Malignant peripheral nerve sheath tumor of the femoral nerve: imaging findings and correlation with histopathology.

Malignant peripheral nerve sheath tumors (MPNST) are rare and aggressive soft tissue sarcomas. MPNST diagnosis is made based on biopsy, but distinct features are present on ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). We present a case of a 24-year-old man presenting with abdominal pain and lower-extremity weakness found to have a large MPNST originating from the left femoral nerve and describe findings on imaging and their histopathologic correlation.

Giant mandibular osteoma, CT findings for the primary care provider.

We report a very rare case of 35-year-old female with a giant mandibular osteoma in the angle of the mandible. We highlight the importance of CT in diagnosing as well as defining the extent of this rare case so that proper management can be undertaken. We also showcase the importance of angiography to show relationship of this mass with the surrounding vessels.

Identification of genes critical for inducing ulcerative colitis and exploring their tumorigenic potential in human colorectal carcinoma.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease leading to continuous mucosal inflammation in the rectum extending proximally towards the colon. Chronic and/or recurrent UC is one of the critical predisposing mediators of the oncogenesis of human colorectal carcinoma (CRC). Perturbations of the differential expression of the UC-critical genes exert an intense impact on the neoplastic transformation of the affected tissue(s). Herein, a comprehensive exploration of the UC-critical genes from the transcriptomic profiles of UC patients was conducted to study the differential expression, functional enrichment, genomic alterations, signal transduction pathways, and immune infiltration level encountered by these genes concerning the oncogenesis of CRC. The study reveals that WFDC2, TTLL12, THRA, and EPHB3 play crucial roles as UC-CRC critical genes and are positively correlated with the molecular transformation of UC to CRC. Taken together, these genes can be used as potential biomarkers and therapeutic targets for combating UC-induced human CRC.

Rib osteochondroma presenting as acute paraparesis.

Osteochondromas are usually osseous outgrowths arising from the metaphyseal region of cortical bone. Moreover, osteochondroma can also arise from flat bones and the spine. However, their origin in the ribs is extremely rare and always near the costochondral junction. We present a 26-year-old male who presented with chief complaints of difficulty in walking for 2 weeks subsequently diagnosed with osteochondroma based on the presence of a cartilage cap on Magnetic resonance imaging.

Oncogenic gain of function due to p53 amyloids occurs through aberrant alteration of cell cycle and proliferation.

Transcription factor p53 (also known as TP53) has been shown to aggregate into cytoplasmic and nuclear inclusions, compromising its native tumor suppressive functions. Recently, p53 has been shown to form amyloids, which play a role in conferring cancerous properties to cells, leading to tumorigenesis. However, the exact pathways involved in p53 amyloid-mediated cellular transformations are unknown. Here, using an in cellulo model of full-length p53 amyloid formation, we demonstrate the mechanism of loss of p53 tumor-suppressive function with concomitant oncogenic gain of functions. Global gene expression profiling of cells suggests that p53 amyloid formation dysregulates genes associated with the cell cycle, proliferation, apoptosis and senescence along with major signaling pathways. This is further supported by a proteome analysis, showing a significant alteration in levels of p53 target proteins and enhanced metabolism, which enables the survival of cells. Our data indicate that specifically targeting the key molecules in pathways affected by p53 amyloid formation, such as cyclin-dependent kinase-1, leads to loss of the oncogenic phenotype and induces apoptosis of cells. Overall, our work establishes the mechanism of the transformation of cells due to p53 amyloids leading to cancer pathogenesis. This article has an associated First Person interview with the first author of the paper.

Proteomic analysis reveals USP7 as a novel regulator of palmitic acid-induced hepatocellular carcinoma cell death.

Nutrient surplus and consequent free fatty acid accumulation in the liver cause hepatosteatosis. The exposure of free fatty acids to cultured hepatocyte and hepatocellular carcinoma cell lines induces cellular stress, organelle adaptation, and subsequent cell death. Despite many studies, the mechanism associated with lipotoxicity and subsequent cell death still remains poorly understood. Here, we have used the proteomics approach to circumvent the mechanism for lipotoxicity using hepatocellular carcinoma cells as a model. Our quantitative proteomics data revealed that ectopic lipids accumulation in cells severely affects the ubiquitin-proteasomal system. The palmitic acid (PA) partially lowered the expression of deubiquitinating enzyme USP7 which subsequently destabilizes p53 and promotes mitotic entry of cells. Our global phosphoproteomics analysis also provides strong evidence of an altered cell cycle checkpoint proteins' expression that abrogates early G2/M checkpoints recovery with damaged DNA and induced mitotic catastrophe leading to hepatocyte death. We observe that palmitic acid prefers apoptosis-inducing factor (AIF) mediated cell death by depolarizing mitochondria and translocating AIF to the nucleus. In summary, the present study provides evidence of PA-induced hepatocellular death mediated by deubiquitinase USP7 downregulation and subsequent mitotic catastrophe.

S-Nitrosylation of OTUB1 Alters Its Stability and Ubc13 Binding.

S-Nitrosylation is a reversible post-translational modification that regulates protein function involving the covalent attachment of the nitric oxide (NO) moiety to sulfhydryl residues of the protein. It is an important regulator in the cell signaling process under physiological conditions. However, the release of an excess amount of NO due to dysregulated NOS machinery causes aberrant S-nitrosylation of proteins, which affects protein folding, localization, and activity. Here, we have shown that OTUB1, a deubiquitinating enzyme, undergoes S-nitrosylation under redox stress conditions in vivo and in vitro. Previously, we have shown that OTUB1 forms an amyloid-like structure that promotes phosphorylation of α-synuclein and neuronal toxicity. However, the mechanistic insight into OTUB1 aggregation remains elusive. Here, we identified that OTUB1 undergoes S-nitrosylation in SH-SY5Y neuroblastoma cells under rotenone-induced stress, as well as excitotoxic conditions, and in rotenone-treated mouse brains. The in vitro S-nitrosylation of OTUB1 followed by mass-spectrometry analysis has identified cysteine-23 and cysteine-91 as S-nitrosylation sites. S-Nitrosylated OTUB1 (SNO-OTUB1) diminished its catalytic activity, impaired its native structure, promoted amyloid-like aggregation, and compromised its binding with Ubc13. Thus, our results demonstrated that nitrosylation of OTUB1 might play a crucial role in regulating the ubiquitin signaling and Parkinson's disease pathology.

Cardiac computed tomography in cardio-oncology: an update on recent clinical applications.

Chemotherapy and radiotherapy have drastically improved cancer survival, but they can result in significant short- and long-term cardiovascular complications, most commonly heart failure from chemotherapy, whilst radiotherapy increases the risk of premature coronary artery disease (CAD), valve, and pericardial diseases. Cardiac computed tomography (CT) with calcium scoring has a role in screening asymptomatic patients for premature CAD, cardiac CT angiography (CTCA) allows the identification of significant CAD, also in the acute settings where concerns exist towards invasive angiography. CTCA integrates the diagnostic work-up and guides surgical/percutaneous management of valvular heart diseases and allows the assessment of pericardial conditions, including detection of effusion and pericardial calcification. It is a widely available and fast imaging modality that allows a one-step evaluation of CAD, myocardial, valvular, and pericardial disease. This review aims to provide an update on its current use and accompanying evidence-base for cardiac CT in the management of cardio-oncology patients.

Socio-Economic Burden of Myocardial Infarction Among Cancer Patients.

Cancer patients face a higher risk of future myocardial infarction (MI), even after completion of anticancer therapies. MI is a critical source of physical and financial stress in noncancer patients, but its impacts associated with cancer patients also saddled with the worry (stress) of potential reoccurrence is unknown. Therefore, we aimed to quantify MI's stress and financial burden after surviving cancer and compare to those never diagnosed with cancer. Utilizing cross-sectional national survey data from 2013 to 2018 derived from publicly available United States datasets, the National Health Interview Survey , and economic data from the National Inpatient Sample , we compared the socio-economic outcomes in those with MI by cancer-status. We adjusted for social, demographic, and clinical factors. Overall, 19,504 (10.2%) of the 189,836 National Health Interview Survey responders reported having cancer for more than 1 year. There was an increased prevalence of MI in cancer survivors compared with noncancer patients (8.8% vs 3.2%, p <0.001). MI was associated with increased financial worry, food insecurity, and financial burden of medical bills (p <0.001, respectively); however, concurrent cancer did not seem to be an effect modifier (p >0.05). There was no difference in annual residual family income by cancer status; however, 3 lowest deciles of residual income representing 21.1% cancer-survivor with MI had a residual income of <$9,000. MI continues to represent an immense source of financial and perceived stress. In conclusion, although cancer patients face a higher risk of subsequent MI, this does not appear to advance their reported stress significantly.

Sequestration of eIF4A by angiomotin: A novel mechanism to restrict global protein synthesis in trophoblast cells.

Enrichment of angiomotin (AMOT) in the ectoplacental cone of E7.5 murine placenta prompted our investigation on the role of AMOT in trophoblast differentiation. We show here that AMOT levels increased in mouse placenta during gestation and also upon induction of differentiation in trophoblast stem cell ex vivo. Proteomic data unravelling AMOT-interactome in trophoblast cells indicated a majority of AMOT interactors to be involved in protein translation. In-depth analysis of AMOT-interactome led to identification of eukaryotic translation initiation factor 4A (eIF4A) as the most plausible AMOT interactor. Loss of function of AMOT enhanced, whereas, gain in function resulted in decline of global protein synthesis in trophoblast cells. Bioinformatics analysis evaluating the potential energy of AMOT-eIF4A binding suggested a strong AMOT-eIF4A interaction using a distinct groove encompassing amino acid residue positions 238 to 255 of AMOT. Co-immunoprecipitation of AMOT with eIF4A reaffirmed AMOT-eIF4A association in trophoblast cells. Deletion of 238 to 255 amino acids of AMOT resulted in abrogation of AMOT-eIF4A interaction. In addition, 238 to 255 amino acid deletion of AMOT was ineffective in eliciting AMOT's function in reducing global protein synthesis. Interestingly, AMOT-dependent sequestration of eIF4A dampened its loading to the m7 -GTP cap and hindered its interaction with eIF4G. Furthermore, enhanced AMOT expression in placenta was associated with intrauterine growth restriction in both rats and humans. These results not only highlight a hitherto unknown novel function of AMOT in trophoblast cells but also have broad biological implications as AMOT might be an inbuilt switch to check protein synthesis in developmentally indispensable trophoblast cells.

Contemporary Trends and Outcomes of Percutaneous and Surgical Mitral Valve Replacement or Repair in Patients With Cancer.

In the era of emerging options for mitral valvular intervention, we sought to characterize the relative utilization, outcomes, and posthospital dispositions of patients referred for transcatheter mitral valve repair (TMVRepair) and surgical mitral valve procedures (SMVP), by cancer-status. Leveraging the National Inpatient Sample, a representative national dataset, ICD-9 codes for all adults >18 years with co-morbid mitral regurgitation, and cancer without metastatic disease admitted from 2003 to 2015 were queried. TMVRepair was performed in 700 hospitalizations from 2012 to 2015, whereas SMVP was utilized during 12,863 hospitalizations from 2003 to 2015. During follow-up, we observed a proportional increase in TMVRepair utilization among cancer patients (vs noncancer), particularly in 2015 (14.2% vs 8.2%, p <0.0001). There was no difference in in-hospital mortality (1.4% vs 1.8%, p = 0.71), ischemic stroke (0.7% vs 0.6%, p = 0.97), major bleeding (8.6% vs 10.9%, p = 0.36), and home discharge (62.1% vs 65.7%, p = 0.45) by cancer-status among patients who underwent TMVRepair; but, cost of care was increased ($52,325 vs $48,832, p <0.0001). Similarly, there was no difference in in-hospital mortality (3.1% vs 3.4%, p = 0.36), ischemic stroke (2.6% vs 3.1%, p = 0.16) as well as the cost-of-care ($58,106 vs $58,844, p = 0.49) among those who underwent SMVP across the same period; but, cancer was associated with increased major bleeding (34.9% vs 30.5%, p <0.0001), and lower likelihood of home discharge (32.8% vs 38.6%, p <0.0001). In conclusion, TMVRepair and SMVP were associated with comparable in-hospital mortality and outcomes in cancer versus noncancer patients. However, cancer patients treated with SMVP experienced more frequent bleeding related complications compared with noncancer patients.

Health care utilization and mortality associated with heart failure-related admissions among cancer patients.

AIMS: Heart failure (HF) outcomes continue to improve with widespread use of new therapies. Concurrently, cancer survival has dramatically improved. Yet whether cancer patients share similar strategies and outcomes of inpatient HF treatment to those without HF is unknown. We sought to assess the contemporary impacts of cancer on inpatient HF outcomes over time. METHODS AND RESULTS: The retrospective National Inpatient Sample (2003-15) and National Readmissions Database (2013-14) registries were queried for adults admitted for HF and stratified for cancer status, excluding cases of metastatic disease. Temporal trends in HF admissions, hospital charge rates, length of hospitalization, HF-related procedure utilization, in-hospital mortality, and hospital readmissions were analysed. Over 13 years of follow-up, there were 12 769 077 HF admissions (mean age 73 years, 50.8% female, 30.8% non-White), among which 1 413 287 (11%) had a co-morbid cancer diagnosis. Cancer patients were older, were predominantly male, and tended to be smokers. Over time, HF admission rates among cancer patients increased, despite a concurrent decrease among patients without cancer (P < 0.0001). After propensity matching, in-hospital mortality was significantly higher among cancer HF patients (5.1% vs. 2.9%, P < 0.0001). Additionally, HF-related procedure utilization was disproportionately lower among cancer patients (0.30 vs. 0.35 procedures/HF hospitalization, P < 0.001); the presence of cancer was associated with increased costs, length of hospitalizations, and all-cause readmissions, but fewer HF readmissions (P < 0.0001, each). CONCLUSIONS: While the incidence of HF hospitalizations has increased among cancer patients, they do not appear to share the same rates of advanced HF care, readmissions trends, or reductions in in-hospital mortality. Future studies targeting modifiable factors related to these differences are needed.

Sinonasal paraganglioma and Cushing's syndrome: A rare association.

In general, paragangliomas are symptomatic tumors, which may be clinically taken for other tumors, benign or malignant lesions. Paragangliomas of the nasal cavity and paranasal sinuses are an extremely rare entity and what is even rarer is its association with ectopic adrenocorticotropic hormone production. We report this very rare case to highlight the rare association of Cushing's syndrome with nasal paraganglioma and the importance of total surgical resection in its treatment.

Strangulated Morgagni's Hernia: A Rare Diagnosis and Management.

Morgagni hernia is a rare type of congenital diaphragmatic hernia. It accounts for only 3% of all diaphragmatic hernias. The defect is small and hernia being asymptomatic in the majority presents late in adulthood. Obstruction or incarceration in Morgagni hernia is uncommon. We report a rare occurrence of strangulated Morgagni hernia. A 40-year-old gentleman presented to our emergency department with features of intestinal obstruction. Computed tomography of the chest and abdomen showed a strangulated right Morgagni hernia. An exploratory laparotomy was performed with resection of the ischemic bowel segment with anastomosis and a primary repair of the diaphragmatic defect. Postoperative recovery was uneventful and asymptomatic at follow-up.

A Case of Lingual Thyroid Presenting with Severe Hematemesis in Pregnancy.

Lingual thyroid is a rare anomaly with symptoms such as upper airway obstruction, dysphagia, or hypothyroidism. However, bleeding is a very rare manifestation. This report describes a case of lingual thyroid in women with 28 weeks of amenorrhea and hematemesis, and its course of diagnosis and treatment. The pathogenesis of lingual thyroid is unknown. Although ectopic lingual thyroid is usually not managed surgically, excision of ectopic lingual thyroid can be lifesaving when it is causing bleeding or airway obstruction. However, during pregnancy, surgery is the preferred mode of treatment.

Rhinosporidiosis: A Rare Cause of Proptosis and an Imaging Dilemma for Sinonasal Masses.

Background. Rhinosporidiosis is a common disease entity in tropical countries; however, it can be encountered in other parts of the world as well due to increasing medical tourism. It may mimic other more malignant and vigorous pathologies of the involved part. Case Report. We present a case of a 36-year-old male presenting with proptosis due to involvement of nasolacrimal duct which is rare. We will discuss typical CT and MRI features of the disease which were present in the case. Conclusion. For a surgeon and a radiologist, this is a necessary differential to be kept in mind for sinonasal masses. CT and MRI are invaluable investigations. However, FNAC is confirmatory. Both clinical and radiological aspects are required to reach correct diagnosis.