Deaths due to suicide, substance use and violence/accident may reflect similar risk factors and overlap in their classification. This study aimed to investigate incidence and risk factors of ...mortality among people with HIV (PWH) due to these three related causes.
Prospectively collected data from PWH at least 18 years old and under active follow-up in the EuroSIDA study from 2007 to 2019 were analysed.
Cause-specific Cox regression analysis was used to assess risk factors.
A total of 17 881 participants were included, comprising 149 327 person-years of follow-up (PYFU). Forty participants died by suicide {incidence rate IR 95% confidence interval (CI): 0.3/1000 PYFU (0.2, 0.4)} 93 from substance use IR (95% CI): 0.6/1000 PYFU (0.5, 0.8), and 57 by violence/accident IR (95% CI): 0.4/1000 PYFU (0.3, 0.5). An AIDS diagnosis within the last 12 months was associated with nine-fold increased risk of suicide vs. no history of AIDS adjusted hazard ratio (aHR): 9.06; 95% CI: 2.07, 39.7. Male gender was associated with double the risk of violent/accidental death (aHR: 2.28; 95% CI: 1.09, 4.78). PWH in Eastern Europe and those who acquired HIV by injection drug use (IDU) demonstrated a greater risk of death due to substance use or violence/accident.
The association between a recent diagnosis of AIDS and suicide highlights a critical period for intervention. HIV infection acquired through IDU demonstrated an expected relationship with death due to substance use and violent/accidental deaths. Increased risk of death due to substance use and violence/accident in Eastern Europe demands investigation into specific differences that may drive that association.
Abstract
Background
Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 IL-6, ...interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 sCD14 and soluble CD163 sCD163) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH.
Methods
We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices.
Results
PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (−212 mL 95% confidence interval, −308 to −116 mL), lower forced vital capacity (−208 mL −322 to −93 mL), and airflow limitation (aOR, 2.62 1.58–4.36) (all P < .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005).
Conclusion
IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases.
Interleukin 6 concentrations were significantly higher in well-treated people with human immunodeficiency virus (HIV) (PWH) than in uninfected controls. Such elevations were independently associated with lower dynamic lung function and airflow limitation in well-treated PWH with undetectable viral replication.
Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV ...from 1999-2020.
Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time.
Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate MR 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio aMRR 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period.
Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.
Abstract Background Within a year of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, vaccines inducing a robust humoral and cellular immune response were implemented ...worldwide. However, emergence of novel variants and waning vaccine-induced immunity led to implementation of additional vaccine boosters. Methods This prospective study evaluated the temporal profile of cellular and serological responses in a cohort of 639 SARS-CoV-2–vaccinated participants, of whom a large proportion experienced a SARS-CoV-2 infection. All participants were infection naïve at the time of their first vaccine dose. Proportions of SARS-CoV-2 spike–specific T cells were determined after each vaccine dose using the activation-induced marker assay, while levels of circulating SARS-CoV-2 antibodies were determined by the Meso Scale serology assay. Results We found a significant increase in SARS-CoV-2 spike–specific CD4+ and CD8+ T-cell responses following the third dose of a SARS-CoV-2 messenger RNA vaccine as well as enhanced CD8+ T-cell responses after the fourth dose. Furthermore, increased age was associated with a poorer response. Finally, we observed that SARS-CoV-2 infection boosts both the cellular and humoral immune response, relative to vaccine-induced immunity alone. Conclusions Our findings highlight the boosting effect on T-cell immunity of repeated vaccine administration. The combination of multiple vaccine doses and SARS-CoV-2 infections maintains population T-cell immunity, although with reduced levels in the elderly.
Donor lymphocyte infusion (DLI) is used to induce remission in patients who relapse after allogeneic stem cell transplantation (allo-HSCT). During the last decade, the hypomethylating agent ...Azacitidine has been used together with DLI for a synergistic graft-versus-leukemia (GVL) effect. Here, we report results of DLI/Azacitidine treatment from a retrospective single-center study.
Fifty AML/MDS patients treated for relapse after allo-HSCT between 2001 and 2020 with DLI at the Department of Hematology, at Rigshospitalet, Copenhagen University Hospital were included for analyses. A subgroup of patients who obtained complete remission (CR) after reinduction chemotherapy, received DLI in combination with low-dose (32 mg/m2) Azacitidine.
Overall survival in all patients after DLI treatment was 59% at 2 years and 20% at 5 years. Relapse-free survival in patients in CR prior to DLI was 32% after 2 years and 7% after 5 years. In the DLI + low-dose-Azacitidine group, 5-year relapse-free survival was 40%.
DLI remains an effective treatment in post-transplant relapse leaving one-fifth of patients' long-term survivors. Our results support the concomitant use of low-dose Azacitidine in the future use of DLI in order to enhance the GVL effect of donor lymphocytes.
Abstract
Background
Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent ...coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified.
Methods
In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses.
Results
Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio GMR 6.79, 95% confidence interval CI 6.05–7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09–1.57) and BA.3 (1.32, 1.09–1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76–0.98), BA.4 (0.85, 0.75–0.97), and BA.5 (0.87, 0.76–0.99) antigens in individuals with a prior infection.
Conclusions
Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of Omicron variants.
Comparison of antibody responses following bivalent BA.1 and BA.4/5 vaccination and impact of previous infection. Prior antigenic exposure leaves a clear serological imprint. Both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of Omicron variants.
Graphical Abstract
Graphical Abstract
https://www.tidbitapp.io/tidbits/omicron-variant-specific-serological-imprinting-following-ba-1-or-ba-4-5-bivalentvaccination-and-previous-sars-cov-2-infection-a-cohort-study/update
Routine monitoring of parvovirus B19 (B19V) the first 6 months posttransplantation was performed in 241 seronegative solid organ transplant (SOT) recipients. Incidence rates during the first month ...and the second to sixth months posttransplantation were 1.2 (95% confidence interval CI, .33-3.2) and 0.21 (95% CI, .06-.57) per 100 recipients per month, respectively. Of the 6 SOT recipients with positive B19V polymerase chain reaction, 3 (50%) were admitted to hospital and 2 (33%) were treated with intravenous immunoglobulin. Thus, routine monitoring of B19V in seronegative SOT recipients may not be necessary. Targeted screening 1 month posttransplantation and screening upon clinical suspicion could be an alternative strategy.
Improved survival after hematopoietic cell transplantation (HCT) and an increasingly comorbid transplant population may give rise to new trends in the causes of death.
This study includes all adult ...allogeneic HCT recipients transplanted at Rigshospitalet between January 1, 2010 and December 31, 2019. Underlying causes of death were determined using the Classification of Death Causes after Transplantation (CLASS) method.
Among 802 HCT recipients, 289 died during the study period. The main causes of death were relapse (N = 133, 46.0%), graft-versus-host disease (GvHD) (N = 64, 22.1%) and infections (N = 35, 12.1%). Multivariable analyses showed that with increasing transplant calendar year, a decreased risk of all-cause mortality (HR 0.92, 95% CI 0.87-0.97) and death from GvHD (HR 0.87, 95% CI 0.78-0.97) was identified, but not for other specific causes. Standardized mortality ratios (SMRs) for all-cause mortality decreased from 23.8 (95% CI 19.1-28.5) to 18.4 (95% CI 15.0-21.9) for patients transplanted in 2010-2014 versus 2015-2019, while SMR for patients who died from GvHD decreased from 8.19 (95% CI 5.43-10.94) to 3.65 (95% CI 2.13-5.18).
As risk of all-cause mortality and death from GvHD decreases, death from relapse remains the greatest obstacle in further improvement of survival after HCT.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background. Low 25-hydroxyvitamin D (25(OH)D) has been associated with inflammation, human immunodeficiency virus (HIV) disease progression, and death. We aimed to identify the prognostic value of ...25(OH) D for AIDS, non-AIDS-defining events and death, and its association with immunological/inflammatory markers. Methods. Prospective 1-1 case-control study nested within the EuroSIDA cohort. Matched cases and controls for AIDS (n = 50 matched pairs), non-AIDS-defining (n = 63) events and death (n = 41), with plasma samples during follow-up were selected. Conditional logistic regression models investigated associations between 25(OH)D levels and annual 25(OH)D change and the probability of events. Mixed models investigated relationships between 25(OH) D levels and immunological/inflammatory markers. Results. In sum, 250 patients were included. Median time between first and last sample and last sample and event was 44.6(interquartile range IQR: 22.7-72.3) and 3.1(IQR: 1.4-6.4) months. Odds of death decreased by 46.0%(95% confidence interval CI, 2.0-70.0, P= .04) for a 2-fold increase in latest 25(OH) D level. There was no association between 25(OH) D and the occurrence of AIDS or non-AIDS-defining events (P >.05). In patients with current 25(OH) D < 10 ng/mL, hsIL-6 concentration increased by 4.7%(95% CI, .2,9.4, P =.04) annually after adjustment for immunological/inflammatory markers, and no change in hsCRP rate was observed (P =.76). Conclusions. Low Vitamin D predicts short term mortality in HIV-positive persons. Effectiveness of vitamin D supplementation on inflammation and patient outcomes should be investigated.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Acute graft-versus-host disease (aGVHD) is a leading cause of transplantation-related mortality after allogeneic hematopoietic stem cell transplantation (aHSCT). 16S ribosomal RNA (16S rRNA) ...gene-based studies have reported that lower gut bacterial diversity and the relative abundance of certain bacteria after aHSCT are associated with aGVHD. Using shotgun metagenomic sequencing and a large cohort, we aimed to confirm and extend these observations. Adult aHSCT recipients with stool samples collected from day −30 to day 100 relative to aHSCT were included. One sample was selected per patient per period (pre-aHSCT (day −30 to day 0), early post-aHSCT (day 1 to day 28), and late post-aHSCT (day 29 to day 100)), resulting in 150 aHSCT recipients and 259 samples. Microbial and clinical factors were tested for differences between time periods and an association with subsequent aGVHD. Patients showed a decline in gut bacterial diversity posttransplant, with several patients developing a dominance of Enterococcus. A total of 36 recipients developed aGVHD at a median of 34 days (interquartile range, 26-50 days) post-aHSCT. Lower microbial gene richness (P = .02), a lower abundance of the genus Blautia (P = .05), and a lower abundance of Akkermansia muciniphila (P = .01) early post-aHSCT was observed in those who developed aGVHD. Myeloablative conditioning was associated with aGVHD along with a reduction in gene richness and abundance of Blautia and A muciniphila. These results confirm low diversity and Blautia being associated with aGVHD. Crucially, we add that pretransplant conditioning is associated with changes in gut microbiota. Investigations are warranted to determine the interplay of gut microbiota and conditioning in the development of aGVHD.
•Lower gene richness and a lower abundance of Blautia and A muciniphila were associated with subsequent aGVHD.•Myeloablative conditioning was associated with aGVHD as well as a reduction in gene richness and abundance of Blautia and A muciniphila.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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