Friction properties of a new silk fibroin scaffold for meniscal replacement.

The menisci protect the articular cartilage by reducing contact pressure in the knee. To restore their function after injury, a new silk fibroin replacement scaffold was developed. To elucidate its tribological properties, friction of the implant was tested against cartilage and glass, where the latter is typically used in tribological cartilage studies. The silk scaffold exhibited a friction coefficient against cartilage of 0.056, which is higher than meniscus against cartilage but in range of the requirements for meniscal replacements. Further, meniscus friction against glass was lower than cartilage against glass, which correlated with the surface lubricin content. Concluding, the tribological properties of the new material suggest a possible long-term chondroprotective function. In contrast, glass always produced high, non-physiological friction coefficients.

Radioablation of adrenal gland malignomas with interstitial high-dose-rate brachytherapy : Efficacy and outcome.

PURPOSE: To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM). MATERIALS AND METHODS: From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5-82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety. In a secondary analysis, risk factors with an influence on survival were identified. RESULTS: The median biological equivalent dose (BED) was 37.4 Gy. Mean LTC after 12 months was 88%; after 24 months this was 74%. According to CTCAE criteria, one grade 3 adverse event occurred. Median OS after first diagnosis of AGM was 18.3 months. Median OS, TTUP, and TTP after iBT treatment were 11.4, 6.6, and 3.5 months, respectively. Uni- and multivariate Cox regression analyses revealed significant influences of synchronous disease, tumor diameter, and the total number of lesions on OS or TTUP or both. CONCLUSION: Image-guided HDR-iBT is safe and effective. Treatment- and primary tumor-independent features influenced survival of patients with AGM after HDR-iBR treatment.

Predictive Value of Asphericity in Pretherapeutic [111In]DTPA-Octreotide SPECT/CT for Response to Peptide Receptor Radionuclide Therapy with [177Lu]DOTATATE.

PURPOSE: The purpose of this study was to assess the value of the spatial heterogeneity of somatostatin receptor (SSR) volume, quantified as asphericity (ASP), and to predict response to peptide receptor radionuclide therapy (PRRT) in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). PROCEDURES: From June 2011 to May 2013, patients suffering from GEP-NEN who underwent pretherapeutic [111In-DTPA0]octreotide scintigraphy (Octreoscan®) prior to [177Lu-DOTA0-Tyr3]octreotate ([177Lu]DOTATATE)-PRRT were enrolled in this retrospective evaluation. SSR expression in 20 NEN patients was qualitatively and quantitatively assessed using the Krenning score, the metastasis to liver uptake ratio (M/L ratio), and ASP at baseline. Response to PRRT was evaluated based on lesions, which were classified as responding lesions (RL) and non-responding lesions (NRL) after 4- and 12-month follow-ups. The values of the Krenning score, M/L ratio, and ASP for response prediction were compared by using the Mann-Whitney U test, Kruskal-Wallis test, and receiver operating characteristic (ROC) curves. RESULTS: Seventy-seven metastases (liver, n = 40; lymph node, n = 24; bone, n = 11; pancreas, n = 2) showed SSR expression. A higher ASP level was significantly associated with poorer response at both time points. ROC analyses revealed the highest area under the curve (AUC) for discrimination between RL and NRL for ASP after 4 months (AUC 0.97; p = 0.019) and after 12 months (AUC 0.96; p < 0.001), followed by the Krenning score (AUC 0.74; p = 0.082 and AUC 0.85; p < 0.001, respectively) and M/L ratio (AUC 0.77; p = 0.107 and AUC 0.82; p < 0.001). The optimal cutoff value for ASP was 5.12 % (sensitivity, 90 %; specificity, 93 %). CONCLUSION: Asphericity of SSR-expressing lesions in pretherapeutic single-photon emission computed tomography with integrated computed tomography (SPECT/CT) is a promising parameter for predicting response to PRRT in gastroenteropancreatic neuroendocrine neoplasms.

Overview of diagnostic performance and results for the first operation phase in Wendelstein 7-X (invited).

Wendelstein 7-X, a superconducting optimized stellarator built in Greifswald/Germany, started its first plasmas with the last closed flux surface (LCFS) defined by 5 uncooled graphite limiters in December 2015. At the end of the 10 weeks long experimental campaign (OP1.1) more than 20 independent diagnostic systems were in operation, allowing detailed studies of many interesting plasma phenomena. For example, fast neutral gas manometers supported by video cameras (including one fast-frame camera with frame rates of tens of kHz) as well as visible cameras with different interference filters, with field of views covering all ten half-modules of the stellarator, discovered a MARFE-like radiation zone on the inboard side of machine module 4. This structure is presumably triggered by an inadvertent plasma-wall interaction in module 4 resulting in a high impurity influx that terminates some discharges by radiation cooling. The main plasma parameters achieved in OP1.1 exceeded predicted values in discharges of a length reaching 6 s. Although OP1.1 is characterized by short pulses, many of the diagnostics are already designed for quasi-steady state operation of 30 min discharges heated at 10 MW of ECRH. An overview of diagnostic performance for OP1.1 is given, including some highlights from the physics campaigns.

[Unicentre Results in Surgery of Primary Hyperparathyroidism with Postoperative Long-Term Follow-Up and Value of Intraoperative Quick Parathormone Test]. / Unizentrische Ergebnisse der Chirurgie des primären Hyperparathyreoidismus mit postoperativer Langzeitbeobachtung sowie Rolle des intraoperativen Quick-Parathormon-Tests.

BACKGROUND: The increasing use of focussed parathyroidectomy is attributed to introduction of intraoperative parathyroid hormone measurement (ioPTH) and novel preoperative imaging techniques. This study assesses the early postoperative and long-term outcomes of surgery and the value of standardised ioPTH in patients undergoing surgery for primary hyperparathyroidism (pHPT). METHODS: From 01/01/1996 to 09/30/2011, all consecutive patients undergoing surgery for pHPT were documented. Data of this observational study were retrospectively evaluated. Patients were subdivided into 2 groups: A.) use of Quick Intraoperative Intact PTH Assay (n = 142; "ioPTH group") vs. B.) control group ("CG", n = 44). For clinical long-term follow-up, also pre- and postoperative signs, symptoms and findings of the initial 43 patients obtained during the first 4 years of the study were semiquantitatively compared. RESULTS: 186 consecutive operations for pHPT were performed - in particular, 73 sole parathyroidectomies; 113 combined thyroid and parathyroid resections. Mean operation time was 87 (SD ± 48) min for parathyroidectomy and 120 (SD ± 49) min for combined resections. A persisting hypercalcaemia was found in 16 patients (8.6%) while postoperative elevation of serum calcium and parathormone occurred in 7 patients (3.8%). Postoperative hypocalcaemia was present in 35 patients (18.8%). Differences between both groups regarding hypocalcaemia (p = 1.0), hypercalcaemia (p = 0.67), hyperparathyrinaemia (p = 0.12) and rate of reintervention (p = 0.055) were not significant. Thirty nine of the initial 43 patients reported one or more signs of pHPT (90.7%). Most frequent symptoms were nephrolithiasis (41.9%), back pain (51.2%), discomfort in the upper abdomen (41.9%), fatigue (41.9%) and general weakness (61.1%). Follow-up investigations (mean, 4.7 [range, 3.2-6.5] years) revealed that 65 % of patients reported improvement of general condition, 27% had no change and 8% reported deterioration. CONCLUSIONS: IoPTH is now standard in parathyroid surgery. Value of ioPTH correlates directly with selected centre-specific intraoperative criteria. The stricter the criteria the more reliable is the exclusion of multiglandular disease. Surgery for pHPT was performed with a very low complication rate. Through the long-term follow-up, nearly two thirds of patients benefited from the operation.

Circular polarization in the optical afterglow of GRB 121024A.

Gamma-ray bursts (GRBs) are most probably powered by collimated relativistic outflows (jets) from accreting black holes at cosmological distances. Bright afterglows are produced when the outflow collides with the ambient medium. Afterglow polarization directly probes the magnetic properties of the jet when measured minutes after the burst, and it probes the geometric properties of the jet and the ambient medium when measured hours to days after the burst. High values of optical polarization detected minutes after the burst of GRB 120308A indicate the presence of large-scale ordered magnetic fields originating from the central engine (the power source of the GRB). Theoretical models predict low degrees of linear polarization and no circular polarization at late times, when the energy in the original ejecta is quickly transferred to the ambient medium and propagates farther into the medium as a blast wave. Here we report the detection of circularly polarized light in the afterglow of GRB 121024A, measured 0.15 days after the burst. We show that the circular polarization is intrinsic to the afterglow and unlikely to be produced by dust scattering or plasma propagation effects. A possible explanation is to invoke anisotropic (rather than the commonly assumed isotropic) electron pitch-angle distributions, and we suggest that new models are required to produce the complex microphysics of realistic shocks in relativistic jets.

[Is there a role for surgery in the treatment of type 2 diabetes?]. / Welche Rolle spielt die Chirurgie bei der Therapie des Diabetes mellitus Typ 2?

Typ 2 diabetes mellitus (T2DM) can be regarded as a chronic and progressive disease which is rapidly increasing worldwide. There is a significant coincidence of T2DM and obesity, the latter playing a major role in the development of insulin resistance. Medical treatment comprises lifestyle counseling, weight management and an increased physical activity, frequently in combination with pharmacotherapy. However, especially in obese patients, metabolic aims are frequently not achieved which can be attributed to the lack of significant weight reduction. Currently, pancreas transplantation plays only a minor role in the treatment of patients with T2DM. Bariatric surgery has been proven to be a safe and effective therapeutic option in obese patients that leads to a significant weight loss. Moreover, in the majority of obese diabetics, a complete or partial remission of T2DM is observed. The significant weight loss is associated with improved insulin sensitivity. There is some evidence that alterations of gut hormones play an additional role in the amelioration of T2DM. However, little is known about the long-term effect of bariatric surgery on diabetes remission. Bariatric procedures should be considered in obese patients with T2DM (BMI > 35 kg/m²) and poorly controlled metabolic status. Despite the encouraging results in normal weight or overweight patients with T2DM, surgery can not yet be recommended in these patients. Intensive research about the impact of bariatric surgery on diabetes remission offers a unique opportunity to understand pathophysiology of T2DM. Furthermore, it may help to develop less invasive interventions and to identify new therapeutic targets for the treatment of T2DM.

[Carcinoma of the pararenal gland infiltrating the surrounding tissue and involving the inferior vena cava]. / Organüberschreitendes Nebennierenrindenkarzinom mit Beteiligung der Vena cava inferior.

UNLABELLED: ▼HISTORY AND ADMISSION FI NDINGS: A 61-year-old woman presented with a 2-month-history of progressive deterioration, increasing exertional dyspnoea and pain in the right upper abdomen (past medical history: bronchial asthma and hypertension). The physical examination showed mild generalized weakness, tenderness in the right upper abdomen, and ascites. INVESTIGATIONS: Laboratory studies did not reveal any hormonal abnormalities. A CT angiogram revealed a mass of the right adrenal gland with distinct invasion into the inferior vena cava, and tumour thrombosis that extended proximally into the right atrium. Distally, the tumour ended at the caudate lobe of the liver with an extensive peripherally engulfed thrombus from the inferior vena cava down to the common iliac -veins. TREATMENT AND COURSE: An open right adrenalectomy with resection of the periadrenal tissue and exstirpation of the intracaval tumour thrombus (by cavotomy under digital occlusion of the blood flow from the vena cava into the right atrium - cardiac surgeon) was carried out with no significant postoperative complications. Subsequently, the patient underwent adjuvant mitotane therapy for 3 years. So far, no recurrence has occurred during a course of 7 years. CONCLUSION: Tumour induced thrombotic occlusion of the inferior vena cava and other veins is rare, especially with right atrium involvement. In the absence of other effective treatment options, the combination of radical resection and adjuvant mitotane therapy remains the only successful curative treatment for primary invasive pararenal gland carcinoma.

[Organ-invasive carcinoma of the pararenal gland involving the inferior vena cava: successful curative and interdisciplinary surgical management]. / Organüberschreitendes Nebennierenrindenkarzinom mit Beteiligung der Vena cava inferior. Kurativ erfolgreiches interdisziplinär-operatives Management.

HISTORY AND ADMISSION FINDINGS: A 61-year-old woman presented with a 2-month-history of progressive deterioration, increasing exertional dyspnoea and pain in the right upper abdomen (past medical history: bronchial asthma and hypertension). The physical examination showed mild generalized weakness, tenderness in the right upper abdomen, and ascites. INVESTIGATIONS: Laboratory studies did not reveal any hormonal abnormalities. A CT angiogram revealed a mass of the right adrenal gland with distinct invasion into the inferior vena cava, and tumour thrombosis that extended proximally into the right atrium. Distally, the tumour ended at the caudate lobe of the liver with an extensive peripherally engulfed thrombus from the inferior vena cava down to the common iliac veins. TREATMENT AND COURSE: An open right adrenalectomy with resection of the periadrenal tissue and extirpation of the intracaval tumour thrombus (by cavotomy under digital occlusion of the blood flow from the vena cava into the right atrium) was carried out with no significant postoperative complications. Subsequently, the patient underwent adjuvant mitotane therapy for three years. So far, no recurrence has occurred during a course of 7 years. CONCLUSION: Tumour induced thrombotic occlusion of the inferior vena cava and other veins is rare, especially with right atrium involvement. In the absence of other effective treatment options, the combination of radical resection and adjuvant mitotane therapy remains the only successful curative treatment for primary invasive adrenal gland carcinoma.

[Preventive bone mineral density measurement in postmenopausal women. Differentiation of treatment of recommendations Guidelines of the Umbrella Organization for Osteology ("Dachverband Osteologie")]. / Präventive Knochendichtemessung bei postmenopausalen Frauen. Differenzierung der Therapieempfehlungen der Leitlinien des Dachverbandes Osteologie (DVO).

BACKGROUND: Osteopenia (OP) or osteoporosis (OST) was diagnosed by bone densitometry (DXA) in postmenopausal women free of known skeletal disorders and without acute fracture. DVO guidelines were applied to define therapeutic indication. METHODS: The study included 94 women aged 59-81 years. Fracture or operation ≤12 months, malignant tumor, ovariectomy, and drugs such as cortisone, strontium, fluorides, bisphosphonates, SERMs, estrogens, and steroids were exclusion criteria. The lowest T-score at the spine, femoral neck, or total hip was decisive. The indication for therapy was determined by evaluating age, BMD, and other risk factors. RESULTS: Using the WHO criteria 22.3% (n=21) had normal BMD, 52.1% (n=49) had OP, and 25.6% (n=24) had OST. According to "Dachverband Osteologie" (DVO) guidelines, 28 women (29.8%) of the whole group needed therapy. Of the 28 women receiving therapy, 9 had OP and 19 had OST. Therapy was indicated in 18.4% for OP and 79.2% for OST. CONCLUSION: A preventive measurement of BMD with DXA provides a benefit for postmenopausal women. Combinatory assessment and consideration of other risk factors allows identification of women who might benefit from early treatment.

Monogenic diabetes in a family with 2 unknown HNF-4A gene mutations.

INTRODUCTION: Diabetes mellitus classified as Maturity Onset Diabetes of the Young (MODY) is characterized by autosomal dominant inheritance with insulin secretory disturbances. CASE REPORT: In 2 siblings with diabetes mellitus manifestation at age under 25 years, low fasting glucose levels, severely elevated glucose levels upon glucose challenge and absent autoantibodies for IA2 and GAD clarification for MODY was sought. Mutational screening for MODY 1-3 mutations was carried out by direct sequencing followed by multiplex ligation-dependent probe amplification (MLPA). CONCLUSION: We identified a mutation within the hepatic nuclear factor 4A (HNF-4A) gene hitherto unreported for MODY-1. A causative role of the mutation is not proven, however in the 2 index patients similar phenotypes are present. These cases underline the necessity to screen for MODY when the medical history and lack of autoantibodies suggest alternative diagnoses beside type 1 diabetes.

Hypopituitarism in a HIV affected patient.

BACKGROUND: The clinical picture of pituitary abscesses may resemble features of other pituitary pathologies including endocrine deficiencies. The characteristic radiological changes, namely the ring enhancement, may aid in the diagnostic work-up of this very rare condition. CASE REPORT: A 40-year-old patient with longstanding HIV infection presented with headache and fatigue. Testing for pituitary function confirmed panhypopitutarism. MRI scanning demonstrated an inhomogeneous pituitary gland with ring-like enhancement and sphenoid sinus mucosa thickening. Transsphenoidal surgery was performed. Histologically CD68 positive macrophages were found supporting the diagnosis of infectious hypophysitis. Under hormone replacement therapy and retroviral treatment the patient clinically normalized. CONCLUSION: A pituitary abscess due to infectious hypophysitis is a rare cause of pituitary failure. Diagnostic signs on imaging may help to rapidly distinguish the cause of pituitary deficiency in patients with HIV infection.

A gamma-ray burst at a redshift of z approximately 8.2.

Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z > 20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy. Here we report that GRB 090423 lies at a redshift of z approximately 8.2, implying that massive stars were being produced and dying as GRBs approximately 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.

Flares from a candidate Galactic magnetar suggest a missing link to dim isolated neutron stars.

Magnetars are young neutron stars with very strong magnetic fields of the order of 10(14)-10(15) G. They are detected in our Galaxy either as soft gamma-ray repeaters or anomalous X-ray pulsars. Soft gamma-ray repeaters are a rare type of gamma-ray transient sources that are occasionally detected as bursters in the high-energy sky. No optical counterpart to the gamma-ray flares or the quiescent source has yet been identified. Here we report multi-wavelength observations of a puzzling source, SWIFT J195509+261406. We detected more than 40 flaring episodes in the optical band over a time span of three days, and a faint infrared flare 11 days later, after which the source returned to quiescence. Our radio observations confirm a Galactic nature and establish a lower distance limit of approximately 3.7 kpc. We suggest that SWIFT J195509+261406 could be an isolated magnetar whose bursting activity has been detected at optical wavelengths, and for which the long-term X-ray emission is short-lived. In this case, a new manifestation of magnetar activity has been recorded and we can consider SWIFT J195509+261406 to be a link between the 'persistent' soft gamma-ray repeaters/anomalous X-ray pulsars and dim isolated neutron stars.

Male infertility as a component of Carney complex.

Carney complex (CNC) is a multiple neoplasia syndrome characterised by endocrine tumours, spotty skin pigmentation, cardiac and other myxomas, psamommatous and pigmented schwannomas, large cell calcifying Sertoli cell tumours, and mammary ductal adenomas and other more rare lesions. CNC is inherited in an autosomal-dominant manner and has been mapped to at least two chromosomal loci. Patients who map to the CNC1 locus located on chromosome 17 carry inactivating mutations of the PRKAR1A gene that encodes the cAMP-dependent protein kinase regulatory subunit type 1-alpha (Kirschner et al., 2000). One gene responsible for type 2 (CNC2) is located on chromosome 2p16. Infertility in CNC can be caused by a number of factors; there is evidence that prkar1a deficiency in mice leads directly to infertility (Burton et al., 2006), but patients with CNC also have Sertoli cell tumours and a number of other reasons to affect fertility. We report on an infertile male with CNC and present evidence that male infertility should be considered as part of the phenotype of CNC.

Diagnostic management of benign and malignant pheochromocytoma.

As rare and thus often overlooked hormone-secreting tumors, pheochromocytomas pose a particular diagnostic challenge. Difficulties involve biochemical confirmation, localizing, and detection of malignancy. Measurement of free plasma metanephrines, genetic testing and specific imaging procedures--such as MIBG and octreotide scintigraphy or fluorodopamine PET--represent a considerable progress, and the management of benign pheochromocytomas has become very effective. However, a comparable improvement in the prognosis of malignant chromaffin cell tumors, which occur in approximately 10-15% of all cases, has not yet been achieved. Here, telomerase catalytic subunit (hTERT) activity and heat shock protein 90 expression could serve both as molecular markers allowing an earlier diagnosis of malignancy and as therapeutic targets. Familial syndromes should be considered both in benign and malignant pheochromocytoma, and should be tested for prior to surgery in selected patient groups.

An optical supernova associated with the X-ray flash XRF 060218.

Long-duration gamma-ray bursts (GRBs) are associated with type Ic supernovae that are more luminous than average and that eject material at very high velocities. Less-luminous supernovae were not hitherto known to be associated with GRBs, and therefore GRB-supernovae were thought to be rare events. Whether X-ray flashes--analogues of GRBs, but with lower luminosities and fewer gamma-rays--can also be associated with supernovae, and whether they are intrinsically 'weak' events or typical GRBs viewed off the axis of the burst, is unclear. Here we report the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. Supernova 2006aj is intrinsically less luminous than the GRB-supernovae, but more luminous than many supernovae not accompanied by a GRB. The ejecta velocities derived from our spectra are intermediate between these two groups, which is consistent with the weakness of both the GRB output and the supernova radio flux. Our data, combined with radio and X-ray observations, suggest that XRF 060218 is an intrinsically weak and soft event, rather than a classical GRB observed off-axis. This extends the GRB-supernova connection to X-ray flashes and fainter supernovae, implying a common origin. Events such as XRF 060218 are probably more numerous than GRB-supernovae.

[Microalbuminuria in diabetes: setting the points for treatment]. / Mikroalbuminurie bei Diabetes: Nicht nur den Nieren droht Gefahr.

Both type 1 and type 2 diabetes mellitus have a cumulative risk of 25-40% for the development of microalbuminuria 25 years into the disease. In type 2 diabetes micro- and macroangiopathic complications, and frequently hypertension, may also develop. This means that the risk of a type 2 diabetic with microalbuminuria of developing cardiovascular disease is three times greater than that of a diabetic with no renal involvement. Annual screening for microalbuminuria should therefore be obligatory. An increasing albumin excretion rate (AER) is considered an indication for an elevated cardiovascular risk. Studies have shown that the rate of cardiovascular events in diabetics with microalbuminuria and hypertension can be reduced only by the combined treatment of hypertension, hyperglycemia, hyperlipidemia and microalbuminuria.