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Background: Attention deficit hyperactive disorder (ADHD) is a neurodevelopmental disorder occurring in children and adults. Pharmacotherapy remains the cornerstone of ADHD treatment. Stimulants such as methylphenidate are effective and have been one of the best studied and most frequently used treatment for ADHD. However, different delivery mechanisms and devices may potentially impact patient experience and real-life outcomes. Aim: This study evaluated the effectiveness of Multiple-Unit Pellet System Delivered Extended-Release Methylphenidate (Contramyl XR) on symptom control and reported outcomes in ADHD patients, in a real-world setting. Setting: A phase IV, open label, flexible dose, prospective, observational study conducted at six sites covering five provinces of South Africa. Methods: About 119 participants with ADHD (both newly diagnosed [treatment-naïve] and methylphenidate-treated [switch-over] patients) were enrolled and initiated either on Contramyl XR or switched over from methylphenidate to Contramyl XR. Primary efficacy was assessed by Weiss Functional Impairment Rating Scale (WFIRS) over 12 weeks. Results: In all, 117 participants completed the study (treatment-naïve patients: 46% [n = 55] and switch-over patients: 54% [n = 64]). Mean change from baseline in total WFIRS (95% confidence interval) was –17.7 (–21.1, –14.3; p 0.001) at week 4 and –29.3 (–33.5, –25.2; p 0.001) at week 12. At week 12, there was significant improvement in WFIRS scores, with treatment satisfaction reported by treatment-naïve patients. Switch-over patients also demonstrated comparable effectiveness. Conclusion: Contramyl XR was found to be clinically effective either as de novo or as switch therapy. It was well tolerated, and all patients chose to continue with the treatment option. Contribution: Despite distinct and different delivery mechanism of Contramyl XR, this study provides evidence for using it as an alternate treatment option versus reference methylphenidate, in both treatment-naïve and switch-over ADHD patients. Study participants willingness to continue Contramyl XR therapy post study, further strengthens the confidence on the effectiveness of Contramyl XR in managing ADHD patients.

Objective The incidence of type 2 diabetes mellitus (T2DM) has risen dramatically. Among people living with HIV (PLHIV), chronic disease (now >15 cases/1000 in the general population worldwide) and long-term exposure to antiretroviral therapy (ART) can alter metabolic processes early, favoring insulin resistance and T2DM. We retrospectively studied the incidence of T2DM and associated factors in the Cohort of the Spanish AIDS Research Network, a prospective cohort of PLHIV enrolled at diagnosis and before initiation of ART. Methods PLHIV were aged >18 years and ART naive at inclusion. The incidence of new diagnoses of T2DM after initiation of ART (per 1000 person-years) was calculated. Predictors of a diagnosis of T2DM were identified by a Cox proportional hazards model adjusted for statistically significant and clinically relevant variables. Results Cumulative incidence was 5.9 (95% CI, 5.1–6.7) per 1000 person-years, increasing significantly in persons aged >50 years to 14.4 (95% CI, 10.4–19.3). Median time to diagnosis of T2DM was 27 months. Only age and higher education were significant. Interestingly, higher education was associated with a 33% reduction in the incidence of T2DM. Having received tenofovir disoproxil fumarate + (lamivudine or emtricitabine) + rilpivirine was almost significant as a protective factor (hazard ratio, 0.49; 95% CI,.24–1.01; P =.05). Conclusions The incidence of T2DM in PLHIV in Spain was high, especially in persons aged >50 years. Age was the factor most closely associated with onset, and educational level was the factor most associated with reduced risk. We highlight the lack of association between HIV-related factors and T2DM and show that, within nonnucleoside reverse transcriptase inhibitors, rilpivirine could prove more benign for metabolic comorbidities. [ABSTRACT FROM AUTHOR]

Abstract Introduction Dolutegravir (DTG)-based regimen was included in the expanded formulary of China's National Free Antiretroviral Treatment Program at the end of 2021. Yet high price of DTG and lack of health economic evaluation in China present barriers for implementation of the regimen. The study aims to investigate the lifetime cost-effectiveness of DTG-based regimen for treatment-naive HIV infection in China. Methods A decision-analytic Markov model was used to obtain the costs and effectiveness of four regimens: Arm A, efavirenz (EFV)-based regimen; Arm B, DTG-based regimen; Arm C, elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (EVG/c/FTC/TAF) regimen; Arm D, abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) regimen. The potential impact of national centralized drug procurement policy was assessed in scenario analysis. The results were further validated through sensitivity analysis. Results Compared with other three regimens, DTG-based regimen led to the fewest cumulative adverse reactions, opportunistic infections and deaths. Compared with EFV-based regimen, the base-case ICERs for DTG-based regimen were 13,357 (USD/QALY) and 13,424 (USD/QALY) from the healthcare system and societal perspective respectively. In the policy scenario analysis with the procurement price of DTG equal to that of LPV/r, DTG-based regimen would be dominant. The model results remained robust in sensitivity analyses. Conclusions DTG-based regimen for treatment-naive patients is likely to be cost-effective and deserve wider implementation in China. This study strongly suggests the centralized procurement of DTG to minimize cost and maximize cost-effectiveness.

Introduction: Dolutegravir (DTG)-based regimen was included in the expanded formulary of China's National Free Antiretroviral Treatment Program at the end of 2021. Yet high price of DTG and lack of health economic evaluation in China present barriers for implementation of the regimen. The study aims to investigate the lifetime cost-effectiveness of DTG-based regimen for treatment-naive HIV infection in China. Methods: A decision-analytic Markov model was used to obtain the costs and effectiveness of four regimens: Arm A, efavirenz (EFV)-based regimen; Arm B, DTG-based regimen; Arm C, elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (EVG/c/FTC/TAF) regimen; Arm D, abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) regimen. The potential impact of national centralized drug procurement policy was assessed in scenario analysis. The results were further validated through sensitivity analysis. Results: Compared with other three regimens, DTG-based regimen led to the fewest cumulative adverse reactions, opportunistic infections and deaths. Compared with EFV-based regimen, the base-case ICERs for DTG-based regimen were 13,357 (USD/QALY) and 13,424 (USD/QALY) from the healthcare system and societal perspective respectively. In the policy scenario analysis with the procurement price of DTG equal to that of LPV/r, DTG-based regimen would be dominant. The model results remained robust in sensitivity analyses. Conclusions: DTG-based regimen for treatment-naive patients is likely to be cost-effective and deserve wider implementation in China. This study strongly suggests the centralized procurement of DTG to minimize cost and maximize cost-effectiveness. [ABSTRACT FROM AUTHOR]

Abstract Introduction The EXPEDITION-8 clinical trial has demonstrated that treatment-naïve patients with compensated cirrhosis (TN/CC) of HCV genotypes 1–6 can achieve a 98% intent-to-treat sustained virologic response rate 12 weeks post-treatment with an 8-week glecaprevir/pibrentasvir (G/P) regimen. Further real-world evidence is needed to support the effectiveness of 8-week G/P in a clinical practice setting and to consolidate these treatment recommendations. The aim of this study is to contribute real-world evidence for the effectiveness of an 8-week G/P treatment in TN/CC patients with HCV genotypes 1–6. Methods Retrospective real-world data from 494 TN/CC patients with HCV genotypes 1–6 were collected between August 2017 to December 2020 from the Symphony Health Solutions administrative claims database. Demographic and clinical characteristics were collected at baseline. Patients were required to have a follow-up HCV ribonucleic acid level at least 8 weeks or more after the end of treatment. The percentage of patients achieving a sustained virologic response (SVR) is reported. Results The majority of patients were male (58%) and Caucasian (40%), with a mean age of 58 years; 74%, 12%, 12%, and 1% of patients were HCV genotype 1, 2, 3, and 4–6 infected, respectively. SVR was achieved in 95.5% of all patients. Across patient subgroups, SVR was achieved in 95.6% of patients with HCV genotype 3 and in 93% of HCV patients with a recent diagnosis of illicit drug use or abuse (within 6 months prior to G/P initiation). Conclusion Early real-world evidence indicates high effectiveness of the 8-week G/P regimen in TN/CC patients of HCV genotypes 1–6 from a large US claims database.

ABSTRACT: Objectives: In Eastern Europe, HIV-1 transmitted drug resistance (TDR) data, especially in the integrase (IN) region, are limited. In Estonia, INSTI (integrase strand transfer inhibitors) TDR has been studied only prior to the INSTI scale-up in late 2010s. The current study aimed to determine the levels of protease (PR), reverse transcriptase (RT) and IN surveillance drug resistance mutations (SDRMs) among newly diagnosed patients in Estonia in 2017. Methods: The study included 216 newly diagnosed HIV-1 individuals from 1 January until 31 December 2017 in Estonia. Demographic and clinical data were obtained from the Estonian Health Board, the Estonian HIV Cohort Study (E-HIV) and clinical laboratories’ databases. The PR-RT and IN regions were sequenced and analysed for SDRMs and subtype determination. Results: Seventy-one percent (151/213) of available HIV-positive samples were successfully sequenced. The overall level of TDR was 7.9% (12/151; 95% CI 4.4%–13.8%); no dual or triple class resistance was detected. No major INSTI mutations were found. The distribution of SDRMs for NNRTI, NRTI and PI was 5.9% (9/151), 1.3% (2/151) and 0.7% (1/151), respectively. The predominant NNRTI mutation was K103N. CRF06_cpx was the predominant variant (59%) in the Estonian HIV-1 population, followed by subtype A (9%) and subtype B (8%). Conclusion: Although no major INSTI mutations were found, close monitoring of INSTI SDRMs is needed considering the extensive use of the first- and second-generation INSTIs. PR-RT TDR is slowly rising in Estonia, indicating the need for continuous surveillance in the future. Low genetic barrier NNRTIs should be avoided in the treatment regimens.

Introduction: The EXPEDITION-8 clinical trial has demonstrated that treatment-naïve patients with compensated cirrhosis (TN/CC) of HCV genotypes 1–6 can achieve a 98% intent-to-treat sustained virologic response rate 12 weeks post-treatment with an 8-week glecaprevir/pibrentasvir (G/P) regimen. Further real-world evidence is needed to support the effectiveness of 8-week G/P in a clinical practice setting and to consolidate these treatment recommendations. The aim of this study is to contribute real-world evidence for the effectiveness of an 8-week G/P treatment in TN/CC patients with HCV genotypes 1–6. Methods: Retrospective real-world data from 494 TN/CC patients with HCV genotypes 1–6 were collected between August 2017 to December 2020 from the Symphony Health Solutions administrative claims database. Demographic and clinical characteristics were collected at baseline. Patients were required to have a follow-up HCV ribonucleic acid level at least 8 weeks or more after the end of treatment. The percentage of patients achieving a sustained virologic response (SVR) is reported. Results: The majority of patients were male (58%) and Caucasian (40%), with a mean age of 58 years; 74%, 12%, 12%, and 1% of patients were HCV genotype 1, 2, 3, and 4–6 infected, respectively. SVR was achieved in 95.5% of all patients. Across patient subgroups, SVR was achieved in 95.6% of patients with HCV genotype 3 and in 93% of HCV patients with a recent diagnosis of illicit drug use or abuse (within 6 months prior to G/P initiation). Conclusion: Early real-world evidence indicates high effectiveness of the 8-week G/P regimen in TN/CC patients of HCV genotypes 1–6 from a large US claims database. [ABSTRACT FROM AUTHOR]

Treatment guidelines recommend integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimens for treatment naïve people living with HIV (PLWH) in the United States (US). This retrospective database study compared weight changes following initiation of INSTI-, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based ART in treatment-naïve PLWH. Adult (≥18 years) PLWH initiated on INSTI, NNRTI, or PI plus ≥2 nucleoside reverse transcriptase inhibitors (NRTI) between 1 January 2014 to 31 August 2019 were identified in IQVIA's Ambulatory Electronic Medical Records (AEMR) linked to prescription drug claims (LRx). Weight changes over up to 36 months (M) of follow-up were compared among PLWH on INSTI- vs. NNRTI- and PI-based ART separately using non-linear mixed effect models, adjusting for demographics and baseline clinical characteristics. The INSTI, NNRTI, and PI cohorts included 931, 245, and 124 PLWH, respectively. For all three cohorts, the majority were male (78.2–81.2%) and overweight/obese (53.6–61.6%) at baseline; 40.8–45.2% of the groups were African American. The INSTI vs. NNRTI/PI cohorts were younger (median age: 38 years vs. 44 years/46 years), had lower weight at ART initiation (mean: 80.9 kg vs. 85.7 kg/85.0 kg), and had higher TAF usage during follow-up (55.6% vs. 24.1%/25.8%; all p <.05). Multivariate models showed higher weight gain among PLWH in INSTI vs. NNRTI and PI cohorts during treated follow-up (estimated weight gain after 36 M: 7.1 kg vs. 3.8 kg and 3.8 kg, both p <.05). Study findings highlight the need to monitor an increase in weight and potential metabolic complications among PLWH starting ART with INSTI. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the morphological macular changes and fluid dynamics under brolucizumab treatment in eyes refractory to previous anti–vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD) compared with treatment-naive eyes. Methods: Retrospective study of all eyes treated with brolucizumab for nAMD between 2020 and 2021 with a fixed injection regimen and one year follow-up. Treatment-naive eyes (TN) were compared with eyes refractory to previous treatment with bevacizumab, ranibizumab, or aflibercept (RT). The primary outcome measure was change of best-corrected visual acuity (BCVA). Secondary outcome measures included foveal central thickness (FCT), presence of intra- or subretinal fluid (IRF, SRF) and presence of pigment epithelial detachment (PED) at any time point during treatment in both groups. Results: Seventeen TN eyes and 17 RT eyes were included. Mean BCVA and mean FCT in TN eyes had significantly improved after 3 months and continued to improve during treatment (p< 0.05 and p=0.001, respectively). In RT eyes, mean BCVA did not change significantly while mean FCT had improved after 3 months of treatment and remained stable thereafter. SRF or PED were more frequent in RT eyes compared with TN eyes (p=0.003 and p=0.005, respectively). Conclusion: After 3 months of treatment, the BCVA increased significantly only in TN eyes, while the FCT was significantly reduced in both groups. IRF appears to be similarly seen in both groups after the loading phase; however, SRF and PED appear to be more frequent in the RT eyes compared with TN eyes. [ABSTRACT FROM AUTHOR]

Isaac Kofi Owusu,1 Yaw Amo Wiafe,2 Stephen Opoku,2 Enoch Odame Anto,2 Emmanuel Acheamfour-Akowuah1 1Department of Medicine, School of Medicine and Dentistry, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; 2Department of Medical Diagnostics, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaCorrespondence: Isaac Kofi Owusu, Email ikeowusu@yahoo.comPurpose: This study determined electrocardiographic and echocardiographic abnormalities of people living with HIV (PLWHIV); comparing the findings of PLWHIV on HAART versus treatment naïve groups.Patients and Methods: In a prospective cross-sectional study, we recruited 157 PLWHIV on Highly Active Antiretroviral Therapy (HAART) and 28 HAART naïve PLWHIV. Clinical examination, electrocardiography and echocardiography were performed on study participants at the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. Sociodemographic data and information about the use of HAART or otherwise was obtained. The Chi and Fisher Exact tests were used to find the significance of difference in proportions of abnormalities between PLWHIV on HAART and treatment naïve groups. Statistical analyses were performed on SPSS version 25.0 and GraphPad Prism version 8.0. P-values less than 0.05 were considered to be statistically significant.Results: Echocardiographic abnormalities in the HAART and treatment naïve groups were 54.1% and 60.7%, respectively. Electrographic abnormalities in the HAART and treatment naïve groups were 45.9% and 50%, respectively. Sinus bradycardia was the most prevalent ECG abnormality in the treatment naïve. Nonspecific T-wave changes (36.1%) and sinus tachycardia (30.6%) were the most common ECG abnormalities seen in HAART treated group. The common echocardiographic abnormalities were pulmonary hypertension (22.7%), pericardial effusion (22.2%) and left ventricular systolic dysfunction (17.8%). There was no significant difference in the proportions of echocardiographic abnormalities between PLWHIV on HAART and the treatment naïve groups (p > 0.05).Conclusion: Cardiac abnormalities are common in PLWHIV regardless of treatment with HAART. Echocardiographic and electrographic assessments are highly recommended for all PLWHIV.Keywords: Ghana, echocardiographic abnormalities, electrocardiographic abnormalities, HIV, treatment naïve

Integrase strand transfer inhibitors (INSTIs) have improved the treatment of human immunodeficiency virus (HIV). There are currently four approved for use in treatment-naïve individuals living with HIV; these include first generation raltegravir, elvitegravir, and second generation dolutegravir and bictegravir. The most recent INSTI, cabotegravir, is approved for (1) treatment of HIV infection in adults to replace current antiretroviral therapy in individuals who maintain virologic suppression on a stable antiretroviral regimen without history of treatment failure and no known resistance to its components and (2) pre-exposure prophylaxis in individuals at risk of acquiring HIV-1 infection. Cabotegravir can be administered intramuscularly as a monthly or bi-monthly injection depending on the indication. This long-acting combination has been associated with treatment satisfaction in clinical studies and may be helpful for individuals who have difficulty taking daily oral medications. Worldwide, second generation INSTIs are preferred for treatment-naïve individuals. Advantages of these INSTIs include their high genetic barrier to resistance, limited drug-drug interactions, excellent rates of virologic suppression, and favorable tolerability. Few INSTI resistance-associated mutations have been reported in clinical trials involving dolutegravir, bictegravir and cabotegravir. Other advantages of specific INSTIs include their use in various populations such as infants and children, acute HIV infection, and individuals of childbearing potential. The most common adverse events observed in clinical studies involving INSTIs included diarrhea, nausea, insomnia, fatigue, and headache, with very low rates of treatment discontinuation versus comparator groups. The long-term clinical implications of weight gain associated with second generation INSTIs dolutegravir and bictegravir warrants further study. This review summarizes key clinical considerations of INSTIs in terms of clinical pharmacology, drug-drug interactions, resistance, and provides perspective on clinical decision-making. Additionally, we summarize major clinical trials evaluating the efficacy and safety of INSTIs in treatment-naïve patients living with HIV as well as individuals at risk of acquiring HIV infection. [ABSTRACT FROM AUTHOR]

Background: Attention deficit hyperactive disorder (ADHD) is a neurodevelopmental disorder occurring in children and adults. Pharmacotherapy remains the cornerstone of ADHD treatment. Stimulants such as methylphenidate are effective and have been one of the best studied and most frequently used treatment for ADHD. However, different delivery mechanisms and devices may potentially impact patient experience and real-life outcomes., Aim: This study evaluated the effectiveness of Multiple-Unit Pellet System Delivered Extended-Release Methylphenidate (Contramyl XR) on symptom control and reported outcomes in ADHD patients, in a real-world setting., Setting: A phase IV, open label, flexible dose, prospective, observational study conducted at six sites covering five provinces of South Africa., Methods: About 119 participants with ADHD (both newly diagnosed [treatment-naïve] and methylphenidate-treated [switch-over] patients) were enrolled and initiated either on Contramyl XR or switched over from methylphenidate to Contramyl XR. Primary efficacy was assessed by Weiss Functional Impairment Rating Scale (WFIRS) over 12 weeks., Results: In all, 117 participants completed the study (treatment-naïve patients: 46% [ n = 55] and switch-over patients: 54% [ n = 64]). Mean change from baseline in total WFIRS (95% confidence interval) was -17.7 (-21.1, -14.3; p < 0.001) at week 4 and -29.3 (-33.5, -25.2; p < 0.001) at week 12. At week 12, there was significant improvement in WFIRS scores, with treatment satisfaction reported by treatment-naïve patients. Switch-over patients also demonstrated comparable effectiveness., Conclusion: Contramyl XR was found to be clinically effective either as de novo or as switch therapy. It was well tolerated, and all patients chose to continue with the treatment option., Contribution: Despite distinct and different delivery mechanism of Contramyl XR, this study provides evidence for using it as an alternate treatment option versus reference methylphenidate, in both treatment-naïve and switch-over ADHD patients. Study participants willingness to continue Contramyl XR therapy post study, further strengthens the confidence on the effectiveness of Contramyl XR in managing ADHD patients., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Introduction: To compare the safety and efficacy of antivascular endothelial growth factor (anti-VEGF) monotherapy vs anti-VEGF and steroid combination therapy in treatment-naïve and treatment-resistant patients with diabetic macular edema (DME). Methods : A systematic literature search was conducted from January 2005 to December 2022. Sixteen randomized control trials (RCTs) published in English that reported the efficacy or safety of monotherapy and combination therapy in patients with DME were included. Results: The 16 RCTs included 1166 eyes. Monotherapy was associated with a significantly better best-corrected visual acuity (BCVA) at the final follow-up (weighted mean difference [WMD], -0.04 logMAR; 95% CI, -0.07 to -0.02; P  = .002; I 2  = 0%). No significant differences were observed in the change in BCVA between groups at the final observation. Monotherapy was associated with a significantly smaller change in retinal thickness at the final follow-up (WMD, 37.63 μm; 95% CI, 11.67-63.60; P  = .005; I 2  = 78%) and with a significantly lower risk for intraocular pressure-related adverse events (AEs) (risk ratio, 0.27; 95% CI, 0.15-0.46; P  ≤ .001; I 2  = 0%). The risk for cataract-related AEs was not significantly different between groups ( P  = .06). The results in treatment-naïve patients were similar. In treatment-resistant patients, the change in retinal thickness at the final follow-up was similar between groups ( P  = .14) but the risk for cataract-related AEs was significantly lower in the monotherapy group in 2 RCTs (risk ratio, 0.09; 95% CI, 0.01-0.66; P  = .02; I 2  = 0%). Conclusions: The changes in BCVA were similar despite combination therapy being associated with greater changes in retinal thickness. However, increased complications were seen with combination therapy. Most results in treatment-naïve patients and treatment-resistant patients were similar., Competing Interests: Dr. Choudhry is a consultant to Topcon, Optos, Bayer, Allergan, Novartis, Carl Zeiss Meditec, and Ellex and receives research equipment from Topcon, Optos, and Carl Zeiss Meditec. None of the other authors declared potential conflicts of interest., (© The Author(s) 2024.)

Abstract Background Migraine sufferers face difficulties getting appropriate care and treatment. Migraine is associated with reduced gray matter volume (GMV) in several brain regions, which could be related to various clinical characteristics of the disorder. Objectives To examine differences in GMV in migraine patients with and without prior clinical care for migraine and examine differences in migraine clinical variables, psychosocial symptoms and their relationship with GMV. Methods We utilized the baseline MRI scan and psychosocial symptom questionnaires from a longitudinal randomized controlled trial. Prior care of migraine was determined by diagnosis by a medical practitioner or prescription of migraine specific medication. Results 117 patients were included in the study. Patients without prior care (n=23) had reduced GMV in the right dorsal medial prefrontal cortex (dMPFC) relative to patients who had prior care (p=0.034, FWE corrected). Both patient groups had reduced GMV compared to healthy controls (n=36). Patient groups did not differ in headache clinical variables. Regardless of care status, increasing scores on the stress (Perceived Stress Score) and depression questionnaires (Patient Health Questionnaire) were associated with increased GMV in the dMPFC. Conclusions Clinical care may impact GMV in migraine patients. Patients may need different treatment options to address this baseline deficit. Trial registration NCT02133209.

HIV drug resistance (HIVDR) can become a public health concern, especially in low- and middle-income countries where genotypic testing for people initiating antiretroviral therapy (ART) is not available. For first-line regimens to remain effective, levels of transmitted drug resistance (TDR) need to be monitored over time. To determine the temporal trends of TDR in Mozambique, a search for studies in PubMed and sequences in GenBank was performed. Only studies covering the pol region that described HIVDR and genetic diversity from treatment naïve patients were included. A dataset from seven published studies and one novel unpublished study conducted between 1999 and 2018 were included. The Calibrated Population Resistance tool (CPR) and REGA HIV-1 Subtyping Tool version 3 for sequences pooled by sampling year were used to determine resistance mutations and subtypes, respectively. The prevalence of HIVDR amongst treatment-naïve individuals increased over time, reaching 14.4% in 2018. The increase was most prominent for non-nucleoside reverse transcriptase inhibitors (NNRTIs), reaching 12.7% in 2018. Subtype C was predominant in all regions, but a higher genetic variability (19% non-subtype C) was observed in the north region of Mozambique. These findings confirm a higher diversity of HIV in the north of the country and an increased prevalence of NNRTI resistance among treatment naïve individuals over time. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Islatravir (MK-8591) is a nucleoside reverse transcriptase translocation inhibitor in development for treatment and prevention of HIV-1. We present efficacy and safety data for islatravir and doravirine (DOR) through 96 weeks of the phase 2b trial (NCT03272347). Methods: In this randomized, double-blind, dose-ranging trial, participants initially received islatravir (0.25, 0.75, or 2.25 mg) with doravirine (100 mg) and lamivudine (3TC, 300 mg) or a fixed-dose combination of doravirine, 3TC, and tenofovir disoproxil fumarate (DOR/3TC/TDF) daily. Beginning at week 24, participants receiving islatravir stopped 3TC if HIV-1 RNA from the prior visit was <50 copies per milliliter and continued taking the assigned islatravir dose (still blinded) with doravirine. All islatravir groups transitioned to open-label use of 0.75 mg between weeks 60 and 84. Efficacy end points at week 96 included the proportion of participants maintaining HIV-1 RNA of <50 copies per milliliter (FDA Snapshot). Safety was assessed by adverse event (AE) reporting. Results: One hundred twenty-one treatment-naive participants received the study drugs and were included in the analyses. Through week 96, HIV-1 RNA<50 copies per milliliter was maintained in 86.2% (25/29), 90.0% (27/30), and 67.7% (21/31) of participants in the 0.25-, 0.75-, and 2.25-mg islatravir groups, respectively, 81.1% (73/90) of the combined islatravir group, and 80.6% (25/31) of the DOR/3TC/TDF group. One participant in the 2.25-mg islatravir group had Protocol-Defined Virologic Failure after week 48. Drug-related AE rates were higher for DOR/3TC/TDF participants (22.6%) compared with islatravir (combined 7.8%). Two participants (2.2%) receiving islatravir with doravirine and one (3.2%) receiving DOR/3TC/TDF discontinued because of an AE. Conclusions: Treatment regimens containing islatravir and doravirine maintained viral suppression through week 96 and were well tolerated regardless of dose. [ABSTRACT FROM AUTHOR]

Mecit Suerdem,1 Hakan Gunen,2 Levent Akyildiz,3 Aykut Cilli,4 Tevfik Ozlu,5 Esra Uzaslan,6 Oznur Abadoglu,7 Hasan Bayram,8 Arif Hikmet Cimrin,9 Bilun Gemicioglu,10 Zeynep Misirligil11 1Department of Chest Diseases, Faculty of Medicine, Selcuk University, Konya, Turkey; 2Sureyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital, Health Sciences University, Istanbul, Turkey; 3Department of Pulmonary Medicine, Memorial Dicle Hospital, Diyarbakır, Turkey; 4Department of Chest Diseases, Faculty of Medicine, Akdeniz University, Antalya, Turkey; 5Department of Chest Diseases, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey; 6Department of Chest Diseases, Faculty of Medicine, Uludag University, Bursa, Turkey; 7Private Office of Pulmonary and Allergic Diseases, Istanbul, Turkey; 8Koc University Research Center for Translational Medicine (KUTTAM), Department of Pulmonary Medicine, Koc University School of Medicine, Istanbul, Turkey; 9Department of Chest Diseases, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey; 10Department of Pulmonary Diseases, Faculty of Cerrahpasa Medicine, Istanbul University, Cerrahpasa, Turkey; 11Department of Pulmonary and Allergic Diseases, Ankara Liv Hospital, Ankara, TurkeyCorrespondence: Mecit SuerdemDepartment of Chest Diseases, Faculty of Medicine, Selcuk University, Konya, TurkeyTel +90 332 241 21 81-82Fax +90 332 241 21 84Email mecsuerdem@gmail.comPurpose: In order to determine the clinical and sociodemographic characteristics of newly diagnosed treatment-naïve asthma and COPD patients in Turkey, a multicenter study in 2012 was initiated . We aimed to investigate the characteristics and therapies of COPD patients in the original study in more detail.Patients and Methods: This nation-wide, multicentric, non-interventional, prospective, real-life observational cohort study was conducted in 122 centers. The newly diagnosed patients were not receiving any treatment before the recruitment. Their general characteristics, the combined GOLD 2011 COPD categories and exacerbation histories were noted. The patients were followed up with 3 voluntary visits for 1 year. Their adherence to the inhaled treatment according to GOLD 2011 was evaluated during follow-up visits.Results: The study included 776 COPD patients. Their mean age was 59.4± 9.1 years, and 11.9% of the patients were female. 35.1% of the patients were in the GOLD 2011 C and D category. 12.6% are frequent exacerbators, and 52.8% had at least one comorbid condition. 71.8% overtreatment rate was detected. Their attendance rates for three follow-up visits became 55.9%, 32.9% and 18.7%, respectively. The adherence rate to the treatment was measured as 81.9%.Conclusion: Although these patients were diagnosed for the first time, the GOLD C and D categories and frequent exacerbator phenotype were found at a high rate. They were usually prescribed an overtreatment regimen. We think that newly diagnosed COPD patients should be evaluated carefully, and best effort should be made to treat these patients in accordance with the recommendations of the major COPD guidelines.Keywords: COPD, newly diagnosed, treatment naïve, exacerbations

Background: AURIGA is the largest prospective real-world study to evaluate intravitreal aflibercept 2 mg (IVT-AFL) treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) and diabetic macular edema. Here we present the 24-month data from the German cohort of treatment-naïve patients with ME due to RVO., Methods: Treatment-naïve patients with ME secondary to RVO were treated with IVT-AFL 2 mg in the routine clinical practice. The primary endpoint was mean change in visual acuity (VA, early treatment diabetic retinopathy, ETDRS, letters) at month 12 compared to baseline. Analyses were descriptive., Results: Analysis included 130 patients with RVO (n = 61, 46.9% with central RVO, n = 69, 53.1% with branch RVO). The mean (± SD) time the RVO patients remained in the study was 18.4 ± 7.4 months. The mean VA gain (95% confidence interval) in the overall cohort was +10.9 (7.5-14.2) letters at month 12 and +9.7 (6.1-13.3) at month 24 (baseline VA 56.5 ± 18.9 letters). At 24 months, 67% of RVO patients gained ≥5 letters and 40% gained ≥15 letters. The mean number of injections was 4.4 ± 1.3 up to month 6, 6.2 ± 2.7 up to month 12 and 8.2 ± 4.5 up to month 24. The mean central retinal thickness (CRT) reduction was -206µm (-252 to -160µm) at 12 months and -219µm (-263 to -175µm) at 24 months (baseline CRT 507 ± 177 µm). The safety profile was consistent with that of previous studies., Discussion: In the German AURIGA cohort of treatment-naïve patients with ME secondary to RVO, IVT-AFL 2 mg treatment in clinical practice resulted in rapid and clinically relevant VA gains and a reduction in CRT. These results were largely maintained over 24 months despite the low injection frequency from month 6., (© 2024. The Author(s).)

Background: Migraine sufferers face difficulties getting appropriate care and treatment. Migraine is associated with reduced gray matter volume (GMV) in several brain regions, which could be related to various clinical characteristics of the disorder. Objectives: To examine differences in GMV in migraine patients with and without prior clinical care for migraine and examine differences in migraine clinical variables, psychosocial symptoms and their relationship with GMV. Methods: We utilized the baseline MRI scan and psychosocial symptom questionnaires from a longitudinal randomized controlled trial. Prior care of migraine was determined by diagnosis by a medical practitioner or prescription of migraine specific medication. Results: 117 patients were included in the study. Patients without prior care (n=23) had reduced GMV in the right dorsal medial prefrontal cortex (dMPFC) relative to patients who had prior care (p=0.034, FWE corrected). Both patient groups had reduced GMV compared to healthy controls (n=36). Patient groups did not differ in headache clinical variables. Regardless of care status, increasing scores on the stress (Perceived Stress Score) and depression questionnaires (Patient Health Questionnaire) were associated with increased GMV in the dMPFC. Conclusions: Clinical care may impact GMV in migraine patients. Patients may need different treatment options to address this baseline deficit. Trial registration: NCT02133209. [ABSTRACT FROM AUTHOR]

Objective: One in seven couples is infertile and ovulatory dysfunction accounts for 25% of the cases. Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy associated with ovulatory dysfunction. Traditionally, clomiphene is considered the first‐line drug for infertile PCOS women. Recently, letrozole was found to be an effective alternative ovulogen. The recent Cochrane review concluded that although live birth was higher with letrozole in unselected PCOS population, evidence was insufficient regarding effect of letrozole in treatment‐naïve women. Materials and Methods: We conducted a cohort study that included treatment‐naïve infertile PCOS women at a tertiary level infertility center in South India. Participants in the prospective arm were given letrozole 2.5 mg daily for 5 days and the retrospective arm included women who had undergone ovulation induction with clomiphene (100 mg) for up to five treatment cycles. The primary outcome was ovulation rate. Secondary outcomes were clinical pregnancy, live birth, multiple pregnancy, and miscarriage rate. The trial was registered under the Clinical Trials Registry, India (CTRI/2018/07/014704). Results: A total of 135 women in the letrozole group and 127 women in the clomiphene group underwent treatment. The ovulation rate per woman was similar in both groups (84.4% vs. 77.2%; p = 0.13). Letrozole was associated with significantly higher clinical pregnancy (38.5% vs. 22.0%; p = 0.004) and live birth rate per woman (30.3% vs. 18.9%; p = 0.03). Conclusion: The current study found letrozole to be a superior ovulation induction agent as compared to clomiphene in treatment‐naïve infertile women with PCOS. [ABSTRACT FROM AUTHOR]

Background People living with human immunodeficiency virus (PLWH) initiating antiretroviral therapy (ART) with viral loads (VLs) ≥100 000 copies/mL are less likely to achieve virologic success, but few studies have characterized real-world treatment outcomes. Methods ART-naive PLWH with VLs ≥100 000 copies/mL initiating dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL), or darunavir (DRV) between 12 August 2013 and 31 July 2017 were identified from the OPERA database. Virologic failure was defined as (i) 2 consecutive VLs ≥200 copies/mL after 36 weeks of ART; (ii) 1 VL ≥200 copies/mL with core agent discontinuation after 36 weeks; (iii) 2 consecutive VLs ≥200 copies/mL after suppression (≤50 copies/mL) before 36 weeks; or (iv) 1 VL ≥200 copies/mL with discontinuation after suppression before 36 weeks. Cox modeling estimated the association between regimen and virologic failure. Results There were 2038 ART-naive patients with high VL who initiated DTG (36%), EVG (46%), DRV (16%), or RAL (2%). Median follow-up was 18.1 (interquartile range, 12.4–28.9) months. EVG and DTG initiators were similar at baseline, but RAL initiators were older and more likely to be female with low CD4 cell counts while DRV initiators differed notably on factors associated with treatment failure. Virologic failure was experienced by 9.2% DTG, 13.2% EVG, 18.4% RAL, and 18.8% DRV initiators. Compared to DTG, the adjusted hazard ratio (95% confidence interval) was 1.46 (1.05–2.03) for EVG, 2.24 (1.50–3.34) for DRV, and 4.13 (1.85–9.24) for RAL. Conclusions ART-naive PLWH with high VLs initiating on DTG were significantly less likely to experience virologic failure compared to EVG, RAL, and DRV initiators. Antiretroviral therapy-naïve people living with HIV (PLWH) initiating therapy with viral loads ≥100,000 copies/mL varied markedly at baseline. In adjusted models, PLWH initiating dolutegravir-based regimens were less likely to experience virologic failure as compared to elvitegravir, raltegravir and darunavir initiators. [ABSTRACT FROM AUTHOR]

Abstract Background The World Health Organisation recommended dolutegravir (DTG)-based antiretroviral therapy (ART) regimens are available but not reimbursed through the public reimbursement system in China. The objective of this analysis was to evaluate the cost-effectiveness of DTG (DTG + TDF/3TC) compared to efavirenz (EFV + TDF/3TC) in treatment-naive and ritonavir-boosted lopinavir (LPV/r + TDF/3TC) in first-line ART failure HIV-1-infected patients in China. Methods A dynamic Markov model comprising of 5 response states and 6 CD4+ count-based health states was used. Efficacy, estimated as probability of virologic suppression (HIV RNA

Abstract Background The use of fixed combination antiretroviral therapy with a low genetic barrier for the treatment of patients infected with human immunodeficiency virus (HIV) may affect the local HIV transmitted drug resistance (TDR) pattern. The present study aimed to investigate changes in the prevalence of HIV TDR following the implementation of a fixed regimen of HIV treatment in Taiwan in 2012. Methods TDR was measured in antiretroviral treatment-naïve HIV-1-infected individuals who participated in voluntary counseling and testing between 2007 and 2015 in southern Taiwan. Antiretroviral resistance mutations were interpreted using the HIVdb program from the Stanford University HIV Drug Resistance Database. Results Sequences were obtained from 377 consecutive individuals between 2007 and 2015. The overall prevalence rates of TDR HIV among the study population from 2007 to 2011 and 2012–2015 were 10.6 and 7.9%, respectively. Among the detected mutations, K103 N and V179D + K103R were more frequently observed after 2012. Four HIV-infected patients with K103 N variants were detected after 2012, and 4 of the 5 patients with V179D + K103R variants were found after 2012. No significant differences were observed in the TDRs among nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), protease inhibitors, multiple drug resistance, and any drug resistance between period 1 (2007–2011) and period 2 (2012–2015). Conclusions A fixed treatment regimen with zidovudine/lamivudine + efavirenz or nevirapine as first-line therapy for treatment-naïve patients infected with HIV did not significantly increase the TDR during the 4-year follow-up period. Due to the increase in NNRTI resistance associated with mutations after 2012, a longer follow-up period and larger sample size are needed in future studies.

This study cross-sectional analytic study was conducted at Department of Medical Unit-1, Services Hospital, Lahore, from 3rd June 2019 to 3rd December 2019 with an objective to measure the frequency of metabolic syndrome in patients with newly diagnosed (treatment naïve) Rheumatoid Arthritis. A total 74 Rheumatoid Arthritis (RA) patients diagnosed according to 2010 American College of Rheumatology-European League against Rheumatism classification criteria were included and were treatment naïve. Age and sex matched apparently healthy controls were also included. Metabolic syndrome (MetS) was diagnosed based on the National Cholesterol Education Program (Adult Treatment Panel III 2004 revised criteria). It was found that 50% of the patients with Rheumatoid Arthritis had Metabolic syndrome and in control group this frequency was 32.43%. The diagnostic criteria used to diagnose MetS was 'National Cholesterol Education Program (Adult Treatment Panel III 2004 revised criteria)' (p<0.05). Rheumatoid Arthritis (RA) group was seen to be more prone to have lower high density lipoproteins (62.16%), higher triglycerides (50%), higher blood pressure levels (40.54%), higher FBG (20.27%) and increased waist circumferences (35.13%). In conclusion, it was observed that metabolic syndrome (MetS) is more prevalent in Rheumatoid Arthritis (RA) group when compared to control group. [ABSTRACT FROM AUTHOR]

Background: Despite improvements in surgical methodologies and perioperative chemo- and radiotherapy, the prognosis for patients with esophageal and gastric cancer remains poor. Hence, there is a great need to identify complementary biomarkers for improved treatment stratification. Tumor-infiltrating immune cells have been shown to impact on outcome in many types of cancer, including gastroesophageal cancer. The aim of this present study was to examine the prognostic value of tumor-infiltrating macrophages in gastroesophageal adenocarcinoma.Methods: The density of CD68+, CD163+, and MARCO+ macrophages was assessed by immunohistochemistry on tissue microarrays with primary tumors from a consecutive, retrospective cohort of 174 patients with treatment-naïve gastroesophageal adenocarcinoma. Total densities and infiltration in tumor nest (TN) were denoted as none/sparse (0), intermediate (1), or high (2). The impact on overall survival (OS) was examined by Kaplan–Meier analysis, log-rank test, and Cox proportional hazards modeling.Results: Increased infiltration of both CD68+ and CD163+, but not MARCO+, macrophages in TN was significantly associated with a stepwise reduced survival. Median OS for patients with none/sparse, intermediate, and high CD68+ TN infiltration was 4.4, 2.6, and 1.0 years, respectively. Median OS for patients with none/sparse, intermediate, and high CD163+ TN infiltration was 4.4, 2.2, and 1.1 years, respectively. High infiltration of CD68+ macrophages remained an independent prognostic factor in adjusted analysis (hazard ratio = 1.61, 95% confidence interval = 1.02–2.55, and p = 0.041).Conclusion: Infiltration of CD68+ and CD163+, but not MARCO+, macrophages is prognostic for OS in gastroesophageal adenocarcinoma. The relevance of this finding in clinical practice remains to be elucidated.

Elisna Syahruddin,1,2 Laksmi Wulandari,3 Nunuk Sri Muktiati,4 Ana Rima,5 Noni Soeroso,6 Sabrina Ermayanti,7 Michael Levi,8 Heriawaty Hidajat,2 Grace Widjajahakim,8 Ahmad Rusdan Handoyo Utomo9 1Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia; 2Department of Pulmonology, Persahabatan Hospital, Jakarta, Indonesia; 3Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga – Soetomo Hospital, Surabaya, Indonesia; 4Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Brawijaya – Saiful Anwar General Hospital, Malang, Indonesia; 5Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sebelas Maret, Dr. Moewardi General Hospital, Surakarta, Indonesia; 6Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, University of Sumatera Utara, Adam Malik General Hospital, Medan, Indonesia; 7Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Andalas University, M. Djamil Hospital, Padang, Indonesia; 8Kalbe Genomics Laboratory, Division of Molecular Pathology Testing Service, PT Bifarma Adiluhung, 9Stem Cell and Cancer Institute, Cancer Diagnostic Research Division, PT Kalbe Farma Tbk, Jakarta, Indonesia Purpose: We aimed to evaluate the distribution of individual epidermal growth factor receptor (EGFR) mutation subtypes found in routine cytological specimens.Patients and methods: A retrospective audit was performed on EGFR testing results of 1,874 consecutive cytological samples of newly diagnosed or treatment-naïve Indonesian lung cancer patients (years 2015–2016). Testing was performed by ISO15189 accredited central laboratory.Results: Overall test failure rate was 5.1%, with the highest failure (7.1%) observed in pleural effusion and lowest (1.6%) in needle aspiration samples. EGFR mutation frequency was 44.4%. Tyrosine kinase inhibitor (TKI)-sensitive common EGFR mutations (ins/dels exon 19, L858R) and uncommon mutations (G719X, T790M, L861Q) contributed 57.1% and 29%, respectively. Approximately 13.9% of mutation-positive patients carried a mixture of common and uncommon mutations. Women had higher EGFR mutation rate (52.9%) vs men (39.1%; p

Aims: This study evaluated the efficacy and safety of teneligliptin in patients with inadequately controlled type 2 diabetes mellitus (T2DM). Settings and Design: This was a randomized, doubleblind, placebocontrolled, parallelgroup, multicenter, Phase III study. Subjects and Methods: Patients with T2DM and inadequate glycemic control (glycosylated hemoglobin [HbA1c]: >7.0-≤8.5%) were enrolled. Patients were randomly assigned (ratio: 2:1) to receive teneligliptin 20 mg (Glenmark) or placebo. The primary efficacy variable was change from baseline in HbA1c at week 16. Additional analyses included the proportion of patients who achieved target of HbA1c ≤7.0%, changes in fasting plasma glucose (FPG), and postprandial glucose (PPG). Statistical Analysis: Mean change in HbA1c was analyzed using an analysis of covariance model, least square (LS) means, 95% confidence intervals (CIs), and P values were calculated. Results: Overall, 237 patients were included. Patients of the teneligliptin group showed reduced HbA1c levels (LS mean difference = −0.304% for intent-to-treat [ITT]; −0.291% for per-protocol (PP) populations) after 16 weeks of treatment, and a statistically significant difference was observed between the ITT (LS mean difference = 0.555; 95% CI: 0.176–0.934; P = 0.0043) and PP populations (LS mean difference = 0.642; 95% CI: 0.233–1.052; P = 0.0023). Target HbA1c level was achieved by a greater proportion of teneligliptin group patients (ITT, 43.4%; PP, 43.6%) than placebo group patients (ITT, 27.3%; PP, 26.6%). Reduction in FPG levels was observed in ITT (LS mean difference: 8.829; 95% CI: −4.357–22.016; P = 0.1883) and PP populations (LS mean difference: 11.710 mg/dL; 95% CI: −2.893-26.312; P = 0.1154). Reduction in PPG levels was higher in teneligliptin group than placebo group in both ITT (LS mean difference = 25.849 mg/dL; 95% CI: 7.143–44.556; P = 0.0070) and PP populations (LS mean difference = 25.683 mg/dL; 95% CI: 5.830–45.536; P = 0.0115). Overall, 44 patients (18.6%) experienced at least one adverse event. Three or more hypoglycemic events were experienced by 2.5% patients of teneligliptin group and none in placebo group. Conclusion: Treatment with once-daily teneligliptin led to statistically significant and clinically meaningful reductions in HbA1c and PPG, and was well tolerated in Indian patients with T2DM.

While current lymphoma therapies induce remission in most dogs, drug‐resistant relapse is common, creating a need for novel agents. Rabacfosadine (RAB), a double prodrug of the acyclic nucleotide phosphonate 9‐(2‐phosphonylmethoxyethel) guanine (PMEG), preferentially targets lymphoma cells with reduced systemic toxicity compared with PMEG. Previous studies evaluating RAB administered every 21 days have suggested efficacy in both naïve and relapsed subjects; however, no large studies of RAB as a single agent have been reported in previously untreated dogs with intermediate to large cell lymphoma. The purpose of this study was to evaluate the safety and efficacy of RAB in dogs with previously untreated (excluding corticosteroids) lymphoma. Sixty‐three dogs received up to five RAB treatments every 21 days (16 at 0.82 mg/kg and 47 at 1.0 mg/kg) as a 30 minutes intravenous infusion, with (n = 23) or without (n = 40) concurrent corticosteroids. Response assessment and adverse event (Ae) evaluation were performed every 21 days via Veterinary Cooperative Oncology Group (VCOG) criteria. The overall response rate was 87% (52% CR, 35% PR). The overall median progression free interval was 122 days (199 for CR, 89 for PR and 153 days for all responders). T‐cell immunophenotype and corticosteroid pre‐treatment were predictive of inferior outcomes on multivariate analysis. AEs were most commonly of gastrointestinal origin (hyporexia/diarrhoea) and generally resolved with supportive treatment and/or dosage adjustment. Three dogs experienced VCOG‐CTCAE grade 5 delayed pulmonary fibrosis. In conclusion, RAB administered every 3 weeks is generally well tolerated and demonstrates substantial antitumour activity in dogs with previously untreated intermediate to large cell lymphoma. [ABSTRACT FROM AUTHOR]

Background: Despite improvements in surgical methodologies and perioperative chemo- and radiotherapy, the prognosis for patients with esophageal and gastric cancer remains poor. Hence, there is a great need to identify complementary biomarkers for improved treatment stratification. Tumor-infiltrating immune cells have been shown to impact on outcome in many types of cancer, including gastroesophageal cancer. The aim of this present study was to examine the prognostic value of tumor-infiltrating macrophages in gastroesophageal adenocarcinoma. Methods: The density of CD68+, CD163+, and MARCO+ macrophages was assessed by immunohistochemistry on tissue microarrays with primary tumors from a consecutive, retrospective cohort of 174 patients with treatment-naïve gastroesophageal adenocarcinoma. Total densities and infiltration in tumor nest (TN) were denoted as none/sparse (0), intermediate (1), or high (2). The impact on overall survival (OS) was examined by Kaplan–Meier analysis, log-rank test, and Cox proportional hazards modeling. Results: Increased infiltration of both CD68+ and CD163+, but not MARCO+, macrophages in TN was significantly associated with a stepwise reduced survival. Median OS for patients with none/sparse, intermediate, and high CD68+ TN infiltration was 4.4, 2.6, and 1.0 years, respectively. Median OS for patients with none/sparse, intermediate, and high CD163+ TN infiltration was 4.4, 2.2, and 1.1 years, respectively. High infiltration of CD68+ macrophages remained an independent prognostic factor in adjusted analysis (hazard ratio = 1.61, 95% confidence interval = 1.02–2.55, and p = 0.041). Conclusion: Infiltration of CD68+ and CD163+, but not MARCO+, macrophages is prognostic for OS in gastroesophageal adenocarcinoma. The relevance of this finding in clinical practice remains to be elucidated. [ABSTRACT FROM AUTHOR]

Background: The PIONEER-HF (comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode) trial demonstrated the efficacy and safety of sacubitril/valsartan (S/V) in stabilized patients with acute decompensated heart failure (HF) and reduced ejection fraction.Objectives: The study sought to determine whether and how prior HF history and treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) affected the results.Methods: The PIONEER-HF trial was a prospective, multicenter, double-blind, randomized clinical trial enrolling 881 patients with an ejection fraction ≤40%. Patients were randomly assigned 1:1 to in-hospital initiation of S/V (n = 440) versus enalapril (n = 441). Pre-specified subgroup analyses were performed based on prior HF history (i.e., de novo HF vs. worsening chronic HF) and treatment with an ACE inhibitor or ARB (i.e., ACE inhibitor or ARB-yes vs. ACE inhibitor or ARB-no) at admission.Results: At enrollment, 303 (34%) patients presented with de novo HF and 576 (66%) patients with worsening chronic HF. A total of 421 (48%) patients had been treated with an ACE inhibitor or ARB, while 458 (52%) had not been treated with an ACE inhibitor or ARB. N-terminal pro-B-type natriuretic peptide declined significantly in all 4 subgroups (p < 0.001), with greater decreases in the S/V versus the enalapril arm (p < 0.001). There was no interaction between prior HF history (p = 0.350) or ACE inhibitor or ARB treatment (p = 0.880) and the effect of S/V versus enalapril on cardiovascular death or rehospitalization for HF. The incidences of adverse events were comparable between S/V and enalapril across all 4 subgroups.Conclusions: Among patients admitted for acute decompensated HF, S/V was safe and well tolerated, led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide, and improved clinical outcomes compared with enalapril irrespective of previous HF history or ACE inhibitor or ARB treatment. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890). [ABSTRACT FROM AUTHOR]

Cancer-related cognitive impairment (CRCI) has not been objectively assessed in chronic lymphocytic leukemia (CLL). It is currently unclear how much of CRCI is attributable to disease, treatment, or both. We used CLL as a novel model to study the differential roles of disease and treatment in CRCI. One hundred and fifty CLL patients (100 treatment-naïve and 50 chemotherapy-treated) including 84 patients with higher-risk of CLL progression completed objective neuropsychological tests. Sociodemographic-adjusted linear regression models examined cognitive outcomes in relation to risk and treatment. Higher-risk patients recalled two fewer words on a memory task (β = −1.8, 95%CI –3.3,−0.3) and took 15 s longer on an executive function task (β = 15.4, 95%CI 3.1, 27.6) than lower-risk patients, independent of treatment. Treated patients reported greater cognitive difficulties than treatment-naive patients (β = −6.1, 95%CI –10.1, −2.2) but did not perform worse on objective measures. Higher-risk patients experienced impairments in executive function and memory suggesting that disease biology contributes to CRCI independent of treatment. [ABSTRACT FROM AUTHOR]

Introduction: Glecaprevir/pibrentasvir (G/P) was approved on 26 September 2019 by the US Food and Drug Administration for 8-week duration in treatment-naïve (TN) hepatitis C virus (HCV)-infected patients with compensated cirrhosis (CC). Evidence from the EXPEDITION-8 study demonstrated that 8 weeks of G/P achieved a 98% intent-to-treat (ITT) sustained virologic response rate 12 weeks post treatment (SVR12) in 343 TN/CC patients. The aim of this study is to demonstrate the first US real-world effectiveness of G/P 8-week treatment in genotype 1-6 TN/CC HCV patients.Methods: Data from 73 TN/CC patients who initiated 8 weeks of G/P treatment between August 2017 and November 2018 were collected electronically from providers and specialty pharmacies of the Trio Health network and analyzed. Cirrhosis was determined by FIB-4 > 5.2 or was physician reported. The primary outcome was Per Protocol (PP) SVR12.Results: The majority (60%) of patients were male, with (mean values): age 59 years, body mass index (BMI) of 30, aspartate aminotransferase (AST) 105, and alanine aminotransferase (ALT) 101 IU/ml. HCV genotypes (GT) were: GT1 81% (59/73), GT2 10% (7/73), GT3 5% (4/73), GT4 3% (2/73), and GT6 1% (1/73). Eight percent (6/73) of patients had concurrent proton pump inhibitor (PPI) use, and 15% (11/72) had a baseline viral load > 6 MM IU/ml. Zero patients discontinued, two patients were reported as lost to follow-up, and there was one virologic failure. PP sustained virologic response at 12 weeks (SVR12) rate was 99% (70/71), and the intent-to-treat (ITT) SVR12 rate was 96% (70/73).Conclusions: Early real-world experience indicates high effectiveness of the 8-week G/P regimen in a diverse treatment-naïve, compensated cirrhotic US population. [ABSTRACT FROM AUTHOR]

Background: Human immune-deficiency virus/acquired immune-deficiency syndrome predisposes to opportunistic parasitic infestations of the gastrointestinal tract. This study aimed to determine the prevalence of intestinal parasites in newly diagnosed treatment naïve HIV/AIDS patients. Methods: This hospital-based cross-sectional study was carried out from December 2010 to June 2011. Questionnaires were administered to 238 HIV/AIDS subjects, and 238 age and sex-matched controls. CD4+ T cell count was carried out on HIV-positive subjects. Stool samples were examined using direct microscopic and modified Ziehl-Neelsen methods. Positivity of intestinal parasites was taken as the presence of worms, oocyst, cyst, ova or larvae in the stool samples. Results: Ninety males and 148 females were studied for the HIV-positive and HIV-negative controls respectively. Intestinal parasitic infestation in HIV-positive subjects was 68.5%, and was significantly higher than in the HIV-negative controls 49.2% (P

Purpose: To evaluate the efficacy and safety of intravitreal aflibercept injections for diabetic macular edema (DME) treatment in a tertiary referral center in Greece., Methods: ADMIRE was a prospective, observational cohort study of patients with DME. Efficacy was assessed by change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month 36 after treatment with intravitreal aflibercept in treatment-naive patients and previously treated patients. Safety was evaluated by recording any patients-reported events., Results: Participants in the study were 94 patients with DME, 70 treatment naive and 24 previously treated with ranibizumab. At month 36 of the follow-up period, the mean change in BCVA was +7.4 letters compared to baseline ( p  < .001). The mean change in BCVA in treatment-naive patients was +8.9 letters and differed significantly compared to previously treated patients (+5.9 letters, p  = .041). In addition, patients who received a loading dose of 5 monthly injections at the initiation of treatment provided better VA outcomes (+11.4 vs. +6.1 letters, p  < .001). Accordingly, the mean CST at month 36 (369.6 ± 72.8 μm) was significantly decreased compared to baseline (479.2 ± 68.3 μm, p  < .001). Overall, the mean number of injections at month 36 was 13.4. Safety analysis showed that the reported ocular adverse events during the 36-month study period were mild and not sight-threatening., Conclusion: Intravitreal aflibercept was found to be safe and effective for the treatment of DME in real-life in a Greek population. Treatment-naive patients and those who received a loading dose of five consecutive monthly injections at initiation of treatment exhibited better outcomes, suggesting that early and effective treatment may prevent vision loss.

Background: Recent functional connectivity (FC) studies have proved the potential value of resting-state functional magnetic resonance imaging (rs-fMRI) in the study of major depressive disorder (MDD); yet, the rs-fMRI-based individualized diagnosis of MDD is still challenging.Methods: We enrolled 82 treatment-naïve first episode depression (FED) adults and 72 matched normal control (NC). A computer-aided diagnosis framework was utilized to classify the FEDs from the NCs based on the features extracted from not only traditional "low-order" FC networks (LON) based on temporal synchronization of original rs-fMRI signals, but also "high-order" FC networks (HON) that characterize more complex functional interactions via correlation of the dynamic (time-varying) FCs. We contrasted a classifier using HON feature (CHON) and compared its performance with using LON only (CLON). Finally, an integrated classification model with both features was proposed to further enhance FED classification.Results: The CHON had significantly improved diagnostic accuracy compared to the CLON (82.47% vs. 67.53%). Joint classification further improved the performance (83.77%). The brain regions with potential diagnostic values mainly encompass the high-order cognitive function-related networks. Importantly, we found previously less-reported potential imaging biomarkers that involve the vermis and the crus II in the cerebellum.Limitations: We only used one imaging modality and did not examine data from different subtypes of depression.Conclusions: Depression classification could be significantly improved by using HON features that better capture the higher-level brain functional interactions. The findings suggest the importance of higher-level cerebro-cerebellar interactions in the pathophysiology of MDD. [ABSTRACT FROM AUTHOR]

Ancillary service needs likely influence time to diagnosis and presentation for HIV care. The effect of both met and unmet needs on late presentation to HIV care is not well understood. We used baseline data from 348 people with HIV (PWH) with no prior HIV care who enrolled in iENGAGE (a randomized controlled trial (RCT) of an intervention to support retention in care) at one of four HIV clinics in the US. A standardized baseline questionnaire collected information on ancillary service needs, and whether each need was presently unmet. We examined covariates known to be associated with disease stage at presentation to care and their association with needs. We subsequently assessed the relationship of needs with CD4 accounting for those other covariates by estimating prevalence ratios (PR) using inverse probability weights. Most patients enrolling in the RCT were male (79%) and the majority were Black (62%); median age was 34 years. Prevalence of any reported individual need was 69%. One-third of the sample had a baseline CD4 cell count <200, 42% between 200 and 499 and 27% ≥500. There was no statistically significant association between need or unmet need and baseline CD4. In general, psychiatric health and SU issues (depression, anxiety, and drug use) were consistently associated with higher prevalence of need (met and unmet). Additionally, the Black race was associated with higher basic resource needs (housing: PR 1.67, 95%CI 1.08–2.59; transportation: PR 1.65, 95% CI 1.12–2.45). Ancillary service needs (met and unmet) were common among patients new to HIV care and impacted vulnerable subgroups. However, we found no evidence that reporting a specific individual need, whether met or unmet, was associated with a timely presentation to HIV care. The impact of needs on subsequent steps of the HIV care continuum will be examined with longitudinal data. [ABSTRACT FROM AUTHOR]

Background: Proton magnetic resonance spectroscopy (1H‐MRS) studies have demonstrated abnormal levels of a variety of neurometabolites in inpatients/outpatients with alcohol use disorder (AUD) following acute alcohol withdrawal relative to healthy controls. In contrast, few studies have compared neurometabolite levels between less severe, treatment‐naïve AUD individuals and light drinkers (LD) or related them to recent alcohol consumption. The present study compared neurometabolite levels between treatment‐naïve AUD and LD individuals. Methods: Twenty treatment‐naïve individuals with AUD and 20 demographically matched LD completed an 1H‐MRS scan, approximately 2.5 days following their last reported drink. 1H‐MRS data were acquired in dorsal anterior cingulate (dACC) using a 2‐dimensional J‐resolved point‐resolved spectroscopy sequence. dACC neurometabolite levels, with a focus on glutamate, glutamine, and GABA, were compared between AUD and LD participants. The associations between metabolite levels and recent drinking were explored. Results: AUD participants had significantly lower concentrations of GABA (Cohen's d = 0.79, p = 0.017) and glutamine (Cohen's d = 1.12, p = 0.005), but not glutamate (Cohen's d = 0.05, p = 0.893), relative to LD. As previously reported, AUD participants' glutamate and N‐acetylaspartate concentrations were inversely associated with their number of heavy drinking days. In contrast, neither number of drinking (mean p = 0.56) nor heavy drinking (mean p = 0.47) days were associated with metabolite concentrations in LD. Conclusions: The present study demonstrated significantly lower levels of prefrontal γ‐aminobutyric acid and glutamine in treatment‐naïve individuals with AUD relative to LD. Whether these findings reflect the neurotoxic consequence and/or neuroadaptive response of alcohol consumption versus a predrinking trait, and therefore a more durable neurochemical disturbance, awaits elucidation from longitudinal studies. Treatment‐naïve individuals with Alcohol Use Disorder (n = 20, M[SD] Age = 26.8[6.2]) had significantly lower levels of dorsal Anterior Cingulate Cortex GABA (Cohen's‐D = 0.79) and Glutamine (Cohen's‐D = 1.12) relative to demographically‐matched light‐drinkers via Proton Magnetic Resonance Spectroscopy. These results are important because they demonstrate AUD‐associated neurochemical disturbances in a younger/less severe sample than has previously been studied with 1H‐MRS. If replicated, these findings may lead to enhanced knowledge of how the GABA and glutamate systems change with drinking and also to novel pharmacological interventional/preventative strategies. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. BRCA‐associated PDAC comprises a clinically relevant subtype. A portion of these patients are highly susceptible to DNA damaging therapeutics, however, responses are heterogeneous and clinical resistance evolves. We have developed unique patient‐derived xenograft (PDX) models from metastatic lesions of germline BRCA‐mutated patients obtained at distinct time points; before treatment and at progression. Thus, closely mimicking clinical scenarios, to further investigate treatment naïve and resistant patients. DNA was isolated from six BRCA‐mutated PDXs and classified by whole‐genome sequencing to stable‐genome or homologous recombination deficient (HRD)‐genome. The sensitivity to DNA‐damaging agents was evaluated in vivo in three BRCA‐associated PDAC PDXs models: (1) HRD‐genome naïve to treatments; (2) stable‐genome naïve to treatment; (3) HRD‐genome resistant to treatment. Correlation between disease course at tissue acquisition and response to PARP inhibitor (PARPi)/platinum was demonstrated in PDXs in vivo. Only the HRD‐genome PDX, naïve to treatment, was sensitive to PARP inhibitor/cisplatin treatments. Our results demonstrate heterogeneous responses to DNA damaging agents/PARPi in BRCA‐associated PDX thus reflecting the wide clinical spectrum. An HRD‐genome PDX generated from a naïve to treatment biopsy was sensitive to platinum/PARPi whereas no benefit was observed in treating a HRD‐genome PDXs generated from a patient that had acquired resistance nor stable‐genome PDXs. [ABSTRACT FROM AUTHOR]

Aims: This study evaluated the efficacy and safety of teneligliptin in patients with inadequately controlled type 2 diabetes mellitus (T2DM). Settings and Design: This was a randomized, doubleblind, placebocontrolled, parallelgroup, multicenter, Phase III study. Subjects and Methods: Patients with T2DM and inadequate glycemic control (glycosylated hemoglobin [HbA1c]: >7.0-=8.5%) were enrolled. Patients were randomly assigned (ratio: 2:1) to receive teneligliptin 20 mg (Glenmark) or placebo. The primary efficacy variable was change from baseline in HbA1c at week 16. Additional analyses included the proportion of patients who achieved target of HbA1c =7.0%, changes in fasting plasma glucose (FPG), and postprandial glucose (PPG). Statistical Analysis: Mean change in HbA1c was analyzed using an analysis of covariance model, least square (LS) means, 95% confidence intervals (CIs), and P values were calculated. Results: Overall, 237 patients were included. Patients of the teneligliptin group showed reduced HbA1c levels (LS mean difference = -0.304% for intent-to-treat [ITT]; -0.291% for per-protocol (PP) populations) after 16 weeks of treatment, and a statistically significant difference was observed between the ITT (LS mean difference = 0.555; 95% CI: 0.176-0.934; P = 0.0043) and PP populations (LS mean difference = 0.642; 95% CI: 0.233-1.052; P = 0.0023). Target HbA1c level was achieved by a greater proportion of teneligliptin group patients (ITT, 43.4%; PP, 43.6%) than placebo group patients (ITT, 27.3%; PP, 26.6%). Reduction in FPG levels was observed in ITT (LS mean difference: 8.829; 95% CI: -4.357-22.016; P = 0.1883) and PP populations (LS mean difference: 11.710 mg/dL; 95% CI: -2.893-26.312; P = 0.1154). Reduction in PPG levels was higher in teneligliptin group than placebo group in both ITT (LS mean difference = 25.849 mg/dL; 95% CI: 7.143-44.556; P = 0.0070) and PP populations (LS mean difference = 25.683 mg/dL; 95% CI: 5.830-45.536; P = 0.0115). Overall, 44 patients (18.6%) experienced at least one adverse event. Three or more hypoglycemic events were experienced by 2.5% patients of teneligliptin group and none in placebo group. Conclusion: Treatment with once-daily teneligliptin led to statistically significant and clinically meaningful reductions in HbA1c and PPG, and was well tolerated in Indian patients with T2DM. [ABSTRACT FROM AUTHOR]

Daunorubicin and Cytarabine (DA; 3 + 7) has been the standard frontline Acute Myeloid Leukemia (AML) induction regimen resulting in Complete Remission (CR) rates of 50–70%. It is associated with induction mortality of 15–30%. We report a comparative analysis of DA versus fludarabine, cytarabine, G-CSF (FLAG) + /- Venetoclax in resource constrained settings. We conducted a single center, retrospective analysis of 37 treatment naïve fit AML patients from May 2021 to December 2022 who received either standard DA regimen (Group 1) or FLAG + /- Venetoclax (Group 2). The median patient age was 36.6 years in DA arm (n = 18) as compared to 40.1 years in FLAG arm (n = 19). CR rates at day 28 were 55.5% in group 1 and 89.4% in group 2 (odds ratio [OR], 7.20; 95% confidence interval [CI], 1.274 −40.678; P = 0.012). Patients in FLAG based therapy arm had shorter duration of neutropenia (P = 0.003), fewer episodes of grade 3 febrile neutropenia (P = 0.0228), shorter duration of antibiotic therapy (P = 0.03), lesser need of 3rd line antibiotic therapy (P = 0.0228). Mortality rates were 16.6% (n = 3) in (group 1) and 0% (n = 0) in (group 2) (p = 0.105). Our analysis supports that FLAG based induction regimen is an effective and well-tolerated therapy in treatment naïve fit AML patients. • Four days of FLAG with or without Venetoclax has non inferior efficacy and tolerability as compared to standard 3 + 7 induction. • Our study provides proof of principle to conduct a larger investigator initiated randomized phase III multicentre study in LMICs like India. [ABSTRACT FROM AUTHOR]

Objectives. Filibuvir is a non-nucleoside inhibitor of hepatitis C virus (HCV) polymerase. This study evaluated the safety and efficacy of filibuvir plus pegylated interferon alfa-2a (pegIFN)/ribavirin.Material and methods. Treatment-naïve, HCV genotype-1 patients were randomized to receive filibuvir 300 or 600 mg twice daily (BID) or placebo plus pegIFN (180 Mg/wk) and ribavirin (1,000/1,200 mg BID) for 24 weeks. Filibuvir patients who achieved defined response through week 24 discontinued therapy at week 24. All other patients continued on open-label peglFN/ribavirin through week 48. The primary endpoint was the proportion of patients who achieved sustained virologic response (SVR) defined as HCV RNA < 15 IU/mL at end of treatment (weeks 24 or 48) and week 72.Results. Overall, 288 patients were randomized and treated. SVR was achieved by 41.7, 39.6, and 45.8% of patients in the filibuvir 300 mg, 600 mg, and placebo arms, respectively. While the addition of filibuvir to pegIFN/ribavirin improved on-treatment virologic response parameters, this did not translate into improved SVR rates due to a high rate of virologic relapse following completion of therapy (300 mg: 35.9%; 600 mg: 42.9%; placebo: 25.4%). The most commonly reported adverse events were nausea, fatigue, headache, and insomnia, and were reported at similar rates across arms. Conclusions. Filibuvir plus pegIFN/ribavirin did not improve the percentage of patients achieving SVR compared with administration of pegIFN/ribavirin alone. However, the agent was well tolerated and was associated with higher on-treatment virologic response parameters. Further evaluation of filibuvir in combination with other direct-acting antiviral agents may be considered.

The use of radioiodine as the first line of treatment in Graves′ disease is restricted in India because of its limited availability and an unrealistic risk perception associated with it. Additionally, the effectiveness of radioiodine ablation in Graves′ disease is influenced by many factors. Prior medical antithyroid therapy is one such important factor. Aims: To analyze the efficacy of low dose radioiodine therapy (5 mCi) in treatment of naive patients of Graves′ disease in comparison to that in which it was already primed with an antithyroid drug, carbimazole. Settings and Design: A non-randomized, interventional study conducted in the Department of Medicine and Endocrinology of a tertiary care institute in South India. Materials and Methods: The study had two groups; Group A (36 treatment naive, uncomplicated Graves′ disease patients) and B (34 Graves′ disease patients on carbimazole prior to radioiodine therapy). Both groups had baseline clinical, biochemical evaluation and were reassessed at 3 and 6 months for evaluating the clinical status for possible documentation of cure. Results: The cure rate was 61.1% in drug naive group and 58.8% in pretreated group at 6 months following radioiodine (P = 0.845). Higher baseline 999m technicium (99m Tc) uptake, male gender, BMI and higher baseline free thyroxine (fT4) level predicted treatment failure following radioiodine therapy. Conclusions: Administration of carbimazole prior to low dose radioiodine therapy does not alter the efficacy of radioiodine. Low fixed dose (5 mCi) of radioactive iodine may be a safe and effective primary therapeutic option in Graves′ disease patients pretreated with antithyroid drugs.

Background Human immune-deficiency virus/acquired immune-deficiency syndrome predisposes to opportunistic parasitic infestations of the gastrointestinal tract. This study aimed to determine the prevalence of intestinal parasites in newly diagnosed treatment naïve HIV/AIDS patients. Methods This hospital-based cross-sectional study was carried out from December 2010 to June 2011. Questionnaires were administered to 238 HIV/AIDS subjects, and 238 age and sex-matched controls. CD4 + T cell count was carried out on HIV-positive subjects. Stool samples were examined using direct microscopic and modified Ziehl-Neelsen methods. Positivity of intestinal parasites was taken as the presence of worms, oocyst, cyst, ova or larvae in the stool samples. Results Ninety males and 148 females were studied for the HIV-positive and HIV-negative controls respectively. Intestinal parasitic infestation in HIV-positive subjects was 68.5%, and was significantly higher than in the HIV-negative controls 49.2% ( P < 0.05). In HIV-positive subjects, Cryptosporidium spp. was the commonest (55.0%) parasite isolated . Others were Cyclospora cayetanensis (41.2%), Isospora belli (3.0%), Entamoeba histolytica (8.4%), Giardia lamblia (3.7%), Ascaris lumbricoides (2.5%), Strongyloides stercoralis (1.7%), Trichuris trichiura (0.8%) and Schistosoma mansoni (0.4%). HIV-positive patients with CD4 + T cell count of less than 200 cells/ul were more at risk of opportunistic parasites compared to the HIV-negative controls. Conclusion The prevalence of intestinal parasites in newly diagnosed HIV/AIDS individuals was high, and its association with CD4 + T cell count was demonstrated. Routine screening for parasitic infestations at diagnosis is indicated to reduce the burden of the disease. [ABSTRACT FROM AUTHOR]

Objective Data on PD-L1 expression in high grade serous ovarian carcinoma (HGSOC) is mixed. Some studies report robust tumor staining and others identify expression limited to tumor-associated macrophages (TAM). TAM PD-L1 expression is induced in HGSOC metastatic implants from patients who have undergone chemotherapy. However, it is unclear whether TAM acquisition of PD-L1 plays a role in treatment naïve tumors. We investigated PD-L1 expression in primary ovarian tumors and matched metastatic implants from predominantly treatment-naïve HGSOC. Methods Sixty one primary HGSOC were evaluated with PD-L1 and CD68 IHC: 40 on TMA and 21 on whole section. Whole section cases were matched to a metastatic implant. TAM were delineated by CD68. Membranous PD-L1 staining was scored separately for tumor cells and TAM. Results Eight percent of primary HGSOC demonstrated PD-L1 expression. In contrast, 74% showed PD-L1 + TAM. In the 16 treatment naïve cases, 13 (81.3%) demonstrated fidelity in intratumoral PD-L1 expression between the primary and metastatic site. Of the 21 matched pairs, only one case (4.8%) did not exhibit PD-L1 positive TAM in the metastatic implant and 19 (90.5%) showed fidelity across both locations. Intratumoral and immune infiltrate PD-L1 expression was not different in cases who received neoadjuvant chemotherapy compared to treatment naïve cases. Conclusions PD-L1 + TAM are common in both primary and metastatic HGSOC however tumoral PD-L1 staining is rare. There was high fidelity of PD-L1 expression when comparing primary tumors and metastatic implants in treatment naïve specimens. Clinical trials are needed to determine whether tumor-associated staining correlates with clinical response to PD-1/PD-L1 inhibition. [ABSTRACT FROM AUTHOR]