Background: Budd-Chiari Syndrome (BCS) is a complex thrombotic disorder caused due to obstruction of hepatic venous outflow involving anywhere from small hepatic venules to the entrance of inferior ...vena cava into the right atrium. This leads to venous stasis and ischemic injury of hepatic parenchyma and sinusoids, with the risk of liver failure. The prognosis of patients with BCS had improved significantly with long-term anticoagulation and measures like Trans-Jugular-Intrahepatic-Porto-Systemic shunt (TIPS) and liver transplantation. We report the outcomes of patients who follow in our hematology practice and describe the factors predicting the need for TIPS/Liver Transplant.
Methods: After appropriate Investigational Review Board permission, we identified patients with a history of BCS following in our thrombosis clinical practice from the year 2010 onwards. We evaluated their laboratory, demographic, anticoagulation data, Model of End-stage Liver Disease (MELD) score, Child-Pugh (CP) score at diagnosis or when earliest available, and other relevant clinical information as outlined. Descriptive statistics with medians, quartiles, frequencies, and percentages are reported. Further, we compared the two categories of patients who needed TIPS/Liver transplants versus those who did not. SAS version 9.4 was used for analysis. For continuous variables, a univariate nonparametric Mann-Whitney test was used. The Fisher's Exact Test was used to associate each variable with the need for TIPS/Liver Transplant.
Results: Our study included 23 patients with baseline characteristics, including median age of 36 years (11-59 years), 91% whites, 61% females, 44% smokers, 61% obese(median BMI 29.9 kg/m 2), 6 of 14 women on oral contraceptive pills, 22% with thrombosis history, 17% with stroke history, median hemoglobin 13.4 gm/dL(8.9-20 gm/dL), white blood cell count 9,400/L (3,050-31,500/L), platelet count 294,000/L(14,000-767,000/L), serum creatinine 0.87 mg/L (0.55-2.52 mg/dL), total protein 6.3 gm/dL (5.2-8.8 gm/dL), Bilirubin 2.1 mg/dL(0.1-20.2 mg/dL), Aspartate Aminotransferase (AST) 61 U/L(16-1037 U/L), Alanine Aminotransferase (ALT) 43U/L(18-1694 U/L), MELD score 15 (range 7-38), CP score 9 (5-14), 74% with cirrhosis, 82% with ascites at one point, 57% with myeloproliferative neoplasm (MPN), 4.3% with Paroxysmal Nocturnal Hemoglobinuria (PNH), 17% with Antiphospholipid antibodies positive (APS), 13% had positive antinuclear antibodies, 35% needed TIPS and 44% required liver transplantation. 57% with Janus Kinase (JAK2) V617F mutation (1 patient with a low variant allele frequency of 1%), 1 patient (4.3%) had Calreticulin (CALR) mutation positive MPN, 91% remained on long-term anticoagulation with 40% using warfarin, 35% apixaban, 9% Enoxaparin or Rivaroxaban for long-term anticoagulation, 13% developed heparin-induced thrombocytopenia (HIT). 8.7% had developed BCS after Ad26.COV2.S vaccine to prevent SARS-CoV-2 infection. Excluding the patients with missing variables, 5 of 12 had Protein C deficiency, 3 or 10 had Protein S deficiency, 8 of 20 with Antithrombin (AT) deficiency, 4 of 14 with heterozygous factor V Leiden mutation, 0 of 10 with prothrombin gene mutation, 1 of 13 with hyper-homocysteinemia. 35% had gastrointestinal bleeding though 65% of patients had evidence of varices by endoscopy. When the group needing TIPS/Liver transplant/died is compared to those who did not, they had higher bilirubin, MELD, PC score, AT deficiency, cirrhosis, ascites, and JAK2 mutation (p-value significant: Table 1). With a median follow-up of 90 months, overall survival was not statistically significant between the two groups (Figure 1). Two patients (8.7%) died out of a total of 23.
Conclusions: Our data indicate that in patients with BCS, neoplasms (61%), particularly MPN (57%), are very commonly diagnosed. Compared to the historical data in patients with BCS with dismal prognosis (60-80% six-month mortality rate), the overall survival had significantly improved, likely due to supportive measures like TIPS/Liver transplant and long-term anticoagulation. Outside the established variables like CP and MELD, lower antithrombin activity and positive JAK2 mutation status also predicted a higher TIPS/Liver transplant need.
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Bhatt: Partnership for health analytic research, LLC: Consultancy; Abbvie: Consultancy, Research Funding; Jazz: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy. Gundabolu: BioMarin Pharmaceuticals: Consultancy; Blueprint Medicines: Consultancy; Bristol-Myers Squibb Company: Consultancy; Pfizer: Research Funding; Samus Therapeutics: Research Funding.
Farm machinery is a major source of injury. The objective of this study is to characterize the incidence, injury characteristics, and outcomes of patients admitted with farm machinery injuries (FMIs) ...to an urban joint trauma system in a rural state. A retrospective 15-year review of the trauma registries of the two trauma centers that function as a single state-designated Level I joint trauma center system was conducted. There were 65 admissions for FMIs at hospital A and 41 at hospital B; this represents under 0.4% of total trauma admissions. The patients ranged in age from 2 to 87 years. At hospital A, 89% of admitted patients sustained extremity injuries, 16% sustained torso trauma, 92% required surgical intervention, and the mortality rate was 0%. At hospital B, 60% of admitted patients sustained extremity injuries, 36.6% of patients sustained torso trauma, 63% required surgical intervention, and the mortality rate was 14.6%. Tractor-related injuries were responsible for 17% of admissions at hospital A and 69% at hospital B. Of the six fatalities, five were tractor related. The data demonstrate that FMIs affect people in nearly all decades of life. FMIs at the two hospitals had differing injury characteristics and outcomes, in large part secondary to the differing frequency of tractor-related injuries. FMIs frequently required surgical intervention.
Patients with chronic pain may be disproportionately impacted by the COVID-19 pandemic due, in part, to shared risk factors for both chronic pain and COVID-19 infection. At the same time, the ...pandemic has increased barriers to participating in interdisciplinary chronic pain rehabilitation programs (ICPRPs). The present study provides preliminary evidence regarding the effects of two ICPRP modifications-reduced program dosage and delivery via telemedicine-designed to increase access during the initial COVID-19 surge but with implications beyond the pandemic. Design: Retrospective cohort comparison evaluating pain severity, pain interference, and beliefs relating pain and disability for groups completing 4-week (110-hour) versus 3-week (73-hour) and in-person versus telemedicine ICPRP formats. Subjects: 103 patients who completed an ICPRP at an academic medical center between April 2019 and July 2021. Results: The 4-week, in person; 3-week, in-person; and 3-week, telemedicine programs were all effective in decreasing pain severity, pain interference, and beliefs relating pain and disability. Compared to the 4-week, in-person version, however, the 3-week, in-person program proved less effective in reducing pain interference and beliefs equating pain with impairment. The 3-week, telemedicine format, in turn, was less effective than the 3-week, in-person version in decreasing beliefs associating pain and disability. Conclusions: Decreasing program dosage and offering participation via telemedicine may be viable strategies for increasing access to ICPRPs, but may result in reduced program effectiveness in certain domains. The study's uncontrolled design and small telemedicine group underscore the need for randomized, controlled trials comparing different ICPRP dosages and modalities.
Background: Acute Lymphoblastic Leukemia (ALL) outcomes have significantly improved over time with multi-agent chemotherapy, and the addition of asparaginase (ASP) has demonstrated the ability to ...prolong overall survival. ASP has multiple toxicities, and it remains a challenge to manage them safely, particularly coagulopathy and thrombosis (30-40% based on historical studies). The best prophylactic anticoagulation strategy in patients with acute leukemias, particularly ALL with asparaginase use, remains unclear due to severe coexisting thrombocytopenia and coagulopathy. Though the current guidelines recommend using Antithrombin (AT) replacement or low molecular weight heparin (LMWH) for thrombosis prophylaxis, the evidence is weak with concerns of thrombosis (Blood (2020) 136 (3): 328-338) with the use of fibrinogen concentrates(cryoprecipitate) and limited efficacy data with AT replacement and unfractionated heparin (UFH) for thrombosis prophylaxis. Due to potential “resistance” to LMWH and UFH from acquired AT deficiency with ASP use, our institution in 2017 has adopted the use of the direct Xa inhibitor, Apixaban for thrombosis prophyalxis. We report the safety and effectiveness of Apixaban for thrombosis prophylaxis with ASP.
Methods: In this retrospective study, we reviewed the data on 20 patients treated with ASP between 2017-2020. Thrombosis prophylaxis was instituted with Apixaban 2.5 mg PO Q 12 hourly for three weeks along with cryoprecipitate as needed for bleeding or fibrinogen levels <100 mg/dL (normal 160-450 mg/dL) to balance the risk of bleeding. Apixaban was held if platelet count <20,000/µL and for invasive procedures or clinically significant bleeding events. We evaluated demographic data, ALL risk category, type of ASP use, laboratory data (Table 1 & 2) for four weeks following ASP, amount of cryoprecipitate used, major bleeding, clinically relevant non-major bleeding (CRNMB), and thrombosis incidence. The medians of pertinent laboratory data were plotted on a graph. Descriptive statistics with medians, quartiles, frequencies, and percentages are reported.
Results: Among the 20 patients treated during this period, 18 (90%) had ALL, and 2(10%) had NK/T cell lymphoma. Of the patients with ALL, 67% had high risk and 33% with standard-risk ALL. The median age of this cohort was 29.5 years (range: 19-63 years), 80% were males, 70% white, 30% were Latino or Hispanic, median body mass index-BMI of 30.2 kg/m 2(19.4-40.7 kg/m 2) and 65% were non-smokers. The median baseline AT activity was 107% (79-221%), 95% used concurrent corticosteroids (65%- Prednisone, and 30% used Dexamethasone). The most common induction treatment was CALGB 10403 (55%). Of the total, 95% received pegylated ASP, and only one patient received Erwinia ASP due to prior history of anaphylaxis. The major toxicities attributed to ASP included 5% grade II and 15% grade III-IV aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation, 20% had bilirubin elevation, 10% developed grade III-IV acute pancreatitis, and 5% developed severe hypertriglyceridemia needing aphaeresis. Two patients (10%) developed thrombosis catheter associated deep venous thrombosis (DVT) and one patient with lower extremity proximal DVT within 4 weeks of use of ASP, with one of the two patients (5%) developing (lower extremity proximal DVT) while on being off anticoagulation due to bleeding. Major bleeding or CRNMB developed in 5% (spontaneous splenic rupture from ALL leading to hemorrhagic shock). The median number of cryoprecipitate units used per patient during weeks 1,2,3, and 4 was 5(0-35), 5(0-40), 5(0-15), 7.5(0-15), respectively; No patients received fresh frozen plasma or AT concentrates.
Conclusions: With the use of Apixaban prophylaxis, the incidence of thrombosis was 10% within four weeks from ASP and 5% while on anticoagulation. The incidence of major bleeding or CRNMB was 5%. Hypofibrinogenemia, acquired AT deficiency due to ASP, was seen between days 7-21 after using ASP (figure 1 & 2) and recovered subsequently. This study demonstrates initial evidence of the safety and efficacy of Apixaban for thrombosis prophylaxis and cryoprecipitate infusions in patients treated with ASP.
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Gundabolu: Samus Therapeutics: Research Funding; Pfizer: Research Funding; BioMarin Pharmaceuticals: Consultancy; Bristol-Myers Squibb Company: Consultancy; Blueprint Medicines: Consultancy. Bhatt: Jazz: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy; Abbvie: Consultancy, Research Funding; Partnership for health analytic research, LLC: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy. Vose: Kite, a Gilead Company: Honoraria, Research Funding. Lunning: Myeloid Therapeutics: Consultancy; Janssen: Consultancy; Kyowa Kirin: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; Novartis: Consultancy; Celgene, a Bristol Myers Squibb Co.: Consultancy; AbbVie: Consultancy; TG Therapeutics: Consultancy; Daiichi-Sankyo: Consultancy; Legend: Consultancy; Kite, a Gilead Company: Consultancy; Verastem: Consultancy; Acrotech: Consultancy; Karyopharm: Consultancy; Spectrum: Consultancy; Beigene: Consultancy; Morphosys: Consultancy. Baljevic: BMS/Celgene: Consultancy; Oncopeptides: Other: Advisory Board; Janssen Research: Other: Advisory Board; Karyopharm: Other: Advisory Board; BMS/Celgene: Other: Advisory Board; Amgen: Research Funding; Exelixis: Research Funding. Ganti: Merck: Research Funding; Apexigen: Research Funding; Nektar: Research Funding; Top Alliance Biosceinces: Research Funding; Lovance: Research Funding; Novartis: Research Funding; WindMil Therapeitucs: Research Funding; Takeda: Research Funding; Flagship Biosciences: Consultancy; AstraZeneca: Consultancy, Other: Advisory Board; Mirati Therapeutics: Consultancy, Other: Advisory Board; G1 Therapeutics: Consultancy, Other: Advisory Board; Blueprint Medicines: Consultancy, Other: Advisory Board; Cardinal Health: Consultancy, Other: Advisory Board; Roche: Consultancy, Other: Advisory Board; YMabS Therapeutics: Other: DSMC Chair.
Nitrite-preserved meats (e.g., hot dogs) may help cause colon cancer because they contain N-nitroso compounds. We tested whether purified hot-dog-derived total apparent N-nitroso compounds (ANC) ...could induce colonic aberrant crypts, which are putative precursors of colon cancer. We purified ANC precursors in hot dogs and nitrosated them to produce ANC. In preliminary tests, CF1 mice received 1 or 3 i.p. injections of 5 mg azoxymethane (AOM)/kg. In Experiments 1 and 2, female A/J mice received ANC in diet. In Experiment 1, ANC dose initially dropped sharply because the ANC precursors had mostly decomposed but, later in Experiment 1 and throughout Experiment 2, ANC remained at 85 nmol/g diet. Mice were killed after 8 (AOM tests) or 17-34 (ANC tests) wk. Median numbers of aberrant crypts in the distal 2 cm of the colon for 1 and 3 AOM injections, CF1 controls, ANC (Experiment 1), ANC (Experiment 2),and untreated A/J mice were 31, 74, 12, 20, 12, and 5-6, with P < 0.01 for both ANC tests. Experiment 2 showed somewhat increased numbers of colonic mucin-depleted foci in the ANC-treated group. We conclude that hot-dog-derived ANC induced significant numbers of aberrant crypts in the mouse colon.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
F-18-fluoro-deoxy-glucose positron emission tomography (PET) is a powerful tool for the imaging of aggressive B-cell lymphomas. In contrast, there is relatively little data on PET in follicular ...lymphoma grade 1 (FL-1) and grade 2 (FL-2). In this manuscript, we present our findings utilizing PET in treated FL-1 and FL-2. A retrospective review of patients who underwent PET examinations at our institution produced 95 PET examinations among 31 patients with FL-1 and FL-2. PET was obtained at initial staging, mid-induction and post-treatment. Results were compared with clinical follow-up. PET had high sensitivity (95%) and specificity (88%) for lesion detection in treated FL-1 and FL-2. Abnormal foci in FL-1 and FL-2 had similar intensities. Post-induction PET positive patients had shorter mean progression free survivals compared with PET negative patients (p-value ≤0.001), post-salvage PET positive trended toward shorter mean response duration compared with negative patients (p-value: 0.09). Our results indicate that PET is accurate in the diagnostic assessment of treated FL-1 and FL-2 and, post-treatment PET positive patients are likely to relapse prior to PET negative patients.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Introduction: Whether adults aged ≥60 years with AML benefit from multiagent (or intensive) chemotherapy is a matter of controversy. Prior studies have demonstrated conflicting results. We performed ...analysis of a large National Cancer Data Base (NCDB) to determine the value of multiagent vs. single agent chemotherapy.
Methods: NCDB captures approximately 70% of all cancer diagnoses in US, and undergoes rigorous quality monitoring. We utilized NCDB to identify patients aged 60-79 years, who were newly diagnosed with AML (other than APL) between the years 2004-2014. Logistic regression model was used to determine factors associated with the use of multiagent chemotherapy. Kaplan-Meier curves were generated and compared using the log rank test. Logistic regression model and Cox Proportional Hazard model were used for one-month mortality and OS analyses, respectively. In a separate analysis, patients who received single agent (n=6743) vs. multiagent chemotherapy (n=6743) were matched based on the variables age, Charlson comorbidity score, and AML subtypes (good-risk AML, therapy-related AML/AML with myelodysplasia related changes, and other intermediate/high-risk AML). A Cox Proportional Hazard model was used for OS analysis of the matched cohort.
Results: Of a total of 25,621 patients, 70% received multiagent chemotherapy. The receipt of multiagent chemotherapy declined with increasing age, Charlson comorbidity score, AML subtypes other than good-risk, female, non-academic center, shorter distance traveled to receive care, lower rate of high school graduation, and more recent year of diagnosis. Patients treated with multiagent chemotherapy had higher likelihood of receiving hematopoietic cell transplant (HCT) (9% vs. 1%); lower one-month mortality (11% vs. 19%); and greater 1-year OS (43% vs. 28%) (Figure 1). The use of multiagent chemotherapy had particularly higher 1-year OS in patients aged 60-64 and 65-69 years, in good-risk AML, patients with Charlson comorbidity score of 0-1 and those who did not receive upfront HCT consolidation (Table 1). One-month mortality (odds ratio 1.64, 95% confidence interval, CI 1.51-1.78) and OS (hazard ratio, HR 1.32, 95% CI 1.28-1.36) remained more favorable for multiagent chemotherapy group in multivariable analyses. Other factors that affected OS included age, comorbidity, AML subtypes, median household income, insurance, use of HCT, academic status of facility, distance traveled to receive care, sex and year of diagnosis. In a matched analysis of 13,486 patients, the use of single agent vs. multiagent chemotherapy resulted in a higher risk of mortality (HR 1.28, 95% CI 1.23-1.32).
Conclusions: In one of the largest real-world studies, we demonstrate an association between factors such as age, comorbidity and AML subtypes and the use of multiagent chemotherapy. After adjusting for covariates, the use of multiagent chemotherapy among older adults was associated with higher receipt of HCT, and improved one-month mortality and OS. Improved OS was confirmed in a matched analysis. Certain groups such as patients younger than 70 years, good-risk AML and those with low Charlson comorbidity score had the greater OS benefit with the use of multiagent chemotherapy. Further studies to determine the role of multiagent or intensive chemotherapy are particularly important with approvals of several new drugs in the recent years and integration of many novel drugs in both low-intensity and intensive chemotherapy regimens.
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Bhatt:Tolero Pharmaceuticals: Research Funding; Incyte: Consultancy, Research Funding; Partner therapeutics: Consultancy; Abbvie: Consultancy; Agios: Consultancy; CSL Behring: Consultancy; National Marrow Donor Program: Consultancy; Pfizer: Consultancy. Holstein:Celgene: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy; Genentech: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sorrento: Consultancy. Al-Kadhimi:Celldex Biotech: Other: Stocks; Seattle Genetics: Other: Stocks. Armitage:Union Pacific: Consultancy; Tesaro bio: Membership on an entity's Board of Directors or advisory committees; Ascentage: Consultancy; Samus Therapeutics: Consultancy; Oncology Analytics: Consultancy; Partner Therapeutics: Consultancy. Gundabolu:Pfizer: Consultancy; Novartis: Consultancy; Jazz pharmaceuticals: Consultancy; Samus Therapeutics: Research Funding.
The fibroblast-populated 3D collagen matrix is a model of tissue and healing which has been used since the 1980's. It was hypothesized that anchorage disruption of the collagen matrix would produce ...p53-dependent apoptosis in the embedded fibroblasts, but results of hypothesis testing were variant.
The response of p53 to anchorage disruption in 3D culture or to UV irradiation in 2D culture was influenced both by fibroblast strain and culture conditions. It also was determined that data scatter in a collagen matrix contraction assay was related to fibroblast strain and possibly to technical factors, such as cell culture technician and/or number of matrices utilized. Subsequent analysis suggested that phenotypic drift and/or inter-strain genetic variability may have been responsible for the data scatter. In addition, several technical factors were identified that may have contributed to the scatter.
Experimentation with human foreskin fibroblasts in both 2D and 3D culture can produce variant data. The underlying cause of the data scatter appears to be partially due to the biologic variability of the fibroblast.
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