Self-Evisceration of Intestines as the Initial Presentation of Schizoaffective Disorder.

Schizoaffective disorder is categorized by major mood episodes and symptoms of schizophrenia that include disorganized speech, delusions, paranoia, and hallucinations. It is associated with risk factors, including a history of abuse and cannabis use, and patients are typically diagnosed in adolescence and young adulthood. In this case report, we describe the unusual case of a 39-year-old male patient with undiagnosed schizoaffective disorder who self-eviscerated his intestines during an episode of psychosis. He received an emergent exploratory laparotomy with a partial colectomy. After medical stabilization and reorientation, the patient recalled a 10-year history of paranoia associated with significant cannabis use, despite otherwise functioning appropriately in society. During a two-week hospital course, his paranoia and hallucinations were remitted on olanzapine and valproic acid. In addition to discussing his presentation and recollection of the incident, we also discuss similar cases of self-mutilation in nonsuicidal patients and the relationship between cannabis use and schizophrenia spectrum disorders.

Stereotactic body radiation therapy (SBRT) for metastatic renal cell carcinoma: A multi-institutional experience.

Objectives: Examine local control(LC), overall survival(OS), and toxicity following stereotactic body radiation therapy(SBRT) for patients with metastatic renal cell carcinoma(mRCC). Methods: A multi-institutional registry was queried. Potential predictive factors of LC and OS were evaluated with a Cox-proportional hazards model for multivariate analysis(MVA). Results: We identified 115 mRCC patients with 181 lesions. Median biologically effective dose (BED7) was 72.9 Gy7 (range: 42.9-231.4 Gy7) with a median dose/fraction of 10 Gy (range: 5-24 Gy). Utilizing both Karnofsky Performance Score (KPS) and presence of osseous metastatic disease as prognostic indicators, estimated 2-year OS rates were 67.7% (95% CI: 49.9-89.5%), 31.8% (95% CI: 19.0-45.3%), and 20% (95% CI: 1.4-54.7%; p=0.0012). One- and 2-year LC rates were 88.2% and 82.7%, respectively, with no prognostic factors identified. Roughly 13% of patients reported toxicities with one Grade 3-5 toxicity. Conclusion: SBRT was well-tolerated with promising LC. Both KPS and osseous metastatic disease should be considered in determining which patients with mRCC may preferentially benefit from SBRT.

Clinical Outcomes Following Stereotactic Body Radiation Therapy (SBRT) for Stage I Medically Inoperable Small Cell Lung Carcinoma: A Multi-Institutional Analysis From the RSSearch Patient Registry.

OBJECTIVES: To utilize the RSSearch Patient Registry (RSSPR) to examine local control (LC), overall survival (OS), and toxicities following stereotactic body radiation therapy (SBRT) for stage I (T1-T2/N0) medically inoperable small cell lung carcinoma (SCLC). MATERIALS AND METHODS: We searched the RSSPR for medically inoperable stage I SCLC patients treated with definitive SBRT. Potential predictive factors of OS were estimated using the Kaplan-Meier method as well as a Cox proportional hazards model. RESULTS: Twenty-one patients were identified with medically inoperable stage I SCLC that met inclusion criteria. Fourteen patients had stage IA SCLC (T1N0) and 7 patients had stage IB SCLC (T2N0) with a median gross tumor volume of 10.1 cm (range: 0.72 to 41.4 cm). The median number of fractions was 4 (range: 3 to 5), and the median BED10 was 105.6 Gy10 (range: 72 to 239.7 Gy10). Four patients received adjuvant chemotherapy. One- and 2-year actuarial OS rates were 73.1% (95% confidence interval [CI]: 36.8%-90.1%) and 36.6% (95% CI: 9.0%-65.7%), respectively. Factors found to be associated with 1-year OS on univariate analysis included T2 disease (85.5% vs. 33.3%; P=0.03), adjuvant chemotherapy (100% vs. 66.3%; P=0.11), and gross tumor volume ≥10 cm (100% vs. 52.5%; P=0.10). On multivariate analysis, adjuvant chemotherapy was associated with improved OS (hazard ratio=0.07 [95% CI: 0.13-0.37; P=0.002]). The 1-, 2-, and 3-year LC rates were 100%, and 1- and 2-year progression-free survival (PFS) rates were 85.7% (95% CI: 33.4-97.9%) and 42.9% (95% CI: 1.1-85.3%), respectively. Similar to OS, patients with T1N0 disease had superior PFS as compared to T2N0 disease (P=0.01). Toxicities were reported by 3/21 (14.3%) of patients with none ≥ grade 3 and no esophageal toxicities. CONCLUSIONS: SBRT was well-tolerated in the treatment of stage I SCLC with excellent LC achieved. Patients with T1N0 stage IA SCLC were noted to have improved PFS and OS following SBRT as compared with T2N0 Stage IB SCLC. Adjuvant chemotherapy was found to result in improved OS for stage I SCLC patients over SBRT alone.

Phenotypic Alteration of Hepatocytes in Non-Alcoholic Fatty Liver Disease.

Non-Alcoholic Fatty Liver Disease (NAFLD) has been recognized as the most common liver disorder in developed countries. NAFLD progresses from fat accumulation in hepatocytes to steatohepatitis to further stages of fibrosis and cirrhosis. Simple steatosis, i.e. fat deposition in the liver, is considered benign and gives way to non-alcoholic steatohepatitis (NASH) with a higher probability of progressing to cirrhosis, and liver-related mortality. Evidence has been found that this progression has been associated with marked alterations in hepatocyte histology and a shift in marker expression of healthy hepatocytes including increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), adipocyte protein (aP2), CD36, interleukin-6 (IL-6), interleukin-18 (IL-18) and adiponectin. This progression shares much in common with the obesity phenotype, which involves a transformation of adipocytes from small, healthy cells to large, dysfunctional ones that contribute to redox imbalance and the progression of metabolic syndrome. Further, activation of Src/ERK signaling via the sodium potassium adenosine triphosphatase (Na/K-ATPase) α-1 subunit in impaired hepatocytes may contribute to redox imbalance, exacerbating the progression of NAFLD. This review hypothesizes that an adipogenic transformation of hepatocytes propagates redox imbalance and that the processes occurring in adipogenesis become activated in fat-laden hepatocytes in liver, thereby driving progression to NAFLD. Further, this review discusses therapeutic interventions to reverse NAFLD including the thiazolidinediones (TZDs) and a variety of antioxidant species. The peptide, pNaKtide, which is an antagonist of Na/K-ATPase signaling, is also proposed as a potential pharmacologic option for reducing reactive oxygen species (ROS) and reversing NAFLD by inhibiting the Na/K-ATPase-modulated ROS amplification loop.

Salvage Stereotactic Body Radiation Therapy for Locally Recurrent Previously Irradiated Head and Neck Squamous Cell Carcinoma: An Analysis from the RSSearch® Registry.

Objectives To report on overall survival (OS), local control (LC), dose-outcome relationships, and related toxicities following stereotactic body radiation therapy (SBRT) for locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN). Methods We queried the prospectively-maintained RSSearch® Registry for patients with rSCCHN treated with five-fraction SBRT from January 2008 to November 2016. Patients with non-squamous cell histology, missing registry data regarding prior irradiation, those treated with less than five fractions of SBRT, and those treated with SBRT in primary or boost settings were excluded. LC and OS were estimated using the Kaplan-Meier method with comparisons between groups completed using log-rank t-tests and multivariable Cox regression. Logistic regression analyses were used to examine factors predictive of toxicity. Results Forty-five rSCCHN patients treated with SBRT delivered in five fractions at 12 radiotherapy centers were identified. Prescription doses ≥ 40 Gy were associated with higher one-year rates of OS, LC, and a higher likelihood of experiencing toxicities. Acute and late toxicity rates were low (22.2% and 15.6%, respectively) and were all Grade 1-2 with only one late Grade 3 esophagitis. Conclusion Salvage SBRT for rSCCHN resulted in outcomes comparable to prior single-institutional reports in a multi-institutional cohort across clinical settings with low toxicity, thus supporting more widespread adoption of SBRT with recommended doses ≥ 40 Gy.

Developing a panel of biomarkers and miRNA in patients with myocardial infarction for early intervention strategies of heart failure in West Virginian population.

BACKGROUND: Myocardial infarction is the most common cause of heart failure. MI has been intricately linked to ventricular remodeling, subsequently leading to the reduction in the cardiac ejection fraction causing HF. The cumulative line of evidence suggests an important role of several biomarkers in modulating the cardiac vasculature, further contributing towards the progression of post-MI complications. Studies have demonstrated, yet not fully established, that an important biomarker, IL-10, has a causal relationship with MI and associated cardiac dysfunction. HYPOTHESIS: This study aims to establish the role of IL-10 as a prognostic marker for the cardiovascular outcomes and to develop a panel of biomarkers and circulating miRNAs that could potentially result in the early detection of HF resulting from MI, allowing for early intervention strategies. METHODS AND RESULTS: Blood was withdrawn and echocardiography assessment was performed on a total of 43 patients that were enrolled, within 24 hours of the incidence of MI. Patients were divided in three main groups, based on the ejection fraction measurement from echocardiography: control (n = 14), MI with normal EF (MI+NEF, n = 13) and MI with low EF (MI+LEF, n = 16). Our results showed that TGFß-1, TNF-α, IL-6 and MMP-9 were upregulated significantly in MI+NEF group and more so in MI+LEF group, as compared to control group (p<0.01). The circulating levels of miR-34a, miR-208b and miR-126 were positively correlated and showed elevated levels in the MI+NEF group, even higher in MI+LEF group, while levels of miR-24 and miR-29a were reduced in MI+NEF, and much lower in MI+LEF, as compared to the control group (p<0.01). Our results also demonstrated a direct correlation of IL-10 with the ejection fraction in patients with MI: IL-10 was elevated in MI+NEF group, however, the levels were significantly low in MI+LEF group suggesting an important role of IL-10 in predicting heart failure. Importantly, our study confirmed the correlation of IL-10 with EF by our follow-up echocardiography assessment that was performed 2 months after the incidence of MI. CONCLUSION: Our results support the clinical application of these serum biomarkers to develop a panel for appropriate prognosis and management of adverse cardiac remodeling and development of heart failure post-myocardial infarction.

Investigating Molecular Connections of Non-alcoholic Fatty Liver Disease with Associated Pathological Conditions in West Virginia for Biomarker Analysis.

Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by a steatosis of the liver that may progress to more serious pathological conditions including: nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. As the prevalence of NAFLD has increased worldwide in recent years, pathophysiology and risk factors associated with disease progression of NAFLD are at the focus of many studies. NAFLD is related to and shares common serum biomarkers with cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome (MetS). West Virginia (WV) is a state with some of the highest rates of CVD, obesity and diabetes mellitus. As NAFLD is closely related to these diseases, it is of particular interest in WV. Currently there is no cost-effective, standardized method used clinically to detect NAFLD prior to the onset of reversible complications. At this time, the diagnosis of NAFLD is made with costly radiologic studies and invasive biopsy. These studies are only diagnostic once changes to hepatic tissue have occurred. The diagnosis of NAFLD by traditional methods may not allow for successful intervention and may not be readily available in areas with already sparse medical resources. In this literature review, we identify a list of biomarkers common among CVD, T2DM, obesity, MetS and NAFLD. From this research we propose the following biomarkers are good candidates for inclusion in a panel of biomarkers for the early detection of NAFLD: adiponectin, AST, ALT, apo-B, CK18, CPS1, CRP, FABP-1, ferritin, GGT, GRP78, HDL-C, IGF-1, IL-1ß, 6, 8, 10, IRS-2PAI-1, leptin, lumican, MDA SREBP-1c and TNF-α. Creating and implementing a biomarker panel for the early detection and attenuation of NAFLD, prior to the onset of irreversible complication would provide maximum benefit and decrease the disease burden on the patients and healthcare system of WV.

Heme Oxygenase Induction Suppresses Hepatic Hepcidin and Rescues Ferroportin and Ferritin Expression in Obese Mice.

Hepcidin, a phase II reactant secreted by hepatocytes, regulates cellular iron levels by increasing internalization of ferroportin-a transmembrane protein facilitating egress of cellular iron. Chronic low-grade inflammatory states, such as obesity, have been shown to increase oxidative stress and enhance hepcidin secretion from hepatocytes and macrophages. Heme-heme oxygenase (HO) is a stress response system which reduces oxidative stress. We investigated the effects of HO-1 induction on hepatic hepcidin levels and on iron homeostasis in hepatic tissues from lean and obese mice. Obese mice exhibited hyperglycemia (p < 0.05); increased levels of proinflammatory cytokines (MCP-1, IL-6, p < 0.05); oxidative stress (p < 0.05); and increased hepatic hepcidin levels (p < 0.05). Enhancement of hepcidin was reflected in the reduced expression of ferroportin in obese mice (p < 0.05). However, this effect is accompanied by a significant decline in ferritin expression. Additionally, there are reduced insulin receptor phosphorylation and attenuation of metabolic regulators pAMPK, pAKT, and pLKB1. Cobalt protoporphyrin- (CoPP-) induced HO-1 upregulation in obese mice reversed these alterations (p < 0.05), while attenuating hepatic hepcidin levels. These effects of CoPP were prevented in obese mice concurrently exposed to an inhibitor of HO (SnMP) (p < 0.05). Our results highlight a modulatory effect of HO on iron homeostasis mediated through the suppression of hepatic hepcidin.

Existence of a Strong Correlation of Biomarkers and miRNA in Females with Metabolic Syndrome and Obesity in a Population of West Virginia.

Objectives: Metabolic syndrome causes complications like cardiovascular disease and type 2 diabetes mellitus (T2DM). As metabolic syndrome develops, altered levels of cytokines and microRNAs (miRNA) are measurable in the circulation. We aimed to construct a panel detecting abnormal levels of cytokines and miRNAs in patients at risk for metabolic syndrome. Methods: Participants included 54 patients from a Family Medicine Clinic at Marshall University School of Medicine, in groups of: Control, Obese, and Metabolic Syndrome (MetS). Results: Serum levels of leptin, adiponectin, leptin: adiponectin ratio, IL-6, six miRNAs (320a, 197-3p, 23-3p, 221-3p, 27a-3p, and 130a-3p), were measured. Among the three groups, leptin, and leptin: adiponectin ratio, and IL-6 levels were highest in MetS, and levels in Obese were greater than Control (p>0.05). Adiponectin levels were lower in Obese compared to Control, but lowest in MetS (p<0.05). MiRNAs levels were lowest in MetS, and levels in Obese were lower than Control (p>0.05). Conclusion: Our results support the clinical application of biomarkers in diagnosing early stage MetS, which will enable attenuation of disease progression before onset of irreversible complications. Since West Virginians are high-risk for developing MetS, our biomarker panel could reduce the disease burden on our population.