Imposter Zoster: An Atypical Case of Varicella-Zoster Virus Infection.

In this report, we describe a case involving an 80-year-old female who presented to the emergency department with an acute onset of left upper quadrant abdominal pain. The chief complaint misled us down multiple pathways of considering ischemic bowel disease, peptic ulcer disease, and small bowel obstruction. As a result, this led to costly and invasive diagnostic studies. However, the actual cause eventually became apparent - a cutaneous varicella-zoster virus infection. This case underscores the significance of maintaining a comprehensive list of potential diagnoses, particularly in elderly adults who commonly present atypically and often face difficulty expressing their symptoms. It also underlines the diagnostic challenges associated with identifying shingles without cutaneous findings. Early detection is crucial in preventing unnecessary tests, minimizing costs, and avoiding treatment delays. Furthermore, the case is a powerful example of the importance of vaccination, which has been proven to be 68-97% effective in preventing shingles and postherpetic neuralgia, depending on the individual's immune function.

Use of liver stiffness measurements in acute decompensated heart failure: new applications of a non-invasive technique.

Heart failure (HF) is a complex disease associated with multisystem organ failure, recurrent hospital admissions, and increased mortality. Acute decompensated heart failure (ADHF) increases central venous pressure (CVP) with resultant hepatic congestion, and this relationship has prognostic significance. The gold standard method of measuring CVP, right heart catheterization, is invasive and costly, prompting further investigation into more accurate non-invasive assessments in HF patients, including liver elastography. Liver elastography relies on imaging techniques to assess liver stiffness measurements (LSM), with high values equating to increased stiffness. While this was developed to assess fibrosis in liver disease, LSM also reflect increased CVP and hepatic congestion. Multiple studies involving ADHF patients, find that increased LSM are independently predictive of increased cardiac events, all-cause mortality, and worse post-operative outcome after both acute HF exacerbation and left ventricular assist device (LVAD) placement. In this review, we discuss the role of LSM as a surrogate for CVP and their applications in determining prognosis in both the ADHF and LVAD populations.

Effects of life-stage and passive tobacco smoke exposure on pulmonary innate immunity and influenza infection in mice.

Limited data are available on the effects of perinatal environmental tobacco smoke (ETS) exposure for early childhood influenza infection. The aim of the present study was to examine whether perinatal versus adult ETS exposure might provoke more severe systemic and pulmonary innate immune responses in mice inoculated with influenza A/Puerto Rico/8/34 virus (IAV) compared to phosphate-buffered saline (PBS). BALB/c mice were exposed to filtered air (FA) or ETS for 6 weeks during the perinatal or adult period of life. Immediately following the final exposure, mice were intranasally inoculated with IAV or PBS. Significant inflammatory effects were observed in bronchoalveolar lavage fluid of neonates inoculated with IAV (FA+IAV or ETS+IAV) compared to PBS (ETS+PBS or FA+PBS), and in the lung parenchyma of neonates administered ETS+IAV versus FA+IAV. Type I and III interferons were also elevated in the spleens of neonates, but not adults with ETS+IAV versus FA+IAV exposure. Both IAV-inoculated neonate groups exhibited significantly more CD4 T cells and increasing numbers of CD8 and CD25 T cells in lungs relative to their adult counterparts. Taken together, these results suggest perinatal ETS exposure induces an exaggerated innate immune response, which may overwhelm protective anti-inflammatory defenses against IAV, and enhances severity of infection at early life stages (e.g., in infants and young children).

TAFRO syndrome: A case report and review of the literature.

TAFRO syndrome is a rare clinicopathologic variant of idiopathic multicentric Castleman disease characterized by Thrombocytopenia, Ascites (anasarca), myeloFibrosis, Renal dysfunction, and Organomegaly. Here, we report a case of TAFRO syndrome in an HIV-negative young Caucasian male who presented with fever, normocytic anemia, thrombocytopenia, and acute renal insufficiency. The serum interleukin-6 (IL-6) level was elevated. Chest and abdominal CT revealed bilateral pleural effusion, ascites, splenomegaly, and multiple mildly enlarged lymph nodes. An excisional biopsy of inguinal lymph node showed a few atrophic follicles and expansion of interfollicular areas by marked vascular proliferation and polytypic plasmacytosis. HHV-8 was negative. Subsequent bone marrow biopsy was normocellular with moderately increased megakaryocytes and occasional megakaryocytic emperipolesis. His signs and symptoms improved after treatment with methylprednisolone and tocilizumab (anti-IL-6 receptor antibody). Our study confirms the distinctive nature of this syndrome, which should allow for better recognition and appropriate therapy.

U.S. Estimates of Pediatric Spinal Cord Injury: Implications for Clinical Care and Research Planning.

The aim of this study was to provide accurate estimates and characterizations of children with spinal cord injuries (SCIs) and for the subset that are appropriate for inclusion in clinical trials. We identified children <18 years of age with SCI International Classifications of Diseases, Ninth Revision, Clinical Modification Codes (ICD-9-CM codes) from the 2006, 2009, and 2012 Kids' Inpatient Database. We excluded those with late effects, transfers to other hospitals, unspecified injury levels, and hospital stays <48 h. We then used conventional rationale to identify children who were eligible for SCI clinical trials. Over 3 years, 2484 children had SCI ICD-9-CM codes; 1342 had coding consistent with true SCI and 706 satisfied clinical trial inclusion criteria, yielding national estimates of 2013 and 1062, respectively. Of children with clinical trial eligible SCI, injuries were more common in the cervical region (66.1%), males (65.5%), older children (51.1% were 16-17 years old), and the South (49.8%). The majority were treated at urban teaching hospitals (84.6%); however, only 20.3% were treated at pediatric-specific centers. Of the 445 sample hospitals treating children with SCI, 66.3% treated just 1 child in the 3-year period. Children eligible for SCI clinical trials represented less than one third of children with SCI ICD-9-CM codes. These children were regionally localized to the South, with few receiving treatment at pediatric-specific centers or centers that frequently care for children with SCI. These findings highlight the importance of carefully assessing the national distribution of children with SCI, so that resources are appropriately allocated to optimize clinical care and research outcomes.

Resistance to angiogenesis inhibitors in renal cell carcinoma.

Antiangiogenic drugs are now available for treatment of renal cell carcinoma and are utilized sequentially to prolong clinical benefit in patients with recurrent disease. These antiangiogenic agents are disease stabilizing in most cases, and resistance eventually develops over time. Because different combinations and sequences are tested in clinical trials, resistance patterns and mechanisms should be investigated. Much effort has been devoted to understanding the biology and elucidating the pathways and additional targets during tumorigenesis and metastasis. Resistance appears to be either primary nonresponsiveness, or it is acquired over time and related to various evasive/escape mechanisms that the tumor develops in response to therapy. Primary resistance is less common, but may be due to an intrinsic redundancy of available angiogenic signals for the tumor, causing unresponsiveness to vascular endothelial growth factor (VEGF)-targeted therapies. During acquired resistance, tumors may activate an "angiogenic switch," which leads to either upregulation of the existing VEGF pathway or recruitment of alternative factors responsible for tumor revascularization. Rationally designed preclinical and clinical trials will shed additional light on our understanding of the potential mechanisms of resistance to antiangiogenic drugs.

Mediastinal staging of non-small-cell lung cancer.

Accurate mediastinal staging is the hallmark of a sound thoracic oncology program. Mediastinal staging remains the most important validated tool for making treatment decisions for patients with non-small-cell lung cancer. The last few years have seen the emergence of several new techniques to improve mediastinal staging. This article summarizes the current state of the art of this rapidly evolving field.

Molecular decoy to the Y-box binding protein-1 suppresses the growth of breast and prostate cancer cells whilst sparing normal cell viability.

The Y-box binding protein-1 (YB-1) is an oncogenic transcription/translation factor that is activated by phosphorylation at S102 whereby it induces the expression of growth promoting genes such as EGFR and HER-2. We recently illustrated by an in vitro kinase assay that a novel peptide to YB-1 was highly phosphorylated by the serine/threonine p90 S6 kinases RSK-1 and RSK-2, and to a lesser degree PKCα and AKT. Herein, we sought to develop this decoy cell permeable peptide (CPP) as a cancer therapeutic. This 9-mer was designed as an interference peptide that would prevent endogenous YB-1(S102) phosphorylation based on molecular docking. In cancer cells, the CPP blocked P-YB-1(S102) and down-regulated both HER-2 and EGFR transcript level and protein expression. Further, the CPP prevented YB-1 from binding to the EGFR promoter in a gel shift assay. Notably, the growth of breast (SUM149, MDA-MB-453, AU565) and prostate (PC3, LNCap) cancer cells was inhibited by ∼90% with the CPP. Further, treatment with this peptide enhanced sensitivity and overcame resistance to trastuzumab in cells expressing amplified HER-2. By contrast, the CPP had no inhibitory effect on the growth of normal immortalized breast epithelial (184htert) cells, primary breast epithelial cells, nor did it inhibit differentiation of hematopoietic progenitors. These data collectively suggest that the CPP is a novel approach to suppressing the growth of cancer cells while sparing normal cells and thereby establishes a proof-of-concept that blocking YB-1 activation is a new course of cancer therapeutics.

Targeting YB-1 in HER-2 overexpressing breast cancer cells induces apoptosis via the mTOR/STAT3 pathway and suppresses tumor growth in mice.

The Y-box binding protein-1 (YB-1) is a transcription/translation factor that is highly expressed in primary breast tumors where it is consistently associated with poor survival. It induces human epidermal growth factor receptor (her-2) along with its dimerization partner egfr by directly binding to their promoters. In addition to promoting growth by inducing receptor tyrosine kinases, YB-1 also protects cells against apoptosis through mechanisms that have not been fully revealed. Given this, we addressed whether YB-1 might be an eventual therapeutic target for breast cancer by inhibiting it with small interfering RNAs in vitro and in vivo. Inhibiting YB-1 suppressed the growth of six of seven breast cancer cell lines that had amplified her-2 or were triple negative. Importantly, targeting YB-1 induced apoptosis in BT474-m1 and Au565 breast cancer cells known to have her-2 amplifications. The potential role of signal transducers and activators of transcription 3 (STAT3) was pursued to address the underlying mechanism for YB-1-mediated survival. Inhibition of YB-1 decreased P-STAT3(S727) but not P-STAT3(Y705) or total STAT3. This was accompanied by decreased P-ERK1/2(T202/Y204), P-mTOR(S2448), and total mammalian target of rapamycin mTOR. Furthering the role of STAT3 in these cells, we show that knocking it down recapitulated the induction of apoptosis. Alternatively, constitutively active P-STAT3 rescued YB-1-induced apoptosis. Finally, targeting YB-1 with 2 different siRNAs remarkably suppressed tumor cell growth in soft agar by >90% and delayed tumorigenesis in nude mice. We conclude that HER-2 overexpressing as well as triple-negative breast cancer cells are YB-1 dependent, suggesting it may be a good therapeutic target for these exceptionally aggressive tumors.