Durée de l’antibiothérapie lors du traitement des pneumopathies acquises sous ventilation mécanique : comparaison entre sept jours et dix jours. Étude pilote

Objective

To compare the efficiency of a 7-day antibiotics regimen with a 10-day regimen for ventilator-associated pneumonia (VAP).

Study design

Prospective randomized study.

Patients and methods

Adults patients ventilated for more than 48 hours in the intensive care unit (ICU) with a clinical diagnosis of VAP documented by positive quantitative cultures of tracheal aspiration were included in this study. All included patients were randomized in two groups. Ten-day group: 10 days antibiotic therapy, and 7-day group: 7 days antibiotic therapy. Primary judgment criteria were 14- and 28-day mortality, the number of days without antibiotics. Secondary judgments criteria were rate of recurrent pulmonary infection, the evolution of the clinical pulmonary infection scores (CPIS), the length of ICU stay and the length of mechanical ventilation.

Results

Thirty patients were included in this study (16 in the 10-day group and 14 in the 7-day group). The demographic and clinical characteristics of the groups assigned to receive antibiotic therapy for 7 or 10 days were generally similar. The 14-day and 28-day mortality rate following VAP onset were 31.2 and 37.5% in the 10-day group and 7.1 and 35.7% in the 7-day group. The difference was not significant. The number of day without antibiotics and without mechanical ventilation turned out: 1.75 and 2.06 days versus 4.14 and 3.43 days in the 10-day group and 7-day group respectively, the recurrent rate of pulmonary infection (12.5% versus 14.3%, p = 0.6), the length of stay in the ICU (27.7 days versus 26.0 days, p = 0.8) and the evolution of the CPIS were no different in the two groups.

Conclusion

In patients with microbiologically confirmed VAP who received appropriate empirical antibiotic therapy, a 7-day antibiotic regimen was as efficient clinically and microbiologically as a 10-day antibiotic regimen with a reduction of antibiotic use.     

A critical role for collagen II in cartilage matrix degradation: Collagen II induces pro‐inflammatory cytokines and MMPs in primary human chondrocytes

We report a process that results in the acceleration of matrix degradation in human articular cartilage, a phenomenon commonly observed in osteoarthritis (OA). The study was conducted by (1) examining the potential of collagen II in modulating the gene expression profile of primary human chondrocytes (PHCs), and (2) investigating the involvement of pro‐inflammatory signaling cascades. We first tested the collagen II‐dependent induction of pro‐inflammatory cytokines and matrix metalloproteinases (MMPs) in PHCs. PHCs were incubated with or without monomeric (i.e., nonfibrillar) collagen II. Cells were then analyzed by RT‐PCR for the expression of MMP1, MMP3, MMP13, MMP14, and IL‐1β. ELISA was used to quantify IL‐6 and IL‐8 release. To examine the influence of collagen II signaling, specifically the role of MAPK p38, a p38‐inhibitor was added prior to collagen treatment. Changes in IκB concentration were monitored by immunoblot analysis to detect NFκB signaling. Results indicated that incubation of PHCs with collagen II did produce a dose‐dependent induction of MMP1, MMP3, MMP13, MMP14, as well as cytokines IL‐1β, IL‐6, and IL‐8. At the same time, inhibition of p38 and IκB degradation revealed that collagen II‐dependent gene induction also involves MAPK p38 and NFκB signaling. Thus, we provide evidence for a collagen II‐dependent feed‐forward mechanism whereby collagen II induces first MMPs and pro‐inflammatory cytokines and then release of collagen II fragments from mature collagen II fibers. This, in turn, induces more pro‐inflammatory cytokines and MMPs, and the process is repeated, which results in the acceleration and perpetuation of cartilage matrix degradation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:65–70, 2009     

Subrupture tendon fatigue damage

The mechanical and microstructural bases of tendon fatigue, by which damage accumulates and contributes to degradation, are poorly understood. To investigate the tendon fatigue process, rat flexor digitorum longus tendons were cyclically loaded (1–16 N) until reaching one of three levels of fatigue damage, defined as peak clamp‐to‐clamp strain magnitudes representing key intervals in the fatigue life: i) Low (6.0%–7.0%); ii) Moderate (8.5%–9.5%); and iii) High (11.0%–12.0%). Stiffness, hysteresis, and clamp‐to‐clamp strain were assessed diagnostically (by cyclic loading at 1–8 N) before and after fatigue loading and following an unloaded recovery period to identify mechanical parameters as measures of damage. Results showed that tendon clamp‐to‐clamp strain increased from pre‐ to post‐fatigue loading significantly and progressively with the fatigue damage level (p ≤ 0.010). In contrast, changes in both stiffness and hysteresis were significant only at the High fatigue level (p ≤ 0.043). Correlative microstructural analyses showed that Low level of fatigue was characterized by isolated, transverse patterns of kinked fiber deformations. At higher fatigue levels, tendons exhibited fiber dissociation and localized ruptures of the fibers. Histomorphometric analysis showed that damage area fraction increased significantly with fatigue level (p ≤ 0.048). The current findings characterized the sequential, microstructural events that underlie the tendon fatigue process and indicate that tendon deformation can be used to accurately assess the progression of damage accumulation in tendons. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:264–273, 2009     

Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model

Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet‐derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 µg) and high (75 ug) doses of recombinant human PDGF‐BB (rhPDGF‐BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle‐treated animals. rhPDGF‐BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF‐BB treatment significantly increased callus peak torque values (p < 0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF‐BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF‐BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF‐BB may be a new therapeutic approach to treat diabetes‐impaired fracture healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1074–1081, 2009     

Novel quinolone CHM‐1 induces apoptosis and inhibits metastasis in a human osterogenic sarcoma cell line

Novel 2‐phenyl‐4‐quinolone compounds have potent cytotoxic effects on different human cancer cell lines. In this study, we examined anticancer activity and mechanisms of 20‐fluoro‐6,7‐methylenedioxy‐2‐phenyl‐4‐quinolone (CHM‐1) in human osterogenic sarcoma U‐2 OS cells. CHM‐1‐induced apoptosis was determined by flow cytometric analysis, DAPI staining, Comet assay, and caspase inhibitors. CHM‐1‐inhibited cell migration and invasion was assessed by a wound healing assay, gelatin zymography, and a Transwell assay. The mechanisms of CHM‐1 effects on apoptosis and metastasis signaling pathways were studied using Western blotting and gene expression. CHM‐1 induced G2/M arrest and apoptosis at an IC₅₀ (3 µM) in U‐2 OS cells and caspase‐3, ‐8, and ‐9 were activated. Caspase inhibitors increased cell viability after exposure to CHM‐1. CHM‐1‐induced apoptosis was associated with enhanced ROS generation, DNA damage, decreased ΔΨ_m levels, and promotion of mitochondrial cytochrome c release. CHM‐1 stimulated mRNA expression of caspase‐3, ‐8, and ‐9, AIF, and Endo G. In addition, CHM‐1 inhibited cell metastasis at a low concentration (<3 µM). CHM‐1 inhibited the cell metastasis through the inhibition of MMP‐2, ‐7, and ‐9. CHM‐1 also decreased the levels of MAPK signaling pathways before leading to the inhibition of MMPs. In summary, CHM‐1 is a potent inducer of apoptosis, which plays a role in the anticancer activity of CHM‐1. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1637–1644, 2009     

Nonparallel cutaneous microcirculatory responses to pharmacologic alterations of systemic arterial pressure in rats

Both hypotension and hypertension aggravate the damage of reperfusion injury after reconstructive microsurgery. The purpose of this study is to establish a theoretical guide for postoperative blood pressure control in optimizing the cutaneous perfusion and flap survival. Systemic arterial pressure was altered by the intravenous infusion of saline, sodium nitroprusside, phentolamine, and phenylephrine in thirty‐two 280–350 g anesthetized Sprague Dawley rats. Power spectral analysis of systemic arterial pressure (SAP) and laser Doppler flowmetry (flux) of epigastric skin were used to reveal the blood pressure and cutaneous blood flow variabilities. Nonparallel responses of cutaneous perfusion and blood pressure were found. The baseline SAP and flux were 126.0 ± 1.4 mmHg and 57.2 ± 1.8 au, respectively. Sodium nitroprusside and phentolamine significantly decreased the SAP (71.1 ± 2.7 and 70.5 ± 1.5 mmHg, P < 0.0001). However, the corresponding responses in cutaneous perfusion were opposite (56.2 ± 3.1 au, P = 0.7389 and 36.2 ± 2.3 au, P < 0.0001). Phenylephrine significantly increased the SAP (171.7 ± 3.0 mmHg, P < 0.0001) but the flux of epigastric skin was decreased (44.4 ± 2.6 au, P < 0.0001). Phentolamine and phenylephrine showed negative effects on the systemic cardiac and vascular sympathetic modulations. Sodium nitroprusside had a trend in increasing systemic vasomotor activity. We suggested not using vasoconstrictors in treating intra and postoperative hypotension associated with free flap transfer. Nitric oxide donors are superior to α‐adrenoceptor antagonists in preserving the cutaneous flap perfusion when treating postoperative hypertension. © 2009 Wiley‐Liss, Inc. Microsurgery, 2009.     

Age as only predictive factor for successful sperm recovery in patients with Klinefelter’s syndrome

The study was performed to determine factors affecting successful sperm retrieval by testicular sperm extraction in patients with nonmosaic Klinefelter’s syndrome (KS). From May 2001 to February 2007, 27 azoospermic patients were diagnosed as having nonmosaic KS. All patients underwent sperm testicular extraction. Patient’s age, testicular volume, serum follicle‐stimulating hormone (FSH) and inhibin B were assessed as predictive factors for successful sperm recovery. Of the 27 Klinefelter’s patients examined, eight (29.6%) had successful sperm recovery. The comparisons of serum FSH, inhibin B and testicular volume between patients with and without successful sperm retrieval did not show any statistical significance. The patients with successful sperm recovery were significantly younger (28.6 ± 3.11 years) than those with failed attempts (33.9 ± 4.5 years, P = 0.002). The rate of positive sperm retrieval was significantly higher in patients younger than 32 years compared with patients older than 32 years (P = 0.01, chi‐squared test). The study showed that clinical parameters such as FSH, inhibin B and testicular volume do not have predictive value for sperm recovery in patients with KS. The mean age of our patients with successful sperm recovery was significantly lower than that of men with unsuccessful results. Testicular sperm extraction or testicular sperm aspiration should be performed before the critical age of 32 years.     

A critical assessment of the prognostic value of clear cell,papillary and chromophobe histological subtypes in renal cell carcinoma: a population‐based study

OBJECTIVE

To assess the magnitude of the effect of histological subtype (HS, the three most common being clear cell, papillary and chromophobe) on cause‐specific mortality (CSM) from renal cell carcinoma (RCC).

PATIENTS AND METHODS

Univariable and multivariable Cox regression models included data from 11 618 patients treated with nephrectomy between 1988 and 2004 in nine Surveillance Epidemiology and End Results registries. We tested whether HS represents an independent predictor of CSM, and whether HS adds to the ability of other variables to predict CSM. The covariates comprised age, year of surgery, T stage, nodal status, M stage and Fuhrman grade.

RESULTS

In a multivariable model predicting CSM, HS was an independent predictor (P = 0.03), but failed to improve the accuracy of the model (+0.1% gain when HS was included in the model).

CONCLUSION

Although we confirmed that HS is an independent predictor for CSM, there was no gain in accuracy when HS was added to standard predictors of CSM. From a practical perspective, this implies that patients with clear cell, papillary and chromophobe HS share similar natural histories after nephrectomy, provided that other cancer characteristics are accounted for. From a statistical perspective, in multivariable models of CSM, the clear cell, papillary and chromophobe HS might be included as a single entity.