Bone marrow mesenchymal stem cells offer an immune-privileged niche to Cutibacterium acnes in case of implant-associated osteomyelitis.

Considered as some of the most devastating complications, Cutibacterium acnes (C. acnes)-related osteomyelitis are among the hardest infections to diagnose and treat. Mesenchymal stem cells (MSCs) secrete number of immunomodulatory and antimicrobial soluble factors, making them an attractive treatment for bacterial infection. In this study, we examined MSCs/C. acnes interaction and analyzed the subsequent MSCs and bacteria's behaviors. Human bone marrow-derived MSCs were infected by C. acnes clinical strain harvested from non-infected bone site. Following 3 h of interaction, around 4% of bacteria were found in the intracellular compartment. Infected MSCs increased the secretion of prostaglandin E2 and indolamine 2,3 dioxygenase immunomodulatory mediators. Viable intracellular bacteria analyzed by infrared spectroscopy and atomic force microscopy revealed deep modifications in the wall features. In comparison with unchallenged bacteria, the viable intracellular bacteria showed (i) an increase in biofilm formation on orthopaedical-based materials, (ii) an increase in the invasiveness of osteoblasts and (iii) persistence in macrophage, suggesting the acquisition of virulence factors. Overall, these results showed a direct impact of C. acnes on bone marrow-derived MSCs, suggesting that blocking the C. acnes/MSCs interactions may represent an important new approach to manage chronic osteomyelitis infections. STATEMENT OF SIGNIFICANCE: The interaction of bone commensal C. acnes with bone marrow mesenchymal stem cells induces modifications in C. acnes wall characteristics. These bacteria increased (i) the biofilm formation on orthopaedical-based materials, (ii) the invasiveness of bone forming cells and (iii) the resistance to macrophage clearance through the modification of the wall nano-features and/or the increase in catalase production.

Interaction of Cutibacterium acnes with human bone marrow derived mesenchymal stem cells: a step toward understanding bone implant- associated infection development.

Crosstalk between mesenchymal stem cells (MSCs) and bacteria plays an important role in regulating the regenerative capacities of MSCs, fighting infections, modulating immune responses and maintaining tissue homeostasis. Commensal Cutibacterium acnes (C. acnes) bacterium becomes an opportunistic pathogen causing implant-associated infections. Herein, we examined MSCs/C. acnes interaction and analysed the subsequent bacteria and MSCs behaviours following infection. Human bone marrow derived MSCs were infected by two clinical and one laboratory C. acnes strains. Following 3h of interaction, all bacterial strains were able to invade MSCs. Viable intracellular bacteria acquired virulence factors by increasing biofilm formation and/or by affecting macrophage phagocytosis. Although the direct and indirect (through neutrophil stimulation) antibacterial effects of the MSCs secretome were not enhanced following C. acnes infection, ELISA analysis revealed that C. acnes clinical strains are able to license MSCs to become immunosuppressive cell-like by increasing the secretion of IL-6, IL-8, PGE-2, VEGF, TGF-ß and HGF. Overall, these results showed a direct impact of C. acnes on bone marrow derived MSCs, providing new insights into the development of C. acnes during implant-associated infections. STATEMENT OF SIGNIFICANCE: The originality of this work relies on the study of relationship between human bone marrow derived mesenchymal stem cells (MSCs) phenotype and C. acnes clinical strains virulence following cell infection. Our major results showed that C. acnes are able to invade MSCs, inducing a transition of commensal to an opportunistic pathogen behaviour. Although the direct and indirect antibacterial effects were not enhanced following C. acnes infection, secretome analysis revealed that C. acnes clinical strains were able to license MSCs to become immunosuppressive and anti-fibrotic cell-like. These results showed a direct impact of C. acnes on bone marrow derived MSCs, providing new insights into the development of C. acnes during associated implant infections.

Relationships among electrophysiological findings and clinical status, heart function, and extent of DNA mutation in myotonic dystrophy.

BACKGROUND: Impulse-conduction abnormalities and arrhythmias are common in myotonic dystrophy (MD). This study was performed to determine whether a correlation exists between electrophysiological (EP) testing data and clinical status, heart function, or size of the DNA abnormality (cytosine-thymine-guanine sequence repeat). METHODS AND RESULTS: Eighty-three MD patients underwent invasive EP studies prompted primarily by the presence of asymptomatic conduction abnormalities. AV conduction disturbances were common and mainly distal (HV interval, 66.2+/-14 ms). AV conduction observed from the surface ECG was generally concordant with endocardial measurements. However, 11 of 20 patients with normal surface ECGs had abnormal subhisian conduction. Atrial arrhythmias were inducible in 41% of cases and correlated with prolongation of the AH interval (P=0.02) and a shorter atrial refractory period (P=0.04). Induction of ventricular arrhythmias (18%) correlated strongly with age (P=0. 0003). After adjustment for age, the extent of DNA mutation correlated with the Walton score (P=0.0018) but not with conduction abnormalities or induction of arrhythmias. CONCLUSIONS: Prolongation of the HV interval is the most common conduction abnormality in MD and can be reliably recognized only by invasive EP testing. It raises the issue of prophylactic pacing to limit the incidence of sudden death in MD. Atrial and ventricular arrhythmias are often inducible, although their predictive value remains to be determined. Young age emerged as the most powerful predictor of inducible ventricular tachyarrhythmias. Conversely, we found no relationship between ECG or EP abnormalities recorded during invasive testing and the DNA mutation size or severity of peripheral muscle involvement.

[Effect of sinorphan, an endopeptidase inhibitor on severe congestive cardiac insufficiency]. / Effet du sinorphan, un inhibiteur des endopeptidases dans l'insuffisance cardiaque congestive sévère.

Sinorphan is a powerful inhibitor of enkephalinases or endopeptidases 24-11, enzymes implicated in the degradation of the atrial natriuretic factor (ANF). In healthy volunteers, it increases plasma concentrations of endogenic ANF and increases diuresis and natriuresis. In order to study the tolerance and biological effects of pharmacological increase of plasma concentrations of endogenic ANF in severe congestive cardiac failure, 12 patients (in functional Classes III or IV of the NYHA classification) were given a single oral dose of 10, 20 or 40 mg of Sinorphan. Sinorphan was clinically well tolerated. The diastolic blood pressure decreased slightly (- 10 +/- 9 mmHg) but significantly (p less than 0.05). Systolic blood pressure and heart rate were unchanged. Despite spontaneously high plasma ANF concentrations (on average 15 times higher than normal subjects), Sinorphan induced an additional increase of 80 to 100% of plasma ANF concentration compared to the initial values (p less than 0.01) with no dose-dependent response for the dosages used. The inhibition of plasma endopeptidase activity attained 47% at the 30th minute. Urinary cyclic GMP excretion increased by 30% at the second hour (p less than 0.05). In addition, a statistically non significant tendency to increase diuresis and natriuresis was observed. These results show that Sinorphan increases plasma ANF concentrations by inhibition of its degradation in severe congestive cardiac failure and that this increase seems to be associated with potentially beneficial biological changes. The concept of endopeptidase inhibition should constitute a new therapeutic approach in cardiac failure, a situation in which the ANF seems to exert a favourable effect.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anti-angina effect of amiodarone versus delayed-action propranolol. A double-blind randomized study]. / Effet anti-angineux de l'amiodarone. Etude randomisée en double aveugle contre le propranolol retard.

Long-acting Propranolol (160 mg/day) and Amiodarone (200 mg/day after impregnation) were compared in chronic stable angina pectoris. Forty-three patients with stable angina of effort were included in a randomised double blind trial (19 in the amiodarone and 24 in the propranolol group). The duration of the study was 8 weeks; the placebo phase (2 weeks) was followed by 6 weeks of active treatment. An exercise stress test was performed before and after the treatment period. The number of episodes of angina and the consumption of glyceryl trinitrate decreased significantly (p less than 0.001) in the same proportion with both drugs with respect to the placebo period. The time to the appearance of criteria of positivity of the exercise stress test increased from 6.82 +/- 0.50 mn to 8.35 +/- 0.50 mn with amiodarone, and from 7.15 +/- 0.47 mn to 9.50 +/- 0.52 with the propranolol preparation. This improvement was very significant compared with the placebo phase (p less than 0.001) but the difference between the two drugs was not statistically significant (p = 0.39). The other parameters which were studied (time to onset of angina, total duration of exercise, maximum heart rate, double product, maximum ST depression) changed in a parallel fashion significantly versus placebo. There were no differences between the two treatment groups with the exception of the resting heart rate which decreased more in patients on propranolol (80.94 +/- 3.92 to 62.47 +/- 1.97) than in patients on amiodarone (84.87 +/- 2.63 to 73.41 +/- 2.01; p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

[Arrhythmogenic effects of extracorporal lithotripsy in desynchronized mode with a later generation lithotriptor]. / Effets arythmogènes de la lithotripsie extracorporelle en mode désynchronisé avec un lithotripteur de dernière génération.

Extracorporal lithotripsy has transformed the treatment of renal stones. However, the shock waves can generate arrhythmias which may be severe. To prevent them, the shocks were synchronised to the absolute refractory period of the cardiac cycle with a corollary, an increase in the procedure time. The latest generation of lithotriptors have a number of technical improvements allowing desynchronisation but with a high theoretic risk of arrhythmias. The aim of this study was to assess the arrhythmogenic effects of desynchronised shocks by Holter ECG monitoring during the procedure. This was a prospective randomised study: 25 patients with no previous cardiovascular history were included: 15 men and 10 women with a mean age of 45 years. The originality of this study was the delivery of shock waves in two phases (synchronised versus desynchronised) in a random fashion, the order being unknown to the cardiologist interpreting the recordings. In the synchronised mode, none of the patients developed an arrhythmia. On the other hand, in the desynchronised mode, hyperexcitability was observed in 7 patients, supraventricular in 6 cases (atrial extrasystoles and atrial doublets) and ventricular in 4 cases (VES, ventricular doublets and 1 unsustained ventricular tachycardia). These arrhythmias were asymptomatic and regressed spontaneously. The authors conclude that although they are arrhythmogenic, desynchronised procedures with the latest lithotriptors are acceptable, provided that the patients undergo a cardiological examination beforehand to identify high risk patients and that there is adequate monitoring during the procedure in the presence of an anaesthetist.

Use of gait patterns to reveal possible disorders in the geriatric patient.

Changes in gait occur frequently with advancing age and are often associated with falls, loss of independence, morbidity, and even mortality. Gait changes may occur as part of the natural process of aging or may be associated with underlying pathology. Careful observation of gait can provide insight into the patient's overall state of health. This article discusses the various types of gait changes that can occur with aging and the significance of these gait abnormalities.

[Non-ruptured calcified aneurysm of the Valsalva's sinus with angina pectoris and aortic insufficiency. Surgical treatment]. / Anévrysme calcifié non rompu du sinus de Valsalva avec angor et insuffisance aortique. Cure chirurgicale.

We report a case of aneurysm of the straight frontal, and not coronary, aortic sinus, non ruptured and calcified, responsible for a refractory angina pectoris and a massive aortic failure in a 71 year old woman. The surgical treatment consisted in the exclusion of the aneurysm of the aortic sinus by a tubular prosthesis in which only two thirds of the circumference have been used, associated with the replacement of an aortic valve by a bioprosthesis, without associated coronary by-pass.

Poly-L-lactic acid rod fixation results in foot surgery.

The purpose of this study was to evaluate the effectiveness and possible complications of polylactic absorbable devices in surgical procedures involving fixation of the foot. This was a prospective study in which biodegradable rods of poly-L-lactide were used in the fixation of 41 metatarsal osteotomies and digital arthrodeses and one midtarsal fusion in 23 patients. The follow-up time ranged from 6 months to 23 months. Ages ranged from 18 to 70 years with a mean age of 42 years. Clinical and radiographic examination was scheduled for each patient postoperatively at 1 week, 3 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years. The gender distribution was 18 female and 5 males. Two patients who had three procedures were lost to follow-up. All of the procedures were evaluated for failure of fixation, radiographic osteolysis, foreign-body reaction, sinus formation, and infection. We noted one failure of fixation and two complications unrelated to the type of fixation. There were no foreign-body reactions, sinus formulations, or infections. We conclude that the poly-L-lactic acid rod is a viable method of fixation for these procedures.

Gliomas and exposure to wood preservatives.

A case-referent study was undertaken to look for occupational risk factors among patients with glioma treated in a neurological hospital in Paris between 1975 and 1984. In the study group were 125 men with gliomas (aged less than or equal to 65) and 238 patients (also less than or equal to 65) admitted for non-neoplastic, non-malformative vascular diseases in the same department during the same period constituting the reference group. All diagnoses were confirmed by tomodensitometry. Information on occupational history was obtained from a postal questionnaire and from medical records. Comparison of cases and referents showed a significant excess risk among teachers (OR = 4.1) and a raised risk among wood workers (OR = 1.6). Four of nine cases of glioma who had been employed as wood workers reported that a colleague had suffered from glioma (those reports were confirmed by hospital records). None were reported among 11 referent wood workers. Using a complementary questionnaire on wood work, exposure assessment to wood preservatives and solvents showed that frequent exposure to organochlorine wood preservatives and to organic solvents occurred more often among cases than referent wood workers (p less than 0.10).

[Clinical and epidemiological aspects of Horton disease based on survey methods in ophthalmology or internal medicine]. / Aspects cliniques et épidémiologiques de la maladie de Horton selon le milieu de recrutement, ophtalmologique ou de médecine interne.

We conducted a retrospective study of 29 consecutive cases of temporal arteritis, all with definite histological diagnostic criteria. The epidemiological aspects of the main clinical and biological features were compared according to their mode of recruitment, the patients being hospitalized either in an ophthalmological unit (n = 15), or in an Internal Medicine unit (n = 14). The level of fever and of sedimentation rate were significantly less in the ophthalmological group (respectively p < 0.001 and p < 0.02), a third of which is represented by the purely ophthalmological manifestation called "occult temporal arteritis". Among the ophthalmological manifestations, despite the fact that the recruitment bias prevented any strict epidemiological comparison, we were surprised to find no significant difference between the two groups concerning the frequency of transient ophthalmological manifestations, which confirmed in half the patients their reputation of forerunners of irreversible lesions. Thus, the presentation of temporal arteritis differs according to its ophthalmological or Internal Medicine recruitment. We were unable to determine a precise chronology difference in the principal manifestations between these two groups. The severity of the ocular manifestations justifies looking for temporal arteritis in all cases of transient ophthalmological manifestations, even if clinically totally isolated.

Prevention of preterm birth: early detection and aggressive treatment with terbutaline.

We evaluated a program for prevention of preterm birth involving early detection and aggressive intervention with subcutaneous terbutaline pump therapy in a high-risk, private patient population. Risk factor screening, frequent cervical examinations, and intensive patient education were used to detect preterm labor before it progressed to an advanced stage. Home terbutaline pump therapy was prescribed for patients with uterine contractions associated with progressive cervical change, after stabilization with IV magnesium sulfate. In this study of 51 patients, home terbutaline pump therapy was successful in 98% of the cases, prolonging pregnancy an average of 6.6 weeks. Mean gestational age at delivery was 37 +/- 1.4 weeks, and infant birth weight averaged 3 kg. Only 22% of infants required admission to the neonatal intensive care unit, with a mean length of stay of 7.25 days. Population factors in this compliant, well-educated patient group may have contributed to the positive outcomes achieved.

Severe cardiac arrhythmias in young patients with myotonic dystrophy type 1.

Cardiac tachyarrhythmias have rarely been studied in young patients with myotonic dystrophy type 1 (DM1). The authors observed major cardiac rhythm disturbances in 11 patients aged 10 to 18 years. Tachyarrhythmic events were more frequent than impulse conduction disorders. Wide variations in CTG expansion were observed among the population. Since physical exercise was a prominent arrhythmogenic factor, systematic exercise tests with EKG monitoring may be indicated in young patients with DM1.