Intravenous electrocardiography guidance to position catheters obtains a satisfactory catheter tip placement that is in accordance with transesophageal echocardiography views. The surface landmark technique does not result in reliable placement at the superior vena cava-right atrium junction.

The switch between latency and the lytic cycle of Kaposi’s sarcoma-associated herpesvirus (KSHV) is controlled by the expression of virally encoded ORF50 protein. Thus far, the regulatory mechanism underlying the protein stability of ORF50 is unknown. Our earlier studies have demonstrated that a protein abundance regulatory signal (PARS) at the ORF50 C-terminal region modulates its protein abundance. The PARS region consists of PARS-I (aa 490–535) and PARS-II (aa 590–650), and mutations in either component result in abundant expression of ORF50. Here, we show that ORF50 protein is polyubiquitinated and its abundance is controlled through the proteasomal degradation pathway. The PARS-I motif mainly functions as a nuclear localization signal in the control of ORF50 abundance, whereas the PARS-II motif is required for the binding of ubiquitin enzymes in the nucleus. We find that human oncoprotein MDM2, an ubiquitin E3 ligase, is capable of interacting with ORF50 and promoting ORF50 degradation in cells. The interaction domains between both proteins are mapped to the PARS region of ORF50 and the N-terminal 220-aa region of MDM2. Additionally, we identify lysine residues at positions 152 and 154 in the N-terminal domain of ORF50 critically involved in MDM2-mediated downregulation of ORF50 levels. Within KSHV-infected cells, the levels of MDM2 were greatly reduced during viral lytic cycle and genetic knockdown of MDM2 in these cells favored the enhancement of ORF50 expression, supporting that MDM2 is a negative regulator of ORF50 expression. Collectively, the study elucidates the regulatory mechanism of ORF50 stability and implicates that MDM2 may have a significant role in the maintenance of viral latency by lowering basal level of ORF50.

In patients who require a permanent central venous catheter (PCVC), the usual aim is to put the catheter tip at the superior vena cava and right atrium (SVC-RA) junction. However, there is no study regarding how to guide the positioning of the catheter tip when the SVC-RA junction cannot be identified on chest radiograph. The objectives of this prospective study were: (1) to investigate the incidence and etiologies of radiographically undetermined SVC-RA junctions in cancer patients undergoing PCVC implantation; and (2) to evaluate the feasibility, effectiveness and safety of combined transesophageal echocardiography (TEE) and laryngeal mask airway (LMA) to guide the positioning of catheters during implantations in patients without this radiographic landmark. Over a 1-year study period, 83 consecutive patients with oncologic diseases who required implantation of a PCVC in a tertiary center were screened. Their preoperative chest radiographs were examined by radiologists to identify the presence of the SVC-RA junction. Patients without a radiographically identifiable SVC-RA junction were classified as cancer-related or cancer-unrelated in terms of etiology. For patients without this landmark, we used TEE with a pediatric biplane transducer and a LMA under intravenous general anesthesia during PCVC implantation to guide the positioning of the catheter tip at the SVC-RA junction. We found that in 16% (13/83) of patients, the SVC-RA junction could not be identified on radiograph. Among the 13 patients, only three (23%) had cancer-related etiologies. In all of the 13 patients, the LMA was successfully placed after the TEE transducer was inserted. No episode of air leak from the LMA was found during surgery. All had the catheter tip positioned in the anatomic SVC-RA junction under TEE guidance. In conclusion, 16% of cancer patients requiring PCVC implantation had no identifiable SVC-RA junction on chest radiograph and most causes were cancer-unrelated. In patients without a radiographically identifiable SVC-RA junction, guidance by TEE under LMA general anesthesia is a feasible, safe and effective management to position a PCVC at the SVC-RA junction.