Under-correction of preoperative varus alignment does not lead to a difference in in-vivo bone loading in 3D-SPECT/CT compared to neutral alignment.

BACKGROUND: The aim was to investigate the correlation of bone tracer uptake (BTU) in SPECT/CT and changes in coronal knee alignment after total knee arthroplasty (TKA). We questioned if undercorrection of preoperative varus alignment leads to a difference in BTU compared to neutral alignment. METHODS: Consecutive 66 patients who received SPECT/CT before and after TKA were retrospectively included. Adjusted mechanical alignment was the alignment target. The alignment of the knee was measured on 3D-CT by selecting standardized landmarks. Maximum (mean ± SD) and relative BTU (ratio to the reference) were recorded using a previously validated localization scheme (p < 0.05). RESULTS: In the native group, 20 knees were aligned (30.3%) in valgus (HKA > 181.5°), 12 (18.2%) in neutral (178.5°-181.5°) and 34 (51.5%) in varus (HKA < 178°). Overall TKA changed the alignment towards neutral. 48.5% remained in the same groups, whereas 50% of native valgus and 33% of varus knees changed to neutral after TKA. In native varus alignment mean BTU was significantly higher in some medial tibial and femoral regions (fem1ia (p = 0.010), fem1ip (p = 0.002), tib1a.mid (p = 0.005), tib1a.tray (p = 0.000), tib1p.tray (p = 0.000)); in native valgus alignment mean BTU was higher in the corresponding lateral tibial and femoral regions (fem2ip (p = 0.001), tib2a.tray (p = 0.011), tib2p.tray (p = 0.002)). After TKA, a significant decrease in femoral and tibial BTU (femoral preoperative BTU 1.64 +/-0.69; femoral postoperative BTU 0.95 +/-0.42; p = 0.000// tibial preoperative BTU 1.65 +/- 0.93; tibial postoperative BTU 1.16 +/- 0.48; p = 0.000) and an increase in patellar BTU was observed (p = 0.025). Native varus alignment correlated with a higher medial BTU decrease medially. Undercorrection of preoperative varus alignment showed no higher BTU after TKA. CONCLUSION: Preoperative varus alignment correlated with a higher decrease in BTU in specific femoral and tibial medial regions. Preoperative valgus alignment correlated with a higher decrease in the corresponding lateral regions. Undercorrection of preoperative varus alignment did not lead to higher bone loading reflected by BTU after TKA.

Increased patellar bone tracer uptake in preoperative SPECT/CT before medial opening high tibial osteotomy correlates with inferior clinical outcome.

PURPOSE: The purpose of this study was to investigate whether specific bone tracer uptake (BTU) patterns on preoperative SPECT/CT could predict which patients with varus alignment and medial overload would particularly benefit from medial opening-wedge high tibial osteotomy (MOWHTO). It was the hypothesis that an increased preoperative BTU relative to the reference BTU of the femur on SPECT/CT in the lateral and patellar compartments of the knee are predictive factors for inferior clinical outcome and that the clinical outcome correlates with the extent of alignment correction. METHODS: Twenty-three knees from 22 patients who underwent MOWHTO for medial compartment overload were investigated preoperatively using Tc-99m-SPECT/CT. BTU was quantified and localised to specific joint areas according to a previously validated scheme. Pre- and postoperative mechanical alignment was measured. Clinical outcome was assessed at a median of 24 months (range 11-30) after MOWHTO by collecting the WOMAC score. RESULTS: Significant correlations between BTU in the patellar area and the total WOMAC score and its subcategories pain and stiffness were found. Thus, BTU in the 1sPat area (superior lateral patellar compartment) correlated with total WOMAC (rho = 0.43, p = 0.04), pain subcategory (rho = 0.43, p = 0.04), and stiffness subcategory (rho = 0.59, p = 0.003). No significant correlations were found between alignment correction, age, gender and WOMAC. CONCLUSION: This study highlights the role of preoperative SPECT in modern knee surgery to obtain information about the loading pattern on different compartments of the knee. Despite the limited number of participants, the present study shows that a preoperative SPECT/CT scan can help the treating surgeons to identify patients who may be at risk of inferior clinical outcome if an MOWHTO is considered, as an elevated BTU in the patellar region on preoperative SPECT/CT appears to be a potential risk factor for postoperative pain and stiffness. LEVEL OF EVIDENCE: Level III.

Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study.

BACKGROUND: There is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features. RESULTS: After correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with qval = 0.029 and qval = 0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL. CONCLUSIONS: Alcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses indicated that dietary folate and alcohol intake may be associated with genomic regions with tumor suppressor activity such as the GSDMD and HOXA5 genes. These results were in line with the hypothesis that epigenetic mechanisms play a role in the association between folate and alcohol, although further studies are warranted to clarify the importance of these mechanisms in cancer.

Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders.

BACKGROUND: In order to optimally integrate the use of high-throughput sequencing (HTS) as a tool in clinical diagnostics of likely monogenic disorders, we have created a multidisciplinary "Genome Clinic Task Force" at the University Hospitals of Geneva, which is composed of clinical and molecular geneticists, bioinformaticians, technicians, bioethicists, and a coordinator. METHODS AND RESULTS: We have implemented whole exome sequencing (WES) with subsequent targeted bioinformatics analysis of gene lists for specific disorders. Clinical cases of heterogeneous Mendelian disorders that could potentially benefit from HTS are presented and discussed during the sessions of the task force. Debate concerning the interpretation of identified variants and the content of the final report constitutes a major part of the task force's work. Furthermore, issues related to bioethics, genetic counseling, quality control, and reimbursement are also addressed. CONCLUSIONS: This multidisciplinary task force has enabled us to create a platform for regular exchanges between all involved experts in order to deal with the multiple complex issues related to HTS in clinical practice and to continuously improve the diagnostic use of HTS. In addition, this task force was instrumental to formally approve the reimbursement of HTS for molecular diagnosis of Mendelian disorders in Switzerland.

Circulating prolactin and breast cancer risk among pre- and postmenopausal women in the EPIC cohort.

BACKGROUND: Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors. PATIENTS AND METHODS: Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. RESULTS: Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)Q4-Q1 = 1.29 (95% confidence interval, CI, 1.05-1.58), Ptrend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [ORQ4-Q1 = 1.45 (95% CI 1.08-1.95), Ptrend = 0.01], whereas no statistically significant association was found for the non-users of HRT [ORQ4-Q1 = 1.11 (95%CI 0.83-1.49), Ptrend = 0.80] (Phet = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [ORQ4-Q1 = 0.70 (95% CI 0.48-1.03), Ptrend = 0.16]. There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. CONCLUSION: Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.

Problems associated with long-term treatment with selective serotonin reuptake inhibitors.

Although the selective serotonin reuptake inhibitors (SSRIs), which are now widely used as a first-line treatment for depression and many other psychiatric conditions, are generally well tolerated, they are not devoid of side effects. Most short-term treatment-related side effects of SSRIs are transient and disappear after a few days or weeks. However, following long-term treatment with the SSRIs, some serious adverse events may occur. Some of them can be difficult to recognise because they can resemble residual symptoms of depression. The most serious can be life threatening. They all have a negative influence on the patient's quality of life and are frequently a prime reason for a lack of long-term compliance with the associated increased risk of recurrence of a depressive episode. This article is an overview of the more common adverse events, which are seen with non-acute treatment with the SSRIs.

[MRI imaging of the neural pituitary]. / Imagerie par résonance magnétique nucléaire de la neurohypohyse.

The main illness of the neural pituitary is diabetes insipidus (DI). MRI is essential if DI occurs during childhood, in order to highlight malignant germinoma prognosis of which remains excellent if the diagnosis is made as early as possible. In adults, primary intracranial tumours causing DI include craniopharyngioma, or pineal tumours. Infiltrative histiocytosis is another frequent aetiology. One third of previously considered idiopathic DI is in fact auto-immune. Early MRI findings advocate for such a diagnosis. Finally, meticulous analysis of the neural pituitary imaging may avoid several pitfalls and help the analysis of adenopituitary abnormalities.

[Germ-cell tumors of the central nervous system in childhood: retrospective study of 13 patients]. / Les tumeurs germinales du système nerveux central de l'enfant : étude rétrospective de 13 patients.

BACKGROUND AND PURPOSE: Germ cell tumors (GCT) of the central nervous system are rare (2% of all brain tumors in children). Although originating from germ cells, GCT cover a spectrum of different tumors with different management and prognosis, depending on whether they secrete tumor markers or not. The aim of this study is to present a series of children with GCT and comment on overall management practices. METHODS: We retrospectively reviewed 13 children under the age of 18 years (nine boys and four girls), treated in the same institution between 1986 and 2006 for one or more primitive GCT of the central nervous system. RESULTS: Median age at diagnosis is 12.9 years (7-17 years). Tumor markers (alpha foetoprotein [alphaFP], human chorionic gonadotrophin [betaHCG]) were assessed 11 times in blood as well as cerebrospinal fluid (CSF). Tumors were located as follows: pineal region (10 cases), hypothalamus (eight cases), basal ganglia (one case) and corpus callosum (one case). Six were bifocal (pineal region and hypothalamus). Clinical signs were mostly dominated by diabetes insipidus and intracranial hypertension. Seven children required surgery for hydrocephalus. Tumor markers were positive in three cases and these children subsequently received chemotherapy followed by radiotherapy, except one child. Eventually, the three patients with positive markers required surgery because of a residual lesion. The eight other patients had a stereotactic biopsy for diagnosis. At the end of follow-up, treatment morbidity appears to be low and neither death nor recurrence was observed. Mean follow-up is 8.85 years (2-20 years). CONCLUSIONS: The prognosis of cerebral GCTs in children is excellent because of their pronounced chemo- and radiosensitivity. Surgery is crucial for diagnosis in the event of negative markers, or if there is evidence of residual tumor with normalization of tumor markers at the end of chemotherapy. Tumor markers must be monitored to check the diagnosis and for follow-up. The place of tumor biopsy during endoscopic third ventriculostomy (performed if hydrocephalus is present) is still debated.

[Complete bed rest prescription in an internal medicine ward: a dangerous treatment?]. / Prescrire "le lit strict" dans un service hospitalier de médecine interne: un traitement dangereux?

A general knowledge led to the assumption that bed rest is beneficial for most illnesses and bed rest is prescribed in a large number of medical conditions. However, evidence from randomised studies and systematic reviews suggest a potentially harmful effect of bed rest. This review article discusses the utility of bed rest in some frequent medical pathologies such as myocardial infarction, pulmonary embolism, community acquired-pneumonia, and low back pain.

[Imaging follow-up of post-traumatic myelomalacia]. / Evolution d'une myelomalacie post-traumatique vers une syringomyelie: suivi iconographique.

The authors report a case of secondary worsening of neurological symptoms in a patient 2 months after cord injury at T5 causing paraplegia. The MRI showed myeolomalacia, which appears as cord oedema, located in the grey matter, extending increasingly from the initial lesion (eighth thoracic vertebra) to the bulb. This cord lesion known as grey matter cytotoxic oedema, evolved into a syringomyelic cavity.

Características del dolor osteomuscular crónico en pacientes de Atención Primaria. Resultados de un centro rural y otro urbano / Epidemiology of osteomuscular chronic pain in Primary Care patients. Results from a rural centre and an urban one

Objetivo: Conocer las características sociodemográficas y clínicas de los pacientes atendidos por dolor osteomuscular crónico usuarios de dos Centros de Atención Primaria, uno rural y otro urbano, y ver si existen diferencias entre ellos. Conocer la relación entre las distintas causas de dolor crónico musculoesquelético y las variables sociodemográficas y clínicas estudiadas. Material y métodos: Diseño descriptivo observacional transversal. Estudio multicéntrico en el que intervienen los Centros de Salud del Puerto de Sagunto (Valencia) y del Alto Palancia (Castellón). Muestra de 320 usuarios de los citados centros que padezcan dolor crónico de origen osteomuscular. Recogida de datos a través de historias clínicas y de entrevistas personales durante el segundo semestre de 2003 y primero de 2004. Resultados: El dolor crónico de origen osteomuscular es más frecuente en mujeres, aumenta conforme avanza la edad, en personas casadas y viudas, de nivel sociocultural bajo y con elevada comorbilidad asociada. Provoca alto índice de incapacidades laborales. Las enfermedades que más frecuentemente provocan este tipo de dolor son la artrosis y las lum-balgias crónicas. La artrosis es la principal causa de dolor, siendo más frecuente en el medio rural. Las lumbalgias se relacionan con la actividad física realizada, predominando en la zona industrial. La mayoría de personas refieren dolor crónico osteomuscular de larga evolución (AU)

Objective: To define the sociodemographic and clinical profile of osteomuscular chronic pain patients attended by two Primary Care Centres, one rural and one urban, and to explore the existing differences between them. To know the relationship between the different causes of musculoskeletal chronic pain and sociodemographic and clinical variables. Material and method: Cross-sectional observational descriptive design. Multicentric study including the Puerto de Sagunto (Valencia) and Alto Palancia (Castellón) Health Centres. Sample of 320 users of the above mentioned centres suffering chronic pain of musculoskeletal origin. Collection of data through clinical records and personal interviews carried out during the second semester of 2003 and the first of 2004. Results: Chronic pain of musculoskeletal origin is more frequent in women, increasing with age, in married people and widows, in subjects with low sociocultural level and with high associated comorbidity. It is a frequent cause of disability. Osteoarthritis and chronic back pain are the most frequent causes. Osteoarthritis is the main cause of pain, more so in rural zones. Back pain is related to physical activity, more predominant in industrial areas. Most subjects refer long-term musculoskeletal chronic pain (AU)

Incidence of Neospora caninum and other intestinal protozoan parasites in populations of Swiss dogs.

The protozoan parasite Neospora caninum is one of the most important abortifacient organisms in cattle worldwide. The dog is known to act as definitive host although its potential role as infection source for bovines still remains unelucidated. The aim of the present study was to compile initial epidemiological data on the prevalence and incidence of N. caninum in Swiss dogs acting as definitive hosts. Thus, 249 Swiss dogs were investigated coproscopically in monthly intervals over a period of 1 year. A total of 3289 fecal samples was tested by the flotation technique. Among these, 202 were shown to contain Sarcocystis sp. (6.1%), 149 Cystoisospora sp. (=Isospora sp.; 4.5%) and 25 Hammondia/Neospora-like oocysts (HNlO) (0.7%). All but one sample containing HNlO were from different dogs; one dog shed HNlO at two subsequent time points. Calculation of the yearly incidence for HNlO resulted in the surprisingly high value of 9.2%. Farm dogs exhibited a higher incidence for HNlO than urban family dogs. Thirteen out of the 25 HNlO-samples showed sporulation after 5 days incubation at room temperature. HNlO were further differentiated by species-specific PCR. However, all HNlO-samples were negative for N. caninum, Hammondia heydorni and Toxoplasma gondii. One reason may be the low oocyst density found in most fecal samples, which did not permit us to carry out PCR under optimal conditions. Three out of the 25 HNlO-cases contained enough oocysts to allow further enrichment and purification by the flotation technique. Subsequently, twenty to fifty sporulated HNlO-oocysts were orally administered to Meriones unguiculatus. All gerbils were seronegative for N. caninum at 5 weeks p.i. A N. caninum-seroprevalence of 7.8% was determined by ELISA upon 1132 serum samples collected from dogs randomly selected by veterinarians among their clinical patients.

[Risks and responsibilities in diagnostic and interventional radiology. Ethical and medicolegal considerations]. / Risques et responsabilités en radiologie diagnostique et interventionnelle. Aspects éthiques et médico-légaux.

Medical risk management has one main purpose: to ensure the safety of care. The law of March 2002 has generated a true cultural revolution. The radiologist is involved with new and difficult areas of medical liability due to technical advances, the increasing number of imaging techniques, the increasing complexity of imaging techniques, their efficiency and the need for multidisciplinary approach. Imaging recommendations requiring increasing levels of technical and clinical skills. The radiologist is liable with regards to the indications of imaging studies, and also with regards to informed consent. The prevention of medicolegal problems is achieved by competency, which must be combined to good liability insurance and ongoing vigilance supported by appropriate continuous medical education.

Individualized treatment of craniopharyngioma in children: ways and means.

BACKGROUND: Medium- and long-term prognosis of craniopharyngioma is overwhelmed by the risks of hypothalamic and visual impairment. This problem has been underestimated for a long time because the major concern for the neurosurgeon was the risk of recurrences, their best prevention being thought to be complete tumour resection. Today, we know that radical surgery not only is not an absolute guarantee against recurrences but also can cause hypothalamic and visual complications. METHODS: The authors suggest that instead of complete removal, the first choice treatment should be, when possible, a less aggressive, multistaged and personalized treatment. In this perspective they focus on other therapeutic methods: endocavity treatment of cysts with rhenium-186, triconformational radiotherapy, radiosurgery, and widespread use of the trans-sphenoidal approach. CONCLUSIONS: These simple methods should reduce the risks of visual aggravation and metabolic syndrome.

Reproducibility over time of measurements of androgens, estrogens and hydroxy estrogens in urine samples from post-menopausal women.

Sex steroid concentrations in urine samples from post-menopausal women have been associated with risk of various chronic diseases. The basic requirement for the assessment of risk in such large-scale epidemiological studies is that subjects be ranked accurately by their average, long-term hormone levels. We examined the reproducibility over time of measurements of urinary testosterone (T), 5alpha-androstane-3alpha, 17beta-diol (ADIOL), estrone (E1), estradiol (E2), 2-hydroxy estrone and 2-hydroxy estradiol, (2(OH)-E), 16alpha-hydroxyestrone (16alpha(OH)-E1) and the ratio of 2(OH)-E and 16alpha(OH)-E1, in a representative sub-sample of post-menopausal women (n = 43) participating in an ongoing prospective cohort study. Women collected three first morning urine voids on different occasions, with average time difference between the first and the third urine sample of 5.1 years. T, ADIOL, E1 and E2 were measured by radio immunoassay after enzymatic hydrolysis, solid-phase extraction and HPLC purification of the samples, while 2(OH)-E and 16alpha(OH)-E1 were assayed by solid-phase enzyme immunoassay after enzymatic hydrolysis. Intra-class correlation co-efficients (ICCs) over time were very good for T (r = 0.85), acceptable for E2, E1 and ADIOL (r > 0.55), but low for 2(OH)-E, 16alpha(OH)-E1 and their ratio (r < 0.46). The adjustment for creatinine concentrations did not increase these correlations.

[Thrombus of the left lateral sinus spreading to the internal jugular vein]. / Thrombose du sinus latéral gauche étendue à la veine jugulaire interne.

Cerebral venous thrombosis is an uncommon event which presents a wide spectrum of sometimes extraneurological signs different from the classical clinical presentation. We report the cases of two middle-aged women who developed thrombosis of the left lateral sinus spread-ing to the internal jugular vein from the sigmoid sinus. The time course of the symptoms suggested that intracranial thrombosis occurred first. No infectious or neoplastic local disease could be found but both women were taking oral contraceptives. Medical treatment led to good reperfusion of the intracranial sinuses but occlusion of the jugular vein persisted despite prolonged oral anticoagulants. Long-term outcome was favorable with residual benign epilepsy in one patient, and occurrence of an arteriovenous fistula in the other.

Quiste óseo traumático bilateral asociado a tratamiento de ortodoncia: presentación de un caso y revisión de la literatura / Bilateral traumatic bone cyst associated with orthodontic treatment: report of a case and review of the literature

El quiste óseo traumático es una cavidad intraósea sin recubrimiento epitelial, es considerado un pseudoquiste maxila. Este quiste, también denominado simple o hemorrágico, tiene una etiología traumática en el 25 por ciento de los casos y también puede originarse de un infarto en la médula ósea o del hueso esponjoso, degeneración quística o alteración de la osificación. Representa del 0,2 al 1 por ciento de la patología quística maxilar y se presenta generalmente de forma asintomática en la mandíbula de jóvenes entre los 5 y 25 años. El pronóstico, tras curetaje simple de la cavidad, es excelente, incluso para la vitalidad de los dientes involucrados. Se presenta un caso de quiste óseo traumático bilateral asociado a trauma por fuerzas excesivas en el tratamiento de ortodoncia, en paciente femenina de 16 años de edad. Se planificó tratamiento quirúrgico, con toma de muestra para estudio histopatológico. Se realizó seguimiento radiográfico durante 1 año, obteniéndose excelentes resultados

Where are the new therapies for anxiety and obsessive-compulsive disorders?

The benzodiazepines have monopolized the acute anxiety market for about 40 years, but their potential for tolerance and dependency has stimulated an interest in alternative anxiolytics. Until recently, however, attention has focused on existing drugs such as monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors. The 5-HT1A partial agonist, buspirone (Bristol-Myers-Squibb), is one of the few compounds developed principally as an anxiolytic since the benzodiazepines. The challenge for the future is not only to find efficacious treatments with a rapid onset of action and an acceptable side effect profile but also to determine the optimal compounds for each of the different anxiety disorders.