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1
Buckner, Jan C., Karla V. Ballman, John C. Michalak, Gary V. Burton, Terrence L. Cascino, Paula J. Schomberg, Roland B. Hawkins, et al. "Phase III Trial of Carmustine and Cisplatin Compared With Carmustine Alone and Standard Radiation Therapy or Accelerated Radiation Therapy in Patients With Glioblastoma Multiforme: North Central Cancer Treatment Group 93-72-52 and Southwest Oncology Group 9503 Trials." Journal of Clinical Oncology 24, no. 24 (August 20, 2006): 3871–79. http://dx.doi.org/10.1200/jco.2005.04.6979.
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Purpose In patients with newly diagnosed glioblastoma multiforme, to determine whether cisplatin plus carmustine (BCNU) administered before and concurrently with radiation therapy (RT) improves survival compared with BCNU and RT and whether survival using accelerated RT (ART) is equivalent to survival using standard RT (SRT). Patients and Methods After surgery, patients were stratified by age, performance score, extent of surgical resection, and histology (glioblastoma v gliosarcoma) and then randomly assigned to arm A (BCNU plus SRT), arm B (BCNU plus ART), arm C (cisplatin plus BCNU plus SRT), or arm D (cisplatin plus BCNU plus ART). Results Four hundred fifty-one patients were randomly assigned, and 401 were eligible. Frequent toxicities included myelosuppression, vomiting, sensory neuropathy, and ototoxicity and were worse with cisplatin. There was no difference in toxicity between SRT and ART. Median survival times and 2-year survival rates for patients who received BCNU plus RT (arms A and B) compared with cisplatin, BCNU, and RT (arms C and D) were 10.1 v 11.5 months, respectively, and 11.5% v 13.7%, respectively (P = .19). Median survival times and 2-year survival rates for patients who received SRT (arms A and C) compared with ART (arms B and D) were 11.2 v 10.5 months, respectively, and 13.8% v 11.4%, respectively (P = .33). Conclusion Cisplatin administered concurrently with BCNU and RT resulted in more toxicity but provided no significant improvement in survival. SRT and ART produced similar toxicity and survival.
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Wu, Hong Lei, Rui Sheng Zheng, Wei Zheng, and Zheng Yan. "Growth of p-Type AlN Crystals by C and Si Codoping." Advanced Materials Research 306-307 (August 2011): 246–50. http://dx.doi.org/10.4028/www.scientific.net/amr.306-307.246.
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Based on our earlier theoretical investigation,p-type C:Si codoped AlN crystals were grown on SiC substrates by a sublimation method in a improved growth reactor. Hall-effect measurement shows that the AlN crystals have a high hole density of 1.4×1014cm-3and mobility of 52 cm2V-1s-1in spite of the high resistivity (896 Ω•cm). In the AlN samples, Si dopants act as donors due to substituting Al atoms, and most of C dopants act as acceptors for replacing N atoms. It is also observed that the activation energy of C acceptors in C:Si codoped AlN is reduced by codoping Si donors, which agrees with the computational results.
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Farias, Miguel Angel, Silvia Andrea Medici, Aldo Fabián Squassi, and Gabriel Antonio Sánchez. "Unmet dental treatment need impairs quality of life in Hepatitis C Virus-infected patients." STOMATOLOGY EDU JOURNAL 7, no. 3 (2020): 191–96. http://dx.doi.org/10.25241/stomaeduj.2020.7(3).art.5.
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Introduction The hepatitis C virus (HCV) infection is a health condition affecting 3% of the world population, which oral manifestations and associated factors interest both physicians and dentists. The aim of this work was to describe the dental treatment need and the impact of the perception of the oral component of health on the quality of life in HCV+ patients. Methodology Descriptive study on a convenience sample. 45 HCV+ patients (46±5 y.o.) completed the OHIP-14 questionnaire, which consists of 14 questions grouped in 7 domains (D1 functional limitation, D2 physical pain, D3 psychological discomfort, D4 physical disability, D5 psychological disability, D6 social disability and D7 general disability). The participants indicated their responses using a Likert-type frequency scale. The Community Caries Index of Treatment Need (CCITN) was determined for each patient. The proportion and CI95% of the social impact on the quality of life were calculated. The association between CCITN and the quality of life was assessed by Chi2 (p<0.05). Results The CCITN was 11 (8-14). The overall social impact was 38% (24-52%). The increasing order relationship of the impact on each of the domains was D1, D7, D6, D4, D5, D2, D3. A significant association between oral health-related quality of life and CCITN was observed (Chi2 = 7.57, p = 0.006), showing greater impairment of the quality of life as the treatment need increased. Conclusion The association between CCITN and quality of life becomes evident using OHIP-14 during dental appointments. The results suggest the need for comprehensive interventions during the provision of oral health care to HCV+ patients.
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Lebenthal, Brener, Hershkovitz, Shehadeh, Shalitin, Lewis, Elias, et al. "A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (Glassia®) in the Treatment of Recent-Onset Type 1 Diabetes." International Journal of Molecular Sciences 20, no. 23 (November 29, 2019): 6032. http://dx.doi.org/10.3390/ijms20236032.
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Our aim was to assess the efficacy, safety, and tolerability of alpha-1 antitrypsin (AAT) as a therapeutic modality for β-cell preservation in patients with recent-onset type 1 diabetes. Seventy type 1 diabetes patients (37 males; mean age 13.1 ± 4.1years) were randomized to treatment with 22 infusions of AAT (Glassia®) (60 or 120 mg/kg) or placebo. The primary outcome was the area under the curve (AUC) of C-peptide from a 2-h mixed-meal tolerance test after 52 weeks. At week 52, C-peptide was 0.9, 0.45, and 0.48 pmol/mL in the AAT-120, AAT-60, and placebo groups (p = 0.170 and p = 0.866 vs. placebo, respectively). The declines in C-peptide glycated hemoglobin (HbA1c) and the total insulin dose (U/kg) were similar across groups. Within the predefined 12–18-years subgroup, the C-peptide AUC decreased significantly in the placebo and AAT-60 groups (−0.34 and −0.54 pmol/mL, respectively, p < 0.01), with a borderline decrease in the AAT-120 group (−0.29 pmol/mL, p = 0.047). The mean HbA1c level was significantly lower in the AAT-120 group compared to the placebo (6.7% ± 0.9% vs. 8.2 ± 1.4%, p = 0.05), and a higher percentage of patients attained HbA1c ≤ 7% (75% vs. 25%, p = 0.05). AAT was tolerated well, with a similar safety profile between groups. The AAT intervention showed promise in the subgroup of adolescents with recent-onset type 1 diabetes. Further studies are warranted to determine the impact and proposed mechanism of action of AAT in β-cell preservation.
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Yuen, Man-Fung, Danny Ka-Ho Wong, Erwin Sablon, He-Jun Yuan, Siu-Man Sum, Chee-Kin Hui, Annie On-On Chan, Benjamin Chun-Yu Wong, and Ching-Lung Lai. "Hepatitis B Virus Genotypes B and C Do Not Affect the Antiviral Response to Lamivudine." Antiviral Therapy 8, no. 6 (August 1, 2002): 531–34. http://dx.doi.org/10.1177/135965350300800610.
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To date, there have been no studies examining the role of hepatitis B virus (HBV) genotypes on the response to lamivudine therapy and the development of YMDD mutations. The present study aimed at determining any differences in the antiviral response and risk of YMDD mutations between lamivudine-treated patients with HBV genotype B and genotype C. Eighty-two patients receiving lamivudine were recruited. HBV genotypes at baseline and YMDD mutations at week 52 were determined by line probe assays (LiPA). HBV DNA levels were determined by the Cobas Amplicor HBV Monitor Test. Seventeen (20.7%) and sixty-four (78%) patients had single genotypes of B and C, respectively. At both week 24 and 52 there were no differences in the median reduction of HBV DNA levels (median 4 logs drop), the median reduction of alanine aminotransferase (ALT) levels, and the proportion with normalization of ALT [8/8 (100%) vs 26/37 (70.3%), P=0.19] between patients with genotypes B and C. The rate of HBeAg seroconversion [3/17 (17.6%) vs 6/64 (9.4%), P=0.39] and the chance of YMDD mutation development [3/17 (17.6%) vs 12/64 (18.8%), P=1.0] at week 52 were also similar between patients with genotype B and C, respectively. In conclusion, there was no difference in the antiviral response and the rate of development of YMDD mutations in Chinese patients with genotype B and C after 1 year of lamivudine. Determination of HBV genotypes before lamivudine therapy was probably not an important pre-treatment investigation to predict antiviral responses in Chinese patients.
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Karzai, Fatima H., Ravi Amrit Madan, Andrea Borghese Apolo, Yangmin M. Ning, Howard L. Parnes, Philip M. Arlen, Melony A. Beatson, et al. "Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations in metastatic castrate resistant prostate cancer (mCRPC)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e16017-e16017. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e16017.
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e16017 Background: We have completed accrual of 63 patients (pts) to our study combining lenalidomide (L), with bevacizumab (B), docetaxel (D), and prednisone (P) (ART-P) in mCRPC. Due to the lack of improved survival and the increased toxicity of anti-angiogenic docetaxel combinations in the MAINSAIL and CALGB 90401 trials, we attempted to compare and contrast our studies with these failed phase III trials. Methods: Among the first 52 pts on ART-P, 3 received L 15 mg daily, 3 received 20 mg daily, and the others received 25 mg daily for 14 days of every 21−day cycle (C). We then enrolled 11 pts at L 15 mg. All pts received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and enoxaparin daily. Pegfilgrastim was given on day 2. Patients on CALGB 90401 received D 75 mg/m2 and B 15 mg/kg on day 1, with P 10 mg. On MAINSAIL, pts received D 75 mg/m2, L 25 mg daily for 14 days of every 21−day cycle with daily P. Patients on CALGB 90401 and MAINSAIL did not receive enoxaparin or pegfilgrastim prophylactically. Results: The median number of Cs on ART-P is 18 (1-52). Median PFS is 19.1 months. Twenty-seven pts had a PR, and one pt with measurable disease had a CR. Two patients (3%) had deep vein thromboses. Of 1,334 Cs given, 14 cycles were complicated by febrile neutropenia (FN) (1%). There were no treatment related deaths. In comparison, median number of Cs in MAINSAIL L+DP arm was 6, with a PFS of 45 weeks and an OS of 77 weeks. Thirty-four pts (6.5%) developed pulmonary emboli and there were 2 deaths due to toxicity in the experimental arm. Nearly 12% of Cs were complicated by FN. In the experimental arm of CALGB 90401 trial, median OS was 22.6 months with median PFS of 9.9 months. The median number of Cs were 8 and 19 pts developed thrombosis/emboli (3.6%). In addition, 37 patients developed FN and treatment related deaths were reported at 4%. Conclusions: The use of supportive care allowed longer treatment duration with the ART-P combination as compared to D+L (MAINSAIL) and D+B (CALGB 90401), potentiating a longer PFS, RR and possibly OS with an improved safety profile. This data demonstrates the potential importance of supportive measures and is hypothesis generating for future combination studies. Clinical trial information: NCT00942578.
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Karzai, Fatima H., Bamidele Adesunloye, Yangmin M. Ning, Ravi Amrit Madan, James L. Gulley, Andrea Borghese Apolo, Melony A. Beatson, et al. "Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations." Journal of Clinical Oncology 31, no. 6_suppl (February 20, 2013): 128. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.128.
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128 Background: We have recently completed accrual of 63 patients (pts) to our study combining lenalidomide (L), with bevacizumab (B), docetaxel (D), and prednisone (P) (ART-P). Due to the lack of improved survival and the increased toxicity of anti-angiogenic docetaxel combinations in the MAINSAIL and CALGB 90410 trials we attempted to contrast and compare our studies with the failed phase III trials. Methods: Among the first 52 pts on the ART-P, 3 received L 15 mg daily, 3 had 20 mg daily, and the rest had 25 mg daily for 14 days of every 21−day cycle (C). We later enrolled 11 more pts at L 15 mg. All pts received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and enoxaparin daily throughout each C. Pegfilgrastim was given on day 2. Patients on CALGB 90410 received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and on MAINSAIL received D 75 mg/m2, L 25 mg daily for 14 days of every 21−day cycle with daily P. Patients on CALGB 90410 and MAINSAIL did not receive enoxaparin or pegfilgrastim prophylactically. Results: Median number of Cs in ART-P was 16 (3−38). PFS was 22 months and median OS has not been reached. Pts with measurable disease had 1 CR and 25 PR (86.7% RR). Two patients (3%) had deep vein thromboses. Of 1,219 cycles given, 14 cycles were complicated by febrile neutropenia (FN) (1.1%). There were no treatment related deaths. In comparison, median number of Cs in MAINSAIL L+DP arm was 6, with a PFS of 45 weeks and an OS of 77 weeks. Thirty-four pts (6.5%) developed pulmonary emboli and there were 2 deaths due to toxicity in the experimental arm. Nearly 12% of Cs were complicated by FN. In the experimental arm of CALGB 90410 trial, median OS was 22.6 months with median PFS of 9.9 months. Median number of Cs was 8, and 19 pts developed thromboses/emboli (3.6%). In addition, 7% of patients developed FN and treatment related deaths were reported at 4%. Conclusions: The use of supportive care allows the ART-P combination to be given for more cycles than were given in MAINSAIL and CALGB 90401 potentiating a longer PFS, RR and possibly OS with an improved toxicity profile. This data demonstrates the potential importance of supportive measures and is hypothesis generating for future combination studies. Clinical trial information: NCT00942578.
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Saito, Hidehiko, Ikuro Maruyama, Shuji Shimazaki, Yasuhiro Yamamoto, Naoki Aikawa, Ryuzo Ohno, Akio Hirayama, et al. "Efficacy and Safety of Recombinant Human Soluble Thrombomodulin (ART-123) in Disseminated Intravascular Coagulation (DIC): Results of Phase III Randomized, Double-Blind, Clinical Trial." Blood 108, no. 11 (November 16, 2006): 576. http://dx.doi.org/10.1182/blood.v108.11.576.576.
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Abstract Background: Thrombomodulin is a thrombin receptor on the endothelial cell surface that plays an important role in the regulation of intravascular coagulation. Recombinant human soluble thrombomodulin (ART-123) is composed of the active, extracellular domain of thrombomodulin. ART-123 has been shown to have a wider safety margin than other anticoagulants and to have a favorable antithrombotic profile with less bleeding in animal and in vitro experiments. ART-123 is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. Objective: We conducted a multicenter, double-blind, randomized parallel-group trial to compare the efficacy and safety of ART-123 to those of heparin for the treatment of disseminated intravascular coagulation (DIC) associated with infection or hematologic malignancy. Methods: DIC was diagnosed according to the diagnostic criteria established by the Japanese Ministry of Health and Welfare. DIC patients were assigned to receive ART-123 (0.06 mg/kg for 30 min, once a day) or heparin sodium (8 units/kg/h for 24 h) for six days using a double dummy method. The primary efficacy endpoint was DIC resolution rate (rate of recovery from DIC). The secondary endpoints included clinical course of bleeding symptoms, and mortality at 28 days. Results: 234 DIC patients were randomized (117 in each arm). DIC resolution rate was 66.1% for the ART-123 group and 49.9% for the heparin group (difference 16.2%; 95% CI 3.3–29.1), thus demonstrating that ART-123 is significantly superior to heparin for the improvement of DIC. Patients in the ART-123 group also showed more marked improvement in clinical course of bleeding symptoms (p=0.0271) and the disappearance rate of bleeding symptoms in the ART-123 group was higher than that in the heparin group (35.2% vs 20.9%; difference 14.3%). The incidence of bleeding-related adverse events up to 7 days after the start of administration was lower in the ART-123 group than in the heparin group (43.1% vs 56.5%; difference; −13.4%; p=0.0487). The mortality rate at 28 days in the ART-123 group was 22.0% vs 25.5% in the heparin group (difference −3.4%; p=0.5396). Although no significant differences were seen, 28-day mortality for the ART-123 group was slightly lower. The mortality rate of patients with DIC secondary to infection in the ART-123 and heparin groups was 28.0% (14/50) and 34.6% (18/52), respectively, indicating a 6.6% lower mortality in the ART-123 group. Conclusion: When compared with low-dose heparin, ART-123 more significantly improves DIC and alleviates bleeding symptoms in DIC patients. The incidence of bleeding-related adverse events is significantly lower with ART-123 than with heparin. Because of its safety and efficacy, ART-123 appears to be a first-line agent in the management of DIC.
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Kharlamova, T. V., S. L. Voznesenskiy, T. N. Ermak, G. M. Kozhevnikova, and P. V. Klimkova. "Infectious endocarditis in HIV-infected intensive care unit patients." Journal Infectology 14, no. 2 (July 13, 2022): 73–79. http://dx.doi.org/10.22625/2072-6732-2022-14-2-73-79.
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Infective endocarditis (IE) is one of the most common cardiac complications in HIV patients who are intravenous drug addicts. The presence of IE and secondary diseases in immunocompromised individuals usually requires specific diagnostic and therapeutic approach.Aim: Optimizing the diagnosis of IE in patients with advanced HIV/AIDS.Materials and methods We reviewed 429 case records of HIV/AIDS ICU patients using the modified duke criteria for diagnosis of infective endocarditis. Statistical significance (p <0.05) of data was assessed using the χ2 test.Results. 25 patients were diagnosed with IE. The male gender dominated – 68%. Mean age was 38. 60% had stage 4B HIV infection. 68% were ART naive. The medium viral load was 294560 copies / ml, while the medium CD4 count was 218 cells / μl. Fever of >38°C was a key symptom found in all patients. Blood cultures were positive in 60% cases. 80% had a high C reactive protein (CRP), and 44% had CRP levels above 100 mg/l. Procalcitonin (PCT) levels were increased in 52%. Echocardiogram revealed IE in 92%. Pneumonia was diagnosed in 92%. Fatal outcome occurred in 76%. Anemia was a predictor of severe outcome (p<0.002), while patients with leukocytosis had good prognosis (p<0.05).Conclusion. Infective endocarditis is a common complication among HIV IDUs. The most common diagnostic criteria are fever >38°C, pneumonia, anemia, leukocytosis, thrombocytopenia and echocardiographic findings. The levels of the hemoglobin and WBCs could evaluate prognosis of the disease outcome.
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Yastrebova, E. B., O. E. Chernova, A. M. Kalyshenko, and G. A. Vertogradova. "Chronic hepatitis C in children with HIV infection: disease phenotype and efficacy of antiviral therapy." Infekcionnye bolezni 19, no. 2 (2021): 52–58. http://dx.doi.org/10.20953/1729-9225-2021-2-52-58.
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Objective. To analyze the course of chronic hepatitis C (CHC) and efficacy of its treatment in children with HIV infection. Patients and methods. This study included 29 children aged 12 to 17 years (mean age 15.1 ± 0.2 years) with perinatal HIV infection and CHC. HIV stages were distributed as follows: stage 4A in 24 individuals (82.8%), stage 4B in 4 individuals (13.8%), and stage 4B in 1 individual (3.4%). All 29 patients received antiretroviral therapy. The distribution of children by HCV genotypes was as follows: 1a in one child (3.4%), 1b in 12 children (41.4%), and 3a in 16 children (55.2%). Antiviral therapy for CHC included glecaprevir/pibrentasvir (3 tablets; 100 mg + 40 mg) once a day for 56 days. Data analysis was performed using the Statistica for Windows software (version 10.0). Results. The mean HCV RNA level was 595,666 ± 34,734 IU/mL (range: 1,100–3,863,025 IU/mL). After 4, 8, or 12 weeks of antiviral therapy for HCV, HCV RNA clearance was achieved in all study participants (p = 0.01). Before treatment initiation, mean CD4+ count was 738 ± 34 cells/μL (above 500 cells/μL), which indicated the absence of immunodeficiency in the group analyzed. Successful antiviral therapy for HCV (sustained virologic response at week 12; SVR 12) also resulted in increase of the CD4+ lymphocytes level, which was considered as a positive effect of glecaprevir/pibrentasvir (p = 0.15). We observed significant differences in the level of liver enzymes (ALT and AST) (p = 0.01) between samples collected before antiviral therapy initiation and those collected during treatment, as well as 12 weeks after its completion (SVR12). All children demonstrated good tolerance of glecaprevir/pibrentasvir; none of them had adverse events, complaints, or clinical/laboratory changes. Conclusion. Thus, all children with HIV infection and CHC achieved SVR12 after the 8-week course of antiviral therapy with glecaprevir/pibrentasvir regardless of HCV genotype. Clinical manifestations (hepatosplenomegaly in 62.1%; asthenovegetative syndrome in 31.0%) were eliminated after 8 weeks of therapy. Laboratory manifestations (hepatic cytolysis (AST/ALT)) were normalized after 4 weeks of therapy. Antiviral treatment for HCV resulted in some increase in the level of CD4+ lymphocytes. We observed no adverse events caused by glecaprevir/pibrentasvir (neither clinical symptoms nor changes in complete blood count or liver function tests), which confirms the safety of this treatment regimen. Key words: antiretroviral therapy, HIV infection, children, direct-acting antivirals, chronic hepatitis C
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Voskaridou, Ersi, Eleni Plata, Dimitrios Christoulas, Charoula Xirakia, Eleni Stoupa, Konstantinos Varvagiannis, Antonios Bilalis, Athanasios Papatheodorou, Panagiotis Tsaftaridis, and Evangelos Terpos. "Deferasirox Reduces Serum TNF-α but Impairs Renal Function in Patients with Thalassemia Major after 12 Months of Therapy." Blood 112, no. 11 (November 16, 2008): 3888. http://dx.doi.org/10.1182/blood.v112.11.3888.3888.
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Abstract Deferasirox is an oral iron chelator approved for the management of iron overload in thalassemia major (TM). However, there are some concerns for its effect on renal function. Cystatin C (Cys-C) is a cysteine protease inhibitor, which is considered as a sensitive marker of GFR. Inflammation process has been recently implicated in TM pathophysiology. The aim of this study was to evaluate the effect of deferasirox on renal function and inflammatory cytokines in 52 TM patients. Deferasirox was administered at a dose between 10–30 mg/kg/day for a 12-month period. Serum Cys-C, serum creatinine (Cr), clearance of Cr (Ccr), albuminuria and inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), IL-1α, IL-1β, IL-4, IL-10 and transforming growth factor (TGF)-β1 and β2, were measured at baseline and then after 6 and 12 months post-deferasirox therapy. Standard hematology and biochemistry was evaluated monthly. Serum Cys-C was measured using a latex particle-enhanced nephelometric immunoassay (Dade Behring, Liederbach, Germany). Serum levels of the above cytokines were determined using ELISA (R&D Systems, Minneapolis, MN, USA, for ILs, and Diaclone, Bensancon, France for TNF-α, TGF-β1 and TGF-β2). Ten healthy blood donors were also evaluated as control group. At baseline, TM patients had elevated values of Cys-C (p<0.0001) compared with controls. Specifically, 21/52 patients (40%) had higher Cys-C values than the upper normal limit according to manufacturer (0.95 mg/L), while no patient had increased levels of serum Cr (>1.4 mg/dl) and only 6 (11.5%) had low Ccr (<80 ml/min). Before deferasirox administration, TM patients had also increased levels of IL-6 (p=0.008), IL-1α (p=0.015), TGF-β2 (p=0.017), IL-10 (0.021), IL-4 (p=0.039), and a borderline increase of TNF-α (p=0.05) compared with controls (Table). Serum levels of Cys-C correlated strongly with Cr (r=0.657, p<0.0001), and Ccr (r=−0.625, p<0.0001) but also with IL-6 (r=0.441, r<0.001) and proteinuria (r=0.261, p=0.037). Il-1a correlated with Hb (r=−0.417, p<0.001) and IL-4 (r=0.474, p<0.001), while IL-6 correlated with TNF-α (r=0.37, p<0.01). After 6 and 12 months of therapy, deferasirox produced a dramatic reduction of ferritin, SGOT and SGPT compared with baseline values (p<0.0001), but concomitantly we observed an increase of Cys-C and Ccr during the same period (p<0.0001). In particular at the end of the study 32/52 patients (61.5%) had increased Cys-C values, while 10 (19.2%) had low Ccr and only one high serum Cr. Interestingly serum levels of TNF-α reduced post-deferasirox administration (p=0.01), while the levels of all other cytokines remained unchanged during therapy (Table). Our study suggests that deferasirox is an effective chelator in TM. However, its effect on renal function is not insignificant and needs further investigation. Inflammatory cytokines seem to have a role in the pathogenesis of TM but further studies are needed to fully elucidate this role as well as the effect of deferasirox, if any, on inflammation. Table 1. Characteristics of patients & controls (mean values ± SD) Parameters Controls (n=10) Patients-baseline values (n=52) p-value (patients vs. controls) Patients-12-month values p-value patients (baseline vs. 12 m) Age(years) 40.8±11.7 39.5±10.9 0.782 Gender(Male/Female) 4/6 22/30 0.346 Hb(g/dL) 14.8±2.6 8.8±1.4 <0.0001 8.7±1.5 AST(U/L) 29.3±10.1 46.7±23.9 <0.0001 35.5±19.2 <0.0001 ALT(U/L) 23.8±12.5 50.7±28.6 <0.0001 34.3±22.1 <0.0001 Ferritin(μg/L) 88±34.2 2355±1380 <0.0001 1516±1320 <0.0001 Serum Creatinine (mg/dL) 0.8±0.1 0.7±0.1 0.823 0.8±0.2 0.001 Creatinine Clearance (ml/min/1.732) 125.2±22.7 126.5±29.9 0.227 117.0±31.1 0.005 Proteinuria(mg/24h) 55.4±28.2 322.9±461.6 <0.0001 323.4±417.0 0.976 Cystatin-C (mg/L) 0.76±0.11 0.93±0.26 <0.0001 1.12±0.37 <0.0001 Inflammatory Cytokines IL-1α (pg/mL) 0.08±0.19 0.65±0.80 0.015 1.06±1.13 0.114 IL-1β (pg/mL) 2.30±2.54 1.68±2.37 0.475 2.05±2.82 0.571 IL-4 (pg/mL) ND 0.78±1.83 0.039 0.28±0.59 0.167 IL-6 (pg/mL) 0.09±0.21 2.50±4.42 0.008 3.00±7.51 0.752 TNF-α (pg/mL) 1.13±2.05 3.85±7.48 0.05 0.46±1.40 0.015 TGF-β1 (ng/mL) 87.1±21.7 107.5±53.6 0.180 112.1±74.0 0.678 TGF-β2 (pg/mL) 5.62±10.5 19.5±26.4 0.017 15.8±29.7 0.318
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Lazova, Snezhina, Tea Alexandrova, Nadzhie Gorelyova-Stefanova, Kalin Atanasov, Iren Tzotcheva, and Tsvetelina Velikova. "Liver Involvement in Children with COVID-19 and Multisystem Inflammatory Syndrome: A Single-Center Bulgarian Observational Study." Microorganisms 9, no. 9 (September 15, 2021): 1958. http://dx.doi.org/10.3390/microorganisms9091958.
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SARS-CoV-2 infection may precede and cause various autoimmune and inflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C). Therefore, we aimed to observe the clinical presentation and laboratory, instrumental and other constellations in children with MIS-C, including liver involvement. We present the outcomes from a single-center prospective observational study in which 89 children was included (60 with proven COVID-19, 10 symptomatic with confirmed COVID-19 contact and 19 diagnosed with MIS-C). Laboratory, instrumental, immunological, and clinical investigations were performed. Only 12% (n = 4) from the COVID-19 group (except the ICU cases), we found elevated AST and/or ALT (up to 100). All of the children with elevated transaminase were overweight or obese, presenting along with moderate COVID-19 pneumonia. The majority of children with MIS-C showed typical laboratory constellations with higher levels of IL-6 (120.36 ± 35.56 ng/mL). About half of the children in the MIS-C group (52%, n = 11) showed elevated transaminases. Eleven children (57.9%) presented with abdominal pain, eight (42.1%) with ascites, two (10.5%) with hepatosplenomegaly, and four (21.1%) with symptoms such as diarrhea. Mesenteric lymphadenitis was observed more often in patients with elevated LDH (327.83 ± 159.39, p = 0.077). Ascites was associated with lymphopenia (0.86 ± 0.80, p = 0.029) and elevated LDH. Hepato-splenomegaly was also more frequent in children with lymphopenia (0.5 ± 0.14, p = 0.039), higher troponin (402.00 ± 101.23, p = 0.004) and low ESR. Diarrhea was more frequent in patients with lower CRP (9.00 ± 3.44 vs. 22.25 ± 2.58, p = 0.04), and higher AST and ALT (469.00 ± 349.59 vs. and 286.67 ± 174.91, respectively, p = 0.010), and D-dimer (4516.66 ± 715.83, p = 0.001). Our data suggest that the liver can also be involved in MIS-C, presenting with typical laboratory and instrumental outcomes.
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Kahl, Lesley, Grace A. McComsey, Monica Coronado Poggio, Sergio Lupo, Joss de Wet, David A. Parks, Brian Wynne, et al. "319. SWORD 1 and 2: Switch from TDF Containing Regimen to DTG+RPV Maintains Bone Mineral Density and Decreases Bone Turnover Markers Over 148 Weeks." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S169—S170. http://dx.doi.org/10.1093/ofid/ofz360.392.
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Abstract Background HIV infection and antiretroviral therapy (ART), particularly tenofovir (TDF), is associated with loss of bone mineral density (BMD). The SWORD studies demonstrated noninferiority of the 2-drug regimen (2DR) dolutegravir (DTG) + rilpivirine (RPV) to continuing current triple-therapy ART (CAR) at 48 weeks and continued viral suppression on DTG+RPV through Week 148. A substudy of SWORD 1 and 2 evaluated a change in BMD by DEXA for those participants who switched from triple ART containing TDF to DTG+RPV. The primary analysis reported at 48 weeks showed a significant increase in total hip and lumbar spine BMD and a significant decrease in bone turnover markers in patients receiving DTG+RPV compared with CAR. Here we present data through Week 148. Methods HIV-infected adult patients with HIV-1 RNA < 50 c/mL received ART containing TDF for ≥6 months prior to randomization to DTG+RPV (Early Switch group, ES) or CAR on Day 1 (Baseline, BL) through Week 48 in SWORD-1/2. CAR patients suppressed at Week 48 switched to DTG+RPV at Week 52 (Late Switch group, LS). Hip and lumbar spine BMD were measured by DEXA scans read centrally. Secondary endpoints include a change in BMD and bone turnover markers through Week 148. Results Following switch to DTG+RPV significant increases were observed for total hip in the ES and LS groups through 100 weeks with a non-significant increase at Week 148 in ES (Figure 1a). Lumbar spine BMD significantly increased from BL at 48 weeks post switch, remained increased, though not significantly from BL through Week 148 (Figure 1b). The BMD of the LS group was similar to that of the ES group through 100 weeks exposure. The majority of patients remained in their pre-switch T-score category or improved a category for both hip and spine through Wk148 (Table 1). Through Wk148, BMI increased minimally and bone turnover markers significantly decreased (P < 0.001 to 0.042 across markers) from BL/LS BL except Type I Collagen C-Telopeptide at Wk148 in the LS group (P = 0.279). Conclusion Switch to the DTG+RPV 2DR was associated with sustained improvements in BMD through Week 148, along with a reduction in bone markers. The favorable effects on skeletal health were observed despite the ageing of study patients and other factors decreasing BMD. A switch to DTG+RPV in suppressed patients provides a robust option for preserving bone health while continuing suppressive HIV treatment. Disclosures All authors: No reported disclosures.
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Kim, Huikyung, Sangwoo Moon, Jinmi Kim, and Jiwoong Lee. "The Effect of Amniotic Membrane Transplantation on Trabeculectomy in Patients with Pseudoexfoliation Glaucoma." Journal of Ophthalmology 2022 (July 30, 2022): 1–10. http://dx.doi.org/10.1155/2022/9355206.
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Purpose. The aim is to evaluate the effect of amniotic membrane transplantation (AMT) on trabeculectomy with mitomycin C in patients with pseudoexfoliation glaucoma (PXG). Methods. This retrospective cohort study included 85 eyes of PXG who underwent trabeculectomy with or without AMT (52/33 eyes in the AMT/control group). Surgical success was defined by these criteria: (1) intraocular pressure (IOP) ≤18 mmHg and IOP reduction ≥ 20% and (2) IOP ≤15 mmHg and IOP reduction ≥ 25%. Criteria A and B defined complete success rates as patients who met these criteria without medication, respectively. Criteria C and D defined qualified success rates as patients who met these criteria with medication, respectively. Cumulative probabilities of success were compared using the Kaplan–Meier survival analysis. Cox proportional hazard models were used to evaluate the influence of AMT on surgical success accounting for confounding variables. Results. For the AMT group, compared with the control group, the complete success rates at 12 months for criterion A were 86.5% and 63.6%, respectively ( P = 0.017 ) and for criterion B, 86.4% and 63.6% ( P = 0.005 ). The qualified success rates at 12 months for criterion C were 92.1% and 75.1%, respectively ( P = 0.047 ) and for criterion D, 92.1% and 72.1% ( P = 0.021 ). On multivariable Cox regression analyses, AMT was associated with a lower failure rate on criteria A, B, and D (all P ≤ 0.047 ). Incidence of avascular bleb was higher in the control group than in the AMT group (7 vs 0 eyes; P = 0.004 ). Conclusions. In patients with PXG, trabeculectomy with AMT was associated with higher success rates and a lower incidence of avascular bleb compared with conventional trabeculectomy. Research Registration. This retrospective cohort study was registered at the Clinical Trial Registry of Korea (https://cris.nih.go.kr/cris/index/index.do, KCT0007228).
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Karnes, Jeffrey, Hussam Al-Deen Ashab, Bruce J. Trock, Ashley Ross, Harrison Tsai, Jeffrey J. Tosoian, Nicholas Erho, et al. "Development and validation of an ADT resistance signature to predict adjuvant hormone treatment failure." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 106. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.106.
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106 Background: Androgen deprivation therapy (ADT) is one of the main treatment options for locally advanced and metastatic prostate cancer. Neuroendocrine prostate cancer (NEPC) is inherently less sensitive or even resistant to ADT. NEPC can be observed de novo (e.g., small cell prostate cancer) but more commonly arises after exposure to ADT. We hypothesized that a gene expression signature of NEPC when measured in primary tumor specimens (RP) of prostatic adenocarcinoma may be useful for predicting patients with innate resistance to ADT. Methods: Expression profiles of 1023 PCa patients treated with RP were obtained from the Decipher GRID database. These were split into training (n=529) and validation (n=494) sets and stratified by the receipt of adjuvant ADT (n=243) or no adjuvant ADT (n=780). A literature review of ADT resistance and neuroendocrine genes identified 1,557 genes as candidates. This set was further filtered, using logistic regression to select a 52-gene ADT resistance signature (ARS). ARS was trained using a generalized linear model with lasso regularization. Survival c-index and Kaplan Meier was used to compare survival differences between treated and untreated patients with high and low ARS scores (defined by median split). Results: In validation cohorts, the ARS was predictive of metastasis in cohorts receiving adjuvant ADT (10-year metastasis free survival c-index of 0.69 (95% CI 0.59-0.78) as compared to 0.45 (95% CI 0.29-0.61) in patients not treated with ADT). Similarly in a separate cohort of untreated patients that received no ADT until after metastatic onset, ARS was not prognostic (c-index 0.53). Among ADT treated patients, those with low ARS scores had a 10 year MFS of 87%, versus 70% in those with high ARS scores (p<0.001). In the subset of men who received ADT after metastatic onset and who developed castrate-resistant prostate cancer (CRPC, n = 41), median time to treatment failure was 1 year in patients with high ARS compared to 2 years for those with low ARS scores (p=0.07). Conclusions: A 52-gene ADT resistance signature was developed which showed significant differences in metastasis-free survival among adjuvant hormone treated but not untreated patients.
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Vaubourdolle, M., O. Chazouillères, I. Briaud, C. Legendre, L. Serfaty, R. Poupon, and J. Giboudeau. "Plasma alpha-glutathione S-transferase assessed as a marker of liver damage in patients with chronic hepatitis C." Clinical Chemistry 41, no. 12 (December 1, 1995): 1716–19. http://dx.doi.org/10.1093/clinchem/41.12.1716.
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Abstract alpha-Glutathione S-transferase (alpha-GST; EC 2.5.1.18) has been advocated as a better marker of hepatocellular damage than the transaminases in toxic and autoimmune hepatitis. We have assessed the potential interest of plasma alpha-GST determination in 94 anti-hepatitis C virus-positive patients with histologically proven chronic hepatitis C (34 women, 60 men, ages 40.0 +/- 11.9 years). Blood samples were assayed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase, alkaline phosphatase, and alpha-GST on the same day a liver biopsy was performed. alpha-GST concentrations were significantly above reference values in 64% of patients (compared with 58% for AST, 68% for ALT), and this increase was seen in 52% of patients with normal values for transaminases and a Knodell score > 3. Furthermore, there was a significant correlation between alpha-GST and lobular necrosis score (r = 0.31; P < 0.01). Our findings suggest that association of plasma alpha-GST with ALT may improve the biochemical assessment of liver damage in patients with chronic hepatitis C.
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Okihara, K., I. Takeuchi, O. Ukimura, N. Takaha, A. Kawauchi, and T. Miki. "Prognostic outcome in Japanese men with prostate cancer treated with androgen-deprivation therapy (ADT) alone: Data from multi-institutional cooperative study in Kyoto Prostate Cancer Registry (KPCR)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e16106-e16106. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e16106.
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e16106 Background: There is scarce data of ADT alone concerning prognostic outcome in terms of clinical stage, and in comparison with radical treatments specifically in men without metastatic diseases. The aim of this study was to analyze prognostic outcome for ADT alone, and to assess the significant prognostic parameters in Japanese men. Methods: Database in the KPCR, which is a multi-institutional urologic cancer registry, was screened to identify prostate cancer patients who received ADT alone between 1988 and 2008. Clinical data including age, clinical stage, biopsy differentiation, initial prostate-specific antigen (PSA) level and type of ADT: luteinizing hormone-releasing hormone (LH-RH) monotherapy or combined androgen blockade (CAB), were analyzed. Time to prostate cancer relapse as well as cause specific survivals were also analyzed. Results: Of 1167 men with prostate cancer registered in KPCR, 373 patients (32%) received primary ADT and continued ADT alone during the observation period. Of those men, age and PSA level ranged from 52 to 95 y.o (median: 75) and from 2.17 to 8,650 ng/ml (median: 23.5), respectively. The numbers of clinical stage in A to B, C and D were 148 (40%), 127 (34%), and 98 (26%), respectively. The observation period ranged from 1 to 125 months (median: 55). Of the 373 men, 113 men (30%) recurred after the primary ADT. Of the 131men, 36 men (10%) changed from LH-RH monotherapy to CAB, and 46 (12%) and 52 men (14%) underwent anti-androgen alternative therapy and secondary hormonal therapy using estramustine phosphate and/or oral dexamethasone, respectively. There was a significant difference in 5-year cause specific survival between stage A-C (98%) and D (63%, p < 0.0001). Cox proportional hazards multivariate regression analyses revealed that localized cancer (stage A and B) was the most significant prognostic factor in the time to relapse (p < 0.0001) as well as the cause specific survival (p < 0.0001). Conclusions: There was substantial number of men with localized disease who were treated ADT alone. The use of ADT therapy alone appeared to have favor prognosis in the majority of patients without metastatic diseases, at least for an intermediate period. No significant financial relationships to disclose.
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Vergote, Ignace, Florian Heitz, Paul Buderath, Matthew A. Powell, Jalid Sehouli, Christine M. Lee, Anne L. Hamilton, et al. "A randomized, double-blind, placebo-controlled phase Ib/II study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine (G) and carboplatin (C) versus GC for women with recurrent platinum-sensitive ovarian cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 5537. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.5537.
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5537 Background: p38 mitogen-activated protein kinase (MAPK) regulates cytokine production in the tumor microenvironment and enables therapeutic resistance of cancer cells. Ralimetinib (R) is a selective small-molecule inhibitor of p38α and p38β MAPKs. Methods: Main inclusion criteria: ≥18 y; recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal, cancer after first-line treatment. Phase (Ph)1b was to determine the recommended Ph2 dose (RP2D) of R administered 12-hourly (Q12H) on Days 1-10 (21-day cycle [Q21D]) in combination with gemcitabine (G: 1000 mg/m2 on Days 3 and 10) and carboplatin (C: AUC 4 on Day 3) for 6 cycles. In Ph2, patients (pts) were randomized double-blind, 1:1 to RP2D R+GC or placebo (P)+GC, for 6 cycles, followed by R 300 mg Q12H or P on Days 1-14, Q28D until disease progression. The stratified log-rank test compared progression-free survival (PFS; primary endpoint) between treatment groups in Ph2, at a 1-sided α level of 0.2. ClinicalTrials.gov, NCT01663857. Results: 118 pts received ≥1 dose of R or P (safety population); 8 in Ph1b and 110 in Ph2 (R+GC N = 58; P+GC N = 52). The RP2D for R in combination with GC was 200 mg Q12H. The study met its primary objective (median PFS: R+GC 10.3 mo vs P+GC 7.9 mo; HR = 0.773, 2-sided p = 0.246). The secondary objectives of median overall survival (R+GC 29.2 mo vs P+GC 25.1 mo; HR = 0.827, p = 0.469) or overall response rate (R+GC 46.6% vs P+GC 46.2%; p = 0.967) were not statistically significant, and 32.4% vs 25.0% of pts had normalized CA125 at the end of cycle 6. Most pts (safety population) experienced ≥1 Grade 3/4 treatment-emergent adverse event (TEAE: R+GC 63/66 [95.5%]; P+GC 48/52 [92.3%]). Decreased neutrophil count (60.6% vs 76.9%), platelet count (43.9% vs 38.5%), and white blood cell count, (30.3% vs 26.9%), anemia (22.7% vs 25.0%), and increased alanine aminotransferase (ALT) (19.7% vs 3.8%) were the Grade 3/4 TEAEs in ≥10% of pts in the R+GC and P+GC arms, respectively. Conclusions: Addition of ralimetinib to GC resulted in modest improvements in PFS. Grade 3/4 elevated ALT was more common in the ralimetinib arm. Clinical trial information: NCT01663857.
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Petri, M. A., G. Bertsias, M. Daniels, N. L. Fox, B. H. Hahn, A. Hammer, J. Harris, H. Quasny, C. Tani, and A. Askanase. "POS0183 THE EFFECT OF BELIMUMAB ON SRI-4 RESPONSE IN MULTIPLE SUBGROUPS OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF A LARGE INTEGRATED ANALYSIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 323.1–323. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1807.
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BackgroundBelimumab (BEL) is approved for the treatment of active autoantibody-positive systemic lupus erythematosus (SLE).1 Four Phase 3 studies have consistently demonstrated greater SLE Responder Index (SRI) response rates with BEL vs placebo (PBO).2-5 This robust dataset allows for additional exploration of the onset of efficacy of BEL and response rates by patient (pt) characteristics.ObjectivesTo perform a post hoc analysis evaluating the effect of BEL on SRI-4 response across a large, pooled population and pt subgroups.MethodsThe Belimumab Summary of Lupus Efficacy (Be-SLE) integrated analysis evaluated data from adults with SLE from 5 double-blind, PBO-controlled BEL trials: BLISS-76, BLISS-52, BLISS-NEA, BLISS-SC, and EMBRACE.2-6 Pts were randomised to BEL (monthly intravenous 10 mg/kg or weekly subcutaneous 200 mg) or PBO, plus standard therapy. Data were collected every 4 weeks (wks) from baseline (BL) to Wk 52. The SRI-4 response rate (a composite measure that includes ≥4-point reduction in Safety of Estrogens in Lupus Erythematosus National Assessment - SLE Disease Activity Index [SELENA-SLEDAI] score, stable Physician Global Assessment [PGA] increase of <0.3, and no new British Isles Lupus Assessment Group [BILAG] 1A/2B organ domain scores) by visit and time to first SRI-4 response maintained through Wk 52 were determined for both treatment groups. SRI-4 response rates at Wk 52 were evaluated by BL characteristic subgroups: SELENA-SLEDAI score; SLE International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score; disease duration; biomarker levels (anti-dsDNA, complement [C]3/C4); glucocorticoid (GC), immunosuppressant (IS), and antimalarial (AM) use.ResultsOverall, 3086 pts were included (BEL, n=1869; PBO, n=1217). Most were female (94.4%); mean (standard deviation [SD]) age was 37.0 (11.6) years. Mean (SD) SLE duration was 6.4 (6.4) years.At Wk 52, in the overall population, significantly more BEL vs PBO pts were SRI-4 responders (Figure 1). A significantly greater proportion of SRI-4 responders was observed with BEL vs PBO as early as Wk 8 (38.4% vs 33.3%; odds ratio, OR [95% confidence interval, CI] 1.25 [1.07, 1.46]; p=0.0060), which continued to increase to Wk 52 (54.8% vs 41.6%; OR [95% CI] 1.70 [1.46, 1.98]; p<0.0001). At Wk 52, more BEL vs PBO pts had a 4-point reduction in SELENA-SLEDAI (56.3% vs 43.1%; OR [95% CI] 1.71 [1.47, 2.00]; p<0.0001), no worsening in PGA (76.6% vs 67.9%; OR [95% CI] 1.52 [1.28, 1.79]; p<0.0001), and no new BILAG 1A/2B organ domain scores (77.1% vs 69.4%; OR [95% CI] 1.47 [1.25, 1.74]; p<0.0001). Pts on BEL were 52% more likely to experience an SRI-4 response that was maintained through Wk 52 (hazard ratio, HR [95% CI] 1.52 [1.36, 1.69]; p<0.0001).Figure 1.SRI-4 response at Wk 52 in the overall population and by BL characteristic subgroups.*OR (95% CI) and p-value are from a logistic regression model for BEL vs PBO comparison with covariates of treatment group, study and BL SELENA-SLEDAI score (≤9 vs ≥10)SRI-4 response rates were significantly higher with BEL vs PBO in most subgroups, with the highest response rates observed in pts with SELENA-SLEDAI score of ≥10, low C3 and/or C4 + anti-dsDNA ≥30 IU/ml, and low C3 and/or C4 at BL (Figure 1).ConclusionSignificantly more pts receiving BEL had SRI-4 response rates that occurred from Wk 8 and were maintained through Wk 52 compared with pts receiving PBO. The efficacy of BEL was consistent across multiple pt subgroups, with higher response rates in pts with SELENA-SLEDAI scores of ≥10, low C3 and/or C4 + anti-dsDNA ≥30 IU/ml and low C3 and/or C4 at BL. These results further substantiate the benefits of BEL in the treatment of adults with SLE.References[1]GlaxoSmithKline. Benlysta US prescribing information. 2021[2]Furie R, et al. Arthritis Rheumatol 2011;63(12):3918–30[3]Navarra SV, et al. Lancet 2011;377(9767):721–31[4]Stohl W, et al. Arthritis Rheum 2017;69(5):1016–27[5]Zhang F, et al. Ann Rheum Dis 2018;77(3):355–63[6] Ginzler E, et al. Arthritis Rheum 2021; doi: 10.1002/art.41900AcknowledgementsThis analysis was funded by GlaxoSmithKline (GSK). Medical writing support was provided by Lulu Hill, MPharmacol, Fishawack Indicia Ltd. UK, part of Fishawack Health, and was funded by GSK.Disclosure of InterestsMichelle A Petri Consultant of: GSK, Grant/research support from: GSK, George Bertsias Speakers bureau: Pfizer, Aenorasis, UCB, Novartis, Lilly, SOBI, Consultant of: Novartis, GSK, AstraZeneca, Grant/research support from: GSK, Pfizer, Mark Daniels Shareholder of: GSK, Employee of: GSK, Norma Lynn Fox Shareholder of: GSK, Employee of: GSK, Bevra H. Hahn Consultant of: UCB, GSK, Anne Hammer Shareholder of: GSK, Employee of: GSK, Julia Harris Shareholder of: GSK, Employee of: GSK, Holly Quasny Shareholder of: GSK, Employee of: GSK, Chiara Tani Speakers bureau: GSK, AstraZeneca, Anca Askanase Consultant of: AstraZeneca, Aurinia Pharmaceuticals Inc., Amgen, AbbVie Inc., BMS, GSK, Grant/research support from: AstraZeneca, Eli Lilly and Company, GSK, Idorsia Pharmaceuticals Ltd, Janssen Pharmaceuticals, Pfizer
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Simoen, Eddy, K. Takakura, Brent Hsu, and Cor Claeys. "(Electronics and Photonics Division Award) The Impact of Defects on the Performance of Semiconductor Devices and Materials." ECS Meeting Abstracts MA2022-01, no. 31 (July 7, 2022): 1299. http://dx.doi.org/10.1149/ma2022-01311299mtgabs.
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Since the early days of the semiconductor industry, defect control has been key to the successful development of devices and circuits. It requires a thorough understanding of their formation and the impact on the electrical material parameters. This has only been possible by the invention of powerful structural, chemical and electrical characterization tools, with the device itself perhaps as the most sensitive probe. This evolution was paralleled by the development of ab initio calculation methods, based on Density Functional Theory and more recently, also TCAD tools allowing more and more refined modelling of the impact of defects on the electrical characteristics of devices. The implementation of other materials than Si and SiO2 in CMOS through the hetero-epitaxial growth on a silicon substrate for example, has renewed the interest in defect engineering during the last two decades, leading to single-defect analysis methods like Random Telegraph Noise (RTN) [1] or novel growth schemes like Aspect Ratio Trapping (ART) [2] for the removal of extended defects from the device active regions. In this presentation, some state-of-the-art analysis techniques will be highlighted, including Deep Level Transient Spectroscopy (DLTS) [3], Generation-Recombination (GR) noise and RTN spectroscopy [1,4] and p-n diode lifetime analysis [5]. These methods will be applied to several case studies. As shown in Fig. 1, threading extended defects impact the recombination lifetime of lowly-doped n-type In0.47Ga0.53As starting from a density of a few 107 cm-2. Likewise, it will be demonstrated that the GR noise observed in GaN-on-Si MOSHEMTs (Fig. 2) most likely originates from threading dislocations [6]. It is concluded that when hetero-epitaxial layers can be grown with a sufficiently low defect density, their impact will be more on the variability of the electrical parameters rather than on the effective values. In addition, the position of the defect with respect to strategic nodes like a p-n junction or depletion region largely determines its electrical impact, as has been validated by TCAD simulations. References [1] E. Simoen and C. Claeys, “Random Telegraph Signals in Semiconductor Devices”, The Institute of Physics, Bristol, UK (2016). [2] J. Z. Li et al., Appl. Phys. Lett., 91, p. 021114 (2007). [3] E. Simoen, J. Lauwaert and H. Vrielinck, Semiconductors and Semimetals, Eds. L. Romano, V. Privitera and C. Jagadish, 91, pp. 205-250, Elsevier 2015. [4] D. Boudier et al., Solid-St. Electron., 128, pp. 102-108 (2017). [5] Po-Chun (Brent) Hsu et al., J. Phys. D: Appl. Phys., 52, p. 485102 (2019). [6] K. Takakura et al., IEEE Trans. Electron Devices, 67, pp. 3062-3068 (2020). Figure 1
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Visconti, M., M. Campanini, A. Fontanella, R. Nardi, and G. Uomo. "Patologia sistemica da virus dell'epatite C: la crioglobulinemia mista e altre manifestazioni extraepatiche." Italian Journal of Medicine 4, no. 1 (March 24, 2016): 1. http://dx.doi.org/10.4081/itjm.q.2016.1.
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<img src="/public/site/images/pgranata/intro.jpg" alt="" /><br /><p class="titolo"><strong>La malattia o sindrome da virus dell’epatite C</strong> 1<br /><em>M. Visconti, R. Nardi</em></p><p class="titolo"><strong>Il virus C</strong> 5<br /><em>V. Iovinella, G. Iovinella</em></p><img src="/public/site/images/pgranata/crio1.jpg" alt="" /><br /><p class="titolo"><strong>Crioglobuline, crioglobulinemie e sindromi crioglobulinemiche</strong> 10<br /><em>M. Visconti, A. Salvio</em></p><p class="titolo"><strong>Patogenesi</strong> 14<br /><em>A. Ilardi</em></p><p class="titolo"><strong>La vasculite cutanea</strong> 19<br /><em>G. Monti, P. Novati, L. Castelnovo, F. Saccardo</em></p><p class="titolo"><strong>Le neuropatie periferiche</strong> 23<br /><em>R. Boni</em></p><p class="titolo"><strong>La sindrome sicca</strong> 29<br /><em>G. Italiano</em></p><p class="titolo"><strong>Il fenomeno di Raynaud</strong> 33<br /><em>F. Gallucci, A. Parisi, R. Buono</em></p><p class="titolo"><strong>La nefropatia crioglobulinemica</strong> 40<br /><em>F. Salvati</em></p><p class="titolo"><strong>I linfomi</strong> 46<br /><em>M. Laccetti</em></p><p class="titolo"><strong>La patologia articolare</strong> 52<br /><em>T. d’Errico, M. Varriale, C. Ambrosca, S. Tassinario</em></p><p class="titolo"><strong>Sindrome da iperviscosità</strong> 56<br /><em>A. Fontanella, L. Fontanella</em></p><p class="titolo"><strong>Diagnosi</strong> 60<br /><em>G. Uomo, F. Gallucci</em></p><p class="titolo"><strong>Terapia antivirale</strong> 65<br /><em>P.G. Rabitti, F. Lampasi</em></p><img src="/public/site/images/pgranata/altre11.jpg" alt="" /><br /><p class="titolo"><strong>Diabete mellito</strong> 74<br /><em>A. Maffettone, M. Rinaldi</em></p><p class="titolo"><strong>Malattie cardiovascolari</strong> 80<br /><em>R. Nardi, D. Borioni</em></p><p class="titolo"><strong>Malattie dermatologiche</strong> 86<br /><em>D. Galasso, D. D’Amico</em></p><p class="titolo"><strong>Malattie neurologiche e psichiatriche</strong> 91<br /><em>M. Imparato</em></p><p class="titolo"><strong>Correlazioni tra patologia epatica e patologia tiroidea. <br />Malattie tiroidee in corso di infezione da virus C</strong> 96<br /><em>M. Grandi, C. Sacchetti, S. Pederzoli</em></p><p class="titolo"><strong>Neoplasie extraepatiche</strong> 101<br /><em>S. Fiorino, A. Domanico, E. Accogli, D. Borioni, P. Leandri</em></p><p class="titolo"><strong>Sarcoidosi e malattie polmonari</strong> 109<br /><em>A. Zuccoli, N. Corcione, V. Nuzzo</em></p>
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Jayakrishnan, Thejus Thayyil, Veli Bakalov, Zena Chahine, Gene Grant Finley, Dulabh K. Monga, and Rodney E. Wegner. "The impact of affordable care act on the treatment disparities for stage-IV colorectal cancer: A contemporary analysis." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e19082-e19082. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e19082.
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e19082 Background: Patients with advanced cancers are among the most vulnerable group of patients. We sought to analyze the impact of Affordable Care Act on the interaction of socioeconomic factors with treatment enrollement and survival in patients with metastatic colorectal cancers. Methods: We queried the National Cancer Database (NCDB) for patients with Stage-IV colon (C-Ca) and rectal cancers (R-Ca) diagnosed from 2004-2015 and excluded those who did not receive any therapies within 6 months of diagnosis. Enrollment rates were calculated as receipt of primary therapy as the incident-event (numerator) over time-to-initiation of therapy (denominator) and used to calculate incident-rate ratios that was further analyzed using Poisson regression analysis- reported as enrollment-rate ratios (ER, < 1 indicating lower enrollment rate). Multivariate Cox-proportional hazard model was performed for survival analysis and reported as calculate Hazard Ratios (HR). Results: We identified 59,211 C-Ca and 4,818 R-Ca for the analysis. Median ages were 64 years vs. 60 years and included 52% vs. 60% males respectively. For C-Ca enrollment to primary therapies were significantly associated (p-value < 0.05) with gender, race, insurance status, educational status and treatment facility. HR < 1 was associated with high-income vs. low-income group- 0.90(0.87-0.94),p-value < 0.005. The HR for non-Hispanic Blacks (NHB) vs. Whites (NHW) improved from 1.1(1.03-1.11),p-value < 0.005 to no-significant difference post-ACA. For R-Ca, the enrollment rates were favorable for NHB vs. NHW and ER improved from 1.15(1.0-1.32),p-value = 0.054) to 1.29(1.06-1.58),p-value = 0.013 post-ACA. Despite this, the HR for mortality were unfavorable - 1.19(1.06-1.33),p-value = 0.003 that persisted through the post-ACA period. The HR was favorable for the insured group in both cancer groups (0.84 for R-Ca,0.86 for C-Ca). Conclusions: Socioeconomic factors influence outcomes for this vulnerable group of patients in terms of enrollment to therapies and survival. The Affordable Care Act appears to have had a positive impact overall but more needs to be done including broadening insurance coverage.
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Ragni, MV, OK Ndimbie, EO Rice, FA Bontempo, and S. Nedjar. "The presence of hepatitis C virus (HCV) antibody in human immunodeficiency virus-positive hemophilic men undergoing HCV "seroreversion"." Blood 82, no. 3 (August 1, 1993): 1010–15. http://dx.doi.org/10.1182/blood.v82.3.1010.1010.
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Abstract Hepatitis C virus (HCV) is a major cause of transfusion-induced chronic liver disease in hemophiliacs, with 70% to 90% being anti-HCV positive. Seroreversion or loss of antibody response to HCV has been observed in a small proportion of human immunodeficiency virus-positive [HIV(+)] anti-HCV(+) hemophilic men. Despite the seroreversion to an anti-HCV- negative state, such patients continue to show serum alanine aminotransferase (ALT) elevations and biopsy evidence of cirrhosis and/or chronic active hepatitis. To determine the cause for the loss of anti-HCV antibody, we compared first- and second-generation anti-HCV enzyme immunosorbent assay (EIA 1.0 and 2.0), second-generation recombinant immunoblot (RIBA 2.0), and HCV-RNA amplification using polymerase chain reaction (PCR) in 19 “seroreverters” before and after seroreversion. There was no difference between 19 seroreverters and 59 persistently anti-HCV-positive hemophiliacs in mean ALT (1.1 +/- 0.1 XUL v 2.0 +/- 0.2 XUL; chi 2 = 1.80, P > .05), in mean CD4 (188 +/- 36/microL v 232 +/- 28/microL; t = 0.965, P > .05), or in the rate of progression to acquired immunodeficiency syndrome (13 of 19 [68.4%] v 30 of 59 [50.9%]; chi 2 = .987, P > .05, respectively). Before seroreversion, all 19 seroreverters (100%) were positive for EIA 1.0 and 2.0 and PCR, and all but 2 of 19 (89.5%) were RIBA 2.0 positive, whereas, after seroreversion, none were positive for EIA 1.0, 15 of 19 (78.9%) were positive for EIA 2.0, 8 of 18 (44.4%) were positive for RIBA 2.0, and 18 of 19 (94.7%) were positive for PCR. There was a lower CD4 lymphocyte number after seroreversion in those who were RIBA 2.0 negative as compared with those who were RIBA 2.0 positive (32 +/- 10/microL v 171 +/- 52/microL; t = 2.638, P > .05). These results indicate that HIV(+) anti-HCV(+) hemophilic men who undergo “HCV seroreversion” are truly infectious and anti-HCV positive by second- generation tests. Anti-HCV detection in immunosuppressed hosts is significantly improved by second-generation EIA and RIBA assays.
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Ragni, MV, OK Ndimbie, EO Rice, FA Bontempo, and S. Nedjar. "The presence of hepatitis C virus (HCV) antibody in human immunodeficiency virus-positive hemophilic men undergoing HCV "seroreversion"." Blood 82, no. 3 (August 1, 1993): 1010–15. http://dx.doi.org/10.1182/blood.v82.3.1010.bloodjournal8231010.
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Hepatitis C virus (HCV) is a major cause of transfusion-induced chronic liver disease in hemophiliacs, with 70% to 90% being anti-HCV positive. Seroreversion or loss of antibody response to HCV has been observed in a small proportion of human immunodeficiency virus-positive [HIV(+)] anti-HCV(+) hemophilic men. Despite the seroreversion to an anti-HCV- negative state, such patients continue to show serum alanine aminotransferase (ALT) elevations and biopsy evidence of cirrhosis and/or chronic active hepatitis. To determine the cause for the loss of anti-HCV antibody, we compared first- and second-generation anti-HCV enzyme immunosorbent assay (EIA 1.0 and 2.0), second-generation recombinant immunoblot (RIBA 2.0), and HCV-RNA amplification using polymerase chain reaction (PCR) in 19 “seroreverters” before and after seroreversion. There was no difference between 19 seroreverters and 59 persistently anti-HCV-positive hemophiliacs in mean ALT (1.1 +/- 0.1 XUL v 2.0 +/- 0.2 XUL; chi 2 = 1.80, P > .05), in mean CD4 (188 +/- 36/microL v 232 +/- 28/microL; t = 0.965, P > .05), or in the rate of progression to acquired immunodeficiency syndrome (13 of 19 [68.4%] v 30 of 59 [50.9%]; chi 2 = .987, P > .05, respectively). Before seroreversion, all 19 seroreverters (100%) were positive for EIA 1.0 and 2.0 and PCR, and all but 2 of 19 (89.5%) were RIBA 2.0 positive, whereas, after seroreversion, none were positive for EIA 1.0, 15 of 19 (78.9%) were positive for EIA 2.0, 8 of 18 (44.4%) were positive for RIBA 2.0, and 18 of 19 (94.7%) were positive for PCR. There was a lower CD4 lymphocyte number after seroreversion in those who were RIBA 2.0 negative as compared with those who were RIBA 2.0 positive (32 +/- 10/microL v 171 +/- 52/microL; t = 2.638, P > .05). These results indicate that HIV(+) anti-HCV(+) hemophilic men who undergo “HCV seroreversion” are truly infectious and anti-HCV positive by second- generation tests. Anti-HCV detection in immunosuppressed hosts is significantly improved by second-generation EIA and RIBA assays.
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Pasticier, Gilles, Sebastien Crouzet, Pascal Pommier, Christian Carrie, Olivier Rouviere, Jean-Yves Chapelon, Muriel Rabilloud, et al. "External beam radiation therapy or high intensity-focused ultrasound for localized prostate cancer: A matched pair analysis in the prostate-specific antigen era." Journal of Clinical Oncology 33, no. 7_suppl (March 1, 2015): 109. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.109.
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109 Background: In the absence of randomised study data institutional series have shown High Intensity Focused Ultrasound (HIFU) to produce excellent overall and cancer specific survival rates in patients with localized prostate cancer (LPCa) compared with alternative curative treatments. The aim of this study was to evaluate the oncologic outcome of patients treated with HIFU versus conformal external beam radiation therapy (C-EBRT) without previous or associated androgen deprivation(AD).This study was designed to overcome limitations of case series studies by using a matched pair design in patients treated contemporaneously with HIFU and C- EBRT in two institutions in the same town. Methods: 256 eligible patients with intermediate risk prostate cancer (d’Amico classification) treated between 2000 and 2005 were prospectively followed and matched to a 1:1 basis following know prognostic variables: prostate-specific antigen (PSA) level and Gleason score.190 perfect matches of patients (95 in each group) were further analysed. Progression free survival rate were the primary endpoint. Other endpoints were secondary used of salvage therapy, and survival rate without salvage palliative androgen deprivation therapy (S-ADT).The progression free survival rates were calculated with Kaplan-Meier estimate. For progression free calculation, failure was defined using the Phoenix definition (nadir + 2ng/ml) or at the time of a salvage treatment for local relapse evidenced by control biopsy. Results: The seven years progression free survival rate was not significantly different after HIFU than after C-EBRT (47% versus 52%, p: 0.311) . The palliative androgen deprivation free rate at seven years was significantly different after HIFU than after C-EBRT (85% versus 58%, p: 0.002). Conclusions: The progression free survival rate was not significantly different after HIFU use than after C-EBRT but the rate of patients who need palliative S-ADT was significantly different after HIFU or C-EBRT: Higher rate of S-ADT was associated with C-EBRT use than with HIFU use.
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Hsu, Cheng-Er, Yen-Chun Liu, Ya-Ting Cheng, Wen-Juei Jeng, Rong-Nan Chien, Chun-Yen Lin, Dar-In Tai, and I.-Shyan Sheen. "Hepatitis B Co-Infection Has Limited Impact on Liver Stiffness Regression in Chronic Hepatitis C Patients Treated with Direct-Acting Antivirals." Viruses 14, no. 4 (April 10, 2022): 786. http://dx.doi.org/10.3390/v14040786.
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Introduction: High sustained virological response (SVR) rate (>95%) and liver stiffness regression can be achieved with direct acting antivirals treatment (DAA) in patients with chronic hepatitis C virus (CHC) infection. Reactivation of hepatitis B virus (HBV) was reported during DAA treatment in patients co-infected with HBV, although its impact on liver stiffness remains unknown. This study aims to investigate whether the liver stiffness (LSM) regression is different between HBV/HCV co-infected and mono-HCV-infected patients. Materials and Methods: CHC patients with/without HBV co-infection who received DAA treatment and achieved SVR12 between March 2015 and December 2019 in Chang Gung Memorial Hospital, Linkou branch were prospectively enrolled. LSM was assessed by transient elastography (TE, Fibroscan) at baseline and after SVR. Propensity score matching (PSM) at 3:1 ratio, adjusted for age, gender, pre-DAA alanine aminotransferase (ALT), platelet count, and LSM, between CHC with and without HBV co-infection, was performed before further analysis. Results: Among 906 CHC patients enrolled, 52 (5.7%) patients had HBV/HCV co-infection. Patients with HBV/HCV co-infection were of younger age (61.8 vs. 63.2, p = 0.31), with a higher proportion of males (53.8% vs. 38.9%, p = 0.03), and lower pretreatment LSM level (8.15 vs. 10.2 kPa, p = 0.09), while other features were comparable. After PSM, patients with HBV/HCV co-infection had insignificantly lower LSM regression compared to mono-HCV-infected patients (−0.85 kPa vs. −1.65 kPa, p = 0.250). Conclusions: The co-infection of HBV among CHC patients has limited impact on liver stiffness regression after successful DAA treatment.
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Dakum, Patrick, Juliet Ajav-Nyior, Timothy A. Attah, Gbenga A. Kayode, Asabe Gomwalk, Helen Omuh, Halima Ibrahim, et al. "Effect of community antiretroviral therapy on treatment outcomes among stable antiretroviral therapy patients in Nigeria: A quasi experimental study." PLOS ONE 16, no. 4 (April 26, 2021): e0250345. http://dx.doi.org/10.1371/journal.pone.0250345.
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Objectives This study evaluates the effect of Community Anti-retroviral Groups on Immunologic, Virologic and clinical outcomes of stable Antiretroviral Therapy patients in Nigeria. Method A cohort of 251 eligible adults (≥18 years) on first-line ART for at least 6 months with CD4 counts >200 cells/mm3 and viral load <1000 c/ml were devolved from 10 healthcare facilities to 51 community antiretroviral therapy groups. Baseline immunologic, virologic and clinical parameters were collected and community antiretroviral therapy group patients were followed up for a year after which Human Immunodeficiency Virus treatment outcomes at the baseline and a year after follow-up were compared using paired sample t-test. All the analyses were performed in STATA version 14. Result Out of the 251 stable antiretroviral therapy adults enrolled, 186 (75.3%) were female, 52 (22.7%) had attained post-secondary education and the mean age of participants was 38 years (SD: 9.5). Also, 66 (27.9%) were employed while 125 (52.7%) were self-employed and 46(19.41%) unemployed. 246 (98.0%) of the participants were retained in care. While there was no statistically significant change in the CD4 counts (456cells/mm3 vs 481cells/mm3 P-0.489) and Log10 viral load (3.54c/ml vs 3.69c/ml P-0.359) after one year of devolvement into the community, we observed a significant increase in body weight (60.8 vs 65, P-0.01). Conclusion This study demonstrates that community antiretroviral therapy has a potential of maintaining optimum treatment outcomes while improving adherence and retention, and reducing the burden of HIV treatment on the health facility. This study provides baseline information for further research and vital information for HIV program implementers planning to decentralize the management of stable antiretroviral therapy clients.
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Muvarak, Nidal E., Shannon M. Kelley, Mario Tarasco, Maria R. Baer, Kara A. Scheibner, and Feyruz Rassool. "C-MYC and C-MYC-Regulated Micrornas Increase The Activity Of The Error-Prone ALT NHEJ Pathway Through Upregulation Of LIG3 and PARP1 In Tyrosine Kinase-Activated Leukemias." Blood 122, no. 21 (November 15, 2013): 809. http://dx.doi.org/10.1182/blood.v122.21.809.809.
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Abstract Constitutively activated tyrosine kinases (TK) BCR-ABL1 and FLT3/ITD not only increase cell survival and proliferation, but also increase levels of endogenous DNA damage and activity of an error-prone DNA double-strand break (DSB) repair pathway. This genomic instability leads to acquisition of genomic alterations that can result in disease progression and/or resistance to therapy. We have previously demonstrated that, in TK-activated leukemias, activity of the classic non homologous end-joining (C-NHEJ) pathway that repairs DSBs is decreased, and, as a consequence, an alternative, highly error-prone form of NHEJ (ALT NHEJ) predominates, evidenced by increased expression of DNA ligase IIIα (LIG3) and PARP1 (components of ALT NHEJ), increased frequency of large DNA deletions, and repair using DNA microhomologies. In this study, we sought to elucidate the role of a key downstream target of TKs, c-MYC, in upregulating LIG3 and PARP1 expression and consequently increasing ALT NHEJ and genomic instability. We demonstrated that MYC increases the expression of LIG3 and PARP1 through two mechanisms: 1) Increased binding to the promoters of LIG3 and PARP1, leading to increased transcription, and 2) Repression of microRNAs (miRs) that putatively regulate LIG3 and PARP1. Chemical and siRNA-mediated knockdown of MYC in MO7e-BCR/ABL and FLT3/ITD(+) MOLM14 cells results in significant reduction (p<0.05) in LIG3 and PARP1 mRNA and protein compared to controls. Chromatin immunoprecipitation assays revealed MYC binding to the promoters of LIG3 and PARP1 in AML (MOLM14) and CML (K562 and MO7e-BCR/ABL) cell lines. Additionally, transfection of PARP1 and LIG3 promoter-luciferase constructs into TK-activated (32D-FLT3/ITD, MO7e-BCR/ABL) cells showed significantly (p<0.01) increased LIG3 and PARP1 promoter activity compared to parental controls (32D, MO7e). Moreover, knockdown of MYC in 32D-FLT3/ITD and MO7e-BCR/ABL cells resulted in a significant reduction of promoter activity in luciferase assays (p<0.05). Conversely, overexpression of c-MYC in 293T cells caused an increase (p<0.05) in LIG3 and PARP1 promoter activity. We next determined whether MYC-repressed miRs that have predicted binding sites in the 3’-UTR and coding regions of LIG3 and PARP1 are involved in regulating expression of LIG3 and PARP1. We found that there was a significant inverse correlation between LIG3 expression and miR-22, miR-23a, and miR-150 (Pearson’s r ≤ -0.3, p<0.05). Similarly, there was a significant inverse correlation between PARP1 expression and miR-22, miR-23a, miR-27a, and miR-150 (Pearson r ≤ -0.3, p<0.05). Over-expression of miR-22 in the CML cell line K562 decreased both LIG3 and PARP1 protein levels by 52% and 63% respectively. Similar results were seen upon over-expression of miR-34a (59% and 45%) and miR-150 (46% and 62%) for LIG3 and PARP1. This indicates that MYC-regulated miRs may function coordinately to regulate NHEJ repair. Importantly, our functional NHEJ assays demonstrate an overall significant (p<0.05) reduction in the average size of deletions at the sites of DSB repair when MYC is knocked down, indicating a reduction in ALT NHEJ activity. To determine whether increased expression of LIG3 and PARP1 correlated with MYC expression in primary leukemia samples, we examined mRNA levels from bone marrow of 21 CML patients (12 chronic phase, 1 accelerated, 7 blast crisis, and 1 unknown). Twelve patients were resistant to Imatinib, 7 were responsive, and 2 undetermined. There was a strong positive correlation between levels of MYC and PARP1 (Pearson’s r= 0.75, p=0.001), as well as MYC and LIG3 (Pearson’s r =0.45, p=0.03). While there was no correlation between levels of gene expression and disease phase, we found that the majority of samples with elevated levels of MYC, LIG3 and PARP1 were from Imatinib-resistant patients (64%), compared to samples from Imatinib-sensitive patients (36%) (p=0.03). Additionally, 2 patient samples with TKI-resistant T315I mutation in BCR-ABL1 exhibited elevated levels of MYC, LIG3 and PARP1. Thus, increased MYC expression, and repression of miRs 22, 150 and 34a augment expression of LIG3 and PARP1, generating DSB repair errors that may lead to resistance to TKI therapy. Altered expression of MYC, LIG3, PARP1 and miRs 22, 150 and 34a may be biomarkers for those patients likely to become resistant to TKI therapy. Disclosures: No relevant conflicts of interest to declare.
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Schmitz, Sandra, Marc Hamoir, Herve Reychler, Michele Magremanne, Birgit Weynand, Renaud Lhommel, Francois-Xavier Hanin, et al. "Safety, molecular, and imaging responses to cetuximab administered in a window pre-operative study in squamous cell carcinoma of the head and neck (SCCHN)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 5519. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.5519.
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5519 Background: Only a minority of SCCHN pts benefits from anti-EGFR mAbs. Trials with pre- and post-therapy tumor biopsies are crucial to better characterize the molecular pathways involved in treatment response or resistance. Targeted agents (TA) are often investigated in unselected end-stage cancer pts, making difficult optimal translational research. One way to resolve this issue is to perform “window” studies where a TA is given during the incompressible period between the diagnosis and surgery. Methods: We conducted a phase I/II study: cetuximab (C) was given pre-operatively to treatment-naïve SCCHN pts selected for primary curative surgery. C (400mg/m2 first wk followed by 250mg/m2/wk) was given during 2 wks (day -15 until day -1, 3 infusions) before surgery (day 0). Tumour biopsies, FDG/PET, and CT were performed at diagnosis and surgery. In the phase I, we investigated the safety of preoperative C by progressively reducing the delay between the last dose of C and surgery (minimum delay : 24 hrs ; 3+3 phase 1 design). The aims of the phase II were (i) safety, (ii) C activity by FDG-PET (Po=0.10, P1=0.35, a=0.05 and b= 0.10). As controls, 5 additional pts were included without C treatment but with the same requirements regarding biopsies and imaging. Results: The phase 1 study (n=18) demonstrated that C infusion given 24 hrs before surgery was safe. Safety was confirmed in the phase II (n=20). 90 % had a FDG-PET partial response (PR) (EORTC guideline) in the C group and 0% in the controls. 52% had a ΔSUVmax decrease of >50%. 2 pts evaluable by CT/MRI had a PR (RECIST). Then, we compared the pre-and post treatment biopsies by immunochemistry. For the whole group, C did not reduce Ki67 (p=0.1) and did not seem to induce apoptosis (caspase). However, for pts with ΔSUVmax decrease > 25% or > 50%, Ki67 was decreased (p=0.04 and 0.006). C induced downregulation of pEGFR (p=0.0004) and pERK (p=0.007) but not pAKT/AKT (Histoscore). Conclusions: Pre-operative study with C is safe. Our findings suggest that the main downstream molecular pathway blocked by C in SCCHN is the RAS/RAF/ERK. Further analyses are ongoing to better characterize molecular response and escape mechanisms.
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Gerber, Suzannah, Jillian Price, Lynn Gerber, Ali Weinstein, and Zobair Younossi. "Diet Satisfaction and Adequate Food Intake in Patients with Chronic Liver Diseases." Current Developments in Nutrition 6, Supplement_1 (June 2022): 21. http://dx.doi.org/10.1093/cdn/nzac047.021.
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Abstract Objectives To describe relationships between diet satisfaction, ability to eat, and CLD. Methods Data collected from 354 patients with CLD was used for this analysis, including 2 items from the validated Chronic Liver Disease Questionnaire (CLDQ): item 7 “ability to eat as much as you like” (EA), and item 14 “bothered by a limitation of your diet” (SWD). Results were stratified by existing diagnosis (Cirrhosis and all-type Hepatitis) and severity of disease [Childs-Pugh score (CP-A, mild; CP-B, moderate; CP-C, severe)]; AST (abnormal > 40 U/L) and ALT (abnormal > 55 U/L). Ordinal Logistic Regression, with odds and likelihood ratios, modeled disease severity CP A-C; general linear models examined EA and SWD. All models adjusted for age and sex. Results 354 CLD patients were included [mean age 50.4y (±11.2); 51% male; 222 cirrhosis; 145 hepatitis; 135 with abnormal AST; 131 abnormal ALT; 100 had CP score A; 83 CP-B; 38 CP-C] Of those included, 31% (n = 110) reported low EA (EA-L), and 25% (n = 88) reported low SWD (SWD-L). In patients with cirrhosis, 36% (n = 80) reported EA-L, and 33% (n = 73) SWD-L. 30% (n = 43) of patients with hepatitis reported EA-L, and 22% SWD-L. 33% (n = 45) of patients with abnormal AST reported EA-L, 30% (n = 41) SWD-L; 40% (n = 52) of those with abnormal ALT reported EA-L, 35% (n = 46) SWD-L. 50% (n = 19) with CP-C had EA-L, 63% (n = 24) SWD-L. 43% (n = 36) with CP-B had EA-L, 39% (n = 32) SWD-L. 25% (n = 25) with CP-A had EA-L, 17% (n = 17) SWD-L. Worsening CP scores were 22.68x (p = .0004) more likely associated with EA-L; the odds of patients with CP-C reporting EA-L was 3.3x greater compared normal CP. Similarly, worse CP scores were 56.99x (p < .0001) more likely associated with SWD-L; odds of patients with CP-C reporting SWD-L were 16.2x greater compared to normal. EA described 23% of variance in SWD (p < .0001), and SWD explained 25% of the variance in EA (p < .0001). Sex was significantly associated with SWD (0.55 ± 0.2, p < .0001), age was not. Neither were significant for EA. Conclusions EA-L and SWD-L strongly relate to worsening disease severity as documented by CP scores. Diet satisfaction and ability to eat as much as you like should be monitored closely for patients with CLD, especially those with cirrhosis because these symptoms signal loss of lean mass– a health risk, and one that may preclude eligibility for life-saving liver transplantation. Funding Sources NIFA National Needs Fellowship
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Čelakovská, Jarmila, Josef Bukač, Eva Cermákova, Radka Vaňková, Hana Skalská, Jan Krejsek, and Ctirad Andrýs. "Analysis of Results of Specific IgE in 100 Atopic Dermatitis Patients with the Use of Multiplex Examination ALEX2—Allergy Explorer." International Journal of Molecular Sciences 22, no. 10 (May 17, 2021): 5286. http://dx.doi.org/10.3390/ijms22105286.
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Background and aim: Progress in laboratory diagnostics of IgE-mediated allergy is the use of component-resolved diagnosis. Our study analyses the results of specific IgE to 295 allergen reagents (117 allergenic extracts and 178 molecular components) in patients suffering from atopic dermatitis (AD) with the use of ALEX2 Allergy Explorer. Method: The complete dermatological and allergological examination, including the examination of the sensitization to molecular components with ALEX2 Allergy Explorer testing, was performed. The statistical analysis of results was performed with these methods: TURF (total unduplicated reach and frequency), best reach and frequency by group size, two-sided tests, Fisher’s exact test, and chi-square test (at an expected minimum frequency of at least 5). Results: Altogether, 100 atopic dermatitis patients were examined: 48 men, 52 women, the average age 40.9 years, min. age 14 years, max. age 67 years. The high and very high level of specific IgE was reached in 75.0% of patients to 18 molecular components: from PR-10 proteins (Aln g 1, Bet v 1, Cor a1.0103, Cor a1.0401, Fag s 1), lipocalin (Can f 1), NPC2 family (Der f 2, Der p 2), uteroglobin (Fel d 1), from Alternaria alternata (Alt a 1), Beta expansin (Lol p 1, Phl p 1), molecular components from Timothy, cultivated rye (Secc pollen) and peritrophin-like protein domain Der p 23. The high and very high level of specific IgE to other lipocalins (Fel d 7, Can f 4), to arginine kinase (Bla g 9, German cockroach), and to allergen extracts Art v (mugwort), and Cyn d (Bermuda grass) reached 52.0% of patients. The severity of AD is in significant relation to the sensitization to molecular components of storage mites (Gly d 2, Lep d 2—NPC2 family), lipocalins (Can f 1, Can f 2, Can f 4, and Can f 6), arginine kinase (Asp f 6, Bla g 9, Der p 20, Pen m 2), uteroglobin (Fel d 1, Ory c 3), Mn superoxide dismutase (Mala s 11), PR-10 proteins (Fag s 1, Mal d 1, Cor a 1.0401, Cor a 1.0103), molecular components of the peritrophin-like domain (Der p 21, Der p 23), and to Secc pollen. In the subgroup of patients suffering from bronchial asthma, the significant role play molecular components from house dust mites and storage mites (Lep d 2, Der p 2, Der f 2—NPC2 family), cysteine protease (Der p 1), peritrophin-like protein domain (Der p 21, Der p 23), enolase from Alternaria alternata (Alt a 6), and Beta expansin Phl p 1. Conclusion: The results of our study demonstrate the detailed profile of sensitization to allergens reagents (allergen extract and molecular components) in patients with atopic dermatitis. We show the significance of disturbed epidermal barrier, resulting in increased penetration of allergens. We confirmed the significant relationship between the severity of AD, the occurrence of bronchial asthma and allergic rhinitis, and high levels of specific IgE to allergen reagents. Our results may be important for regime measures and immunotherapy; Der p 23 shall be considered as an essential component for the diagnosis and specific immunotherapy of house dust mite allergy.
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Birzu, C., A. Hillairet, M. Giry, N. Grandin, P. Verrelle, K. Mokhtari, Y. Marie, et al. "OS9.7 Telomere length, TERTp mutation and ALT status in adult diffuse gliomas." Neuro-Oncology 21, Supplement_3 (August 2019): iii19—iii20. http://dx.doi.org/10.1093/neuonc/noz126.065.
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Abstract BACKGROUND The current classification of adult diffuse gliomas integrates two alternative telomere maintenance mechanisms: reactivation of telomerase activity by TERT promoter (TERTp) mutations or ATRX mutations associated with alternative length telomere (ALT). We investigated here the relation between these two mechanisms, telomere length, and outcome in a large series of diffuse gliomas. MATERIAL AND METHODS We performed C-circle assay (CCA) to determine ALT status, determined telomere length in tumor (RTLt) and leukocyte (RTLl) in a cohort of 354 adult diffuse gliomas, and sequenced ATRX gene. We calculated an age-adjusted telomere score considering tumor and leukocyte (blood) telomere length and corrected by age. This score was used in univariate and multivariate survival analyses to evaluate the potential impact of telomere length on the prognosis of gliomas. We used the TCGA LGG-GBM dataset to validate our findings in an independent cohort. RESULTS RTLl and RTLt were associated with ATRX mutation and ALT phenotype, and negatively associated with age and TERTp mutations. ATRX mutations (found in 52% (64/123) of samples) were mostly transitions (C>T or T>C), and were associated with ALT phenotype. None of 1p/19q co-deleted oligodendrogliomas harbored an ALT phenotype. No patients with TERTp mutations had ALT phenotype except for a very small subgroup of patients (3/87, 3.4%) suggesting that multiple ways of telomere maintenance, may co-exist in a single tumor, probably expressed in different clones. Telomere age-adjusted score was independently associated with better outcome (HR= 0.73 [95% CI 0.56–0.97], p-value 0.03 adjusted for age, TERTp mutation, IDH mutation, 1p/19q co-deletion and WHO grade). These results were validated using the LGG-GBM TCGA dataset. CONCLUSION We unravel the relation between RTLl and RTLt, TERTp mutation and ALT phenotype and describe a novel telomere age-adjusted score independently associated with better prognosis in adult diffuse gliomas.
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Miluski, Piotr, Marcin Kochanowicz, Jacek Zmojda, and Dominik Dorosz. "Multicolor emission of Tb3+/Eu3+ co-doped poly(methyl methacrylate) for optical fibre technology." Photonics Letters of Poland 9, no. 4 (December 31, 2017): 110. http://dx.doi.org/10.4302/plp.v9i4.788.
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The article presents multicolor emission observed in poly(methyl methacrylate) specimens co-doped by trivalent terbium and europium ions. The bright luminescence was obtained using organometallic complexes of lanthanides and energy transfer antenna effect. Spectroscopic characterization exhibit wide excitation spectrum according to chelating structure of used complexes and characteristic Tb3+ and Eu3+ emission peaks in luminescence spectra. The calculated CIE 1931 chromaticity coordinates confirm that colorful emission from green to red can be obtained using proposed materials. Full Text: PDF ReferencesJ.-H. Jou, M.-C. Sun, H.-H. Chou, C.-H. Li, "White organic light-emitting devices with a solution-processed and molecular host-employed emission layer", Appl. Phys. Lett. 87, 043508 (2005). CrossRef R. Mac Ciarnain, D. Michaelis, T. Wehlus, A. F. Rausch, N. Danz, A. Brauer, A. Tünnermann, "Emission from outside of the emission layer in state-of-the-art phosphorescent organic light-emitting diodes", Organic Electronics 44, 115 (2017). CrossRef G. Williams, C. Backhouse, H. Aziz, "Integration of Organic Light Emitting Diodes and Organic Photodetectors for Lab-on-a-Chip Bio-Detection Systems", Electronics 3, 43 (2014). CrossRef P. Miluski, D. Dorosz, M. Kochanowicz and J. Żmojda, "Fluorescent polymeric optical fibre illuminator", Electronics Letters, 52, 18 (2016). CrossRef L. Bilro, N. Alberto, J. L.Pinto, R. Nogueira, "Optical Sensors Based on Plastic Fibers", Sensors 12, 12184 (2012). CrossRef P. Miluski, D. Dorosz, J. Żmojda, M. Kochanowicz, J. Dorosz, "Luminescent Polymer Optical Fibre Sensor for Temperature Measurement", Acta Phys. Pol. A 127, 730 (2015) CrossRef C. Lethien, C. Loyez, J. P. Vilcot, N. Rolland, P. A. Rolland, "Exploit the Bandwidth Capacities of the Perfluorinated Graded Index Polymer Optical Fiber for Multi-Services Distribution", Polymers 3, 1006 (2011). CrossRef J. Zubia, J. Arrue, "Plastic Optical Fibers: An Introduction to Their Technological Processes and Applications", Opt. Fiber Technol. 7, 101 (2001). CrossRef N. Sultanovaa, S. Kasarovaa, I. Nikolov, "Dispersion Properties of Optical Polymers", Acta Physica Polonica A 116, 585 (2009). CrossRef J. Arrue, F. Jiménez, I. Ayesta, M. Asunción Illarramendi, J. Zubia, "Polymer-Optical-Fiber Lasers and Amplifiers Doped with Organic Dyes", Polymers 3,1162 (2011). CrossRef P. Miluski, M. Kochanowicz, J. Żmojda, "Spectroscopic investigation of organic co-doped PMMA for optical fiber technology", Journal Of Optoelectronics And Advanced Materials, 19, 379 (2017). DirectLink P. Miluski, M. Kochanowicz, J. Żmojda, and D. Dorosz, "Emission properties and energy transfer in Perylene-Rhodamine 6 G co-doped polymeric fiber", Chinese Optics Letters 14, 12, 121602 (2016). CrossRef H. Liang, Z. Yang, L. Xiao, F. Xie, " Radiative transition probability of a europium (III) chelating polymer", Optoelectronics And Advanced Materials ? Rapid Communications 4, 9, 1396 (2010). CrossRef H. Jiu, J. Ding, Y. Sun, J. Bao, C. Gao, Q. Zhang, "Fluorescence enhancement of europium complex co-doped with terbium complex in a poly(methyl methacrylate) matrix", Journal of Non-Crystalline Solids 352, 197 (2006). CrossRef K. Kuriki, S. Nishihara, Y. Nishizawa, A. Tagaya, Y. Koike, Y. Okamoto, "Spectroscopic properties of lanthanide chelates in perfluorinated plastics for optical applications", Journal of the Optical Society of America B 19, 8, 1844 (2002). CrossRef P. Miluski, M. Kochanowicz, J. Żmojda, D. Dorosz, "Luminescent properties of Tb3+-dopedpoly(methyl methacrylate) fiber" Chinese Optics Letters, 15, 7, 070602 (2017). DirectLink P. Miluski, M. Kochanowicz, J. Żmojda, D. Dorosz, "Properties of Eu3+ doped poly(methyl methacrylate) optical fiber", Optical Engineering, 56, 2, 027106 (2017). CrossRef D. Oh, N. Song and J.-J. Kim, "Plastic optical amplifier using europium complex", Proc. SPIE, 4282, (2001). CrossRef X. Xu, H. Ming, Q. Zhang, "Optical-transition probabilities of Nd3+ ions in polymer optical fibers", Optics Communications 199, 369 (2001). CrossRef Z.-Q. Zheng, H. Liang, H. Ming, Q.-J. Zhang, X.-H. Han, G.-Z. Wang, J.-P. Xie, "Optical Transition Probability of Sm 3+ Ions in a Polymer Optical Fibre", Chin. Phys. Lett. 21, 2, 291 (2004). CrossRef
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Grimstad, Tore, Ingeborg Kvivik, Jan Terje Kvaløy, Lars Aabakken, and Roald Omdal. "Heat-shock protein 90α in plasma reflects severity of fatigue in patients with Crohn’s disease." Innate Immunity 26, no. 2 (October 10, 2019): 146–51. http://dx.doi.org/10.1177/1753425919879988.
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Heat-shock proteins (HSPs) are evolutionarily conserved proteins with important cellular homeostasis functions during harmful conditions, including inflammation. Some HSPs are secreted extracellularly and act on distant cells by down-regulating inflammation and increasing cellular stress defence mechanisms. HSP90α has been postulated to signal fatigue in chronic inflammation. We investigated whether HSP90α is associated with fatigue in patients with Crohn’s disease. Fifty-three patients with newly diagnosed Crohn’s disease were included in a cross-sectional study. Data on demographics and disease distribution were obtained. Fatigue was measured by the fatigue visual analogue scale (fVAS). Disease activity was assessed by the Simple Endoscopic Score for Crohn’s disease and Harvey Bradshaw Index. C-reactive protein, faecal calprotectin and HSP90α were also measured. The median fVAS score was 52 mm, indicating significant fatigue. HSP90α scores correlated significantly with fVAS ( r = 0.31, P = 0.03). In a multivariate regression model, HSP90α was the only significant contributor to fVAS scores (β = 0.31, P = 0.03). When patients were dichotomised into groups with high and low HSP90α concentrations, significantly higher fVAS scores were demonstrated in the group with high HSP90α ( M = 62.4, confidence interval 53.0–71.8 vs. 43.3, 31.6–55.0; P = 0.01). Thus, HSP90α may contribute to fatigue generation and/or modulation in patients with Crohn’s disease.
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Mian, Caterina, Gianmaria Pennelli, Susi Barollo, Elisabetta Cavedon, Davide Nacamulli, Federica Vianello, Isabella Negro, et al. "Combined RET and Ki-67 assessment in sporadic medullary thyroid carcinoma: a useful tool for patient risk stratification." European Journal of Endocrinology 164, no. 6 (June 2011): 971–76. http://dx.doi.org/10.1530/eje-11-0079.
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ObjectiveMedullary thyroid carcinoma (MTC) derives from the parafollicular C cells, being sporadic in 75% of cases and familial in 25%, due to RET proto-oncogene germinal mutations. In sporadic forms, stage at diagnosis is the most important negative prognostic factor. The aim of this study was to evaluate the prognostic impact of molecular and immunohistochemical markers in sporadic MTC.Design and methodsWe studied 60 patients with sporadic MTC. For each case, we sought RET somatic mutations in the primary cancer and in lymph node metastases. The primary cancer also underwent immunohistochemical examination for Ki-67.ResultsA somatic RET mutation was found in 38% of patients, being M918T in 52% of them. We observed a statistically significant association between RET mutations and male gender (P<0.01), tumor size (P<0.05), lymph nodes (P<0.05) and distant metastases (P<0.001), advanced stage (P<0.05), increased risk of persistent disease (P=0.01), and low overall survival (P<0.01). High Ki-67 levels were similarly associated with extra-thyroid spread (P<0.05), lymph nodes (P<0.05) and distant metastases (P<0.001), advanced stage (P=0.01), and low overall survival (P=0.01).Combining somatic RET analysis with Ki-67 assessment seems to be useful for increasing the specificity of Ki-67 assessment alone and identifying patients with a more aggressive cancer: in our series, only the patients who died during the follow-up had both a somatic RET mutation and a Ki-67 expression level >50 cells/mm2.ConclusionsThe combined evaluation of RET and Ki-67 could act as an adjuvant prognostic marker useful for ameliorating the initial risk stratification of patients with sporadic MTC.
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Yesilipek, M. Akif, Gulsun Karasu, Zuhre Kaya, Baris B. Kuskonmaz, Vedat Uygun, Ilkiz Dag, Asli Birkent, and Mehmet Ertem. "Interim Results from a Phase 2, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with Beta-Thalassemia Major." Blood 126, no. 23 (December 3, 2015): 959. http://dx.doi.org/10.1182/blood.v126.23.959.959.
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Abstract Introduction: Hematopoietic stem cell transplantation (HSCT) is being increasingly used as curative therapy for severe disorders of the hematopoietic system and transfusional iron overload (TIO) contributes considerably to treatment-related morbidity and mortality after HSCT. Management of iron overload in the post-HSCT setting may be complicated since the use of therapeutic phlebotomies is often not feasible due to ongoing anemia and compliance to deferoxamine is low. Studies that evaluate the safety dose of deferasirox (DFX), which is the most commonly used chelation therapy, in this setting are limited. Purpose & Methods: This is a prospective, phase 2, multicenter, single-arm study to evaluate the efficacy and safety of iron chelation with oral DFX in beta-thalassemia major (TM) patients who have undergone HSCT. The study was conducted in 7 centers from Turkey. The primary objective was to evaluate if DFX could provide clinically safe chelation in a target pool of 26 pediatric patients with TIO within a minimum of 6 months and maximum of 2 years after related/unrelated HSCT. Patients had to be transfusion-independent and have iron overload at screening defined by serum ferritin (SF) of >1000 μg/L or cardiac MRI T2* <20 ms or liver iron concentration (LIC, by MRI R2) of ≥5 mg/g. The study included male and female TM patients ≥2 to <18 years old who had undergone HSCT with a washout period from immunosuppressive therapy of at least 3 months. Patients received DFX at an initial dose of 10 mg/kg/day with up titration every 3 months by 5 mg/kg/day per investigator judgment to a maximum of 20 mg/kg/day. Therapy continued for 52 weeks or until SF reached below 500 μg/L. Aside from AE monitoring, assessments were undertaken at baseline and every 28 days (unless closer assessments were need for dose initiation and adjustment) and included complete blood counts, biochemistry and urinalysis, and SF. MRI assessment of liver (R2) and cardiac (T2*) iron were also conducted at baseline and 52 weeks. Results: Interim data from the first 18 of 26 patients (mean age 8.3 years, 66.7% males) who completed 12 months follow up are presented in this analysis. A total of 97 AEs were recorded in the 18 patients. The majority of AEs were of Grade I (n=57) or II (n=34) severity. Five (5.2%) were suspected to be related to study drug and 6 AEs (6.2%) were considered serious. Five (5.2%) AEs resulted in study drug temporary interruption or dose adjustment, 2 (2.1%) required hospitalization, 54 (55.7%) required concomitant medication, while 36 (37.1%) had no action taken. Three patients had dose decrease due to AEs. The dose was re-escalated up to 20 mg/kg/day after the AEs resolved. In total, 11 (61.1%) patients achieved 20 mg/kg/day. Only one patient dropped out due to progressive ALT increase. Median ALT level decreased from 26 IU/L (range: 10-117) at baseline to 18 IU/L (range: 9-101) at week 52. The median SCr was similar at baseline 0.4 mg/dL (range: 0.2-0.6) and week 52 0.4 mg/dL (range: 0.2-0.8). Median cystatin C was similar at baseline 0.7 mg/mL (range: 0.6-0.9) and week 52 0.7 mg/mL (range: 0.5-1.1) (Figure 1A-B). Five patients had proteinuria at baseline and increased proteinuria compared to previous visit by dipstick analysis was described in 7 (38.9%) patients, irrespective of DFX dose by 52 weeks. No patient with proteinuria required any dose adjustments by 52 weeks. SF significantly and consistently decreased throughout the 52 weeks from a median of 1752.3 μg/L (range: 873.7-2716) to 915.2 μg/L (range: 250.1-2740), p<0.001 (Figure 2). At week 52, 6 (33.3%) patients had reached SF <500 μg/L. LIC also significantly decreased from a median of 9.9 mg/g (range: 4.8-43) to 4.1 mg/g (range 0.9-8.5), p<0.001. Cardiac T2* increased from a median of 26.1 ms (range: 18.7-41) to 28.8 ms (18.5-44), p=0.605. Conclusions: Our preliminary results showed that DFX up to 20 mg/kg/day is safe and effective in reducing iron burden for TM patients following HSCT. This was evident through significant reductions of systemic, hepatic and cardiac iron overload. Final data from the completed study should confirm these findings and establish the role for DFX in this patient population. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Dag: Novartis: Employment. Birkent:Novartis: Employment.
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Wu, R., L. Wang, X. Zheng, Y. Wang, G. Wang, X. Li, and X. Li. "THU0242 REGULATORY ROLE OF TRANSCRIPTION FACTOR BLIMP-1 IN SJÖGREN’S SYNDROME." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 348. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2618.
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Background:The pathogenesis of primary sjögren’s syndrome (pSS) is multifactorial. Self-antigen-driven responses perform a vital function in the development of autoimmune diseases [1]. B cells, only 20-25% of total infiltrating cells in labial glands, are the cellular basis for spontaneous antibody production [2].Genome-wide association studies (GWAS) have identified Blimp-1 as a susceptibility gene for autoimmune diseases and played an important role in the pathogenesis of autoimmune diseases [3].Objectives:To investigate the expression and effect of B lymphocyte induced maturation protein 1 (Blimp-1) in pSS and the correlation of Blimp-1 with B cell subsets and clinical features.Methods:The PRDM1 mRNA expression in B lymphocyte and labial gland were examined by RT-PCR. The levels of B cell subsets were examined by flow cytometry. Hematoxylin-eosin (HE) staining and immunohistochemistry (IHC) were used to examine the invasion degree of lymph cell and Blimp-1 distribution, respectively. The correlation of PRDM1 mRNA with B cell subsets and clinical indicators were also analyzed.Results:The levels of PRDM1 mRNA expression of B cells were significantly higher in SS than in healthy controls (HC) and which were also significantly higher in the high immunoglobulin (Ig) group than that in normal Ig group (P<0.02, Fig. 1a-b). The number of CD19+B cells and CD138+ plasma cells(PC) have increased while the CD27+ cells decreased in SS(P<0.05). The percentage of PC and PC/B is positively correlated with PRDM1 mRNA(r=0.380,P=0.002;r=0.317,P=0.009, Fig. 1c-d). Blimp-1 expression level showed a positive correlation with invasion degree of lymph cell in histology (Fig. 2a-c), Ig levels and ESSDAI score and an inverse correlation with the glucocorticoids usage (Fig. 3c).Fig. 1(a-b) RT-PCR showed that PRDM1 mRNA expression in SS patients and HC. (c-d) Correlation between PRDM1 mRNA expression and PC and PC/B.Fig. 2(a) Expression of Blimp-1 in labial glands of sjögren’s syndrome. (b) PRDM1 mRNA levels in different invasion degree of lymph cell group. (c) Correlation between PRDM1 mRNA expression and invasion degree of lymph cell. *p<0.05, ***p<0.001.Fig. 3(a-b) RT-PCR showed that PRDM1 mRNA expression in different usage of glucocorticoids. (c) Correlation between PRDM1 mRNA expression and different glucocorticoid usage. **p<0.01, ***p<0.001.Conclusion:Blimp-1 displayed high expression in SS, which could affect pSS disease activity. SS activity is suppressed by glucocorticoid which might be through inhibition of Blimp-1.References:[1]Kapsogeorgou EK, Abu-Helu RF, Moutsopoulos HM, Manoussakis MN (2005) Salivary gland epithelial cell exosomes: A source of autoantigenic ribonucleoproteins. Arthritis Rheum 52(5):1517-21.https://doi.org/10.1002/art.21005[2]Arneth BM (2019) Impact of B cells to the pathophysiology of multiple sclerosis. J Neuroinflammation 16(1):128.https://doi.org/10.1186/s12974-019-1517-1[3]Bönelt P, Wöhner M, Minnich M et al (2019) Precocious expression of Blimp-1 in B cells causes autoimmune disease with increased self-reactive plasma cells. EMBO J 38(2). pii:e100010.https://doi.org/10.15252/embj.2018100010Table 1.Clinical characteristics of pSS and HC.HC(n=17)pSS(n=50)Sex (Male/Female)0/170/50Age(x±s)45.24±18.5546.8±11.05Xerostomia(positive/negative)0/1743/7Keratoconjunctivitis sicca0/1735/15Arthralgia0/1732/18Fatigue0/1718/32ESSDAI(x±s)-2.78±1.61 (0~7)ESSPRI(x±s)-3.3±1.39 (1~6)ANA(positive/negative)-49/1SSA-49/1SSB-18/32pSS: primary sjögren ‘s syndrome; HC: Healthy controls; ESSDAI: The European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index; ESSPRI: EULAR Sjögren’s Syndrome Patient Reported Index.** P<0.01,*** P<0.001.Acknowledgments :This study was supported by the grants from the National Natural Science Foundation of China (81871271).Disclosure of Interests: :None declared
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Osbrough, S. L., J. S. Frederiksen, and C. S. Frederiksen. "The effects of model climate bias on ENSO variability and ensemble prediction." ANZIAM Journal 60 (October 18, 2019): C215—C230. http://dx.doi.org/10.21914/anziamj.v60i0.14092.
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New methods are presented for determining the role of coupled ocean-atmosphere model climate bias on the strength and variability of the El Nino-Southern Oscillation (ENSO) and on the seasonal ensemble prediction of El Nino and La Nina events. An intermediate complexity model with a global atmosphere coupled to a Pacific basin ocean is executed with parallelised algorithms to produce computationally efficient year-long forecasts of large ensembles of coupled flow fields, beginning every month between 1980 and 1999. Firstly, the model is provided with forcing functions that reproduce the average annual cycle of climatology of the atmosphere and ocean based on reanalysed observations. We also configure the model to generate realistic ENSO fluctuations. Next, an ensemble prediction scheme is employed which produces perturbations that amplify rapidly over a month. These perturbations are added to the analyses and give the initial conditions for the ensemble forecasts. The skill of the forecasts is presented and the dependency on the annual and ENSO cycles determined. Secondly, we replace the forcing functions in our model with functions that reproduce the averaged annual cycles of climatology of two state of the art, comprehensive Coupled General Circulation Models. The changes in skill of subsequent ensemble forecasts elucidate the roles of model bias in error growth and potential predictability.
References C. S. Frederiksen, J. S. Frederiksen, and R. C. Balgovind. ENSO variability and prediction in a coupled ocean-atmosphere model. Aust. Met. Ocean. J., 59:35–52, 2010a. URL http://www.bom.gov.au/jshess/papers.php?year=2010. C. S. Frederiksen, J. S. Frederiksen, and R. C. Balgovind. Dynamic variability and seasonal predictability in an intermediate complexity coupled ocean-atmosphere model. In Proceedings of the 16th Biennial Computational Techniques and Applications Conference, CTAC-2012, volume 54 of ANZIAM J., pages C34–C55, 2013a. doi:10.21914/anziamj.v54i0.6296. C. S. Frederiksen, J. S. Frederiksen, J. M. Sisson, and S. L. Osbrough. Trends and projections of Southern Hemisphere baroclinicity: the role of external forcing and impact on Australian rainfall. Clim. Dyn., 48:3261–3282, 2017. doi:10.1007/s00382-016-3263-8. J. S. Frederiksen, C. S. Frederiksen, and S. L. Osbrough. Seasonal ensemble prediction with a coupled ocean-atmosphere model. Aust. Met. Ocean. J., 59:53–66, 2010b. URL http://www.bom.gov.au/jshess/papers.php?year=2010. J. S. Frederiksen, C. S. Frederiksen, and S. L. Osbrough. Methods of ensemble prediction for seasonal forecasts with a coupled ocean-atmosphere model. In Proceedings of the 16th Biennial Computational Techniques and Applications Conference, CTAC-2012, volume 54 of ANZIAM J., pages C361–C376, 2013b. doi:10.21914/anziamj.v54i0.6509. P. R. Gent, G. Danabasoglu, L. J. Donner, M. M. Holland, E. C. Hunke, S. R. Jayne, D. M. Lawrence, R. B. Neale, P. J. Rasch, M. Vertenstein, P. H. Worley, Z.-L. Yang, and M. Zhang. The community Climate System Model version 4. J. Clim., 24:4973–4991, 2011. doi:10.1175/2011JCLI4083.1. S. Grainger, C. S. Frederiksen, and X. Zheng. Assessment of modes of interannual variability of Southern Hemisphere atmospheric circulation in CMIP5 models. J. Clim., 27:8107–8125, 2014. doi:10.1175/JCLI-D-14-00251.1. E. Kalnay, M. Kanamitsu, R. Kistler, W. Collins, D. Deaven, L. Gandin, M. Iredell, S. Saha, G. White, J. Woollen, Y. Zhu, M. Chelliah, W. Ebisuzaki, W. Higgins, J. Janowiak, K. C. Mo, C. Ropelewski, J. Wang, A. Leetmaa, R. Reynolds, R. Jenne, and D. Joseph. The NCEP/NCAR 40-year reanalysis project. B. Am. Meteorol. Soc., 77:437–472, 1996. doi:10.1175/1520-0477(1996)077<0437:TNYRP>2.0.CO;2. H. A. Rashid, A. Sullivan, A. C. Hirst, D. Bi, X. Zhou, and S. J. Marsland. Evaluation of El Nino-Southern Oscillation in the ACCESS coupled model simulations for CMIP5. Aust. Met. Ocean. J., 63:161–180, 2013. doi:10.22499/2.6301.010. K. E. Taylor, R. J. Stouffer, and G. A. Meehl. An overview of CMIP5 and the experiment design. Bull. Am. Meteorol. Soc., 93:485–498, 2012. doi:10.1175/BAMS-D-11-00094.1.
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Delaloge, S., K. L. Tedesco, J. Blum, A. Gonçalves, J. Lubinski, N. Efrat, C. Osborne, C. Lebedinsky, J. C. Tercero, and F. A. Holmes. "Preliminary safety and activity results of trabectedin in a phase II trial dedicated to triple-negative (ER-, PR-, HER2-), HER2+++, or BRCA1/2 germ-line-mutated metastatic breast cancer (MBC) patients (pts)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 1010. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.1010.
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1010 Background: Trabectedin ([T]; Yondelis) binds to the minor groove of DNA; its cytotoxicity is determined by the synergistic action of two DNA repair mechanisms, the efficient nucleotide excision repair (NER) and deficient homologous recombination repair (HRR) machinery. T has EMEA authorization in soft tissue sarcoma after failure of standard treatment. Preliminary data have shown activity of T as single agent in MBC. Clinical and preclinical data suggested T may display specific activity among certain NER-intact or HRR-deficient MBC, and prompted this phase II trial dedicated to 3 subgroups: triple-negative (TN), HER-2-overexpressed, and BRCA1/2 germline-mutated MBC. Methods: T was given at 1.3 mg/m2 as a 3- hour iv infusion every 3 weeks to pts with pretreated progressive MBC: Group A: TN; Group B: HER-2+++; Group C: BRCA1/2 mutation carriers. Endpoints were objective response (OR) rate by RECIST, duration of response, progression free survival (PFS), tumor volume changes, safety and exploratory pharmacogenomics (PGx). Results: A total of 95 women (median [med] age 52, ECOG 0/1 48/52%) have been enrolled (A:50, B:24, C:21) with data available for 72 pts. Med number of prior chemotherapy regimens: 4 (1–10). Med number of T cycles administered: 2 (1–12) for all groups. The most commonly reported grade 3/4 AEs are neutropenia (29/21%), ALT (28/2%) and AST (13/0). Alopecia/stomatitis, only G1, was reported in <2% each. Long-lasting disease stabilizations were described in all groups. While OR were rare among TN MBC pts (2PR/43 evaluable), preliminary analysis by investigator shows efficacy in group C (4PR/11 evaluable). Tissue samples from 36 pts were collected for RNA expression analysis (XPG + ERCC1 + BRCA1). Preliminary results show high XPG is associated with longer PFS: 4.1 months (95% CI 2.6-not reached) versus 1.3 months (95% CI 1.2–3.7), p = 0.01. Analyses are ongoing. Conclusions: Trabectedin shows a manageable safety profile in the 3 groups of MBC with promising efficacy in certain DNA-repair machinery sub-categories defined molecularly. TN group was closed due to low response. More mature PGx results will be discussed to help selecting the patients who are at highest chance for response. [Table: see text]
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Arcasoy, Murat O., Paul Hanlon, Ping Fu, Charles Steenbergen, and Elizabeth Murphy. "Mechanisms of Erythropoietin-Mediated Cardioprotection during Ischemia-Reperfusion Injury: Role of Protein Kinase C Signaling." Blood 104, no. 11 (November 16, 2004): 2907. http://dx.doi.org/10.1182/blood.v104.11.2907.2907.
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Abstract The biologic effects of erythropoietin (EPO) are mediated by its cellular receptor EPOR, a member of the cytokine receptor superfamily. EPOR expression in non-hematopoietic cells is associated with novel biologic effects for EPO in diverse organ systems. We recently demonstrated functional EPOR expression in adult rat cardiac myocytes and found that recombinant EPO exerts a rapid cardioprotective effect during ischemia-reperfusion injury of the isolated, perfused heart. Here we investigated the mechanisms of the cardioprotective effect of EPO using Langendorff-perfused rat hearts while left-ventricular-developed pressure (LVDP) was measured continuously to assess contractile function. Hearts were treated directly with EPO in the presence or absence of inhibitors of specific signal transduction pathways prior to normothermic global ischemia followed by reperfusion. Post-ischemic recovery of contractile function was determined by measuring LVDP at the end of reperfusion and expressed as a percentage of the baseline pre-treatment measurement. We investigated EPO-mediated activation of signal transduction pathways in the isolated, perfused heart and observed phosphorylation of p44/p42 MAP kinases ERK 1/2 (Thr202/Tyr204) and protein kinase B/Akt (Ser473), a downstream target of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Furthermore, EPO treatment of the isolated, perfused heart was associated with translocation of protein kinase C (PKC) ε and δ isoforms to the membrane fraction. We investigated the role of specific signaling pathways in EPO-mediated cardioprotection by employing inhibitors targeting PI3K, PKC and MAP kinase kinase (MEK1). PI3K inhibitors LY294002 and wortmannin attenuated EPO-induced phosphorylation of Akt but had no effect on EPO-mediated cardioprotection. MEK1 inhibitor U0126 had no effect on EPO-mediated cardioprotection. The PKC catalytic inhibitor chelerythrine (chel) significantly inhibited EPO-mediated improvement in post-ischemic recovery of LVDP (figure 1). Hearts pre-treated with EPO exhibited significantly improved post-ischemic recovery of LVDP compared to control hearts (mean±SE: 72±3 in EPO-treated versus 35±3% in control hearts, P<0.05 by ANOVA and Bonferroni post-hoc test, n=10 experiments each group) and the protective effect of EPO was significantly inhibited in chel-treated hearts (52±4% in EPO+chel versus 72±3% in EPO-treated hearts, P<0.05, n=10). As a control, treatment of the hearts with chelerythrine alone had no significant effect on LVDP (49±4%) compared to control hearts. These data demonstrate that EPO-mediated activation of the PKC signaling pathway is required for the cardioprotective effect of EPO during ischemia-reperfusion injury. Figure Figure
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Holle, Julia U., Christin Dubrau, Karen Herlyn, Martin Heller, Petra Ambrosch, Bernhard Noelle, Eva Reinhold-Keller, and Wolfgang L. Gross. "Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations." Annals of the Rheumatic Diseases 71, no. 3 (October 21, 2011): 327–33. http://dx.doi.org/10.1136/ard.2011.153601.
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ObjectiveFirst, to investigate the overall efficacy and safety of rituximab (RTX) in refractory granulomatosis with polyangiitis (GPA) in a tertiary referral centre. Second, to compare the efficacy of RTX in granulomatous and vasculitic manifestations in GPA.Patients and methodsThis study comprised a retrospective, standardised data collection from all patients who received RTX for refractory Wegener's granulomatosis from 2002 to 2010. Patients were assessed by a standardised interdisciplinary diagnostic procedure (including ear, nose and throat and ophthalmology assessment, MRI, immunodiagnostics, B-cell levels and Birmingham Vasculitis Activity Score) and were treated by standardised therapeutic regimens according to available evidence.Results59 patients received 75 cycles of RTX. 9.3% achieved complete remission. A response was documented in 61.3% (improvement in 52%, unchanged disease activity in 9.3%), 26.7% had refractory disease. Birmingham Vasculitis Activity Score, disease extent index, erythrocyte sedimentation rate, C-reactive protein and prednisolone demand decreased significantly. All patients achieved B-cell depletion. Granulomatous manifestations such as orbital granuloma and pachymeningitis were more frequently refractory to RTX than vasculitis or other granulomatous manifestations. Thus, for example, complete remission/improvement was found in 89.2% of patients with renal disease and in only 44.4% of those with orbital masses (p=0.003). The relapse rate was 44.4% after a median period of 13.5 months. Adverse events occurred in 29%, pneumonia in 15% and death in 3%.ConclusionThe overall response rate of refractory GPA to RTX was high (61.3% complete remission or improvement). Response rates of vasculitic manifestations were excellent; failure of response/progress was mostly due to granulomatous manifestations, especially orbital masses. Relapse rates were high (40%) despite maintenance treatment.
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Merli, Michele, Alessandro Re, Michele Bibas, Davide Dalu, Emanuele Ravano, Guido Gini, Carlo Visco, et al. "Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases." Blood 138, Supplement 1 (November 5, 2021): 1434. http://dx.doi.org/10.1182/blood-2021-151174.
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Abstract Background: Hepatitis C virus (HCV) chronic infection has been associated with increased risk of non-Hodgkin lymphoma (NHL) in people living with human immunodeficiency virus (HIV) as well as with a trend of inferior overall survival (OS) in HIV-associated NHL in the modern antiretroviral therapy (ART) era (Besson 2020). The recent introduction of interferon (IFN)-free direct-acting antivirals (DAAs) led to the achievement of sustained virologic response (SVR) in nearly all treated patients (pts) with negligible toxicity in all settings, including HIV/HCV coinfected pts, in which, however, careful attention to interactions with ART is required. We recently showed that DAAs' administration after immuno-chemotherapy (I-CT) may improve long-term outcome in HIV-negative HCV-associated diffuse large B-cell lymphomas (DLBCL) pts (Merli 2019), however, only scant data have been reported so far about the use of DAAs in HIV/HCV coinfected NHL pts. METHODS: We retrospectively collected clinical and virological features, treatments and outcome data of all consecutive pts with NHL and HIV/HCV co-infection, diagnosed and treated at 13 Italian centers between 2005 and 2021, with a special focus on pts affected by DLBCL and treated with DAAs. Only pts who received ART were included. The primary endpoints were SVR rate after DAAs and 2-year OS in HIV/HCV-positive NHL pts. RESULTS: Overall, we collected data of 74 HIV/HCV coinfected pts with NHL (69 males, 93%), including 52 DLBCL, 13 Burkitt lymphoma (BL), 5 plasmablastic lymphoma (PL), 1 anaplastic large-cell ALK negative, 1 T lymphoblastic, 1 gastric MALT and 1 lymphoplasmacytic lymphoma (Table 1). Median age was 51 years (22-57). Previous AIDS defining event was recorded in 16 cases (22%). The main HIV transmission group was represented by intravenous drug users (69%). Stage was III-IV in 63 pts (85%) and aaIPI was ≥2 in 57 pts (77%). At NHL diagnosis 38% of pts had CD4+ <200/mmc and 31% ≥400 HIV-RNA copies/ml. ARL-IPI score was intermediate or high in 49 pts (64%). HCV genotype was 1 in 26 pts (58%), 3 in 12 (27%) and 4 in 7 (15%). Cirrhosis was present in 39% of pts (Child-Pugh B or C in 25%). Overall, 70 pts underwent curative first line therapy alongside ART, including (R-)CHOP-like in 50 (71%), (R-)EPOCH in 9 (13%), (R-)CODOX-M/IVAC in 8 (11%). Rituximab was used in 53% of cases (60% in DLBCL). 46 pts (66%) achieved a complete response (CR), 7 (10%) a partial response (PR), while 17 (24%) did not respond or progressed. At a median follow-up of 1.8 years (95%CI 0.1-12.3), 33 pts (45%) progressed, with a 2-year PFS of 53.5% (95%CI 40.7-64.8), and 38 (51%) died (30 due to NHL, 7 to infections and 1 to hepatocellular carcinoma), with a 2-year OS of 58.2% (95%CI 45.7-78.9). Two-year OS for DLBCL was 61.4% (95%CI 46.3-73.4), significantly higher than BL (39%, 95%CI 14.1-62.8; p=.0.47, Fig. 1). Considering anti-HCV therapy, 13 pts received IFN-based regimens, 5 of whom achieved SVR (38%). After 2016, 21 pts (14 DLBCL, 3 BL, 2 indolent and 2 T-cell lymphoma), including 4 who previously failed IFN, received various DAAs regimens after I-CT (sofosbuvir-based in 20). Toxicity of DAAs was minimal, with only 2 grade (G) ≥2 adverse events (1 G2 peripheral neuropathy and 1 G2 insomnia). SVR was achieved in 20/21 pts (95%): notably, the only non-responder had discontinued DAAs autonomously. DAAs use was associated with improved OS in all pts (p=0.01) and in DLBCL (p=0.04) and with better PFS (p=0.01) in all pts. Similarly, the achievement of SVR after either DAAs or IFN predicted a better OS (Fig.2) and PFS in all pts (p=0.005 and p=0.008, respectively) and in DLBCL (p=0.018 and p=0.047, respectively). The impact of DAAs and SVR on OS remained significant also if considering only pts who achieved CR or PR after I-CT (p<0.05). At univariate analysis, age >60 years (p=0.02), ARL-IPI (p=0.013), PS ECOG ≥2 (p=0.018) were associated with inferior OS. By applying multivariate Cox regression analysis, age >60 years (HR 67.9, 95% CI 7.2- 643.3, p<0.001), ARL-IPI (HR 2.87, 95%CI 1.03-8.06, p=0.044) and SVR after IFN or DAAs (HR 0.30, 95%CI 0.12-0.75, p=0.01) retained independent prognostic influence on OS. CONCLUSIONS: In this very high risk series of HIV/HCV coinfected pts with NHL, mainly represented by DLBCL, the administration of DAAs after I-CT resulted feasible and effective (SVR 95%), and displayed an independent favourable influence on OS. These results strongly support DAAs' use in this hard to treat population. Figure 1 Figure 1. Disclosures Tisi: Incyte: Membership on an entity's Board of Directors or advisory committees; BWS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Takeda: Other: travel expenses, accommodation; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau. Passamonti: AbbVie: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Arcaini: Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Gilead Sciences: Research Funding; Celgene: Speakers Bureau.
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Abdul Razzack, A., S. Abdul Razzack, P. Shenasan, N. Shenasan, S. Mishra, R. Zarrar, J. Pablo Sosa, et al. "POS0701 ANIFROLUMAB, AN ANTI-INTERFERON-Α RECEPTOR MONOCLONAL ANTIBODY IN SYSTEMIC LUPUS ERYTHEMATOSUS- A META ANALYSIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 600.1–600. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2782.
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Background:Type I interferons such as Anifrolumab have been implicated in Systemic lupus erythematosus (SLE) pathogenesis on the basis of increased interferon-stimulated gene expression and genetic susceptibility. Little is known regarding its efficacy and safety profile.Objectives:To assess the efficacy and safety of Anifrolumab in patients with SLE.Methods:Electronic databases (PubMed, Embase, Scopus, Cochrane) were searched from inception until December 15th, 2020. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p<0.05. The primary outcome of interest was British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). Secondary outcomes included the proportion of patients who achieved an SLE responder index of 4 (SRI-4) reduction of 50% or more in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), reductions in the glucocorticoid dose and adverse effects.Results:A total of three studies1,2,3 with 839 participants (Anifrolumab=372, Placebo=467) were included in our analysis. Follow-up duration was at week 52. A statistically significant different was observed in the Anifrolumab arm in terms of BICLA response (OR 0.44 95%CI 0.34-0.59;p < 0.00001, I2=4), ≥50% reduction in CLASI activity score (OR 0.36 95%CI 0.21-0.60;p=0.0001, I2=0), glucocorticoid reduction (OR 0.41 95%CI 0.28-0.59;p<0.00001; I2=0) and SRI-4 response (OR 0.52 95% CI 0.30-0.90; p=0.02, I2=75). However, Adverse events were less likely in the placebo arm as compared to Anifrolumab (OR 1.54 95%CI 1.05-2.25; p=0.03; I2=0).Conclusion:Anifrolumab was found to be more effective than placebo for the management of SLE, but may also cause more severe adverse effects.References:[1]Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, Bae SC, Brohawn PZ, Pineda L, Berglind A, Tummala R; TULIP-2 Trial Investigators. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020 Jan 16;382(3):211-221. doi: 10.1056/NEJMoa1912196. Epub 2019 Dec 18. PMID: 31851795.[2]Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, Illei GG, Drappa J, Wang L, Yoo S; CD1013 Study Investigators. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017 Feb;69(2):376-386. doi: 10.1002/art.39962. PMID: 28130918; PMCID: PMC5299497.[3]Furie RA, Morand EF, Bruce IN, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol 2019; 1(4):e208-e219.Disclosure of Interests:None declared
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Koh, Min Jung, Mwanasha H. Merrill, Min Ji Koh, Robert N. Stuver, Carolyn D. Alonso, Francine M. Foss, Angel M. Mayor, et al. "Comparative Analysis of Mature T-Cell and NK/T-Cell Lymphomas in Patients with and without HIV: Results from the NA-Accord and Complete Cohorts." Blood 138, Supplement 1 (November 5, 2021): 1380. http://dx.doi.org/10.1182/blood-2021-147837.
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Abstract Background: Clinicopathological characteristics and prognosis for patients with HIV (PWH) and T-cell lymphomas (TCLs) in the current antiretroviral therapy (ART) era remains unknown. The primary objective of this study was to determine outcomes of patients with mature T and NK/T-cell lymphomas with and without HIV (PWoH) in North America. A secondary objective was to define variations in the survival of patients with TCLs and AIDS-defining B-cell lymphomas (A-BCLs) in the presence of ART. Methods: The study population included patients from two source populations, the NA-ACCORD (The North American AIDS Cohort Collaboration on Research and Design) and COMPLETE (Comprehensive Oncology Measures for Peripheral T-cell Lymphoma), both of which have been previously described. The NA-ACCORD collaborates with >20 longitudinal cohorts of adults (aged ≥ 18 years) with HIV in the United States and Canada. Within the NA-ACCORD cohort, we included patients with a validated incidental diagnosis of mature T and NK/TCL (n=52) or the most common A-BCLs including Burkitt's lymphoma (n=101), diffuse large B-cell lymphoma (DLBCL, n=500) and primary CNS lymphoma (PCNSL, n=64) between 1996 and 2016. COMPLETE is a prospective, multicenter cohort study of patients with newly diagnosed incidental mature TCLs in the United States between 2010 and 2014. Of the 452 eligible patients, 450 were included for analysis after exclusion of two patients with HIV infection. Patients were followed from diagnosis to the first of death, loss to follow-up or administrative censoring at 5 years. Kaplan-Meier and log-rank tests were used to estimate and compare survival. Results: At the time of TCL diagnosis, PWH were significantly younger than patients without HIV (PWoH) (49 years vs. 60 years respectively; p<0.001). PWH were predominantly men (96% vs. 63%; p<0.001), of white race (64% vs. 77%; p<0.006), with chronic kidney disease (19% vs. 2.2%; p<0.001) and with co-infections such as hepatitis B virus (13% vs. 0.9%; p<0.001) and hepatitis C virus (19% vs. 1.1%; p<0.001). Anaplastic large-cell lymphoma (ALCL, n=26) was the most common histological subtype within PWH relative to peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS, n=143) among PWoH. More than 92% of the patients within the NA-ACCORD cohort were on at least one class of ART during their cohort enrollment period. Median duration of ART prior to lymphoma diagnosis was 2.9 years (0.7-9.4) and comparable for patients with TCLs and A-BCLs. The median time from NA-ACCORD cohort enrollment to lymphoma diagnosis was 2.3 years (IQR: 0.3-5.9 years) for TCLs and comparable for patients with the A-BCL subgroups (2.8 years, IQR: 0.6-7.2 years; p=0.21). At the end of the 5-year follow-up period, the survival probability since TCL diagnosis was markedly lower at 0.32 (95% confidence interval [CI]: 0.21-0.49) among PWH in contrast to 0.45 (95% CI: 0.41-0.51) for PWoH. Specifically, survival probability since ALCL diagnosis was distinctively lower at 0.23 (95% CI: 0.11-0.47) among PWH in contrast to 0.76 (95% CI: 0.66-0.87) for PWoH. Mortality following lymphoma diagnosis was elevated for PWH vs. PWoH even after adjusting for statistically significant baseline clinical characteristics such as age, race, and ALCL status in multivariate analysis (adjusted HR: 1.92; 95% CI: 1.27, 2.91). Among PWH with TCL, CD4 <200 and viral load (VL) >500 (n=10) was associated with a lower survival relative to those with counts >200 and/or VL <500 (n=12, p=0.031). Upon stratification of PWH into different calendar periods based on year of diagnosis (1996-1999 vs. 2000-2009 vs. 2010-2016), we observed an improvement in survival for all subgroups over time. Overall, among PWH, PCNSL had the worst median overall survival (3.8 months, 95% Cl: 2.0-7.2 months) followed by ALCL (10.6 months, 95% Cl: 2.1-33.4 months), DLBCL (15.6 months, 95% CI: 12.7-22.2 months) and Burkitt's lymphoma. Conclusions: Our report based on two large observational cohorts in North America highlights poor outcomes for TCLs among PWH compared to PWoH. In addition, within the PWH group, our study is the first to delineate inferior survival for patients with ALCLs relative to DLBCL and Burkitt's lymphoma accentuating the need for novel therapies. However, the overall prognosis for these lymphomas among PWH has improved in the last two decades, particularly among those with CD4>200, underscoring the impact of early and sustained ART. Disclosures Alonso: Merck: Research Funding. Foss: Kyowa: Honoraria; Acrotech: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Mallinckrodt: Honoraria; Daiichi Sankyo: Honoraria; Kura: Honoraria. Jain: Trillium Therapeutics, Inc: Research Funding; Acro Biotech, Inc: Research Funding; Abcuro, Inc: Research Funding.
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Ispiroglu, Murat, Ibrahim Halil Bahcecioglu, Ulvi Demirel, and Mehmet Yalniz. "Impact of interleukin 28B rs12979860 C/T polymorphism on severity of disease and response to treatment in hepatitis delta." Journal of Infection in Developing Countries 11, no. 01 (January 30, 2017): 58–64. http://dx.doi.org/10.3855/jidc.6872.
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Introduction: Pegylated-interferon alpha (Peg-IFN α) is the therapy most commonly used to treat chronic hepatitis delta virus (HDV) infection. In the present study, we planned to investigate effect of IL28B polymorphism on response to Peg-IFN α therapy and disease progression in patients with chronic HDV. Methodology: A total of 47 patients who received Peg-IFNα therapy for at least one year were investigated. The patients were divided into three groups based on their response to treatment: sustained viral response (SVR) (32%), unresponsive (53%), and relapse (15%). The groups were compared in terms of age, gender, blood biochemistry (albumin, total bilirubin, lactic acid dehydrogenase, ALT, AST, ALP, GGT), complete blood count, HBeAg, HBsAg, HBV-DNA, HDV-RNA, IL28B genotypes (CC, CT, TT), and results of liver biopsy. Results: Regarding the investigation of IL28B genotype, the prevalence of CC, CT, and TT showed no difference among the three groups. In the SVR group, the prevalence of CC was 53%, CT was 47%, but there was no patient with TT. In the unresponsive group, prevalence of CC was 52%, CT was 32%, and TT was 16%. In the relapse group, prevalence of CC was 43%, CT was 57%, but there was no patient with TT genotype. No significant difference was found among the groups with sustained response, no response, and relapse in terms of CC and CT polymorphisms (p>0.05). Conclusions: No relationship was found between IL28B rs12979860 polymorphism and response to treatment and disease severity in patients with chronic HDV infection.
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Zheng, Wen-bin, Yi Dai, Jing Hu, Di-chen Zhao, Ou Wang, Yan Jiang, Wei-bo Xia, Xiao-ping Xing, and Mei Li. "EFFECTS OF BISPHOSPHONATES ON OSTEOPOROSIS INDUCED BY DUCHENNE MUSCULAR DYSTROPHY: A PROSPECTIVE STUDY." Endocrine Practice 26, no. 12 (December 2020): 1477–85. http://dx.doi.org/10.4158/ep-2020-0073.
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Objective: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD. Methods: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (β-CTX) were evaluated. Results: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group ( P<.01). Serum β-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline). Conclusion: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol. Abbreviations: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; β-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid
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Liu, Yan, Zhimin Xing, Junge Wang, and Congli Geng. "Salivary Immunoglobulin A, E, and G4 Levels Specific to Dermatophagoides pteronyssinus in Allergic Rhinitis Patients Treated With Subcutaneous Immunotherapy." American Journal of Rhinology & Allergy 32, no. 6 (August 20, 2018): 458–64. http://dx.doi.org/10.1177/1945892418793470.
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Background Allergen-specific immunotherapy (AIT) is an effective treatment for allergic rhinitis (AR). During the course of AIT, many biomarkers in body fluids change. It is necessary to find effective indicators of AIT. Objective To examine levels of salivary immunoglobulin A, E, and G4 (IgA, IgE, and IgG4, respectively) specific to Dermatophagoides pteronyssinus (Dp-IgA, Dp-IgE, and Dp-IgG4, respectively) and their changes in AR patients undergoing subcutaneous immunotherapy (SCIT). Methods This study included 82 patients with AR sensitized only to Dp and 14 healthy controls. Among patients with AR, 30 patients were not treated with specific immunotherapy (group A), while the remainder (n = 52) received house dust mite SCIT in the up-dosing phase (n = 27; group B) or the maintenance treatment phase (n = 25; group C). Dp-IgA, Dp-IgE, and Dp-IgG4 levels in the saliva were measured using the enzyme-linked immunosorbent assay. Clinical symptoms, concomitant medication, and the Rhinoconjunctivitis Quality of Life Questionnaire score were recorded and correlated with immunoglobulin levels. Results Salivary Dp-IgG4 and Dp-IgA levels were significantly lower in AR patients than in healthy controls ( P < .001 for both), while Dp-IgE levels were significantly higher ( P < .001). SCIT resulted in sustained increases in Dp-IgG4 and Dp-IgA in the maintenance phase compared to the up-dosing phase ( P < .001 for both), whereas Dp-IgE only increased in the up-dosing phase ( P = .004, P < .0125). There was no correlation between the different salivary immunoglobulins and clinical scores during SCIT. Conclusions This study shows that allergen-specific IgE levels are increased in the saliva of sensitized patients, suggesting that measuring salivary IgE testing should be further considered for the diagnosis of AR. Moreover, allergen-specific IgA and IgG4 in the saliva, which may play protective roles against allergy, may serve as objective indicators for evaluating treatment response to SCIT. However, none of the immunoglobulin reflects subjective symptoms.
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Merli, Michele, Michele Spina, Stefano Luminari, Claudia Basilico, Clara Targhetta, Carlo Visco, Alessandro Levis, et al. "Prognostic Models to Predict Survival In Indolent and Aggressive Non-Hodgkin's Lymphomas Associated with Hepatitis C Virus Infection: a Multicenter Italian Study on 1,043 Patients." Blood 116, no. 21 (November 19, 2010): 2821. http://dx.doi.org/10.1182/blood.v116.21.2821.2821.
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Abstract Abstract 2821 Epidemiological studies demonstrated that HCV is associated with B-cell NHL. A precise prognostication of HCV+ NHL is not available; in particular, the impact of liver toxicity on the outcome of pts treated with (immuno)-chemotherapy is not fully clarified. Aim of the present study was to analyse clinical and virological characteristics, toxicity and prognosis of a large series of indolent and aggressive HCV+ NHL. We studied 1,043 pts with HCV+ NHL diagnosed and treated from January 1993 to December 2009 in 15 italian hematologic institutions; 539 cases were aggressive NHL (522 DLBCL) and 504 indolent NHL (265 MZL). All pts were HIV negative, 3% carried HBsAg and 91% were HCV-RNA+. Thirteen out of 56 HCV-RNA negative pts cleared HCV by means of antiviral therapy before NHL diagnosis. An (immuno)-chemotherapy regimen was administered as first-line treatment in 859 pts: 537 received CHOP-like regimen (+ Rituximab 243), 66 III generation regimen, 174 alkylators, 30 purine analogues, 31 other regimens, 21 R alone. Doses of chemotherapy since first cycle were reduced in 31% of pts. A watch-and-wait policy was adopted in 82 pts, other treatments in 68 pts and anti-HCV antiviral therapy in 34 pts with indolent NHL (12 of whom obtained both a complete virologic and hematologic response). Hepatic toxicity was evaluable in 597 patients: among 347 pts with normal ALT at NHL diagnosis, 52 (15%) developed WHO hepatic toxicity ≥ grade 2; among 250 pts (42%) with abnormal ALT, 26 (11%) experienced ALT increase >3.5 times baseline value. Overall, a significant liver toxicity developed in 78 pts (13%) (15% of aggressive NHL and 10% of indolent NHL). Use of Rituximab was not associated with significant liver toxicity (p=0.4); particularly, in DLBCL, R-CHOP and CHOP showed the same rate of significant hepatic toxicity (15%, p=ns), although maximum grade of liver toxicity was registered earlier in patients treated with R-CHOP than in those treated with CHOP (before 3rd cycle respectively in 57% vs 41%, p=0.006). Planned treatment was not completed in 134 pts (29 for liver toxicity). After a median F-UP of 2.6 years, 321 pts died (24 for liver failure). 5-yrs OS was 76% for indolent NHL and 62% for DLBCL. In indolent NHL, the parameters associated with a shorter OS in univariate analysis were: elevated LDH (p<0.001), ECOG ≥2 (p<0.001), AA stage III-IV (p=0.04), age > 60 yrs (p<0.001), B symptoms (p<0.001), serum albumin <3.5 g/dl (p<0.001), Child score (p=0.003), HCV-RNA >106 UI/ml (p<0.02), no antiviral therapy at any time (p<0.001). According to a forward stepwise multivariate Cox regression analysis on OS the following parameters retained statistical significance: ECOG ≥2 (HR 2.82, p=0.005), age > 60 yrs (HR 2.11, p=0.02), AA stage III-IV (HR 2.0, p=0.04), no antiviral therapy at any time (HR 2.56, p=0.01). In DLBCL, the parameters associated with a shorter OS in univariate analysis were: elevated LDH (p<0.001), ECOG ≥2 (p<0.001), AA stage III-IV (p<0.001), age > 60 yrs (p=0.003), liver involvement by lymphoma (p=0.02), B symptoms (p<0.001), serum albumin <3.5 g/dl (p<0.001), INR >1.7 (p=0.01), Child score (p<0.001), HCV-RNA >106 UI/ml (p<0.001), HBsAg+ (p=0.01), HAI grade >9 and/or fibrosis stage >2 at liver biopsy (p=0.03). Moreover IPI, aaIPI and R-IPI were predictive for OS (p<0.001). According to a forward stepwise multivariate Cox regression analysis on OS the following parameters retained statistical significance: ECOG ≥2 (HR 3.12, p=0.001), HCV-RNA >106 UI/ml (HR 3.59, p=0.001), serum albumin <3.5 g/dl (HR 2.53, p=0.01), while other IPI factors (age, AA stage, LDH, extranodal sites) were excluded from the final model. We combined the 3 factors significantly associated to a worse OS (ECOG, albumin, HCV-RNA load) in a new HCV Prognostic Score (HPS) able to discriminate 3 categories of risk (low=0; intermediate=1; high risk ≥2 factors) (p<0.001) (Fig. 1). After adjusting by IPI in multivariate Cox regression analysis, the HPS retained prognostic effect (p<0.001), while IPI itself did not. In conclusion, a significant proportion of pts with HCV+ NHL, when treated with conventional (immuno)-chemotherapy, develops severe liver toxicity. In indolent NHL, employment of antiviral therapy at any time during lymphoma history ameliorates OS. In HCV+ DLBCL, addition of rituximab to CHOP scheme does not increase hepatic toxicity; moreover, the new score HPS performs better than IPI in discriminating different risk categories. Disclosures: No relevant conflicts of interest to declare.
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Wadhva, Rajesh Kumar, Muhammad Manzoorul Haque, Nasir Hassan Luck, Abbas Ali Tasneem, Zaigham Abbas, and Muhammad Mubarak. "Diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis 4 scores in predicting advanced liver fibrosis in patients with end-stage renal disease and chronic viral hepatitis: Experience from Pakistan." Journal of Translational Internal Medicine 6, no. 1 (March 28, 2018): 38–42. http://dx.doi.org/10.2478/jtim-2018-0008.
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Abstract Objectives The aim was to assess the diagnostic accuracy of APRI and FIB-4 in assessing the stage of liver fibrosis in end stage renal disease (ESRD) patients with chronic viral hepatitis and to compare the two tests with standard tru-cut liver biopsy. Material and Methods The study was conducted at Sindh Institute of Urology and Transplantation Karachi (SIUT) from May 2010 to May 2014. All ESRD patients, being considered as candidates for renal transplantation and in whom liver biopsy was performed were included. Fibrosis stage was assessed on liver biopsy using Ishak scoring system. The serum transaminases and platelet counts were used to calculate APRI and FIB-4 scores. Results Out of 109 patients, hepatitis C and B virus infections were present in 104 (95.4%) and 3(2.8%), respectively, while 2 (1.8%) patients had both infections. The mean Ishak fibrosis score was 1.95 ± 2. Advanced fibrosis was noted in 37 (34%) patients. Univariate analysis showed that advanced liver fibrosis was associated with lower platelets counts (P=0.001) and higher aspartate aminotransferase (AST) (P=0.001), alanine aminotransferase (ALT) (P=0.022), APRI score (P=0.001) and FIB-4 score (P=0.001). On logistic regression analysis, only APRI score (P < 0.001) was found to be the independent variable associated with advanced liver fibrosis. APRI score cutoff ≥1 indicating advanced fibrosis showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 91.9%, 90.3%, 82.9%, 95.6%, respectively with area under the curve (AUC) of 0.97. Similarly, a FIB-4 score cutoff ≥1.1 had sensitivity, specificity, PPV and NPV of 70.27%, 66.67%, 52% and 81.36%, respectively with AUC of 0.74. Conclusion APRI is more accurate noninvasive test for assessing advanced liver fibrosis in ESRD patients as compared to FIB-4. It can be used to obviate the need for liver biopsy in this high risk population.
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Akdogan, Muberra, Yasemin Ustundag, M. Cem Sabaner, and Mustafa Dogan. "Comparison of Serum Biochemical and Haematological Analyses in Patients with Age-Related Macular Degeneration and Diabetic Retinopathy." Journal of Molecular Biology Research 9, no. 1 (May 11, 2019): 41. http://dx.doi.org/10.5539/jmbr.v9n1p41.
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We evaluated biochemical analysis results with the aim of discovering serum levels that have possible effects and differences on age-related macular degeneration (AMD) and diabetic retinopathy (DRP).
A retrospective case-control study was conducted between January 2017 and January 2018 on a total of 114 patients (84 DRP, 30 AMD) and 24 age and sex-matched control individuals. Four groups were created; 52 patients with proliferative DRP (PDR), 32 patients with nonproliferative PDR (non-PDR), 30 patients with wet AMD and 24 control individuals. Serum biochemical (HbA1C, fasting glucose, AST, ALT, C-reactive protein, albumin, total protein, uric acid, triglyceride, HDL, LDL, total cholesterol, Na, K, urine albumin) and complete blood count (CBC) analyses were performed at the time of diagnosis. Descriptive statistics, one-way ANOVA and Kruskal-Wallis tests were performed using SPSS to analyse data (Version 22.0).
The mean age of patients was 63.3 years ± 6.4 (49-91year), and that of control individuals was 65.3 years ± 9.3 (50-88 year). Post hoc analysis showed statistically significant differences in HbA1c and fasting glucose levels among PDR-AMD, PDR-control, non-PDR-AMD, and non-PDR-control groups (whole, P