2,521 results on '"Therapy naive"'
Search Results
2. Gp120 substitutions at positions associated with resistance to fostemsavir in treatment-naive HIV-1-positive individuals.
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Lepore, Luciana, Fabrizio, Claudia, Bavaro, Davide Fiore, Milano, Eugenio, Volpe, Anna, Lagioia, Antonella, Angarano, Gioacchino, Saracino, Annalisa, and Monno, Laura
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HIV , *AMINO acids , *HIV-1 glycoprotein 120 - Abstract
Objectives: Fostemsavir, a novel attachment inhibitor targeting the HIV-1 gp120, has demonstrated wide in vitro activity. However, the high rate of HIV gp120 substitutions could jeopardize its efficacy. We investigated envelope (env) substitutions at positions associated with resistance to fostemsavir in patients with a new HIV-1 diagnosis according to HIV subtype and tropism.Methods: Gp120 sequences from 409 subjects were retrospectively analysed and the presence of the L116P, A204D, S375H/M/T, M426L, M434I and M475I mutations was evaluated. Other amino acid changes at the same positions were also recorded. The variability at each amino acid position was evaluated using Shannon entropy.Results: The frequency of mutations was: S375T (13.2%); M426L (6.8%); M434I (2.9%); M475I (2.7%); S375H (1.0%)/M (0.8%) and L116P (0.31%). Statistically significant differences were found at positions 375 (R5/non-R5 strains and B/non-B subtypes) and 426 (B/non-B subtypes); post hoc analysis revealed that significance for position 375 was steered by S375T while for position 426 significance was governed by unusual substitutions, in particular M426R (B/non-B, P < 0.00001). The variability of env constant domains appeared to be more relevant in the non-B virus population.Conclusions: In conclusion, gp120 substitutions were detected in different subtypes and in both R5 and non-R5 variants. Despite the great variability of gp120, the frequency of mutations was low overall and the predominant substitution was S375T, the role of which in reducing fostemsavir efficacy is less substantial. [ABSTRACT FROM AUTHOR]- Published
- 2020
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3. Variability of the HIV-1 3' polypurine tract (3'PPT) region and implication in integrase inhibitor resistance.
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Malet, Isabelle, Delelis, Olivier, Nguyen, Thuy, Leducq, Valentin, Abdi, Besma, Morand-Joubert, Laurence, Calvez, Vincent, and Marcelin, Anne-Geneviève
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INTEGRASE inhibitors , *MEDICAL databases , *VIRAL mutation , *VIRAL proteins , *MUPIROCIN - Abstract
Background: Integrase strand-transfer inhibitors (INSTIs) are efficient at impairing retroviral integration, which is a critical step in HIV-1 replication. To date, resistance to these compounds has been explained by mutations in the viral protein integrase, which catalyses the integration step. Recently, it has been shown that selected mutations in the 3' polypurine tract (3'PPT), a sequence involved in the reverse transcription mechanism, result in high-level resistance to these compounds. This observation was reinforced by the description of a patient who failed INSTI treatment by selecting mutations in the 3'PPT sequence.Methods: Sequences of the 3'PPT region were analysed in 30706 treatment-naive patients from the public Los Alamos database belonging to six different subtypes and, in parallel, in 107 patients failing INSTI treatment.Results: The analysis showed that the sequences of patients failing INSTI treatment, in the same way as those of treatment-naive patients, are very well conserved regardless of the presence or absence of resistance mutations in the integrase gene.Conclusions: This study confirms that the selection of a mutation in the 3'PPT region conferring high-level resistance to INSTIs is a rare event. It would require a particular in vivo context and especially a long enough time to be selected, this exposure time being generally reduced by the rapid change of treatment in the case of virological failure. Larger-scale studies in patients with INSTI treatment failure are needed to determine whether the 3'PPT region can play an important role in vivo in INSTI resistance. [ABSTRACT FROM AUTHOR]- Published
- 2019
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4. Weight Status, Medication Use, and Recreational Activities of Treatment-Naïve Transgender Youth
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Mirae J. Fornander, Christine N. Moser, Timothy A. Roberts, and Anna M. Egan
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Male ,Gerontology ,Gender dysphoria ,Pediatric Obesity ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Overweight ,Transgender Persons ,Body Mass Index ,Therapy naive ,Transgender ,Weight management ,Humans ,Medicine ,Growth Charts ,Child ,Weight status ,Recreation ,Nutrition and Dietetics ,business.industry ,Infant, Newborn ,medicine.disease ,Obesity ,Pediatrics, Perinatology and Child Health ,Female ,medicine.symptom ,business ,human activities - Abstract
Background: Studies of transgender/gender diverse (TGD) youth indicate a high prevalence of overweight/obesity and concern for unhealthy weight management behavior. This study describes the associa...
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- 2022
5. Resistance to integrase inhibitors: a national study in HIV-1-infected treatment-naive and -experienced patients.
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Marcelin, Anne-Genevieve, Grude, Maxime, Charpentier, Charlotte, Bellecave, Pantxika, Guen, Laura Le, Pallier, Coralie, Raymond, Stéphanie, Mirand, Audrey, Bocket, Laurence, Fofana, Djeneba Bocar, Delaugerre, Constance, Nguyen, Thuy, Montès, Brigitte, Jeulin, Hélène, Mourez, Thomas, Fafi-Kremer, Samira, Amiel, Corinne, Roussel, Catherine, Dina, Julia, and Trabaud, Mary-Anne
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INTEGRASE inhibitors , *ANTIRETROVIRAL agents , *GENOTYPES , *INTEGRASES - Abstract
Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice.Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated.Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure.Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care. [ABSTRACT FROM AUTHOR]- Published
- 2019
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6. Dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA <500 000 copies/mL: week 48 outcomes from ACTG 5353.
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Nyaku, Amesika N, Zheng, Lu, Gulick, Roy M, Olefsky, Maxine, Berzins, Baiba, Wallis, Carole L, Godfrey, Catherine, Sax, Paul E, Acosta, Edward P, Haas, David W, Smith, Kimberly Y, Sha, Beverly E, Dam, Cornelius N Van, Taiwo, Babafemi O, Van Dam, Cornelius N, and ACTG A5353 Study Team
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HIV infections , *LAMIVUDINE , *GENETIC mutation , *MEDICAL care , *RANDOMIZED controlled trials - Abstract
Background: The AIDS Clinical Trials Group study A5353 demonstrated the efficacy and safety of dolutegravir and lamivudine for initial treatment of HIV-1 infection at week 24 in individuals with HIV-1 RNA 1000-500 000 copies/mL. Optimal ART for treatment-naive individuals must be durable.Objectives: The aim of this study was to estimate the efficacy and safety of dolutegravir plus lamivudine at week 48 and compare the efficacy in participants with baseline HIV-1 RNA ≤100 000 copies/mL versus >100 000 copies/mL.Methods: Virological success was defined as HIV-1 RNA <50 copies/mL by FDA Snapshot criteria. Definition of virological failure included confirmed HIV-1 RNA >200 copies/mL at week 24 or later. The proportion of participants with virological success was estimated using two-sided exact Clopper-Pearson 95% CI. Comparison between screening HIV-1 RNA (≤100 000 versus >100 000 copies/mL) strata was carried out by Fisher's exact test. The study was registered with ClinicalTrials.gov, number NCT02582684.Results: A total of 120 enrolled eligible participants were included in the analysis. At week 48, 102 of the 120 participants (85%; 95% CI 77%-91%) had virological success. Virological success was similar between screening HIV-1 RNA groups. Six (5%) participants had virological non-success and one additional participant experienced virological failure while on study but off study treatment. No new drug resistance mutations were observed. Six (5%) participants had study-related grade 3 or higher adverse events and none discontinued study treatment.Conclusions: These results add to the evidence that dolutegravir plus lamivudine is a safe and effective option for initial ART in individuals with HIV-1 RNA <500 000 copies/mL. [ABSTRACT FROM AUTHOR]- Published
- 2019
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7. Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain.
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Requena, S, Lozano, A B, Caballero, E, García, F, Nieto, M C, Téllez, R, Fernández, J M, Trigo, M, Rodríguez-Avial, I, Martín-Carbonero, L, Miralles, P, Soriano, V, Mendoza, C de, de Mendoza, C, and HIV-2 Spanish Study Group
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HIV-positive persons , *ANTIRETROVIRAL agents , *VIREMIA , *DRUG resistance , *CHEMICAL inhibitors - Abstract
Background: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2.Methods: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modalities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed.Results: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126 cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1).Conclusions: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individuals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options. [ABSTRACT FROM AUTHOR]- Published
- 2019
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8. Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients.
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Soulie, Cathia, Santoro, Maria Mercedes, Charpentier, Charlotte, Storto, Alexandre, Paraskevis, Dimitrios, Carlo, Domenico Di, Gennari, William, Sterrantino, Gaetana, Zazzi, Maurizio, Perno, Carlo Federico, Calvez, Vincent, Descamps, Diane, Ceccherini-Silberstein, Francesca, Marcelin, Anne-Geneviève, and Di Carlo, Domenico
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DARUNAVIR , *RILPIVIRINE , *NEVIRAPINE , *EFAVIRENZ , *RITONAVIR - Abstract
Background: Doravirine is a novel HIV-1 NNRTI recently shown to be non-inferior to both darunavir/ritonavir and efavirenz in combination therapy with two NRTIs in treatment-naive patients. Doravirine has an in vitro resistance profile that is distinct from other NNRTIs and retains activity against viruses containing the most frequently transmitted NNRTI mutations.Objectives: The aim of this study was to examine the prevalence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients in Europe.Methods: From 2010 to 2016, 9764 treatment-naive patients were tested for NNRTI antiretroviral drug resistance by bulk sequencing in Greece, Italy and France. We studied the prevalence of doravirine resistance-associated mutations previously identified in vitro: V106A/M, V108I, Y188L, V190S, H221Y, F227C/L/V, M230I/L, L234I, P236L, Y318F and K103N/Y181C.Results: Among 9764 sequences, 53.0% and 47.0% of patients had B and non-B subtypes, respectively. Overall, the presence of at least one doravirine resistance-associated mutation (n = 137; 1.4%) or the K103N/Y181C mutations (n = 5; 0.05%) was very rare. The most prevalent mutations were V108I (n = 62; 0.6%), Y188L (n = 18; 0.2%), H221Y (n = 18; 0.2%) and Y318F (n = 23; 0.2%). The frequency of doravirine resistance-associated mutations was similar between B and non-B subtypes. In comparison, the prevalence of rilpivirine, etravirine, nevirapine and efavirenz resistance was higher whatever algorithm was used (ANRS: 8.5%, 8.1%, 8.3% and 3.9%, respectively; Stanford: 9.9%, 10.0%, 7.5% and 9.4%, respectively).Conclusions: The prevalence of doravirine resistance-associated mutations is very low in antiretroviral-naive patients. These results are very reassuring for doravirine use in naive patients. [ABSTRACT FROM AUTHOR]- Published
- 2019
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9. Real-world experience of treatment with thrombopoietin receptor agonists in anti-thymocyte globulin-naïve patients with aplastic anemia: an observational retrospective analysis in a single institution
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Masaki Iino, Atsushi Jinguji, Ayato Nakadate, and Tomoya Sato
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Thrombopoietin Receptor Agonists ,business.industry ,Anemia, Aplastic ,Hematology ,medicine.disease ,Anti-thymocyte globulin ,Therapy naive ,Treatment Outcome ,Immunology ,Retrospective analysis ,Medicine ,Humans ,Observational study ,Single institution ,Aplastic anemia ,business ,Receptors, Thrombopoietin ,Aged ,Antilymphocyte Serum ,Retrospective Studies - Abstract
Thrombopoietin receptor agonists (TPO-RAs) are used to treat bone marrow failure in aplastic anemia (AA). Treatment with TPO-RAs, cyclosporine A (CsA) and anti-thymocyte globulin (ATG) induces remission and a sustained response. However, the efficacy of TPO-RAs without ATG remains unclear. We retrospectively assessed 45 patients with AA refractory to CsA and naïve for ATG treatment who received eltrombopag without ATG at our hospital during 2017-2021. Of these, 28 (62%) achieved a hematologic response in at least one lineage after six months of treatment, and 38 (84%) achieved best response at any point during the follow-up period. Four patients (25%) achieved trilineage responses during the follow-up period. Five patients switched from eltrombopag to romiplostim because of adverse events or lack of efficacy. Two developed hematologic malignancies. Eltrombopag was effective even in elderly ATG-ineligible patients with severe AA. The two-year overall survival rate was 84.3%, with a median follow-up of 26.3 months. Time from diagnosis to eltrombopag treatment initiation tended to affect the response (p = 0.0727), but no factors that significantly predicted hematologic response were identified. In conclusion, patients who are ineligible for ATG treatment because of age, complications, or even severe AA should nevertheless be considered for TPO-RA treatment.
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- 2022
10. Utility of multiple core biopsies during transperineal template-guided mapping biopsy for patients with large prostates and PI-RADS 1–2 on multiparametric magnetic resonance imaging
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Chung Un Lee, Seong Soo Jeon, Hyun Hwan Sung, Jae Hoon Chung, Wan Song, Byong Chang Jeong, Hyun Moo Lee, Minyong Kang, Hwang Gyun Jeon, and Seong Il Seo
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medicine.medical_specialty ,medicine.diagnostic_test ,Urinary retention ,business.industry ,Urology ,medicine.disease ,PI-RADS ,Therapy naive ,Prostate cancer ,medicine.anatomical_structure ,Prostate ,Biopsy ,medicine ,Radiology ,medicine.symptom ,business ,Core biopsy ,Multiparametric Magnetic Resonance Imaging - Abstract
Background We investigated the necessity of multiple core biopsies when performing transperineal template-guided mapping biopsy (TTMB) for patients with large prostates and no suspicious lesions on multiparametric magnetic resonance imaging (mpMRI). Materials and methods We retrospectively analyzed 304 patients on active surveillance (AS), 212 patients with previously negative transrectal ultrasound-guided biopsy (TRUS-Bx) and 67 biopsy naive patients who underwent TTMB between May 2017 and December 2020. The number of core biopsies and acute urinary retention (AUR) rates were analyzed in relation to the prostate volume (PV). Cancer detection rate according to the prostate volume and Prostate Imaging-Reporting and Data System (PI-RADS) scores were compared using the Pearson Chi-square test. Results AUR occurred more frequently in patients with PV over 39 cc (5.5% vs. 24.4%, P Conclusion Increasing the number of core biopsies of prostates measuring ≥39 cc with PI-RADS 1–2 on mpMRI does not significantly increase the detection rates of any prostate cancer or csPCA.
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- 2022
11. Association between blood pressure and the risk of chronic kidney disease in treatment-naïve hypertensive patients
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Hyunjin Noh, Soon Hyo Kwon, Jin Seok Jeon, Hyoungnae Kim, Haekyung Lee, and Dong Cheol Han
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Therapy naive ,medicine.medical_specialty ,Blood pressure ,business.industry ,Internal medicine ,Incidence (epidemiology) ,medicine ,cardiovascular diseases ,General Medicine ,medicine.disease ,business ,circulatory and respiratory physiology ,Kidney disease - Abstract
Background: Although hypertension is a well-known risk factor for chronic kidney disease (CKD), the blood pressure (BP) at which antihypertensive interventions should be initiated remains to be determined. Therefore, we investigated the association between BP and CKD in treatment-naïve individuals.Methods: This prospective cohort study considered 7,343 individuals in the Korean Genome and Epidemiology Study who were not taking antihypertensive medications. Subjects were categorized into six groups according to their systolic BP (SBP) and five groups according to their diastolic BP (DBP). The primary outcome was incident CKD, which was defined as an estimated glomerular filtration rate of
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- 2022
12. Antiretroviral potency of 4'-ethnyl-2'-fluoro-2'-deoxyadenosine, tenofovir alafenamide and second-generation NNRTIs across diverse HIV-1 subtypes.
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Njenda, Duncan T, Aralaguppe, Shambhu G, Singh, Kamalendra, Rao, Rohit, Sönnerborg, Anders, Sarafianos, Stefan G, and Neogi, Ujjwal
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ANTIRETROVIRAL agents , *DEOXYADENOSINE , *NON-nucleoside reverse transcriptase inhibitors , *TENOFOVIR , *VIROLOGY , *BIOCHEMISTRY , *HIV infections , *ADENOSINES , *COMPARATIVE studies , *DRUG resistance in microorganisms , *GENETICS , *HIV , *RESEARCH methodology , *MEDICAL cooperation , *GENETIC mutation , *PROTEINS , *PURINES , *RESEARCH , *EVALUATION research , *TREATMENT effectiveness , *REVERSE transcriptase inhibitors , *CHEMICAL inhibitors , *PHARMACODYNAMICS - Abstract
Objectives: 4'-Ethnyl-2'-fluoro-2'-deoxyadenosine (EFdA) is a novel translocation-defective reverse transcriptase inhibitor. We investigated the virological and biochemical inhibitory potentials of EFdA against a broad spectrum of subtype-specific chimeric viruses and compared it with tenofovir alafenamide, nevirapine, efavirenz, rilpivirine and etravirine.Methods: pNL4.3 chimeric viruses encoding gag-pol from treatment-naive patients (n = 24) and therapy-failure patients (n = 3) and a panel of reverse transcriptase inhibitor-resistant strains (n = 7) were used to compare the potency of reverse transcriptase inhibitor drugs. The phenotypic drug susceptibility assay was performed using TZM-bl cells. In vitro inhibition assays were done using patient-derived reverse transcriptase. IC50 values of NNRTIs were calculated using a PicoGreen-based spectrophotometric assay. Steady-state kinetics were used to determine the apparent binding affinity (Km.dNTP) of triphosphate form of EFdA (EFdA-TP) and dATP.Results: Among the chimeric treatment-naive viruses, EFdA had an ex vivo antiretroviral activity [median (IQR) EC50 = 1.4 nM (0.6-2.1 nM)] comparable to that of tenofovir alafenamide [1.6 nM (0.5-3.6 nM)]. Subtype-specific differences were found for etravirine (P = 0.004) and rilpivirine (P = 0.017), where HIV-1C had the highest EC50 values. EFdA had a greater comparative efficiency [calculated by dividing the efficiency of monophosphate form of EFdA (EFdA-MP) incorporation (kcat.EFdA-TP/Km.EFdA-TP) over the efficiency of dATP incorporation (kcat.dATP/Km.dATP)] compared with the natural substrate dATP, with a fold change of between 1.6 and 3.2. Ex vivo analysis on reverse transcriptase inhibitor-resistant strains showed EFdA to have a higher potency. Despite the presence of rilpivirine DRMs, some non-B strains showed hypersusceptibility to rilpivirine.Conclusions: Our combined virological and biochemical data suggest that EFdA inhibits both WT and reverse transcriptase inhibitor-resistant viruses efficiently in a subtype-independent manner. In contrast, HIV-1C is least susceptible to etravirine and rilpivirine. [ABSTRACT FROM AUTHOR]- Published
- 2018
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13. Sputum microbiota profiles of treatment-naïve TB patients in Uganda before and during first-line therapy
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Adrian Muwonge, Edgar Kigozi, Fred A Katabazi, Moses Joloba, David P. Kateete, Lydia Nakiyingi, Sharon Namiiro, Aliphonse Okwera, Willy Ssengooba, Faith Nakazzi, and Monica Mbabazi
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Adult ,Male ,medicine.medical_specialty ,Treatment response ,Tuberculosis ,Molecular biology ,Science ,Antitubercular Agents ,Diseases ,Biology ,Sputum sample ,Microbiology ,Article ,Therapy naive ,03 medical and health sciences ,fluids and secretions ,First line therapy ,Medical research ,Internal medicine ,medicine ,Humans ,Uganda ,Longitudinal Studies ,Tuberculosis, Pulmonary ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,Multidisciplinary ,Bacteria ,030306 microbiology ,Microbiota ,Sputum ,medicine.disease ,3. Good health ,stomatognathic diseases ,Medicine ,Female ,medicine.symptom ,Pulmonary tb ,Microbiota composition - Abstract
Information on microbiota dynamics in pulmonary tuberculosis (TB) in Africa is scarce. Here, we sequenced sputa from 120 treatment-naïve TB patients in Uganda, and investigated changes in microbiota of 30 patients with treatment-response follow-up samples. Overall, HIV-status and anti-TB treatment were associated with microbial structural and abundance changes. The predominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria and Actinobacteria, accounting for nearly 95% of the sputum microbiota composition; the predominant genera across time were Prevotella, Streptococcus, Veillonella, Haemophilus, Neisseria, Alloprevotella, Porphyromonas, Fusobacterium, Gemella, and Rothia. Treatment-response follow-up at month 2 was characterized by a reduction in abundance of Mycobacterium and Fretibacterium, and an increase in Ruminococcus and Peptococcus; month 5 was characterized by a reduction in Tannerella and Fusobacterium, and an increase in members of the family Neisseriaceae. The microbiota core comprised of 44 genera that were stable during treatment. Hierarchical clustering of this core’s abundance distinctly separated baseline (month 0) samples from treatment follow-up samples (months 2/5). We also observed a reduction in microbial diversity with 9.1% (CI 6–14%) of the structural variation attributed to HIV-status and anti-TB treatment. Our findings show discernible microbiota signals associated with treatment with potential to inform anti-TB treatment response monitoring.
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- 2021
14. Clinical Outcomes of Aflibercept Treatment for Treatment-naive Exudative Age-related Macular Degeneration
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In Young Chung, Young Je Choi, Woong-Sun Yoo, Yong Wun Cho, and Yu-Jin Choi
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Therapy naive ,medicine.medical_specialty ,business.industry ,Ophthalmology ,medicine ,business ,Exudative age-related macular degeneration ,Aflibercept ,medicine.drug - Published
- 2021
15. Follicular lymphoma subgroups with and without t(14;18) differ in their N-glycosylation pattern and IGHV usage
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German Ott, Valter Gattei, Alberto Zamò, Claudia Maier, Heike Horn, Filippo Vit, Riccardo Bomben, Alessandro Bosi, Ellen Leich, and Andreas Rosenwald
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Glycosylation ,Immunoglobulin genes ,Follicular lymphoma ,breakpoint cluster region ,High-Throughput Nucleotide Sequencing ,Hematology ,Biology ,medicine.disease ,Molecular biology ,Cohort Studies ,Therapy naive ,N-linked glycosylation ,Follicular phase ,Fresh frozen ,medicine ,Humans ,IGHV@ ,Lymphoma, Follicular - Abstract
We previously reported that t(14;18)-negative follicular lymphomas (FL) show a clear reduction of newly acquired N-glycosylation sites (NANGS) in immunoglobulin genes. We therefore aimed to investigate in-depth the occurrence of NANGS in a larger cohort of t(14;18)-positive and t(14;18)-negative FL, including early (I/II) and advanced (III/IV) stage treatment-naive and relapsed tumors. The clonotype was determined by using a next-generation sequencing approach in a series of 68 FL with fresh frozen material [36 t(14;18) positive and 32 t(14;18) negative]. The frequency of NANGS differed considerably between t(14;18)-positive and t(14;18)-negative FL stage III/IV, but no difference was observed among t(14;18)-positive and t(14;18)-negative FL stage I/II. The introduction of NANGS in all t(14;18)-negative clinical subgroups occurred significantly more often in the FR3 region. Moreover, t(14;18)-negative treatment-naive FL, specifically those with NANGS, showed a strong bias for IGHV4-34 usage compared with t(14;18)-positive treatment-naive cases with NANGS; IGHV4-34 usage was never recorded in relapsed FL. In conclusion, subgroups of t(14;18)-negative FL might use different mechanisms of B-cell receptor stimulation compared with the lectin-mediated binding described in t(14;18)-positive FL, including responsiveness to autoantigens as indicated by biased IGHV4-34 usage and strong NANGS enrichment in FR3.
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- 2021
16. Tumor characteristics of hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C: Comparative analysis with antiviral therapy-naive patients
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Elham Ahmed, Magdy Fouad, Mohamed El Kassas, and Reem El Sheemy
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Direct-acting antiviral treatment ,Hepatology ,Hepatocellular carcinoma ,business.industry ,Antiviral therapy ,Hepatitis C ,Case Control Study ,medicine.disease ,digestive system diseases ,Therapy naive ,Occurrence ,Tumor behavior ,Cancer research ,Medicine ,Antiviral treatment ,business ,Direct acting - Abstract
BACKGROUND Insufficient and contradictory data are available about the relation between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) development in patients with hepatitis C virus (HCV). AIM To analyze differences in basic clinical, radiological, and laboratory characteristics in addition to tumor behavior upon HCC diagnosis between patients with and without a previous history of DAAs exposure. METHODS This multicenter case-control study included 497 patients with chronic HCV-related HCC, allocated into one of two groups according to their history of antiviral treatment for their HCV. RESULTS Group I included 151 HCC patients with a history of DAAs, while 346 patients who had never been treated with DAAs were assigned to group II. A significant difference was observed between both groups regarding basic assessment scores (Child, MELD, and BCLC), which tended to have more advanced liver disease and HCC stage upon diagnosis in group I. However, serum albumin was significantly affected, and serum α-fetoprotein was significantly higher in group II (P < 0.001). In addition, group I showed significant HCC multicentricity than group II, while the incidence of portal vein thrombosis was significantly higher in group I (P < 0.001). CONCLUSION The basic clinical scores and laboratory characteristics of HCC patients are advanced in patients who are naïve to DAAs treatment; however, HCC behavior is more aggressive in DAA-treated patients.
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- 2021
17. Psychoradiological abnormalities in treatment‐naive noncomorbid patients with posttraumatic stress disorder
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Huaiqiang Sun, Lingjiang Li, Du Lei, Jing Yang, Kun Qin, Graham J. Kemp, Wenbin Li, Qiyong Gong, and Xueling Suo
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medicine.medical_specialty ,business.industry ,Radial diffusivity ,Brain ,White Matter ,behavioral disciplines and activities ,Stress Disorders, Post-Traumatic ,White matter ,Correlation ,Therapy naive ,Psychiatry and Mental health ,Clinical Psychology ,Posttraumatic stress ,Diffusion Magnetic Resonance Imaging ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,Neuroimaging ,Internal medicine ,Fractional anisotropy ,medicine ,Cardiology ,Anisotropy ,Humans ,business ,Diffusion MRI - Abstract
Background Neuroimaging studies in posttraumatic stress disorder (PTSD) have identified various alterations in white matter (WM) microstructural organization. However, it remains unclear whether these are localized to specific regions of fiber tracts, and what diagnostic value they might have. This study set out to explore the spatial profile of WM abnormalities along defined fiber tracts in PTSD. Methods Diffusion tensor images were obtained from 77 treatment-naive noncomorbid patients with PTSD and 76 demographically matched trauma-exposed non-PTSD (TENP) controls. Using automated fiber quantification, tract profiles of fractional anisotropy, axial diffusivity, mean diffusivity, and radial diffusivity were calculated to evaluate WM microstructural organization. Results were analyzed by pointwise comparisons, by correlation with symptom severity, and for diagnosis-by-sex interactions. Support vector machine analyses assessed the ability of tract profiles to discriminate PTSD from TENP. Results Compared to TENP, PTSD showed lower fractional anisotropy accompanied by higher radial diffusivity and mean diffusivity in the left uncinate fasciculus, and lower fractional anisotropy accompanied by higher radial diffusivity in the right anterior thalamic radiation. Tract profile alterations were correlated with symptom severity, suggesting a pathophysiological relevance. There were no significant differences in diagnosis-by-sex interaction. Tract profiles allowed individual classification of PTSD versus TENP with significant accuracy, of potential diagnostic utility. Conclusions These findings add to the knowledge of the neuropathological basis of PTSD. WM alterations based on a tract-profile quantification approach are a potential biomarker for PTSD.
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- 2021
18. Cysteamine bitartrate delayed‐release capsules control leukocyte cystine levels and promote statural growth and kidney health in an open‐label study of treatment‐naïve patients <6 years of age with nephropathic cystinosis
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Gregg Checani, Craig B. Langman, Heather E. Price, Juliana Caires de Oliveira Achili Ferreira, Kyleen D. Young, Saba Sile, and Maria Helena Vaisbich
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Research Report ,Cysteamine Bitartrate ,Endocrinology, Diabetes and Metabolism ,Cystine ,QH426-470 ,Pharmacology ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Diseases of the endocrine glands. Clinical endocrinology ,Therapy naive ,chemistry.chemical_compound ,children ,Open label study ,Nephropathic Cystinosis ,Genetics ,Internal Medicine ,medicine ,cysteine ,Kidney ,business.industry ,delayed‐release cysteamine ,Research Reports ,Delayed release (linguistics) ,RC648-665 ,cystinosis ,medicine.anatomical_structure ,chemistry ,immediate‐release cysteamine ,business ,anthropometric parameters - Abstract
Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disease that is characterized by accumulation of cysteine and formation of crystals within cells of different organs and tissues causing systemic manifestations in childhood that include poor linear growth, ocular involvement, hypothyroidism, and progressive kidney disease. This study was a long‐term, prospective open‐label evaluation of twice‐daily delayed release (DR) cysteamine capsules in cystinosis patients
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- 2021
19. Decreased CSF Dynamics in Treatment-Naive Patients with Essential Hypertension: A Study with Phase-Contrast Cine MR Imaging
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Xiang Xiao, Xia Li, Haimei Cao, Xiaoli Liu, Yi-Long Wu, Lichao Ma, Liuji Guo, W. He, and Yikai Xu
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medicine.medical_specialty ,business.industry ,Adult Brain ,Phase contrast microscopy ,Dynamics (mechanics) ,Magnetic Resonance Imaging, Cine ,Essential hypertension ,medicine.disease ,Magnetic Resonance Imaging ,law.invention ,Therapy naive ,Blood pressure ,Volume (thermodynamics) ,Peak velocity ,law ,Internal medicine ,Cardiology ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,In patient ,Neurology (clinical) ,Essential Hypertension ,business ,Cerebrospinal Fluid - Abstract
BACKGROUND AND PURPOSE: Arterial sclerosis resulting from hypertension slows CSF transportation in the perivascular spaces, showing the intrinsic relationship between the CSF and the blood vasculature. However, the exact effect of hypertension on human CSF flow dynamics remains unclear. The present study aimed to evaluate CSF flow dynamics in treatment-naive patients with essential hypertension using phase-contrast cine MR imaging. MATERIALS AND METHODS: The study included 60 never-treated patients with essential hypertension and 60 subjects without symptomatic atherosclerosis. CSF flow parameters, such as forward flow volume, forward peak velocity, reverse flow volume, reverse peak velocity, average flow, and net flow volume, were measured with phase-contrast cine MR imaging. Differences between the 2 groups were assessed to determine the independent determinants of these CSF flow parameters. RESULTS: Forward flow volume, forward peak velocity, reverse flow volume, reverse peak velocity, and average flow in the patients with hypertension significantly decreased (all, P
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- 2021
20. Interim clinical trial analysis of intraoperative mass spectrometry for breast cancer surgery
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Mehra Golshan, Elizabeth C. Randall, Melissa Anne Mallory, David Calligaris, Sylwia A. Stopka, Sankha S. Basu, Michael S. Regan, Isaiah Norton, Deborah A. Dillon, Walid M. Abdelmoula, Begoña Gimenez-Cassina Lopez, Sandro Santagata, Fa-Ke F. Lu, and Nathalie Y. R. Agar
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Lumpectomy ,Normal tissue ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Surgery ,Resection ,Therapy naive ,Clinical trial ,Breast cancer ,Oncology ,medicine ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,business ,Research setting ,RC254-282 - Abstract
Optimal resection of breast tumors requires removing cancer with a rim of normal tissue while preserving uninvolved regions of the breast. Surgical and pathological techniques that permit rapid molecular characterization of tissue could facilitate such resections. Mass spectrometry (MS) is increasingly used in the research setting to detect and classify tumors and has the potential to detect cancer at surgical margins. Here, we describe the ex vivo intraoperative clinical application of MS using a liquid micro-junction surface sample probe (LMJ-SSP) to assess breast cancer margins. In a midpoint analysis of a registered clinical trial, surgical specimens from 21 women with treatment naïve invasive breast cancer were prospectively collected and analyzed at the time of surgery with subsequent histopathological determination. Normal and tumor breast specimens from the lumpectomy resected by the surgeon were smeared onto glass slides for rapid analysis. Lipidomic profiles were acquired from these specimens using LMJ-SSP MS in negative ionization mode within the operating suite and post-surgery analysis of the data revealed five candidate ions separating tumor from healthy tissue in this limited dataset. More data is required before considering the ions as candidate markers. Here, we present an application of ambient MS within the operating room to analyze breast cancer tissue and surgical margins. Lessons learned from these initial promising studies are being used to further evaluate the five candidate biomarkers and to further refine and optimize intraoperative MS as a tool for surgical guidance in breast cancer.
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- 2021
21. Evaluation of macular perfusion in patients with treatment-naive overt hypothyroidism using optical coherence tomography angiography
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Sami Yilmaz, Gülçin Şahingöz Erdal, Ali Atakhan Yildiz, Hatice Nur Tarakcioglu, and Aysegul Mavi Yildiz
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Therapy naive ,Ophthalmology ,medicine.medical_specialty ,Göz Hastalıkları ,business.industry ,medicine ,Choroidal flow,Hypothyroidism,Macular perfusion,Optic coherence tomography angiography,Vessel density ,In patient ,Radiology ,Optical coherence tomography angiography ,business ,Perfusion - Abstract
Background/Aim: Thyroid hormones play an essential role in retinal development and physiological functions. Although the effects of hyperthyroidism on ocular circulation are well-defined, no studies report the effects of clinical hypothyroidism on retinal and choroidal circulation. We aimed to compare the macular vessel density and flow indexes of patients with treatment-naive hypothyroidism and healthy controls using optical coherence tomography angiography (OCTA).Methods: This case-control study included 104 eyes of 52 participants. Group 1 (n=24) consisted of patients with treatment-naive overt hypothyroidism, while Group 2 (n=28) consisted of age and sex-matched healthy controls. Images were obtained using AngioVue software 2.0 of the OCTA device in a 6 × 6 mm area centered on the macula. Foveal avascular zone (FAZ) area, macular retinal thickness, FAZ perimeter (PERIM), choroidal flow index (CF), outer retinal flow index (ORF) and macular vessel density (VD) in the superficial (SCP) and deep retinal capillary plexus (DCP) were recorded for all patients.Results: The whole [Group 1: 49.9 (7.0)%; Group 2: 54.6 (5.9)%], parafoveal [Group 1: 54.7 (4.8)%; Group 2: 58.6 (3.9)%] and perifoveal [Group 1: 51.5 (7.2)%; Group 2: 55.9 (6.8)% ] VD in DCP were significantly lower in Group 1 compared to Group 2 (P=0.012; P=0.002 and P=0.028 respectively). However, parafoveal VD in SCP was significantly higher in Group 1 [52.4 (2.26)] than in Group 2 [49.9 (6.87)] (P=0.032). The mean VD in DCP was significantly positively correlated with the choroidal (P=0.021) and outer retinal flow indexes (P=0.033). The mean foveal VD in DCP was significantly positively correlated with the mean foveal (P
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- 2021
22. Dexamethasone intravitreal implant in treatment-naïve diabetic macular oedema: findings from the prospective, multicentre, AUSSIEDEX study
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Jennifer J. Arnold, Susan Simonyi, Hyong Kwon Kang, Paul Mitchell, Samantha Fraser-Bell, and Jodi Tainton
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medicine.medical_specialty ,Endothelial Growth Factors ,Visual acuity ,genetic structures ,business.industry ,medicine.medical_treatment ,Cataract surgery ,eye diseases ,Sensory Systems ,Therapy naive ,Cellular and Molecular Neuroscience ,Ophthalmology ,Diabetic macular oedema ,medicine ,Dexamethasone Intravitreal Implant ,sense organs ,medicine.symptom ,Trial registration ,business - Abstract
AimTo evaluate the effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX; Ozurdex) monotherapy in the patient subgroup of the AUSSIEDEX study with treatment-naïve diabetic macular oedema (DME).MethodsThe open-label, prospective, phase 4, real-world study included pseudophakic eyes and phakic eyes scheduled for cataract surgery that were treatment-naïve or non-responsive to antivascular endothelial growth factors. No eyes were excluded based on baseline best-corrected visual acuity (BCVA) or central subfield retinal thickness (CRT). After the initial DEX injection at the baseline visit, reinjection was permitted at ≥16-week intervals. Week-16 and week-52 visits were mandatory. Primary endpoints were changes in mean BCVA and CRT from baseline to 52 weeks.ResultsOf 200 eyes enrolled in the AUSSIEDEX study, 57 were treatment-naïve. Baseline mean BCVA was 58.8 letters and baseline mean CRT was 418.6 µm; changes in mean BCVA and CRT from baseline to 52 weeks in this subgroup were 3.4 letters (p=0.042) and –89.6 µm (pConclusionIn this largest prospective, real-world study of DEX monotherapy for DME to date, DEX significantly improved CRT and BCVA at 52 weeks in treatment-naïve eyes, without new safety concerns, supporting DEX use in treatment-naïve DME.Trial registration numberNCT02731911.
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- 2021
23. Can Systemic Immune-Inflammation Index Detect the Presence of Exxaggerated Morning Blood Pressure Surge in Newly Diagnosed Treatment-Naive Hypertensive Patients?
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Remzi Sarıkaya and Faysal Saylik
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Inflammation ,medicine.medical_specialty ,Physiology ,business.industry ,Blood Pressure ,General Medicine ,Newly diagnosed ,Blood Pressure Monitoring, Ambulatory ,Gastroenterology ,Target organ damage ,Therapy naive ,Blood pressure ,Internal medicine ,Hypertension ,Internal Medicine ,medicine ,Humans ,Lymphocytes ,Neutrophil to lymphocyte ratio ,business ,Morning ,Immune inflammation - Abstract
Background: The exaggerated morning blood pressure surge (MS) is associated with target organ damage and cardiovascular events. Systemic immune-inflammation index (SII) has been detected as a usefu...
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- 2021
24. Effectiveness, Durability, and Safety of Dolutegravir and Lamivudine Versus Dolutegravir, Lamivudine, and Abacavir in a Real-Life Cohort of HIV-Infected Adults
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Miguel Angel Torralba, Inés Mendoza, and Alicia Lázaro
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Anti-HIV Agents ,Pyridones ,030106 microbiology ,HIV Infections ,Piperazines ,Therapy naive ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Abacavir ,Hiv infected ,Internal medicine ,Oxazines ,Humans ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,business.industry ,Lamivudine ,Viral Load ,Antiretroviral therapy ,Dideoxynucleosides ,chemistry ,Cohort ,Dolutegravir ,business ,Heterocyclic Compounds, 3-Ring ,medicine.drug - Abstract
Background: Dolutegravir (DTG) plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment. Objective: To analyze the effectiveness, durability, and safety of 2-DR compared with DTG plus abacavir/lamivudine (3-DR). Methods: This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) patients who started 2-DR or 3-DR between July 1, 2018, and November 30, 2020. The primary end point was noninferiority, at 24 and 48 weeks, of 2-DR versus 3-DR regarding the percentage of patients with viral load (VL)≥50 and 200 copies/mL in TN (4% margin) and VLResults: 242 patients were included (53 TN and 189 TE). Two TN patients on 2-DR had VL≥50 copies/mL and 1 had VL≥200 copies/mL at week 24. In TE patients on 2-DR, 90.2% achieved VLConclusion and Relevance: Our results did not show noninferiority in terms of virological effectiveness. Nevertheless, all effectiveness measures support the use of 2-DR in a real-life cohort of TN and TE. Additionally, durability and safety of 2-DR were confirmed to be similar to that of 3-DR.
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- 2021
25. Peg‐interferon alpha add‐on Tenofovir disoproxil fumarate achieved more HBsAg loss in HBeAg‐positive chronic hepatitis B naïve patients
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Dong-Hua Zhang, Weimin She, Xuehua Sun, Yanhong Liu, Qi-Ming Gong, Jie-Hong Jiang, Lihong Qu, Xinxin Zhang, Liang Chen, Qin Zhang, Demin Yu, Yueqiu Gao, Dong Wei, Jiming Zhang, Yue Han, Jing Li, and J Chen
- Subjects
Hepatitis B virus ,HBsAg ,medicine.medical_specialty ,Tenofovir ,Alpha (ethology) ,Antiviral Agents ,Gastroenterology ,Polyethylene Glycols ,Therapy naive ,Hepatitis B, Chronic ,Virology ,Internal medicine ,Clinical endpoint ,Humans ,Medicine ,Hepatitis B e Antigens ,Prospective Studies ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,Interferon-alpha ,virus diseases ,digestive system diseases ,Clinical trial ,Regimen ,Treatment Outcome ,Infectious Diseases ,HBeAg ,DNA, Viral ,Drug Therapy, Combination ,business ,medicine.drug - Abstract
Several studies have showed that combining peg-interferon alpha (Peg-IFNα) with nucleotide analogues has complementary effects in chronic hepatitis B (CHB), but the optimal regimen and potential mechanisms remain unclear. This was a prospective, longitudinal and multicentre clinical trial (NCT03013556). HBeAg-positive CHB naïve patients were randomly assigned to three groups: tenofovir disoproxil fumarate (TDF) monotherapy for 96 weeks, TDF alone for 48 weeks and sequentially Peg-IFNα added for 48 weeks, TDF de novo combination with Peg-IFNα for 48 weeks then TDF alone for 48 weeks. The primary endpoint was HBeAg seroconversion at week 96 and HBsAg loss as the secondary endpoint. Furthermore, the levels of 12 cytokines in serum were assessed at different time points. A total of 133 patients were included in the analysis. The rates of HBeAg seroconversion at 96 weeks were not significant different among the three groups (p = 0.157). Interestingly, patients in the Peg-IFNα add-on group showed markedly lower HBsAg level compared with the other two groups at week 96. In addition, only three patients in the Peg-IFNα add-on group achieved HBsAg loss. For the following 24 weeks from week 96, no HBsAg reappearance in the three patients and no new patients with HBsAg loss were observed in the three groups. Serum cytokine analysis showed that the baseline level of interferon-inducible protein-10 (IP-10) was strongly higher in HBeAg conversion patients and HBsAg loss patients. Compared with de novo combination and TDF alone, the addition of Peg-IFNα in TDF-treated group might be an effective strategy for HBsAg loss in HBeAg-positive CHB naïve patients.
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- 2021
26. Evaluation of standard of care intravitreal aflibercept treatment of diabetic macular oedema treatment-naive patients in the UK: DRAKO study 12-month outcomes
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Moneeb Saddiq, Jackie Napier, Ajay Kotagiri, Hellen McGoey, Simon P Kelly, Andrew Nolan, James S Talks, Sobha Sivaprasad, Faruque Ghanchi, and Peter H Scanlon
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medicine.medical_specialty ,Standard of care ,Visual acuity ,genetic structures ,business.industry ,RA645.D54 ,Therapy naive ,03 medical and health sciences ,Ophthalmology ,0302 clinical medicine ,Diabetic macular oedema ,Cohort ,030221 ophthalmology & optometry ,Medicine ,RE ,030212 general & internal medicine ,medicine.symptom ,business ,Adverse effect ,Cohort study ,Aflibercept ,medicine.drug - Abstract
Objectives DRAKO (NCT02850263) is a 24-month, prospective, non-interventional, multi-centre cohort study which enroled patients diagnosed with centre-involving diabetic macular oedema (DMO). The study aims to evaluate standard of care with intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the anti-vascular endothelial growth factor (anti-VEGF) treatment-naive patient cohort after 12-month follow-up. Methods Study eyes were treated with IVT-AFL as per local standard of care. The mean change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline at 12 months were measured and stratified by baseline factors. The number of injections and safety data were also evaluated. Results A total of 507 patients were enroled from 35 centres. Mean (SD) baseline BCVA was 71.4 (12.0) letters and CST was 448.7 (88.7) µm, with 63.1% of patients presenting with baseline BCVA ≥ 70 letters (mean 78.1). Mean (SD) change in BCVA of 2.5 (12.2) letters and CST of −119.1 (116.4) µm was observed at month 12. A 7.3 letter gain was observed in patients with baseline BCVA Conclusion Year one results indicated that IVT-AFL was an effective treatment for DMO in standard of care UK clinical practice, maintaining or improving visual acuity in treatment-naive patients with good baseline visual acuity, despite some patients being undertreated versus the summary of product characteristics. These results also demonstrated the clinical importance and meaningful impact of diabetic retinopathy screening in the UK.
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- 2021
27. First-Line Efficacy of Anti-HER2 Treatments in Previously Treated HER2-Positive Metastatic Breast Cancer Patients: A Retrospective Observational Study Investigating the Efficacy of Re-Exposure to Anti-HER2 Therapy for HER2-Positive Metastatic Breast Cancer Patients in Comparison with Naïve Patients
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Barliz Waissengrin, Eliya Shachar, Amir Sonnenblick, Ido Wolf, and Roni Levin
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Oncology ,medicine.medical_specialty ,business.industry ,First line ,Retrospective cohort study ,medicine.disease ,Metastatic breast cancer ,Therapy naive ,Internal medicine ,medicine ,Surgery ,Anti her2 ,skin and connective tissue diseases ,Previously treated ,business ,neoplasms ,Research Article - Abstract
Background: Most patients with HER2-positive metastatic breast cancer (MBC) receive first-line treatment with anti-HER2 agents and have already received anti-HER2 therapy as adjuvant or neoadjuvant therapy in the local setting of their disease presentation. Despite that, they constitute only a minority among clinical trials, and their response to reintroduction to anti-HER2 treatments is inconclusive based upon conflicting studies. We aimed to examine if previous exposure influences the clinical outcome of patients treated with anti-HER2 treatments compared to patients who were naïve to anti-HER2 agents. Methods: We conducted a retrospective observational study of HER2-positive MBC patients who were treated with trastuzumab and pertuzumab from 2014 to 2018. We collected and analyzed data including patients’ demographic characteristic as well as extracted data of previous treatment regimens and the efficiency of the anti-HER2 therapy measured by response rate (RR), time to tumor progression (TTP), and overall survival (OS). Results: Eighty patients met the inclusion criteria, 26 (32.5%) of them were previously exposed to anti-HER2 treatments and 54 (67.5%) were not previously exposed to anti-HER2 therapy. No significant differences were detected in RR after 3 months of treatment (p = 0.684). TTP was significantly better among patients with no previous exposure in comparison with patients with previous exposure to anti-HER2 therapy (21 vs. 14 months, p = 0.044) and we noted a trend in better OS (p = 0.056). Conclusion: Our analysis suggests that previous exposure to anti-HER2 agents might influence the clinical outcome of first-line treatment in metastatic HER2 patients. These findings justify further exploration of the benefit of reintroduction of anti-HER2 treatment enabling the optimal treatment for patients with previous anti-HER2 therapy exposure.
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- 2021
28. Atypical Late-Onset Exudative Retinal Detachment in a Treatment-Naïve Infant With Retinopathy of Prematurity
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G. Baker Hubbard, Lauren R. Schaffer, Prethy Rao, and Krishna Mukkamala
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Male ,medicine.medical_specialty ,genetic structures ,Gestational Age ,Late onset ,Therapy naive ,Neovascularization ,Ophthalmology ,medicine ,Humans ,Retinopathy of Prematurity ,Retina ,Laser Coagulation ,business.industry ,Infant, Newborn ,Retinal Detachment ,Postmenstrual Age ,Infant ,Retinopathy of prematurity ,Exudative retinal detachment ,Infant, Low Birth Weight ,medicine.disease ,eye diseases ,medicine.anatomical_structure ,Gestation ,sense organs ,medicine.symptom ,business - Abstract
A male infant born at 23 weeks gestation with a birthweight of 660 grams presented with retinopathy of prematurity (ROP) that began progressing at 44 weeks. He subsequently developed Zone III, Stage 3, pre-plus disease in both eyes (OU), as well as scattered exudates in the macula, dragged vessels temporally, and an exudative retinal detachment temporally in the left eye after a period of regressing and stable ROP. After bilateral laser photocoagulation, there was regression of the neovascularization, resolution of the exudative detachment, and eventual stabilization of disease OU by 12 months postmenstrual age. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:403–406.]
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- 2021
29. Patients' preferences for treatment with the new direct acting antiviral therapies for chronic hepatitis C virus infection
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O Rojo, Pablo Ryan, and M A Simón
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Pediatrics ,medicine.medical_specialty ,Original ,diagnosis ,MEDLINE ,Hepacivirus ,Disease ,prioridad del paciente ,Antiviral Agents ,patients ,Therapy naive ,Health problems ,tratamiento ,pacientes ,Humans ,Medicine ,Dosing ,treatment ,business.industry ,General Medicine ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Patient preference ,diagnóstico ,Telephone interview ,hepatitis C ,Public aspects of medicine ,RA1-1270 ,business ,patient preference - Abstract
Objectives: The efficacy of new direct-acting antivirals (DAAs) in treating hepatitis C infection can depend on treatment adherence, which may be influenced by the patient's current lack of awareness of the disease. This study set out to understand the treatment naïve chronic hepatitis C patients' preferences for new DAAs (attributes) and to compile information about the diagnosis process. Material and method: Spanish quantitative market research study conducted between November 2018 and January 2019 to assess the posology preferences of treatment-naïve patients with chronic hepatitis C before starting treatment (seen by hepatologists and infectious diseases specialists). A telephone interview was carried out to collect demographic, diagnostic and treatment preference data, consisting of two dosing OPTIONS: 1) three tablets/day (single dose), at the same time, with food (8 weeks). 2) single tablet/day, at any time with/without food (12 weeks). A descriptive analysis of pooled results was performed. Results: 104 patients (mean age: 49 years) with hepatitis C diagnosed 7.3±9.7 years ago (average), mainly in primary care (PC) (42%). The most common reasons for not having started treatment were health problems/comorbidities (31%). Fifty-eight percent of patients were not informed about the available treatments. Seventy-two percent of patients preferred a simple tablet/day, at any time, with/without food (12 weeks), and considered compatibility with other treatments, side effects, ease of administration, treatment duration and the number of tablets to be very important. Discussion: Patient preferences are mainly driven by dosing flexibility and simplicity, including freedom to take the medication with/without food. The role of PC in the diagnosis should be taken into account. There are still patients who are untreated after diagnosis.
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- 2021
30. MET Amplification (MET/CEP7 Ratio ≥ 1.8) Is an Independent Poor Prognostic Marker in Patients With Treatment-naive Non–Small-cell Lung Cancer
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Melissa Robinson, Zhenya Tang, Wei Yin, Ming Guo, Gokce Altay Toruner, Shimin Hu, Joanne Cheng, L. Jeffrey Medeiros, and Guilin Tang
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Adult ,Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Multivariate analysis ,Gene Dosage ,Met amplification ,Cohort Studies ,Therapy naive ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,In patient ,Lung cancer ,In Situ Hybridization, Fluorescence ,Aged ,Aged, 80 and over ,Chromosome 7 (human) ,medicine.diagnostic_test ,business.industry ,Hazard ratio ,Gene Amplification ,Middle Aged ,Proto-Oncogene Proteins c-met ,Prognosis ,medicine.disease ,Survival Rate ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business ,Fluorescence in situ hybridization - Abstract
Introduction The MET pathway is a promising target in patients with non–small-cell lung cancer (NSCLC). Fluorescence in situ hybridization analysis has become a standard method to detect MET amplification. However, no consensus has been reached regarding the definition of MET amplification. We aimed to find clinically meaningful cutoffs for MET amplification that could be used as a prognostic marker and/or indication for MET inhibitor therapy. Patients and Methods We reviewed the fluorescence in situ hybridization results of MET/CEP7 (centromere of chromosome 7) for 2260 patients with treatment-naive NSCLC from 2014 to 2019. Clinical and pathologic data were collected from the medical records. Log-rank tests and Cox proportional hazard models were used to estimate the overall survival (OS) among patients with different MET/CEP7 ratios and/or MET copy numbers. Results Of the 2260 patients, 130 (5.8%) had had a MET/CEP7 ratio of ≥ 1.8 and 13 (0.6%) had had a ratio of ≥ 5.0. Of these 130 patients with a MET/CEP7 ratio of ≥ 1.8, 123 (95%) also had a MET copy number of ≥ 5. In general, a higher MET copy number and higher MET/CEP7 ratio were associated with advanced tumor stage. The OS was significantly shorter when the MET copy number was ≥ 10 and/or when the MET/CEP7 ratio was ≥ 1.8. A MET/CEP7 ratio of ≥ 1.8 remained a significant hazard to OS on multivariate analysis (hazard ratio, 1.63; P = .019). Conclusions Patients with a MET copy number of ≥ 10 and/or MET/CEP7 ratio of ≥ 1.8 showed significantly poorer survival, and a MET/CEP7 ratio of ≥ 1.8 was an independent poor prognostic factor.
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- 2021
31. Evaluation of adhesion molecules and immune parameters in HIV-infected patients treated with an atazanavir/ritonavir- compared with a lopinavir/ritonavir-based regimen.
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Squillace, Nicola, Trabattoni, Daria, Muscatello, Antonio, Sabbatini, Francesca, Maloberti, Alessandro, Giannattasio, Cristina, Masetti, Michela, Fenizia, Claudio, Soria, Alessandro, Clerici, Mario, Gori, Andrea, and Bandera, Alessandra
- Subjects
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CELL adhesion molecules , *HIV-positive persons , *ATAZANAVIR , *RITONAVIR , *LOPINAVIR-ritonavir , *HIV infection complications , *ATHEROSCLEROSIS , *CARDIOVASCULAR disease diagnosis , *COMPARATIVE studies , *EPITHELIAL cells , *HETEROCYCLIC compounds , *HIV infections , *IMMUNOLOGY technique , *LONGITUDINAL method , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *STATISTICAL sampling , *T cells , *EVALUATION research , *RANDOMIZED controlled trials , *HIGHLY active antiretroviral therapy , *ANTI-HIV agents , *CAROTID intima-media thickness - Abstract
Objectives: To evaluate changes in pro-atherosclerotic biomarkers and endothelial function in patients initiating two different PI-based regimens as part of ART.Design: Prospective randomized 24 week study. Treatment-naive HIV-infected patients with CD4+ T cell count >250 cells/mm3 started PI-based regimens including atazanavir/ritonavir (Group A) or lopinavir/ritonavir (Group B) and were followed up in an observational follow-up study until week 96.Methods: The expression of immune activation and adhesion molecules on CD4+ and CD8+ cells and plasma cytokine levels were assessed at weeks 0, 4, 12, 24, 48, 72 and 96. Flow-mediated dilation (FMD), pulse-wave velocity (PWV) and intima-media thickness (IMT) were measured at weeks 0 and 24. Median changes within (signed rank test) and between (Wilcoxon test) arms were calculated.Results: Twenty-seven patients were enrolled, of whom 15 were treated with atazanavir/ritonavir and 12 with lopinavir/ritonavir. After 96 weeks of ART, CD25+/CD8+ T cells and plasma concentration of MCP-1/CCL-2 rose whereas CD44+/CD8+ T cells decreased significantly in both groups. Differences between treatments were noted for HLA-DRII+/CD8+, CD44+/CD4+ and CD11a+/CD4+, with significant increases in Group B versus Group A. No differences between groups regarding IMT, PWV and FMD were found at baseline and week 24.Conclusions: ART initiation with PI-based regimens led to a decrease in pro-atherosclerotic biomarkers at week 24, which then rebounded at week 96. Lopinavir/ritonavir treatment resulted in an unfavourable modulation of such markers compared with atazanavir/ritonavir treatment. [ABSTRACT FROM AUTHOR]- Published
- 2018
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32. Pars Plana Vitrectomy with Internal Limiting Membrane Peeling for Treatment-Naïve Diabetic Macular Edema: A Prospective, Uncontrolled Pilot Study
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Ryan B. Rush and Sloan W Rush
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Pars plana ,medicine.medical_specialty ,Visual acuity ,genetic structures ,medicine.medical_treatment ,Diabetic macular edema ,vitrectomy ,Vitrectomy ,law.invention ,Therapy naive ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Ophthalmology ,medicine ,business.industry ,Internal limiting membrane ,Clinical Ophthalmology ,Diabetic retinopathy ,medicine.disease ,eye diseases ,medicine.anatomical_structure ,Clinical Trial Report ,internal limiting membrane peeling ,030221 ophthalmology & optometry ,sense organs ,medicine.symptom ,diabetic macular edema ,business ,030217 neurology & neurosurgery - Abstract
Ryan B Rush,1– 4 Sloan W Rush2,3 1Instituto de la Visión– Hospital La Carlota, Montemorelos, Nuevo León, 67530, México; 2Panhandle Eye Group, Amarillo, TX, 79106, USA; 3Department of Surgery, Texas Tech University Health Science Center, Amarillo, TX, 79106, USA; 4Southwest Retina Specialists, Amarillo, TX, 79106, USACorrespondence: Ryan B RushSouthwest Retina Specialists, 7411 Wallace Blvd, Amarillo, TX, 79106, USATel +1 806 351-1870Email ryan.rush.md@gmail.comPurpose: To report the outcomes in subjects undergoing pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for the management of treatment-naïve diabetic macular edema (DME).Methods: Ten treatment-naïve subjects with non-proliferative diabetic retinopathy prospectively underwent PPV with ILM peeling for the treatment of DME at a single university-affiliated institution. The preoperative features, intraoperative details and postoperative outcomes were collected and analyzed.Results: All 10 subjects underwent PPV with ILM peeling without significant intraoperative or postoperative complications at 6 months follow-up. Visual acuity improved from a baseline of 0.74 (95% CI: 0.48– 1.0) logMAR (Snellen 20/110) to 0.46 (95% CI: 0.3– 0.62) logMAR (Snellen 20/58) at 6 months follow-up (p=0.045). Optical coherence tomography central macular thickness reduced from a baseline of 456 (95% CI: 394.7– 516.4) microns to 316.8 (95% CI: 275.9– 357.7) microns at 6 months follow-up (p < 0.001).Conclusion: This pilot study suggests that PPV with ILM peeling may be a viable treatment option for the management of treatment naïve DME in subjects with non-proliferative diabetic retinopathy. Development of a randomized controlled trial may be justified to validate the results of this study.Clinicaltrials.gov Identifier #: NCT03660345.Keywords: vitrectomy, internal limiting membrane peeling, diabetic macular edema
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- 2021
33. A structural magnetic resonance imaging study in therapy-naïve transsexual individuals
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Branislav Filipović, Zoran Radojicic, Ana Starcevic, and Marko Dakovic
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medicine.medical_specialty ,Histology ,050109 social psychology ,Nucleus accumbens ,Grey matter ,Audiology ,Hippocampus ,Transgender Persons ,Structural magnetic resonance imaging ,Therapy naive ,0502 economics and business ,Transgender ,medicine ,Humans ,0501 psychology and cognitive sciences ,Segmentation ,Gray Matter ,10. No inequality ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Brain ,Magnetic resonance imaging ,Magnetic Resonance Imaging ,Transsexual ,medicine.anatomical_structure ,050211 marketing ,Anatomy ,business - Abstract
Background: Transsexuality is explained and defined as a gender-identity disorder, characterised by very strong conviction of belonging to the opposite sex and has been associated with a distinct neuroanatomical pattern. Materials and methods: We performed a structural analysis in search of possible differences in grey matter structures based on magnetic resonance imaging scans of the brains of 26 individuals between 19 and 38 years of age. The participants were divided into two groups of 15 controls and 11 transgender individuals. The segmentation of subcortical grey matter was performed using FIRST model a model-based segmentation/registration tool, from FSL software package. Results: The results showed that the volume of the brain region called nucleus accumbens on the left side was significantly smaller in the group of transgender individuals compared to the control. It was the most important parameter which was shown to make distinction between two examined groups. Conclusions: The results also showed decreased volumes of the left thalamus, right hippocampus and right caudate nucleus.
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- 2021
34. EASL‐ALEH 2015 algorithm for the use of transient elastography in treatment‐naive patients with hepatitis B: An independent validation
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Tarik Asselah, Jean Nana, Jean-Pierre Zarski, Nathalie Sturm, Vincent Leroy, Michael Adler, Jean Luc Bosson, and Kristina Skaare
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Liver Cirrhosis ,Biopsy ,Liver fibrosis ,Population ,Therapy naive ,03 medical and health sciences ,Hepatitis B, Chronic ,0302 clinical medicine ,Virology ,medicine ,Humans ,030212 general & internal medicine ,education ,Retrospective Studies ,education.field_of_study ,Hepatology ,medicine.diagnostic_test ,business.industry ,Fibrosis stage ,Hepatitis B ,medicine.disease ,Confidence interval ,Infectious Diseases ,Liver ,Liver biopsy ,Elasticity Imaging Techniques ,030211 gastroenterology & hepatology ,business ,Transient elastography ,Algorithm ,Algorithms - Abstract
Various non-invasive methods have been evaluated in chronic hepatitis B, but none of them have been fully validated for the assessment of liver fibrosis. The issued EASL-ALEH 2015 guidelines provide detailed algorithms based on LSM and ALT serum levels. The aim of our study was to validate the diagnostic accuracy of this algorithm and to better understand discrepancies. Four hundred and thirteen patients from 3 centres were retrospectively included. All included patients were classified for fibrosis stage according to results of a liver biopsy. The overall diagnostic value was expressed with AUROCs given with 95% confidence intervals for the diagnostic targets. For each diagnostic target, optimal cut-offs were determined according to the Youden method. For the population of patients with ALTN (n = 65), the AUROCs of TE were 0.75 (0.62-0.88) and 0.72 (0.56-0.88) for F ≥ 2 and F ≥ 3 diagnostic targets. Taking the EASL cut-offs, the prevalence of significant fibrosis was 8%, 38% and 67% when LSM was6kPa, between 6 and 9 kPa or9 kPa, respectively. For patients with ALTN but ≤5N (n = 306), AUROCs of transient elastography were 0.79 (0.73-0.84) and 0.84 (0.75-0.92) for F ≥ 2 and F ≥ 3 diagnostic targets. The prevalence of significant fibrosis was, respectively, 15%, 52% and 85% when LSM was6kPa, between 6 and 12 kPa or12 kPa. Our study independently validates the EASL-ALEH algorithm based on ALT levels and LSM assessed by transient elastography.
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- 2021
35. Prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients
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Charlotte Charpentier, Sidonie Lambert-Niclot, Marc Wirden, Karine Lacombe, Anne-Geneviève Marcelin, Valentine Marie Ferré, Alexandre Storto, Jade Ghosn, Romain Palich, Christine Katlama, Roland Landman, V Joly, Diane Descamps, Laurence Morand-Joubert, Vincent Calvez, and Cathia Soulié
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Anti-HIV Agents ,Pyridones ,Baseline risk ,HIV Infections ,Drug resistance ,Therapy naive ,chemistry.chemical_compound ,Cabotegravir ,Risk Factors ,Polymorphism (computer science) ,Internal medicine ,Drug Resistance, Viral ,Genotype ,Prevalence ,medicine ,Humans ,Pharmacology (medical) ,Pharmacology ,business.industry ,Rilpivirine ,Infectious Diseases ,chemistry ,HIV-1 ,Genotypic resistance ,business - Abstract
Background Multivariable baseline factor analysis across cabotegravir + rilpivirine clinical trials showed that HIV-1 subtypes A6/A1 and the presence of rilpivirine resistance-associated mutations (RAMs) were associated with an increased risk of virological failure of this dual therapy. The aim of this study was to describe the prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients. Patients and methods From 2010 to 2020, 4212 sequences from ARV-naive patients were collected from three large Parisian academic hospital genotypic databases. Cabotegravir and rilpivirine RAMs were defined according to the ANRS algorithm. Results Among 4212 ARV-naive patients, 38.6% were infected with subtype B, 32.4% with CRF02_AG (32.4%) and 5.1% with subtype A (85.5% being A6/A1 subtype). Overall, the presence of at least one cabotegravir or rilpivirine RAM was 16.2% and 14.3%, respectively. Considering genotypic resistance interpretation, using the ANRS algorithm, 0.74% (n = 31), 6.2% (n = 261) and 0.09% (n = 4) of sequences were resistant to cabotegravir, rilpivirine or both, respectively. The overall prevalence of L74I in integrase and E138A in RT was 13.0% and 3.2%, respectively, and stable over the decade. Thus, adding 183 subtype A6/A1 sequences to 244 sequences interpreted as resistant to rilpivirine led to 427 (10.1%) sequences combining both baseline virological risk factors for cabotegravir + rilpivirine dual-therapy failure. Conclusions Among large sequence databases, when adding prevalence of rilpivirine-resistant viruses and HIV-1 subtype A6/A1 sequences, 10.1% of patients would not be eligible for cabotegravir + rilpivirine dual therapy. These data re-emphasize the need for a pre-therapeutic genotypic resistance test to detect polymorphisms and transmitted drug resistance and to define HIV-1 subtype.
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- 2021
36. Efficacy of infliximab in treatment-naïve patients with stricturing small bowel Crohn’s disease
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Hong-bin Liu, Ze-min Han, Pei-chun Xu, Bing-xia Chen, Qian Zhou, and Fachao Zhi
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musculoskeletal diseases ,Crohn's disease ,medicine.medical_specialty ,Delayed Diagnosis ,business.industry ,Gastroenterology ,Constriction, Pathologic ,Disease ,medicine.disease ,Infliximab ,digestive system diseases ,Therapy naive ,stomatognathic diseases ,Treatment Outcome ,Crohn Disease ,immune system diseases ,Internal medicine ,medicine ,Humans ,skin and connective tissue diseases ,business ,Retrospective Studies ,medicine.drug - Abstract
The efficacy of infliximab in treatment-naïve patients with stricturing small bowel Crohn's disease (CD) has not been well studied. We aimed to evaluate the efficacy of infliximab in these patients.This was a retrospective study of all consecutive treatment-naïve patients with newly diagnosed CD with small bowel stricture who started regular infliximab therapy in Nanfang Hospital between January 2015 and December 2019. An effective infliximab therapy was defined as infliximab continuation without the use of steroids, new biologics, endoscopic interventions or intestinal surgery.Seventy-nine patients were included. After a median 38 months follow-up, an effective infliximab therapy was achieved in 37 patients. Long diagnostic delay (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.19-0.78;Infliximab is effective in nearly 50% of treatment-naïve patients with CD with small bowel stricture, and an effective therapy is more likely to be achieved in patients without long diagnostic delay, pre-stenotic dilatation, long segmental stricture or penetrating disease.
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- 2021
37. Étude des récidives exsudatives chez 42 yeux naïfs atteints de dégénérescence maculaire liée à l’âge suivis plus de 2 ans
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Olivier Lebreton, F. Bodénès, Michel Weber, and H. Masse
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Gynecology ,Therapy naive ,03 medical and health sciences ,Ophthalmology ,medicine.medical_specialty ,0302 clinical medicine ,business.industry ,Age related ,030221 ophthalmology & optometry ,medicine ,Anti vegf treatment ,business - Abstract
Resume Introduction L’objectif de l’etude a ete d’etudier la reproductibilite ou la variabilite des delais des recidives exsudatives chez des patients ayant recu un traitement par injections intra-vitreennes (IVT) d’anti-VEGF (ranibizumab, aflibercept) dans le cadre d’une degenerescence maculaire liee a l’âge (DMLA) de type exsudative. Les donnees etudiees ont ete le nombre de recidives annuelles, la duree ecoulee entre la recidive et la derniere IVT ainsi que la fluctuation dans le temps chez un meme patient, et les modifications de prise en charge therapeutique de ces recidives exsudatives concernant la realisation d’un nouveau traitement d’induction de trois IVT, d’un changement de protocole de suivi, et d’un changement de molecule anti-VEGF. Materiels et methodes Nous avons mene une etude retrospective de « vraie-vie », monocentrique au CHU de Nantes, concernant 33 patients (42 yeux) qui ont ete inclus entre mars 2012 et mars 2017. Il s’agissait de patients naifs d’IVT, chez lesquels un traitement par IVT d’anti-VEGF a ete initie dans le cadre de la prise en charge d’une DMLA exsudative, avec une duree de suivi d’au moins deux annees consecutives. Le critere de jugement principal etait la fluctuation des delais de recidives pour un meme patient. Resultats Sur les 33 patients inclus, 9 presentaient une atteinte bilaterale, soit un total de 42 yeux. Vingt etaient des femmes (60,6 %), l’âge median a l’inclusion etait de 78,5 ans pour une duree de suivi de 3,7 annees. Le delai de recidive moyen etait de 11,6 semaines apres la derniere IVT. La 1re recidive survenait dans un delai de 9,8 semaines apres la derniere IVT. 12,3 % des yeux presentaient des delais de recidives fixes avec fluctuations inferieures a 2 semaines entre les differentes recidives sur les deux annees de suivi. Un total de 7,1 % des yeux ne presentaient aucune recidive exsudative dans la suite du suivi. La premiere recidive exsudative avait lieu en moyenne a 38,2 semaines de suivi apres le diagnostic de la pathologie soit 37,2 semaines apres la premiere IVT. Un total de 14,3 % des recidives ont conduites a la realisation d’un nouveau traitement d’induction de trois IVT d’anti-VEGF, 8,6 % ont conduites a un changement de molecule anti-VEGF, et 7,1 % a une modification du schema de traitement. Discussion Cette etude avait pour but d’etudier la variabilite des delais de recidive exsudative chez les patients traites par IVT d’anti-VEGF dans le cadre d’une DMLA exsudative, car depuis l’avenement des IVT d’anti-VEGF en 2007, peu de donnees existent concernant le suivi a long terme et les fluctuations des delais de recidive, a propos de patients qui beneficieront d’un traitement durant plusieurs annees. Conclusion Les delais de recidives ne sont pas reproductibles au cours du temps, notamment chez les patients ayant realise leur premiere recidive exsudative au-dela de 8 semaines et chez les patients presentant de nombreuses recidives exsudatives.
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- 2021
38. Plasma Cytokine Levels As Predictors of Global and Domain-Specific Human Immunodeficiency Virus-Associated Neurocognitive Impairment in Treatment-Naive Individuals
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Graeme Brendon Jacobs, Soraya Seedat, Robert H. Paul, John A. Joska, Vurayai Ruhanya, George Nyandoro, Richard H. Glashoff, and Susan Engelbrecht
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Adult ,Male ,Adolescent ,medicine.medical_treatment ,Immunology ,Central nervous system ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,Domain (software engineering) ,Therapy naive ,South Africa ,Young Adult ,Memory ,Antiretroviral Therapy, Highly Active ,Virology ,Humans ,Medicine ,Cognitive Dysfunction ,Neuroinflammation ,business.industry ,Cell Biology ,Middle Aged ,Viral Load ,Prognosis ,CD4 Lymphocyte Count ,Cross-Sectional Studies ,medicine.anatomical_structure ,Cytokine ,Cytokines ,Female ,business ,Neurocognitive ,Biomarkers - Abstract
Central nervous system dysfunction, associated with human immunodeficiency virus (HIV) infection, remains a significant clinical concern, affecting at least 50% of infected people. Imbalances in cytokine expression levels have been linked to HIV-associated neurocognitive disorders. The aim of this study was to evaluate plasma cytokine levels as predictor neurocognitive impairment in HIV infection using a multiplex profiling kit. Stepwise regression model was used to identify cytokine biomarkers of overall and domain-specific cognitive performance. Higher interleukin (IL)-2 (
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- 2021
39. S770 Health-Related Quality of Life With Ustekinumab vs Adalimumab for Induction and Maintenance Therapy in Biologic-Naïve Patients With Moderate-To-Severe Crohn’s Disease: IBDQ in the SEAVUE Study
- Author
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Matthieu Allez, Christopher Gasink, Silvio Danese, Bruce E. Sands, Peter M. Irving, Zhijie Ding, Erik Muser, Remo Panaccione, Tony Ma, Edward V. Loftus, James L. Izanec, Timothy Hoops, and James D. Lewis
- Subjects
Moderate to severe ,Health related quality of life ,medicine.medical_specialty ,Crohn's disease ,Hepatology ,business.industry ,Gastroenterology ,medicine.disease ,Therapy naive ,Maintenance therapy ,Internal medicine ,Ustekinumab ,Adalimumab ,medicine ,business ,medicine.drug - Published
- 2021
40. Highlighting recent treatment advances in metastatic prostate cancer: expanding the treatment arsenal
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Theodore Stewart Gourdin
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Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Pyrimidinones ,Therapy naive ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,Clinical Trials, Phase II as Topic ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Metastasis ,Randomized Controlled Trials as Topic ,business.industry ,Phenylurea Compounds ,Prostatic Neoplasms ,Treatment options ,medicine.disease ,Androgen ,Immune therapy ,Prostatic Neoplasms, Castration-Resistant ,030104 developmental biology ,Clinical Trials, Phase III as Topic ,Docetaxel ,030220 oncology & carcinogenesis ,Radiopharmaceuticals ,Lhrh antagonist ,business ,medicine.drug - Abstract
Purpose of review Present highlights from recent research examining the treatment of advanced prostate cancer. Recent findings Although debate remains about the optimal sequencing of docetaxel and novel androgen directed therapies in addition to androgen deprivation therapy (ADT) in the treatment of men with new metastatic prostate cancer, the novel LHRH antagonist relugolix seems poised to become an appealing option in a choice of initial ADT. Novel radioisotopes, genomically selected therapies, and immune therapy combinations show progress in opening up new treatment options for men with castration-resistant prostate cancer. Summary Although no clear consensus has emerged, evolving data continue to refine the selection of systemic therapies in treatment naive metastatic prostate cancer. With potentially less cardiotoxic androgen deprivation therapies, novel radioisotopes, targeted pharmaceuticals, and immune therapy combinations, progress appears to be on the horizon in improving outcomes for men with advanced prostate cancer.
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- 2021
41. The Effect of Medical Lowering of Intraocular Pressure on Peripapillary and Macular Blood Flow as Measured by Optical Coherence Tomography Angiography in Treatment-naive Eyes
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Tin Aung, Eray Atalay, Ruthra M Umapathi, Chang Liu, Leopold Schmetterer, Pui Yi Boey, Rahat Husain, and Monisha E. Nongpiur
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medicine.medical_specialty ,Intraocular pressure ,genetic structures ,medicine.drug_class ,Glaucoma ,Therapy naive ,chemistry.chemical_compound ,Ophthalmology ,medicine ,Humans ,Fluorescein Angiography ,Latanoprost ,Intraocular Pressure ,business.industry ,Retinal Vessels ,Optical coherence tomography angiography ,Blood flow ,medicine.disease ,eye diseases ,chemistry ,Case-Control Studies ,Optic nerve ,sense organs ,Prostaglandin analogue ,business ,Tomography, Optical Coherence - Abstract
PRCIS Reduction of intraocular pressure (IOP) by latanoprost in treatment-naive eyes is significantly correlated to an increase in vessel density (VD) at the optic nerve head (ONH). PURPOSE To evaluate the effect of topical latanoprost on ocular microvasculature using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS In this prospective case-control study, 26 eyes from 18 treatment-naive subjects in whom prostaglandin analogue (PGA) latanoprost 0.005% was initiated were included as cases. In 10 out of the 18 subjects, medication was initiated in only 1 eye; their contralateral untreated eyes were used as controls. OCTA (AngioVue, Optovue Inc., Fremont, CA) was performed at baseline and ≥3 weeks after commencing treatment. Main outcome measures were change in flow area and VD at the ONH, radial peripapillary capillaries (RPC), and macula. Comparison between the 2 visits was performed using a linear mixed model adjusted for intereye correlation and mean ocular perfusion pressure. RESULTS IOP decreased by 26.1%±11.3% (P
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- 2021
42. Characteristics of treatment-naïve quiescent choroidal neovascularization detected by optical coherence tomography angiography in patients with age-related macular degeneration
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Tomohiro Iida, Akira Fukushima, Ichiro Maruko, Hisaya Arakawa, Kyoko Chujo, and Taiji Hasegawa
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Male ,medicine.medical_specialty ,Visual acuity ,genetic structures ,Visual Acuity ,Therapy naive ,Macular Degeneration ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Initial visit ,Ophthalmology ,Age related ,medicine ,Humans ,In patient ,Fluorescein Angiography ,030304 developmental biology ,0303 health sciences ,business.industry ,Optical coherence tomography angiography ,Macular degeneration ,medicine.disease ,Choroidal Neovascularization ,eye diseases ,Sensory Systems ,Choroidal neovascularization ,030221 ophthalmology & optometry ,Female ,sense organs ,medicine.symptom ,business ,Tomography, Optical Coherence - Abstract
To determine the characteristics of eyes with treatment-naive quiescent choroidal neovascularization (CNV) detected by optical coherence tomography angiography (OCTA). Thirty-eight eyes of 37 treatment-naive consecutive patients (30 men, 7 women, average 69.8 years) were studied. Quiescent CNVs were detected by OCTA (RTVue XR Avanti, Optovue, Fremont, CA) in all eyes. Swept-source OCT (SS-OCT; DRI-OCT, Topcon, Japan) confirmed the absence of exudation. The symptoms, visual acuity, CNV size, and status of the fellow eye were evaluated. Patients were followed longitudinally and the length of follow-up period and development of exudation were recorded for each patient. We also investigated patients’ medical records from their referral hospitals in search of prior exudation. All eyes with quiescent CNV were diagnosed at the initial visit with sub-retinal pigment epithelium CNVs, i.e., type 1 CNV, from the OCT and OCTA images. Prior exudation was confirmed in 15 eyes (39.5%) from their medical records of the referral hospitals. Symptoms were present in 18 eyes (47.3%). An exudative CNV was present in 12 of the fellow eyes. Exudation developed in 12 eyes (31.6%) during an average follow-up period of 25.1 months. One-half of the eyes had a prior exudation. The CNV at the baseline in eyes that developed exudation during the follow-up period was larger than eyes without exudation; however, the difference was not significant (0.59±0.47 vs 0.48±0.32 mm2, P = 0.50). Quiescent CNVs will develop exudation in approximately 30% of the eyes during a mean 2-year follow-up period. These findings must be remembered when investigating quiescent CNVs that could not be distinguished from eyes with former active CNV and naturally deactivate CNV.
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- 2021
43. Primary Tumor Radiotherapy During EGFR-TKI Disease Control Improves Survival of Treatment Naïve Advanced EGFR-Mutant Lung Adenocarcinoma Patients
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Jeng-Sen Tseng, Kuo-Hsuan Hsu, Jeremy J.W. Chen, Kuan-Wen Chen, Tsung-Ying Yang, Kun-Chieh Chen, Jing Wen Huang, Sung-Liang Yu, Yen Hsiang Huang, Gee-Chen Chang, and Yih Chyang Weng
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Gastroenterology ,OncoTargets and Therapy ,Therapy naive ,03 medical and health sciences ,0302 clinical medicine ,radiotherapy to primary lung tumor ,EGFR-TKI ,Internal medicine ,medicine ,Pharmacology (medical) ,Epidermal growth factor receptor ,Stage (cooking) ,polymetastasis ,Original Research ,Lung ,biology ,business.industry ,lung adenocarcinoma ,medicine.disease ,Primary tumor ,Radiation therapy ,oligometastasis ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,RTPLT ,030220 oncology & carcinogenesis ,biology.protein ,Adenocarcinoma ,business ,Brain metastasis - Abstract
Kuo-Hsuan Hsu,1,2,* Jing-Wen Huang,2,3,* Jeng-Sen Tseng,2,4,5 Kuan-Wen Chen,6 Yih-Chyang Weng,7 Sung-Liang Yu,8– 12 Tsung-Ying Yang,4,5 Yen-Hsiang Huang,2,4 Jeremy JW Chen,2 Kun-Chieh Chen,4,13– 15 Gee-Chen Chang2,4,5,13– 15 1Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Institute of Biomedical Sciences, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; 3Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan; 4Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 5Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 6Department of Radiation Oncology, Taichung Tzu-Chi Hospital, Buddhist Tzu-Chi Medical Foundation, Taichung, Taiwan; 7Radiation Oncology, Nantou Hospital of Ministry of Health and Welfare, Nantou City, Taiwan; 8Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; 9Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; 10Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; 11Department of Pathology and Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan; 12Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 13Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; 14Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 15School of Medicine, Chung Shan Medical University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Gee-Chen Chang; Kun-Chieh ChenDivision of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan, Republic of ChinaTel +886-4-24739595 ext. 34412Fax +886-4-24739595 #34710Email cshy1888@csh.org.tw; ckjohn@mail2000.com.twBackground: Whether radiotherapy only for primary lung tumor (RTPLT) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy improves survival of treatment naïve advanced EGFR-mutant lung adenocarcinoma (LAD) patients with/without polymetastasis.Materials and Methods: This was a retrospective, single-center, observational study. Patients with stage IIIB-IV EGFR-mutant LAD with disease control by EGFR-TKI therapy were divided into curative RTPLT, and control, without radiotherapy (WRTPLT) groups.Results: A total of 138 patients were enrolled; 46 in the RTPLT group and 92 in the WRTPLT group. Amongst them, 37% had oligometastasis, and 26.1% brain metastasis. The RTPLT group had both significantly longer progression-free survival (PFS) (27.5 months [95% CI 18.1– 36.9] vs 10.9 months [95% CI 6.3– 15.5], P< 0.001) and overall survivor (OS) (NR [95% CI NR-NR] vs 38.0 months [95% CI 31.2– 44.8], P< 0.001), respectively, when compared to the WRTPLT group. In multivariate analysis, the adjusted HR of radiotherapy on PFS was 0.30 (0.19– 0.47) and on OS, 0.11 (0.04– 0.30). Patients with oligometastasis had significantly longer PFS than those with polymetastasis with an HR of 0.35 (0.14– 0.85), P=0.02. Patients with either oligometastasis or polymetastasis had significant longer PFS when undergoing radiotherapy than those without (both P< 0.05). An EGFR-TKI to radiotherapy interval < 24 weeks seemed more beneficial (P=0.097). Radiation pneumonitis comprised 32 (69.6%), 12 (26.1%), and two (4.3%) cases of common terminology criteria grade I, II, and III, respectively.Conclusion: Curative RTPLT can prolong survival in patients with LAD following EGFR-TKI disease control, both involving oligometastasis and polymetastasis. RTPLT within 24 weeks after EGFR-TKI initiation appeared to be more beneficial with tolerable radiation pneumonitis.Keywords: radiotherapy to primary lung tumor, RTPLT, EGFR-TKI, lung adenocarcinoma, oligometastasis, polymetastasis
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- 2021
44. Real-World Study on Patient Satisfaction and Tolerability After Switching to Preservative-Free Latanoprost
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Carl Erb, Francisco J. Muñoz-Negrete, Milko E Iliev, and Ingeborg Stalmans
- Subjects
medicine.medical_specialty ,conjunctival hyperaemia ,patient satisfaction ,Glaucoma ,Therapy naive ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Patient satisfaction ,ocular surface disease ,Internal medicine ,Ophthalmology ,Epidemiology ,medicine ,Preservative free ,tolerability ,Latanoprost ,intra-ocular pressure ,Original Research ,Ocular surface disease ,business.industry ,preservative-free latanoprost ,Clinical Ophthalmology ,medicine.disease ,glaucoma ,tear substitutes ,Tolerability ,chemistry ,030221 ophthalmology & optometry ,prostaglandin ,business ,030217 neurology & neurosurgery - Abstract
Carl Erb,1 Ingeborg Stalmans,2 Milko Iliev,3 Francisco José Muñoz-Negrete4 1Eye Clinic Wittenbergplatz, Berlin, Germany; 2Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium; 3Ophthalmology Department, University of Bern, Inselspital, Bern, Switzerland; 4Servicio de Oftalmología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, IRYCIS, Madrid, EspañaCorrespondence: Francisco José Muñoz-NegreteServicio de Oftalmología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, IRYCIS, Madrid, EspañaTel +34 913 36 80 00Email franciscojmunoz@telefonica.netPurpose: Patient satisfaction is important in the treatment of glaucoma. Suboptimal compliance and impaired long-term outcome are a likely result of poor tolerability. The present multicentre, international, transverse, epidemiological survey was conducted to assess the satisfaction of patients who had received preservative-free latanoprost (PFL) for at least 3 months.Patients and Methods: A total of 1872 patients from 6 European countries, treated with PFL for at least 3 months, were included in this survey. Prior to PFL treatment, patients were to be treatment naïve or currently treated for their glaucoma. During a single routine consultation, patients completed a questionnaire concerning global satisfaction and satisfaction based on tolerability.Results: In total, 76.2% had been previously treated; 69.4% had received preserved and 6.8% preservative-free (PF) topical treatment. After 3 months of PFL treatment, a large majority of patients (95.3%) were satisfied or very satisfied with their PFL treatment and were, overall, significantly (p< 0.0001) more satisfied with PFL than with their previous treatment; 4.2% were either unsatisfied or very unsatisfied. Overall, 97.3% of originally treatment-naïve patients were satisfied (50.1%) or very satisfied (47.2%) with their PFL. Ocular surface disease was diagnosed in 9.2% of patients (n=173) and was mainly mild (76.9%). Patient satisfaction with PFL was very high.Conclusion: PFL may be considered a valuable first-choice treatment in glaucoma patients.Keywords: glaucoma, prostaglandin, preservative-free latanoprost, patient satisfaction, tolerability, tear substitutes, intra-ocular pressure, ocular surface disease, conjunctival hyperaemia
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- 2021
45. Nivolumab Plus Ipilimumab for Treatment-Naïve Metastatic Uveal Melanoma: An Open-Label, Multicenter, Phase II Trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402)
- Author
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Teresa Curiel, J.M. Piulats, Salvador Martín-Algarra, Montserrat Gomà, Miriam Redrado, Luis Merino, Alfonso Berrocal-Jaime, Mar Varela, Rafael López Castro, Lorenzo Alonso Carrión, Alfonso Calvo González, Enrique Espinosa, Delvys Rodriguez-Abreu, and Antonio Rullan
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Melanoma ,Ipilimumab ,medicine.disease ,Therapy naive ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,In patient ,Open label ,Nivolumab ,business ,Survival analysis ,medicine.drug - Abstract
PURPOSE This study aimed to assess the efficacy of the combination of nivolumab (nivo) plus ipilimumab (ipi) as a first-line therapy with respect to the 12-month overall survival (OS) in patients with metastatic uveal melanoma (MUM) who are not eligible for liver resection. METHODS This was a single-arm, phase II trial led by the Spanish Multidisciplinary Melanoma Group (GEM) on nivo plus ipi for systemic treatment-naïve patients of age > 18 years, with histologically confirmed MUM, Eastern Cooperative Oncology Group-PS 0/1, and confirmed progressive metastatic disease (M1). Nivo (1 mg/kg once every 3 weeks) and ipi (3 mg/kg once every 3 weeks) were administered during four inductions, followed by nivo (3 mg/kg once every 2 weeks) until progressive disease, toxicity, or withdrawal. The primary end point was 12-month OS. OS, progression-free survival (PFS), and overall response rate were evaluated every 6 weeks using RECIST (v1.1). Safety was also evaluated. Logistic regression and Cox proportional hazard models comprising relevant clinical factors were used to evaluate the potential association with response to treatment and survival. Cytokines were quantified in serum samples for their putative role in immune modulation/angiogenesis and/or earlier evidence of involvement in immunotherapy. RESULTS A total of 52 patients with a median age of 59 years (range, 26-84 years) were enrolled. Overall, 78.8%, 56%, and 32% of patients had liver M1, extra-liver M1, and elevated lactate dehydrogenase. Stable disease was the most common outcome (51.9%). The primary end point was 12-month OS, which was 51.9% (95% CI, 38.3 to 65.5). The median OS and PFS were 12.7 months and 3.0 months, respectively. PFS was influenced by higher LDH values. CONCLUSIONS Nivo plus ipi in the first-line setting for MUM showed a modest improvement in OS over historical benchmarks of chemotherapy, with a manageable toxicity profile.
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- 2021
46. Cost-effectiveness study of treatment with biologic disease-modifying antirheumatic drugs in adult patients with active ankylosing spondylitis
- Author
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R. O. Dreval
- Subjects
medicine.medical_specialty ,Immunology ,Therapy naive ,03 medical and health sciences ,Indirect costs ,0302 clinical medicine ,ixekizumab ,Rheumatology ,adalimumab ,Internal medicine ,ankylosing spondylitis ,Health care ,medicine ,Immunology and Allergy ,Pharmacology (medical) ,golimumab ,030203 arthritis & rheumatology ,business.industry ,secukinumab ,cost-effectiveness analysis ,Budget impact ,Cost-effectiveness analysis ,Reference drug ,Infliximab ,certolizumab pegol ,budget impact ,Medicine ,biologic disease-modifying antirheumatic drugs ,netakimab ,infliximab ,business ,Antirheumatic drugs ,etanercept ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Objective: to conduct a cost-effectiveness study of major biologic disease-modifying antirheumatic drugs (bDMARDs) used for the treatment of ankylosing spondylitis (AS) in Russian health care system with the focus on the new effective drug netakimab (NTK).Patients and methods. Based on the available meta-analysis, a Markov model for therapy was constructed using reference drugs. Then, based on the simulation results, a Cost-Effectiveness Analysis (CEA) and a Budget Impact Analysis (BIA) were carried out. The robustness of the result has been confirmed by several sensitivity analyzes.Results and discussion. NTK showed an advantage in CEA, including the cases when the direct costs of therapy were lower for the reference drug (which shows the greater efficacy of NTK). According to the BIA, the extension of NTK administration in naive patients was consistently associated with a decrease in the budgetary burden. Sensitivity analyzes confirmed the robustness of the result.Conclusion. NTK has clinical and economic advantage in the treatment of AS, it is attractive in terms of both patient's and health care benefit in general. More extensive use of NTK can save more than 5 billion RUB.
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- 2021
47. The Diagnostic Capability of Swept Source OCT Angiography in Treatment-Naive Exudative Neovascular Age-Related Macular Degeneration
- Author
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Katharina Krepler, Maximilian Gabriel, Stefan Kickinger, Alexandra Graf, Martin Stattin, Siamak Ansari-Shahrezaei, Anna-Maria Haas, and Daniel Ahmed
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medicine.medical_specialty ,Retina ,Retinal pigment epithelium ,Visual acuity ,Article Subject ,genetic structures ,medicine.diagnostic_test ,business.industry ,RE1-994 ,Macular degeneration ,medicine.disease ,eye diseases ,Therapy naive ,Neovascularization ,Ophthalmology ,Oct angiography ,medicine.anatomical_structure ,Angiography ,Medicine ,sense organs ,medicine.symptom ,business ,Research Article - Abstract
Purpose. To evaluate the capability of swept source-optical coherence tomography angiography (SS-OCTA) in the detection and localization of treatment-naive macular neovascularization (MNV) secondary to exudative neovascular age-related macular degeneration (nAMD). Methods. In this prospective, observational case series, 158 eyes of 142 patients were diagnosed with exudative nAMD using fluorescein (FA) and indocyanine green angiography (ICGA) and evaluated by SS-OCTA in a tertiary retina center (Rudolf Foundation Hospital Vienna, Austria). The main outcome measure was the sensitivity of SS-OCTA compared to the standard multimodal imaging approach. Secondary outcome measure was the anatomic analysis of MNV in relation to the retinal pigment epithelium. Results. En-face SS-OCTA confirmed a MNV in 126 eyes (sensitivity: 79.8%), leaving 32 eyes (20.2%) undetected. In 23 of these 32 eyes (71.9%), abnormal flow in cross-sectional SS-OCTA B-scans was identified, giving an overall SS-OCTA sensitivity of 94.3%. Eyes with a pigment epithelium detachment (PED) ≥ 300 μm had a smaller probability for correct MNV detection ( p = 0.015 ). Type 1 MNV showed a trend ( p = 0.051 ) towards smaller probability for the correct detection compared to all other subtypes. Other relevant factors for the nondetection of MNV in SS-OCTA were image artifacts present in 3 of 32 eyes (9.4%). SS-OCTA confirmed the anatomic localization of 93 in 126 MNVs as compared to FA (sensitivity: 73.8%). There was no influence of age, gender, pseudophakia, visual acuity, central foveal thickness, or subfoveal choroidal thickness on the detection rate of MNV. Conclusions. SS-OCTA remains inferior to dye-based angiography in the detection rate of exudative nAMD consistent with type 1 MNV and a PED ≥300 µm. The capability to combine imaging modalities and distinguish the respective MNV subtype improves its diagnostic value.
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- 2021
48. Abstract PS17-47: Treatment naïve patient-derived xenograft model compared to the post-neoadjuvant model from the same patient diagnosed with triple negative breast cancer
- Author
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Khoa Nguyen, Steven G. Elliott, Matthew E. Burow, Bridgette M. Collins-Burow, Margarite D. Matossian, Maryl K. Wright, and Gabrielle O. Windsor
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Oncology ,Therapy naive ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,business ,Tumor xenograft ,Triple-negative breast cancer - Abstract
Triple negative breast cancer (TNBC) is an aggressive and difficult-to-treat subtype of breast cancer that typically exhibits rapid growth rates, high rates of metastasis, and resistance to commonly used oncological drugs. Historically, cell lines have been utilized in order to study TNBC; recently, however, patient derived xenografts (PDX) models have evolved as the new standard that offers a translational approach to the research and subsequent treatment of breast cancer. Here, we characterize two novel PDX models for TNBC: TU-BcX-4QA and TU-BcX-4QAN. The former derived from a biopsy specimen prior to any therapies, and the latter derived from a mastectomy of the same patient after three rounds of AC-T therapy (doxorubicin and cyclophosphamide followed by paclitaxel). In establishing a treatment naïve and post-neoadjuvant therapy PDX model pair, we created a prime model that examines the effects of chemotherapy on tumor heterogeneity, clonal selection, and the overall characteristics of a tumor. Furthermore, we examined the evolution of the characteristics of the post-neoadjuvant therapy PDX model after continual passaging within the SCID/Beige murine models. Through serial implantation in SCID/Beige murine models for tissue propagation, we observed that TU-BcX-4QAN consistently had a higher tumor growth rate and a smaller number of metastatic lesions that developed on the lungs and liver in comparison to the TU-BcX-4QA model. In treating the tumor derived cell lines with NCI-approved oncological drugs, we distinguished the variations in their responses to various, commonly used therapies, and determined that TU-BcX-4QAN had a more resistant profile. Using qRT-PCR, we further discovered the differences between the two models in their contrasting gene expression; preliminary data indicates an increase in certain mesenchymal genes (CDH2, VIM, and ZEB2), a decrease in cell cycle genes (p21, p53), and an increase in proliferation genes (MK167) in TU-BcX-4QAN compared to TU-BcX-4QA. Additionally, serial passages are correlated with a decrease trend in human gene expression within TU-BcX-4QAN. This suggest that treatment can select for certain cancer cells within the primary tumor that allows for the growth of a different tumor altogether and illustrates both the advantages and limitations of the TU-BcX-4QA andTU-BcX-4QAN model pair in translational research. Citation Format: Gabrielle Olivia Windsor, Margarite Matossian, Maryl Wright, Steven Elliott, Khoa Nguyen, Bridgette Collins-Burow, Matthew Burow. Treatment naïve patient-derived xenograft model compared to the post-neoadjuvant model from the same patient diagnosed with triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-47.
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- 2021
49. Can Zonulin level be a new diagnosis and follow-up criterion in active ulcerative colitis?
- Author
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Enver Akbaş and Gözde Ülfer
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Significant difference ,Zonulin ,Inflammatory Bowel Diseases ,Colonoscopy ,medicine.disease ,Ulcerative colitis ,Gastroenterology ,New diagnosis ,Therapy naive ,Internal medicine ,medicine ,In patient ,business - Abstract
Objective: In this study, we compared the serum zonulin levels in patients diagnosed for the first time with active ulcerative colitis with those in healthy cases and attempted to determine whether serum zonulin levels were different in the active ulcerative colitis. Material and Methods: A total of 53 naive patients admitted to our hospital between 2019 and 2020 and diagnosed with active ulcerative colitis by colonoscopy were included as a group of cases and 37 patients with no acute or chronic diseases whose colonoscopy was normal as the control group. Results: The study was conducted on 90 cases, 65.5% male and 34.5% female. The patients with ulcerative colitis were compared with the control group in terms of serum zonulin levels. Average serum zonulin levels of the patients with ulcerative colitis (16.73 ± 5.49 ng/ml) were not significantly different than those in the control group 17.48 ± 8.31 ng/ml). Serum zonulin levels of the patients were also compared according to location and severity of disease and did not differ statistically significantly between the groups in terms of the Montreal Classification. When serum zonulin levels were grouped according to the Truelove and Witts criteria, there was no statistically significant difference between the patient groups themselves and the control group. Conclusion: Serum zonulin levels were not greater in the patients with naive active ulcerative colitis compared to the healthy controls. Several previous studies have shown that serum zonulin levels are elevated in patients with ulcerative colitis, but more studies are needed on this subject.
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- 2021
50. Treatment-naïve quiescent macular neovascularization secondary to AMD: The 2019 Young Investigator Lecture of Macula Society
- Author
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Giuseppe Querques, Riccardo Sacconi, Eric H Souied, Alexandra Miere, Lea Querques, Donato Colantuono, Adriano Carnevali, Vittorio Capuano, Eliana Costanzo, Francesco Bandello, Marco Battista, Mariacristina Parravano, and Enrico Borrelli
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0301 basic medicine ,medicine.medical_specialty ,Therapy naive ,Neovascularization ,03 medical and health sciences ,0302 clinical medicine ,Ophthalmology ,medicine ,Humans ,Macula Lutea ,Longitudinal Studies ,Fluorescein Angiography ,Aged ,Retrospective Studies ,Aged, 80 and over ,Retina ,business.industry ,Macular disease ,General Medicine ,Uvea ,Choroidal Neovascularization ,030104 developmental biology ,medicine.anatomical_structure ,Wet Macular Degeneration ,030221 ophthalmology & optometry ,medicine.symptom ,business ,Tomography, Optical Coherence - Abstract
Purpose: To analyze different clinical and anatomical features in treatment-naïve non-exudative macular neovascularizations (MNVs) secondary to age-related macular disease (AMD). Methods: In this retrospective longitudinal study with a minimum follow-up of 1 year, 31 eyes of 28 consecutive AMD patients (mean age 75 ± 9 years) with treatment-naïve non-exudative MNV were enrolled. Patients were divided in: short-term activated MNV group (exudation before 6-month) and quiescent MNV group (per definition no exudation during a minimum 6-month follow-up) showing no or late activation during follow-up (persistently quiescent and long-term activated MNV group, respectively). Results: During the follow-up (mean duration: 22 ± 9 months) four eyes (13%) showed exudation before 6-month follow-up (short-term activated MNV group), whereas 21 eyes (68%) did not develop signs of exudation (persistently quiescent group), and six eyes (19%) developed exudation after the minimum 6-month follow-up (long-term activated MNV group). Monthly MNV growth rate was significantly higher in the short-term activated MNV group (growth rate of 13.30%/month), vs persistently quiescent MNV group (0.64%/month, p Conclusion: We reported two different patterns for subclinical MNVs: subclinical MNVs characterized by short-term activation which could represent simply a pre-exudative stage in the development of an ordinary type 1 MNV, and quiescent MNVs characterized by low rate of growth and possible long-term activation. Analysis of OCT-A features may predict short-term activation for subclinical MNV but no features could predict the long-term activation.
- Published
- 2021
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