The association of six autoimmune bullous diseases with thyroid disorders: a population-based study.

BACKGROUND: The association of autoimmune bullous diseases (AIBDs) with thyroid disorders remains to be profoundly investigated. OBJECTIVE: To evaluate the epidemiological association between six AIBDs and thyroid disorders. METHODS: A population-based cross-sectional study enrolled patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with these six AIBDs were compared with six age- and sex-matched control groups regarding the prevalence of thyroiditis and hyperthyroidism. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for thyroid disorders. RESULTS: The study population included 1,743, 251, 106, 126, 860 and 103 patients with BP, MMP, EBA, PG, PV and PF respectively. The corresponding control groups consisted of 10,141, 1,386, 606, 933, 5,142 and 588 matched controls respectively. A significant association was found between thyroiditis and BP (OR, 1.98; 95% CI, 1.18-3.35; P = 0.010), MMP (OR, 7.02; 95% CI, 1.87-26.33; P = 0.004) and PV (OR, 2.73; 95% CI, 1.45-5.15; P = 0.002). With regards to hyperthyroidism, PF was the only AIBD to demonstrate significant comorbidity (OR, 2.42; 95% CI, 1.13-5.21; P = 0.024). EBA and PG were not found to cluster with any of the investigated thyroid conditions. CONCLUSION: Patients with BP, MMP, PV and PF experience an elevated burden of thyroid disorders. Patients with these AIBDs presenting with suggestive symptoms may be carefully screened for comorbid thyroid disorders.

The burden of neurological comorbidities in six autoimmune bullous diseases: a population-based study.

BACKGROUND: Apart from bullous pemphigoid (BP), the association of other autoimmune bullous diseases (AIBDs) with neurological conditions is poorly understood. OBJECTIVE: To estimate the association between a wide array of AIBDs and neurological conditions. METHODS: A retrospective cross-sectional study recruited patients with BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV) and pemphigus foliaceus (PF). These patients were compared with their age- and sex-matched control subjects with regard to the lifetime prevalence of Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy and multiple sclerosis (MS). Logistic regression was used to calculate OR for specified neurological disorders. RESULTS: The current study included 1743, 251, 106, 126, 860 and 103 patients diagnosed with BP, MMP, EBA, PG, PV and PF, respectively. These patients were compared with 10 141, 1386, 606, 933, 5142 and 588 matched controls, respectively. Out of the investigated neurological conditions, PD associated with BP (OR, 2.71; 95% CI, 2.19-3.35); AD with BP (OR, 2.11; 95% CI, 1.73-2.57), MMP (OR, 2.37; 95% CI, 1.03-5.47), EBA (OR, 6.00; 95% CI, 1.90-18.97) and PV (OR, 2.24; 95% CI, 1.40-3.60); stroke with BP (OR, 1.84; 95% CI, 1.55-2.19) and EBA (OR, 2.79; 95% CI, 1.11-7.01); and epilepsy with BP (OR, 2.18; 95% CI, 1.72-2.77) and PV (OR, 1.80; 95% CI, 1.19-2.73). MS did not significantly cluster with any of the six AIBDs. CONCLUSION: In addition to BP, EBA and PV were found to cluster with neurological comorbidities. Patients with these AIBDs with compatible symptoms may be carefully assessed for comorbid neurological disorders.

Incidence of pemphigoid diseases in Northern Germany in 2016 - first data from the Schleswig-Holstein Registry of Autoimmune Bullous Diseases.

BACKGROUND: Autoimmune bullous diseases (AIBD) are rare disorders characterized by autoantibody formation against components of adhesion molecules; in pemphigoid diseases (PD), these are proteins of hemidesmosomes and basement membrane, important for cell-matrix adhesion in skin and/or mucous membranes. Incidences of these diseases vary considerably between different populations. OBJECTIVES: To establish a registry prospectively recruiting all AIBD patients in a geographically well-defined region in Northern Germany (Schleswig-Holstein). METHODS: Only patients with verified disease (by clinical presentation, histology, direct and/or indirect immunofluorescence and /or ELISA) living in Schleswig-Holstein were included. Incidences of PD were estimated based on the total number of inhabitants in Schleswig-Holstein, stratified by birth year and sex. RESULTS: Of 67 patients with PD [35 male, 32 female, mean age 75 (standard deviation 14.3 years)], 83% were patients with bullous pemphigoid [n = 56, 28 male, 28 female, mean age 78 (SD 9.9)]. The resulting crude incidences were 23.4 patients/million/year for all pemphigoid patients, 19.6 patients/million/year for bullous pemphigoid (age-standardized 16.9 patients/million/year) with a strong increase in bullous pemphigoid patients in the age group of 85-90 years with 262 patients/million/year. Incidences for bullous pemphigoid were higher in urban compared to rural areas. Other PD (mucous membrane pemphigoid, linear IgA disease, anti-p200 pemphigoid) were less frequent with crude incidences of 2.1, 1.0 and 0.7 patients/million/year, respectively. CONCLUSIONS: This study prospectively analyses the incidence of PD in a carefully defined geographical area. The highest incidence among PD patients was found for bullous pemphigoid. The incidence of bullous pemphigoid is considerably increased compared to previous reports and reveals regional differences. Further studies are needed in order to clarify these findings.

Prevalence and age distribution of pemphigus and pemphigoid diseases among paediatric patients in Germany.

BACKGROUND: Autoimmune bullous diseases are rare and mostly occur in adults. Several cases and small case series have been described in children, but no systematic study about the prevalence of autoimmune bullous diseases (AIBD) in children is available. PATIENTS AND METHODS: We analysed data of 1.7 million children insured in the largest German health insurance company based on the ICD-10-GM classification for the year 2015. Data were adjusted to the general German population based on the data of the Federal Statistical Office for the year 2015. RESULTS: The prevalence of AIBD was calculated to 101.1/million children in 2015, resulting in about 1351 patients below the age of 18 years in Germany. The highest prevalence of all AIBD was seen for pemphigus vulgaris (30.5/million children) followed by linear IgA disease (24.5/million children) and bullous pemphigoid (4.9/million children). CONCLUSION: Autoimmune bullous diseases in minors are scarce but should be taken into consideration in patients with pruritus and/or blisters and erosions on the skin and/or mucous membranes. Treatment is challenging, and due to the rarity of AIBD in minors, the management of these disorders in this patient population is best performed in specialized centres in a multidisciplinary approach, including paediatric dermatologists or dermatologists and paediatricians.

Validation of a mathematical model for laser-induced thermotherapy in liver tissue.

The purpose of the study was to develop a simulation approach for laser-induced thermotherapy (LITT) that is based on mathematical models for radiation transport, heat transport, and tissue damage. The LITT ablation was applied to ex vivo pig liver tissue. Experiments were repeated with different laser powers, i.e., 22-34 W, and flow rates of the cooling water in the applicator system, i.e., 47-92 ml/min. During the procedure, the temperature was measured in the liver sample at different distances to the applicator as well as in the cooling circuit using a fiber optic thermometer. For validation, the simulation results were compared with the results of the laser ablation experiments in the ex vivo pig liver samples. The simulated and measured temperature curves presented a relatively good agreement. The Bland-Altman plot showed an average of temperature differences of -0.13 ∘C and 95%-limits-of-agreement of ±7.11 ∘C. The standard deviation amounted to ±3.63 ∘C. The accuracy of the developed simulation is comparable with the accuracy of the MR thermometry reported in other clinical studies. The simulation showed a significant potential for the application in treatment planning.

Depression and quality of life in terms of personal resources in heart transplant recipients.

BACKGROUND: Heart transplantation is the first option for treatment of heart failure engendering increased survival and quality of life among recipients. However, this surgical intervention causes many psychological problems such as depression and anxiety. Protective factors and personal recourses are significant forces behind healthy adjustments to life stresses. PURPOSE: The aim of this study was to estimate the prevalence of depression among heart transplant recipients. PROCEDURE: The study consisted of a sample of 46 patients after heart transplantation. Standardized instruments used to measure the key constructs were Beck Depression Inventory Short Form for the prevalence of depression, World Health Organization Quality of Life--BREF for quality of life, Sense of Coherence (SOC-29), and Coping Orientation to Problems Experienced BREF to identify coping strategies. The data were analyzed statistically. RESULTS: We found that sense of coherence and coping strategies were significant predictors for quality of life and prevalence of depression, which were significantly associated with each others. Strategies focused on the problem are moderate quality of life with an age of recipient. Recipients who have a tendency to use emotion-focused strategies and are older showed a poorer quality of life, were less satisfied with their health, and displayed a prevalence of depression. CONCLUSIONS: These results suggested that assessment of coping strategies and sense of coherence should be explored in heart transplant recipients with skills training in this domain.

Mechanical gluteal soft tissue material parameter validation under complex tissue loading.

BACKGROUND: Finite element (FE) simulations of mechanical tissue loading help provide insight into internal tissue stress and strain distribution. Thus, better understanding of pressure sore aetiology and pressure sore prophylaxis can be acquired. Indispensable in the simulation process is adequate mechanical description of interacting soft tissue and body support materials. Sufficient verification of employed material parameters is required. METHOD OF APPROACH: Gluteal soft tissue material parameters, previously derived from experimental tissue indentation of a geometrically limited buttock sub-domain are shown to be suitable in simulating complex deformation of the entire buttocks. In the context of parameter verification, defined tissue loading via a soft foam material specimen was performed. Making use of magnetic resonance imaging (MRI), the scenario was scanned to gain tissue displacement information. Anatomical surface data was reconstructed and an FE-model of the experimental situation was generated and simulated. MR-image information was compared with simulation results. RESULTS: Deformation of gluteal skin/fat and passive muscle tissue and support material under loading was in good agreement with the corresponding MR-image data. Visual accordance was found for deformed skin boundary as well as for internal fat-muscle tissue boundaries by superimposing experimental and numerical output. In addition, section surface boundaries of the MR-images and the FE-model of skin/fat and muscle at the deformed state were discretized and sufficient sample points were provided. A correlation factor of R2= 0.998 for skin/fat deformation was derived, comparing simulation with MRI output. CONCLUSION: Reliability of employed tissue material parameters for use in realistic loading scenarios at finite strains including complex tissue and bone anatomy, non-linear tissue support material, multiple tissue types and contact interactions is shown.

Analysis of mechanical interaction between human gluteal soft tissue and body supports.

Pressure sores are the most common complication associated with patient immobilization. They develop through sustained localized tissue strain and stress, primarily caused by body supports. Modifying support design can reduce the risk and extent of pressure sore development with computational simulations helping to provide insight into tissue stress-strain distribution. Appropriate material parameters for human soft tissue and support material, as well as precise anatomical modelling, are indispensable in this process. A finite element (FE) model of the human gluteal region based on magnetic resonance imaging (MRI) data has been developed. In vivo human gluteal skin/fat and muscle long-term material parameters as well as open-cell polyurethane foam support long-term material parameters have been characterised. The Ogden form for slightly compressible materials was employed to describe human gluteal soft tissue behaviour. Altering support geometries and support materials, effects on human gluteal soft tissue could be quantified. FE-analysis indicated maximal tissue stress at the muscle-bone interface, not at the skin. Shear strain maxima were found in the muscle layer near the fat-muscle interface. Maximum compressive stress magnitude at the sacral bone depended strongly on the behaviour of the pelvic diaphragm musculature. We hypothesize that the compliance of the muscles forming the pelvic diaphragm govern the relative motion of the buttock tissue to the adjacent bone structure under compression, thus influencing tissue stress magnitudes.

A method for a mechanical characterisation of human gluteal tissue.

The most common complication associated with immobilization is pressure sores caused by sustained localized tissue strain and stress. Computational simulations have provided insight into tissue stress-strain distribution, subject to loading conditions. In the simulation process, adequate soft tissue material parameters are indispensable. An in vivo procedure to characterise material parameters of human gluteal skin/fat and muscle tissue has been developed. It employs a magnetic resonance imaging (MRI) device together with an MRI compatible loading device. Using the derived data as constraints in an iterative optimization process the inverse finite element (FE) method was applied. FE-models were built and the material constants describing skin/fat and muscle tissue were parameterized and optimized. Separate parameter sets for human gluteal skin/fat and muscle were established. The long-term shear modulus for human gluteal skin/fat was G_{infinity, S/F}= 1182 Pa and for muscle G_{infinity, M} = 1025 Pa. The Ogden form for slightly compressible materials was chosen to define passive human gluteal soft tissue material behaviour. To verify the approach, the human skin/fat-muscle tissue compound was simulated using the derived material parameter sets and the simulation result was compared to empirical values. A correlation factor of R;{2} = 0.997 was achieved.

[MR thermometry for laser-induced thermotherapy at 1.5 Tesla]. / MR-Thermometrie bei 1,5 Tesla zur thermischen Ablation mittels laserinduzierter Thermotherapie.

PURPOSE: Evaluation of thermometry with fast MR sequences for laser-induced interstitial laser therapy (LITT) and verification of the thermometric results with a fiber-optic thermometer. METHOD AND MATERIALS: In vitro experiments were conducted using an agarose gel mixture and pig liver lobes. MR-guided LITT was performed using a laser power between 3 and 15 watts. Thermometry was performed using longitudinal relaxation time T1 and proton resonance frequency shift (PRF) methods under acquisition of amplitude and phase shift images. PRF was measured with a fast spoiled GRE sequence. Four different sequences were used for T1 thermometry: gradient echo (GE), TrueFISP (TRUFI), Saturation Recovery Turbo-FLASH (SRTF) and Inversion Recovery Turbo-FLASH (IRTF) sequences. The temperature was controlled using a fiber-optic Luxtron device and correlated with the MR temperature. The range of applied and monitored temperatures exceeded 80 degrees Celsius. RESULTS: The temperature dependence showed a good linear relationship up to 60 degrees Celsius. Calibration experiments for the T1 method delivered coefficients of determination from 0.977 to 0.997 for agarose and from 0.958 to 0.995 for the pig liver samples. The IRTF sequence had the highest temperature sensitivity (agarose 0.99, liver 1.19). During LITT the TRUE-FISP sequence exhibited a strong nonlinear relationship. R (2) of this sequence was 0.809 in the agarose experiments. The average temperature errors when heated up to 80 degrees Celsius were 3.86-11.38 degrees Celsius for Agarose gel and 5.7-12.16 degrees Celsius for the liver tissue. SRTF and IRTF sequences exhibited the most linear relationship with temperature but were more dependent on tissue differences. CONCLUSION: The accuracy of the temperature measurement is sufficient for controlling the coagulation area of the LITT. PRF is the method of choice since it shows the best linear correlation with fiber-optic temperature. If only T1 sequences are concerned, the FLASH sequence is preferred. It is the most robust, though not the most accurate, T1 sequence.

[In vivo proton MR spectroscopy of normal liver parenchyma: technique and results]. / In-vivo-Protonenspektroskopie des Leberparenchyms: Technik und Ergebnisse.

PURPOSE: To analyze the proton magnetic resonance spectroscopic data ( (1)H MRS) of normal liver parenchyma with regard to age, sex, body mass index and location in the liver. MATERIALS AND METHODS: 45 healthy volunteers age 24 to 65 years were examined with an optimized single-voxel (1)H MRS using a 1.5-T scanner. A spin echo sequence with a TR of 1500 ms and a TE of 135 ms was used, allowing in-phase detection of the choline signal. Weak water suppression was achieved using a chemical shift selective suppression (CHESS) technique. Each examination included the measurement of three voxels with a voxel size of 18 x 18 x 18 mm (3) in different areas of the liver. The volunteers were divided into different age-based groups (young: < or = 44 years; older: > or = 44 years), BMI (normal weighted: < 25 kg/m (2); obese: > 25 kg/m (2)) and sex. RESULTS: In the acquired spectra different lipid (e. g. [CH (2)] (n)), choline, glutamine, glutamate and glycogen-glucose-complex resonances were detected. The analysis of the spectra, however, only focused on the concentrations of choline and (CH (2)) (n) and the relative concentrations of the choline-to-(CH (2)) (n)-ratios. In the older volunteers the relative concentration of the choline-to-(CH (2)) (n)-ratio was significantly decreased by 0.213 +/- 0.193 in comparison to the younger subjects (p = 0,031). Further statistical analysis confirmed a significant decrease of the choline-to-(CH (2)) (n)-ratio by 0.223 +/- 0.180 in obese volunteers compared to volunteers of a standard weight (p = 0,016). The significant difference between the choline-to-(CH (2)) (n)-ratio in female versus male volunteers was calculated with an increase of 0.483 +/- 0.172 (p = 0,000). The location of the voxel in the liver parenchyma did not yield a significant difference in the choline-to-(CH (2)) (n)-ratio. CONCLUSION: The analysis of the proton liver MRS of healthy volunteers indicated a significant difference in the choline-to-(CH (2)) (n)-ratio depending on age, sex, and BMI with a confidence interval of 95 %. The different choline-to-(CH (2)) (n)-ratio could be the result of the body fat distribution depending on age and sex and also of the increased fat portion of the body in obese volunteers.

[Neurogenic thoracic outlet syndrome. Long-term results of supraclavicular decompression]. / Neurogenes Thoracic-outlet-Syndrom. Langzeitergebnisse der supraklavikulären Dekompression.

OBJECTIVES: Neurogenic thoracic outlet syndrome (TOS) is one of the most controversial entrapment syndromes of the upper extremity. There are two different surgical approaches for its primary surgical treatment: supraclavicular decompression and transaxillary first rib resection. The aim of this study was to evaluate long-term results and surgical risks of the former. METHODS: This retrospective long-term study examines a series of 50 supraclavicular decompressions in 45 patients. Follow-up was for at least 24 months. All patients were reexamined regularly in nonstandardized fashion. Finally, each patient underwent a telephone interview with a standardized questionnaire. RESULTS: There was a significant deterioration of primary results during follow-up. About 30.0% of cases worsened within 24 months after operation. In the long run, about 80.0% of cases showed improvement of symptoms (26.0% excellent, 36.0% good, 18.0% moderate). The complication rate was 4.0%. CONCLUSION: Due to secondary deterioration of treatment during follow-up, only long-term studies are suited for the examination of neurogenic TOS. Results after supraclavicular decompression are satisfactory, and the complication rate is low.

Approach-related complications of transthoracic spinal reconstruction procedures.

Direct surgical repair of instabilities of the anterior spinal column has gained in importance. New techniques and instruments have led to better operative results. Inspite of the growing number of interventions at the anterior spinal column only little data is available on the typical intra- and postoperative complications of these anterior approaches Between 4/1998 and 8/2002, 85 patients in two neurosurgical centres were treated using an anterolateral transthoracic approach for various lesions of the thoracic and thoracolumbar spine. We used a minithoracotomy with video-endoscopic guidance in 75 of these patients. Intra- and postoperative complications were evaluated retrospectively. Two operations had to be abandoned, in all other cases surgery was performed as planned. Postoperatively, eleven patients complained of temporary intercostal neuralgia (12.9%), two patients (2.3%) had a pulmonary insufficiency which was treated conservatively, another patient needed drainage of a pleural effusion. One intraoperative injury to the thoracic duct was treated conservatively, one hernia of the abdominal wall had to be corrected surgically. Relevant injuries to the vessels did not occur, blood loss was 520 ml on average. There was no surgical mortality; one revision surgery had to be performed because of bone graft dislocation. The rate of severe approach-related complications was 4/85 = 4.7% (two abandoned procedures, one injury to the thoracic duct, one abdominal hernia). Transthoracic anterolateral stabilisation via a minithoracotomy with video-endoscopic guidance is an effective surgical approach to treat instabilities of the anterior parts of the thoracic spine and the thoracolumbar area with low complication rates.

First clinical experiences with a new cervical fixation device - technical report.

In a first clinical series of ten patients the new cervical fixation device StarLock trade mark (Synthes, Umkirch, Germany) was implanted.[nl]Characteristics of the device are deep threaded screws with higher pullout resistance and a high angular tolerance while inserting the rods thus simplifying the implantation.[nl]62 lateral mass screws in ten patients were inserted. In 2 cases placement of screws was insufficient (3.2 %) because of surgical difficulties not attributable to the system technique.[nl]In all other cases a radiologically proven stabilization was created. [nl]Due to the high angular tolerance of the screw clamps bending of rods is simplified, especially in cases of longer constructs, and shortens the operation time.[nl]The design of the StarLock trade mark system allows an easy application of computer-navigated placing of transpedicular screws.[nl]This new cervical fixation device is easy to handle and simplifies rod application especially in longer constructs.

Case reports of symptomatic metastases in four patients with primary intracranial gliomas.

Four patients with primary intracranial high-grade gliomas are reported. Three of them developed spinal symptoms and signs generated by spinal metastases a few months after first diagnosis, the last patient developed an extraspinal metastasis in cervical lymph nodes. The spinal metastasis of a 30 years old patient was located intradurally at L5/S1, in the second patient at level L3, the third patient presented with multiple metastases in the cervical, thoracic and lumbar spine. Previously reported cases are reviewed, are discussed in the light of our own observations and analysed for the various therapeutic options.

Switzerland, the law, and HIV: an overview.

From the first appearance of HIV/AIDS in Switzerland in the mid 1980s, various legal tools have been implemented to combat the disease, most of them based on legislation already in force. To date, there has been no specific AIDS-related legislation, but if the formal legal framework has changed very little, practice has developed and demonstrates the extent to which the law reflects current societal values. At the risk of "giving the game away," it must be said at the outset that there are virtually no major HIV/AIDS-related legal problems in Switzerland.

Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants.

Although nitric oxide (NO) and antioxidants inhibit adhesion molecule expression, their inhibitory effects on nuclear factor kappaB (NF-kappaB) activation may differ. The NO donors, but not 8-bromo-cGMP, decreased tumor necrosis factor alpha (TNF-alpha)-induced VCAM-1, ICAM-1, and E-selectin expression by 11-70%. In contrast, NAC completely abolished VCAM-1 and E-selectin expression and decreased ICAM-1 expression by 56%. Gel shift assays demonstrate that NF-kappaB activation was inhibited by both NO and antioxidants. The activation of NF-kappaB involves the phosphorylation and degradation of its cytoplasmic inhibitor IkappaB-alpha by 26S proteasomes. The 26S proteasome inhibitor MG132 prevented the degradation of phosphorylated IkappaB-alpha. NAC inhibited IkappaB kinase (IKK) activity and prevented IkappaB-alpha phosphorylation and degradation. In contrast, NO did not inhibit IKK activity, IkappaB-alpha phosphorylation, or IkappaB-alpha degradation. However, NO, but not antioxidants, induced IkappaB-alpha promoter activity. The inhibitory effects of NO on adhesion molecule expression, therefore, differs from that of antioxidants in terms of the mechanism by which NF-kappaB is inactivated.

[The value of aspiration cytology within the scope of triple diagnosis of palpable breast changes]. / Der Stellenwert der Aspirationszytologie im Rahmen der Tripel-Diagnostik tastbarer Mamma-Veränderungen.

The diagnostic value of aspiration cytology and the overall diagnostic quality of the so-called triple test (aspiration cytology, mammography and physical examination) in the evaluation of palpable breast masses were investigated in a retrospective study. 608 histologically evaluated cancers and 224 benign lesions were investigated. A main purpose of the study was to find out whether the triple diagnostic test can replace surgical biopsy and thereby reduce the number of unnecessary biopsies. All lesions triple-diagnosed as malignant were histologically proved to be malignant, i.e. there were no false positive results. The rate of false negative results was found to be within the range reported for false negative results in fresh frozen sections. Based on these results we state that the dogmatic statement "every palpable mass in the breast must be excised" should be replaced by the recommendation "every palpable mass must be assessed and clarified". A great number of retrospectively unnecessary biopsies can be avoided by a systematic use of the triple diagnosis. The diagnostic safety of this method is close to that of open biopsy. In all cases where positive or negative concordant triplets are found, histological confirmation by biopsy can be avoided. Patients with benign lesions can be thoroughly followed up by repeated physical and radiological examinations. Patients with triple diagnostic malignant results can be adequately treated. Lesions for which triple diagnosis yields neither benign nor malignant, must be biopsied: This is also necessary in all cases with suspicious findings in mammography without a palpable mass, if the equipment for stereotactic or ultrasound- guided biopsies is not available.(ABSTRACT TRUNCATED AT 250 WORDS)