Clinical Presentation, Treatment Response and Virology Outcomes of Women who Seroconverted in the Dapivirine Vaginal Ring Trials – The Ring Study and DREAM

alexandrossfakianakis shared this article with you from Inoreader Clinical Presentation, Treatment Response and Virology Outcomes of Women who Seroconverted in the Dapivirine Vaginal Ring Trials – The Ring Study and DREAM via Clinical Infectious Diseases Advance Access Abstract Background Participants who HIV seroconverted in The Ring Study, a Phase III trial of Dapivirine Vaginal Ring (DVR), or in the open-label extension trial DREAM, were offered enrollment in an observational cohort study (IPM 007) to assess clinical presentation and response to antiretroviral treatment (ART). Methods Participants' HIV infection was managed at local treatment clinics according to national treatment guidelines. IPM 007 study visits occurred 3 and 6 months after enrollment, and every 6 months thereafter. Assessments included plasma HIV-1 RNA, CD4+ T-cell counts, and recording of HIV/AIDS-associated events and ARV use. Post-hoc virology analyses were performed for participants identified with virologic failure. Results One-hundred-and-fifty-one of 179 eligible participants (84.4%) enrolled into IPM 007; 103 had previously received the DVR in the Ring or DREAM studies; 48 had received placebo in The Ring Stu dy. HIV-1 RNA and CD4+ T-cell counts after 12 months' follow-up were similar for participants who used the DVR in The Ring Study and DREAM, compared to those who received placebo. Of the 78 participants with a study visit approximately 6 months after ART initiation, 59 (75.6%) had HIV-1 RNA <40 copies/mL (The Ring Study: placebo: 13/23; 56.5%; DVR: 32/39; 82.1%; DREAM [DVR]: 14/16; 87.5%). Post-hoc virology analysis indicated that genotypic patterns observed at virologic failure were as expected of an NNRTI-based regimen. Conclusions Seroconversion during DVR use did not negatively affect clinical presentation or treatment outcome. Mutation patterns at virologic failure were in line with individuals failing an NNRTI-based regimen. View on Web

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Impact of respiratory infection and chronic comorbidities on early pediatric antibiotic dispensing in the United States

alexandrossfakianakis shared this article with you from Inoreader Impact of respiratory infection and chronic comorbidities on early pediatric antibiotic dispensing in the United States via Clinical Infectious Diseases Advance Access Abstract Background In the United States, children under age 5 receive high volumes of antibiotics, which may contribute to antibiotic resistance. It has been unclear what role preventable illnesses and chronic comorbidities play in prompting antibiotic prescriptions. Methods We conducted an observational study with a cohort of 124,759 children under age 5 born in the United States between 2008 and 2013 with private medical insurance. Study outcomes included the cumulative number of antibiotic courses dispensed per child by age 5 and the proportion of children for whom at least one antibiotic course was dispensed by age 5. We identified which chronic medical conditions predicted whether a child would be among the top 20% of antibiotic recipients. Results Children received a mean of 6.8 (95% confidence interval [CI] 6.7, 6.9) antibiotic courses by age five, and 91% (95% CI 90, 92) of children had received at least one antibiotic course by age five. Most antibiotic courses (71%, 95% CI 70, 72) were associated with respiratory infections. Presence of a pulmonary/respiratory, otologic, and/or immunological comorbidity substantially increase a child's odds of being in the top 20% of antibiotic recipients. Children with at least one of these conditions received a mean of 10.5 (95% CI 10.4, 10.6) antibiotic courses by age 5. Conclusions Privately insured children in the US receive high volumes of antibiotics early in their lives, largely related to respiratory infections. Antibiotic dispensing is unequally distributed among children, with substantially more antibiotics dispensed to children with select comorbidities. View on Web

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Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV

alexandrossfakianakis shared this article with you from Inoreader Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV via Clinical Infectious Diseases Advance Access Abstract Background People with HIV on antiretroviral therapy with good CD4 T cell counts make effective immune responses following vaccination against SARS-CoV-2. There are few data on longer term responses and the impact of a booster dose. Methods Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed twelve months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µl. Immune responses to the ancestral strain and variants of concern were measured by anti-spike IgG ELISA, MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, Activation Induced Marker (AIM) assay and T cell proliferation. Findings 54 participants received two doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) one year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titres (MSD), ACE-2 inhibition and IgG ELISA results were significantly higher compared to Day 182 titres (P < 0.0001 for all three). SARS-CoV-2 specific CD4+ T cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4 + and CD8+ T cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron. Conclusions In PWH receiving a third vaccine dose, there were significant increases in B and T cell immunity, including to known VOCs. View on Web

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Inhibition of TRPC6 suppressed TGFβ-induced fibroblast-myofibroblast transdifferentiation in renal interstitial NRK-49F cells

alexandrossfakianakis shared this article with you from Inoreader Inhibition of TRPC6 suppressed TGFβ-induced fibroblast-myofibroblast transdifferentiation in renal interstitial NRK-49F cells via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 4 October 2022 Source: Experimental Cell Research Author(s): Shan Jiang, Lifei Gu, Yixin Hu, Younan Ren, Zhao Yang, Chengzhi Chai, Boyang Yu, Haitao Ge, Zhengyu Cao, Fang Zhao View on Web

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Imaging of pediatric neuroblastoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric neuroblastoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper via Pediatric Blood & Cancer ABSTRACT Neuroblastoma is the most common extracranial solid neoplasm in children. This manuscript provides consensus-based imaging recommendations for pediatric neuroblastoma patients at diagnosis and during follow-up. View on Web

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Irinotecan dose schedule for the treatment of Ewing sarcoma

alexandrossfakianakis shared this article with you from Inoreader Irinotecan dose schedule for the treatment of Ewing sarcoma via Pediatric Blood & Cancer Abstract Irinotecan and temozolomide achieve objective responses in patients with Ewing sarcoma that recurs after initial therapy. Optimal dose schedules have not been defined. We reviewed published series of patients treated with irinotecan and temozolomide for Ewing sarcoma that recurred after initial therapy. We compared objective response rates for patients who received 5-day irinotecan treatment schedules to response rates for patients who achieved 10-day irinotecan treatment schedules. Among 89 patients treated with a 10-day irinotecan schedule, there were 47 objective responses (53%). Among 180 patients treated with a 5-day irinotecan schedule, there were 52 responses (29%). In the treatment of recurrent Ewing sarcoma, investigators should consider the use of a 10-day schedule for administration of irinotecan. View on Web

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Refractory pediatric acute myeloid leukemia expressing NUP98‐NSD1 fusion gene responsive to chemotherapy combined with venetoclax and decitabine

alexandrossfakianakis shared this article with you from Inoreader Refractory pediatric acute myeloid leukemia expressing NUP98‐NSD1 fusion gene responsive to chemotherapy combined with venetoclax and decitabine via Pediatric Blood & Cancer View on Web

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