Persistent left superior vena cava: Review of the literature, clinical implications, and relevance of alterations in thoracic central venous anatomy as pertaining to the general principles of central venous access device placement and venography in cancer patients

Persistent left superior vena cava (PLSVC) represents the most common congenital venous anomaly of the thoracic systemic venous return, occurring in 0.3% to 0.5% of individuals in the general population, and in up to 12% of individuals with other documented congential heart abnormalities. In this regard, there is very little in the literature that specifically addresses the potential importance of the incidental finding of PLSVC to surgeons, interventional radiologists, and other physicians actively involved in central venous access device placement in cancer patients. In the current review, we have attempted to comprehensively evaluate the available literature regarding PLSVC. Additionally, we have discussed the clinical implications and relevance of such congenital aberrancies, as well as of treatment-induced or disease-induced alterations in the anatomy of the thoracic central venous system, as they pertain to the general principles of successful placement of central venous access devices in cancer patients. Specifically regarding PLSVC, it is critical to recognize its presence during attempted central venous access device placement and to fully characterize the pattern of cardiac venous return (i.e., to the right atrium or to the left atrium) in any patient suspected of PLSVC prior to initiation of use of their central venous access device

Circulating Tumor DNA Tracking Through Driver Mutations as a Liquid Biopsy-Based Biomarker for Uveal Melanoma

Background: Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite good primary tumor control, up to 50% of patients develop metastasis, which is lethal. UM often presents asymptomatically and is usually diagnosed by clinical examination and imaging, making it one of the few cancer types diagnosed without a biopsy. Hence, alternative diagnostic tools are needed. Circulating tumor DNA (ctDNA) has shown potential as a liquid biopsy target for cancer screening and monitoring. The aim of this study was to evaluate the feasibility and clinical utility of ctDNA detection in UM using specific UM gene mutations. Methods: We used the highly sensitive digital droplet PCR (ddPCR) assay to quantify UM driver mutations (GNAQ, GNA11, PLCβ4 and CYSTLR2) in cell-free DNA (cfDNA). cfDNA was analyzed in six well established human UM cell lines with known mutational status. cfDNA was analyzed in the blood and aqueous humor of an UM rabbit model and in the blood of patients. Rabbits were inoculated with human UM cells into the suprachoroidal space, and mutated ctDNA was quantified from longitudinal peripheral blood and aqueous humor draws. Blood clinical specimens were obtained from primary UM patients (n = 14), patients presenting with choroidal nevi (n = 16) and healthy individuals (n = 15). Results: The in vitro model validated the specificity and accuracy of ddPCR to detect mutated cfDNA from UM cell supernatant. In the rabbit model, plasma and aqueous humor levels of ctDNA correlated with tumor growth. Notably, the detection of ctDNA preceded clinical detection of the intraocular tumor. In human specimens, while we did not detect any trace of ctDNA in healthy controls, we detected ctDNA in all UM patients. We observed that UM patients had significantly higher levels of ctDNA than patients with nevi, with a strong correlation between ctDNA levels and malignancy. Noteworthy, in patients with nevi, the levels of ctDNA highly correlated with the presence of clinical risk factors. Conclusions: We report, for the first time, compelling evidence from in vitro assays, and in vivo animal model and clinical specimens for the potential of mutated ctDNA as a biomarker of UM progression. These findings pave the way towards the implementation of a liquid biopsy to detect and monitor UM tumors.info:eu-repo/semantics/publishedVersio

Observer variation in chest radiography of acute lower respiratory infections in children: a systematic review

<p>Abstract</p> <p>Background</p> <p>Knowledge of the accuracy of chest radiograph findings in acute lower respiratory infection in children is important when making clinical decisions.</p> <p>Methods</p> <p>I conducted a systematic review of agreement between and within observers in the detection of radiographic features of acute lower respiratory infections in children, and described the quality of the design and reporting of studies, whether included or excluded from the review.</p> <p>Included studies were those of observer variation in the interpretation of radiographic features of lower respiratory infection in children (neonatal nurseries excluded) in which radiographs were read independently and a clinical population was studied. I searched MEDLINE, HealthSTAR and HSRPROJ databases (1966 to 1999), handsearched the reference lists of identified papers and contacted authors of identified studies. I performed the data extraction alone.</p> <p>Results</p> <p>Ten studies of observer interpretation of radiographic features of lower respiratory infection in children were identified. Seven of the studies satisfied four or more of the seven design and reporting criteria. Six studies met the inclusion criteria for the review. Inter-observer agreement varied with the radiographic feature examined. Kappa statistics ranged from around 0.80 for individual radiographic features to 0.27–0.38 for bacterial <it>vs</it> viral etiology.</p> <p>Conclusions</p> <p>Little information was identified on observer agreement on radiographic features of lower respiratory tract infections in children. Agreement varied with the features assessed from "fair" to "very good". Aspects of the quality of the methods and reporting need attention in future studies, particularly the description of criteria for radiographic features.</p