22 results on '"Jurgis Alvikas"'
Search Results
2. EFFECT OF IRRIGATION FLUID COMPOSITION ON HEMOSTASIS IN MOUSE BLEEDING MODELS
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Nijmeh Alsaadi, Adnan Hassoune, Shannon Haldeman, Kelly M. Williamson, William Plautz, Lara Hoteit, Jurgis Alvikas, Elizabeth A. Andraska, Amudan J. Srinivasan, Jillian Bonaroti, Anupamaa Seshadri, Roberto Mota-Alvidrez, Melanie J. Scott, Paul A. Gardner, Carl H. Snyderman, and Matthew D. Neal
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Emergency Medicine ,Critical Care and Intensive Care Medicine - Published
- 2022
3. Nanomedicine platform for targeting activated neutrophils and neutrophil–platelet complexes using an α1-antitrypsin-derived peptide motif
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Michelle A. Cruz, Dillon Bohinc, Elizabeth A. Andraska, Jurgis Alvikas, Shruti Raghunathan, Nicole A. Masters, Nadine D. van Kleef, Kara L. Bane, Kathryn Hart, Kathryn Medrow, Michael Sun, Haitao Liu, Shannon Haldeman, Ankush Banerjee, Emma M. Lessieur, Kara Hageman, Agharnan Gandhi, Maria de la Fuente, Marvin T. Nieman, Timothy S. Kern, Coen Maas, Steven de Maat, Keith B. Neeves, Matthew D. Neal, Anirban Sen Gupta, and Evi X. Stavrou
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Neutrophils ,Biomedical Engineering ,Bioengineering ,Hematology ,Condensed Matter Physics ,Article ,Atomic and Molecular Physics, and Optics ,Mice ,Nanomedicine ,Clinical Research ,5.1 Pharmaceuticals ,alpha 1-Antitrypsin Deficiency ,Nanoparticles ,Animals ,Humans ,Nanotechnology ,General Materials Science ,Development of treatments and therapeutic interventions ,Nanoscience & Nanotechnology ,Electrical and Electronic Engineering ,Leukocyte Elastase ,Hydroxychloroquine - Abstract
Targeted drug delivery to disease-associated activated neutrophils can provide novel therapeutic opportunities while avoiding systemic effects on immune functions. We created a nanomedicine platform that uniquely utilizes an α(1)-antitrypsin-derived peptide to confer binding specificity to neutrophil elastase on activated neutrophils. Surface decoration with this peptide enabled specific anchorage of nanoparticles to activated neutrophils and platelet–neutrophil aggregates, in vitro and in vivo. Nanoparticle delivery of a model drug, hydroxychloroquine, demonstrated significant reduction of neutrophil activities in vitro and a therapeutic effect on murine venous thrombosis in vivo. This innovative approach of cell-specific and activation-state-specific targeting can be applied to several neutrophil-driven pathologies.
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- 2022
4. Failure to Thrive Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy: Causes and Consequences
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Caroline J. Rieser, Jurgis Alvikas, Heather Phelos, Lauren B. Hall, Amer H. Zureikat, Andrew Lee, Melanie Ongchin, Matthew P. Holtzman, James F. Pingpank, David L. Bartlett, and M. Haroon A. Choudry
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Oncology ,Surgery - Published
- 2022
5. EFFECT OF IRRIGATION FLUID COMPOSITION ON HEMOSTASIS IN MOUSE BLEEDING MODELS
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Nijmeh, Alsaadi, Adnan, Hassoune, Shannon, Haldeman, Kelly M, Williamson, William, Plautz, Lara, Hoteit, Jurgis, Alvikas, Elizabeth A, Andraska, Amudan J, Srinivasan, Jillian, Bonaroti, Anupamaa, Seshadri, Roberto, Mota-Alvidrez, Melanie J, Scott, Paul A, Gardner, Carl H, Snyderman, and Matthew D, Neal
- Abstract
Introduction: Intraoperative irrigation, usually with normal saline (NS), aids in bleeding identification and management. We investigated the effect of different irrigation fluids, with additives, on hemostasis using two bleeding models. Methods: C57BL/6 J mice were subjected to a tail bleed model or uncontrolled abdominal hemorrhage via liver laceration followed by abdominal cavity irrigation. We compared NS, lactated Ringer's (LR), and PlasmaLyte. We examined NS and LR at different temperatures. Normal saline or LR with calcium (Ca 2+ ) or tranexamic acid (TXA) was studied. Results: Compared with room temperature (RT), increasing the temperature of the irrigation fluid to 37°C and 42°C reduced tail vein bleeding times substantially in both NS and LR (all P0.001), with no significant differences between the two fluids. At RT, LR, but not PlasmaLyte, substantially reduced bleeding times in comparison to NS ( P0.0001). Liver injury blood loss was lower with LR ( P0.01). Normal saline supplemented with 2.7 mEq/L of Ca 2+ decreased bleeding time and blood loss volume ( P0.001 and P0.01, respectively) to similar levels as LR. Normal saline with 150 mg/mL of TXA markedly reduced bleeding time ( P0.0001), and NS with 62.5 mg/mL TXA decreased blood loss ( P0.01). Conclusion: Whereas Ca 2+ - and TXA-supplemented NS reduced bleeding, LR remained superior to all irrigation fluid compositions. As LR contains Ca 2+ , and Ca 2+ -supplemented NS mirrored LR in response, Ca 2+ presence in the irrigation fluid seems key to improving solution's hemostatic ability. Because warming the fluids normalized the choice of agents, the data also suggest that Ca 2+ -containing fluids such as LR may be more suitable for hemostasis when used at RT.
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- 2022
6. Rapid detection of platelet inhibition and dysfunction in traumatic brain injury: A prospective observational study
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Jurgis Alvikas, Jan O. Jansen, Adnan Hassoune, Heather M Phelos, Mazen S. Zenati, Matthew D. Neal, Insiyah Campwala, and David O. Okonkwo
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Male ,medicine.medical_specialty ,Platelet Aggregation ,Platelet Function Tests ,Traumatic brain injury ,Platelet Transfusion ,Critical Care and Intensive Care Medicine ,Independent Submissions ,traumatic ,Trauma Centers ,brain injuries ,Internal medicine ,Brain Injuries, Traumatic ,Humans ,Medicine ,Medical history ,Clinical significance ,Platelet ,Hospital Mortality ,Aged ,Whole blood ,Platelet function testing ,Aspirin ,business.industry ,Length of Stay ,Clopidogrel ,medicine.disease ,Intracranial Hemorrhage, Traumatic ,United States ,Intensive Care Units ,Treatment Outcome ,Platelet transfusion ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Cardiology ,Female ,Surgery ,Blood Platelet Disorders ,business ,Platelet Aggregation Inhibitors ,intracranial hemorrhage ,medicine.drug - Abstract
Supplemental digital content is available in the text., BACKGROUND Rapid platelet function testing is frequently used to determine platelet function in patients with traumatic intracranial hemorrhage (tICH). Accuracy and clinical significance of decreased platelet response detected by these tests is not well understood. We sought to determine whether VerifyNow and whole blood aggregometry (WBA) can detect poor platelet response and to elucidate its clinical significance for tICH patients. METHODS We prospectively enrolled patients with isolated tICH between 2018 and 2020. Demographics, medical history, injury characteristics, and patient outcomes were recorded. Platelet function was determined by VerifyNow and WBA testing at the time of arrival to the trauma bay and 6 hours later. RESULTS A total of 221 patients were enrolled, including 111 patients on no antiplatelet medication, 78 on aspirin, 6 on clopidogrel, and 26 on aspirin and clopidogrel. In the trauma bay, 29.7% and 67.7% of patients on no antiplatelet medication had poor platelet response on VerifyNow and WBA, respectively. Among patients on aspirin, 72.2% and 82.2% had platelet dysfunction on VerifyNow and WBA. Among patients on clopidogrel, 67.9% and 88.9% had platelet dysfunction on VerifyNow and WBA. Patients with nonresponsive platelets had similar in-hospital mortality (3 [3.0%] vs. 6 [6.3%], p = 0.324), tICH progression (26 [27.1%] vs. 24 [26.1%], p = 0.877), intensive care unit admission rates (34 [34.3%] vs. 38 [40.0%), p = 0.415), and length of stay (3 [interquartile range, 2–8] vs. 3.2 [interquartile range, 2–7], p = 0.818) to those with responsive platelets. Platelet transfusion did not improve platelet response or patient outcomes. CONCLUSION Rapid platelet function testing detects a highly prevalent poor platelet response among patients with tICH, irrespective of antiplatelet medication use. VerifyNow correlated fairly with whole blood aggregometry among patients with tICH and platelet responsiveness detectable by these tests did not correlate with clinical outcomes. In addition, our results suggest that platelet transfusion may not improve clinical outcomes in patients with tICH. LEVEL OF EVIDENCE Diagnostic tests, level II.
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- 2021
7. Outcomes and Patient Selection in Laparoscopic vs. Open Liver Resection for HCC and Colorectal Cancer Liver Metastasis
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Jurgis Alvikas, Winifred Lo, Samer Tohme, and David A. Geller
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Cancer Research ,Oncology - Abstract
Hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) are the two most common malignant tumors that require liver resection. While liver transplantation is the best treatment for HCC, organ shortages and high costs limit the availability of this option for many patients and make resection the mainstay of treatment. For patients with CRLM, surgical resection with negative margins is the only potentially curative option. Over the last two decades, laparoscopic liver resection (LLR) has been increasingly adopted for the resection of a variety of tumors and was found to have similar long-term outcomes compared to open liver resection (OLR) while offering the benefits of improved short-term outcomes. In this review, we discuss the current literature on the outcomes of LLR vs. OLR for patients with HCC and CRLM. Although the use of LLR for HCC and CRLM is increasing, it is not appropriate for all patients. We describe an approach to selecting patients best-suited for LLR. The four common difficulty-scoring systems for LLR are summarized. Additionally, we review the current evidence behind the emerging robotically assisted liver resection technology.
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- 2023
8. Platelet-mimicking procoagulant nanoparticles augment hemostasis in animal models of bleeding
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Ujjal Didar Singh Sekhon, Kelsey Swingle, Aditya Girish, Norman Luc, Maria de la Fuente, Jurgis Alvikas, Shannon Haldeman, Adnan Hassoune, Kaisal Shah, Youjoung Kim, Steven Eppell, Jeffrey Capadona, Andrew Shoffstall, Matthew D. Neal, Wei Li, Marvin Nieman, and Anirban Sen Gupta
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Blood Platelets ,Hemostasis ,Mice ,Models, Animal ,Animals ,Nanoparticles ,Hemorrhage ,General Medicine ,Article ,Rats - Abstract
Treatment of bleeding disorders using transfusion of donor-derived platelets faces logistical challenges due to their limited availability, high risk of contamination, and short (5 to 7 days) shelf life. These challenges could be potentially addressed by designing platelet mimetics that emulate the adhesion, aggregation, and procoagulant functions of platelets. To this end, we created liposome-based platelet-mimicking procoagulant nanoparticles (PPNs) that can expose the phospholipid phosphatidylserine on their surface in response to plasmin. First, we tested PPNs in vitro using human plasma and demonstrated plasmin-triggered exposure of phosphatidylserine and the resultant assembly of coagulation factors on the PPN surface. We also showed that this phosphatidylserine exposed on the PPN surface could restore and enhance thrombin generation and fibrin formation in human plasma depleted of platelets. In human plasma and whole blood in vitro, PPNs improved fibrin stability and clot robustness in a fibrinolytic environment. We then tested PPNs in vivo in a mouse model of thrombocytopenia where treatment with PPNs reduced blood loss in a manner comparable to treatment with syngeneic platelets. Furthermore, in rat and mouse models of traumatic hemorrhage, treatment with PPNs substantially reduced bleeding and improved survival. No sign of systemic or off-target thrombotic risks was observed in the animal studies. These findings demonstrate the potential of PPNs as a platelet surrogate that should be further investigated for the management of bleeding.
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- 2022
9. Reduced cleavage of von willebrand factor by ADAMTS13 is associated with microangiopathic acute kidney injury following trauma
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Mitchell Dyer, Jay S. Raval, Shannon Haldeman, Marian A. Rollins-Raval, Nijmeh Alsaadi, Patricia Loughran, Jurgis Alvikas, Adnan Hassoune, William E. Plautz, Francis X. Guyette, Roberto I. Mota, Brian S. Zuckerbraun, Jason L. Sperry, Lara Hoteit, and Matthew D. Neal
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ADAMTS13 protein ,biology ,Chemistry ,Acute kidney injury ,Hematology ,General Medicine ,Original Articles ,wounds and injuries ,Acute Kidney Injury ,von Willebrand factor ,medicine.disease ,Cleavage (embryo) ,Kidney ,Molecular biology ,ADAMTS13 ,Molecular Weight ,Mice ,Plasma ,Von Willebrand factor ,hemic and lymphatic diseases ,medicine ,biology.protein ,Animals ,Humans ,thrombophilia - Abstract
Acute kidney injury (AKI) is common after trauma, but contributory factors are incompletely understood. Increases in plasma von Willebrand Factor (vWF) with concurrent decreases in ADAMTS13 are associated with renal microvascular thrombosis in other disease states, but similar findings have not been shown in trauma. We hypothesized that molecular changes in circulating vWF and ADAMTS13 promote AKI following traumatic injury. VWF antigen, vWF multimer composition and ADAMTS13 levels were compared in plasma samples from 16 trauma patients with and without trauma-induced AKI, obtained from the Prehospital Air Medical Plasma (PAMPer) biorepository. Renal histopathology and function, vWF and ADAMTS13 levels were assessed in parallel in a murine model of polytrauma and haemorrhage. VWF antigen was higher in trauma patients when compared with healthy controls [314% (253–349) vs. 100% (87–117)] [median (IQR)], while ADAMTS13 activity was lower [36.0% (30.1–44.7) vs. 100.0% (83.1–121.0)]. Patients who developed AKI showed significantly higher levels of high molecular weight multimeric vWF at 72-h when compared with non-AKI counterparts [32.9% (30.4–35.3) vs. 27.8% (24.6–30.8)]. Murine plasma cystatin C and vWF were elevated postpolytrauma model in mice, with associated decreases in ADAMTS13, and immunohistologic analysis demonstrated renal injury with small vessel plugs positive for fibrinogen and vWF. Following traumatic injury, the vWF-ADAMTS13 axis shifted towards a prothrombotic state in both trauma patients and a murine model. We further demonstrated that vWF-containing, microangiopathic deposits were concurrently produced as the prothrombotic changes were sustained during the days following trauma, potentially contributing to AKI development.
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- 2021
10. Failure to Thrive Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy: Causes and Consequences
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Caroline J, Rieser, Jurgis, Alvikas, Heather, Phelos, Lauren B, Hall, Amer H, Zureikat, Andrew, Lee, Melanie, Ongchin, Matthew P, Holtzman, James F, Pingpank, David L, Bartlett, and M Haroon A, Choudry
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Survival Rate ,Postoperative Complications ,Humans ,Female ,Cytoreduction Surgical Procedures ,Hyperthermia, Induced ,Combined Modality Therapy ,Patient Readmission ,Peritoneal Neoplasms ,Failure to Thrive ,Retrospective Studies - Abstract
Failure to thrive (FTT) is a complex syndrome of nutritional failure and functional decline. Readmission for FTT following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS HIPEC) is common but underexamined. This study aims to determine features, risk factors, and prognostic significance of FTT following CRS HIPEC.We reviewed patients who underwent CRS HIPEC from 2010 to 2018 at our institution. Patients were categorized into no readmission, FTT readmission, and other readmission. FTT was determined by coding and chart review. We compared baseline characteristics, oncologic data, perioperative outcomes, and survival among the three cohorts.Of 1068 discharges examined, 379 patients (36%) were readmitted within 90 days, of which 134 (12.5%) were labeled as FTT. Patients with FTT readmission had worse preoperative functional status, higher rates of malnutrition, more complex resections, longer hospital stays, and more postoperative complications (all p 0.001). Ostomy creation [relative risk ratio (RRR) 4.06], in-hospital venous thromboembolism (VTE), discharge to nursing home (RRR 2.48), pre-CRS HIPEC chemotherapy (RRR 1.98), older age (RRR 1.84), and female gender (RRR 1.69) were all independent predictors for FTT readmission on multinomial regression (all p 0.01). FTT readmission was associated with worse median overall survival on multivariate analysis [hazard ratio (HR) 1.60, p 0.001] after controlling for oncologic, perioperative, and baseline factors.FTT is common following CRS HIPEC and appears to be associated with baseline patient characteristics, operative burden, and postoperative complications. Perioperative strategies for improving nutrition and activity, along with early recognition and intervention in FTT may improve patient outcomes.
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- 2021
11. Implication of DNA repair genes in Lynch-like syndrome
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Rajyasree Emmadi, Victoria Alagiozian-Angelova, Francesc López-Giráldez, Priti Marwaha, Sonia S. Kupfer, Jurgis Alvikas, Maureen Regan, Rosa M. Xicola, Julia Clark, Nathan A. Ellis, Jungmin Choi, Timothy J. Carroll, and Xavier Llor
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Adult ,Male ,0301 basic medicine ,Heterozygote ,Cancer Research ,030105 genetics & heredity ,Biology ,Gene mutation ,MLH1 ,DNA Mismatch Repair ,Article ,Germline ,Loss of heterozygosity ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Genetics ,medicine ,Humans ,Exome ,Germ-Line Mutation ,Genetics (clinical) ,Aged ,Mismatch Repair Endonuclease PMS2 ,Aged, 80 and over ,Microsatellite instability ,Sequence Analysis, DNA ,DNA Methylation ,Middle Aged ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,digestive system diseases ,Lynch syndrome ,DNA-Binding Proteins ,MutS Homolog 2 Protein ,Oncology ,030220 oncology & carcinogenesis ,Female ,Microsatellite Instability ,MutL Protein Homolog 1 - Abstract
Many colorectal cancers (CRCs) that exhibit microsatellite instability (MSI) are not explained by MLH1 promoter methylation or germline mutations in mismatch repair (MMR) genes, which cause Lynch syndrome (LS). Instead, these Lynch-like syndrome (LLS) patients have somatic mutations in MMR genes. However, many of these patients are young and have relatives with cancer, suggesting a hereditary entity. We performed germline sequence analysis in LLS patients and determined their tumor's mutational profiles using FFPE DNA. Six hundred fifty-four consecutive CRC patients were screened for suspected Lynch syndrome using MSI and absence of MLH1 methylation. Suspected LS cases were exome sequenced to identify germline and somatic mutations. Single nucleotide variants were used to characterize mutational signatures. We identified 23 suspected LS cases. Germline sequence analysis of 16 available samples identified 5 cases with LS mutations and 11 cases without LS mutations, LLS. Most LLS tumors had a combination of somatic MMR gene mutation and loss of heterozygosity. LLS patients were relatively young and had excess first-degree relatives with cancer. Four of the 11 LLS patients had rare likely pathogenic variants in genes that maintain genome integrity. Moreover, tumors from this group had a distinct mutational signature compared to tumors from LLS patients lacking germline mutations in these genes. In summary, more than a third of the LLS patients studied had germline mutations in genes that maintain genome integrity and their tumors had a distinct mutational signature. The possibility of hereditary factors in LLS warrants further studies so counseling can be properly informed.
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- 2019
12. Preoperative Systemic Immune-Inflammation Index Predicts Recurrence after Resection of Pancreatic Neuroendocrine Tumors
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Caroline J. Rieser, Amer H. Zureikat, Alessandro Paniccia, Jurgis Alvikas, Andrea J. Ibarra, and Jian Zheng
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medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Surgery ,Neuroendocrine tumors ,business ,medicine.disease ,Gastroenterology ,Resection ,Immune inflammation - Published
- 2021
13. Nanomedicine platform for targeting activated neutrophils and neutrophil-platelet complexes using an α
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Michelle A, Cruz, Dillon, Bohinc, Elizabeth A, Andraska, Jurgis, Alvikas, Shruti, Raghunathan, Nicole A, Masters, Nadine D, van Kleef, Kara L, Bane, Kathryn, Hart, Kathryn, Medrow, Michael, Sun, Haitao, Liu, Shannon, Haldeman, Ankush, Banerjee, Emma M, Lessieur, Kara, Hageman, Agharnan, Gandhi, Maria, de la Fuente, Marvin T, Nieman, Timothy S, Kern, Coen, Maas, Steven, de Maat, Keith B, Neeves, Matthew D, Neal, Anirban, Sen Gupta, and Evi X, Stavrou
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Mice ,Nanomedicine ,Neutrophils ,alpha 1-Antitrypsin Deficiency ,Animals ,Humans ,Leukocyte Elastase ,Hydroxychloroquine - Abstract
Targeted drug delivery to disease-associated activated neutrophils can provide novel therapeutic opportunities while avoiding systemic effects on immune functions. We created a nanomedicine platform that uniquely utilizes an α
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- 2021
14. Moderately Macrosteatotic Livers Have Acceptable Long-Term Outcomes but Higher Risk of Immediate Mortality
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Kristina Lemon, Xilin Chen, Christopher Hughes, Jurgis Alvikas, Andrew-Paul Deeb, Hanna E. Labiner, Abhinav Humar, Shahid M. Malik, Amit D. Tevar, Anthony J. Demetris, Dana R. Jorgensen, and Marta I. Minervini
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Liver transplantation ,Gastroenterology ,Severity of Illness Index ,Article ,Body Mass Index ,End Stage Liver Disease ,Liver disease ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Transplantation ,business.industry ,Proportional hazards model ,Middle Aged ,medicine.disease ,Liver Transplantation ,Fatty Liver ,Treatment Outcome ,Liver ,Hepatocellular carcinoma ,Cohort ,Surgery ,Female ,Steatosis ,business ,Body mass index - Abstract
Background and aims Liver transplantation is the most effective treatment for end-stage liver disease (ESLD). Whether moderately macrosteatotic livers (30%-60%) represent a risk for worsened graft function is controversial. The uncertainty, in large part, is owing to the heterogeneous steatosis grading. Our aim was to determine the short- and long-term outcomes of moderately macrosteatotic allografts that were graded according to a standardized institutional protocol. Methods We performed a retrospective analysis of transplants performed between 1994 and 2014. All patients with allografts biopsied pretransplantation were included. Relevant donor and recipient variable were recorded. Moderately macrosteatotic livers were compared with mildly macrosteatotic and nonsteatotic livers. Primary outcomes of interest were patient survival at 90 days, 1 year, and 5 years. Cox regression analyses were carried out to compare survival between the 2 groups. Results We compared 65 allografts with moderate macrosteatosis and 810 with no or mild macrosteatosis. Patients with moderately macrosteatotic allografts were 2.69 times as likely to die within the first 90 days after transplant (75.1% vs 91.6% survival) after adjusting for donor age, donor race, recipient age, recipient race, recipient body mass index, recipient diabetes, presence of hepatocellular carcinoma, days on waitlist, Model for End-Stage Liver Disease (MELD) score at transplantation, cold ischemia time. However, for recipients who survive 90 days, moderately macrosteatotic allografts had comparable long-term survival. Conclusion Our study shows that moderate macrosteatosis is a strong predictor of early but not late mortality. Further studies are needed to distinguish the specific cohort of patients for whom moderately macrosteatotic allografts will lead to acceptable outcomes.
- Published
- 2020
15. A systematic review and meta-analysis of traumatic intracranial hemorrhage in patients taking prehospital antiplatelet therapy: Is there a role for platelet transfusions?
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Bellal Joseph, Andrew R. Guillotte, Jurgis Alvikas, Cody Doberstein, David O. Okonkwo, Matthew D. Neal, Matthew R. Rosengart, Sara P. Myers, Carlos Pelaez, and Charles B. Wessel
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medicine.medical_specialty ,Platelet Transfusion ,Critical Care and Intensive Care Medicine ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,Aspirin ,business.industry ,030208 emergency & critical care medicine ,Retrospective cohort study ,Evidence-based medicine ,Odds ratio ,Precipitating Factors ,Intracranial Hemorrhage, Traumatic ,Clopidogrel ,Platelet transfusion ,Systematic review ,Treatment Outcome ,Cardiovascular Diseases ,Meta-analysis ,Practice Guidelines as Topic ,Disease Progression ,Platelet aggregation inhibitor ,Surgery ,Observational study ,business ,Platelet Aggregation Inhibitors - Abstract
Background Platelet transfusion has been utilized to reverse platelet dysfunction in patients on preinjury antiplatelets who have sustained a traumatic intracranial hemorrhage (tICH); however, there is little evidence to substantiate this practice. The objective of this study was to perform a systematic review on the impact of platelet transfusion on survival, hemorrhage progression and need for neurosurgical intervention in patients with tICH on prehospital antiplatelet medication. Methods Controlled, observational and randomized, prospective and retrospective studies describing tICH, preinjury antiplatelet use, and platelet transfusion reported in PubMed, Embase, Cochrane Reviews, Cochrane Trials and Cochrane DARE databases between January 1987 and March 2019 were included. Investigations of concomitant anticoagulant use were excluded. Risk of bias was assessed using the Newcastle-Ottawa scale. We calculated pooled estimates of relative effect of platelet transfusion on the risk of death, hemorrhage progression and need for neurosurgical intervention using the methods of Dersimonian-Laird random-effects meta-analysis. Sensitivity analysis established whether study size contributed to heterogeneity. Subgroup analyses determined whether antiplatelet type, additional blood products/reversal agents, or platelet function assays impacted effect size using meta-regression. Results Twelve of 18,609 screened references were applicable to our questions and were qualitatively and quantitatively analyzed. We found no association between platelet transfusion and the risk of death in patients with tICH taking prehospital antiplatelets (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.76-2.18; p = 0.346; I = 32.5%). There was no significant reduction in hemorrhage progression (OR, 0.88; 95% CI, 0.34-2.28; p = 0.788; I = 78.1%). There was no significant reduction in the need for neurosurgical intervention (OR, 1.00; 95% CI, 0.53-1.90, p = 0.996; I = 59.1%; p = 0.032). Conclusion Current evidence does not support the use of platelet transfusion in patients with tICH on prehospital antiplatelets, highlighting the need for a prospective evaluation of this practice. Level of evidence Systematic Reviews and Meta-Analyses, Level III.
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- 2020
16. ASO Visual Abstract: Failure to Thrive Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy: Causes and Consequences
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Caroline J. Rieser, Jurgis Alvikas, Heather Phelos, Lauren B. Hall, Amer H. Zureikat, Andrew Lee, Melanie Ongchin, Matthew P. Holtzman, James F. Pingpank, David L. Bartlett, and M. Haroon A. Choudry
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Oncology ,Surgery - Published
- 2022
17. Platelet-derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice
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Will Plautz, Patricia Loughran, Yingjie Liu, Yoel Sadovsky, Matthew D. Neal, Wyeth Alexander, Brian S. Zuckerbraun, Tomasz Brzoska, Hui Li, Qiwei Chen, Prithu Sundd, Mitchell Dyer, Shannon Haldeman, Brian A. Boone, Jurgis Alvikas, and Adnan Hassoune
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Adult ,Blood Platelets ,Male ,Time Factors ,Platelet Aggregation ,Deep vein ,030204 cardiovascular system & hematology ,Pharmacology ,Article ,03 medical and health sciences ,Extracellular Vesicles ,0302 clinical medicine ,Fibrinolytic Agents ,Bleeding time ,medicine ,Animals ,Humans ,Platelet ,Platelet activation ,Thrombus ,Aged ,Venous Thrombosis ,Hemostasis ,medicine.diagnostic_test ,business.industry ,Multiple Trauma ,fungi ,Thrombin ,Hematology ,Middle Aged ,medicine.disease ,Thrombosis ,Mice, Inbred C57BL ,Disease Models, Animal ,medicine.anatomical_structure ,Traumatic injury ,Female ,business ,Platelet Aggregation Inhibitors ,Hydroxychloroquine ,Signal Transduction - Abstract
Background Traumatic injury can lead to dysregulation of the normal clotting system, resulting in hemorrhagic and thrombotic complications. Platelet activation is robust following traumatic injury and one process of platelet activation is to release of extracellular vesicles (PEV) that carry heterogenous cargo loads and surface ligands. Objectives We sought to investigate and characterize the release and function of PEVs generated following traumatic injury. Methods PEV content and quantity in circulation following trauma in humans and mice was measured using flow cytometry, size exclusion chromatography, and nanoparticle tracking analysis. PEVs were isolated from circulation and the effects on thrombin generation, bleeding time, hemorrhage control, and thrombus formation were determined. Finally, the effect of hydroxychloroquine (HCQ) on PEV release and thrombosis were examined. Results Human and murine trauma results in a significant release of PEVs into circulation compared with healthy controls. These PEVs result in abundant thrombin generation, increased platelet aggregation, decreased bleeding times, and decreased hemorrhage in uncontrolled bleeding. Conversely, PEVs contributed to enhanced venous thrombus formation and were recruited to the developing thrombus site. Interestingly, HCQ treatment resulted in decreased platelet aggregation, decreased PEV release, and reduced deep vein thrombosis burden in mice. Conclusions These data demonstrate that trauma results in significant release of PEVs which are both pro-hemostatic and pro-thrombotic. The effects of PEVs can be mitigated by treatment with HCQ, suggesting the potential use as a form of deep vein thrombosis prophylaxis.
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- 2019
18. Modern Techniques for DNA, RNA, and Protein Assessment
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Matthew D. Neal and Jurgis Alvikas
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Transcriptome ,chemistry.chemical_compound ,Metabolomics ,Standard of care ,chemistry ,Transcription (biology) ,RNA ,Computational biology ,Disease ,Biology ,Precision medicine ,DNA - Abstract
Advances in molecular and cellular biology have led to an in-depth understanding of the basic mechanisms of life and disease. Elucidation of principles of genetic information storage in DNA, transcription of this information into RNA, and translation of RNA into proteins have led to an exponential growth of techniques useful for screening, diagnosis, prognostication, and treatment. In a wide range of medical and surgical specialties, many of these techniques are already standard of care and are used on a daily basis. In an emerging model of precision medicine, data from DNA, RNA, and protein assessment of an individual patient will be used to guide their care. While much progress has been made, our understanding of majority of surgical diseases is incomplete. An academic surgeon with a career of scientific pursuit must have a thorough understanding of the current state of laboratory techniques for DNA, RNA, and protein analysis and of the knowledge gaps that future investigations should address. This chapter reviews the basics of genetic, genomic, transcriptomic, proteomic, and metabolomic analyses.
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- 2019
19. Platelet Transfusion for Patients with Traumatic Intracranial Hemorrhage Taking Prehospital Antiplatelet Medication: A Systematic Review and Meta-Analysis
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Jurgis Alvikas, Matthew R. Rosengart, Charles B. Wessel, Sara A. Myers, Cody Doberstein, Wael F. Asaad, and Matthew D. Neal
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medicine.medical_specialty ,Platelet transfusion ,business.industry ,Meta-analysis ,medicine ,Surgery ,Intensive care medicine ,business - Published
- 2019
20. β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications
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Jurgis Alvikas, Qian Bian, Andrew S. Belmont, and Nimish Khanna
- Subjects
Chromatin Immunoprecipitation ,Chromosomes, Artificial, Bacterial ,Heterochromatin ,beta-Globins ,Methylation ,Article ,Epigenesis, Genetic ,Histones ,Mice ,Gene cluster ,Animals ,Humans ,Epigenetics ,Chromosome Positioning ,Cells, Cultured ,Research Articles ,Locus control region ,Pericentric heterochromatin ,Genetics ,Regulation of gene expression ,biology ,Gene targeting ,Cell Biology ,Histone ,Gene Expression Regulation ,biology.protein - Abstract
Multiple cis-elements surrounding the β-globin gene locus combine to target this locus to the nuclear periphery through at least two different epigenetic marks., Increasing evidence points to nuclear compartmentalization as a contributing mechanism for gene regulation, yet mechanisms for compartmentalization remain unclear. In this paper, we use autonomous targeting of bacterial artificial chromosome (BAC) transgenes to reveal cis requirements for peripheral targeting. Three peripheral targeting regions (PTRs) within an HBB BAC bias a competition between pericentric versus peripheral heterochromatin targeting toward the nuclear periphery, which correlates with increased H3K9me3 across the β-globin gene cluster and locus control region. Targeting to both heterochromatin compartments is dependent on Suv39H-mediated H3K9me3 methylation. In different chromosomal contexts, PTRs confer no targeting, targeting to pericentric heterochromatin, or targeting to the periphery. A combination of fluorescent in situ hybridization, BAC transgenesis, and knockdown experiments reveals that peripheral tethering of the endogenous HBB locus depends both on Suv39H-mediated H3K9me3 methylation over hundreds of kilobases surrounding HBB and on G9a-mediated H3K9me2 methylation over flanking sequences in an adjacent lamin-associated domain. Our results demonstrate that multiple cis-elements regulate the overall balance of specific epigenetic marks and peripheral gene targeting.
- Published
- 2013
21. 775 Unveiling New Colorectal Cancer Phenotypes With Mismatch Repair Deficiency
- Author
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Nathan A. Ellis, Jurgis Alvikas, Maureen Regan, Julia Clark, Sonia S. Kupfer, Rajyasree Emmadi, Priti Marwaha, Timothy J. Carroll, Rosa M. Xicola, Victoria Alagiozian-Angelova, and Xavier Llor
- Subjects
Hepatology ,business.industry ,Colorectal cancer ,Gastroenterology ,Cancer research ,MISMATCH REPAIR DEFICIENCY ,Medicine ,business ,medicine.disease ,Phenotype - Published
- 2016
22. Su1993 Somatic Mutations in the Mismatch Repair System Are Responsible for a Majority of Unexplained Lynch Syndrome Cases: Time to Revise Lynch Syndrome Screening?
- Author
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Rajyasree Emmadi, Nathan A. Ellis, Priti Marwaha, Jurgis Alvikas, Maureen Regan, Sonia S. Kupfer, Xavier Llor, Kisha A. Mitchell, Rosa M. Xicola, Victoria Alagiozian-Angelova, Joanna Gibson, and Timothy P. Carroll
- Subjects
Genetics ,medicine.medical_specialty ,education.field_of_study ,Hepatology ,Atrophic gastritis ,business.industry ,Population ,Gastroenterology ,Cancer ,Intestinal metaplasia ,Context (language use) ,Methylation ,medicine.disease ,Lynch syndrome ,Internal medicine ,medicine ,Gastritis ,medicine.symptom ,education ,business - Abstract
G A A b st ra ct s gastric tissue samples harvested from an independent population ofH. pylori-infected persons in New Orleans to assess expression and methylation status of HIF-1α in vivo. Gastric tissue specimens from African-American subjects harboring an increased risk for gastric cancer exhibited marked decreases in methylation of HIF-1α with increasing disease severity. The highest levels of HIF-1α methylation were found in patients with non-atrophic gastritis and this decreased as disease progressed to atrophic gastritis (0.5-fold) and intestinal metaplasia (0.2-fold), versus gastritis alone. Consistent with decreasing HIF-1α methylation status, gastric tissue from African-American patients harbored increased levels of HIF-1α expression with increasing disease progression and this was not observed in Caucasian patients. Collectively, these data indicate that H. pylori induces HIF-1α in gastric epithelial cells and this is augmented under conditions of iron deficiency. HIF-1α expression in vivo increases in conjunction with decreased HIF-1α methylation and the development of premalignant lesions, which may provide a mechanism underpinning the link between high altitude, iron depletion, and increased gastric cancer rates within the context of H. pylori infection.
- Published
- 2015
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