Frailty of the elderly in orthopaedic surgery and body composition changes: the musculoskeletal crosstalk through irisin.

In recent years, scientific interest has been developed towards irisin, a novel molecule of the family of myokines, which is directly involved in body mass composition balance, chronic diseases susceptibility and physiologic resilience to stressful events, including surgery. In the context of musculoskeletal disease, the role of this molecule has been associated to the balance of lean and fatty mass, and the production of irisin is subordinated to a healthy lifestyle and exercise. The mechanism of action of irisin on tissues is complex, and several studies described the molecular pathways in animal model and human subjects. In particular, in adipose cells, the key-role of irisin is to stimulate the differentiation of white adipose tissue to brown adipose tissue, through the action on the uncoupling protein 1. Furthermore, in the bony tissue, irisin stimulates osteogenesis through expression of Sost and Opn genes. These features make irisin a suitable molecule to use as a biomarker of the overall musculoskeletal health of the elderly, before undergoing orthopaedic surgery. Further research on this topic should be carried out to highlight the possible clinical role and predictive value of irisin in a multidisciplinary approach to the elderly before musculoskeletal surgery.

Preliminary results of video-assisted anal fistula treatment (VAAFT) in children.

BACKGROUND: Anal fistula is a common acquired anorectal disorder in children. Treatment methods that have been used are associated with inconsistent results and possible serious complications. In 2011 a minimally invasive approach, video-assisted anal fistula treatment (VAAFT) was described for adult patients. The aim of the present study was to assess the first series of pediatric patients treated with VAAFT. METHODS: All patients who underwent VAAFT between August 2013 and May 2015 were included. Demographics, clinical features, preoperative imaging, surgical details, outcome, and medium-term data were prospectively collected for each patient. RESULTS: Thirteen procedures were performed in nine patients. The male to female ratio was 8:1, and the median age was 9.6 years. Five fistulas were idiopathic, three iatrogenic, and one associated with Crohn's disease. Eight complete VAAFT procedures were performed. The remaining five procedures were either fistuloscopy and cutting seton placement or fistuloscopy and electrocoagulation, both without mucosal sleeve. The median length of surgery was 41 min. The median hospital stay was 24 h, and the median length of follow-up was 10 months. Resolution of the fistula was observed in all patients who underwent a complete VAAFT. In four out of five patients who underwent an incomplete procedure (without mucosal sleeve), the fistula recurred. No incontinence or soiling was reported in the medium term. CONCLUSIONS: VAAFT proved to be feasible and safe in children. It also proved to be versatile as it could be applied to fistulas of different etiologies. The key to success seems to be an adequate mucosal sleeve. Older children and adolescents benefit most from VAAFT which is a valid alternative to available surgical procedures.

Shape and size of the medial patellofemoral ligament for the best surgical reconstruction: a human cadaveric study.

PURPOSE: The aim of this study was to investigate the shape and the attachments of the medial patellofemoral ligament (MPFL) in cadaver specimens to determine an anatomical basis for the best MPFL reconstruction. METHODS: Twenty fresh-frozen knees were used. Dissection protocol implied performing dissections from within the knee joint. We investigated the shape and the attachments between the MPFL and the quadriceps tendon, the patellar and femur insertions, and all the other relationships with the medial soft tissues of the knee. RESULTS: The distal fibers of MPFL were interdigitated with the deep layer of the medial retinaculum. All isolated ligament had a sail-like shape with the patellar side bigger than the femoral side. The femoral insertion, distinct both from medial epicondyle and adductor tubercle, was located at 9.5 mm (range 4-22) distal and anterior respect to adductor tubercle and proximal and posterior to epicondyle. The medial third of the thickness of patella was involved in the insertion. The proximal third of the patella is always involved in the MPFL attachment; in 45% of the cases, it was extended to the medial third and in one case, an extension at the distal third was found. Additionally in 35% (7 cases), it extended to the quadriceps tendon and it were inconstantly attached at the vastus medialis obliques (VMO) tendon and at the vastus intermedius (VI) tendon in an aponeurotic structure. CONCLUSIONS: The MPFL is a distinct structure that goes from patella to femur with a sail-like shape; its patellar insertion, that mostly occur via an aponeurosis tissue with VMO and VI, is at the proximal third of the patella but it may extend in some cases to the medial third patella or to the quadriceps tendon, or very rarely to the distal third of the patella. In the femoral side, the MPFL is inserted in its own site, in most cases distinct both from epicondyle and adductor tubercle, located on average at a 9.5 mm distance distally and anteriorly in respect to the adductor tubercle. Its lower margin was difficult to define. Given the importance of this structure, it must be reconstructed as anatomically as possible in its insertion and in its shape. Many attempts have been made to make functional reconstructions with less than excellent results.

[Emerging biomarkers for the diagnosis, staging and prognosis of prostate cancer]. / Les biomarqueurs émergents du diagnostic, du staging et du pronostic du cancer de la prostate.

The introduction and widespread adoption of prostate-specific antigen (PSA) has revolutionized the way prostate cancer is diagnosed and treated. However, the use of PSA has also led to overdiagnosis and overtreatment of prostate cancer resulting in controversy about its use for screening. PSA also has limited predictive accuracy for predicting outcomes after treatment and for making clinical decisions about adjuvant and salvage therapies. Hence, there is an urgent need for novel biomarkers to supplement PSA for detection and management of prostate cancer. A plethora of promising blood- and urine-based biomarkers have shown promise in early studies and are at various stages of development (Human kallikrein 2, Early Prostate Cancer Antigen, Transforming Growth Factor-Beta 1 and Interleukin-6, Endoglin, PCA3, AMACR and ETS Gene Fusions). In this article, we review those biomarkers and then discuss the challenges a biomarker has to undergo before it is approved in a clinical use.

[Bladder located gastric heterotopy: a case report confronting embryology to histopathology]. / Hétérotopie gastrique de siège vésical: un cas clinique au carrefour de l'embryologie et de l'histopathologie.

We report a case of bladder located gastric heterotopy, which has never been described, to our mind in the scientific literature. We discuss the diagnosis and the physiopathological mechanisms that may have been involved in the genesis of such a lesion.

[Does the urologist in formation have a burnout syndrome? Evaluation by Maslach Burnout Inventory (MBI)]. / Les urologues en formation ont-ils un syndrome d'épuisement professionnel ? Évaluation par le Maslach Burn-out Inventory (MBI).

OBJECTIVES: To assess the burn-out syndrome in the population of urologists in training. MATERIAL AND METHODS: A trans-sectional study was carried out among the French urologists in training association (AFUF) members. A questionnaire including the Maslach Burnout Inventory and questions on the age, gender, professional and familial status, working time and hobbies was emailed. RESULTS: The response rate was 65.5 %. Mean burn-out, emotional exhaustion and depersonalization scores were 15.57 ± 8.55 (low burn-out), 8.56 ± 5.52 (moderate burn-out) and 37.19 ± 6.21 (moderate burn-out), respectively. Forty-five (24 %) had a severe burn-out syndrome, 11 an emotional exhaustion and 41 a depersonalization. Urologists in couple had a significant lower emotional exhaustion level than single. Depersonalization and low personal accomplishment scores were related to the age and working time. Having at least one hobby prevented emotional exhaustion and improved personal accomplishment levels. Gender had no impact on burn-out syndrome. CONCLUSION: Quarter of French urologists in training had a burn-out syndrome. Factors preventing it were working time reduction, being in couple and having at least one hobby. burn-out syndrome severity decreased with age and senior status.

Oncocytic choroid plexus carcinoma: case report.

Herein, we report an unusual choroid plexus carcinoma with extensive oncocytic transformation. A 13-month-old girl presented with acute lethargy which quickly progressed to coma. A CT scan of the head revealed impending herniation due to hemorrhage within an intracranial tumor. An MRI scan showed a large, partly cystic and highly vascular left lateral ventricular mass. A near total resection was achieved. Microsections revealed a WHO Grade III choroid plexus carcinoma with extensive oncocyti c transformation. A minor portion of the moderately to poorly differentiated tumor exhibited classical microscopic features of choroid plexus carcinoma, including marked nuclear atypia, brisk mitotic activity (78/10 HPF), a high MIB-1 labeling index (44%) and zones of necrosis. In contrast, the large, eosinophilic, cytologically malignant but granular-appearing oncocytes comprising the majority of the lesion showed scant (1/10 HPF) mitotic activity and only a low MIB-1 labeling index (5%). A subsequent recurrence at 1 year consisted entirely of non-oncocytic tumor. Choroid plexus carcinoma with oncocytic transformation has not been previously reported. The remarkable extent of this alteration and its clinical significance remains to be determined.

[Stenosis of the upper renal pelvis: rare complication of an incomplete ureteral duplicity. Embryological investigation]. / La sténose du pyélon supérieur : complication rare d'une bifidité urétérale. Enquête embryologique.

A stenosis of the upper pole of an incomplete renal duplication is presented. The prenatal diagnosis of a right renal ureteropyelic junction syndrome, isolated, with a normal amniotic liquid was confirmed at birth. Intravenous pyelogram 8 days after birth showed three right dilated calical groups with a dilated renal ureteropyelic junction, but an normal inferior calical group suspected a renal bifidity. Renal MagIII scintigraphy evaluated the anatomical and functional stenosis and indicated surgery. Postoperative followings were simple and results good 3 years after. From this rare case, embryogenesis is discussed.

[Results of an investigation by questionnaire into interest in neuro-urology of urology residents]. / Résultat d'une enquête par questionnaire sur l'intérêt porté à la neuro-urologie par les urologues en formation.

OBJECTIVES: To evaluate the interest borne towards neuro-urology within the community of the urology residents. MATERIALS AND METHODS: Between January and May 2009, all urology residents received an anonymous questionnaire by e-mail estimating their interest for neuro-urology. The analyzed data were: epidemiologic data; participation in theoretical learning and training courses practices; interest and investment in the speciality; opinion on the current formation. The qualitative variables were compared by the chi-2 test. P values <0,05 were considered significant. RESULTS: The rate of answer was 45,3 %. The middle age was 28,7+/-2,3 years. Ninety-two (70,7 %) of the 130 urologist residents questioned wished to exert full-time or divided in a hospital structure. They were 40 % to have a multidisciplinary neuro-urology staff, and 80 % were in a service which dealt with suffering patients of neurological bladder. The percentage of urologist residents interested by neuro-urology was 69,2 %, and 61,5 % of them wished to practice this activity in their future exercise. This wish was significantly higher for those resulting from the ENC (p<0,05), for those wishing to exert at the hospital (p<0,01) and for those who practice urology at a level of expertise in neuro-urology (p<0,01). The theoretical and practical teaching of neuro-urology were considered as being insufficient for respectively 73,9 % and 64,2 % of the urologist residents. In contrast, the average note allotted to the neuro-urology module of the ECU was of 7,47 out of 10. CONCLUSION: Neuro-urology seems to be particularly attractive for the urologist residents, and many wished to integrate it in their future exercise. The motivation was more important for those who wished to carry out a career in hospital. Even if the quality of the teaching was very noted, their modalities were considered to be insufficient by most of them.

[Demography of residents in urology in France: appraisal and perspectives]. / Etat des lieux et perspectives sur la démographie des internes en urologie en 2008.

PURPOSE: The objective was to identify the number of residents registered in the course of urology in France in 2008, and to make a forecast in the number of posts of fellow and specialist assistant available at the end of their course. MATERIAL: From January to February 2008, a questionnaire identified in all French University Hospital the number of residents enrolled in the urology course, and the number of posts of fellow and specialist assistant in urology in the region. The year of the end of the course has been determined for each resident in compliance with seniority, and taking into account the availability. The number of fellow and specialist assistant posts available in the same period was estimated by considering the duration of each postinternship, and any change in the number of posts. RESULTS: Our census counted 207 residents, 76 fellow posts, 10 specialist assistant posts. Of the 207 residents, 29 completed their studies in 2008, 57 in 2009, 60 in 2010, 61 in 2011. Following our methodology, there was a lack of fellow and specialist assistant posts available from November 2010 (-15 posts in 2010, -7 posts in 2011). CONCLUSION: Our study showed an increase in the number of residents enrolled in urology course by years of promotion, causing a lack of fellow and specialist assistant posts from 2010. Apart from an opening of additional fellows and specialist assistants at that time, our study highlights the long-term regulation of entries in the urology course ensuring a postinternship quality.

Treatment of hypertension in the elderly: effects on blood pressure, heart rate, and physical fitness.

The subjects were 36 hypertensive patients aged 61 to 79 years (mean, 66 years). After a placebo run-in period of one month, each patient was randomly assigned to two months of treatment with 100 mg of metoprolol, 50 mg of captopril, or 25 mg of hydrochlorothiazide plus 2.5 mg of amiloride daily, or placebo. The doses were doubled if diastolic pressure was above 95 mm Hg after one month of treatment. Blood pressure, heart rate, and physical fitness (endurance during a standard cycle ergometer exercise) were measured and side effects assessed after each two-month treatment period. Mean blood pressures were significantly lower after treatment with metoprolol (154/92 mm Hg), captopril (157/92 mm Hg), and hydrochlorothiazide-amiloride (152/91 mm Hg) than after placebo (170/101 mm Hg). Heart rate was significantly lower after treatment with metoprolol (64 beats/minute) than after placebo (77 beats/minute). Exercise endurance was lower after treatment with metoprolol (498 seconds) and hydrochlorothiazide-amiloride (519 seconds) than after placebo (529 seconds) and higher after captopril (541 seconds). More patients reached the target exercise work load after captopril than after the other treatments. No patients withdrew from treatment because of side effects or abnormal laboratory test results. All three active treatments benefited the elderly hypertensive patients and did not lower their physical fitness. Captopril appeared to be more effective than the other two treatments.

Laparoscopic vs open approach for the treatment of gastroesophageal reflux in children.

BACKGROUND: The laparoscopic approach has become increasingly popular for fundoplication over the last few years; however many surgeons are skeptical about its real advantages. METHODS: We conducted a prospective comparative study of children operated on for gastroesophageal reflux (GER). Exclusion criteria included age <1 YEAR AND >14 years, previous surgery on the esophagus or stomach, and neurologic impairment. We compared two groups of patients who met the same inclusion/exclusion criteria. One group was treated via a laparotomic approach between January 1993 and December 1997; the other was treated via a laparoscopic approach between September 1998 and December 2000. A 360 degrees wrap was performed in each group. RESULTS: Group 1 (laparotomic approach) included 17 patients; mean operative time was 100 min and postoperative time was 7 days. Group 2 comprised 49 children operated on via a laparoscopic approach; mean operative time was 78 min and postoperative time was 48 hours. No major complications were encountered in either group. In postoperative period, two patients in group 1 had complications. One had a prolonged bout of gastroplegia, which required nasogastric drainage, and then recovered spontaneously after 20 days; the other had stenosis of the wrap, which required dilation. No relapses occurred during a follow-up of 6 months. Long-term follow-up data are not presented. Comparative analysis of the short-term functional results indicated that there were no differences between the two groups. CONCLUSION: This study confirms that the minimally invasive approach is safe and effective for the treatment of primary gastroesophageal reflux disease in children.

Loxapine intoxication: case report and literature review.

Loxapine is a dibenzoxazepine tricyclic compound used to treat schizophrenia in the United States since 1976. Metabolism includes demethylation to its primary metabolite, amoxapine. There are few documented reports of the disposition of loxapine in deaths due to overdose. This report discusses the overdose suicide of a 69-year-old white female found dead in her home by her husband. A prescription for loxapine (50-mg capsules) was found near the body. An autopsy was performed and heart blood, bile, vitreous humor, and gastric contents were submitted for toxicological analysis. The blood specimen was subjected to comprehensive testing that included volatile analysis by headspace gas chromatography (GC); acidic/neutral and basic drug screening by GC; benzodiazepine screening by high-performance liquid chromatography; opiate screening by modified immunoassay; and acetaminophen, salicylate, and ethchlorvynol screening by colorimetry. Loxapine and amoxapine were detected in the basic drug screen. No other drugs were detected in the case specimens. The respective concentrations of loxapine and amoxapine in each specimen were as follows: heart blood, 9.5 and 0.6 mg/L; bile, 28.8 and 4.7 mg/L; gastric, 278 mg/L and negative; and vitreous, 1.5 mg/L and negative. A review of the literature showed that the heart blood concentration of loxapine measured in this case was the highest reported to date. Based on the autopsy findings, patient history, and toxicology results, the cause of death was determined to be acute intoxication of loxapine and the manner, suicide.

Anorectal malformations associated with enteric dysganglionosis in Danforth's short tail (Sd) mice.

BACKGROUND: The spontaneous mutant Danforth's short tail (Sd) mouse has been studied over the last 60 years from the morphological, embryological, and genetic point of view. The Sd mutation affects a gene essential to notochordal development, and the Sd mouse phenotype represents an analogue of human caudal regression syndrome. The Sd/Sd mouse presents different types of anorectal malformations (ARM) and was suggested as a simple and cheap model of investigation of ARM morphology and embryology. In the current study, the Sd mouse enteric nervous system (ENS) was thoroughly investigated with specific immunohistochemical markers. METHODS: Macroscopic analysis, normal histology, and immunohistochemical techniques for detecting neurofilaments (NF) and NOS1 were used to study ENS of 138 Sd mice and 25 controls. RESULTS: The surprising results of this study showed that Sd mutation is associated with different degrees of hypoganglionosis and aganglionosis. In 41% of Sd/SD-affected mice, the rectal pouch was aganglionic and in the remaining 58% was severely hypoganglionic. In addition, 4.1% of heterozygous mice presented a distal aganglionosis and 8.3% hypoganglionosis. CONCLUSIONS: These results suggest that Sd mutation independently affects distinct cell lines during early organogenesis, as notochord cells, ventral hingut endoderm, and neuroblasts migrating from neural crest cells. Comparing the Sd murine model with human pathology, this study confirms that the association between ARM and intestinal dysganglionosis is not rare and underlines the importance of detecting in every ARM patient the innervation abnormalities of rectal pouch and fistulas.

GDNF deficit in Hirschsprung's disease.

BACKGROUND/PURPOSE: In 1996, the glial cell line-derived neurotrophic factor (GDNF) was identified as one of the ligands of the RET transmembrane receptor. In the same year, GDNF mutations were found in association with RET protooncogene mutations in Hirschsprung patients. Mutations in GDNF per se are thought neither necessary nor sufficient to cause Hirschsprung's disease (HD). To date, our study group has identified GDNF mutations only in 2 of 98 cases of intestinal dysganglionosis. The aim of our study was to investigate a possible expression deficit of GDNF in the enteric nervous system of Hirschsprung patients not mutated for the GDNF gene. METHODS: We used rabbit polyclonal antibodies raised against a peptide corresponding to amino acids 186-205 mapping within the carboxy-terminal domain of human GDNF. GDNF expression was studied immunohistochemically in surgical specimens from 30 HD cases (27 classic forms and 3 ultralong forms) and from 10 age-matched controls. Serial sections from the same full-thickness specimens were investigated with the following histochemical and immunohistochemical techniques: acetylcholinesterase, lactate dehydrogenase, succinic dehydrogenase, alpha-naphthyl-esterase, glial fibrillary acid protein, S-100 protein, and neuron-specific enolase. RESULTS: A high level of GDNF expression was found in normal intestine and in Hirschsprung ganglionic segment. Satellite elements of myenteric ganglia presented a strong immunoreactivity to GDNF. Conversely, the aganglionic segment showed cholinergic hyperinnervation and hypertrophic trunks of nerve fibers in the muscular interstitium with complete absence of GDNF expression. The small ganglia of the hypoganglionic segment showed a reduced GDNF immunoreactivity. CONCLUSIONS: GDNF, a distantly related member of the transforming growth factor-beta superfamily, is a potent neurotrophic and survival factor for neurons and enteric ganglion cells. Mutations of the GDNF gene or GDNF expression deficit interrupt the faithful GDNF signaling via Ret, contributing to HD pathogenesis.

Comparative evaluation of three dosages of slow-release isosorbide dinitrate (60, 80, 100 mg) in chronic angina of the aged.

In a single-blind, placebo-controlled study the acute and chronic antianginal effects of three slow-release (SR) new formulations of isosorbide dinitrate (ISDN 60, 80, 100 mg) have been comparatively evaluated in a group of aged affected by chronic stable effort-induced angina. Compared to placebo, overall the active dose paritetically improved the effort tolerance up to 24 h after the first assumption. In the time course of the trial (2 and 4 weeks) the resting hemodynamic changes induced by the first dose were partially blunted without affecting the exercise related-parameters. Also if plasma levels of ISDN and of its metabolites did not correlate to the degree of physical improvement, the peak increase in effort tolerance was observed under 100 mg treatment. Mild to moderate transient headache was experienced by 50% of actively treated and by 20% of placebo treated patients and no other serious adverse effects have been noted. One may conclude that ISDN in slow-release formulations of 60-100 mg isan effective, safe and well tolerated medication in the management of angina in the aged.