IU Indianapolis ScholarWorks :: Browsing by Subject "Prognosis"

Browsing by Subject "Prognosis"

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ADAM8 is expressed widely in breast cancer and predicts poor outcome in hormone receptor positive, HER-2 negative patients
(BMC, 2023-08-11) Pianetti, Stefania; Miller, Kathy D.; Chen, Hannah H.; Althouse, Sandra; Cao, Sha; Michael, Steven J.; Sonenshein, Gail E.; Mineva, Nora D.; Biostatistics and Health Data Science, School of Medicine
Background: Breast malignancies are the predominant cancer-related cause of death in women. New methods of diagnosis, prognosis and treatment are necessary. Previously, we identified the breast cancer cell surface protein ADAM8 as a marker of poor survival, and a driver of Triple-Negative Breast Cancer (TNBC) growth and spread. Immunohistochemistry (IHC) with a research-only anti-ADAM8 antibody revealed 34.0% of TNBCs (17/50) expressed ADAM8. To identify those patients who could benefit from future ADAM8-based interventions, new clinical tests are needed. Here, we report on the preclinical development of a highly specific IHC assay for detection of ADAM8-positive breast tumors. Methods: Formalin-fixed paraffin-embedded sections of ADAM8-positive breast cell lines and patient-derived xenograft tumors were used in IHC to identify a lead antibody, appropriate staining conditions and controls. Patient breast cancer samples (n = 490) were used to validate the assay. Cox proportional hazards models assessed association between survival and ADAM8 expression. Results: ADAM8 staining conditions were optimized, a lead anti-human ADAM8 monoclonal IHC antibody (ADP2) identified, and a breast staining/scoring control cell line microarray (CCM) generated expressing a range of ADAM8 levels. Assay specificity, reproducibility, and appropriateness of the CCM for scoring tumor samples were demonstrated. Consistent with earlier findings, 36.1% (22/61) of patient TNBCs expressed ADAM8. Overall, 33.9% (166/490) of the breast cancer population was ADAM8-positive, including Hormone Receptor (HR) and Human Epidermal Growth Factor Receptor-2 (HER2) positive cancers, which were tested for the first time. For the most prevalent HR-positive/HER2-negative subtype, high ADAM8 expression identified patients at risk of poor survival. Conclusions: Our studies show ADAM8 is widely expressed in breast cancer and provide support for both a diagnostic and prognostic value of the ADP2 IHC assay. As ADAM8 has been implicated in multiple solid malignancies, continued development of this assay may have broad impact on cancer management.
Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis
(BMC, 2019-03-14) Lawlor, Rita T.; Veronese, Nicola; Pea, Antonio; Nottegar, Alessia; Smith, Lee; Pilati, Camilla; Demurtas, Jacopo; Fassan, Matteo; Cheng, Liang; Luchini, Claudio; Pathology and Laboratory Medicine, School of Medicine
Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by a broad range of neoplasms to maintain telomere length, permitting uncontrolled replication during their progression. ALT has been described in different types of sarcoma, but a comprehensive analysis of its clinical significance is still lacking. Therefore, we provide here the first meta-analysis on this topic. METHODS: We searched SCOPUS and PubMed through July 2018 to identify all studies that investigated the prognostic role of ALT in sarcomas. We considered the risk of death (risk ratio, RR) calculated as the number of death vs. total participants during follow-up in ALT+ versus ALT- patients as the primary outcome. The secondary outcome was the hazard ratio (HR), adjusted for the maximum number of covariates available, using ALT- patients as reference. RESULTS: Eight articles comprising a total of 551 patients with sarcomas (226 ALT+ and 325 ALT-) were selected. The ALT+ group showed a higher mitotic count and a higher tumor grade compared with the ALT- group (p < 0.01). Furthermore, we demonstrate a strong impact of ALT on survival. In fact, ALT+ patients showed a statistically significant higher risk of death than ALT- patients, when also considering data from multivariate analyses (RR = 1.50; 95% CI: 1.15-1.96; p = 0.003; HR = 2.02; 95% CI: 1.22-3.38; p = 0.007). CONCLUSIONS: Our results indicate that ALT is associated with an increased risk of death in patients with sarcoma. In these neoplasms, ALT should be taken into account for a precise prognostic stratification and design of potential therapeutic strategies.
Assessment and Management of Hypertension among Patients on Peritoneal Dialysis
(American Society of Nephrology., 2019-02-07) Vaios, Vasilios; Georgianos, Panagiotis I.; Liakopoulos, Vassilios; Agarwal, Rajiv; Medicine, School of Medicine
Approximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.
Chromosomal 1q21 abnormalities in multiple myeloma: a review of translational, clinical research, and therapeutic strategies
(Taylor & Francis, 2021) Bisht, Kamlesh; Walker, Brian; Kumar, Shaji K.; Spicka, Ivan; Moreau, Philippe; Martin, Tom; Costa, Luciano J.; Richter, Joshua; Fukao, Taro; Macé, Sandrine; van de Velde, Helgi; Medicine, School of Medicine
Multiple myeloma (MM) remains an incurable disease with a median overall survival of approximately 5 years. Gain or amplification of 1q21 (1q21+) occurs in around 40% of patients with MM and generally portends a poor prognosis. Patients with MM who harbor 1q21+ are at increased risk of drug resistance, disease progression, and death. New pharmacotherapies with novel modes of action are required to overcome the negative prognostic impact of 1q21+. Areas covered: This review discusses the detection, biology, prognosis, and therapeutic targeting of 1q21+ in newly diagnosed and relapsed MM. Patients with MM and 1q21+ tend to present with higher tumor burden, greater end-organ damage, and more co-occurring high-risk cytogenetic abnormalities than patients without 1q21+. The chromosomal rearrangements associated with 1q21+ result in dysregulation of genes involved in oncogenesis. Identification and characterization of the 1q21+ molecular targets are needed to inform on prognosis and treatment strategy. Clinical trial data are emerging that addition of isatuximab to combination therapies may improve outcomes in patients with 1q21+ MM. Expert opinion: In the next 5 years, the results of ongoing research and trials are likely to focus on the therapeutic impact and treatment decisions associated with 1q21+ in MM.
Circulating Extracellular Vesicles Carrying Sphingolipid Cargo for the Diagnosis and Dynamic Risk Profiling of Alcoholic Hepatitis
(Wolters Kluwer, 2021) Sehrawat, Tejasav S.; Arab, Juan P.; Liu, Mengfei; Amrollahi, Pouya; Wan, Meihua; Fan, Jia; Nakao, Yasuhiko; Pose, Elisa; Navarro-Corcuera, Amaia; Dasgupta, Debanjali; Liao, Chieh-Yu; He, Li; Mauer, Amy S.; Avitabile, Emma; Ventura-Cots, Meritxell; Bataller, Ramon A.; Sanyal, Arun J.; Chalasani, Naga P.; Heimbach, Julie K.; Watt, Kymberly D.; Gores, Gregory J.; Gines, Pere; Kamath, Patrick S.; Simonetto, Douglas A.; Hu, Tony Y.; Shah, Vijay H.; Malhi, Harmeet; Medicine, School of Medicine
Background and aims: Alcoholic hepatitis (AH) is diagnosed by clinical criteria, although several objective scores facilitate risk stratification. Extracellular vesicles (EVs) have emerged as biomarkers for many diseases and are also implicated in the pathogenesis of AH. Therefore, we investigated whether plasma EV concentration and sphingolipid cargo could serve as diagnostic biomarkers for AH and inform prognosis to permit dynamic risk profiling of AH subjects. Approach and results: EVs were isolated and quantified from plasma samples from healthy controls, heavy drinkers, and subjects with end-stage liver disease (ESLD) attributed to cholestatic liver diseases and nonalcoholic steatohepatitis, decompensated alcohol-associated cirrhosis (AC), and AH. Sphingolipids were quantified by tandem mass spectroscopy. The median plasma EV concentration was significantly higher in AH subjects (5.38 × 1011 /mL) compared to healthy controls (4.38 × 1010 /mL; P < 0.0001), heavy drinkers (1.28 × 1011 /mL; P < 0.0001), ESLD (5.35 × 1010 /mL; P < 0.0001), and decompensated AC (9.2 × 1010 /mL; P < 0.0001) disease controls. Among AH subjects, EV concentration correlated with Model for End-Stage Liver Disease score. When EV counts were dichotomized at the median, survival probability for AH subjects at 90 days was 63.0% in the high-EV group and 90.0% in the low-EV group (log-rank P value = 0.015). Interestingly, EV sphingolipid cargo was significantly enriched in AH when compared to healthy controls, heavy drinkers, ESLD, and decompensated AC (P = 0.0001). Multiple sphingolipids demonstrated good diagnostic and prognostic performance as biomarkers for AH. Conclusions: Circulating EV concentration and sphingolipid cargo signature can be used in the diagnosis and differentiation of AH from heavy drinkers, decompensated AC, and other etiologies of ESLD and predict 90-day survival permitting dynamic risk profiling.
Circulating Tumor Cells in Renal Cell Carcinoma: Recent Findings and Future Challenges
(Frontiers, 2019-04-05) Santoni, Matteo; Cimadamore, Alessia; Cheng, Liang; Lopez-Beltran, Antonio; Battelli, Nicola; Massari, Francesco; Scarpelli, Marina; Galosi, Andrea Benedetto; Bracarda, Sergio; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
Clinical Utility of the 40-Gene Expression Profile (40-GEP) Test for Improved Patient Management Decisions and Disease-Related Outcomes when Combined with Current Clinicopathological Risk Factors for Cutaneous Squamous Cell Carcinoma (cSCC): Case Series
(Springer, 2022-02) Au, Jeremiah H.; Hooper, Perry B.; Fitzgerald, Alison L.; Somani, Ally-Khan; Dermatology, School of Medicine
Introduction While improvements have been made to risk assessment of cutaneous squamous cell carcinoma (cSCC) patients, there is a critical need for a uniform and more precise stratification system of their care. To address this unmet clinical need, a prognostic 40-gene expression profile (40-GEP) test has recently been developed and independently validated to show improved stratification of metastatic risk in high-risk cSCC patients compared with current staging systems. Methods Two cSCC cases, both male with similar patient profiles and the same staging status across two different staging systems, yet with opposing outcomes, were chosen for retrospective review of their primary biopsy using the 40-GEP test. Results Case 1 declined further treatment, even when presented with evidence of a small focus of cSCC found in the last layer of nonmarginal tissue obtained from Mohs micrographic surgery (MMS). Case 1 remained recurrence free, and retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 1 result (low likelihood of metastasis). Case 2, even with subsequent clearing of the primary cSCC with MMS, noted another metastatic cSCC 3 months later. Case 2, after multimodal adjuvant treatments, died due to disease progression. Retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 2B result (high likelihood of metastasis). Conclusions The cases discussed highlight the utility in 40-GEP to provide additional information to guide treatment decisions and improve outcomes. Integrating novel molecular prognostication with traditional clinicopathological risk factors can improve stratification of high-risk cSCC patients and may inform selection of risk-appropriate treatment and surveillance strategies.
Comparison of CSF phosphorylated tau 181 and 217 for cognitive decline
(Wiley, 2022) Mielke, Michelle M.; Aakre, Jeremiah A.; Algeciras-Schimnich, Alicia; Proctor, Nicholas K.; Machulda, Mary M.; Eichenlaub, Udo; Knopman, David S.; Vemuri, Prashanthi; Graff-Radford, Jonathan; Jac, Clifford R., Jr.; Petersen, Ronald C.; Dage, Jeffrey L.; Neurology, School of Medicine
Introduction: The prognostic utility of cerebrospinal fluid (CSF) phosphorylated tau 217 (p-tau217) and p-tau181 is not understood. Methods: Analyses included 753 Mayo Clinic Study on Aging participants (median age = 71.6; 57% male). CSF amyloid beta (Aβ)42 and p-tau181 were measured with Elecsys immunoassays. CSF p-tau181 and p-tau217 were also measured with Meso Scale Discovery (MSD). We used Cox proportional hazards models for risk of mild cognitive impairment (MCI) and linear mixed models for risk of global and domain-specific cognitive decline and cortical thickness. Analyses were stratified by elevated brain amyloid based on CSF Aβ42 or amyloid positron emission tomography for those with imaging. Results: CSF p-tau217 was superior to p-tau181 for the diagnosis of Alzheimer's disease (AD) pathology. CSF MSD p-tau181 and p-tau217 were associated with risk of MCI among amyloid-positive individuals. Differences between CSF p-tau measures predicting cortical thickness were subtle. Discussion: There are subtle differences for CSF p-tau217 and p-tau181 as prognostic AD markers.
Computational Image Analysis Identifies Histopathological Image Features Associated With Somatic Mutations and Patient Survival in Gastric Adenocarcinoma
(Frontiers Media, 2021-03-31) Cheng, Jun; Liu, Yuting; Huang, Wei; Hong, Wenhui; Wang, Lingling; Zhan, Xiaohui; Han, Zhi; Ni, Dong; Huang, Kun; Zhang, Jie; Medicine, School of Medicine
Computational analysis of histopathological images can identify sub-visual objective image features that may not be visually distinguishable by human eyes, and hence provides better modeling of disease phenotypes. This study aims to investigate whether specific image features are associated with somatic mutations and patient survival in gastric adenocarcinoma (sample size = 310). An automated image analysis pipeline was developed to extract quantitative morphological features from H&E stained whole-slide images. We found that four frequently somatically mutated genes (TP53, ARID1A, OBSCN, and PIK3CA) were significantly associated with tumor morphological changes. A prognostic model built on the image features significantly stratified patients into low-risk and high-risk groups (log-rank test p-value = 2.6e-4). Multivariable Cox regression showed the model predicted risk index was an additional prognostic factor besides tumor grade and stage. Gene ontology enrichment analysis showed that the genes whose expressions mostly correlated with the contributing features in the prognostic model were enriched on biological processes such as cell cycle and muscle contraction. These results demonstrate that histopathological image features can reflect underlying somatic mutations and identify high-risk patients that may benefit from more precise treatment regimens. Both the image features and pipeline are highly interpretable to enable translational applications.
Cystic fibrosis related diabetes (CFRD) prognosis
(Elsevier, 2021-11-19) Sandouk, Zahrae; Khan, Farah; Khare, Swapnil; Moran, Antoinette; Medicine, School of Medicine
Cystic fibrosis related diabetes (CFRD) occurs in at least 40-50% of adults with CF. With other forms of diabetes, microvascular and macrovascular disease are the major causes of morbidity and mortality. Macrovascular disease is rare in CF. While microvascular disease does occur in this population, there are CF-specific diabetes complications that have a more important impact on prognosis. The additional diagnosis of diabetes in CF is associated with decreased lung function, poor nutritional status, and an overall increase in mortality from lung disease. These negative findings start even before the clinical diagnosis of CFRD, during the period when patients experience abnormal glucose tolerance related to insulin insufficiency. The main mechanisms by which CFRD negatively affects prognosis are thought to be a combination of 1) protein catabolism, decreased lean body mass and undernutrition resulting from insulin insufficiency, and 2) an increased pro-inflammatory and pro-infectious state related to intermittent hyperglycemia. With the introduction of CFTR modulators, the care of CF patients has been revolutionized and many aspects of CF health such as BMI and lung function are improving. The impact of these drugs on the adverse prognosis related to the diagnosis of diabetes in CF, as well as the potential to delay or prevent onset of CFRD remain to be determined.

Browsing by Subject "Prognosis"

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