Cronobacter Sakazakii Bacteremia in a 76-year-old Woman: A Case Report

Cronobacter sakazakii, commonly found in contaminated infant formula and thereby causes infantile bacteremia, is rarely associated with adult bacteremia. We present the tenth case of C. sakazakii bacteremia in adults. The patient is a 76-year-old woman who resides in a skilled nursing facility and presents with risk factors including bullous pemphigoid, Type II diabetes mellitus, hypertension, hyperlipidemia, chronic kidney disease, and anemia. The therapy was started with intravenous ciprofloxacin and vancomycinempirically. After consultation with an Infectious Diseases specialist, ciprofloxacin and vancomycin was replaced with meropenem based on the patient’s extensive bullous lesions, history of ESBL infections, and possible pneumonia. Later, the therapy was de-escalated to intravenous ceftriaxone and vancomycin after culture and sensitivity testing were available and clinical signs of improvements were evident. She was sent back to her skilled nursing but was re-admitted 10-days later. She was placed on dialysis for altered mental status secondary to acute renal failure. Blood and urine cultures were repeated and had no evidence of bacterial growth

Towards Universal Screening for Colon Cancer: A Cheap, Reliable, Noninvasive Test Using Gene Expression Analysis of Rectal Swabs

Though colon cancer is the second leading cause of cancer deaths in the US, it is entirely preventable through early screening to detect and remove adenomatous polyps. Colonoscopy has long been regarded as the “gold standard” but is expensive, invasive, and uncomfortable, and only about half those considered at risk for colon cancer currently submit to colonoscopy or to less reliable alternatives such as fecal occult blood test. Here we describe the use of gene expression analysis to detect altered expression of certain genes associated with not only colon cancer but also polyps. The analysis can be performed on rectal swabs, with specimens provided in a routine doctor's office visit. The existence of this cheap and simple test, together with an active program to encourage individuals to submit to screening, could help eradicate colon cancer

A Systematic Review of Proton Therapy for the Management of Nasopharyngeal Cancer

PURPOSE: With improved technology, more patients with nasopharyngeal cancer (NPC) are receiving definitive treatment with proton therapy, which allows greater sparing of dose to normal tissues without compromising efficacy. As there is no randomized data, the purpose of this study was to systematically review the available literature on proton therapy in this setting, focusing on the toxicity endpoints. MATERIALS AND METHODS: A systematic search using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was conducted in 5 databases: PubMed, Embase, SCOPUS, Web of Science, and the Cochrane Central Register of Controlled Trials. A total of 491 studies were found on the topic of NPC and proton therapy. Following independent study selection by 2 investigators, 9 studies were found to have sufficient focus and relevance to be incorporated into the systematic review. RESULTS: All 9 studies were retrospective and examined only NPC patients except for one that also included paranasal sinus cancer. One study was a reirradiation study. Four studies used 3D or double scatter technique, while all others used intensity-modulated proton therapy. Oncologic outcomes were similar to intensity-modulated radiation therapy (IMRT) rates, with 2-year local and regional progression-free survival (LRFS) ranging from 84% to 100%, 2-year progression-free survival (PFS) ranging from 75% to 88.9%, and 2-year overall survival (OS) ranging from 88% to 95% in the up-front setting. Four comparison studies with IMRT found significantly lower feeding tube rates (20% versus 65%, P = .015; and 14% versus 85%, P < .001) with proton therapy as well as lower mucositis (G2 46% versus 70%, P = .019; and G3 11% versus 76%, P = .0002). All other acute and late effects were largely improved with proton therapy but not statistically significant. CONCLUSIONS: NPC patients receiving proton therapy maintain good outcomes with improved toxicity profile, likely due to sparing of dose to normal structures. Prospective studies are ongoing to better quantify the magnitude

Systems-Level Comparison of Host-Responses Elicited by Avian H5N1 and Seasonal H1N1 Influenza Viruses in Primary Human Macrophages

Human disease caused by highly pathogenic avian influenza (HPAI) H5N1 can lead to a rapidly progressive viral pneumonia leading to acute respiratory distress syndrome. There is increasing evidence from clinical, animal models and in vitro data, which suggests a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. The key target cells for the virus in the lung are the alveolar epithelium and alveolar macrophages, and we have shown that, compared to seasonal human influenza viruses, equivalent infecting doses of H5N1 viruses markedly up-regulate pro-inflammatory cytokines in both primary cell types in vitro. Whether this H5N1-induced dysregulation of host responses is driven by qualitative (i.e activation of unique host pathways in response to H5N1) or quantitative differences between seasonal influenza viruses is unclear. Here we used microarrays to analyze and compare the gene expression profiles in primary human macrophages at 1, 3, and 6 h after infection with H5N1 virus or low-pathogenic seasonal influenza A (H1N1) virus. We found that host responses to both viruses are qualitatively similar with the activation of nearly identical biological processes and pathways. However, in comparison to seasonal H1N1 virus, H5N1 infection elicits a quantitatively stronger host inflammatory response including type I interferon (IFN) and tumor necrosis factor (TNF)-α genes. A network-based analysis suggests that the synergy between IFN-β and TNF-α results in an enhanced and sustained IFN and pro-inflammatory cytokine response at the early stage of viral infection that may contribute to the viral pathogenesis and this is of relevance to the design of novel therapeutic strategies for H5N1 induced respiratory disease

Locally Advanced and Unresectable Cutaneous Squamous Cell Carcinoma: Outcomes of Concurrent Cetuximab and Radiotherapy

Background. Advanced age and immune dysfunction are risk factors for cutaneous squamous cell carcinoma (cSCC) and often render patients with locally-advanced disease medically inoperable or surgically unresectable, but potentially curable with radiotherapy. Concurrent chemotherapy and radiotherapy may not be well tolerated in this population, but another systemic therapy may improve disease control. Objective. Determine the tolerance and efficacy of concurrent cetuximab and radiotherapy (CRT) for patients with locally advanced and unresectable cSCC. Methods. Retrospective analysis of 12 patients treated with CRT for locally advanced and unresectable cSCC. Results. Patients were elderly and 75% had moderate-to-severe comorbidities, while 42% had immune dysfunction. Grades 3-4 adverse events were noted in 83% of patients; 67% required hospital admission for adverse events. Complete and partial response was noted in 36% and 27% (response rate, 64%). Stable and progressive disease was noted in 3 and 1 patients, respectively (disease control rate, 91%). Median progression-free and overall survival were 6.4 and 8.0 months, respectively. Limitations. Retrospective small-cohort, single-institution analysis. Conclusion. Patients selected for CRT were elderly, with comorbidities and immune dysfunction, but treatment responses were observed. Patients selected for this treatment approach have a poor prognosis with limited capacity for therapy; more effective treatment is needed

A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations

SummaryAccumulating evidence implicates heterogeneity within cancer cell populations in the response to stressful exposures, including drug treatments. While modeling the acute response to various anticancer agents in drug-sensitive human tumor cell lines, we consistently detected a small subpopulation of reversibly “drug-tolerant” cells. These cells demonstrate >100-fold reduced drug sensitivity and maintain viability via engagement of IGF-1 receptor signaling and an altered chromatin state that requires the histone demethylase RBP2/KDM5A/Jarid1A. This drug-tolerant phenotype is transiently acquired and relinquished at low frequency by individual cells within the population, implicating the dynamic regulation of phenotypic heterogeneity in drug tolerance. The drug-tolerant subpopulation can be selectively ablated by treatment with IGF-1 receptor inhibitors or chromatin-modifying agents, potentially yielding a therapeutic opportunity. Together, these findings suggest that cancer cell populations employ a dynamic survival strategy in which individual cells transiently assume a reversibly drug-tolerant state to protect the population from eradication by potentially lethal exposures.PaperCli

Outcomes of surgery and postoperative radiation therapy in managing medullary thyroid carcinoma

Background and Objectives We evaluated the outcomes of surgery with or without postoperative radiation therapy (PORT) in the management of medullary thyroid carcinoma (MTC). Methods From two tertiary cancer centers, 297 consecutive patients with MTC treated with PORT (n = 46) between 1990 and 2016 or surgery alone (n = 251) between 2000 and 2016 were reviewed. Results Ten-year cumulative incidences of locoregional and distant failure were 30.2% and 24.9% in the surgery cohort, and 16.9% and 55.2% in the PORT cohort. In the surgery alone cohort, T4 disease, extrathyroidal extension, N1 disease, extranodal extension (ENE), and residual disease after surgery were associated with local failure. The PORT cohort had significantly higher proportions of patients with T4 disease, N1 disease, ENE, and residual disease. Conclusions High-risk clinical features can help identify patients with MTC at high-risk for local failure after surgery alone. Patients with high-risk clinical features had effective locoregional control after PORT