Igor Tauveron

Culture of per-wound bone specimens: a simplified approach for the medical management of diabetic foot osteomyelitis

Surgical percutaneous bone biopsy specimen after a 14-day antibiotic-free period represents the gold standard of care for diabetic foot osteomyelitis but may be difficult to implement in many institutions. We evaluate a simplified strategy based on the results of per-wound bone specimen culture. For that purpose, we retrospectively reviewed the charts of 80 consecutive patients with diabetic osteomyelitis and bone sample obtained via the wound after a careful debridement. The outcome was defined as favourable if there was a complete healing of the wound with no sign of infection and stable or improved bone X-ray 6 months after antibiotic therapy completion. Culture of bone specimens was positive in 96% of patients, although half of the patients did receive a course of antimicrobials within 14 days of the bone specimen being obtained. A total of 129 bacterial isolates were obtained from bone cultures with a mean of 1.6 ± 1 isolates per patient (Staphylococcus aureus: 33%; central nervous system: 14%; streptococci: 9%; enterococci: 12%; corynebacteria: 4%; Gram-negative bacilli: 20%; anaerobes: 4%). Forty-six percent of cultures were monomicrobial. The mean duration of follow-up from diagnosis was 17 ± 1 months. Six months after discontinuation of antibiotic, six patients (7.5%) had died, nine were considered as therapeutic failures and 65 were considered as cured. Fifty-four of these 65 patients had follow-up data available at 1 year and remained in remission. In conclusion, a simplified procedure based on the culture of bone sample obtained via the ulcer after a careful debridement of the wound is effective in the medical management of diabetic foot osteomyelitis.

Aggressive silent GH pituitary tumor resistant to multiple treatments, including temozolomide.

Temozolomide (TMZ) has been proposed as a therapeutic option in aggressive pituitary tumors. Among the published cases, GH expressing tumors were rare. We describe a patient with initially benign silent GH adenoma that transformed into an aggressive GH secreting tumor resistant to usual therapy. MGMT expression was high and the MGMT promoter was unmethylated. Before this aggressive course, patient received three cycles of TMZ; no response was observed. Four cases of GH aggressive tumor treated by TMZ have been reported. Response to TMZ was observed in one of these four patients. Predictive factors of failure of TMZ remain unclear.

PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development

Adrenal cortex physiology relies on functional zonation, essential for production of aldosterone by outer zona glomerulosa (ZG) and glucocorticoids by inner zona fasciculata (ZF). The cortex undergoes constant cell renewal, involving recruitment of subcapsular progenitors to ZG fate and subsequent lineage conversion to ZF identity. Here we show that WNT4 is an important driver of WNT pathway activation and subsequent ZG differentiation and demonstrate that PKA activation prevents ZG differentiation through WNT4 repression and WNT pathway inhibition. This suggests that PKA activation in ZF is a key driver of WNT inhibition and lineage conversion. Furthermore, we provide evidence that constitutive PKA activation inhibits, whereas partial inactivation of PKA catalytic activity stimulates β-catenin-induced tumorigenesis. Together, both lower PKA activity and higher WNT pathway activity lead to poorer prognosis in adrenocortical carcinoma (ACC) patients. These observations suggest that PKA acts as a tumour suppressor in the adrenal cortex, through repression of WNT signalling.

Acute and Chronic Pheochromocytoma-Induced Cardiomyopathies: Different Prognoses?: A Systematic Analytical Review.

AbstractPheochromocytoma and paraganglioma (PPG) are rare and late-diagnosed catecholamine secreting tumors, which may be associated with unrecognized and/or severe cardiomyopathies.We performed a computer-assisted systematic search of the electronic Medline databases using the MESH terms “myocarditis,” “myocardial infarction,” “Takotsubo,” “stress cardiomyopathy,” “cardiogenic shock”, or “dilated cardiomyopathy,” and “pheochromocytoma” or “paraganglioma” from 1961 to August 2012. All detailed case reports of cardiomyopathy due to a PPG, without coronary stenosis, and revealed by acute symptoms were included and analyzed.A total of 145 cases reports were collected (49 Takotsubo Cardiomyopathies [TTC] and 96 other Catecholamine Cardiomyopathies [CC]). At initial presentation, prevalence of high blood pressure (87.7%), chest pain (49.0%), headaches (47.6%), palpitations (46.9%), sweating (39.3%), and shock (51.0%) were comparable between CC and TTC. Acute pulmonary edema (58.3% vs 38.8%, Pu200a=u200a0.03) was more frequent in CC. There was no difference in proportion of patients with severe left ventricular systolic dysfunction (LV Ejection Fraction [LVEF]u200a<u200a30%) at initial presentation between both groups (Pu200a=u200a0.15). LVEF recovery before (64.9% vs 40.8%, Pu200a=u200a0.005) and after surgical resection (97.7% vs73.3%, Pu200a=u200a0.001) was higher in the TTC group. Death occurred in 11 cases (7.6%). In multivariate analysis, only TTC was associated with a better LV recovery (0.15 [0.03–0.67], Pu200a=u200a0.03).Pheochromocytoma and paraganglioma can lead to different cardiomyopathies with the same brutal and life-threatening initial clinical presentation but with a different recovery rate. Diagnosis of unexplained dilated cardiomyopathy or TTC should lead clinicians to a specific search for PPG.

Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: a pilot prospective clinical trial

BackgroundRecommendations for cardiovascular disease prevention advocate lowering both cholesterol and low-density lipoprotein cholesterol systemic levels, notably by statin intake. However, statins are the subject of questions concerning their impact on male fertility. This study aimed to evaluate, by a prospective pilot assay, the efficacy and the toxicity of a decrease of cholesterol blood levels, induced by atorvastatin on semen quality and sexual hormone levels of healthy, normocholesterolaemic and normozoospermic men.MethodsAtorvastatin (10xa0mg daily) was administrated orally during 5xa0months to 17 men with normal plasma lipid and standard semen parameters. Spermatozoa parameters, accessory gland markers, semen lipid levels and blood levels of gonadal hormones were assayed before statin intake, during the treatment, and 3xa0months after its withdrawal.ResultsAtorvastatin treatment significantly decreased circulating low-density lipoprotein cholesterol (LDL-C) and total cholesterol concentrations by 42% and 24% (pu2009<u20090.0001) respectively, and reached the efficacy objective of the protocol. During atorvastatin therapy and/or 3xa0months after its withdrawal numerous semen parameters were significantly modified, such as total number of spermatozoa (-31%, pu2009<u20090.05), vitality (-9.5%, pu2009<u20090.05), total motility (+7.5%, pu2009<u20090.05), morphology (head, neck and midpiece abnormalities, pu2009<u20090.05), and the kinetics of acrosome reaction (pu2009<u20090.05). Seminal concentrations of acid phosphatases (pu2009<u20090.01), α-glucosidase (pu2009<u20090.05) and L-carnitine (pu2009<u20090.05) were also decreased during the therapy, indicating an alteration of prostatic and epididymal functions. Moreover, we measured at least one altered semen parameter in 35% of the subjects during atorvastatin treatment, and in 65% of the subjects after withdrawal, which led us to consider that atorvastatin is unsafe in the context of our study.ConclusionsOur results show for the first time that atorvastatin significantly affects the sperm parameters and the seminal fluid composition of healthy men.Trial registrationClinicalTrials.gov: NCT02094313.

Once and for all, LXRα and LXRβ are gatekeepers of the endocrine system

Liver X receptors (LXRs) α and β are nuclear receptors whose transcriptional activity is regulated by oxysterols, the oxidized forms of cholesterol. Described in the late 1990s as lipid sensors, both LXRs regulate cholesterol and fatty acid homeostasis. Over the years, deep phenotypic analyses of mouse models deficient for LXRα and/or LXRβ have pointed out various other physiological functions including glucose homeostasis, immunology, and neuroprotection. This review enlightens the endocrine functions of LXRs; they deeply impact plasma glucose directly and by modulating insulin signaling, renin-angiotensin-aldosterone axis, thyroid and pituitary hormone levels, and bone homeostasis. Besides, LXR signaling is also involved in adrenal physiology, steroid synthesis, and male and female reproduction. Hence, LXRs are definitely involved in the endocrine system and could thus be considered as endocrine receptors, even though oxysterols do not fully correspond to the definition of hormones. Finally, because they are ligand-regulated transcription factors, LXRs are potential pharmacological targets with promising beneficial metabolic effects.

Acute prediction of laryngeal outcome during thyroid surgery by electromyographic laryngeal monitoring

The purpose of this study was to evaluate the contribution of laryngeal intraoperative nerve monitoring (IONM) during thyroidectomy in predicting postoperative laryngeal mobility.

Screening for deprivation using the EPICES score: A tool for detecting patients at high risk of diabetic complications and poor quality of life

AIMnDeprivation has been linked to more complicated and uncontrolled diabetes. The validated Évaluation de la précarité et des inégalités de santé dans les centres dexamens de santé (EPICES; Evaluation of the Deprivation and Inequalities of Health in Healthcare Centres) score could help to identify such deprived patients. The present study evaluated the relationships between deprivation and prevalence of complications, uncontrolled diabetes and quality of life.nnnMETHODSnThis prospective study was conducted in the diabetology department of a tertiary university hospital from November 2006 to July 2007. Patients with diabetes were divided into two groups, according to their deprivation status [non-deprived: EPICES score<30.17; deprived: EPICES score≥30.17 (56.5%)]. Diabetes control, complications and quality of life [Short Form Health Survey (SF-36)] were compared in the two groups.nnnRESULTSnOf a total of 102 patients, 97 completed all of the questionnaires: 18 had type 1 diabetes and 79 had type 2 diabetes, in a geographical area moderately affected by deprivation. No statistical relationship could be demonstrated between deprivation and HbA(1c). Deprived patients with diabetes presented with higher levels of fasting blood glucose, lower levels of LDL cholesterol and a significantly higher risk of obesity (P=0.0020). As for complications, microalbuminuria was linked to deprivation (P=0.03), but no associations with other complications were found. Quality of life was poorer for all physical, mental and social dimensions in deprived patients.nnnCONCLUSIONnIn this diabetic population, deprivation and glycaemic control were not associated. However, more deprived subjects with diabetes were at higher risk of renal disease. A deprived state was related to an altered quality of life as assessed by the SF-36 score.

Identification of the Functions of Liver X Receptor-β in Sertoli Cells Using a Targeted Expression-Rescue Model

Liver X receptors (LXRs) are key regulators of lipid homeostasis and are involved in multiple testicular functions. The Lxrα(-/-);Lxrβ(-/-) mice have illuminated the roles of both isoforms in maintenance of the epithelium in the seminiferous tubules, spermatogenesis, and T production. The requirement for LXRβ in Sertoli cells have been emphasized by early abnormal cholesteryl ester accumulation in the Lxrβ(-/-) and Lxrα(-/-);Lxrβ(-/-) mice. Other phenotypes, such as germ cell loss and hypogonadism, occur later in life in the Lxrα(-/-);Lxrβ(-/-) mice. Thus, LXRβ expression in Sertoli cells seems to be essential for normal testicular physiology. To decipher the roles of LXRβ within the Sertoli cells, we generated Lxrα(-/-);Lxrβ(-/-):AMH-Lxrβ transgenic mice, which reexpress Lxrβ in Sertoli cells in the context of Lxrα(-/-);Lxrβ(-/-) mice. In addition to lipid homeostasis, LXRβ is necessary for maintaining the blood-testis barrier and the integrity of the germ cell epithelium. LXRβ is also implicated in the paracrine action of Sertoli cells on Leydig cells to modulate T synthesis. The Lxrα(-/-);Lxrβ(-/-) and Lxrα(-/-);Lxrβ(-/-):AMH-Lxrβ mice exhibit lipid accumulation in germ cells after the Abcg8 down-regulation, suggesting an intricate LXRβ-dependent cooperation between the Sertoli cells and germ cells to ensure spermiogenesis. Further analysis revealed also peritubular smooth muscle defects (abnormal lipid accumulation and disorganized smooth muscle actin) and spermatozoa stagnation in the seminiferous tubules. Together the present work elucidates specific roles of LXRβ in Sertoli cell physiology in vivo beyond lipid homeostasis.

Heart rate variability in type 2 diabetes mellitus: A systematic review and meta– analysis

Background Cardiac autonomic neuropathy in type 2 dibetes mellitus (T2DM) patients is frequent and associated with high cardiovascular mortality. Heart rate variability (HRV) is the gold standard to measure cardiac autonomic neuropathy. We aimed to conduct a systematic review and meta–analysis to evaluate the impact of T2DM on HRV parameters. Methods The PubMed, Cochrane Library, Embase and Science Direct databases were searched on 1st October 2017 using the keywords “diabetes” AND (“heart rate variability” OR “HRV”). Included articles had to report HRV parameters in T2DM patients and healthy controls measured during 24 hours with a Holter–electrocardiogram. Measurements of HRV retieved were: RR–intervals (or Normal to Normal intervals—NN), standard deviation of RR intervals (SDNN), percetange of adjacent NN intervals differing by more than 50 milliseconds (pNN50), square root of the mean squared difference of successive RR intervals (RMSSD), total power, Low Frequency (LF), High Frequency (HF) and LF/HF ratio, as per Task Force recommendations. Results We included twenty-five case-control studies with 2,932 patients: 1,356 with T2DM and 1,576 healthy controls. T2DM patients had significantly (P<0.01) lower RR–intervals (effect size = –0.61; 95%CI –1.21 to –0.01), lower SDNN (–0.65; –0.83 to –0.47), lower RMSSD (–0.92; –1.37 to –0.47), lower pNN50 (–0.46; –0.84 to –0.09), lower total power (–1.52; –2.13 to –0.91), lower LF (–1.08; –1.46 to –0.69]), and lower HF (–0.79; –1.09 to –0.50). LF/HF did not differ between groups. Levels of blood glucose and HbA1c were associated with several HRV parameters, as well as Time from diagnosis of T2DM Conclusions T2DM was associated with an overall decrease in the HRV of T2DM patients. Both sympathetic and parasympathetic activity were decreased, which can be explained by the deleterious effects of altered glucose metabolism on HRV, leading to cardiac autonomic neuropathy.