Differential diagnosis of a ring-enhancing brain lesion in the setting of metastatic cancer and a mycotic aneurysm.

A diagnostic challenge arises when a patient presents with a ring-enhancing lesion of the brain in the setting of both metastatic cancer and a source of infection. We report a case depicting this dilemma in an 80-year-old man with a history of metastatic oral squamous cell carcinoma who presented for left-sided hemiparesis. Computed tomography and magnetic resonance imaging revealed a ring-enhancing lesion of the right parietal vertex without signs of stroke. He was also found to have an aneurysm of the right common carotid artery with abnormal surrounding soft tissue density and gas, findings suspicious for a mycotic aneurysm. The likelihood of the brain lesion being an abscess formed by septic embolization was raised, leading to the recommendation to surgically explore the brain lesion and repair the aneurysm. Nevertheless, a high index of suspicion for a brain abscess and mycotic aneurysm is necessary in this type of clinical scenario.

Reversal of warfarin anticoagulation in geriatric traumatic brain injury due to ground-level falls.

BACKGROUND: The efficacy of prothrombin complex concentrate (PCC) compared with fresh frozen plasma (FFP) for reversal of oral anticoagulants has not been investigated in geriatric patients suffering intracranial hemorrhage (ICH) due to a ground-level fall (GLF). METHODS: Patients 65 years and older who were treated at Santa Barbara Cottage Hospital between January 2011 and March 2018 with ICH after a GLF while taking warfarin were reviewed. Patients were reversed with either FFP (n=25) or PCC (n=27) and patient outcomes were compared. Separate analyses were conducted for patients who received adjuvant vitamin K administration and those who did not. RESULTS: Mortality rates, hospital length of stay, intensive care unit admission and length of stay were similar for both FFP and PCC intervention. There was no difference in radiological progression of hemorrhage within the first 24 hours of admission (FFP: 36%, PCC: 43%, p=0.365). In patients who had international normalized ratio (INR) values measured prior to intervention, 81% (17 out of 21) of the PCC group reached an INR value below 1.5 within an 8-hour period, whereas only 29% (4 out of 14) of the FFP group did (p=0.002). Vitamin K was concomitantly given to 28% of the patients receiving FFP, and 81% of those patients receiving PCC. No significant differences in outcomes were found whether adjunctive vitamin K was administered or not, in either FFP or PCC group. However, when vitamin K was not administered, the PCC group had a higher rate of INR reversal (80% vs. 10% for FFP, p=0.006). CONCLUSION: Administration of PCC is as effective in short-term outcomes as FFP in treating geriatric patients on warfarin sustaining an ICH after a GLF. INR reversal was more successful, significantly faster, and required lower infusion volumes in patients receiving PCC. LEVEL OF EVIDENCE: Level III.

Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes.

To further understand the molecular distinctions between kidney cancer subtypes, we analyzed exome, transcriptome and copy number alteration data from 167 primary human tumors that included renal oncocytomas and non-clear cell renal cell carcinomas (nccRCCs), consisting of papillary (pRCC), chromophobe (chRCC) and translocation (tRCC) subtypes. We identified ten significantly mutated genes in pRCC, including MET, NF2, SLC5A3, PNKD and CPQ. MET mutations occurred in 15% (10/65) of pRCC samples and included previously unreported recurrent activating mutations. In chRCC, we found TP53, PTEN, FAAH2, PDHB, PDXDC1 and ZNF765 to be significantly mutated. Gene expression analysis identified a five-gene set that enabled the molecular classification of chRCC, renal oncocytoma and pRCC. Using RNA sequencing, we identified previously unreported gene fusions, including ACTG1-MITF fusion. Ectopic expression of the ACTG1-MITF fusion led to cellular transformation and induced the expression of downstream target genes. Finally, we observed upregulation of the anti-apoptotic factor BIRC7 in MiTF-high RCC tumors, suggesting a potential therapeutic role for BIRC7 inhibitors.

Atlanto-occipital dislocation: Case report and discussion.

Traumatic atlanto-occipital dislocation is an uncommon injury that frequently results in either a fatal outcome or severe neurologic deficit. This diagnosis must be considered for any patients who may have had cervical spine damage after high trauma, even in the absence of neurologic signs, as there have been reports of cases without neurologic impairment. In addition to radiographic examination, including lateral cervical radiographs, supplemental imaging with CT or MRI may be required to confirm diagnosis in equivocal cases, and to help in evaluation of bone and nervous structures. Moreover, these modalities allow measurement of the magnitude of dislocation and aid in classification of type of dislocation, which helps guide management. A systematic approach to evaluating the cranio-cervical relationship is critical to identifying atlanto-occipital dislocation. This case report presents and discusses imaging findings that will assist in the diagnosis of atlanto-occipital dislocation.

Highly efficient somatic-mutation identification using Escherichia coli mismatch-repair detection.

The discovery of somatic mutations in cancer tissue is extremely laborious, time-consuming and costly. In an evaluation comparing mismatch repair detection (MRD) against Sanger sequencing for somatic-mutation detection, we found that MRD had a specificity of 96% and a sensitivity of 92%. Our results showed that MRD is a robust and cost-effective alternative to Sanger sequencing for identifying somatic mutations in human tumors.

A rapid method for estimation of baculovirus titer based on viable cell size.

Baculovirus protein expression system is a powerful tool for producing recombinant proteins. To optimize conditions for efficient recombinant protein expression, it is important to determine titer of virus stock for arriving at an optimal multiplicity of infection (MOI) that maximizes recombinant protein expression. Traditionally plaque assays have been used for titer determination. Other methods such as endpoint dilution, quantitative real-time polymerase chain reaction and flow cytometry have been developed to aid the determination of virus titers. However, most of these methods are time-consuming and labor intensive. In this regard, a simple and rapid method for determination of virus titers based on the cytopathic effects that lead to viable cell size increase following virus infection is presented in this paper. In this study, the Vi-CELL (Beckman Coulter) was used to measure cell-diameter over a range of virus dilutions, following infection. Applying statistical modeling techniques, the viable cell-diameter data was used to estimate the virus titer. The results indicated that the viable cell-diameter based titer estimation to be reliable and comparable to titers determined by the traditional plaque assay.

The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

A large-scale effort, termed the Secreted Protein Discovery Initiative (SPDI), was undertaken to identify novel secreted and transmembrane proteins. In the first of several approaches, a biological signal sequence trap in yeast cells was utilized to identify cDNA clones encoding putative secreted proteins. A second strategy utilized various algorithms that recognize features such as the hydrophobic properties of signal sequences to identify putative proteins encoded by expressed sequence tags (ESTs) from human cDNA libraries. A third approach surveyed ESTs for protein sequence similarity to a set of known receptors and their ligands with the BLAST algorithm. Finally, both signal-sequence prediction algorithms and BLAST were used to identify single exons of potential genes from within human genomic sequence. The isolation of full-length cDNA clones for each of these candidate genes resulted in the identification of >1000 novel proteins. A total of 256 of these cDNAs are still novel, including variants and novel genes, per the most recent GenBank release version. The success of this large-scale effort was assessed by a bioinformatics analysis of the proteins through predictions of protein domains, subcellular localizations, and possible functional roles. The SPDI collection should facilitate efforts to better understand intercellular communication, may lead to new understandings of human diseases, and provides potential opportunities for the development of therapeutics.