Dorsal Root Ganglion Volumetry by MR Gangliography.

BACKGROUND AND PURPOSE: Dorsal root ganglion MR imaging (MR gangliography) is increasingly gaining clinical-scientific relevance. However, dorsal root ganglion morphometry by MR imaging is typically performed under the assumption of ellipsoid geometry, which remains to be validated. MATERIALS AND METHODS: Sixty-four healthy volunteers (37 [57.8%] men; mean age, 31.5 [SD, 8.3] years) underwent MR gangliography of the bilateral L4-S2 levels (3D-T2WI TSE spectral attenuated inversion recovery-sampling perfection with application-optimized contrasts by using different flip angle evolution, isotropic voxels = 1.1 mm³, TE = 301 ms). Ground truth dorsal root ganglion volumes were bilaterally determined for 96 dorsal root ganglia (derivation cohort) by expert manual 3D segmentation by 3 independent raters. These ground truth dorsal root ganglion volumes were then compared with geometric ellipsoid dorsal root ganglion approximations as commonly practiced for dorsal root ganglion morphometry. On the basis of the deviations from ellipsoid geometry, improved volume estimation could be derived and was finally applied to a large human validation cohort (510 dorsal root ganglia). RESULTS: Commonly used equations of ellipsoid geometry underestimate true dorsal root ganglion volume by large degrees (factor = 0.42-0.63). Ground truth segmentation enabled substantially optimizing dorsal root ganglion geometric approximation using its principal axes lengths by deriving the dorsal root ganglion volume term of [Formula: see text]. Using this optimization, the mean volumes of 510 lumbosacral healthy dorsal root ganglia were as follows: L4: 211.3 (SD, 52.5) mm³, L5: 290.7 (SD, 90.9) mm³, S1: 384.2 (SD, 145.0) mm³, and S2: 192.4 (SD, 52.6) mm³. Dorsal root ganglion volume increased from L4 to S1 and decreased from S1 to S2 (P < .001). Dorsal root ganglion volume correlated with subject height (r = . 22, P < .001) and was higher in men (P < .001). CONCLUSIONS: Dorsal root ganglion volumetry by measuring its principal geometric axes on MR gangliography can be substantially optimized. By means of this optimization, dorsal root ganglion volume distribution was estimated in a large healthy cohort for the clinically most relevant lumbosacral levels, L4-S2.

Training in Bariatric Surgery: a National Survey of German Bariatric Surgeons.

INTRODUCTION: Skill in bariatric surgery has been associated with postoperative outcome. Appropriate surgical training is of paramount importance. In order to continuously improve training strategies, it is necessary to assess current practices. AIM: To determine how German bariatric surgeons have been trained and to assess current training strategies. METHODS: Between February 2017 and March 2017, an online census of surgeons registered as members of the German Society for Bariatric and Metabolic Surgery was conducted. A total of three reminders were sent out. Data were analyzed using descriptive statistics. Data was reported as median (interquartile range); percentages were adjusted for completed answers only. RESULTS: A response rate of 51% (n = 214) was achieved. Surgeons reported a median of 14.5 (8-20) years of surgical experience after initial training, with a specific bariatric experience of 7 (4-13) years. The total cumulative bariatric case volume was 240 (80-500) cases, with an annual case volume of 50 (25-80). The most commonly applied approaches to bariatric skills acquisition were "learning by doing" (71%), "course participation" (70%) and "observerships" (70%). Fellowships and the use of operating videos were less frequently applied strategies (19%/ 47%). Interestingly, observerships (94%) and course participation (89%) were rated as very important/important, whereas "learning by doing" (62%), watching operation videos (59%), and fellowships (48%) were less frequently perceived as important/very important training strategies. CONCLUSIONS: The majority of surgeons performing bariatric cases were senior surgeons with more than 10 years of post-training experience; nevertheless, the survey revealed a lack of structured approaches to bariatric specialization training.

[Treatment of rheumatic disease with renal insufficiency]. / Therapie rheumatischer Erkrankungen mit Niereninsuffizienz.

BACKGROUND: Reduced renal function is not rare in patients with inflammatory rheumatic diseases and is associated with an increased risk of treatment-induced and perioperative adverse events. METHOD: A literature search was carried out for the medical treatment and perioperative management of rheumatic disease in the presence of renal insufficiency. RESULTS: Patients with rheumatic disease and renal insufficiency have a higher risk of cardiovascular disease, bone loss and immunodeficiency than those without kidney disease. The perioperative rate of cardiovascular and infectious complications and the risk of acute kidney failure are elevated in these patients. The pharmacokinetics of many drugs used in rheumatology is influenced by the kidney function. Especially methotrexate is contraindicated in patients with an estimated glomerular filtration rate (eGFR) <45 ml/min. Nonsteroidal anti-inflammatory drugs (NSAIDS) and cyclooxygenase (COX)-2 inhibitors should not be used with renal insufficiency or only for a short term with the lowest effective dose. The treatment of osteoporosis with antiresorptive drugs may lead to adynamic bone disease in advanced kidney disease, and, therefore, the use of these drugs is controversial. CONCLUSION: Medication should be modified in patients with rheumatic disease and kidney involvement according the grade of renal insufficiency. There is also a need for special perioperative management in these patients, with interdisciplinary cooperation of rheumatologists, nephrologists and orthopedic doctors.

[Barriers to the German Society for General and Visceral Surgery (DGAV) accreditation "Center for bariatric and metabolic surgery"]. / Barrieren auf dem Weg zur DGAV-Zertifizierung "Zentrum für Adipositas- und metabolische Chirurgie".

INTRODUCTION: The certification and accreditation process of the German Society for General and Visceral Surgery (DGAV) aims to improve the quality of care and enhance transparency in accredited centers. To achieve these goals a high level of infrastructural and staffing requirements are set out by the DGAV. AIMS: The Surgical Working Group on Obesity Treatment and Metabolic Surgery (CAADIP) survey 2017 of the members of the German Bariatric Society aimed to identify the perceived and encountered barriers in the DGAV accreditation process. METHODS: Between February and March 2017 an online poll was conducted of all members of the CAADIP on topics pertaining to the accreditation process. RESULTS: A total of 214 (51%) CAADIP members participated in the poll, 47% reported that they worked at a non-certified center and 53% worked at a DGAV certified center. Of these, 68% reported employment in a unit with the lowest accreditation level, 21% in an intermediate level center, 11% reported employment in a unit with the highest accreditation level (Center of Excellence) and 86% of those currently working in non-accredited units stated that they aimed for future accreditation. Reasons stated for not having obtained accreditation were recent establishment of the new bariatric specialty (54%), lack of bariatric case numbers (71%), lack of human resources and infrastructure (28% and 13%, respectively). Of those surgeons in non-accredited centers 24% stated that the hospital management had no interest in a certification and 12% of the surgeons themselves felt that accreditation was unnecessary. CONCLUSION: The majority of CAADIP members strived for DGAV certification. The main barriers encountered and perceived were the specific time (reference years) and caseload requirements.

[Quality indicators for metabolic and bariatric surgery in Germany : Evidence-based development of an indicator panel for the quality of results, indications and structure]. / Qualitätsindikatoren für die metabolische und Adipositaschirurgie : Evidenzbasierte Entwicklung eines Indikatorensets für die Ergebnis­, Indikations- und Strukturqualität.

An expert committee was appointed by the German Society for General and Visceral Surgery to develop a panel of appropriate quality indicators to collate the quality of results, indications and structure in metabolic and bariatric surgery. This entailed assimilating the available evidence (systematic literature search), results from the national registry of the society (StuDoQ|MBE) and specific socioeconomic aspects (e. g. severely limited access to metabolic and bariatric surgery in Germany). These quality parameters were to be incorporated into the national guidelines and the rules of procedure for certification in the future. The committee concluded that mortality, MTL30 and severe complications needing intervention (Clavien-Dindo ≥ 3b) are suitable indicators to measure surgical outcome quality due to their relevance, scientific soundness and practicability. As a systematic follow-up is mandatory after bariatric surgery, a minimum follow-up quota is now required using reported quality of life data as an indicator of process quality. As intestinal bypass procedures have been shown to be superior in the treatment of type 2 diabetes, these procedures should be offered to eligible patients and also be performed. The proposed threshold values based on the results of the available literature and StuDoQ registry are to be considered as preliminary and need to be validated and adjusted if necessary in the future. The StuDoQ|MBE is considered a valuable tool to gather this information and also represents the appropriate infrastructure for the collation of relevant risk adjustors.

Health Care Economics: A Study Guide for Neuroradiology Fellows, Part 1.

Few resources are available in the medical literature for a comprehensive review of current health care economics as it relates to radiologists, specifically framed by topics defined by the Accreditation Council for Graduate Medical Education in the evaluation of neuroradiology fellows. Therefore, we present a comprehensive review article as a study guide for fellows to learn from and gain competence in the Accreditation Council for Graduate Medical Education neuroradiology milestones on health care economics.

Health Care Economics: A Study Guide for Neuroradiology Fellows, Part 2.

In this second article, we continue the review of current health care economics as it relates to radiologists, specifically framed by topics defined by the Accreditation Council for Graduate Medical Education in the evaluation of neuroradiology fellows. The discussion in this article is focused on topics pertaining to levels 4 and 5, which are the more advanced levels of competency defined by the Accreditation Council for Graduate Medical Education Neuroradiology Milestones on Health Care Economics and System Based Practice.

Functional genomics in the wild: a case study with paper wasps shows challenges and prospects for RNA interference in ecological systems.

RNA interference (RNAi) is a useful tool to assess gene function by knocking down expression of a target gene and has been used successfully in domestic and laboratory organisms. However, the use of RNAi for functional genomics has not fully extended into ecological model organisms in natural environments. Assessment of gene function in the wild is important because gene function can be environmentally and context dependent. Here, we present a case study using RNAi to assess gene function in wild paper wasps Polistes metricus, to test roles for two candidate genes (NADH dehydrogenase (NADHdh) and retinoid and fatty acid binding protein (RfaBp)) in the development of reproductive castes. Previous studies have shown that these genes are upregulated in larvae that become queens compared to workers, but this pattern was reversed in the laboratory, making field-based studies necessary. We orally administered dsRNA to larvae in field colonies and found evidence of a short-term knockdown followed by a compensatory rebound in expression for RfaBp. We also observed the predicted worker-like decrease in lipid stores in NADHdh dsRNA treated wasps, suggesting a possible role for NADHdh in caste development. We discuss our results in the context of challenges for using RNAi for functional genomics in ecological model organisms in the field.

[Anastomosis and suture insufficiency after interventions for bariatric and metabolic surgery]. / Anastomosen- und Nahtinsuffizienzen nach Eingriffen in der Adipositas- und metabolischen Chirurgie.

BACKROUND: Metabolic surgery is internationally well-established for the treatment of obesity and its comorbidities. The numbers of procedures performed is steadily increasing. The results of surgery are superior in comparison to conservative treatment options regarding weight loss and resolution of comorbidities. The insufficiency of suture lines is a well-known and feared complication in the stapling procedures and is associated with an increased morbidity as well as mortality, especially in super obese patients. MATERIAL AND METHODS: The current literature was reviewed and the results are reported within the context of own experience. RESULTS: The most severe complications are staple line leakage after sleeve gastrectomy, leakage of anastomoses after bypass procedures and duodenal stump insufficiency. For the treatment of sleeve leakage various endoscopic procedures, such as over the scope (OTS) clips, stents and endoluminal vacuum therapy are available. Surgical revision, such as oversuturing, drainage and redo surgery are well-established. The management of all other complications is mainly by surgical intervention. Intraoperative standardization of procedures and knowledge of the physical foundations are essential for the prevention of leakage. Several preventive methods are available but randomized controlled trials are missing. CONCLUSION: The therapy of leakages in the field of bariatric surgery is an interdisciplinary approach and dependent on the available resources in the treating hospital. The data reported show good results but the different reports published are inconsistent. Leakages often do not occur in the immediate postoperative period but in the sense of a long-term complication; therefore standardization of procedures and follow-up as well as complication management is mandatory. Randomized controlled studies must be promoted.

[Dosage and toxicity of antirheumatic drugs in renal insufficiency]. / Dosierung und Toxizität von Antirheumatika bei Niereninsuffizienz.

BACKGROUND: Patients with inflammatory rheumatic diseases frequently have a reduced renal function. The risk of adverse events is increased in these patients and treatment options in patients with rheumatic disease and renal failure are poorly studied. METHODS: A selective literature search was carried out for pharmocokinetics, dosage and toxicity of antirheumatic drugs in patients with renal insufficiency. RESULTS: The use of nonsteroidal anti-inflammatory drugs (NSAID), cyclooxygenase(COX)-2 inhibitors, gold and cyclosporine is limited in renal insufficiency due to nephrotoxicity. Methotrexate should not be used in patients with a glomerular filtration rate (eGFR) < 45 ml/min, because of the unpredictable pharmacokinetics with a risk for fatal pancytopenia. The dosage of sulfasalazine, azathioprine, mycophenolate mofetil, cyclophosphamide and antimalarial drugs should be reduced in patients with moderate and severe renal insufficiency. In contrast, leflunomide and numerous biologics can be used without dosage modification; however, biologics with a molecular weight < 60 kDa (e.g. anakinra) are an exception and should be reduced in patients with renal insufficiency. Overall, there are only limited data on the use of biologics in this population. Numerous comorbidities and the high risk for infection should be kept in mind when patients with rheumatic disease and renal failure are treated with immunosuppressive drugs. CONCLUSION: Further studies are necessary to obtain more evidence on the use of disease-modifying antirheumatic drugs (DMARD) and biologics in patients with renal insufficiency.

Initial orthodontic tooth movement of a multirooted tooth: a 3D study of a rat molar.

OBJECTIVE: To elucidate the 3D interactions in the tooth-PDL-bone complex immediately after application of orthodontic forces and their implications on tooth movement and function. METHODS: A special visualization method using microCT allows us to directly image in 3D the movements of a multirooted molar tooth inside the alveolar bone as well as the collagenous network of the PDL. Using fresh, unstained rat mandibular 1st molar under mesial loads of 0.5-1 N, we address basic concepts in orthodontics during the initial stages of orthodontic movement. RESULTS: We show that immediately after the application of orthodontic load, direct distinct contacts between the tooth and the bone form in the furcation area. These contacts limit tooth movement and interfere with whole body translation. Only localized sites of highly compressed PDL between the root surfaces and the bone were observed. In general, the collagenous network of the PDL appeared loose and not densely packed in the compressed side. On the tension side, the fibers maintained their overall orientation without any significant extension of the fibers. CONCLUSIONS: Localized direct contact areas between the tooth roots and the bone at the furcation already form within a few minutes of orthodontic tooth movement. This direct and localized bone involvement guides the movement trajectory and provides a mechanism for the miscorrelation found between force levels and tooth movement during the initial stages of an orthodontic tooth movement.

[Management of complications in bariatric surgery]. / Management von Frühkomplikationen in der Adipositaschirurgie.

Bariatric surgery is known to be the most effective and long-lasting treatment for morbid obesity and associated comorbidities. These comorbidities together with cardiopulmonary decompensation make morbidly obese patients a high risk group for operative interventions. Early detection of postoperative complications is a challenging task in these patients and requires accurate and timely interpretation of any alarm signals. Symptoms, such as tachycardia and abdominal pain are highly suspicious. The same applies to elevated inflammatory parameters and fever. Early diagnostic laparoscopy is mandatory once cardiopulmonary complications have been excluded. Moreover, it has a higher sensitivity and specificity than other radiological modalities and is a minimally invasive procedure with a highly satisfactory outcome.

The effect of hydration on mechanical anisotropy, topography and fibril organization of the osteonal lamellae.

The effect of hydration on the mechanical properties of osteonal bone, in directions parallel and perpendicular to the bone axis, was studied on three length scales: (i) the mineralized fibril level (~100 nm), (ii) the lamellar level (~6 µm); and (iii) the osteon level (up to ~30 µm).We used a number of techniques, namely atomic force microscopy (AFM), nanoindentation and microindentation. The mechanical properties (stiffness, modulus and/or hardness) have been studied under dry and wet conditions. On all three length scales the mechanical properties under dry conditions were found to be higher by 30-50% compared to wet conditions. Also the mechanical anisotropy, represented by the ratio between the properties in directions parallel and perpendicular to the osteon axis (anisotropy ratio, designated here by AnR), surprisingly decreased somewhat upon hydration. AFM imaging of osteonal lamellae revealed a disappearance of the distinctive lamellar structure under wet conditions. Altogether, these results suggest that a change in mineralized fibril orientation takes place upon hydration.

Obesity and metabolic surgery in type 1 diabetes mellitus.

BACKGROUND: Obesity surgery is an effective method for treating obesity and diabetes mellitus type 2. This type of diabetes can be completely resolved in 78.1% of diabetic patients and can be improved or resolved in 86.6% of diabetic patients. But little is known about bariatric surgery in type 1 diabetes mellitus. METHODS: We report of 6 female obese patients with diabetes mellitus type 1 who had bariatric surgery. Two of them underwent Roux-en Y gastric bypass (RNYGB), one of them had sleeve gastrectomy and the remaining three had biliopancreatic diversion with duodenal-switch (BPD-DS). RESULTS: Our results showed a remarkable weight reduction as well as an improvement in their blood glucose control and the insulin requirement in the followup years after surgery. Pre-surgery the BMI of our 6 patients ranged between 37.3-46.0 kg/m2 and improved to 25.8-29.0 kg/m2 one year after surgery. HbA1c decreased from 6.7-9.8% pre-surgery to 5.7-8.5% after one year post-surgery. The total amount of daily insulin requirement was reduced from 62-150 IU/day pre-surgery to 15- 54 IU/day after one year. CONCLUSION: The results are impressive and show an improvement in insulin sensitivity following obesity surgery. However, an optimal blood glucose control still remains very important in the therapy of diabetes mellitus type 1 to avoid long-term-complications.

Introducción: La cirugía de la obesidad es un método eficaz para el tratamiento de la obesidad y la diabetes mellitus tipo 2. Este tipo de diabetes puede se resuelve por completo en el 78,1% de los pacientes diabéticos y mejora en el 86,6% de los pacientes diabéticos. Sin embargo, poco se sabe acerca de la cirugía bariátrica en la diabetes mellitus tipo 1. Métodos: Presentamos 6 pacientes mujeres obesas con diabetes mellitus tipo 1 que se sometieron a cirugía bariátrica. Dos de ellas fueron sometidas a un bypass gástrico en-Y-Roux (BPGYR), una se le realizó una gastrectomía en manga y a las tres restantes una derivación biliopancreática con-switch duodenal (DBP-SD). Resultados: Nuestros resultados mostraron una reducción de peso notable, así como una mejora en el control de la glucosa en sangre y el requerimiento de insulina en los años de seguimiento después de la cirugía. El IMC prequirúrgico de las 6 pacientes osciló entre 37,3-46,0 kg/m2 y mejoró a 25,8-29,0 kg/m2 un año después de la cirugía. La HbA1c disminuyó de 6,7-9,8% antes de la cirugía a 5,7-8,5% un año después de la cirugía. El requerimiento diario de insulina se redujo de 62-150 UI/día antes de la cirugía a 15-54 UI /día al cabo de un año. Conclusión: Los resultados son impresionantes y muestran una mejora en la sensibilidad a la insulina tras una cirugía de la obesidad. No obstante, un control óptimo de la glucosa de sangre sigue siendo muy importante en la terapia de la diabetes mellitus tipo 1 para evitarcomplicaciones a largo plazo.

Quality of life of diabetic patients with medical or surgical treatment.

INTRODUCTION: In general, most of the studies agree in that the quality of life (QoL) of patients with diabetes is worse than that of the general population. Furthermore, these same studies have also described very positive effects on quality of life after bariatric surgery. The aim of this study was to analyze whether the impact on quality of life of diabetic patients after being submitted to bariatric surgery is the one supposed to be. METHODS: We prospectively analyzed our data on 524 diabetic patients submitted to bariatric surgery between 2001 and 2005. All the patients filled up three QoL questionnaires before the surgery and at 1, 3, 6, and 12 months after the surgery. The answers were gathered from an annual database. All patients were submitted to adjustable gastric band surgery, Y-Roux gastric bypass, or BPD-Scopinaro. RESULTS: We obtained complete data on 89 patients that were included into the study. One year after the surgery, the QoL had significantly improved independent of disease remission and weight loss. Diabetes got improved in all the cases. The improvement on the quality of life was higher in the patients with total remission of the disease than in those only improving their health status, although it was lower than that of those patients without diabetes before the surgery. CONCLUSIONS: After a literature review and with our own prospective data, we may conclude that the benefits obtained by diabetic patients from bariatric surgery are mainly due to improvement of their diabetes, irrespective of their initial BMI and the BMI decrease after the intervention. Further studies are needed to investigate the results of the QoL test in diabetics with low BMI after bariatric surgery and in the long run.

Introducción: En general, la mayoría de los estudios coinciden en que la calidad de vida de las personas con diabetes es peor que la calidad de vida de la población general (QoL). Además, estos mismos estudios también han descrito efectos muy positivos sobre la calidad de vida tras cirugía bariátrica. El objetivo de este estudio fue analizar si el impacto sobre la calidad de vida de los pacientes diabéticos después de ser sometidos a cirugía bariátrica según el test (QoL) es el que se supone debería ser. Métodos: Analizamos nuestra colección de datos prospectivos de 524 pacientes diabéticos que se sometieron a cirugía bariátrica entre 2001 y 2005. Todos los pacientes realizaron 3 cuestionarios de calidad de vida antes de la cirugía y después de 1, 3, 6 y 12 meses. Las respuestas se recogieron en una base de datos anual. Todos los pacientes se sometieron a una intervención de banda gástrica ajustable, Bypass Gástrico en-Y-Roux o BPD-Scopinaro. Resultados: En total se obtuvieron los datos completos de 89 pacientes que fueron incluidos en el estudio. 1 año después de la cirugía, la calidad de vida mejoró de manera significativa e independientemente de la remisión de la enfermedad y de la pérdida de peso. La diabetes mejoró en todos los casos. La mejora en la calidad de vida fue superior en los pacientes con remisión de la enfermedad que en los que únicamente mejoraron su estado, pero inferior que en los pacientes que no tenían diabetes antes de la operación. Conclusiones: Tras el análisis de la literatura y de nuestros propios datos prospectivos, podemos concluir que los beneficios que obtienen los pacientes diabéticos tras la cirugía bariátrica son debidos principalmente a la mejora de su diabetes, independientemente del IMC inicial y de la disminución del IMC tras la intervención. Se necesitan más estudios para investigar los resultados del test QoL en diabéticos con bajo índice de masa corporal tras la cirugía bariátrica y a largo plazo.

Assessment of the genotoxic and carcinogenic risks of p-nitrophenol when it is present as an impurity in a drug product.

According to the 2008 US FDA (draft) and 2006 EMEA guidance documents for genotoxic impurities, an impurity that is positive in an in vitro genotoxicity study, in the absence of in vivo genotoxicity or carcinogenicity data, should be treated as genotoxic and typically controlled to 1.5 microg/day for chronic use. For p-nitrophenol (PNP), existing study results (i.e., positive in vitro clastogenicity in mammalian cells, no information on its in vivo genotoxicity, and negative with respect to carcinogenicity in a dermal mouse study with no confirmation of systemic exposure) indicated that it should be considered genotoxic and exposure as a drug impurity limited. Therefore, to more completely characterize the genotoxic potential of PNP (consistent with the guidance documents), in vivo mouse micronucleus and dermal pharmacokinetic bridging studies were conducted. In the micronucleus study, PNP was negative, demonstrating that the reported in vitro clastogenicity is not present in vivo. In the pharmacokinetic study, PNP was well absorbed dermally, validating the negative dermal carcinogenicity assessment. These results indicate that PNP should be considered a non-genotoxic impurity and, as a drug impurity, a threshold limit of 4 mg/day would be set (per ICH Q3C). This threshold limit is higher than the EPA reference dose (listed in the 2006 Edition of the Drinking Water Standards and Health Advisories), so if present at such levels, the specification limits for PNP should be determined on a case-by-case basis, based on risk-benefit.