‐of‐illness of chronic leg ulcers in Germany

Chronic wounds are important because of their frequency, their chronicity and high costs of treatment. However, there are few primary data on the cost‐of‐illness in Germany. The aim was to determine the cost‐of‐illness of venous leg ulcers (VLU) in Germany. Prospective cost‐of‐illness study was performed in 23 specialised wound centres throughout Germany. Direct, medical, non medical and indirect costs to the patient, statutory health insurers and society were documented. Thereover, health‐related quality of life (QoL) was recorded as intangible costs using the Freiburg quality of life assessment for wounds (FLQA‐w, Augustin). A total of 218 patients (62.1% female) were recruited consecutively. Mean age was 69.8 ± 12.0 years. The mean total cost of the ulcer per year and patient was € 9569, [ € 8658.10 (92%) direct and € 911.20 (8%) indirect costs]. Of the direct costs, € 7630.70 was accounted for by the statutory health insurance and € 1027.40 by the patient. Major cost factors were inpatient costs, outpatient care and non drug treatments. QoL was strikingly reduced in most patients. In Germany, VLU are associated with high direct and indirect costs. As a consequence, there is a need for early and qualified disease management. Deeper‐going cost‐of‐illness‐studies and cost‐benefit analyses are necessary if management of chronic wounds is to be improved.     

Effects of hyperglycemia, hyperinsulinemia, and hyperosmolarity on neutrophil apoptosis

BACKGROUND: Hyperglycemia is an independent risk factor for increased mortality of critically ill surgical patients, but despite the recognized clinical benefits of early insulin treatment, there is a lack of understanding of the cellular and molecular mechanisms behind this phenomenon. We hypothesized that polymorphonuclear neutrophils, the first line of the innate immune defense system, suffer from altered apoptotic turnover when exposed to hyperglycemic conditions, ultimately decreasing the number of viable cells active at a site of infection. METHODS: Venous blood samples were drawn from 10 volunteers and incubated for 0.5 or 24 h in a 1:10 dilution with RPMI 1640 medium at various glucose and insulin concentrations. Mannitol was used to control for increased osmolarity. In addition, all samples were incubated either with low-dose lipopolysaccharide (LPS) (1 ng/mL) or without LPS. Neutrophils were extracted using Ficoll-Hypaque density centrifugation and stained with annexin V and propidium iodide. Fluorescence was detected by flow cytometry and analyzed using CellQuest software. RESULTS: The mean percentage of apoptotic neutrophils after 24 h of incubation at physiologic glucose concentrations (100 mg/dL) was 42.2 +/- 4.1%; exposure to low-dose LPS decreased this number to 18.4 +/- 2.5% (p < 0.01). Neither the exposure to low (10 mg/dL) nor increasingly high (200 or 400 mg/dL) glucose concentrations altered these percentages significantly. Exposing whole blood to increasing osmolarity (addition of 5.5 mM and 16.5 mM mannitol to simulate 200 and 400 mg/dL glucose) led to a mean absolute reduction of the percentage of apoptotic neutrophils to 34.6 +/- 3.6% (+5.5 mOsm; p < 0.05) and 32.3 +/- 4.5% (16.5 mOsm; p < 0.01), respectively. CONCLUSIONS: The ability of neutrophils to enter their apoptotic program in cultured whole blood withstands short-term changes in glucose and insulin concentrations. Neither hyperglycemia nor hypoglycemia led to a significant alteration of the apoptotic turnover of these cells, suggesting that the increased rate of infectious complications in short-term hyperglycemic critically ill patients may not be traced to increased apoptosis of neutrophils. However, isolated hyperosmolarity reduces neutrophil apoptosis, an observation that may warrant future investigation.     

Biomaterials as Scaffold for Bone Tissue Engineering

Abstract Almost 20 years after the invention of tissue engineering, autogenous bone grafting has remained the favored strategy for the treatment of bone defects. As an alternative, a vast variety of bone substitutes has been developed and is available for clinical use. The ongoing search for bone substitutes, however, reflects the limitations imposed to both autogenous and allogenous bone grafts as well as to bone substitute materials. The concept of tissue engineering holds great promise for the future treatment of osseous defects. Research in this interdisciplinary field is carried out to find a way of producing biologic substitutes as functional tissue replacement. For this, functionally active cells are applied on supporting scaffolds under controlled stimulation with growth factors. Scaffolds are temporary matrices for bone growth and provide a specific environment and architecture for tissue development. Ideally, scaffolds favor cellular attachment, growth and differentiation in vitro and in vivo. Especially ceramics and biodegradable polymers are widely used and have been tested in various animal studies. Yet, to allow for precise production of specific custom-made scaffolds, rapid prototyping (RP) techniques have recently drawn a lot of attention. Using these methods scaffolds with a predefined, well-controlled internal and external architecture mimicking the structure of natural bone can be generated. Although biocompatibility of the materials used in the process and the structural resolution that can be technically achieved so far limit the range of use, rapid manufacturing techniques do offer great opportunities to generate suitable scaffolds for bone tissue engineering in the near future.     

Gadolinium-enhanced MR angiography of the breast: Is breast cancer associated with ipsilateral higher vascularity?

The aim of this study was to assess a possible association between breast malignancy and ipsilateral higher vascularity on gadolinium-enhanced MR angiography. One hundred six patients were examined by dynamic gadolinium-enhanced 3D MR imaging. Magnetic resonance angiographic views were generated by image subtraction and maximum intensity projection. The study included 85 patients with unilateral malignant breast neoplasms and 21 with unilateral benign lesions. Three blinded readers independently reviewed the MR angiograms after masking the lesions and the corresponding contralateral sites. The readers were asked to determine whether vascularity was higher on the right side, higher on the left side, or equal on both sides. The results were analyzed by the Kappa statistic and Pearson's chi-square test. The blood vessels of the breasts were clearly seen in all cases. There was good agreement among the observers (kappa > 0.54 ) in assessing vascularity on both sides. Breasts harboring malignant neoplasms were found to have a higher vascularity than the contralateral breasts (p < 0.005). This sign of malignancy had a sensitivity of 76.5 %, a specificity of 57 %, and an accuracy of 72.6 %. Blood vessels of the breast can be depicted by MR angiography. Unilateral malignant neoplasms are associated with a higher ipsilateral vascularity. In conjunction with other indications of malignancy on gadolinium-enhanced MR images, a higher ipsilateral vascularity may serve as an additional sign of malignancy. Received: 4 April 2000 Revised: 14 August 2000 Accepted: 18 August 2000     

Direct comparison of 3D spiral vs. Cartesian gradient-echo coronary magnetic resonance angiography.

While 3D thin-slab coronary magnetic resonance angiography (MRA) has traditionally been performed using a Cartesian acquisition scheme, spiral k-space data acquisition offers several potential advantages. However, these strategies have not been directly compared in the same subjects using similar methodologies. Thus, in the present study a comparison was made between 3D coronary MRA using Cartesian segmented k-space gradient-echo and spiral k-space data acquisition schemes. In both approaches the same spatial resolution was used and data were acquired during free breathing using navigator gating and prospective slice tracking. Magnetization preparation (T(2) preparation and fat suppression) was applied to increase the contrast. For spiral imaging two different examinations were performed, using one or two spiral interleaves, during each R-R interval. Spiral acquisitions were found to be superior to the Cartesian scheme with respect to the signal-to-noise ratio (SNR) and contrast-to-noise-ratio (CNR) (both P < 0.001) and image quality. The single spiral per R-R interval acquisition had the same total scan duration as the Cartesian acquisition, but the single spiral had the best image quality and a 2.6-fold increase in SNR. The double-interleaf spiral approach showed a 50% reduction in scanning time, a 1.8-fold increase in SNR, and similar image quality when compared to the standard Cartesian approach. Spiral 3D coronary MRA appears to be preferable to the Cartesian scheme. The increase in SNR may be "traded" for either shorter scanning times using multiple consecutive spiral interleaves, or for enhanced spatial resolution.     

Role of motor-evoked potential monitoring in conjunction with temporary clipping of spinal nerve roots in posterior thoracic spine tumor surgery

Background contextThe vascular supply of the thoracic spinal cord depends on the thoracolumbar segmental arteries. Because of the small size and ventral course of these arteries in relation to the dorsal root ganglion and ventral root, they cannot be reliably identified during surgery by anatomic or morphologic criteria. Sacrificing them will most likely result in paraplegia.PurposeThe goal of this study was to evaluate a novel method of intraoperative testing of a nerve root's contribution to the blood supply of the thoracic spinal cord.Study design/settingThis is a clinical retrospective study of 49 patients diagnosed with thoracic spine tumors. Temporary nerve root clipping combined with motor-evoked potential (MEP) and somatosensory-evoked potential (SSEP) monitoring was performed; additionally, postoperative clinical evaluation was done and reported in all cases.MethodsAll cases were monitored by SSEP and MEPs. The nerve root to be sacrificed was temporarily clipped using standard aneurysm clips, and SSEP/MEP were assessed before and after clipping. Four nerve roots were sacrificed in four cases, three nerve roots in eight cases, and two nerve roots in 22 cases. Nerve roots were sacrificed bilaterally in 12 cases.ResultsMost patients (47/49) had no changes in MEP/SSEP and had no neurological deficit postoperatively. One case of a spinal sarcoma demonstrated changes in MEP after temporary clipping of the left T11 nerve root. The nerve was not sacrificed, and the patient was neurologically intact after surgery. In another case of a sarcoma, MEPs changed in the lower limbs after ligation of left T9 nerve root. It was felt that it was a global event because of anesthesia. Postoperatively, the patient had complete paraplegia but recovered almost completely after 6 months.ConclusionsTemporary nerve root clipping combined with MEP and SSEP monitoring may enhance the impact of neuromonitoring in the intraoperative management of patients with thoracic spine tumors and favorably influence neurological outcome.     

Autosomal dominant polycystic kidney disease: risk factor for nonmelanoma skin cancer following kidney transplantation

Nonmelanoma skin cancers (NMSC) are the most common malignant tumors following solid organ transplantation. Risk factors for NMSC mainly include immunosuppression, age, sun exposure and patient phototype. Recent findings have suggested that autosomal dominant polycystic kidney disease (ADPKD) may increase the risk of developing NMSC. We performed a monocenter retrospective study including all kidney recipients between 1985 and 2006 (n = 1019). We studied the incidence of NMSC, solid cancers and post‐transplantation lymphoproliferative disease (PTLD), and analyzed the following parameters: age, gender, phototype, time on dialysis, graft rank, immunosuppressive regimen, history of cancer and kidney disease (ADPKD versus others). Median follow‐up was 5.5 years (range: 0.02–20.6; 79 838 patient‐years). The cumulated incidence of NMSC 10 years after transplantation was 12.7% (9.3% for solid cancers and 3.5% for PTLD). Autosomal dominant polycystic kidney disease and age were risk factors for NMSC (HR 2.63; P < 0.0001 and HR 2.21; P < 0.001, respectively) using univariate analysis. The association between ADPKD and NMSC remained significant after adjustments for age, gender and phototype using multivariate analysis (HR 1.71; P = 0.0145) and for immunosuppressive regimens (P < 0.0001). Autosomal dominant polycystic kidney disease was not a risk factor for the occurrence of solid cancers after transplantation (HR 0.96; P = 0.89). Our findings suggest that ADPKD is an independent risk factor for developing NMSC after kidney transplantation.     

The 3-step approach for the treatment of multisegmental thoraco-abdominal aortic pathologies

Open in a separate window OBJECTIVESThe goal of this study was to describe our 3-step approach to treat multisegmental thoraco-abdominal aortic disease due to aortic dissection and to present our initial clinical results.METHODSNine patients with multisegmental thoraco-abdominal aortic pathology due to aortic dissection underwent our 3-step approach, which consisted of total aortic arch replacement via the frozen elephant trunk technique, thoracic endovascular aortic repair for distal extension down to the level of the thoraco-abdominal transition and, finally, open thoraco-abdominal aortic replacement for the remaining downstream aortic segments. We assessed their baseline and aortic characteristics, previous aortic procedures, intraoperative details, clinical outcomes and follow-up data.RESULTSThe median age was 58 (42–66) years; 4 patients (44%) presented connective tissue disease. Eight patients (89%) had undergone previous aortic surgery for aortic dissection. In-hospital mortality was 0% (n = 0). None suffered symptomatic spinal cord injury or disabling stroke. During the follow-up period, 1 patient died of acute biliary septic shock 6 months after thoraco-abdominal aortic replacement.CONCLUSIONSThe 3-step approach to treat multisegmental thoraco-abdominal aortic pathology due to aortic dissection, which involves applying both open and endovascular techniques, is associated with an excellent clinical outcome and low perioperative risk. Distal shifting of the disease process through the thoracic endovascular aortic repair extension—and thereby necessitating limited open thoraco-abdominal aortic repair—seems to be the major factor enabling these favourable results.IRB approvalIRB approval was obtained (No. 425/15) from the institutional review board of the University of Freiburg.     

Early commercial experience with a newly designed balloon-expandable transcatheter heart valve: 30-day outcomes and implications of preprocedural computed tomography

OBJECTIVESWe herein report a single-centre experience with the SAPIEN 3 Ultra balloon-expandable transcatheter aortic valve implantation (TAVI) system.METHODSBetween March 2019 and January 2020, a total of 79 consecutive patients received transfemoral TAVI using the SAPIEN 3 Ultra device. Data were retrospectively analysed according to updated Valve Academic Research Consortium-2 definitions. Detailed analysis of multislice computed tomography data was conducted to identify potential predictors for permanent pacemaker (PPM) implantation and residual paravalvular leakage (PVL) post TAVI.Open in a separate windowGraphical AbstractRESULTSDevice success and early safety were 97.5% (77/79) and 94.9% (75/79) with resulting transvalvular peak/mean pressure gradients of 21.1 ± 8.2/10.9 ± 4.4 and PVL >mild in 0/79 patients (0%). Mild PVL was seen in 18.9% (15/79) of cases. Thirty-day mortality was 2.5% (2/79). The Valve Academic Research Consortium-2 adjudicated clinical end points disabling stroke, acute kidney injury and myocardial infarction occurred in 1.3% (1/79), 5.1% (4/79) and 0% (0/79) of patients. Postprocedural PPM implantation was necessary in 7.6% (6/79) of patients. Multislice computed tomography analysis revealed significantly higher calcium amounts of the right coronary cusp in patients in need for postprocedural PPM implantation and a higher eccentricity index in patients with postinterventional mild PVL.CONCLUSIONSFirst experience with this newly designed balloon-expandable-transcatheter heart valve demonstrates adequate 30-day outcomes and haemodynamic results with low mortality, low rates of PPM implantation and no residual PVL >mild. The herein-presented multislice computed tomography values with an elevated risk for PPM implantation and residual mild PVL may help to further improve outcomes with this particular transcatheter heart valve in TAVI procedures.     

Hybrid Renal Cell Carcinomas Containing Histopathologic Features of Chromophobe Renal Cell Carcinomas and Oncocytomas Have Excellent Oncologic Outcomes

Background

Modern histopathology is able to differentiate chromophobe renal cell carcinomas (cRCCs), oncocytomas, and chromophobe–oncocytic hybrid RCCs; however, the true frequency and clinical courses of these tumors remain unclear.

Objective

To determine the clinical course of hybrid RCC.

Design, setting, and participants

Ninety-one surgically treated tumors, originally classified as oncocytoma or cRCC, were slide reviewed and reclassified by an experienced uropathologist. Immunohistochemical cytokeratin-7 (CK7) staining was used to distinguish oncocytoma (CK7 positive in <10% of the cells) and hybrid RCCs (CK7 positive in >10% of the cells).

Interventions

Radical tumor nephrectomy or nephron-sparing surgery.

Measurements

Recurrence-free and tumor-specific survival.

Results and limitations

Overall, 16 tumors (17.6%) were hybrid RCCs, 32 tumors were cRCCs, and 43 tumors were pure oncocytomas. Perinephric tissue invasion (pT3a) was found in one pure oncocytoma and in two hybrid RCCs. The pathologic stage for cRCC was pT1 in 50% of tumors (n = 17), pT2 in 23.5% of tumors (n = 8), and pT3a in 26.5% of tumors (n = 9). Low-grade RCC was found in 76.5% of tumors (n = 26), and vascular invasion was found in 11.8% of tumors (n = 4). After a mean follow-up of 50 mo, no oncocytomas or hybrid RCCs were found, but two cRCCs had recurred. The 3-yr tumor-specific survival rates for patients with oncocytoma, hybrid RCCs, and cRCC were 100%, 100%, and 97%, respectively.

Conclusions

Hybrid RCCs are more common than expected. The survival rate is 100% for both hybrid RCCs and oncocytomas. Hybrid RCCs may be candidates for active surveillance, and surgery may be unnecessary. CRCCs should be treated because a small proportion of these tumors exhibit aggressive clinical courses.