The role of the computerized tomography scanner in the cross-transmission of carbapenem-resistant Acinetobacter baumannii between hospitalized patients

ObjectiveTo assess the role of the computerized tomography (CT) scanner in cross-transmission of carbapenem-resistant Acinetobacter baumannii between hospitalized patients undergoing CT scan.MethodsA single-centre retrospective observational analysis of inpatients undergoing CT scans. Patient-unique CT scans were defined as ‘index cases’ (patients undergoing CT scan with carbapenem-resistant Acinetobacter baumannii (CRAB) colonization documented during the previous 60 days), ‘incident cases’ (patients found colonized with CRAB within 14 days following CT scan), and ‘negative cases’ (negative for CRAB before and after CT scan). CRAB acquisition was analysed by time interval between CT scan and CT scan of the prior index-case patient.ResultsAmongst 73 047 CT scans performed over 5 years, 4834 scans were performed within 12 hours of an index case. CRAB acquisition was detected in 20 patients (incident cases), including 16/2725 (5.8/1000 scans) who underwent CT scan within 6 hours of an index-case CT scan and 4/2109 (1.9/1000 scans) who had their CT scan 7–12 hours after the CT scan of an index-case patient (p 0.033, risk ratio 3.1, 95%CI 1.03–9.25). Patient characteristics for the two time periods were similar. While not the only significant predictor of CRAB acquisition (others included age and length of hospital stay prior to the CT scan), the time elapsed from an index case remained a significant predictor for CRAB acquisition on multivariate analysis (OR 0.84, 95%CI 0.74–0.95, p 0.007).ConclusionsPerforming a CT scan within 6 hours of a CT scan performed in a CRAB-positive patient was an independent predictor of CRAB acquisition, approximately tripling the risk. This probably reflects poor infection control practice in the CT suite.     

The OPCML tumor suppressor functions as a cell surface repressor-adaptor, negatively regulating receptor tyrosine kinases in epithelial ovarian cancer

Epithelial ovarian cancer is the leading cause of death from gynecologic malignancy, and its molecular basis is poorly understood. We previously demonstrated that opioid binding protein cell adhesion molecule (OPCML) was frequently epigenetically inactivated in epithelial ovarian cancers, with tumor suppressor function in vitro and in vivo. Here, we further show the clinical relevance of OPCML and demonstrate that OPCML functions by a novel mechanism in epithelial ovarian cancer cell lines and normal ovarian surface epithelial cells by regulating a specific repertoire of receptor tyrosine kinases: EPHA2, FGFR1, FGFR3, HER2, and HER4. OPCML negatively regulates receptor tyrosine kinases by binding their extracellular domains, altering trafficking via nonclathrin-dependent endocytosis, and promoting their degradation via a polyubiquitination-associated proteasomal mechanism leading to signaling and growth inhibition. Exogenous recombinant OPCML domain 1-3 protein inhibited the cell growth of epithelial ovarian cancers cell in vitro and in vivo in 2 murine ovarian cancer intraperitoneal models that used an identical mechanism. These findings demonstrate a novel mechanism of OPCML-mediated tumor suppression and provide a proof-of-concept for recombinant OPCML protein therapy in epithelial ovarian cancers. SIGNIFICANCE: The OPCML tumor suppressor negatively regulates a specific spectrum of receptor tyrosine kinases in ovarian cancer cells by binding to their extracellular domain and altering trafficking to a nonclathrin, caveolin-1–associated endosomal pathway that results in receptor tyrosine kinase polyubiquitination and proteasomal degradation. Recombinant OPCML domain 1-3 recapitulates this mechanism and may allow for the implementation of an extracellular tumor-suppressor replacement strategy.     

Transesophageal evaluation of asymptomatic Wolff-Parkinson-White syndrome

Background: Risk stratification for Wolff‐Parkinson‐White (WPW) by intracardiac electrophysiology study (ICEPS) carries risks related to catheterization. We describe an alternative approach by using transesophageal electrophysiology study (TEEPS). Methods: The pediatric electrophysiology database was reviewed for patients with WPW and no documented clinical supraventricular tachycardia (SVT) who underwent risk stratification by TEEPS from October 2005 to November 2010. Of those who underwent subsequent ICEPS, only those with data available to compare accessory pathway (AP) conduction during ICEPS and TEEPS were included. Results: Of 65 patients who underwent TEEPS, 42 were found to have an indication for ablation. The most common indication for ICEPS was inducible SVT, which was induced in 67% of patients. Of 42 patients who underwent subsequent ICEPS, 23 had sufficient data for comparison of AP conduction between ICEPS and TEEPS. There was no difference between the baseline minimum 1:1 antegrade conduction through the accessory pathway found at TEEPS versus ICEPS (312 ± 51 ms vs 316 ± 66 ms, P = 0.5). There was no significant difference between the baseline antegrade AP‐effective refractory period found at TEEPS versus ICEPS (308 ± 34 ms vs 297 ± 37 ms, P = 0.07). There were no complications related to TEEPS or ICEPS. Conclusion: TEEPS is a safe and feasible alternative to ICEPS for risk stratification in patients with asymptomatic WPW and should be considered before ICEPS and ablation. (PACE 2012; 1–5)     

Revision Total Knee Arthroplasty Using an Uncemented Metaphyseal Sleeve,Rotating Hinge Prosthesis: A Case Series of 99 Patients

BackgroundHinge knee replacement is a salvage procedure with historically high failure and complication rates. We aim to analyze the use of an uncemented metaphyseal sleeve revision knee replacement in our unit—a third-generation rotating hinge knee prosthesis. This is the largest reported series of this implant with longest follow up.MethodsWe retrospectively identified 99 revision cases performed (2002-2018). In total, 67 of 99 (68%) cases were performed for aseptic etiology, whereas 32 of 99 (32%) cases were performed for infection. Clinical outcomes were assessed using the Oxford Knee Score, survivorship analysis, and incidence of revision/reoperations. Mean follow-up was 7 years (range 1.5-18).ResultsAt follow-up, the mean Oxford Knee Score had improved from 10 points to 25 points. At mean 7 years of follow up, 18 of 99 cases had undergone revision giving a survivorship of 81% (90% aseptic). In total, 10 of 18 cases were performed for infection (10%) and 9 of 18 cases were performed for aseptic reasons (9%), of which 5 were for patella resurfacing (2 revision), 2 for failure of bony ingrowth, and 1 for fracture. Twenty-six patients (26%) had complications postoperatively, with patella disorders and reduced range of movement the most common. Patients who did not undergo patella resurfacing were significantly more likely to need revision of any cause (P = .01).ConclusionThis is the largest study of this prosthesis with longest follow-up. It demonstrates good survivorship and improvement in knee pain. Those with infection are at greatest risk of revision. Significant numbers have patella dysfunction/anterior knee symptoms therefore patella resurfacing should be considered when using this implant.Level of EvidenceIV.     

Targeted measles virus vector displaying echistatin infects endothelial cells via alpha(v)beta3 and leads to tumor regression

Targeting tumor-associated vascular endothelium by replication-competent viral vectors is a promising strategy for cancer gene therapy. Here we describe the development of a viral vector based on the Edmonston vaccine strain of measles virus targeted to integrin alpha(v)beta3, which is expressed abundantly on activated but not quiescent vascular endothelium. We displayed a disintegrin, M28L echistatin that binds with a high affinity to integrin alpha(v)beta3 on the COOH terminus of the viral attachment (H) protein and rescued the replication-competent recombinant virus by reverse genetics. The new targeted virus was named measles virus echistatin vector (MV-ERV). Its native binding to CD46 was purposefully retained to allow virus infection of tumor cells expressing this receptor. MV-ERV correctly displayed echistatin on the outer surface of its envelope and produced interesting ring formation phenomena due to cell detachment upon infection of susceptible Vero cells in vitro. MV-ERV grew to 10(6) plaque-forming units/mL, slightly lower than the parental Edmonston strain of measles virus (MV-Edm), but it selectively infected Chinese hamster ovary cells expressing integrin alpha(v)beta3. It also selectively infected both bovine and human endothelial cells on matrigels and unlike MV-Edm, MV-ERV infected newly formed blood vessels in chorioallantoic membrane assays. In animal models, MV-ERV but not the control MV-Edm caused the regression of s.c. xenografts of resistant multiple myeloma tumors (MM1) in severe combined immunodeficient mice. The tumors were either completely eradicated or their growth was significantly retarded. The specificity, potency, and feasibility of MV-ERV infection clearly show the potential use of MV-ERV in gene therapy for targeting tumor-associated vasculature for the treatment of solid tumors.     

Diagnosing undernutrition

Because of its wide prevalence and its grave consequences on the health of older persons, malnutrition requires immediate attention. Physicians in general have been described as being nutritionally blind in their slowness to recognize undernutrition. A high degree of suspicion, a thorough history and physical examination, and pertinent laboratory data can identify patients at risk. When a more comprehensive assessment is needed; screening tools, dietary history, and special biochemical parameter can be used.