Background Fungal infection at an arthroplasty site is rare and poses a therapeutic challenge. To the best of our knowledge, no reports have been published thus far on the success rate of prosthesis reimplantation after fungal prosthetic joint infections. Questions/purposes We asked: (1) What is the success rate in terms of infection eradication using a two-stage exchange arthroplasty in patients with hip or knee fungal periprosthetic joint infections, particularly focusing on Candida infections? (2) What patient-, infection-, and treatment-related variables are associated with the success or failure of treatment? Methods From January 2000 to December 2010, 16 patients with hip or knee candidal periprosthetic joint infections were treated with two-stage exchange arthroplasty at our institute. Treatment success was defined as a well-functioning joint without relapse of candidal infection after prosthesis reimplantation, while treatment failure was defined as uncontrolled or relapse of candidal infection or mortality. Variables, including age, sex, comorbidities, microbiology, antimicrobial agents used, and operative methods, were analyzed. Minimum followup was 28 months (mean, 41 months; range, 28-90 months). Results At latest followup, the treatment failed to eradicate the infection in eight of the 16 patients, and there were four deaths related to fungemia. Four patients required permanent resection arthroplasty owing to uncontrolled or recurrent candidal infections. All eight patients (50% successful rate) who had their infections eradicated and successful prosthesis reimplantation had prolonged treatment with oral fluconazole before (mean, 8 months) and after (mean, 2.2 months) prosthesis reimplantation. The antifungal therapy correlated with successful treatment. Renal insufficiency, hypoalbuminemia, anemia, and chronic obstructive pulmonary disease were significantly more prevalent in the treatmentfailure group than in the treatment-success group.

BackgroundMonomicrobial necrotizing fasciitis is rapidly progressive and life-threatening. This study was undertaken to ascertain whether the clinical presentation and outcome for patients with this disease differ for those infected with a gram-positive as compared to gram-negative pathogen.MethodsForty-six patients with monomicrobial necrotizing fasciitis were examined retrospectively from November 2002 to January 2008. All patients received adequate broad-spectrum antibiotic therapy, aggressive resuscitation, prompt radical debridement and adjuvant hyperbaric oxygen therapy. Eleven patients were infected with a gram-positive pathogen (Group 1) and 35 patients with a gram-negative pathogen (Group 2).ResultsGroup 2 was characterized by a higher incidence of hemorrhagic bullae and septic shock, higher APACHE II scores at 24 h post-admission, a higher rate of thrombocytopenia, and a higher prevalence of chronic liver dysfunction. Gouty arthritis was more prevalent in Group 1. For non-survivors, the incidences of chronic liver dysfunction, chronic renal failure and thrombocytopenia were higher in comparison with those for survivors. Lower level of serum albumin was also demonstrated in the non-survivors as compared to those in survivors.ConclusionsPre-existing chronic liver dysfunction, chronic renal failure, thrombocytopenia and hypoalbuminemia, and post-operative dependence on mechanical ventilation represent poor prognostic factors in monomicrobial necrotizing fasciitis. Patients with gram-negative monobacterial necrotizing fasciitis present with more fulminant sepsis.

An amino-linked nitrogen heterocyclic carbene (amino-NHC), 1-tBu, has been shown to mediate carbon-carbon coupling through the direct C-H functionalization of benzene and pyridine in the absence of a metal catalyst. Using EPR, the first spectroscopic evidence corroborating the single electron transfer mechanism for the metal-free carbon-carbon coupling manifold, as reported by others, is introduced.

The paper describes the synthetic development of Bertrand-type acyclic carbodicarbene scaffolds derived from an unsymmetrical bis(benzimidazol-2-yl)methane bearing two sterically demanding pendant arms, isopropyl (6a) or cyclohexyl (6b). X-ray crystallographic analysis shows that the impact of these pendant arms on the overall structural parameters of carbodicarbenes is minimal. The chemical reactivity of the carbodicarbenes was evaluated with iodomethane to afford compound 7, illustrating its nucleophilic properties. Finally, experiments were also undertaken to investigate the coordination ability of carbodicarbene toward the formation of rhodium carbonyl (10) and palladium allyl complexes (11). The crystal structures of the metal complexes have been determined, revealing that their metal−carbene distances are elongated only slightly, this fact was rationalized on the basis of geometrical steric considerations with regard to the ligand.

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The formation of a hitherto unknown three-coordinate dicationic hydrido boron complex is described. Interestingly, supporting ligand carbodicarbene gave unprecedented reaction with BH3 without using more highly electrophilic Lewis acid precursors. Spectroscopic, crystallographic, and computational analysis was performed to understand the electronic features of these species.

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BackgroundThe application of computational and multi-omics approaches has aided our understanding of carcinogenesis and the development of therapeutic strategies. NSC765598 is a novel small molecule derivative of salicylanilide. This study aims to investigate the ligand-protein interactions of NSC765598 with its potential targets and to evaluate its anticancer activities in vitro.MethodsWe used multi-computational tools and clinical databases, respectively, to identify the potential drug target for NSC765598 and analyze the genetic profile and prognostic relevance of the targets in multiple cancers. We evaluated the in vitro anticancer activities against the National Cancer Institute 60 (NCI60) human tumor cell lines and used molecular docking to study the ligand-protein interactions. Finally, we used the DTP-COMPARE algorithm to compare the NSC765598 anticancer fingerprints with NCI standard agents.ResultsWe identified mammalian target of rapamycin (mTOR)/epidermal growth factor receptor (EGFR)/inducible nitric oxide synthase (iNOS)/mitogen-activated protein 2 kinase 1 (MAP2K1)/fibroblast growth factor receptor (FGFR)/transforming growth factor-β1 (TGFB1) as potential targets for NSC765598. The targets were enriched in cancer-associated pathways, were overexpressed and were of prognostic relevance in multiple cancers. Among the identified targets, genetic alterations occurred most frequently in EGFR (7%), particularly in glioblastoma, esophageal squamous cell cancer, head and neck squamous cell cancer, and non–small-cell lung cancer, and were associated with poor prognoses and survival of patients, while other targets were less frequently altered. NSC765598 displayed selective antiproliferative and cytotoxic preferences for NSCLC (50% growth inhibition (GI50) = 1.12–3.95 µM; total growth inhibition (TGI) = 3.72–16.60 μM), leukemia (GI50 = 1.20–3.10 µM; TGI = 3.90–12.70 μM), melanoma (GI50 = 1.45–3.59 µM), and renal cancer (GI50 = 1.38–3.40 µM; TGI = 4.84–13.70 μM) cell lines, while panels of colon, breast, ovarian, prostate, and central nervous system (CNS) cancer cell lines were less sensitive to NSC765598. Interestingly, NSC765598 docked well into the binding cavity of the targets by conventional H-bonds, van der Waal forces, and a variety of π-interactions, with higher preferences for EGFR (ΔG = −11.0 kcal/mol), NOS2 (ΔG = −11.0 kcal/mol), and mTOR (ΔG = −8.8 kcal/mol). NSC765598 shares similar anti-cancer fingerprints with NCI standard agents displayed acceptable physicochemical values and met the criteria of drug-likeness.ConclusionNSC765598 displayed significant anticancer and potential multi-target properties, thus serve as a novel candidate worthy of further preclinical studies.