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1. Pulmonary Embolism in Autosomal Dominant Polycystic Kidney Patient Induced by Inferior Vena Cava Mechanical Compression

Author

Maamoun Basheer, Elias Saad, and Assy Nimer

Subjects
autosomal dominant polycystic kidney disease, renal cyst, inferior vena cava, pulmonary embolism, Medicine
Abstract

Introduction: Autosomal dominant polycystic kidney disease is a common syndrome. Renal and hepatic cysts can cause discomfort, bleeding, rupture, infection, hypertension and a mass effect with compression of adjacent organs. Case presentation: A 48-year-old man with polycystic kidney disease and hypertension presented to the emergency department for bilateral flank pain. An abdominal computed tomography scan with contrast showed a 7 cm heterogeneous process posteriorly and laterally to the right kidney. It appeared to be a renal cyst associated with bleeding and bilateral pulmonary artery filling defects, apparently due to pulmonary embolism. Cavography following inferior vena cava filter insertion did not show any deep vein thrombosis. Discussion and conclusion: The pulmonary embolism was probably caused by extrinsic inferior vena cava compression by a liver cyst. Virchow's triad of stasis, vessel damage and hypercoagulability probably resulted in a thrombus which moved on the right side to the pulmonary artery.

Published
2021
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2. Hepatitis C virus leaves an epigenetic signature post cure of infection by direct-acting antivirals.

Author

Shira Perez, Antony Kaspi, Tom Domovitz, Ateret Davidovich, Anat Lavi-Itzkovitz, Tomer Meirson, Jacinta Alison Holmes, Chia-Yen Dai, Chung-Feng Huang, Raymond T Chung, Assy Nimer, Assam El-Osta, Gur Yaari, Salomon M Stemmer, Ming-Lung Yu, Izhak Haviv, and Meital Gal-Tanamy

Subjects
Genetics, QH426-470
Abstract

The increasing worldwide prevalence of Hepatocellular carcinoma (HCC), characterized by resistance to conventional chemotherapy, poor prognosis and eventually mortality, place it as a prime target for new modes of prevention and treatment. Hepatitis C Virus (HCV) is the predominant risk factor for HCC in the US and Europe. Multiple epidemiological studies showed that sustained virological responses (SVR) following treatment with the powerful direct acting antivirals (DAAs), which have replaced interferon-based regimes, do not eliminate tumor development. We aimed to identify an HCV-specific pathogenic mechanism that persists post SVR following DAAs treatment. We demonstrate that HCV infection induces genome-wide epigenetic changes by performing chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) for histone post-translational modifications that are epigenetic markers for active and repressed chromatin. The changes in histone modifications correlate with reprogramed host gene expression and alter signaling pathways known to be associated with HCV life cycle and HCC. These epigenetic alterations require the presence of HCV RNA or/and expression of the viral proteins in the cells. Importantly, the epigenetic changes induced following infection persist as an "epigenetic signature" after virus eradication by DAAs treatment, as detected using in vitro HCV infection models. These observations led to the identification of an 8 gene signature that is associated with HCC development and demonstrate persistent epigenetic alterations in HCV infected and post SVR liver biopsy samples. The epigenetic signature was reverted in vitro by drugs that inhibit epigenetic modifying enzyme and by the EGFR inhibitor, Erlotinib. This epigenetic "scarring" of the genome, persisting following HCV eradication, suggest a novel mechanism for the persistent pathogenesis of HCV after its eradication by DAAs. Our study offers new avenues for prevention of the persistent oncogenic effects of chronic hepatitis infections using specific drugs to revert the epigenetic changes to the genome.

Published
2019
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3. Antibody Repertoire Analysis of Hepatitis C Virus Infections Identifies Immune Signatures Associated With Spontaneous Clearance

Author

Sivan Eliyahu, Oz Sharabi, Shiri Elmedvi, Reut Timor, Ateret Davidovich, Francois Vigneault, Chris Clouser, Ronen Hope, Assy Nimer, Marius Braun, Yaacov Y. Weiss, Pazit Polak, Gur Yaari, and Meital Gal-Tanamy

Subjects
hepatitis C virus, antibody repertoire, neutralizing antibodies, infectious disease, immune signature, Immunologic diseases. Allergy, RC581-607
Abstract

Hepatitis C virus (HCV) is a major public health concern, with over 70 million people infected worldwide, who are at risk for developing life-threatening liver disease. No vaccine is available, and immunity against the virus is not well-understood. Following the acute stage, HCV usually causes chronic infections. However, ~30% of infected individuals spontaneously clear the virus. Therefore, using HCV as a model for comparing immune responses between spontaneous clearer (SC) and chronically infected (CI) individuals may empower the identification of mechanisms governing viral infection outcomes. Here, we provide the first in-depth analysis of adaptive immune receptor repertoires in individuals with current or past HCV infection. We demonstrate that SC individuals, in contrast to CI patients, develop clusters of antibodies with distinct properties. These antibodies' characteristics were used in a machine learning framework to accurately predict infection outcome. Using combinatorial antibody phage display library technology, we identified HCV-specific antibody sequences. By integrating these data with the repertoire analysis, we constructed two antibodies characterized by high neutralization breadth, which are associated with clearance. This study provides insight into the nature of effective immune response against HCV and demonstrates an innovative approach for constructing antibodies correlating with successful infection clearance. It may have clinical implications for prognosis of the future status of infection, and the design of effective immunotherapies and a vaccine for HCV.

Published
2018
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4. The detrimental danger of water-pipe (Hookah) transcends the hazardous consequences of general health to the driving behavior

Author

Elias Wafa, Assy Nimer, Elias Ibrahim, Toledo Tomer, Yassin Mustafa, and Bowirrat Abdalla

Subjects
WPS, Driving behavior, Road crashes, Carbon monoxide, Medicine
Abstract

Abstract Objective To determine whether the consumption of tobacco used in Water-Pipe by drivers increases the risk of a motor vehicle collision as a consequence of hypoxia. Design Analytical case–control study. Data sources Seventy exclusive Water-Pipe smokers (Experimental Group - EG) - mean age ± SD: 29.47 ± 10.45 years; mean number of weekly WPS, (6.9 ± 3.7); mean duration of WPS (WPS) is (7.5 ± 2.1 years) - and thirty non-smoker (Control Group – CG; mean age ± SD: 36.33 ± 13.92 years) were recruited during 2011 from two Arab villages located in the Galilee, northern Israel. Methods We performed a case–control study exclusively among Water-Pipe smokers with an appropriate non smokers control group. Demographic questionnaire, Pulse Oxymeter for blood oxygenation measure and a driver simulator for measuring various participants driving behaviors were utilized. Statistical analysis for analyzing the different variables, Pearson’s x2 analysis for the comparison of categorical variables, continuous variable is compared using Student’s t-test and for testing the correlation between the different variables and bivariate correlation analysis were applied. Results In the (EG) following WPS, we observed increase in the pulse rate - from 80 to 95 (t = 11.84, p Conclusion The results show that WPS has a significant impact on driving behavior and on the risk of being involved in road accidents and causing driving to become riskier and less careful and stable. To the best of our knowledge, this is the first time such relationships have been tested. After WPS the total number of traffic accidents and driving violations increase. The results show a significant increase in the pulse rate immediately after WPS with a decrease in the saturation rate (the level of blood oxygenation); these changes continue half an hour after WPS.

Published
2012
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5. The changes in renal function after a single dose of intravenous furosemide in patients with compensated liver cirrhosis

Author

Mejirisky Yoram, kayal Mohib, Assy Nimer, Gorenberg Miguel, Hussein Osamah, and Schlesinger Sorina

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background Patients with compensated Child-A cirrhosis have sub clinical hypovolemia and diuretic treatment could result in renal impairment. Aim To evaluate the changes in renal functional mass as reflected by DMSA uptake after single injection of intravenous furosemide in patients with compensated liver cirrhosis. Methods Eighteen cirrhotic patients were divided in two groups; eight patients (group 1, age 56 ± 9.6 yrs, Gender 5M/3F, 3 alcoholic and 5 non alcoholic) were given low intravenous 40 mg furosemide and ten other patients (group 2, age 54 ± 9.9, Gender 6M/4F, 4 alcoholic and 6 non alcoholic) were given high 120 mg furosemide respectively. Renoscintigraphy with 100MBq Of Tc 99 DMSA was given intravenously before and 90 minutes after furosemide administration and SPECT imaging was determined 3 hours later. All patients were kept under low sodium diet (80mEq/d) and all diuretics were withdrawn for 3 days. 8-hours UNa exertion, Calculated and measured Creatinine clearance (CCT) were performed for all patients. Results Intravenous furosemide increased the mean renal DMSA uptake in 55% of patients with compensated cirrhosis and these changes persist up to three hours after injection. This increase was at the same extent in either low or high doses of furosemide. (From 12.8% ± 3.8 to 15.2% ± 2.2, p < 0.001 in Gr I as compared to 10.6% ± 4.6 to 13.5% ± 3.6 in Gr 2, p < 0.001). In 8 patients (45%, 3 pts from Gr 1 and 5 pts from Gr 2) DMSA uptake remain unchanged. The mean 8 hrs UNa excretion after intravenous furosemide was above 80 meq/l and was higher in Gr 2 as compared to Gr 1 respectively (136 ± 37 meq/l) VS 100 ± 36.6 meq/l, P = 0.05). Finally, basal global renal DMSA uptake was decreased in 80% of patients; 22.5 ± 7.5% (NL > 40%), as compared to normal calculated creatinine clearance (CCT 101 ± 26), and measured CCT of 87 ± 30 cc/min (P < 0.001). Conclusion A single furosemide injection increases renal functional mass as reflected by DMSA in 55% of patients with compensated cirrhosis and identify 45% of patients with reduced uptake and who could develop renal impairment under diuretics. Whether or not albumin infusion exerts beneficial effect in those patients with reduced DMSA uptake remains to be determined.

Published
2006
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6. Early Elevated Inflammatory Markers in SARS-CoV-2 Vaccinated Patients Are Associated with Reduced Mortality, Morbidity, and Lung Injury.

Author

Khayat, Osama, Basheer, Maamoun, Derawy, Mayss, and Assy, Nimer

Subjects
COVID-19 vaccines, BLOOD urea nitrogen, OXYGEN therapy, ELECTRONIC health records, VACCINE development
Abstract

Background The development of vaccines against SARS-CoV-2 has proved to be a highly successful strategy. In this work, the aim is to study the effects of the SARS-CoV-2 vaccine on the production of inflammatory markers and how this affect morbidity and mortality. Electronic medical record (EMR) data from 210 patients diagnosed with COVID-19 from November 2020 to June 2021 were collected. The admitted patients were divided into three groups, the one-dose vaccinated, two-dose vaccinated, and the non-vaccinated. All patients were moderate or severe in disease level as defined by the WHO classification. The results show that CRP was 101 ± 5.3, 97 ± 10.8, and 145 ± 17.3 (p < 0.05), fibrinogen 529 ± 16.3, 397 ± 33.8, and 610 ± 15 (p < 0.05), D-dimer 1244 ± 89, 1279 ± 297, and 1615 ± 224 (p < 0.05), ferritin was 1170 ± 122, 999 ± 202, and 1663 ± 409 (p < 0.05), IL-6 was 196 ± 12, 96 ± 5, and 580 ± 402 (NS), for the non-vaccinated, one-dose vaccinated, and two-dose vaccinated groups, respectively. The high level of CRP up to 150–200 mg/dL was more common among the surviving vaccinated patients. Oxygen supplementation, mechanical ventilation, and mortality were higher in the non-vaccinated group. Blood urea nitrogen (BUN) level was higher in the vaccinated patients, 25 ± 0.14 vs. 33 ± 6.15, respectively (p < 0.05). Inflammation markers were significantly higher in the vaccinated groups compared to non-vaccinated groups. On the other hand, extremely high levels of CRP (>200 mg/dL) were correlated with high mortality incidence. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study

Author

Ferrante, Marc, D'Haens, Geert, Jairath, Vipul, Danese, Silvio, Chen, Minhu, Ghosh, Subrata, Hisamatsu, Tadakazu, Kierkus, Jaroslaw, Siegmund, Britta, Bragg, Sonja Michelle, Crandall, Wallace, Durand, Frederick, Hon, Emily, Lin, Zhantao, Lopes, Michelle Ugolini, Morris, Nathan, Protic, Marijana, Carlier, Hilde, Sands, Bruce E, Tron, Emiliano, Dorado, Fernanda Dorado, Thin, Lena, Leong, Rupert, Seltenreich, Hans, Christensen, Britt, Croft, Anthony, Ghaly, Simon, Koch, Robert, Reinisch, Walter, Heeren, Sonja, Bossuyt, Peter, Ferrante, Marc, Maximiano, Fabio Luiz, Sassaki, Ligia Yukie, Baia, Carolina, Poli, Debora, de Sousa Carlos, Alexandre, de Magalhaes Francesconi, Carlos Fernando, De Sa Rolim, Alexander, Razera, Julio, Simoes Neto, Joaquim, Rocco, Rodrigo, Stifft, Jonathas, Soldera, Jonathan, Silva, Genoile, Mendes Clemente, Cintia, Di Felice Boratto, Sandra, Teixeira de Campos, Luciana, Rodrigues Borba, Marcelo, Rosenfeld, Gregory, Ponich, Terry, Lim, Allen, Williams, Chadwick, Musgrave, Bruce, Gauthier, Stephane, Liu, Wenjia, Wang, Chengdang, Guo, Hong, Chen, Chunxiao, Chen, Yan Chen, Cao, Qian, Zhong, Jie, Xu, Min, Wang, Yufang, Zheng, Changqing, Gao, Xiang, Chen, Youxiang, Miao, Yinglei, Wang, Lin, Liu, Deliang, Wang, Bangmao, Song, Zhengji, Liu, Xiaowei, Chen, Baili, Jiang, Yi, Zhan, Qiang, Zhang, Kaiguang, Shen, Hong, Li, Zhaotao, Wang, Xiaoyan, Wang, Mei Wang, Tian, De'an, Chen, Lei, Tang, Wen, Borzan, Vladimir, Krznaric, Zeljko, Volfova, Miroslava, Pumprla, Jiri, Veberova, Lucie, Tichy, Michal, Gregar, Jan, Stepek, David, Ulbrych, Jan, Drastich, Pavel, Papik, Zdenek, Matous, Jan, Lukas, Martin, Koskova, Radka, Fallingborg, Jan, Altwegg, Romain, Fotsing, Ginette, Laharie, David, Nancey, Stephane, Peyrin, Laurent, Schreiber, Stefan, Hoffmann, Jörg, Seidler, Ursula, Fechner, Lars, Arelin, Katrin, Contzen, Christel, Trenn, Guido, Schaum, Thomas, Schoettker, Katrin, Bachmann, Oliver, Encke, Jens, Ibe, Michael, Jakobeit, Christian, Varga, Marta, Salamon, Agnes, Kafony, Andras, Horvat, Gyula, Heringh, Zsanett, Bezzegh, Katalin, Izbeki, Ferenc, Szalai, Laszlo, Schnabel, Robert, Samanta, Jayanta, Banerjee, Rupa, Subramanian, Ganesh, Mukewar, Shrikant, Bansal, Naresh Kumar, Sood, Ajit, Shankar Bagepally, Ravi, Kumar, Porika Shravan, Shrimal, Pankaj, Shah, Saumin, Pai, Nitin, Ahuja, Vineet, Melzer, Ehud, Assy, Nimer, Goldin, Eran, Shirin, Haim, Segal, Arik, Lahat, Adi, Saibeni, Simone, Luzza, Francesco, Danese, Silvio, Caprioli, Flavio, Annunziata, Maria Laura, Fantini, Massimo, Matsuda, Koichiro, Takagi, Sho, Kanmura, Shuji, Goto, Mitsuhide, Ashida, Toshifumi, Nishimata, Nobuaki, Kawakami, Kazuhiko, Ishiguro, Yoh Ishiguro, Maemoto, Atsuo Maemoto, Naito, Yuji Naito, Naoe, Hideaki, Nakase, Hiroshi, Iida, Tomohiro, Akiyama, Junichi, Yoshioka, Masao, Abe, Yasuhiko, Takeuchi, Ken, Kawai, Mikio, Hirai, Fumihito, Horiki, Noriyuki, Park, Sang Hyoung, Park, Dong II, Kang, Sang Bum, Jung, Min Kyu, Jang, Byung Ik, Lee, Yoo Jin, Shin, SungJae, Kim, Tae-oh, Kim, Hyun-Soo, Lee, Bo-In, Lee, Jonghun, Kim, Hyo Jong, Choi, Chang Hwan, Kim, Dongwoo, Eun, Chang Soo, Kang, Ben, Pokrotnieks, Juris, Kiudelis, Gediminas, Ramirez, Karina, Vega Fonseca, Jose Luis, Laheij, Robert, Kierkus, Jaroslaw, Klopocka, Maria, Wylegala, Zbigniew, Mroziak, Beata, Wojcik, Katarzyna, Korczowski, Bartosz, Gawdis, Beata, Danilkiewicz, Wit, Olszanecka, Magdalena, Krzykowska, Jolanta, Jamrozik, Zofia, Duszynska, Malgorzata, Ciesiolkiewicz, Agnieszka, Baluta, Malgorzata, Horynski, Marek, Leszczyszyn, Jaroslaw, Rozumek, Grzegorz, Firkowski, Lukasz, Konopko, Marzena, Orleanski, Jakub, Filip, Rafal, Wiechowska, Anna, Niezgoda, Krzysztof, Mateescu, Radu, Craciun, Eugeniu, Chioncel, Camelia, Musat, Marioara, Voiosu, Theodor Alexandru, Trofimov, Vasily, Shchukina, Oksana, Pershko, Anatoly, Fedorishina, Olga, Chumakova, Galina, Bakulin, Igor, Osipenko, Marina, Nikolin, Denis, Barysheva, Olga, Alexeeva, Olga, Zakharov, Konstantin, Khodareva, Irina, Tkachev, Alexander, Golovenko, Alexey, Popova, Veronika, Kashnikov, Vladimir, Vershinina, Maria, Makarchuk, Pavel, Valuyskikh, Ekaterina, Crevar, Slobodanka, Svorcan, Petar, Radakovic, Tatjana, Hlavaty, Tibor, Bunganic, Ivan, Fedurco, Miroslav, Kalisova, Iveta, Balaz, Jozef, Mihalkanin, Lubomir, Martin Arranz, Maria Dolores, De Teresa Parreno, Luis, Sans Cuffi, Miquel, Hernandez Camba, Alejandro, Brand, Stephan, Juillerat, Pascal, Seibold, Frank, Demirci, Hakan, Tezel, Ahmet, Simsek, Halis, Kiyici, Murat, Gonen, Can, Hulagu, Sadettin, Karakan, Tarkan, Cekin, Ayhan, Altintas, Engin, Guven, Kadri, Akpinar, Hale, Ozin, Yasemin, Erzin, Yusuf, Demir, Mehmet, Temel, Tuncer, Lohdanidi, Tetiana, Ivanov, Valeriy, Ivanishyn, Olha, Golovchenko, Oleksandr, Gerasymenko, Oksana, Danyliuk, Svitlana, Vyshyvanyuk, Vira, Datsenko, Olena, Stanislavchuk, Mykola, Rishko, Yaroslava, Kyrychenko, Olga, Donets, Dmytro, Shapovalova, Yana, Yurkiv, Andriy, Oliinyk, Oleksandr, Tsarynna, Nataliia, Fediv, Oleksandr, Poplyonkin, Yevgen, Kaser, Arthur, Hoque, Syed, Thomas, Hawys, Iyengar, Shalini, Newman, Frederic, Fogel, Ronald, Pedersen, Peder, Gonzales, Chad, McCord, Gregory, Galambos, Michael, Lamb, Paul, Schneider, Jeffrey, Bhandari, Bal Raj, Weiss, Michael, Thai, Christine, Shapiro, Michael, Younes, Ziad, Murali, Narayanachar, Hou, Jason, Williams, Todd, Khalid, Omer, Hsu, Connie, Bartalos, Christopher, Arimie, Calin, Mumtaz, Syed, Crespo, Israel, Marchioni Beery, Renee, Tuskey, Anne, Gaible, Ryan, Cutler, Alan, Afzali, Anita, Stuart, Kevin, Ibegbu, Eric, Irizarry-Roman, Moises, Harris, Kimberly, Agyei, Kwadwo, Jones, Frances, Sheikh, Aasim, Zakko, Liam, Cohen, Erica, Duvall, George, Al Kharrat, Houssam, Wohlman, Robert, Holderman, William, Schulman, Alan, Lidofsky, Sheldon, Wayne, Peter, Victores, Luis, Stone, Christian, Onwueme, Kenolisa, Fischer, Monika, Shahid, Shabana, Moore, Keith, Katz, Jeffry, Bullock, Jeff, and Fahed, Julien

Abstract

Mirikizumab, a humanised monoclonal antibody that inhibits IL-23p19, is effective in moderate-to-severe ulcerative colitis. We aimed to evaluate the efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease.

Published
2024
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9. Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO 2 Requirements.

Author

Neuenschwander, Fernando Carvalho, Barnett-Griness, Ofra, Piconi, Stefania, Maor, Yasmin, Sprinz, Eduardo, Assy, Nimer, Khmelnitskiy, Oleg, Lomakin, Nikita V., Goloshchekin, Boris Mikhailovich, Nahorecka, Ewelina, Joaquim Westheimer Calvacante, Adilson, Ivanova, Anastasia, Vladimirovich Zhuravel, Sergey, Yurevna Trufanova, Galina, Bonora, Stefano, Saffoury, Amer, Mayo, Ami, Shvarts, Yury G., Rizzardini, Giuliano, and Sobroza de Mello, Rogerio

Subjects
COVID-19, SPHINGOSINE kinase, OXYGEN therapy, ORAL drug administration, ARTIFICIAL respiration
Abstract

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Significance of Smoking in Patients with Acute ST Elevation Myocardial Infarction (STEMI) Undergoing Primary Percutaneous Coronary Intervention: Evaluation of Coronary Flow, Microcirculation and Left Ventricular Systolic Function.

Author

Boulos, Mariana, Sharif, Yasmine, Assy, Nimer, and Sharif, Dawod

Subjects
ST elevation myocardial infarction, THROMBOLYTIC therapy, PERCUTANEOUS coronary intervention, ANTERIOR wall myocardial infarction, MYOCARDIAL infarction, CREATINE kinase
Abstract

In the thrombolytic care era, myocardial infarction in cigarette smokers was associated with better six-month outcomes compared to non-smokers. Aims: We tested the hypothesis that in patients with anterior myocardial infarction with ST-segment elevation (STEMI) treated with primary percutaneous coronary intervention (PPCI), cigarette smoking is associated with better coronary artery flow, myocardial perfusion, and left ventricular systolic function. Methods: Ninety-nine patients (sixty-six smokers) with anterior STEMI treated with PPCI were studied. Angiographic coronary artery flow TIMI grades, myocardial blush grades (MBGs) before and after PPCI, ST-segment elevation resolution, maximal troponin I and creatine phosphokinase blood levels, left ventricular echocardiographic systolic function as well as left anterior descending coronary artery (LAD) velocity parameters at admission and at discharge were evaluated. Results: Smokers and non-smokers were treated similarly. In smokers, the age was significantly younger, 54 ± 10, compared to non-smokers, 71.8 ± 10 years, p < 0.05, and had a lower prevalence of women, 13.6% compared to 36.6%. TIMI and MBG before and after PPCI were similar between smokers and non-smokers. Smokers had a lower prevalence of complete ST elevation resolution, 33% compared to 50% in non-smokers. Diastolic LAD velocity and integral were lower in smokers, p < 0.05. Maximal biomarker blood levels as well as LV systolic function at admission and on discharge were similar. Conclusions: Cigarette smokers with anterior STEMI treated with PPCI were younger with a lower prevalence of women and of complete ST elevation resolution and had lower LAD diastolic velocity and integral late after PPCI. However, angiographic parameters and LV systolic function parameters were similar. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Neurosarcoidosis: The Presentation, Diagnosis and Treatment Review of Two Cases.

Author

Basheer, Maamoun, Waked, Hamd, Jeries, Helana, Azrilin, Olga, Paz, Dan, Assy, Nimer, Naffaa, Mohammad E., and Badarny, Samih

Subjects
PERIPHERAL nervous system, CHRONIC granulomatous disease, DIAGNOSIS, NERVOUS system, SYMPTOMS, URODYNAMICS
Abstract

Sarcoidosis is a chronic granulomatous disease of unknown cause characterized by the presence of non-caseating granulomas. The disease can affect any organ including the nervous system. Neurosarcoidosis occurs in about 5% patients with sarcoidosis. The clinical presentation of neurosarcoidosis is varied, and it can involve the brain, spinal cord and peripheral nervous system, separately or in different combinations. The diagnosis of neurosarcoidosis is challenging, as biopsies from the nervous system are not readily available. Anti-TNFα agents are becoming one of the cornerstone treatments for neurosarcoidosis. In this case-based review, we discuss two cases of neurosarcoidosis with different clinical presentations. The first patient presented with confusion, while the second presented with walking difficulty and neurogenic bladder. Both patients were treated with methylprednisolone pulse therapy with rapid, but non-complete, improvement. Therefore, infliximab was initiated in both cases with subsequent improvement in the clinical manifestations and imaging findings, emphasizing the effectiveness and safety of infliximab in cases of severe neurosarcoidosis. In conclusion, the goal of neurosarcoidosis management is to prevent organ system damage and minimize the toxic cumulative adverse effects of glucocorticoid use. In this case-based review we discuss the various presentations, the diagnosis and the treatment of neurosarcoidosis. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Increased Red Blood Cell Distribution Predicts Severity of Chronic Obstructive Pulmonary Disease Exacerbation

Author

Elias Saad, Basheer Maamoun, and Assy Nimer

Subjects
Medicine (miscellaneous)
Abstract

Introduction: Increased red blood cell distribution width (RDW) has been reported to be related to underlying chronic inflammation. Our aim is to investigate the relationship of different complete blood count (CBC) parameters such as hemoglobin level, mean corpuscular volume (MCV), mean platelet volume (MPV) or RDW with COPD exacerbation severity. Methods: In the present retrospective analysis, consecutive patients admitted with the diagnosis of “COPD Exacerbation” between 1 January 2012 and 31 December 2015 were evaluated. Results: The study population included 804 patients with COPD exacerbation. The maximal partial pressure of carbon dioxide in the arterial blood (PaCO2) during hospital stay was significantly higher in patients with high MCV (p < 0.001), and in patients with a high RDW (p < 0.001). The hospitalization duration was significantly longer in patients with high RDW (p < 0.001) and in patients with elevated C-reactive protein (CRP) levels (p < 0.001). CRP levels strongly correlated to RDW (p = 0.001). Conclusions: Our study demonstrated that different CBC parameters, such as MCV and RDW, are in correlation with the severity of acute exacerbation of COPD reflected by the PaCO2 level and the duration of hospitalization. Furthermore, we also found a positive correlation between RDW and CRP levels. This finding supports the hypothesis that RDW is a good biomarker of acute inflammation.

Published
2023
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21. Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Pneumonia

Author

Carvalho Neuenschwander, Fernando, primary, Barnett-Griness, Ofra, additional, Piconi, Stefania, additional, Maor, Yasmin, additional, Sprinz, Eduardo, additional, Assy, Nimer, additional, Khmelnitskiy, Oleg, additional, Lomakin, Nikita, additional, Goloshchekin, Boris Mikhailovich, additional, Nahorecka, Ewelina, additional, Calvacante, Adilson Joaquim Westheimer, additional, Ivanova, Anastasia, additional, Zhuravel, Sergey Vladimirovich, additional, Trufanova, Galina Yurevna, additional, Bonora, Stefano, additional, Saffoury, Amer, additional, Mayo, Ami, additional, Shvarts, Yury, additional, Rizzardini, Giuliano, additional, Sobroza de Mello, Rogerio, additional, Pilau, Janaina, additional, Klinov, Alexey, additional, Valente-Acosta, Benjamin, additional, Burlaka, Oleg Olegovich, additional, Bakhtina, Natalia, additional, Bar-Meir, Maskit, additional, Shishimorov, Ivan Nikolaevich, additional, Oñate-Gutierrez, Jose, additional, Rincon, Cristian Ivan Garcia, additional, Martynenko, Tatiana Ivanovna, additional, Abrahão Hajjar, Ludhmila, additional, Procopio, Ana Carolina Nazare de Mendonca, additional, Simon, Krzystof, additional, Santiago, Walter Gabriel Chaves, additional, Fronczak, Adam, additional, Filho, Conrado Roberto Hoffmann, additional, Hussein, Osama, additional, Martynov, Vladimir Aleksandrovich, additional, Chichino, Guido, additional, Blewaska, Piotr, additional, Wroblewski, Jacek, additional, Santana, Sergio Saul Irizar, additional, Agudelo, Andres Felipe Ocampo, additional, Barczyk, Adam, additional, Gerlach, Rachael L., additional, Campbell, Eppie, additional, Bibliowicz, Aida, additional, Fathi, Reza, additional, Anderson, Patricia, additional, Raday, Gilead, additional, Klein, Michal, additional, Fehrmann, Clara, additional, Eagle, Gina, additional, Katz Ben-Yair, Vered, additional, and Levitt, Mark L., additional

Published
2022
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37. A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of MHAA4549A, a Monoclonal Antibody, plus Oseltamivir in Patients Hospitalized with Severe Influenza A Virus Infection

Author

Lim, Jeremy J., primary, Nilsson, Anna C., additional, Silverman, Michael, additional, Assy, Nimer, additional, Kulkarni, Priya, additional, McBride, Jacqueline M., additional, Deng, Rong, additional, Li, Chloe, additional, Yang, Xiaoying, additional, Nguyen, Allen, additional, Horn, Priscilla, additional, Maia, Mauricio, additional, Castro, Aide, additional, Peck, Melicent C., additional, Galanter, Joshua, additional, Chu, Tom, additional, Newton, Elizabeth M., additional, and Tavel, Jorge A., additional

Published
2020
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41. Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial

Author

Ruilope, Luis M, Agarwal, Rajiv, Anker, Stefan D, Bakris, George L, Filippatos, Gerasimos, Nowack, Christina, Kolkhof, Peter, Joseph, Amer, Mentenich, Nicole, Pitt, Bertram, Diego, Besada, Alfredo, Wassermann, Julio, Bittar, Alicia, Elbert, Augusto, Vallejos, Gloria, Viñes, Hugo, Sanabria, Federico Pérez Manghi, Alberto, Liberman, Inés, Bartolacci, Diego, Aizenberg, Mariano, Chahin, Laura, Maffei, Elizabeth, Gelersztein, Bernhard, Ludvik, Hans-Robert, Schönherr, Heinz, Drexel, Wolfgang, Preiß, Ursula, Hanusch, Peter, Neudorfer, Friedrich, Prischl, Bernhard, Paulweber, Christoph, Ebenbichler, Rudolf, Prager, Harald, Sourij, Gerit-Holger, Schernthaner, Martin, Clodi, Evelyn, Fliesser-Görzer, Elif, Ekinci, Richard, Macisaac, David, Packham, Hugo, Stephenson, Michael, Suranyi, Gary, Wittert, Katie-Jane, Wynne, Alexia, Pape, Duncan, Topliss, Peter, Colman, Craig, Nelson, James, Vandeleur, David, Colquhoun, Simon, Roger, Peak Mann Mah, Walter, Abhayaratna, Luc VAN Gaal, Pieter, Gillard, Jean-Michel, Hougardy, Marijn, Speeckaert, Koen, Stas, Wendy, Engelen, Francis, Duyck, André, Scheen, Hilde, Vanbelleghem, Peter, Doubel, Svetla, Vasileva, Rosen, Rashkov, Boyan, Nonchev, Theodora, Temelkova-Kurktschieva, Mariana, Yoncheva-Mihaylova, Rangel, Rangelov, Neli, Klyuchkova, Pavel, Stanchev, Zhivko, Tagarev, Radostina, Boshnyashka, Petya, Manova, Zhulieta, Prakova, Mariya, Lucheva, Valentina, Gushterova, Ghassan, Farah, Dimitar, Georgiev, Mariyana, Pichmanova, Dotska, Minkova, Bilyana, Stoyanovska-Elencheva, Maria Eugenia Canziani, Miguel, Hissa, Irene, Noronha, Joao Eduardo Salles, Daniela, Antunes, Freddy, Eliaschewitz, Carlos Eduardo Figueiredo, Rogerio de Paula, Luis, Canani, Maurilo Leite Jr, Bruno, Paolino, Rosangela, Rea, Sergio, Vencio, Claudia, Brito, Raphael, Paschoalin, Roberto Pecoits Filho, Eduardo, Vasconcellos, Nathalia, Paschoalin, Adriana, Forti, Roberto, Botelho, Miguel, Riella, Dalton, Precoma, Maria, Cerqueira, Lilia, Maia, Evandro, Portes, Marcio, Pereira, Joanne, Liutkus, Dennis, O Keefe, Richard, Tytus, Brian, Carlson, James, Conway, Michael, Walsh, Igor, Wilderman, Andrew, Steele, Sheldon, Tobe, Louise, Vitou, Karthik, Tennankore, Valdemar, Martinho, Philip, Mcfarlane, Daniel, Shu, Serge, Cournoyer, Richard, Dumas, Giuseppe, Mazza, Guy, Tellier, George, Tsoukas, Stanley, Weisnagel, Jean-Francois, Yale, Sameh, Fikry, Randolph, Hart, Pavel, Hamet, Francois, Madore, Paul, Barre, Daniel, Schwartz, Allan, Kelly, Ivor, Teitelbaum, Sean, Peterson, Sam, Henein, Richard, Goluch, Gregoire, Wuerzner, Markus, Laimer, Stefan, Bilz, Marc, Donath, Gottfried, Rudofsky, Christopher, Strey, Antoinette, Pechère-Bertschi, Paola, Varleta, Fernando, González, Marcelo, Medina, Carmen, Romero, Victor, Saavedra, Juan Carlos Prieto, Eliana, Reyes, Juan Carlos Palma, Jorge, Cobos, Zhihong, Liu, Dalong, Zhu, Nan, Chen, Fang, Liu, Wang, Li, Qing, Su, Bingyin, Shi, Aiping, Yin, Hao, Wang, Yan, Li, Jianying, Niu, Chaoqing, Wu, Xinjun, Wang, Ying, Zhang, Peng, Ai, Jianhua, Ma, Yuxiu, Li, Hongguang, Zheng, Minxiang, Lei, Zhaohui, Mo, Nanwei, Tong, Jinluo, Cheng, Youping, Dong, Xudong, Xu, Qinkai, Chen, Tianjun, Guan, Gang, Long, Changying, Xing, Ling, Li, Yinghong, Liu, Hao, Zhang, Ling, Zhong, Zhonghe, Li, Longyi, Zeng, Jiali, Wei, Hanqing, Cai, Tianfeng, Wu, Weiping, Lu, Ning, Xu, Yibing, Lu, Dejun, Chen, Ruifang, Bu, Jiansong, Shen, Junwu, Dong, Zhiquan, Zhao, Fei, Xiong, Fangfang, Jiang, Jinkui, Yang, Jian, Kuang, Guoyuan, Lu, Lihua, Wang, Yanlin, Zhang, Shuifu, Tang, Weiying, Guo, Jian, Liu, Sheng, Jiang, Fang, Yi, Yuming, Du, Zhuxing, Sun, Yuantao, Liu, Liyong, Zhong, Dongmei, Li, Hongmei, Li, Chuanming, Hao, Feixia, Shen, Jianqin, Wang, Jingmei, Li, Dora, Molina, Carlos, Cure, Jaime, Ibarra, Gustavo, Aroca, Hernán, Yupanqui, Eric, Hernández, Mónica, López, Gregorio, Sánchez, Germán, Barreto, Edgar, Arcos, Miguel, Urina, William, Kattah, Carlos, Durán, Clara, Arango, Julian, Coronel, Guillermo, Blanco, Mónica, Terront, Gustavo, Guzmán, Luis, García, Carlos, Jaramillo, Manuel, Liévano, Diego, Benitez, Tatiana, Cárdenas, Iván, Villegas, Sandra, Barrera, Nicolás, Jaramillo, Rodrigo, Botero, Nelly Beltrán López, Freddy, Trujillo, Martin, Prazny, Jitka Hasalova Zapletalova, Libor, Okenka, Dino, Alferi, Tomas, Edelsberger, Pavel, Tomanek, Jiri, Brezina, Olga, Hola, Jana, Houdova, Petr, Bucek, David, Karasek, Sarka, Kopecka, Richard, Kovar, Michal, Brada, Lucie, Hornova, Eva, Krcova, Hana, Lubanda, Vlasta, Kutejova, Jiri, Kuchar, Helena, Hrmova, Jiri, Pumprla, Magdalena, Mokrejsova, Drahomira, Gulakova, Ivo, Matyasek, Thilo, Krüger, Hermann, Haller, Thorsten, Koch, Ludger, Rose, Diethelm, Tschöpe, Lutz, Stemler, Volker, Schettler, Andreas, Pfützner, Karl, Derwahl, Thomas, Horacek, Helena, Sigal, Heidrun, Täschner, Ingolf, Schiefke, Andreas, Hagenow, Andreas, Birkenfeld, Christoph, Axthelm, Christoph, Wanner, Klaus, Busch, Heike, Schlichthaar, Christoph, Hasslacher, Stefan, Degenhardt, Markus van der Giet, Georg, Strack, Norbert, Schöll, Bernhard, R Winkelmann, Lars, Rump, Ruth, Nischik, Bernd, Schröppel, Thomas, Giebel, Achim, Ulmer, Andrea, Rinke, Christel, Contzen, Wolfgang, Jungmair, Nicole, Toursarkissian, Christof, Kloos, Joachim, Müller, Thomas, Schürholz, Hermann, Braun, Frank, Pistrosch, Per, Poulsen, Claus, Juhl, Joan, Nielsen, Jesper, Bech, Ole, Rasmussen, Peter, Rossing, Jens, Faber, Thure, Krarup, Morten, Lindhardt, Ulrik Pedersen-Bjergaard Pedersen-Bjergaard, Karoline, Schousboe, Jørgen, Hangaard, Sten, Madsbad, Gunnar, Gislason, Grzegorz Jaroslaw Pacyk, Olga González Albarrán, Carlos Sánchez Juan, José Julián Segura de la Morena, Secundino Cigarrán Guldris, Francisco Martínez Deben, José María Pascual Izuel, Julio Pascual Santos, Francesca, Calero, Alfonso, Soto, Manuel Polaina Rusillo, Josep, Redón, Josep, Galcerán, Juan, Mediavilla, Mª Dolores Martínez Esteban, Alfredo, Michán, Fernando de Álvaro, Javier Escalada San Martín, Josep Cruzado Garrit, Cristina, Castro, Fernando Cereto Castro, Rafael Santamaría Olmo, Esteban, Poch, Judith, Martins, Julio Hernández Jaras, Meritxell, Ibernón, Daniel, Seron, Hanane, Bouarich, Maribel, Troya, Jorma, Strand, Ilkka, Kantola, Sakari, Nieminen, Arvo, Koistinen, Kristiina, Kananen, Sakari, Sulosaari, Mikko, Honkasalo, Pirkko, Korsoff, Tuomo, Nieminen, Karita, Sadeharju, Kari, Humaloja, Jorma, Lahtela, Philippe, Zaoui, Jean-Pierre, Fauvel, Ronan, Roussel, Didier, Gouet, Pierre, Serusclat, Sylvaine, Clavel, Bruno, Guerci, Bruno, Verges, Olivier, Moranne, Arnaud, Monier, Alexandre, Klein, François, Chantrel, Yannick LE Meur, Rafik, Mesbah, Bertrand, Cariou, Dominique, Guerrot, Karim, Gallouj, Kieran, Mccafferty, Arutchelvam, Vijayaraman, Yuk-Ki, Wong, Dhanya, Kalathil, Sam, Rice, Sui Phi Kon, Hassan, Kahal, Cuong, Dang, Fahmy, Hanna, Christina, Kyriakidou, Imrozia, Arif, Anne, Kilvert, Pauline, Swift, Ioannis, Stefanidis, Ploumis, Passadakis, Aikaterini, Papagianni, Erifili, Hatziagelaki, Dorothea, Papadopoulou, Ioannis, Boletis, Ioanna, Makriniotou, Theodora, Kounadi, Ioannis, Ioannidis, Paul, Lee, Ching Wan Ronald Ma, Vincent, Yeung, Tai Pang Ip, Ebrahim, Noori, Julianna, Kiss, Eleonora, Harcsa, Albert, Szocs, Szilard, Vasas, Krisztina, Wudi, Robert, Kirschner, Dora, Bajcsi, Beata, Lamboy, Botond, Literati-Nagy, Gabor, Nyirati, Gizella, Petro, Karoly, Schneider, Katalin, Keltai, Akos, Kalina, Peter, Danos, Szilvia, Kazup, Zsolt, Zilahi, Judit, Simon, Laszlo, Kovacs, Marianna, Zsom, Margit, Mileder, Laszlo, Nagy, Yoram, Yagil, Julio, Wainstein, Ofri, Mosenzon, Rosane Abramof Ness, Sydney Ben Chetrit, Faiad, Adawi, Idit, Liberty, Ehud, Grossman, Mazen, Elias, Zaher, Armaly, Evgeny, Farber, Assy, Nimer, Amir, Bashkin, Gil, Chernin, Shai, Efrati, Doron, Schwartz, Noa Berar Yanay, Mariela, Glandt, Robert, Zukermann, Majdi, Halabi, Shaul, Atar, Mahmud, Darawsha, Norberto, Perico, Gaetano La Manna, Giovanni Giorgio Battaglia, Domenico, Santoro, Piermarco, Piatti, Bonora, Enzo, Davide Carlo Maggi, Paolo, Calabrò, Roberto, Cimino, Roberto, Trevisan, Paolo, Fiorina, Antonio, Pisani, Antonello, Pani, Gennaro, Santorelli, Carlo Antonio Bossi, Giancarlo, Tonolo, Enrico, Fiaccadori, Anna Maria Veronelli, Michele, Emdin, Paola, Ponzani, Maria Cristina Gregorini, Franco Luigi Cavalot, Carlo Bruno Giorda, Taro, Shibasaki, Akihiro, Hamasaki, Takashi, Nomiyama, Sunao, Matsubayashi, Junji, Shinoda, Kazunari, Matsumoto, Hideo, Kanehara, Yoshihide, Hirohata, Masayo, Yamada, Jun, Nakazawa, Yoshimitsu, Yamasaki, Mikihiro, Nakayama, Ryuichi, Furuya, Osamu, Ebisui, Satsuki, Kawasaki, Daishiro, Yamada, Masayuki, Noritake, Tamayo, Ishiko, Nobuhiro, Sasaki, Daisuke, Suzuki, Asami, Tanaka, Miyuki, Kubota, Hideo, Araki, Hiroshi, Ohashi, Takeshi, Osonoi, Kazuo, Yamagata, Naruhiro, Fujita, Daisuke, Kanda, Seiichi, Tanaka, Junko, Koide, Masao, Ishii, Takayuki, Ogiwara, Masaaki, Suzuki, Taiji, Sekigami, Takayuki, Higashi, Yuko, Yambe, Yoshiro, Kusano, Hidetoshi, Kikuchi, Hiroaki, Miyaoka, Kiyoe, Kato, Masayuki, Kashima, Fumiko, Yamakawa, Shuji, Horinouchi, Hirofumi, Imoto, Hiroshi, Sobajima, Hidetoshi, Kanai, Naoki, Matsuoka, Hirotaka, Shibata, Akemi, Inagaki, Toshiyuki, Sugiura, Toru, Sugiyama, Hidekatsu, Yanai, Yoshiyuki, Hamamoto, Masahiro, Hatazaki, Terumasa, Hayashi, Kunihisa, Kobayashi, Satoshi, Murao, Makoto, Ujihara, Kazuya, Sugitatsu, Katsunori, Kawamitsu, Ken, Yamakawa, Izumi, Tsunematsu, Fumi, Kikuchi, Hideaki, Jinnouchi, Tetsuyuki, Yasuda, Hajime, Maeda, Yasuto, Matsuo, Hideki, Okamoto, Takeshi, Katsuki, Ken, Yajima, Takeshi, Morita, Masayuki, Inagaki, Wooje, Lee, Jungoo, Kang, Cheol Young Park, Hyesoon, Kim, Singon, Kim, Youcheol, Hwang, Injoo, Kim, Jaehyeon, Kim, Young Min Cho, Byungwan, Lee, Choonhee, Chung, Soo, Lim, Jae Myung Yu, Dovile, Kriauciuniene, Antanas, Navickas, Audrone, Velaviciene, Egle, Urbanaviciene, Gediminas, Urbonas, Jurate, Lasiene, Lina, Radzeviciene, Ron, Gansevoort, Adriaan, Kooy, G Lieverse, A, L Penne, E, Ruud J, M van Leendert, M van Buren, H Boonstra, A, C Bakker, R, Marielle, Krekels, B Brouwer, C, T Luik, P, J N, M Barendregt, Bert-Jan van den Born, Trine, Finnes, Thomas, Karlsson, Hilde, Selsås, Emil, Asprusten, Robert, Hagemeier, Erik, Eriksen, Knut, Risberg, Hans, Høivik, Leidulv, Solnør, Frode, Thorup, Jan, Rocke, Rick, Cutfield, Peter, Dunn, Jeremy, Krebs, Russell, Scott, Kingsley, Nirmalaraj, Nine, Smuts, John, Baker, Veronica, Crawford, Albert, Bautista, Roberto, Mirasol, Elizabeth, Catindig, Glenda, Pamugas, Louie, Tirador, Maribel, Tanque, Janusz, Gumprecht, Piotr, Napora, Edward, Franek, Andrzej, Stankiewicz, Katarzyna, Landa, Agnieszka, Tiuryn-Petrulewicz, Kazimierz, Ciechanowski, Bogna, Wierusz-Wysocka, Barbara, Rewerska, Grazyna, Cieslik, Michal, Hoffmann, Michal, Nowicki, Jolanta, Krzykowska, Stanislaw, Mazur, Katarzyna, Wasilewska, Anna, Ocicka-Kozakiewicz, Ewa, Skokowska, Renata, Wnetrzak-Michalska, Jan, Ruxer, Patrycja, Butrymowicz, Katarzyna, Madziarska, Ilona, Kurnatowska, Teresa, Rusicka, Adam, Madrzejewski, Tomasz, Stompor, Jose, Guia, Amalia, Pereira, Pedro, Melo, Cristina, Roque, Francisco, Rosario, Fernando Teixeira, E Costa, Fernando, Nolasco, Edgar, Almeida, Pedro, Matos, Cesar, Esteves, Rui, Carvalho, Ilidio, Brandao, Susana, Heitor, Ana Vila Lobos, Rosa, Ballesteros, Gil, Silva, Carlos, Barreto, Ana, Silva, Natalya, Vorokhobina, Alexander, Sherenkov, Ivan, Gordeev, Olga, Semenova, Sergey, Levashov, Vyacheslav, Marasaev, Ruslan, Sardinov, Vadim, Klimontov, Vitaliy, Baranov, Nadezhda, Verlan, Albert, Galyavich, Arkadiy, Demko, Zhanna, Kobalava, Elena, Zakharova, Lyudmila, Kvitkova, Oleg, Solovev, Elena, Smolyarchuk, Larisa, Zhukova, Elena, Zhdanova, Andrey, Babkin, Galina, Nechaeva, Olga, Barbarash, Elena, Rechkova, Roman, Libis, Elena, Kosmacheva, Tatyana, Rodionova, Irina, Ipatko, Alexander, Dreval, Nina, Petunina, Elena, Chernyavskaya, Alsu, Zalevskaya, Yuriy, Khalimov, Tatyana, Zykova, Anton, Edin, Ashot, Mkrtumyan, Shamil, Palyutin, Vyacheslav, Mareev, Leonid, Strongin, Olga, Ukhanova, Mikhail, Antsiferov, Davyd, Yakhontov, Leonid, Pimenov, Natalya, Koziolova, Konstantin, Nikolaev, Imad, Merai, Olga, Zanozina, Leyla, Gaysina, Mikhail, Arkhipov, Natalia, Malykh, Oksana, Rymar, Vladimir, Martynenko, Sofya, Malyutina, Polina, Ermakova, Marina, Kalashnikova, Bengt-Olov, Tengmark, Carl-Johan, Lindholm, Dan, Curiac, Ken, Eliasson, Erik, Rein-Hedin, Gregor, Guron, Inga, Soveri, Annette, Bruchfeld, Jonas, Spaak, Malin, Frank, Magnus, Löndahl, Hans, Larnefeldt, Margareta, Hellgren, Olof, Hellberg, Yong Mong Bee, Chee Fang Sum, Ru San Tan, Piyamitr, Sritara, Chaicharn, Deerochanawong, Chatlert, Pongchaiyakul, Natapong, Kosachunhanan, Bancha, Satirapoj, Ahmet, Temizhan, Ibrahim, Gul, Ramazan, Sari, Aytekin, Oguz, Mustafa, Tigen, Huseyin, Yilmaz, Ozer, Badak, Oner, Ozdogan, Talat, Tavli, Necmi, Eren, Murat, Cayli, Sedat, Ustundag, Yavuz, Yenicerioglu, Ismail, Kocyigit, Abdulbaki, Kumbasar, Idris, Sahin, Lee-Ming, Chuang, Ju-Ying, Jiang, Chien-Te, Lee, Der-Cherng, Tarng, Shih-Te, Tu, Mai-Szu, Wu, Ming-Ju, Wu, Chiz-Tzung, Chang, Cheng-Chieh, Hung, Liubov, Sokolova, Borys, Mankovsky, Dmytro, Kogut, Viktoriia, Chernikova, Kateryna, Malyar, Nonna, Kravchun, Volodymyr, Botsyurko, Vitaliy, Maslyanko, Liliya, Martynyuk, Oleksandr, Serhiyenko, Vasyl, Stryzhak, Halyna, Myshanych, Oleksandra, Donets, Iryna, Bondarets, Maryna, Vlasenko, Nataliia, Pertseva, Mariia, Grachova, Ivan, Smirnov, Larysa, Pererva, Ivan, Fushtey, Julia, Komisarenko, Anna, Isayeva, Carl, Meisner, Bobby, Khan, Louis, Maletz, Bradley, Dixon, Ahmed, Arif, Timothy, Jackson, Mirela, Ponduchi, Mahfouz El Shahawy, Salil, Nadkarni, Daniel, Urbach, Jorge, Paoli-Bruno, Henry, Lora, Umar, Farooq, Steven, Zeig, Lance, Rudolph, Nabil, Andrawis, William, Kaye, Jill, Meyer, Khalid, Bashir, Glenn, Heigerick, James, Smelser, Javier Ricardo Colomar, David, Scott, Brian, First, Stuart, Handelsman, Jose, Bautista, Rajesh, Patel, Stephen, Minton, Juan, Frias, Luis, Ramos-Gonez, John, Bertsch, Ali, Iranmanesh, Vivian, Fonseca, Michael, Yuryev, Larry, Popeil, Jose, Cardona, Sanjeev, Saxena, Santosh, Sharma, Edgar, Gonzalez, Richard, Solomon, Muhammad, Khan, Ahmed, Awad, David, Fitz-Patrick, Douglas, Linfert, David, Grant, Susan, Brian, Leon, Fogelfeld, Rafael, Canadas, Pablo, Pergola, Joseph, Soufer, Rakesh, Patel, Shujauddin, Valika, Jonathan, Winston, Allison, D, Maria, Caramori, Stanley, Koch, Anjay, Rastogi, Jonathan, Bornfreund, Michael, Rocco, Maxine, Hamilton, Luis, Garcia-Mayol, Peter, Weissman, Suzanne, Oparil, Gary, Ruoff, Kyaw, Soe, Gary, Korff, Robert, Busch, Alexander, Lurie, Israel, Hartman, Garfield, Samuels, Derek, Lejeune, Visal, Numrungroad, Stephen, Brietzke, Zeid, Kayali, Harold, Szerlip, Steven, Barag, Gilberto, Seco, Damaris, Vega, Osvaldo, Brusco, Camil, Kreit, Humberto, Cruz, Bharat, Mocherla, Sharma, Prabhakar, George, Fadda, Martin, Valdes, Eugene, Soroka, Ramin, Berenji, Sreedhara, Alla, Shweta, Bansal, Odugbesan, A, Karlton, Pettis, Masoud, Azizad, Idalia, Acosta, Atoya, Adams, William, Sanchez, Rosa, Suarez, Efrain, Reisin, Carlos, Herrera, Keung, Lee, Csaba, Kovesdy, Adam, Whaley-Connell, Aldo, Peixoto, Ronald, Mayfield, Mahendra, Jain, Earl, Martin, Paul, Norwood, Jonathan, Wise, Hugo, Romeu, Stephen, Halpern, Mustafa, Mandviwala, Thomas, Turk, Anna, Burgner, David, Bleich, Ankur, Doshi, Jose, Carpio, Jorge, Posada, Alexander, Magno, Samer, Nakhle, Gary, Goldstein, Caroline, Mbogua, Dierdre, Mcmullen, Dilawar, Ajani, Wayne, Kotzker, Nelson, Kopyt, Richard, Treger, Yusuf, Ruhullah, Sharon, Adler, Harjeet, Brar, Marc, Rendell, Dennis, Ross, Srinivasan, Beddhu, German, Hernandez, Sylvia, Rosas, M Sue Kirkman, Mohammed, El-Shahawy, Jeffrey, Rothman, Ahmad, Barakzoy, Aparna, Tamirisa, Sabrina, Benjamin, Michael, Bahrami, Prabir, Roy-Chaudhury, Ramprasad, Dandillaya, Gretel, Trullenque, Jose, Birriel, John, Flack, Karen, Johnson, Brenda, Lemus, Guillermo, Umpierrez, Geetha, Maddukuri, Kenneth, Jamerson, Christopher, Case, Patrick, Fluck, Saeed, Kronfli, Violet, Habwe, Bala, Subramanian, Tariq, Shafi, Rupesh, Raina, Roland, Fernando, Sourabh, Kharait, Carlos, Hernandez-Cassis, Raymond, Fink, Jamal, Hammoud, Amer, Al-Karadsheh, Manuel, Montero, Philip, Nicol, Jesus, Navarro, Michael, Shanik, Zia, Din, Francisco, Gonzalez-Abreu, Sam, Lerman, Claude, Galphin, John, Evans, Ashwini, Gore, Radica, Alicic, Mandeep, Sahani, Roberto, Pisoni, Tuan-Huy, Tran, Jeffrey, Ryu, Harvey, Serota, Nilda, Neyra, Richard, O Donovan, Sreedhar, Mandayam, Moustafa, Moustafa, Mark, Smith, Arvind, Krishna, Arjun, Sinha, Anuj, Bhargava, Kodangudi, Ramanathan, Soni, Dhanireddy, Stephen, Thomson, Romanita, Nica, Emaad, Abdel-Rahman, Mark, Barney, Mariana, Markell, Nauman, Shahid, David, Oliver, Tran, Khanh, Pham Nguyen Son, Lam VAN Hoang, Boi Ngoc Nguyen, Nguyen Minh Nui, Lan Phuong Tran, Fayzal, Ahmed, Dorothea, Urbach, Dirkie Jansen van Rensburg, Gracjan, Podgorski, Aslam, Amod, Sindeep, Bhana, Shaifali, Joshi, Essack, Mitha, Deepak, Lakha, Louis van Zyl, Trokis, J, Naresh, Ranjith, Mary, Seeber, Mohamed, Sarvan, Mohammed, Tayob, Brian, Rayner, Larry, Distiller, Heidi, Siebert, Mukesh, Joshi, Paul, Rheeder, Magdalena Madero Rovalo, Gustavo Solache Ortiz, Gustavo Méndez Machado, Rafael Valdez Ortiz, Juan Villagordoa Mesa, Saúl Irizar Santana, Sandro Avila Pardo, Jorge Escobedo de la Peña, Guillermo González Gálvez, Leobardo Sauque Reyna, Miriam Bastidas Adrian, Guillermo Fanghänel Salmón, Ramiro Gutiérrez Ochoa, Luis Nevarez Ruiz, Gabriel Ramos López, Alfredo Chew Wong, Arturo Saldaña Mendoza, Pedro García Hernández, José González González, Melchor Alpizar Salazar, José Lazcano Soto, Amaury, Roman-Miranda, Gregorio, Cortes-Maisonet, Liana, Turcu, Adriana, Dumitrescu, Gabriela, Radulian, Hortensia, Barbonta, Cristina, Mistodie, Georgeta, Vacaru, Alexandrina, Popescu, Adrian, Vlad, Silvia, Paveliu, Nicoleta, Mindrescu, Adrian, Albota, Ella, Pintilei, Lavinia, Pop, Gabriela, Negrisanu, Doina, Catrinoiu, Cornelia, Bala, Amorin, Popa, Iosif, Szilagyi, Ciprian, Constantin, Elena, Caceaune, Adriana, Onaca, Li Yuan Lee, Nor Azizah Aziz, Wan Mohd Izani Wan Mohamed, Wan Hasnul Halimi Bin Wan Hasan, Jeyakantha, Ratnasingam, Nik Nur Fatnoon Nik Ahmad, Rizmy Najme Khir, Norhaliza Mohd Ali, Masni, Mohamad, Chek Loong Loh, Joe, Eustace, John, Holian, Donal, Reddan, Yvonne, O Meara, Mensud, Hatunic, Zuzana, Ochodnicka, Dalibor, Sosovec, Andrej, Dzupina, Ingrid, Buganova, Jana, Babikova, Denisa, Spodniakova, Ruilope, L, Agarwal, R, Anker, S, Bakris, G, Filippatos, G, Nowack, C, Kolkhof, P, Joseph, A, Mentenich, N, Pitt, B, Trevisan, R, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Diabetes Clinic

Subjects
Male, Endocrinology, Diabetes and Metabolism, Enfermedad cardiovascular, 030232 urology & nephrology, BAY 94-8862, Type 2 diabetes, 030204 cardiovascular system & hematology, Diabete, Kidney, Aparato circulatorio, Azúcar, chemistry.chemical_compound, Mineralocorticoid Receptor Antagonists/therapeutic use, 0302 clinical medicine, Medicine and Health Sciences, Diabetic Nephropathies, Myocardial infarction, Renal Insufficiency, Chronic, Aldosterone, Outcome, Mineralocorticoid Receptor Antagonists, RISK, COMPLICATIONS, Diabetes, Middle Aged, SPIRONOLACTONE, CHRONIC HEART-FAILURE, Treatment Outcome, Mineralocorticoid, Nephrology, Cardiovascular Diseases, Research Design, Disease Progression, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Type 2, Glomerular Filtration Rate, medicine.medical_specialty, Finerenone, Naphthyridines/therapeutic use, Renal function, Outcomes, 03 medical and health sciences, Clinical, Double-Blind Method, Diabetes mellitus, Internal medicine, medicine, Diabetes Mellitus, Humans, Naphthyridines, Renal Insufficiency, Chronic, ANTAGONIST, Sistema cardiovascular, Aged, Patient-Oriented, Translational Research: Research Article, Diabetic Nephropathies/complications, Renal Insufficiency, Chronic/drug therapy, RECEPTOR, Aldosterone, Clinical, Diabetes, Kidney, Mineralocorticoid, Outcomes, business.industry, Cardiovascular Diseases/epidemiology, Diabetes Mellitus, Type 2/complications, MILD, WORSENING RENAL-FUNCTION, EFFICACY, medicine.disease, chemistry, Diabetes Mellitus, Type 2, Spironolactone, Albuminuria, business, Kidney disease, Follow-Up Studies
Abstract

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

Published
2019
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42. High frequency of multiclass HCV resistance-associated mutations in patients failing direct-acting antivirals: real-life data

Author

Yoram Menachem, Tarek Saadi, Oren Shibolet, Rawi Hazzan, Assy Nimer, Ehud Zigmond, Yana Davidov, Michal Cohen-Naftaly, Amir Shlomai, Avia Rakovsky, Eli Zuckerman, Rifaat Safadi, Yoav Lurie, Yael Gozlan, Ella Mendelson, Eitan Galun, Helena Katchman, Rachel Shirazi, Ziv Ben-Ari, Orna Mor, Yaakov Maor, Abu Moch Saif, Efrat Bucris, Marius Braun, Ohad Etzion, and Ella Veizman

Subjects
Oncology, Male, medicine.medical_specialty, Genotype, Drug resistance, Hepacivirus, 030312 virology, Viral Nonstructural Proteins, DIRECT ACTING ANTIVIRALS, Antiviral Agents, Treatment failure, Virological response, 03 medical and health sciences, Pharmacotherapy, Internal medicine, Drug Resistance, Viral, medicine, Prevalence, Humans, Pharmacology (medical), In patient, Treatment Failure, Israel, Pharmacology, 0303 health sciences, business.industry, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, Middle Aged, Real life data, Hepatitis C, Infectious Diseases, Retreatment, Drug Therapy, Combination, Female, business
Abstract

Background Direct-acting antiviral (DAA) therapy has dramatically increased sustained virological response rates in HCV-infected patients. However, resistance-associated substitutions (RAS) interfering with NS3- and NS5A-targeted therapy, still emerge. This real-life study analysed the type and frequency of RAS in rare cases of patients failing DAA regimens in 12 clinical centres in Israel. Methods Blood samples and clinical data from 49 patients who failed various DAAs were collected. RAS identified in the NS3 and NS5A regions by population (Sanger) and next-generation sequencing (NGS) were compared by treatment regimen and HCV subtypes. Results The majority (71.4%, 35/49) of patients were infected with the genotype (GT)1b strain, while 12.2% (6/49) carried GT1a and 14.3% GT3a/b (7), GT4a (1) and GT1b/GT3a. RAS were identified in 85.7% (42/49) of failures, of which 90.5% (38/42) were clinically relevant RAS (known to be associated with a specific GT and DAA in patients failing therapy or those with more than twofold change in in vitro replicon assays). The most abundant RAS were 168A/E/Q/G/N/V (32.6%, 16/49) identified in NS3, and 93H/N (61.2%, 30/49), 31I/M/V (34.7%, 17/49) and 30R/H/K (12.2%, 6/49), identified in NS5A. Significantly more clinically relevant RAS were identified in NS5A (82.2%, 37/45) than in NS3 (35.7%, 10/28; PConclusions Our findings, together with additional real-life data, will contribute to the optimization of retreatment in DAA failure, when cost-related and suboptimal regimens must be employed.

Published
2019

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