Comparison of the in vitro activities of delafloxacin and comparators against Staphylococcus epidermidis clinical strains involved in osteoarticular infections: a CRIOGO multicentre retrospective study.

OBJECTIVES: Staphylococcus epidermidis bone and joint infections (BJIs) on material are often difficult to treat. The activity of delafloxacin has not yet been studied on S. epidermidis in this context. The aim of this study was to assess its in vitro activity compared with other fluoroquinolones, against a large collection of S. epidermidis clinical strains. METHODS: We selected 538 S. epidermidis strains isolated between January 2015 and February 2023 from six French teaching hospitals. One hundred and fifty-two strains were ofloxacin susceptible and 386 were ofloxacin resistant. Identifications were performed by MS and MICs were determined using gradient concentration strips for ofloxacin, levofloxacin, moxifloxacin and delafloxacin. RESULTS: Ofloxacin-susceptible strains were susceptible to all fluoroquinolones. Resistant strains had higher MICs of all fluoroquinolones. Strains resistant to ofloxacin (89.1%) still showed susceptibility to delafloxacin when using the Staphylococcus aureus 2021 CA-SFM/EUCAST threshold of 0.25 mg/L. In contrast, only 3.9% of the ofloxacin-resistant strains remained susceptible to delafloxacin with the 0.016 mg/L S. aureus breakpoint according to CA-SFM/EUCAST guidelines in 2022. The MIC50 was 0.094 mg/L and the MIC90 was 0.38 mg/L. CONCLUSIONS: We showed low delafloxacin MICs for ofloxacin-susceptible S. epidermidis strains and a double population for ofloxacin-resistant strains. Despite the absence of breakpoints for S. epidermidis, delafloxacin may be an option for the treatment of complex BJI, including strains with MICs of ≤0.094 mg/L, leading to 64% susceptibility. This study underlines the importance for determining specific S. epidermidis delafloxacin breakpoints for the management of BJI on material.

Barriers and Advances in Kidney Preservation.

Despite the fact that a significant fraction of kidney graft dysfunctions observed after transplantation is due to ischemia-reperfusion injuries, there is still no clear consensus regarding optimal kidney preservation strategy. This stems directly from the fact that as of yet, the mechanisms underlying ischemia-reperfusion injury are poorly defined, and the role of each preservation parameter is not clearly outlined. In the meantime, as donor demography changes, organ quality is decreasing which directly increases the rate of poor outcome. This situation has an impact on clinical guidelines and impedes their possible harmonization in the transplant community, which has to move towards changing organ preservation paradigms: new concepts must emerge and the definition of a new range of adapted preservation method is of paramount importance. This review presents existing barriers in transplantation (e.g., temperature adjustment and adequate protocol, interest for oxygen addition during preservation, and clear procedure for organ perfusion during machine preservation), discusses the development of novel strategies to overcome them, and exposes the importance of identifying reliable biomarkers to monitor graft quality and predict short and long-term outcomes. Finally, perspectives in therapeutic strategies will also be presented, such as those based on stem cells and their derivatives and innovative models on which they would need to be properly tested.

First case report of a human sepsis involving a recently identified anaerobic agent: Bacteroides faecis.

Up until now, Bacteroides faecis, a Gram-negative, anaerobic, non-motile, nonsporeforming rod has been principally described as a commensal microbe isolated from the feces of healthy adults. We report the first case of human Bacteroides faecis sepsis after removal of suspected post-colonic ischemia colonized epicardic electrodes. Electrodes and blood cultures both grew Gram-negative anaerobic rods but usual phenotypic methods and 16S rARN gene sequencing failed to ensure its species identification. B. faecis was finally identified using hsp60 gene sequencing. Because this species is not well-known and is difficult to identify, it may have been overlooked or misidentified in previous studies.

Effects of warm ischaemia combined with cold preservation on the hypoxia-inducible factor 1α pathway in an experimental renal autotransplantation model.

BACKGROUND: The increased use of marginal donors highlights the importance of organ quality in transplantation and the identification of prognostic biomarkers. This experimental study investigated modulation of the hypoxia-inducible factor (HIF) 1α pathway in kidney grafts in relation to different degrees of ischaemia. METHODS: In a porcine autotransplantation model, two different kidney graft protocols were compared: standard 24-h cold storage (CS) and 24-h CS preceded by 1 h warm ischaemia (WI + CS). The renal HIF-1α pathway and tubular dedifferentiation were analysed in the early phase of reperfusion and at 3 months. RESULTS: There was a relationship between the degree of ischaemic injury and the outcome of the kidney graft. During the first week of reperfusion, WI + CS grafts showed a higher degree of injury. The observed tubular dedifferentiation was associated with delayed HIF-1α expression, and with loss of its role in transcription. In highly injured kidneys, deregulation of the HIF-1α pathway was also observed in the chronic phase, with reduced production of vascular endothelial growth factor (VEGF) A, and upregulation of VEGF receptor 1 (Flt-1) and thrombospondin 1. In addition, these kidneys displayed altered kidney histology and decreased function. CONCLUSION: The HIF-1α pathway appears to be abolished early in response to severe ischaemia. A high degree of ischaemic injury also results in chronic activation of the HIF-1α pathway, diverting it away from the beneficial activation of angiogenesis. Further studies on the finely tuned balance of signals in this pathway may provide diagnostic biomarkers that can determine organ quality during kidney transplantation. Surgical relevance The increased use of marginal donors has highlighted the importance of organ quality in transplantation. Renal ischaemia-reperfusion injury following transplantation induces graft dysfunction. In a porcine model of renal autotransplantation, the induction of regenerative processes, in response to graded degrees of ischaemia, was studied in the post-transplantation phase. There was early abrogation of the hypoxia-inducible factor (HIF) 1α pathway in response to severe ischaemia. High degrees of ischaemic injury induced chronic activation of the HIF-1α pathway, diverting it from the beneficial activation of angiogenesis. Identification of the mechanisms involved in renal regeneration, such as those related to the HIF-1α pathway, are important as these mechanisms can be used to identify novel therapeutic targets or develop diagnostic biomarkers to determine organ quality early in the transplantation process.

Surgical management of an epithelioid hemangioendothelioma of the superior vena cava protruding into the right atrium.

Epithelioid hemangioendothelioma (EH) is a rare malignant tumor of vascular origin that often involves soft tissues and visceral organs, and less commonly, large veins. We report a case of EH of the superior vena cava protruding into the right atrium and its surgical management.

Identification of a novel water-soluble activator of wild-type and F508del CFTR: GPact-11a.

One of the major therapeutic strategy in cystic fibrosis aims at developing modulators of cystic fibrosis transmembrane conductance regulator (CFTR) channels. We recently discovered methylglyoxal alpha-aminoazaheterocycle adducts, as a new family of CFTR inhibitors. In a structure-activity relationship study, we have now identified GPact-11a, a compound able not to inhibit but to activate CFTR. Here, we present the effect of GPact-11a on CFTR activity using in vitro (iodide efflux, fluorescence imaging and patch-clamp recordings), ex vivo (short-circuit current measurements) and in vivo (salivary secretion) experiments. We report that GPact-11a: 1) is an activator of CFTR in several airway epithelial cell lines; 2) activates rescued F508del-CFTR in nasal, tracheal, bronchial, pancreatic cell lines and in human CF ciliated epithelial cells, freshly dissociated from lung samples; 3) stimulates ex vivo the colonic chloride secretion and increases in vivo the salivary secretion in cftr(+/+) but not cftr(-/-) mice; and 4) is selective for CFTR because its effect is inhibited by CFTR(inh)-172, GlyH-101, glibenclamide and GPinh-5a. To conclude, this work identifies a selective activator of wild-type and rescued F508del-CFTR. This nontoxic and water-soluble agent represents a good candidate, alone or in combination with a F508del-CFTR corrector, for the development of a CFTR modulator in cystic fibrosis.

Influence of nephron mass and a phosphorylated 38 mitogen-activated protein kinase inhibitor on the development of early and long-term injury after renal warm ischaemia.

BACKGROUND: Renal ischaemia is accompanied by acute and chronic complications. Tumour necrosis factor (TNF) alpha production via p38 mitogen-activated protein kinase (MAPK) is one of the pivotal mechanisms linking ischaemia to inflammation and could be a therapeutic target. FR167653 (FR), an inhibitor of p38 MAPK and TNF-alpha production, may ameliorate renal damage through its effects on TNF-alpha. METHODS: Warm ischaemia (WI) was induced in male pigs by bilateral clamping of the renal pedicle for 60 min or unilateral renal clamping after contralateral nephrectomy. FR was administered before and during WI, and continuously for 3 h during reperfusion in pigs exposed to the same WI conditions. Experimental groups were compared with sham-operated pigs and those subjected to unilateral nephrectomy without renal ischaemia. Renal function, fibrosis and inflammation were evaluated, and expression of monocyte chemoattractant protein 1, transforming growth factor beta and TNF-alpha was determined after 12 weeks. RESULTS: FR significantly reduced renal failure in groups subjected to unilateral nephrectomy and bilateral renal ischaemia. Proteinuria was significantly reduced, and inflammation and expression of proinjury proteins were diminished, accompanied by a reduction in renal fibrosis. CONCLUSION: Control of TNF-alpha production and activity prevents renal damage after prolonged WI.

Antithrombin level and circuit thrombosis during hemofiltration after cardiopulmonary bypass.

OBJECTIVE: Hemofilter thrombosis occurs frequently during continuous veno-venous hemofiltration in intensive care units. Among coagulation disorders, antithrombin deficiency has been shown to be linked to hemofilter thrombosis. We investigated whether there was an association between antithrombin level activity and hemofilter thrombosis occurrence during early continuous hemofiltration following cardiopulmonary bypass. DESIGN: Prospective observational study. SETTING: Intensive care unit in University Teaching Hospital. PATIENTS AND PARTICIPANTS: Forty-eight consecutive patients. MEASUREMENTS AND RESULTS: Antithrombin level activity was measured just before the start of hemofiltration, and repeated at 24 h intervals for a total of 3 days. Hemofilter thrombosis episodes were recorded at each 24-h interval following antithrombin level activity measurement. Subjects were classified as HT when one or more episodes of hemofilter thrombosis appeared in this period and NHT if none. Morbidity parameters and mortality were recorded. Mean initial antithrombin level activity was low and not different in HT and NHT groups at day 0 (60.6 +/- 20.9% vs. 63.4 +/- 19.9%, P = 0.68). Antithrombin level activity was lower at day 1 (47.2 +/- 12.0% vs. 58.2 +/- 15.2%, P = 0.03) and day 2 (41.2 +/- 15.3% vs. 53.5 +/- 14.1%, P = 0.04) in HT group. However, antithrombin level activity was not shown to be predictive of HT in multivariate analysis. Morbidity and mortality did not differ significantly between the two groups. CONCLUSION: Only a weak association was found between antithrombin level activity and HT during early veno-venous hemofiltration post-cardiopulmonary bypass. This result was not confirmed in multivariate analysis. DESCRIPTOR: Renal failure: dialysis and hemofiltration.

[Multiple myxomata: about one case]. / Myxomes multiples: à propos d'un cas.

Among the primitive cardiac tumours, myxoma is the most common. This benign tumour is sometimes described in the context of Carney's syndrome, in which cardiac myxoma, cutaneous myxoma, lentigo and pigmentary nevus cutaneous lesions, endocrine disorders, and testicular, thyroid and hypophyseal tumours are associated. The cardiac myxomata observed are multiple, recurrent, and involve the four cardiac chambers, with a peak incidence at 25 years of age. These observations may exist in a familial context, linked to an autosomal dominant genetic factor, localized on the 17q2 chromosome with polymorphism of the PRKAR1a gene. As in the case of sporadic myxoma, rapid surgical treatment with cardio-pulmonary bypass is indicated, bearing in mind the increased risk of thromboembolic phenomena and sudden death from valvular encroachment. We report a case of bi-atrial myxoma observed in the context of Carney's syndrome.

[Complications of pulmonary resection]. / Les complications des résections pulmonaires.

INTRODUCTION: Surgical pulmonary resection remains the most effective treatment of non-small cell lung cancer which is its principal indication. Peri-operative mortality remains fairly high and is associated with post operative complications. BACKGROUND: Complications can involve all the thoracic organs: lung, pleura, bronchi and chest wall and also the heart, blood vessels, nervous system and digestive tract. Individually, but often in combination, these complications can lead to post-operative respiratory failure which has a poor prognosis. Beside the pulmonary conditions that are familiar to the respiratory physician other factors add to the morbidity, notably: age, cardiovascular disease and neo-adjuvent therapies. Many of these complications can be explained by the operative procedure: extent of resection, lymph node dissection, adhesions, dissection of the mediastinum etc. These factors should be considered at an early stage in order to achieve prompt diagnosis and management. Broncho-pleural fistulae present major problems on account of both their prognosis and difficult management. CONCLUSION: Many complications, especially cardiovascular, should be anticipated by the pre-operative investigations. Pneumonectomy remains a procedure with high morbidity and mortality. The risk factors should be taken into account when making a decision on surgical treatment.

Protective role of selectin ligand inhibition in a large animal model of kidney ischemia-reperfusion injury.

Experiments in rodents have demonstrated an important role for selectins in kidney ischemia-reperfusion injury (IRI). However, the relevance of this in larger mammals, as well as the impact on long-term structure and function is unknown. We tested the hypothesis that small molecule selectin ligand inhibition attenuates IRI, cellular inflammation, and long-term effects on renal interstitial fibrosis. We used a porcine model of kidney IRI and used Texas Biotechnology Corporation (TBC)-1269, a selectin ligand inhibitor. Renal function, tissue inflammation, and tubulointerstitial fibrosis development were evaluated up to 16 weeks. Both warm and cold ischemia models were studied for relevance to native and transplant kidney injury. Pigs treated with TBC-1269 during 45 min of warm ischemia (WI) showed significantly increased glomerular filtration rate compared to control animals. In pigs with severe IRI (WI for 60 min), TBC-1269 treatment during IRI significantly increased renal recovery. Cellular inflammation was strongly reduced, particularly influx of CD4 cells. Quantitative measurement of fibrosis by picrosirius red staining showed strong reduction in TBC-1269-treated groups. TBC-1269 also reduced cold IRI, inflammation, and fibrosis in kidneys preserved for 24 h at 4 degrees C and autotransplanted. The selectin ligand inhibitor TBC-1269 provides a novel and effective approach to attenuate IRI in both warm and cold ischemia in large mammals, in both short and long terms. Selectin ligand inhibition is an attractive strategy for evaluation in human kidney IRI.

Post-mediastinitis ventricle rupture: closing the chest without closing the heart?

Right ventricular rupture following mediastinitis is an unusual but potentially life-threatening complication of cardiac surgery, related to the "open" debridement technique. There are few reports of complex surgical management including repair of the tear and wound closure with omentoplasty or muscle flap with ECC. We report the case of a patient with a right ventricular rupture complicating mediastinitis, which was successfully treated by direct closure of the chest wall without repairing the ventricle tearing and without ECC. We believe that it can be a quick and effective solution at first attempt, and may be a successful and definitive treatment.

[Management of thymic cysts]. / Prise en charge des kystes thymiques.

OBJECTIVE: The thymic cysts are rare tumors of the neck and anterior mediastinum. The management of these patients in our institution is reported. Minimally invasive procedures are discussed. PATIENTS AND METHODS: Six patients operated in our institution within ten years, with a follow-up of 7.1 +/-3.7 years are studied retrospectively. RESULTS: There were four women and two men with an average of 39.8 +/-16.5 years. The tumor was found on chest radiograph in four asymptomatic patients, one took medical advice for laryngeal discomfort and another for dysphagia and dyspnea. The tumor was localized in the anterior mediastinum in three cases, in the cervicomediastinal site in two cases and in the cervical site in one case. CT scan was practiced in three patients with a mediastinal tumor and MR imaging in one of them. In patients with cervical or cervicomediastinal tumor, a cervical echography was practiced. All patients were operated on: three by cervicotomy, one by sternotomy, one by partial upper mini-sternotomy and one by right lateral video-assisted mini-thoracotomy. Histology confirmed benign epithelial thymic cyst. CONCLUSION: There is no specific marker of thymic cysts. Only the surgical management, leads to precise the diagnosis and to treat these tumors. No mortality, no complications or recurrences are reported. The minimally invasive surgery takes an interesting place for thoracic location, to explore and treat these benign mediastinal lesions.

[French national survey of the use of monitoring devices during cardiopulmonary bypass in 2001]. / Enquête française sur les dispositifs de surveillance de la CEC en 2001.

OBJECTIVES: To study the different monitoring devices used during cardiopulmonary bypass (CPB) and to determine the factors, which may influence the choice of these equipments. STUDY DESIGN: Survey. METHODS: A postal questionnaire was send to the 66 French cardiac surgery centres. Results have been analysed about the economic status (public health service or private institution) and the business of the centre (less than 500, between 500 to 800 and more than 800 cardiopulmonary bypass/year). RESULTS: The rate of answer reached 73%. In 40% of centres, the cardiovascular perfusionist was not alone during the procedure. The percentage of centres using a checklist was 80%, a neurologic monitoring 42%, anaesthesia depth monitoring 40%, venous reservoir level detector 52%, arterial line bubble detector 38%, cardioplegia circuit bubble detector 6%, transoesophageal echocardiography 48%, pipe's temperature monitoring 90%; oxymetry 44%, capnography 25%, SvO2 98%, blood gas analysis outside the OR 46% and computer records 35%. No difference was observed between public and private institution for these latter devices. However, a significant difference was noticed among the low, intermediate and highly busy centres for the use of checklist, the EEG monitoring, the pipe and water circuit temperature monitoring, capnography and location of the biologic analysers. CONCLUSION: Equipments were not similar among the different French cardiac surgery centres. Furthermore, the French practice seems different from American, UK and Australian's one. These results highlight the need of establishing French guidelines, which are absent.

[Radial artery aneurysm: an unusual complication of radial artery catheterization]. / L'anévrisme de l'artère radiale: une complication inhabituelle du cathétérisme radial.

Percutaneous arterial cannulation is systematically used in cardiac surgery and reanimation for hemodynamic monitoring. It was frequently used in coronarography. Risk factors for occurrence of radial aneurysm after catheterization may include advanced age, longer duration of catheterization, hospitalization duration, and general infection with Staphylococcus aureus. We report an uncommon case of radial artery aneurysm, after cardiac surgery. We operated the patient with a good result.

[Rupture of ascending aortic aneurysm revealing Takayasu's arteritis]. / Rupture d'un anévrisme de l'aorte ascendante révélant une artérite de Takayasu.

Takayasu's disease is rare in Western countries. It is most often revealed by stenosing lesions, aneurysmal attacks being less frequent, generally multifocal, and associated with stenoses. An isolated aneurysmal attack of the ascending aorta is exceptional. It is a deleterious factor in the disease process, and one of the causes of death in this disease. We report a case of isolated aneurysm of the ascending aorta extending to the aortic arch, undergoing emergency surgery at the rupture phase, revealing Takayasu's arteritis. Classically, isolated, asymptomatic, small aneurysms without lesions of other branches are slow to evolve with prolonged corticosteroid therapy. Our observation was contrary to these data, with rapid growth in a major inflammatory context, and rupture. It would seem important to rapidly diagnose and treat Takayasu's disease aneurysms of the ascending aorta, given their progressive potential. In a young female the signs of parietal thickening of the aneurysm must provoke diagnosis and treatment rapidly.