Effect of Hypochlorites on the Compressive Strength and Surface Hardness of Type V Dental Stone: An In Vitro Study.

AIM: The study aimed to evaluate the compressive strength and surface hardness of a type V dental stone after hypochlorite disinfection. MATERIALS AND METHODS: Two types of specimens were made according to the American Dental Association (ADA) specification no. 25 for each wet compressive strength, dry compressive strength, and surface hardness. The specimens were split into three groups with 30 samples each according to the type of disinfection. All specimens were immersed in their respective disinfecting solutions for 30 minutes at room temperature and after removal, they were left to dry for 24 hours at room temperature. Total five cycles of immersion and drying were followed. A compressive strength test was done using a universal testing machine. Wet compressive strength was tested one hour after the last cycle and dry compressive strength was tested 7 days after the last cycle. Surface hardness was measured after 48 hours using Vickers hardness test. The results were statistically analyzed. RESULTS: There was a statistical difference between the calcium hypochlorite and sodium hypochlorite groups for both dry and wet compressive strength. The mean wet compressive strength of calcium hypochlorite was higher when compared to the sodium hypochlorite group and it was statistically significant (p = 0.042). The results were similar and statistically significant (p = 0.003) for dry compressive strength. When the mean surface hardness of the sodium hypochlorite (As) group was compared to calcium hypochlorite the results were highly significant (p = 0.0001) with the mean surface hardness of the calcium hypochlorite group more than the sodium hypochlorite group. CONCLUSION: Calcium hypochlorite used as a disinfectant showed better compressive strength and surface hardness when compared to sodium hypochlorite as a disinfectant. CLINICAL SIGNIFICANCE: Dental casts poured in the contaminated impressions which might not be disinfected at all or properly. They also come in contact with the prosthesis that might be tried inside the patient's mouth and sent to a lab for corrections without disinfecting the cast causing cross-contamination between patients, dentists, and laboratory personnel. However, immersion disinfection with sodium or calcium hypochlorite might affect important properties of the cast. Any negative effect on the mechanical or physical properties of the cast will affect the final outcome of the prosthesis.

Lactate Dehydrogenase B and Pyruvate Oxidation Pathway Associated With Carfilzomib-Related Cardiotoxicity in Multiple Myeloma Patients: Result of a Multi-Omics Integrative Analysis.

Multiple myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), an irreversible proteasome inhibitor being used to treat relapsed and refractory MM, has been associated with cardiotoxicity, including heart failure. We hypothesized that a multi-omics approach integrating data from different omics would provide insights into the mechanisms of CFZ-related cardiovascular adverse events (CVAEs). Plasma samples were collected from 13 MM patients treated with CFZ (including 7 with CVAEs and 6 with no CVAEs) at the University of Florida Health Cancer Center. These samples were evaluated in global metabolomic profiling, global proteomic profiling, and microRNA (miRNA) profiling. Integrative pathway analysis was performed to identify genes and pathways differentially expressed between patients with and without CVAEs. The proteomics analysis identified the up-regulation of lactate dehydrogenase B (LDHB) [fold change (FC) = 8.2, p = 0.01] in patients who experienced CVAEs. The metabolomics analysis identified lower plasma abundance of pyruvate (FC = 0.16, p = 0.0004) and higher abundance of lactate (FC = 2.4, p = 0.0001) in patients with CVAEs. Differential expression analysis of miRNAs profiling identified mir-146b to be up-regulatein (FC = 14, p = 0.046) in patients with CVAE. Pathway analysis suggested that the pyruvate fermentation to lactate pathway is associated with CFZ-CVAEs. In this pilot multi-omics integrative analysis, we observed the down-regulation of pyruvate and up-regulation of LDHB among patients who experienced CVAEs, suggesting the importance of the pyruvate oxidation pathway associated with mitochondrial dysfunction. Validation and further investigation in a larger independent cohort are warranted to better understand the mechanisms of CFZ-CVAEs.

Newly diagnosed cardiovascular disease in patients treated with immune checkpoint inhibitors: a retrospective analysis of patients at an academic tertiary care center.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients treated with ICIs at a large, tertiary care center. METHODS: All patients with a cancer diagnosis who received any ICI treatment in the University of Florida's Integrated Data Repository from 2011 to 2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. RESULTS: Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55-4.95, p = 0.0006). CONCLUSIONS: This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy in a real-world clinical setting.

Extramedullary Hematopoiesis in Mismatch Repair Deficient Colon Cancer Patient on Adjuvant Chemotherapy.

A 59-year-old male presented with a two-month history of abdominal pain and was found to have an obstructing cecal mass. Colonoscopy and biopsy confirmed invasive adenocarcinoma. Immunohistochemical analyses for mismatch repair (MMR) proteins revealed the loss of MLH1 as well as PMS2 in cancerous nuclei, which makes the tumor MMR deficient. Negative germline testing for MMR proteins ruled out the Lynch syndrome. After negative staging computerized tomography scan for distant metastases, he underwent ileocolectomy with ileotransverse colonic anastomosis. Final pathological analysis revealed poorly differentiated adenocarcinoma with signet ring features, negative margins, and 3/22 lymph nodes positive, classified as stage IIIB (T4aN1bM0). Adjuvant chemotherapy with modified FOLFOX (leucovorin calcium/folinic acid, fluorouracil, and oxaliplatin) was started without the use of any growth factor support. After cycle 9 of 12, he developed mild transaminitis, carcinoembryonic antigen elevation, and interval development of two heterogeneously enhancing hepatic lesions. Biopsy of both of these lesions revealed extramedullary hematopoiesis (EMH), with no evidence of metastatic disease. He completed adjuvant chemotherapy without complication, and these liver lesions have decreased in size during the follow-up period of almost two years thus far. EMH is extremely rare in patients with colon cancer. Contributing factors include therapy-specific (growth factor support), bone marrow suppression secondary to chemotherapy and radiation therapy, and tumor-specific factors (cytokine and growth factors released by the tumor). To the best of our knowledge, this is the first case report of EMH in an MMR deficient colon cancer patient on adjuvant FOLFOX. MMR-deficient tumors show signs of a high degree of infiltration with CD8+ cytotoxic T lymphocytes as well as helper T cells, leading to increased production of cytokines, such as interferon-γ. This could be a potential etiology behind EMH in our patient who was MMR deficient. The role of the MMR-deficient state in the development of EMH should be explored further.

Orbital metastasis of squamous cell cervical cancer: A case report and review of literature.

Common sites of metastatic disease seen in cervical cancer most often include the lungs and liver. Orbital metastasis secondary to cervical carcinoma is a rare form of metastatic disease. We report a 73-year-old woman who presented with ocular symptoms found to be secondary to orbital metastasis of cervical cancer. She underwent palliative radiation to the orbit and pelvis followed by systemic chemotherapy with carboplatin, paclitaxel, and bevacizumab. Prompt intervention was able to salvage her vision and improve her quality of life significantly. We identified 5 similar reported cases in which orbital metastasis was diagnosed simultaneously at the time of cervical cancer diagnosis. In these five cases, patients were treated with a combination of radiation and chemotherapy. Our case demonstrates an unusual presentation of isolated orbital metastatic disease secondary to squamous cell carcinoma of the cervix. Physicians should be aware that cervical cancer may metastasize to the eye leading to vision loss, and prompt intervention may be able to salvage one's vision and improve quality of life.

Acquired von Willebrand syndrome in association with multiple myeloma: remission after stem cell transplant.

Acquired von Willebrand syndrome is a rare bleeding disorder characterised by a later age of onset without a personal or family history of bleeding diathesis. It is vital to discern acquired von Willebrand syndrome from inherited von Willebrand disease and other acquired bleeding disorders as management differs significantly. Acquired von Willebrand syndrome is usually secondary to an underlying disorder such as lymphoproliferative disorder, myeloproliferative neoplasm, solid tumour, cardiovascular disorder, autoimmune disorders or hypothyroidism. Diagnosis is often delayed with a significant risk of morbidity and even mortality. Here we present a case of a 74-year-old man with an acquired bleeding disorder and work up suggestive of acquired von Willebrand syndrome secondary to immunoglobulin G kappa multiple myeloma. He was treated successfully with intravenous immunoglobulin, von Willebrand Factor/Coagulation Factor VIII Complex (human), myeloma directed chemotherapy and autologous stem cell transplantation. We also discuss the management strategies that are largely based on retrospective studies and case reports.

Bleeding and Thrombotic Risk in Low Dose Heparin Infusion as Compared to Standard Dose Heparin Infusion.

Intravenous unfractionated heparin (UFH) remains one of the most commonly used anticoagulants in the hospital setting. The optimal protocol for initiation and maintenance of UFH has been difficult to determine. Over the past two decades, weight-based nomogram protocols have gained favor. Herein, we present a retrospective study of 377 patients at a single tertiary academic center treated with low intensity (LI) and standard intensity (SI) UFH protocols for therapeutic anticoagulation. UFH levels are measured by anti-Xa assay activity with therapeutic levels of 0.30 to 0.70 IU/mL for SI and 0.25 to 0.35 IU/mL for LI.  Patients treated on the LI protocol were more likely to have had a previous history of bleeding and lower baseline hemoglobin. Incidence of new or worsening thrombus while on UFH was comparable between both protocols (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.29-2.98, p=0.899). Patients on LI protocol had higher incidence of bleeding while on UFH (OR 1.21, 95% CI 0.51-2.89, p=0.667). Our study thus suggests that the LI protocol may have comparable efficacy to the SI protocol in treating venous thromboembolism (VTE) and that target anti-Xa levels of 0.25 to 0.35 IU/mL may be more optimal in high-risk patients.

Predicting in-hospital mortality of patients with febrile neutropenia using machine learning models.

BACKGROUND: Febrile neutropenia (FN) has been associated with high mortality among adults with cancer. Current systems for early detection of inpatient FN mortality are based on scoring indexes that require intensive physicians' subjective evaluation. OBJECTIVE: In this study, we leveraged machine learning techniques to build a FN mortality risk evaluation tool focused on FN admissions without physicians' subjective evaluation. METHODS: We used the National Inpatient Sample and Nationwide Inpatient Sample (NIS) that included mortality data among adult inpatients who were diagnosed with FN during a hospital admission. Machine learning techniques that we compared included linear models (ridge logistic regression and linear support vector machine) and non-linear models (gradient boosting tree and neural network). The primary outcome for this study was death among individuals with a recorded FN admission. Model comparison was evaluated based on areas under the receiver operating characteristic curve (AUROC) and model performance was estimated using 30 % test set created via stratified split. RESULTS: Our analysis detected 126,013 adult admissions within the NIS data that were diagnosed with FN, among which 5,856 were declared as deceased (4.6 %). Our machine learning results demonstrate linear models and non-linear models achieved areas under the receiver operating characteristic (AUROC) around 92 % in survival prediction. CONCLUSIONS: We developed machine learning models that do not require physicians' subjective evaluation for FN mortality risk prediction.

Single-institution Retrospective Analysis of Prognostic Factors Influencing Very Late-onset Post-transplant Lymphoproliferative Disorder.

Background Post-transplant lymphoproliferative disorder (PTLD) is a rare complication following transplant (solid organ or allogeneic) due to the proliferation of lymphoid cells in the immunosuppressed state. The incidence of PTLD follows a bimodal distribution, with high incidence immediately after transplant (early-onset PTLD), followed by a decline and then a high-incidence again five years after transplantation (late-onset PTLD). This study exclusively aims to identify prognostic factors for the subgroup of PTLD, described as very late-onset PTLD, occurring after 10 years of transplant. Methods This study was conducted at the University of Florida, with the requisite study population identified through the cancer registry. Data were collected by individual chart review and analyzed. Survival estimates and univariate and multivariate analyses were performed to measure the effects of each variable on overall survival. Results A total of 33 patients were identified, with a median age at transplant of 42.3 years, while the median age at PTLD diagnosis was 54.7 years. Median time from transplant to PTLD diagnosis was 13.3 years. Kidney (30.3%), liver (27.3%), and heart (24.2%) transplants were the most common allografts associated with very late PTLD development. The most common pathology was diffuse large B-cell lymphoma (DLBCL) in 45.5% of patients. CHOP+/-R (cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), prednisone, rituximab) was the most common chemo regimen used as the initial choice in 36.4% of patients. Median survival was 5.4 years. Univariate analysis showed that age at diagnosis over 65, male gender, bone marrow involvement, past medical history (PMH) of malignancy, immunosuppression regimen at PTLD diagnosis, and initial and final best response to treatment were statistically significant (p <0.05) factors associated with survival. On multivariate analysis, bone marrow involvement was significantly associated with poor survival (p=0.008). Surprisingly, performance status, Epstein-Barr virus (EBV) status, pathology type, Ann-Arbor stage, and chemotherapy regimen were not significantly associated with survival. At the end of the study, 48.5% of patients achieved complete remission and the allograft survived in 84.8%. Conclusions In this retrospective study of very-late onset PTLD, we identified factors associated with survival different from early and late PTLD. These factors should be considered during the treatment of this subgroup of PTLD patients.

Survival trends of metastatic small intestinal neuroendocrine tumor: a population-based analysis of SEER database.

BACKGROUND: Incidence of small intestinal neuroendocrine tumors (SNETs) is increasing and they now comprise the most common types of small intestinal cancer. SNETs frequently present with distant metastasis. Significant uncertainty prevails with regards to the surgical management strategies in metastatic SNETs. Therefore, we aim to analyze survival trends in metastatic SNET patients stratified by type of surgical treatment. METHODS: We analyzed the data from the SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2016 Sub (1973-2014 varying). Relative survival rates (RSRs) and hazard ratios (HRs) were measured for patients diagnosed with metastatic SNET between 2000 and 2014. Treatment received was divided into two broad categories; surgical resection and no surgery and further subcategorized into local resection (LR) (surgery of the primary tumor only) and radical resection (RR) (surgery for primary tumor and metastasectomy). RESULTS: We identified 1,138 metastatic SNET cases. Median age was 61 years. Median survival was 41 months and 5 year RSR was 72%. Age >50 years (HR 2.10, P<0.001), poorly differentiated histology (HR 3.50, P<0.001) and tumor size >2 cm (HR 1.27, P=0.07), showed poor outcome. The group which did not receive any tumor directed surgery showed the worst survival (5 years RSR 45.30% vs. 76%, respectively for no surgery vs. surgery group, P<0.001). We found no significant difference in survival between LR and RR (HR 1.01, 95% CI: 0.73-1.40, P=0.92). Upon further stratification, surgery significantly improved survival on patients who were >50 years (HR 0.37), and for primary tumor location in the duodenum (HR 0.13). CONCLUSIONS: Surgery for the primary tumor (LR or RR) significantly improved 5-year survival even in the presence of distant metastasis irrespective of primary tumor size, grade, or histology. Poor prognostic factors include, age >50 years, duodenal primary, tumor size >2 cm, and poorly differentiated histology.

Cardiotoxicity due to targeted anticancer agents: a growing challenge.

The emergence of various targeted anticancer agents has led us to uncharted territory secondary to their cardiotoxic potential with many burning questions, which in turn has led to the evolution of the cardio-oncology field. These targeted agents differ in their cardiovascular complication (CVC) potential even within the same class and it is very difficult to design screening tests that can predict CVCs. Moreover, there is a need for more research to answer many crucial questions, since these toxicities are unanticipated and can lead to poor overall survival of cancer patients. We still do not clearly understand the mechanism for such toxicity, risk factors, and natural history. A better understanding of the underlying risk factors and identification of biomarkers would help us develop protocols for appropriate monitoring strategies which in turn would help capture these toxicities at early stages. In this succinct review, we try to focus on CVC definition, summarize some published research, and point to areas of unmet need in this new field.

EUS-FNA for pancreatic neuroendocrine tumors: a tertiary cancer center experience.

OBJECTIVES: Pancreatic neuroendocrine tumors (PNET) are fairly uncommon. Recent data highlight the importance of EUS in diagnosis of PNET. With this background, we decided to review our experience from a tertiary cancer center with regard to the presentation and clinical features of PNET and the diagnostic utility of EUS-FNA in this scenario. METHODS: We identified patients who underwent EUS at our institution between January 1st 2001 and December 31st 2009 for a suspected PNET. Data on clinical features, cross-sectional imaging findings, EUS findings, and cytology results were collected. RESULTS: A total of 81 patients were referred for EUS-FNA for a suspected PNET. Mean age was 58.1 years. There were 41 (50.6%) males. PNET was found incidentally in 38 (46.9%) patients. Computed tomography scanning identified a pancreatic mass in 72 out of 79 (91.1%) cases. Mean diameter of the largest lesion seen on EUS was 27.5 mm (range: 6.9-80 mm). The most common site (34; 42%) was the head of the pancreas. EUS-FNA correctly confirmed a PNET in 73 out of 81 cases with diagnostic accuracy of 90.1%. Seven (8.6%) out of 81 patients had functional lesions, including three gastrinomas and four insulinomas. Liver metastases were found in 31 out of 81 (38.3%) cases. Of the 31 patients with liver metastasis, the mean diameter of lesions on EUS was 33.9 mm compared with 23.5 mm in patients without liver metastasis (P = 0.005). CONCLUSION: EUS-FNA is a reliable modality for further characterization of suspected lesions and for establishing a tissue diagnosis. The occurrence of complications of EUS-FNA in this setting is low. Non-functional PNET are more frequently encountered than functional PNET.