Safety and accuracy of robot-assisted versus fluoroscopy-guided pedicle screw insertion for degenerative diseases of the lumbar spine: a matched cohort comparison.

Object Recent years have been marked by efforts to improve the quality and safety of pedicle screw placement in spinal instrumentation. The aim of the present study is to compare the accuracy of the SpineAssist robot system with conventional fluoroscopy-guided pedicle screw placement. Methods Ninety-five patients suffering from degenerative disease and requiring elective lumbar instrumentation were included in the study. The robot cohort (Group I; 55 patients, 244 screws) consisted of an initial open robot-assisted subgroup (Subgroup IA; 17 patients, 83 screws) and a percutaneous cohort (Subgroup IB, 38 patients, 161 screws). In these groups, pedicle screws were placed under robotic guidance and lateral fluoroscopic control. In the fluoroscopy-guided cohort (Group II; 40 patients, 163 screws) screws were inserted using anatomical landmarks and lateral fluoroscopic guidance. The primary outcome measure was accuracy of screw placement on the Gertzbein-Robbins scale (Grade A to E and R [revised]). Secondary parameters were duration of surgery, blood loss, cumulative morphine, and length of stay. Results In the robot group (Group I), a perfect trajectory (A) was observed in 204 screws (83.6%). The remaining screws were graded B (n = 19 [7.8%]), C (n = 9 [3.7%]), D (n = 4 [1.6%]), E (n = 2 [0.8%]), and R (n = 6 [2.5%]). In the fluoroscopy-guided group (Group II), a completely intrapedicular course graded A was found in 79.8% (n = 130). The remaining screws were graded B (n = 12 [7.4%]), C (n = 10 [6.1%]), D (n = 6 [3.7%]), and E (n = 5 [3.1%]). The comparison of "clinically acceptable" (that is, A and B screws) was neither different between groups (I vs II [p = 0.19]) nor subgroups (Subgroup IA vs IB [p = 0.81]; Subgroup IA vs Group II [p = 0.53]; Subgroup IB vs Group II [p = 0.20]). Blood loss was lower in the robot-assisted group than in the fluoroscopy-guided group, while duration of surgery, length of stay, and cumulative morphine dose were not statistically different. Conclusions Robot-guided pedicle screw placement is a safe and useful tool for assisting spine surgeons in degenerative spine cases. Nonetheless, technical difficulties remain and fluoroscopy backup is advocated.

Sauerstoffsättigung der retinalen Gefässe bei hereditären Netzhauterkrankungen Retinal Vessel Oxygen Saturation in Patients Suffering from Inherited Diseases of the Retina.

Purpose: The aim of this study was to evaluate the oxygen saturation in patients with inherited diseases of the retina. Methods: Fundus oximetry images were taken using a retinal vessel analyser (IMEDOS Systems UG, Jena, Germany). Retinal vessel oximetry was performed in 53 eyes of 27 patients suffering from inherited retinal diseases and compared to 22 eyes of 11 healthy controls. The oxygen saturation in all four major retinal arterioles (A-SO2) and venules (V-SO2) were measured and their difference (A - V SO2) was calculated. The data were compared within groups and to controls. Results: Based on V-SO2 values, the rod-cone dystrophy group (66.46 %; SD, ± 5.09) could well be differentiated from controls 54.02 % (SD, ± 3.04), from cone-rod dystrophies 57.56 % (SD, ± 5.66), as well as from inherited maculopathies 58.42% (SD, ± 4.74). The mean A-SO2 in the rod-cone dystrophy group was increased to 98.96 % (SD, ± 6.06, p < 0.014), while in the cone-rod group and in the maculopathy group it was 92.75 % (SD, ± 3.75), respectively 94.44 % (SD ± 4.85), closer to the normal values (92.68 %; SD, ± 3.53, p > 0.05). The A - V SO2 difference, as an indirect indicator for retinal oxygen use, was reduced in the rod-cone patients, however only when the controls were taken into account (p = 0.01). Conclusion: This is to our knowledge the first study which proposes the retinal vessel oximetry to be a sensitive measure for differentiating rod-cone dystrophy patients not only from controls, but also from patients with other inherited retinal dystrophies.

Diagnosis by imaging : the case of textbooks of diseases of the nervous system (1850-1920)

Les traités scientifiques ne font que depuis peu d'années l'objet d'études en histoire des sciences. Pourtant, ces traités ont énormément à apporter car ils renseignent sur la manière de raisonner des auteurs, ainsi que sur le développement d'une discipline. Dans ce travail de doctorat, différents traités des maladies du système nerveux ont été dépouillés, notamment le traité de Sémiologie des affections du système nerveux (1914) de Jules Dejerine (1849-1917). Ce traité a été analysé de trois manières différentes. Il a tout d'abord été comparé à une édition précédente publiée sous forme de chapitre (1901), révélant un large remodelage du contenu du traité, suggérant une évolution rapide de la discipline neurologique en l'espace de quelques années. Deuxièmement, l'analyse de la Sémiologie a permis de recréer un réseau de professionnels avec qui Jules Dejerine était en contact et, en parcourant les livres publiés par ces auteurs, il a été possible de décrire de quelle manière ces auteurs se citent mutuellement. Finalement, ces livres contiennent de nombreuses illustrations, qui sont associées à la notion de « preuve » : les auteurs utilisent des images sous forme de dessins, de photographies ou de schémas qui illustrent des patients ou des pièces anatomiques pour « montrer » la maladie ou la lésion. Chaque illustration a un rôle à jouer pour décrire la lésion, montrer la progression de la maladie et elle aide le médecin à poser le diagnostic. Grâce à ces trois axes de recherche, un traité devient un outil de travail dynamique, qui évolue au fil des rééditions, influencé par les critiques et commentaires retrouvés dans d'autres traités et articles, et par les progrès accomplis dans la discipline traitée. Des, passages et certaines images de l'ouvrage circulent également de traité en traité et véhiculent l'autorité de l'auteur de ces passages et images qui en viennent à représenter la maladie. Ce transfert d'images joue également un rôle dans la standardisation du diagnostic et dans l'unification de la neurologie à travers le monde occidental au début du XXe siècle, une période charnière pour l'histoire de la médecine. -- Au début du XXe siècle, la neurologie est une jeune spécialité médicale qui se développe rapidement. Les différents médecins publient des traités, communiquent entre eux et échangent leurs données. Un traité scientifique est un outil de travail dynamique qui évolue avec les rééditions et le développement d'une discipline. Ces ouvrages recèlent toutes sortes d'informations et leur analyse ne fait que depuis peu de temps l'objet d'études en histoire des sciences. Ces traités regorgent notamment d'illustrations qui sont associées à la notion de « preuve » : les auteurs utilisent des images sous forme de dessins, de photographies ou de schémas qui représentent des patients ou des pièces anatomiques afin de « montrer » la maladie ou la lésion. Chaque illustration a un rôle à jouer pour décrire la pathologie, montrer la progression de la maladie et elle aide le médecin à poser le diagnostic. Les auteurs des traités, qui viennent d'Europe et d'Amérique du Nord, se citent mutuellement, permettant au lecteur de recréer leur réseau de professionnels au niveau international. De plus, comme ces auteurs réutilisent les observations et les illustrations des autres, celles-ci circulent de traité en traité et en viennent à représenter la maladie. Ce transfert d'images joue également un rôle dans la standardisation du diagnostic et dans l'unification de la neurologie à travers le monde occidental au début du XXe siècle, une période charnière pour l'histoire de la médecine. -- Until recently, the study of textbooks has been neglected in the history of the sciences. However, textbooks can provide fruitful sources of information regarding the way authors work and the development of a particular discipline. This dissertation reviews editions of a single textbook, the Sémiologie des affections du système nerveux (1914) by Jules Dejerine (1849-1917). This textbook enabled the description of three axes of research. Firstly, by comparing the book to a first edition published as a chapter, one can acknowledge an extensive remodeling of the content of the book, suggesting a vast increase in knowledge over time. Secondly, by looking at the authors that Dejerine quotes repeatedly, it becomes possible to recreate his professional network, to review the works of these authors and to determine how they cross-reference each other. Thirdly, these textbooks contain numerous medical illustrations, which are linked with the concept of "proof;" the authors demonstrate a willingness to "show" the lesion or the pathology by publishing an image. Drawings, schematic representations, radiographies, or photographs of patients or of anatomical preparations all have their own purpose in describing the lesion and the progression of the disease. They assist in the diagnosis of the pathology. By looking at all of these aspects, it is therefore possible to conclude that a neurological textbook is a dynamic object that evolves through re-editions, comments and references found in other textbooks and by the circulations of parts of these books, such as the images. The illustrations also carry the author's authority, since their ongoing use claims that the work by the owner of the image has been endorsed by others. At the same time, it validates the borrowers' arguments. By using medical illustrations from different authors worldwide, the authors are also making a claim to a common language, to a similar way of examining patients, and about how much they depend on medical imagery to prove their points. In that sense, by focusing upon these textbooks, one can affirm that neurology already existed as a worldwide specialty at the turn of the twentieth century. Much more than mere accompaniments to the text, images were of paramount importance to the unification of neurology.

High occurrence of hepatitis E virus in samples from wastewater treatment plants in Switzerland and comparison with other enteric viruses.

Hepatitis E virus (HEV) is responsible for many enterically transmitted viral hepatitides around the world. It is currently one of the waterborne diseases of global concern. In industrialized countries, HEV appears to be more common than previously thought, even if it is rarely virulent. In Switzerland, seroprevalence studies revealed that HEV is endemic, but no information was available on its environmental spread. The aim of this study was to investigate -using qPCR- the occurrence and concentration of HEV and three other viruses (norovirus genogroup II, human adenovirus-40 and porcine adenovirus) in influents and effluents of 31 wastewater treatment plants (WWTPs) in Switzerland. Low concentrations of HEV were detected in 40 out of 124 WWTP influent samples, showing that HEV is commonly present in this region. The frequency of HEV occurrence was higher in summer than in winter. No HEV was detected in WWTP effluent samples, which indicates a low risk of environmental contamination. HEV occurrence and concentrations were lower than those of norovirus and adenovirus. The autochthonous HEV genotype 3 was found in all positive samples, but a strain of the non-endemic and highly pathogenic HEV genotype I was isolated in one sample, highlighting the possibility of environmental circulation of this genotype. A porcine fecal marker (porcine adenovirus) was not detected in HEV positive samples, indicating that swine are not the direct source of HEV present in wastewater. Further investigations will be necessary to determine the reservoirs and the routes of dissemination of HEV.

Presentation and treatment outcome of diverticulitis in younger adults: a different disease than in older patients?

PURPOSE: The severity and most appropriate treatment of diverticulitis in young patients are still controversial. The aim of this study is to compare young patients (<or=50 years) with older patients (>50 years) regarding clinical and radiologic parameters of acute left colonic diverticulitis and to determine whether differences exist in presentation and treatment. METHODS: We reviewed medical records of 271 consecutive patients with left colonic acute diverticulitis admitted to our institution from 2001 through 2004: 71 patients were aged 50 years or younger and 200 patients were older than 50. Clinical and radiologic parameters were analyzed. Conservative treatment was standardized, and included antibiotic therapy and bowel rest. Criteria for emergency surgical treatment were diffuse peritonitis, pneumoperitoneum, and septic shock. RESULTS: Conservative treatment alone was successful in 64 patients (90.1%) in the younger group and in 152 patients (76%) in the older group (P = .017). The percentage of patients requiring surgery at admission or during the hospital stay was significantly lower in younger than in older patients (5.6% vs 20.5%, P = .007), and the percentage of patients requiring emergency end colostomy was higher (although not significantly) in the older group (1.4% vs 9.0%, P = .059). No differences in rate of successful conservative treatment were observed between patients with a first episode and those with recurrence in either age group (P = .941 in the younger group; P = .227 in the older group). CONCLUSION: Young age is not a predictive factor of poor outcome in the management of first or recurrent episodes of acute diverticulitis. Patients older than 50 years more frequently need emergency surgical treatment.

Exploration of the visual system : Part 2. In vivo analysis methods : virtual-reality optomotor system, fundus examination and fluorescent angiography

The mouse has emerged as an animal model for many diseases. At IRO, we have used this animal to understand the development of many eye diseases and treatment of some of them. Precise evaluation of vision is a prerequisite for both these approaches. In this unit we describe three ways to measure vision: testing the optokinetic response, and evaluating the fundus by direct observation and by fluorescent angiography.

Top Three Pharmacogenomics and Personalized Medicine Applications at the Nexus of Renal Pathophysiology and Cardiovascular Medicine.

Pharmacogenomics is a field with origins in the study of monogenic variations in drug metabolism in the 1950s. Perhaps because of these historical underpinnings, there has been an intensive investigation of 'hepatic pharmacogenes' such as CYP450s and liver drug metabolism using pharmacogenomics approaches over the past five decades. Surprisingly, kidney pathophysiology, attendant diseases and treatment outcomes have been vastly under-studied and under-theorized despite their central importance in maintenance of health, susceptibility to disease and rational personalized therapeutics. Indeed, chronic kidney disease (CKD) represents an increasing public health burden worldwide, both in developed and developing countries. Patients with CKD suffer from high cardiovascular morbidity and mortality, which is mainly attributable to cardiovascular events before reaching end-stage renal disease. In this paper, we focus our analyses on renal function before end-stage renal disease, as seen through the lens of pharmacogenomics and human genomic variation. We herein synthesize the recent evidence linking selected Very Important Pharmacogenes (VIP) to renal function, blood pressure and salt-sensitivity in humans, and ways in which these insights might inform rational personalized therapeutics. Notably, we highlight and present the rationale for three applications that we consider as important and actionable therapeutic and preventive focus areas in renal pharmacogenomics: 1) ACE inhibitors, as a confirmed application, 2) VDR agonists, as a promising application, and 3) moderate dietary salt intake, as a suggested novel application. Additionally, we emphasize the putative contributions of gene-environment interactions, discuss the implications of these findings to treat and prevent hypertension and CKD. Finally, we conclude with a strategic agenda and vision required to accelerate advances in this under-studied field of renal pharmacogenomics with vast significance for global public health.

Potentiel des liposomes pour l'injection intravitréenne de molécules thérapeutiques [Potential of liposomes for the intravitreal injection of therapeutic molecules].

Intravitreal administration has been widely used since 20 years and has been shown to improve the treatment of diseases of the posterior segment of the eye with infectious origin or in edematous maculopathies. This route of administration allows to achieve high concentration of drug in the vitreous and avoids the problems resulting from systemic administration. However, two basic problems limit the use of intravitreal therapy. Many drugs are rapidly cleared from the vitreous humor; therefore, to reach and to maintain effective therapy repeated injections are necessary. Repeated intravitreal injections increase the risk of endophthalmitis, damage to lens, retinal detachment. Moreover, some drugs provoke a local toxicity at their effective dose inducing side-effects and possible retinal lesions. In this context, the development and the use of new drug delivery systems for intravitreal administration are necessary to treat chronic ocular diseases. Among them, particulate systems such as liposomes have been widely studied. Liposomes are easily injectable and permit to reduce the toxicity and to increase the residence time of several drugs in the eye. They are also able to protect in vivo poorly-stable molecules from degradation such as peptides and nucleic acids. Some promising results have been obtained for the treatment of retinitis induced by cytomegalovirus in human and more recently for the treatment of uveitis in animal. Finally, the fate of liposomes in ocular tissues and fluids after their injection into the vitreous and their elimination routes begin to be more known.

Transanal endoscopic microsurgery resection of rectal tumors: outcomes and recommendations.

PURPOSE: Transanal endoscopic microsurgery provides a minimally invasive alternative to radical surgery for excision of benign and malignant rectal tumors. The purpose of this study was to review our experience with transanal endoscopic microsurgery to clarify its role in the treatment of different types of rectal pathology. METHODS: A prospective database documented all patients undergoing transanal endoscopic microsurgery from October 1996 through June 2008. We analyzed patient and operative factors, complications, and tumor recurrence. For recurrence analysis, we excluded patients with fewer than 6 months of follow-up, previous excisions, known metastases at initial presentation, and those who underwent immediate radical resection following transanal endoscopic microsurgery. RESULTS: Two hundred sixty-nine patients underwent transanal endoscopic microsurgery for benign (n = 158) and malignant (n = 111) tumors. Procedure-related complications (21%) included urinary retention (10.8%), fecal incontinence (4.1%), fever (3.8%), suture line dehiscence (1.5%), and bleeding (1.5%). Local recurrence rates for 121 benign and 83 malignant tumors were 5% for adenomas, 9.8% for T1 adenocarcinoma, 23.5% for T2 adenocarcinoma, 100% for T3 adenocarcinoma, and 0% for carcinoid tumors. All 6 (100%) recurrent adenomas were retreated with endoscopic techniques, and 8 of 17 (47%) recurrent adenocarcinomas underwent salvage procedures with curative intent. CONCLUSIONS: Transanal endoscopic microsurgery is a safe and effective method for excision of benign and malignant rectal tumors. Transanal endoscopic microsurgery can be offered for (1) curative resection of benign tumors, carcinoid tumors, and select T1 adenocarcinomas, (2) histopathologic staging in indeterminate cases, and (3) palliative resection in patients medically unfit or unwilling to undergo radical resection.

Molecular genetics of rare hereditary diseases via genome-wide and integrated approaches

ABSTRACTThe Online Mendelian Inheritance in Man database (OMIM) reports about 3000 Mendelian diseases of known causal gene and about 2000 that remain to be mapped. These cases are often difficult to solve because of the rareness of the disease, the structure of the family (too big or too small) or the heterogeneity of the phenotype. The goal of this thesis is to explore the current genetic tools, before the advent of ultra high throughput sequencing, and integrate them in the attempt to map the genes behind the four studied cases. In this framework we have studied a small family with a recessive disease, a modifier gene for the penetrance of a dominant mutation, a large extended family with a cardiac phenotype and clinical and/or allelic heterogeneity and we have molecularly analyzed a balanced chromosomal translocation.RESUMELa base de données des maladies à transmission mendélienne, Online Mendelian Inheritance in Man (OMIM), contient environ 3000 affections à caractère mendélien pour lesquelles le gène responsable est connu et environ 2000 qui restent à élucider.Les cas restant à résoudre sont souvent difficiles soit par le caractère intrinsèquement rare de ces maladies soit à cause de difficultés structurelles (famille trop petite ou trop étendue) ou hétérogénéité du phénotype ou génétique. Cette thèse s'inscrit avant l'arrivée des nouveaux outils de séquençage à haut débit. Son but est d'explorer les outils génétiques actuels, et de les intégrer pour trouver les gènes impliqués dans quatre cas représentant chacun une situation génétique différente : nous avons étudié une famille de quatre individus avec une transmission récessive, recherché un gène modificateur de la pénétrance de mutations dominantes, étudié une famille étendue présentant un phénotype cardiaque cliniquement et/ou allèliquement hétérogène et nous avons fait l'analyse moléculaire d'une translocation chromosomique balancée.

Genetics of calcium homeostasis in humans: continuum between monogenic diseases and continuous phenotypes

Extracellular calcium participates in several key physiological functions, such as control of blood coagulation, bone calcification or muscle contraction. Calcium homeostasis in humans is regulated in part by genetic factors, as illustrated by rare monogenic diseases characterized by hypo or hypercalcaemia. Both serum calcium and urinary calcium excretion are heritable continuous traits in humans. Serum calcium levels are tightly regulated by two main hormonal systems, i.e. parathyroid hormone and vitamin D, which are themselves also influenced by genetic factors. Recent technological advances in molecular biology allow for the screening of the human genome at an unprecedented level of detail and using hypothesis-free approaches, such as genome-wide association studies (GWAS). GWAS identified novel loci for calcium-related phenotypes (i.e. serum calcium and 25-OH vitamin D) that shed new light on the biology of calcium in humans. The substantial overlap (i.e. CYP24A1, CASR, GATA3; CYP2R1) between genes involved in rare monogenic diseases and genes located within loci identified in GWAS suggests a genetic and phenotypic continuum between monogenic diseases of calcium homeostasis and slight disturbances of calcium homeostasis in the general population. Future studies using whole-exome and whole-genome sequencing will further advance our understanding of the genetic architecture of calcium homeostasis in humans. These findings will likely provide new insight into the complex mechanisms involved in calcium homeostasis and hopefully lead to novel preventive and therapeutic approaches. Keyword: calcium, monogenic, genome-wide association studies, genetics.

Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes.

Plasma liver-enzyme tests are widely used in the clinic for the diagnosis of liver diseases and for monitoring the response to drug treatment. There is considerable evidence that human genetic variation influences plasma levels of liver enzymes. However, such genetic variation has not been systematically assessed. In the present study, we performed a genome-wide association study of plasma liver-enzyme levels in three populations (total n = 7715) with replication in three additional cohorts (total n = 4704). We identified two loci influencing plasma levels of alanine-aminotransferase (ALT) (CPN1-ERLIN1-CHUK on chromosome 10 and PNPLA3-SAMM50 on chromosome 22), one locus influencing gamma-glutamyl transferase (GGT) levels (HNF1A on chromosome 12), and three loci for alkaline phosphatase (ALP) levels (ALPL on chromosome 1, GPLD1 on chromosome 6, and JMJD1C-REEP3 on chromosome 10). In addition, we confirmed the associations between the GGT1 locus and GGT levels and between the ABO locus and ALP levels. None of the ALP-associated SNPs were associated with other liver tests, suggesting intestine and/or bone specificity. The mechanisms underlying the associations may involve cis- or trans-transcriptional effects (some of the identified variants were associated with mRNA transcription in human liver or lymphoblastoid cells), dysfunction of the encoded proteins (caused by missense variations at the functional domains), or other unknown pathways. These findings may help in the interpretation of liver-enzyme tests and provide candidate genes for liver diseases of viral, metabolic, autoimmune, or toxic origin. The specific associations with ALP levels may point to genes for bone or intestinal diseases.

Reduction of choroidal neovascularization in mice by adeno-associated virus-delivered anti-vascular endothelial growth factor short hairpin RNA.

BACKGROUND: Strategies leading to the long-term suppression of inappropriate ocular angiogenesis are required to avoid the need for repetitive monthly injections for treatment of diseases of the eye, such as age-related macular degeneration (AMD). The present study aimed to develop a strategy for the sustained repression of vascular endothelial growth factor (VEGF), which is identified as the key player in exudative AMD. METHODS: We have employed short hairpin (sh)RNAs combined with adeno-associated virus (AAV) delivery to obtain the targeted expression of potent gene-regulatory molecules. Anti-VEGF shRNAs were analyzed in human retinal pigment epithelial (RPE) cells using Renilla luciferase screening. For in vivo delivery of the most potent shRNA, self-complementary AAV vectors were packaged in serotype 8 capsids (scAAV2/8-hU6-sh9). In vivo efficacy was evaluated either by injection of scAAV2/8-hU6-sh9 into murine hind limb muscles or in a laser-induced murine model of choroidal neovascularization (CNV) following scAAV2/8-hU6-sh9 subretinal delivery. RESULTS: Plasmids encoding anti-VEGF shRNAs showed efficient knockdown of human VEGF in RPEs. Intramuscular administration led to localized expression and 91% knockdown of endogenous murine (m)VEGF. Subsequently, the ability of AAV2/8-encoded shRNAs to impair vessel formation was evaluated in the murine model of CNV. In this model, the sizes of the CNV were significantly reduced (up to 48%) following scAAV2/8-hU6-sh9 subretinal delivery. CONCLUSIONS: Using anti-VEGF vectors, we have demonstrated efficient silencing of endogenous mVEGF and showed that subretinal administration of scAAV2/8-hU6-sh9 has the ability to impair vessel formation in an AMD animal model. Thus, AAV-encoded shRNA can be used for the inhibition of neovascularization, leading to the development of sustained anti-VEGF therapy. Copyright © 2012 John Wiley & Sons, Ltd.

Therapeutic applications of viscous and injectable poly(ortho esters).

Poly(ortho esters) (POE) are hydrophobic and bioerodible polymers that have been investigated for pharmaceutical use since the early 1970s. Among the four described generations of POE, the third (POE III) and fourth (POE IV) are promising viscous and injectable materials which have been investigated in numerous biomedical applications. POE III has been extensively studied for ophthalmic drug delivery, it presents an excellent biocompatibility and is currently being investigated as a vehicle for sustained drug delivery to treat diseases of the posterior segment of the eye. POE IV is distinguishable by a highly reproducible and controlled synthesis, a higher hydrophobicity, and an excellent biocompatibility. It is currently under development for a variety of applications, such as ocular delivery, periodontal disease treatment and applications in veterinary medicine. This review will also focus on new perspectives for this promising family of polymers, such as guided tissue regeneration, treatment of osteoarthritis, as well as peptide and protein delivery.