Association between obesity and cancer risk in HIV-infected Asians.

INTRODUCTION: This study aimed to investigate the association between obesity and cancer risk as well as site-specific cancer risks in adults with HIV using a nationwide health screening database in Korea. METHODS: Of the 16,671 adults with a new diagnosis of HIV from 2004 to 2020, 456 incident cancer cases and 1,814 individually matched controls by sex, year of birth, year of HIV diagnosis, and follow-up duration (1:4 ratio) were included in this nested case-control study. The association between obesity (body mass index ≥25 kg/m 2 ) and cancer risks was estimated and presented as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 456 cancer incident cases, there were 146 AIDS-defining cancer cases and 310 non-AIDS-defining cancer cases. Compared with non-obese adults with HIV, obese adults with HIV were at higher risk of non-AIDS-defining cancer (OR = 1.478, 95% CI = 1.118-1.955). Otherwise, the overall risk of AIDS-defining cancer (OR = 0.816, 95% CI = 0.520-1.279) and each type of AIDS-defining cancer (Kaposi sarcoma and non-Hodgkin's lymphoma) were not high in obese adults with HIV. Of the specific types of non-AIDS-defining cancers, obesity was associated with an increased risk of colorectal cancer (OR = 3.090, 95% CI = 1.110-8.604) and liver, bile duct, and pancreatic cancers (OR = 2.532, 95% CI = 1.141-5.617). CONCLUSIONS: Obesity, which is one of the important health concerns in HIV management, was associated with an increased risk of non-AIDS-defining cancer but not AIDS-defining cancer.

Omicron BA.2 breakthrough infection elicits CD8+ T cell responses recognizing the spike of later Omicron subvariants.

Here, we examine peripheral blood memory T cell responses against the SARS-CoV-2 BA.4/BA.5 variant spike among vaccinated individuals with or without Omicron breakthrough infections. We provide evidence supporting a lack of original antigenic sin in CD8+ T cell responses targeting the spike. We show that BNT162b2-induced memory T cells respond to the BA.4/BA.5 spike. Among individuals with BA.1/BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.4/BA.5 spike increased. In a subgroup with BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.2-mutated spike region increased and correlated directly with responses against the BA.4/BA.5 spike, indicating that BA.2 spike-specific CD8+ T cells elicited by BA.2 breakthrough infection cross-react with the BA.4/BA.5 spike. We identified CD8+ T cell epitope peptides that are present in the spike of BA.2 and BA.4/BA.5 but not the original spike. These peptides are fully conserved in the spike of now-dominant XBB lineages. Our study shows that breakthrough infection by early Omicron subvariants elicits CD8+ T cell responses that recognize epitopes within the spike of newly emerging subvariants.

Pentraxin 3 as an Immune Recovery Marker in HIV Infection After Combination Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection causes chronic inflammation in affected individuals. Chronic inflammation may hinder immunological recovery. Treatment with combination antiretroviral therapy (cART) is insufficient to reduce inflammation. Pentraxin 3 (PTX3) is an inflammatory marker associated with cardiovascular disease, malignancy, and acute infection. This study evaluated the usefulness of serum PTX3 levels in measuring inflammation levels, which may be associated with the probability of immune recovery in people living with HIV (PLH). In this single-center prospective study, we measured serum PTX3 levels in PLH treated with cART. Clinical information on HIV status, type of cART administered, and CD4+ and CD8+ T cell counts at the initial diagnosis of HIV and at study enrollment was obtained from each participant. PLH were divided into good and poor responder groups according to their CD4+ T cell counts at enrollment. A total of 198 PLH were enrolled in this study. A total of 175 and 23 participants were assigned to the good and poor responder groups, respectively. The poor responder group exhibited higher PTX3 levels (0.53 ng/mL vs. 1.26 ng/mL, p = .032). Logistic regression analysis demonstrated that low body mass index [odds ratio (OR) = 0.8, p = .010], low initial CD4+ T cell counts at diagnosis (OR = 0.994, p = .001), and high PTX3 levels (OR = 1.545, p = .006) are clinical factors that were significantly associated with poor immune recovery in PLH. According to the Youden index, PTX3 levels >1.25 ng/mL are associated with poor immune recovery. PLH should be clinically, virologically, and immunologically evaluated. Serum PTX level is a useful inflammatory marker associated with immune recovery in PLH treated with cART.

Alismol Purified from the Tuber of Alisma orientale Relieves Acute Lung Injury in Mice via Nrf2 Activation.

Since the ethanol extract of Alisma orientale Juzepzuk (EEAO) suppresses lung inflammation by suppressing Nuclear Factor-kappa B (NF-κB) and activating Nuclear Factor Erythroid 2-related Factor 2 (Nrf2), we set out to identify chemicals constituting EEAO that suppress lung inflammation. Here, we provide evidence that among the five most abundant chemical constituents identified by Ultra Performance Liquid Chromatography (UPLC) and Nuclear Magnetic Resonance (NMR), alismol is one of the candidate constituents that suppresses lung inflammation in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model and protects mice from ALI-like symptoms. Alismol did not induce cytotoxicity or reactive oxygen species (ROS). When administered to the lung of LPS-induced ALI mice (n = 5/group), alismol decreased the level of neutrophils and of the pro-inflammatory molecules, including Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Monocyte Chemoattractant Protein-1 (MCP-1), Interferon-gamma (IFN-γ), and Cyclooxygenase-2 (COX-2), suggesting an anti-inflammatory activity of alismol. Consistent with these findings, alismol ameliorated the key features of the inflamed lung of ALI, such as high cellularity due to infiltrated inflammatory cells, the development of hyaline membrane structure, and capillary destruction. Unlike EEAO, alismol did not suppress NF-κB activity but rather activated Nrf2. Consequently, alismol induced the expression of prototypic genes regulated by Nrf2, including Heme Oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase-1 (NQO-1), and glutamyl cysteine ligase catalytic units (GCLC). Alismol activating Nrf2 appears to be associated with a decrease in the ubiquitination of Nrf2, a key suppressive mechanism for Nrf2 activity. Together, our results suggest that alismol is a chemical constituent of EEAO that contributes at least in part to suppressing some of the key features of ALI by activating Nrf2.

Trends, clinical characteristics, antimicrobial susceptibility patterns, and outcomes of Campylobacter bacteraemia: a multicentre retrospective study.

PURPOSE: We aimed to explore the clinical characteristics of Campylobacter bacteraemia and identify the trends, risk factors for mortality, and antimicrobial susceptibility patterns from clinical samples. METHODS: This retrospective cohort study included patients confirmed to have Campylobacter bacteraemia from seven hospitals between January 2010 and June 2021. Data on demographics and underlying history, clinical manifestation, and antimicrobial susceptibility patterns were collected and analyzed. Annual cases of Campylobacter enteritis were extracted from a public database. RESULTS: A total of 108 patients were included, and five species were isolated. Campylobacter jejuni accounted for 54 (50.0%) cases and 17 (16%) patients had no symptoms other than fever. In-hospital mortality occurred in 14 (13.0%) patients. C. jejuni bacteraemia was associated with lower mortality compared to non-C. jejuni bacteraemia. Underlying cancer and septic shock were the significant factors associated with in-hospital mortality. Quinolone resistance was high (59%), whereas only 4% of isolates exhibited macrolide resistance. There has been a significant increase in the number of Campylobacter enteritis cases, which was strongly correlated with the number of Campylobacter bacteraemia cases (Pearson's coefficient: 0.953; p < 0.0001). CONCLUSION: The notably increasing incidence of Campylobacter bacteraemia and antibiotic resistance patterns can challenge the treatment, necessitating collective efforts of national surveillance and networks by many departments.

Risk of lymphadenopathy from SARS-CoV-2 vaccination in Korea: a self-controlled case series analysis.

OBJECTIVES: To assess the risk of lymphadenopathy following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS: A self-controlled case series design was used to determine whether the risk of lymphadenopathy was higher in the 1-day to 42-day risk interval after coronavirus disease 2019 (COVID-19) vaccination compared to the control period. In addition, subgroup analyses were conducted according to baseline characteristics, time since vaccination, and sensitivity analyses adjusted for the length of the risk interval. RESULTS: The risk of developing lymphadenopathy in the risk interval (1-42 days) after COVID-19 vaccination compared to the control period was significantly increased, with a relative incidence (RI) of 1.17 (95% confidence interval [CI], 1.17 to 1.18) when the first, second, and third doses were combined. The RI was greater on the day of vaccination (1.47; 95% CI, 1.44 to 1.50). In subgroup analyses by baseline characteristics, a significantly increased risk or trend toward increased risk was observed in most subgroups except for those aged 70 years and older, with a significant increase in risk in younger individuals, those with a Charlson's comorbidity index <5, and those who received mRNA vaccines (mRNA-1273>BNT162b2). Within the 1-day to 42-day post-dose risk period, the relative risk was highest during the 1-day to 7-day post-dose period (1.59; 95% CI, 1.57 to 1.60) compared to the control period, and then the risk declined. In the sensitivity analysis, we found that the longer the risk window, the smaller the RI. CONCLUSIONS: SARS-CoV-2 vaccination is associated with a statistically significant increase in the risk of lymphadenopathy, and this risk was observed only with mRNA vaccines.

Novel Anti-Melanoma Compounds Are Efficacious in A375 Cell Line Xenograft Melanoma Model in Nude Mice.

Despite the successes of immunotherapy, melanoma remains one of the deadliest cancers, therefore, the need for innovation remains high. We previously reported anti-melanoma compounds that work by downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compounds were non-toxic to Balb/C mice at 50 mg/kg suggesting their utility in in vivo studies. In the present study, we aimed to assess the efficacy of these compounds by testing them in A375 cell-line xenograft in nude athymic mice. Animals were randomized into four groups (n = 12/group): 10 mg/kg vemurafenib, and 25 mg/kg 2155-14 and 2155-18 thrice a week for 15 days along with a control group. The results revealed that both 2155-14 and 2155-18 significantly decreased the growth of A375 tumors, which was comparable to vemurafenib. These results were confirmed by tumor volume, weight, and histopathological examination. In conclusion, these results demonstrate the therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2.

Assessment of Disease Burden and Immunization Rates for Vaccine-Preventable Diseases in People Living with HIV: The Korea HIV/AIDS Cohort Study.

BACKGROUND: Prophylactic immunization is important for human immunodeficiency virus (HIV)-infected patients; however, there are insufficient data on the burden of vaccine-preventable diseases (VPDs), vaccination rates, and factors influencing vaccination. MATERIALS AND METHODS: The incidence and prevalence of VPDs in HIV-infected patients between 2006 and 2017 were estimated using the Korean HIV/acquired immune deficiency syndrome (AIDS) cohort database. In addition, we evaluated the vaccination rates and influencing factors for vaccination in HIV-infected patients through multilevel analysis of clinico-epidemiological factors, immune status, and psychological status. A questionnaire survey was conducted among experts to determine whether they recommend vaccination for HIV-infected patients. RESULTS: The incidence rates of hepatitis B virus (HBV) infection, herpes zoster, and anogenital warts were 1.74, 7.38, and 10.85 per 1,000 person-years, respectively. The prevalence of HBV infection and anogenital warts at enrollment was 4.8% and 8.6%, respectively, which increased to 5.3% and 12.0%, respectively, by 2017. In HIV-infected patients, HBV (21.7% in 2008, 56.3% in 2013, and 75.4% in 2017) and pneumococcal vaccination rates (3.0% in 2015, 7.6% in 2016, and 9.6% in 2017) increased annually, whereas the influenza vaccination rate remained similar by season (32.7 - 35.6%). In the multilevel analysis, peak HIV viral load (≥50 copies/mL: odds ratio [OR] = 0.64, 95% confidence interval [CI]: 0.44 - 0.93; reference, <50 copies/mL) was an influencing factor for pneumococcal vaccination, while nadir CD4 T-cell counts (200 - 350 cells/mm3: OR = 0.54, 95% CI: 0.38 - 0.76; <200 cells/mm3: OR = 0.89, 95% CI: 0.62 - 1.28; reference, ≥350 cells/mm3) was an influencing factor for HBV vaccination. Influenza vaccination was associated with male sex (OR = 1.94) and the number of antiretroviral therapy (ART) regimen change (OR = 1.16), but was not significantly associated with HIV viral load or CD4 T-cell counts. Most experts responded that they administer hepatitis A virus, HBV, pneumococcal, and influenza vaccines routinely, but not human papillomavirus (12.9%) or herpes zoster vaccines (27.1%). CONCLUSION: The burden of vaccine-preventable diseases was quite high in HIV-infected patients. Nadir CD4 T-cell counts, peak HIV viral loads, and the number of ART regimen change are significant factors related to vaccination. Considering the low vaccination rates for VPDs, there was a discordance between experts' opinions and real clinical practice in the medical field.

Long-term prognosis and overall mortality in patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis.

Lysosomal dysfunction in Down syndrome and Alzheimer mouse models is caused by v-ATPase inhibition by Tyr682-phosphorylated APP ßCTF.

Lysosome dysfunction arises early and propels Alzheimer's disease (AD). Herein, we show that amyloid precursor protein (APP), linked to early-onset AD in Down syndrome (DS), acts directly via its ß-C-terminal fragment (ßCTF) to disrupt lysosomal vacuolar (H+)-adenosine triphosphatase (v-ATPase) and acidification. In human DS fibroblasts, the phosphorylated 682YENPTY internalization motif of APP-ßCTF binds selectively within a pocket of the v-ATPase V0a1 subunit cytoplasmic domain and competitively inhibits association of the V1 subcomplex of v-ATPase, thereby reducing its activity. Lowering APP-ßCTF Tyr682 phosphorylation restores v-ATPase and lysosome function in DS fibroblasts and in vivo in brains of DS model mice. Notably, lowering APP-ßCTF Tyr682 phosphorylation below normal constitutive levels boosts v-ATPase assembly and activity, suggesting that v-ATPase may also be modulated tonically by phospho-APP-ßCTF. Elevated APP-ßCTF Tyr682 phosphorylation in two mouse AD models similarly disrupts v-ATPase function. These findings offer previously unknown insight into the pathogenic mechanism underlying faulty lysosomes in all forms of AD.

Utility of Plasma Microbial Cell-Free DNA Whole-Genome Sequencing for Diagnosis of Invasive Aspergillosis in Patients With Hematologic Malignancy or COVID-19.

BACKGROUND: We evaluated the clinical accuracy and utility of whole-genome sequencing (WGS) of plasma microbial cell-free DNA (cfDNA) as a novel noninvasive method in diagnosing invasive aspergillosis (IA) in patients with hematologic malignancy (HM) or coronavirus disease 2019 (COVID-19). METHODS: Adults with HM or COVID-19 and suspected IA were recruited. IA cases were retrospectively diagnosed according to EORTC/MSG definitions and ECMM/ISHAM criteria for HM and COVID-19 patients, respectively. The results of cfDNA WGS were compared with the conventional diagnosis. RESULTS: Microbial cfDNA WGS was performed 53 times from 41 participants (19 from HM, 16 from COVID-19, and 7 from the control group). In participants with HM, Aspergillus cfDNA was detected in 100% of proven IA and 91.7% of probable IA cases. In participants with COVID-19, 50.0% of probable IA were positive for Aspergillus in cfDNA WGS. Concordance between Aspergillus cfDNA detection and proven/probable IA conventional diagnosis was significantly higher in participants with HM than in those with COVID-19. IA diagnosed using EORTC/MGS definitions showed significantly high concordance between Aspergillus cfDNA detection and proven/probable IA. CONCLUSIONS: Aspergillus cfDNA detection strongly correlated with proven/probable IA diagnosed using EORTC/MSG definitions and could be used as an additional diagnostic tool for IA.

Cortical and Trabecular Bone Deficit in Middle-Aged Men Living with HIV.

A significant increase in the risk of hip fracture was observed in middle-aged men living with human immunodeficiency virus (MLWH), almost a decade earlier than those without infection. Data regarding cortical and trabecular bone deficit of hip, an important determinant of bone strength, in MLWH are limited. Quantitative CT was performed in consecutive MLWH aged ≥30 years between November 2017 and October 2018 at Severance Hospital, Seoul, Korea. Volumetric bone mineral density (vBMD) and cortical bone mapping parameters of hip (cortical thickness [CTh], cortical bone vBMD [CBMD], cortical mass surface density [CMSD], endocortical trabecular density [ECTD]) were compared to age-matched and body mass index (BMI)-matched controls (1:2) using a community-based healthy adults cohort. Among 83 MLWH and 166 controls (mean age: 47.2 years; BMI: 23.6 kg/m2 ), MLWH had lower total hip vBMD (280 ± 41 versus 296 ± 41 mg/cm3 ), CMSD (155 versus 160 mg/cm2 ), and ECTD (158 versus 175 mg/cm3 ) than controls that remained robust after adjustment for covariates (adjusted ß: total hip vBMD, -18.8; CMSD, -7.3; ECTD, -18.0; p < 0.05 for all). Cortical bone mapping revealed localized deficit of CTh, CBMD, and CMSD in the anterolateral trochanteric region and femoral neck in MLWH compared to controls, with a more extensive ECTD deficit. In MLWH, lower CD4 T-cell count (/100 cells/mm3 decrement) and protease inhibitor (PI)-based regimen (versus non-PI regimen) at the time of antiretroviral treatment initiation were associated with lower total hip vBMD (adjusted ß -7.5 for lower CD4 count; -28.3 for PI-based regimen) and CMSD (adjusted ß -2.6 for lower CD4 count; -12.7 for PI-based regimen; p < 0.05 for all) after adjustment for covariates including age, BMI, smoking, alcohol use, hepatitis C virus co-infection, tenofovir exposure, and CT scanner types. MLWH had lower hip bone density with cortical and trabecular bone deficit compared to community-dwelling controls. © 2023 American Society for Bone and Mineral Research (ASBMR).

Structure-Based Development of Isoform-Selective Inhibitors of Casein Kinase 1ε vs Casein Kinase 1δ.

Specific inhibition of a single kinase isoform is a challenging task due to the highly conserved nature of ATP-binding sites. Casein kinase 1 (CK1) δ and ε share 97% sequence identity in their catalytic domains. From a comparison of the X-ray crystal structures of CK1δ and CK1ε, we developed a potent and highly CK1ε-isoform-selective inhibitor (SR-4133). The X-ray co-crystal structure of the CK1δ-SR-4133 complex reveals that the electrostatic surface between the naphthyl unit of SR-4133 and CK1δ is mismatched, destabilizing the interaction of SR-4133 with CK1δ. Conversely, the hydrophobic surface area resulting from the Asp-Phe-Gly motif (DFG)-out conformation of CK1ε stabilizes the binding of SR-4133 in the ATP-binding pocket of CK1ε, leading to the selective inhibition of CK1ε. The potent CK1ε-selective agents display nanomolar growth inhibition of bladder cancer cells and inhibit the phosphorylation of 4E-BP1 in T24 cells, which is a direct downstream effector of CK1ε.

Immunogenicity Differences of the ChAdOx1 nCoV-19 Vaccine According to Pre-Existing Adenovirus Immunity.

This study investigated the immunogenicity of, and reactogenicity to, the ChAdOx1 nCoV-19 vaccine according to pre-existing adenovirus immunity. Individuals scheduled for COVID-19 vaccination were prospectively enrolled in a tertiary hospital with 2400 beds from March 2020 onwards. Pre-existing adenovirus immunity data was obtained before ChAdOx1 nCoV-19 vaccination. A total of 68 adult patients administered two doses of the ChAdOx1 nCoV-19 vaccine were enrolled. Pre-existing adenovirus immunity was identified in 49 patients (72.1%), but not in the remaining 19 patients (27.9%). The geometric mean titer of S-specific IgG antibodies was statistically higher in individuals without pre-existing adenovirus immunity at several time points: before the second ChAdOx1 nCoV-19 dose (56.4 (36.6-125.0) vs. 51.0 (17.9-122.3), p = 0.024), 2-3 weeks after the second ChAdOx1 nCoV-19 dose (629.5 (451.5-926.5) vs. 555.0 (287.3-926.0), p = 0.049), and 3 months after the second ChAdOx1 nCoV-19 dose (274.5 (160.5-655.3) vs. 176.0 (94.3-255.3), p = 0.033). In the absence of pre-existing adenovirus immunity, systemic events were observed with higher frequency, especially chills (73.7% vs. 31.9%, p = 0.002). In conclusion, individuals without pre-existing adenovirus immunity showed a higher immune response to ChAdOx1 nCoV-19 vaccination and a higher frequency of reactogenicity to ChAdOx1 nCoV-19 vaccination was observed.

Identification of a novel spirocyclic Nek2 inhibitor using high throughput virtual screening.

NIMA Related Kinase 2 (Nek2) kinase is an attractive target for the development of therapeutic agents for several types of highly invasive cancers. Despite this, no small molecule inhibitor has advanced to the late clinical stages thus far. In this work, we have identified a novel spirocyclic inhibitor (V8) of Nek2 kinase, utilizing a high-throughput virtual screening (HTVS) approach. Using recombinant Nek2 enzyme assays, we show that V8 can inhibit Nek2 kinase activity (IC50 = 2.4 ± 0.2 µM) by binding to the enzyme's ATP pocket. The inhibition is selective, reversible and is not time dependent. To understand the key chemotype features responsible for Nek2 inhibition, a detailed structure-activity relationships (SAR) was performed. Using molecular models of the energy-minimized structures of Nek2-inhibitory complexes, we identify key hydrogen-bonding interactions, including two from the hinge-binding region, likely responsible for the observed affinity. Finally, using cell-based studies, we show that V8 attenuates (a) pAkt/PI3 Kinase signaling in a dose-dependent manner, and (b) proliferative and migratory phenotypes of highly aggressive human MDA-MB-231 breast and A549 lung cancer cell lines. Thus, V8 is an important novel lead compound for the development of highly potent and selective Nek2 inhibitory agents.

Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study.

PURPOSE: We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). Materials and Methods: Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector-based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. RESULTS: Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. CONCLUSION: CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Factors associated with reduced function and quality of life among adult people with HIV with depression and substance use in the Asia-Pacific region.

BACKGROUND: Depression and substance use (SU) disorders are prevalent among people with HIV (PWH) and impact health outcomes despite successful antiretroviral therapy (ART). We explored quality of life, functional ability and associated factors among PWH screened positive for depression and/or SU. METHODS: This cross-sectional study recruited adult PWH during routine follow-up at five HIV clinical sites in the Asia-Pacific region. Participants were screened for depression using Patient Health Questionnaire-9 and SU using Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Quality of life (QoL) was assessed with WHOQOL-HIV BREF and functional ability with World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Factors associated with mean QoL and disability scores were analysed using linear regression. RESULTS: Of 864 PWH enrolled, 753 screened positive for depression or SU. The median (interquartile range, IQR) age was 38 (31-47) years and 97% were on ART. Overall mean WHOQOL-HIV BREF and WHODAS scores indicated greater impairment with increasing depressive symptom severity and SU risk. In multivariate analysis, PWH reporting previous trauma/stress (difference = 2.7, 95% confidence interval [CI] 1.5-3.9, P  < 0.001) and past mental health diagnosis (difference = 5.0, 95% CI 2.9-7.1, P  < 0.001) were associated with greater disability and poorer QoL scores across multiple domains ( P < 0.01 for all). Higher CD4 T-cell counts was also associated with better QoL scores and functional ability. CONCLUSION: PWH with depression/SU experienced poorer QoL and function despite routine engagement in HIV care. Efforts to integrate mental health services and interventions addressing disability into HIV management should be prioritized in the region.

Impact of the Duration of Postoperative Antibiotics on the Prognosis of Patients with Infective Endocarditis.

Appropriate postoperative antibiotic treatment in patients with infective endocarditis (IE) reduces the risks of recurrence and mortality. However, concerns about adverse drug reactions arise due to prolonged antibiotic usage. Therefore, we compared the recurrence and mortality rates according to the duration of postoperative antibiotic therapy in patients with IE. From 2005 to 2017, we retrospectively reviewed 416 patients with IE treated at a tertiary hospital in South Korea; among these, 216 patients who underwent heart valve surgery and received appropriate antibiotics were enrolled. The patients were divided into two groups based on the duration of usage of postoperative antibiotic therapy; the duration of postoperative antibiotic therapy was more than two weeks in 156 patients (72.2%) and two weeks or less in 60 patients (27.8%). The primary endpoint was IE relapse. The secondary endpoints were 1-year IE recurrence, 1-year mortality, and postoperative complication rates. The median age was 53 (interquartile range: 38-62) years. The relapse rate of IE was 0.9% (2/216). There was no statistical difference in relapse (0.0% vs. 1.3%, p = 0.379), 1-year recurrence (1.7% vs. 1.3%, p = 0.829), or 1-year mortality (10.0% vs. 5.8%, p = 0.274) between patients with postoperative antibiotic administration of two weeks or less versus more than two weeks. The duration of postoperative antibiotic therapy did not affect the 1-year mortality rate (log-rank test, p = 0.393). In conclusion, there was no statistically significant difference in recurrence, mortality, or postoperative complications according to the duration of postoperative antibiotic therapy.

Enhanced antibody responses in fully vaccinated individuals against pan-SARS-CoV-2 variants following Omicron breakthrough infection.

Omicron has become the globally dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. Compared with two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augments serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern.

Mortality and Causes of Death among Individuals Diagnosed with Human Immunodeficiency Virus in Korea, 2004-2018: An Analysis of a Nationwide Population-Based Claims Database.

The mortality rate and causes of death among individuals diagnosed with human immunodeficiency virus (HIV) infection in Korea were described and compared to those of the general population of Korea using a nationwide population-based claims database. We included 13,919 individuals aged 20-79 years newly diagnosed with HIV between 2004 and 2018. The patients' vital status and cause of death were linked until 31 December 2019. Standardized mortality ratios (SMRs) for all-cause death and specific causes of death were calculated. By the end of 2019, 1669 (12.0%) of the 13,919 HIV-infected participants had died. The survival probabilities of HIV-infected individuals at 1, 5, 10, and 15 years after diagnosis in Korea were 96.2%, 91.6%, 85.9%, and 79.6%, respectively. The main causes of death during the study period were acquired immunodeficiency syndrome (AIDS; 59.0%), non-AIDS-defining cancer (8.2%), suicide (7.4%), cardiovascular disease (4.9%), and liver disease (2.7%). The mortality rate of men and women infected with HIV was 5.60-fold (95% CI = 5.32-5.89) and 6.18-fold (95% CI = 5.30-7.09) that of men and women in the general population, respectively. After excluding deaths due to HIV, the mortality remained significantly higher, with an SMR of 2.16 (95% CI = 1.99-3.24) in men and 3.77 (95% CI = 3.06-4.48) in women. HIV-infected individuals had a higher overall mortality than the general population, with AIDS the leading cause of mortality. Additionally, mortality due to non-AIDS-related causes was higher in HIV-infected individuals.