Framingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART.

INTRODUCTION: Immune dysregulation persists in people with HIV (PWH) on antiretroviral therapy (ART) and may lead to accelerated vascular ageing and cardiovascular disease (CVD). While delayed time to initiation of ART has been linked to worse cardiovascular outcomes, the effect of ART initiation during acute infection on these outcomes is not well understood. METHODS: Participants were enrolled from the SEARCH010/RV254 acute HIV (AHI) and HIV-NAT chronic HIV (CHI) cohorts in Thailand. Participants with 6-year follow-up and viral suppression (viral load < 50 copies/µL) at follow-up were included. Both unmatched cohorts and age and gender-matched cohorts were analysed. Demographics, HIV laboratories, and cardiovascular risk factors from enrolment and 6-year follow-up were obtained from electronic records. Framingham Risk Score (FRS), vascular age (VA), vascular age deviation (VAD), and 10-year atherosclerotic cardiovascular disease (ASCVD) risk were calculated from previously published equations. Vascular outcomes in AHI and CHI cohorts were compared, and univariable and multivariable linear regression analyses were used to investigate risk factors associated with worse vascular scores. RESULTS: In all, 373 AHI participants and 608 CHI participants were identified. AHI participants were of younger age, had a higher prevalence of syphilis and a lower prevalence of prior hepatitis B, tuberculosis, diabetes, and hypertension. Higher CD4 T-cell and lower CD8 T-cell counts were seen in the AHI cohort at enrolment and 6-year follow-up. In all participants, the AHI cohort had a lower median FRS (p < 0.001) and VA (p < 0.001), but higher VAD (p < 0.001). However, in matched cohorts, no differences were found in FRS-based outcomes. In all participants, higher VAD after 6 years of ART was associated with higher body mass index (p < 0.001) and higher CD4 count (p < 0.001), which persisted in multivariable analysis. When FRS components were analysed individually, CD4 count was associated only with male sex and cholesterol. CONCLUSIONS: We did not identify differences in FRS-based vascular outcomes at 6 years in matched cohorts of participants who started ART during AHI versus CHI. We identified a correlation between higher CD4 count and worse FRS-based vascular outcomes, which may be driven by underlying metabolic risk factors. Further study is needed to confirm these findings and evaluate underlying mechanisms.

Improvement of adenoma detection rate by two computer-aided colonic polyp detection systems in high adenoma detectors: a randomized multicenter trial.

BACKGROUND: This study aimed to evaluate the benefits of a self-developed computer-aided polyp detection system (SD-CADe) and a commercial system (CM-CADe) for high adenoma detectors compared with white-light endoscopy (WLE) as a control. METHODS: Average-risk 50-75-year-old individuals who underwent screening colonoscopy at five referral centers were randomized to SD-CADe, CM-CADe, or WLE groups (1:1:1 ratio). Trainees and staff with an adenoma detection rate (ADR) of ≥35% were recruited. The primary outcome was ADR. Secondary outcomes were the proximal adenoma detection rate (pADR), advanced adenoma detection rate (AADR), and the number of adenomas, proximal adenomas, and advanced adenomas per colonoscopy (APC, pAPC, and AAPC, respectively). RESULTS: The study enrolled 1200 participants. The ADR in the control, CM-CADe, and SD-CADe groups was 38.3%, 50.0%, and 54.8%, respectively. The pADR was 23.0%, 32.3%, and 38.8%, respectively. AADR was 6.0%, 10.3%, and 9.5%, respectively. After adjustment, the ADR and pADR in both intervention groups were significantly higher than in controls (all P<0.05). The APC in the control, CM-CADe, and SD-CADe groups was 0.66, 1.04, and 1.16, respectively. The pAPC was 0.33, 0.53, and 0.64, respectively, and the AAPC was 0.07, 0.12, and 0.10, respectively. Both CADe systems showed significantly higher APC and pAPC than WLE. AADR and AAPC were improved in both CADe groups versus control, although the differences were not statistically significant. CONCLUSION: Even in high adenoma detectors, CADe significantly improved ADR and APC. The AADR tended to be higher with both systems, and this may enhance colorectal cancer prevention.

The plasma kynurenine-to-tryptophan ratio as a biomarker of tuberculosis disease in people living with HIV on antiretroviral therapy: an exploratory nested case-control study.

BACKGROUND: Non-sputum-based tests are needed to predict or diagnose tuberculosis (TB) disease in people living with HIV (PWH). The enzyme indoleamine 2, 3-dioxygenase-1 (IDO1) is expressed in tuberculoid granuloma and catabolizes tryptophan (Trp) to kynurenine (Kyn). IDO1 activity compromises innate and adaptive immune responses, promoting mycobacterial survival. The plasma Kyn-to-Trp (K/T) ratio is a potential TB diagnostic and/or predictive biomarker in PWH on long-term antiretroviral therapy (ART). METHODS: We compared plasma K/T ratios in samples from PWH, who were followed up prospectively and developed TB disease after ART initiation. Controls were matched for age and duration of ART. Kyn and Trp were measured at 3 timepoints; at TB diagnosis, 6 months before TB diagnosis and 6 months after TB diagnosis, using ultra performance liquid chromatography combined with mass spectrometry. RESULTS: The K/T ratios were higher for patients with TB disease at time of diagnosis (median, 0.086; IQR, 0.069-0.123) compared to controls (0.055; IQR 0.045-0.064; p = 0.006), but not before or after TB diagnosis. K/T ratios significantly declined after successful TB treatment, but increased upon treatment failure. The K/T ratios showed a parabolic correlation with CD4 cell counts in participants with TB (p = 0.005), but there was no correlation in controls. CONCLUSIONS: The plasma K/T ratio helped identify TB disease and may serve as an adjunctive biomarker for for monitoring TB treatment in PWH. Validation studies to ascertain these findings and evaluate the optimum cut-off for diagnosis of TB disease in PWH should be undertaken in well-designed prospective cohorts. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00411983.

Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis With Liver Fibrosis as Predictors of New-Onset Diabetes Mellitus in People With HIV: A Longitudinal Cohort Study.

BACKGROUND: We investigated the association between nonalcoholic fatty liver disease (NAFLD) plus or minus a concurrent diagnosis of nonalcoholic steatohepatitis (NASH) and incident diabetes mellitus (DM) and the risk factors associated with NAFLD or NASH development. METHODS: In this prospective study, we analyzed people with human immunodeficiency virus (HIV; PWH) aged ≥18 years without excessive alcohol consumption or hepatitis coinfections. NAFLD was defined as controlled attenuation parameter ≥248 dB/m, whereas NASH with significant disease activity and liver fibrosis was defined as a FibroScan-AST score ≥0.67. Cox proportional hazard regression was used to investigate the association between NAFLD with or without NASH and new-onset DM. RESULTS: Of 847 PWH, the median age at baseline was 45 years (interquartile range, 38-51; 43% female). Baseline NAFLD was associated with 2.8-fold higher risk of new-onset DM after adjusting for age, sex, family history of DM, antiretroviral therapy duration, smoking, statin use, stavudine/didanosine/zidovudine exposure, time-updated body mass index, hypertension, and dyslipidemia. Combined NAFLD and NASH at baseline had 3.1-fold higher new-onset DM risk. In separate analyses, baseline DM did not predict progression to NAFLD or NASH, but tenofovir alafenamide use was associated with an increased risk of NAFLD (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.02-4.02) or NASH development (2.31; 95% CI, 1.12-5.11). CONCLUSIONS: NAFLD alone or combined with NASH strongly predicts new-onset DM. This highlights the need for systematic risk assessments and management of NAFLD/NASH, as it may contribute to metabolic complications such as DM and subsequent cardiovascular diseases in PWH.

Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

Impact of steatotic liver disease and non-alcoholic steatohepatitis on cognitive impairment in people living with HIV: A cross-sectional study.

INTRODUCTION: The link between fatty liver diseases and cognitive impairment among people living with HIV (PLWH) remains unclear. We investigated the association of steatotic liver disease (SLD), advanced liver fibrosis and non-alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis with cognitive impairment in PLWH. METHODS: Cognitive performance was assessed for PLWH aged ≥50 years on stable antiretroviral therapy (ART) with the Thai-validated version of the Montreal Cognitive Assessment (MoCA), and a cut-off of <25/30 was used to define cognitive impairment. SLD and NASH with significant activity and liver fibrosis were defined as having a controlled attenuation parameter value ≥248 dB/m and a FibroScan-AST (FAST) score ≥0.67, respectively. Multivariable logistic regression was employed to investigate the association of cognitive impairment with SLD or NASH. RESULTS: Of the 319 PLWH (63.3% male and 98% had HIV-1 RNA ≤50 copies/mL) included, 74 (38%) had SLD. NASH with significant activity and liver fibrosis was present in 66 (20.1%) participants. Some 192 (60.2%) participants had cognitive impairment. In a multivariable analysis, NASH with significant activity and liver fibrosis was significantly associated with cognitive impairment (adjusted odds ratio [aOR] 2.01, 95% CI 1.02-3.98, p = 0.04), after adjusting for HIV-related parameters, age, sex, body mass index, employment status, education, income level, smoking, alcohol use, diabetes mellitus, hypertension and HIV-related parameters. The association of a lone diagnosis of SLD and cognitive impairment was not statistically significant. CONCLUSIONS: NASH with significant activity and liver fibrosis was associated with lower cognitive performance, even after controlling for demographics and HIV disease parameters. Additional research is needed to better understand the underlying mechanisms.

Metabolic-Associated Fatty Liver Disease (MAFLD) is associated with immune activation, increased epicardial fat volume, and steatohepatitis among people with HIV in a Thai cohort.

INTRODUCTION: A change in terminology from fatty liver disease to metabolic-associated fatty liver disease (MAFLD), along with modified diagnostic criteria, was proposed in 2020, and data regarding MAFLD burden in people living with HIV are limited. We investigated associations between MAFLD and immune activation, cardiovascular disease (CVD) risks including epicardial fat volume, and steatohepatitis in an Asian cohort. METHODS: We evaluated CVD risk (epicardial fat tissue, coronary artery calcium [CAC] score, and 10-year atherosclerotic CVD [ASCVD] score) in people living with HIV aged >50 years. Individuals with excessive alcohol consumption and viral hepatitis infections were excluded. MAFLD diagnosis was based on 2020 International Consensus criteria. Non-alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis was defined as FibroScan-aspartate aminotransferase (FAST) score ≥0.67 and >0.35. Multivariate logistic regression models were used to investigate factors associated with MAFLD and NASH with significant activity and liver fibrosis. RESULTS: The median age was 54 years (interquartile range [IQR] 52-60) and current CD4 count was 613 (IQR 467-804) cells/mm3 . A total of 37% were female, and most (98%) people living with HIV were virally suppressed. The prevalence of MAFLD and non-alcoholic fatty liver disease was 35% and 38%, respectively. In multivariate analyses, higher body mass index, albumin, epicardial fat volume, and liver stiffness were significantly associated with MAFLD. A higher CD4/CD8 ratio was associated with a lower risk of MAFLD. People with HIV with MAFLD had higher odds of having NASH with significant activity and liver fibrosis (adjusted odds ratio 3.3; 95% confidence interval 1.6-6.6), and similar associations were also observed among different MAFLD categories. CONCLUSIONS: The complex relationship between MAFLD and immune activation, steatohepatitis, and epicardial fat tissue suggests an increased risk of advanced liver disease and CVDs beyond the traditional risk factors in people living with HIV with fatty liver disease.

Computer-aided detection, mucosal exposure device, their combination, and standard colonoscopy for adenoma detection: a randomized controlled trial.

BACKGROUND AND AIMS: Computer-aided detection (CADe) and a mucosal exposure device can improve adenoma detection rate (ADR). Potential benefits of combining the 2 modalities have never been studied. This study aimed to compare ADR differences among CADe alone, endocuff-assisted colonoscopy (EAC) alone, and the combination of CADe and EAC (CADe+EAC) with standard colonoscopy. METHODS: This prospective randomized controlled study included 1245 participants who underwent screening colonoscopy. Participants were randomized to CADe, EAC, CADe+EAC, and standard colonoscopy as a control. The primary outcome was ADR. Secondary outcomes were proximal ADR (pADR), advanced ADR (AADR), and the number of adenomas per colonoscopy (APCs). RESULTS: ADRs from the control, CADe, EAC, and CADe+EAC groups were 41.9%, 52.2%, 54.0%, and 58.8%, respectively; pADRs were 25.2%, 33.3%, 34.9%, and 37.0%, respectively; AADRs were 7.7%, 8.3%, 8.3%, and 13.6%, respectively; and APCs were .76, 1.11, 1.18, and 1.31, respectively. Significant increases in ADR and pADR were observed between the intervention and control groups (P < .05 in all comparisons). The AADR was significantly higher only in the CADe+EAC group than in the control group (P = .02). The adjusted incidence rate ratios of APCs were significantly higher in the intervention groups versus the control group (P < .01 in all comparisons). CONCLUSIONS: CADe+EAC significantly improve ADR and AADR over standard colonoscopy. However, although CADe or EAC alone can substantially increase the detection of adenomas, they do not lead to increased detection of advanced adenomas unless used in combination. (Clinical trial registration number: TCTR20200929003.).

Clinical validation and comparison of the Comprehensive Complication Index and Clavien-Dindo classification in predicting post-operative outcomes after cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: The Comprehensive Complication Index (CCI) is an instrument used to measure cumulative post-operative complications. Our study aimed to validate the CCI after cytoreductive surgery for primary advanced-stage epithelial ovarian cancer, and to compare its diagnostic performance with the Clavien-Dindo classification. METHODS: This prospective cohort study classified post-operative complications according to the Clavien-Dindo classification and the CCI. Logistic regression was used to determine the association between both classifications with intensive care unit admission, prolonged length of hospital stay (defined as stays longer than the 75th percentile of all stays in this study), 30-day readmission, and time to initiating chemotherapy after surgery >42 days. Area under the receiver operating characteristic curves (AUC) were used to assess the discriminative performance of each classification. RESULTS: A total of 300 patients were included in the analysis. Most patients (n=255, 85%) underwent interval cytoreductive surgery. Complete cytoreduction was achieved in 235 (78%) patients. Overall, 30-day post-operative complications classified by the Clavien-Dindo classification occurred in 147 (49%) patients. Severe complications (grade ≥3a) occurred in 51 (17%) patients. Approximately 30% (n=82) had multiple complications. The CCI showed an excellent correlation with the Clavien-Dindo classification (r=0.906, p<0.001). In comparison with the Clavien-Dindo classification, the proportion of patients classified with severe complications increased from 17% to 30% when stratified with the CCI, and 20% of patients were diagnosed with a CCI score that correlated with a higher Clavien-Dindo classification grade. On regression analysis, both Clavien-Dindo classification and CCI had associations with intensive care unit admission, prolonged length of hospital stay, 30-day readmission, and time to chemotherapy >42 days (all p<0.05). AUC demonstrated that CCI (0.842, 95% CI 0.792 to 0.893) and Clavien-Dindo classification (0.813, 95% CI 0.762 to 0.864, p<0.001) had a good diagnostic performance for prolonged length of hospital stay. CONCLUSIONS: Both the Clavien-Dindo classification and CCI showed significant associations with all surgical outcomes. However, the cumulative complications score of the CCI demonstrated a more superior discriminative performance than the Clavien-Dindo classification for prolonged length of hospital stay in advanced-stage epithelial ovarian cancer.

Weight change with integrase strand transfer inhibitors among virally suppressed Thai people living with HIV.

BACKGROUND: We compared weight changes in virally suppressed people living with HIV (PLWH) switching to integrase strand transfer inhibitors (INSTIs) with those remaining on an INSTI or non-INSTI regimen. METHODS: PLWH aged ≥18 years with weight measurements available at baseline between 2001 and 2020 were included. Viral suppression was defined as having had a viral load <400 copies/mL for 6 months. Baseline was defined as the time of switching from a non-INSTI to an INSTI regimen whilst virally suppressed (switch group) or the time that viral suppression was achieved (remain groups). Generalized estimating equations adjusted for age, sex and baseline weight were used to model weight changes 6, 12, 18 and 24 months after baseline. RESULTS: A total of 1673 PLWH contributed 1952 episodes of viral suppression-143 (7.3%) episodes were among PLWH who had switched from a non-INSTI to an INSTI, 102 (5.2%) episodes were among PLWH who remained on an INSTI and 1707 (87.4%) episodes were among PLWH who remained on a non-INSTI. PLWH in the switch group had significantly greater weight gain than those in the remain groups at 6, 12 and 18 months after achieving viral suppression. By 24 months, weight change on all regimens started to converge. Tenofovir alafenamide use was not significantly associated with weight gain in adjusted models. CONCLUSIONS: Our findings suggest that the mechanisms of weight gain due to INSTI use go beyond their superior efficacy over other antiretrovirals in controlling HIV or the effect of the 'return-to-health' phenomenon. Further research is needed to understand the mechanisms of such weight gain.

Lupus band test for diagnostic evaluation in systemic lupus erythematosus.

BACKGROUND: The lupus band test (LBT) using a sample of clinically normal skin was proposed as a useful diagnostic test for systemic lupus erythematosus (SLE). It is mostly performed to help diagnosing SLE in patients with insufficient clinical and serological profiles. However, most published studies on its utility are outdated and the results remain controversial. OBJECTIVES: To determine the diagnostic performance of LBT on non-lesion sun-protected (NLSP) and sun-exposed (NLSE) skin for SLE. METHODS: Consecutively presenting patients with clinical and serological suspicion of SLE who had LBT performed on non-lesion skin during January 2012 to August 2021 were retrospectively studied. LBT performed on either NLSE or NLSP skin biopsies were all included. Laboratory characteristics, number, types and patterns of deposited immunoreactants and disease activity were also assessed. RESULTS: LBT was performed in 57 patients with suspected SLE. LBT was positive in 18/57, 9/28 and 6/21 patients in overall non-lesion, NLSE and NLSP, respectively. Of all patients, 23 patients were diagnosed with SLE and 34 patients with other diseases. Overall, the sensitivity and specificity of LBT on non-lesion skin was 56.5% and 88.2%, respectively. The ability of the test to discriminate between those with and without SLE, assessed by the area under the Receiver-Operating Characteristic curve, was 0.72 (0.61-0.84). The sensitivity and specificity of LBT on NLSE skin was 58.3% and 87.5% while those of NLSP skin, were 57.1% and 85.7%, respectively. We found no significant correlation between the positivity of LBT and overall disease activity. Types, number and pattern of deposited immunoreactants also showed no correlation with disease activity (all p > 0.05). CONCLUSIONS: Used as a diagnostic adjunct, non-lesion LBT is still of value for diagnosing SLE in inconclusive cases.

Validation and prognostic value of EZ-ALBI score in patients with intermediate-stage hepatocellular carcinoma treated with trans-arterial chemoembolization.

BACKGROUND: Heterogeneity of liver function and tumor burden in intermediate-stage hepatocellular carcinoma (HCC) results in different outcomes after transarterial chemoembolization (TACE). Easy albumin-bilirubin (EZ-ALBI), a simplified albumin-bilirubin (ALBI) score, has recently been proposed as a new prognostic score for HCC. This study aimed to validate the EZ-ALBI score and evaluate the impact of dynamic changes in patients with intermediate-stage HCC undergoing TACE. METHODS: All patients with HCC treated with TACE at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between January 2015 and December 2019 were prospectively enrolled. Intermediate-stage HCC was defined as Barcelona Clinic Liver Cancer (BCLC) stage B or unresectable single HCC with size > 5 cm in BCLC stage A. EZ-ALBI and ALBI scores were calculated and stratified into three different grades. Overall survival (OS) and prognostic factors were assessed using the Kaplan-Meier curve and Cox proportional hazard model. Decision analysis curves were used to evaluate the clinical utility of the predictive scores. RESULTS: Among 672 patients with HCC treated with TACE, 166 patients with intermediate-stage HCC who met the eligibility criteria were enrolled. The median OS of all patients in the cohort was 21 months. A good correlation between the EZ-ALBI and ALBI scores was observed (correlation coefficient 1.000, p < 0.001). The baseline EZ-ALBI grades 1, 2, and 3 were 24.5%, 70%, and 5.5%, respectively. EZ-ALBI grade can stratify patients with significantly different prognoses (p = 0.002). Baseline EZ-ALBI grade 2, 3, and serum alpha-fetoprotein > 20 ng/ml were significantly associated with OS [hazard ratio (HR) 2.20 (95% confidence interval [CI] 1.24-3.88, p = 0.007), 3.26 (95% CI 1.24-8.57, p = 0.016), and 1.77 (95% CI 1.10-2.84, p = 0.018), respectively]. Following TACE, 42 (29.6%) patients had a worsening EZ-ALBI grade. However, the EZ-ALBI grade migration was not significantly correlated with OS. EZ-ALBI and ALBI score provided improved discriminatory ability (Harrell's concordance index 0.599 and 0.602, respectively) and better net benefit compared with Child-Turcotte-Pugh and Model for End-stage Liver Disease scores. CONCLUSIONS: The baseline EZ-ALBI score demonstrated good predictive performance for survival and a strong correlation with conventional ALBI scores. Both the EZ-ALBI and ALBI scores outperformed other prognostic models in patients with intermediate-stage HCC receiving TACE. However, the dynamic change in the EZ-ALBI grade after TACE was not associated with postprocedural survival.

Incidence and factors associated with active tuberculosis among people living with HIV after long-term antiretroviral therapy in Thailand: a competing risk model.

BACKGROUND: Antiretroviral therapy (ART) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLWH). However, studies describing the impact of long-term ART and CD4 count recovery on TB incidence remain scarce due to limited follow up in previous studies. We evaluated TB incidence in a long-term cohort of PLWH on ART in Thailand. METHODS: We conducted an analysis of PLWH aged ≥ 18 years who started ART between 1996 and December 2020. Participants were followed up every 6 months for routine HIV care. TB risk factors, body mass index (BMI), physical examination and full differential blood counts were evaluated at each clinic visit, and CD4 cell counts and HIV RNA every 12 months. Participants diagnosed with TB > 3 months after starting ART were classified as incident cases. Time to event models with death as a competing risk, were used to derive the TB cumulative incidence function (CIF) after ART initiation, and assess time-updated factors associated with incident TB using a six month lag. RESULTS: A total of 2,636 PLWH contributing 24,229 person years (PY) of follow-up on ART were analysed. Median age was 32.0 (IQR 27.4-37.6) years; 67.5% were male. Median CD4 cell count at ART initiation was 264 (IQR 167-379) cells/mm3 and median follow-up duration was 7.6 (IQR 1.9-15.7) years. During follow-up, 113 PLWH developed TB. The probability of incident TB was 0.7%, 1.7%, 3.3% and 4.3%, at 1, 2, 5 and 7 years after ART initiation, respectively. TB CIF was highest among participants with CD4 < 50 cells/mm3. The overall crude incidence of TB was 4.66 (95% CI 3.87-5.60) per 1000 PY. Low CD4 count, BMI < 18 kg/m2, and substance use in the previous six months were significantly associated with incident TB. Incidence declined with time on suppressive ART, but remained higher than the Thai general population 7 years after ART initiation (2.2 vs 1.5/1000 PY, respectively). CONCLUSION: Despite a marked reduction in TB incidence following ART, ongoing TB risk remains high among PLWH, despite long-term suppressive ART. Those with low CD4 cell counts, who are underweight, or currently having substance abuse should be carefully monitored.

Influenza vaccination during pregnancy and risk of selected major structural noncardiac birth defects, National Birth Defects Prevention Study 2006-2011.

PURPOSE: To assess associations between influenza vaccination during etiologically-relevant windows and selected major structural non-cardiac birth defects. STUDY DESIGN: We analyzed data from the National Birth Defects Prevention Study, a multisite, population-based case-control study, for 8233 case children diagnosed with a birth defect and 4937 control children without a birth defect with delivery dates during 2006-2011. For all analyses except for neural tube defects (NTDs), we classified mothers who reported influenza vaccination 1 month before through the third pregnancy month as exposed; the exposure window for NTDs was 1 month before through the first pregnancy month. For defects with five or more exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; maternal age, race/ethnicity, smoking and alcohol use, low folate intake; and, for NTDs, folate antagonist medications. RESULTS: There were 334 (4.1%) case and 197 (4.0%) control mothers who reported influenza vaccination from 1 month before through the third pregnancy month. Adjusted ORs ranged from 0.53 for omphalocele to 1.74 for duodenal atresia/stenosis. Most aORs (11 of 19) were ≤1 and all adjusted CIs included the null. The unadjusted CIs for two defects, hypospadias and craniosynostosis, excluded the null. These estimates were attenuated upon covariate adjustment (hypospadias aOR: 1.25 (95% CI 0.89, 1.76); craniosynostosis aOR: 1.23 (95% CI: 0.88, 1.74)). CONCLUSIONS: Results for several non-cardiac major birth defects add to the existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. Under-reporting of vaccination may have biased estimates downward.

Diagnostic performance of digital and video cholangioscopes in patients with suspected malignant biliary strictures: a systematic review and meta-analysis.

BACKGROUND: Per-oral cholangioscopy (POC) has evolved over the past decade from fiberoptic to digital and video imaging systems. Nowadays, only direct per-oral cholangioscopy (DPOC) and digital single-operator cholangioscopy (DS) are performed in daily practice. With better image resolution, POC is increasingly used as diagnostic tools in patients with suspected malignant biliary stricture (MBS). We aimed to evaluate the diagnostic yield of digital/video cholangioscopes for the diagnosis of MBS. METHODS: A systematic search was performed in MEDLINE, Embase, and ISI Web of Knowledge databases until April 2020, to identify randomized controlled trials and prospective studies using digital or video POC. The meta-analysis of diagnostic accuracy study was performed to calculate summary estimates of the primary outcomes, including pooled sensitivity, and specificity of POC to diagnose MBS using bivariate random-effects models. Tissue histopathology was used as the reference standard for MBS diagnosis. For benign stricture, negative tissue histopathology and at least 6 months clinical follow-up were required. RESULTS: Thirteen original articles with 876 patients were identified. The overall pooled sensitivity and specificity were 88 (95% CI 83-91) and 95 (95% CI 89-98), respectively. The area under the curve (AUROC) was 0.94 (95% CI 0.92-0.96). Subgroup analysis showed that cholangioscopic image impression provided significantly higher sensitivity (93% (95% CI 88-96) vs 82% (95% CI 76-87); p = 0.007), but lower specificity 86% (95% CI 75-92) vs 98 (95% CI 95-99); p < 0.001) than the tissue diagnosis from cholangioscopic-guided biopsy. In addition, biopsy obtained from DPOC had significantly higher sensitivity than that of DS (92% (95% CI 81-97) vs 79% (95% CI 72-84); p = 0.004). Diagnostic performance under image-enhanced endoscopy was not significantly better from white light endoscopy. CONCLUSIONS: Digital/video POC has very high diagnostic performance to diagnose MBS. While image diagnosis provides higher sensitivity than biopsy, its specificity drops as a trade-off.

Association of Phenotypic Aging Marker with comorbidities, frailty and inflammatory markers in people living with HIV.

BACKGROUND: Aging characteristics in people living with HIV (PLWH) are heterogeneous, and the identification of risk factors associated with aging-related comorbidities such as neurocognitive impairment (NCI) and frailty is important. We evaluated predictors of novel aging markers, phenotypic age (PhenoAge) and phenotypic age acceleration (PAA) and their association with comorbidities, frailty, and NCI. METHODS: In a cohort of PLWH and age- and sex-matched HIV-negative controls, we calculated PhenoAge using chronological age and 9 biomarkers from complete blood counts, inflammatory, metabolic-, liver- and kidney-related parameters. PAA was calculated as the difference between chronological age and PhenoAge. Multivariate logistic regression models were used to identify the factors associated with higher (>median) PAA. Area under the receiver operating characteristics curve (AUROC) was used to assess model discrimination for frailty. RESULTS: Among 333 PLWH and 102 HIV-negative controls (38% female), the median phenotypic age (49.4 vs. 48.5 years, p = 0.54) and PAA (- 6.7 vs. -7.5, p = 0.24) was slightly higher and PAA slightly less in PLWH although this did not reach statistical significance. In multivariate analysis, male sex (adjusted odds ratio = 1.68 [95%CI = 1.03-2.73]), current smoking (2.74 [1.30-5.79]), diabetes mellitus (2.97 [1.48-5.99]), hypertension (1.67 [1.02-2.72]), frailty (3.82 [1.33-10.93]), and higher IL-6 levels (1.09 [1.04-1.15]), but not HIV status and NCI, were independently associated with higher PAA. PhenoAge marker discriminated frailty better than chronological age alone (AUROC: 0.75 [0.66-0.85] vs. 0.65 [0.55-0.77], p = 0.04). In the analysis restricted to PLWH, PhenoAge alone predicted frailty better than chronological age alone (AUROC: 0.7412 vs. 0.6499, P = 0.09) and VACS index (AUROC: 0.7412 vs. 0.6811, P = 0.34) despite not statistically significant. CONCLUSIONS: While PLWH did not appear to have accelerated aging in our cohort, the phenotypic aging marker was significantly associated with systemic inflammation, frailty, and cardiovascular disease risk factors. This simple aging marker could be useful to identify high-risk PLWH within a similar chronological age group.

Variation in United States COVID-19 newborn care practices: results of an online physician survey.

BACKGROUND: Newborn care practices that best promote the health and well-being of mother-infant dyads after birth while minimizing transmission of COVID-19 were uncertain at the onset of the COVID-19 pandemic. OBJECTIVE: Examine variation in COVID-19 newborn care practices among U.S. birth hospitals and by hospital characteristics (U.S. census region, highest level of neonatal level of care, and Baby-Friendly hospital status). STUDY DESIGN: We surveyed physicians via American Academy of Pediatrics email listservs and social media between 5/26/2020-6/8/2020. Physicians identified the birth hospital in which they provided newborn care and their hospital's approach to obstetrical and newborn care related to COVID-19. Chi-square tests were used to examine variation in hospital practices by U.S. census region, highest level of neonatal care, and Baby-Friendly hospital status. RESULTS: Four hundred thirty three physicians responded from 318 hospitals across 46 states. Variation in care of SARS-CoV-2 positive mother-infant dyads was greatest for approaches to location of newborn care (31% separation, 17% rooming-in, and 51% based on shared-decision making), early skin-to-skin care (48% prohibited/discouraged, 11% encouraged, and 40% based on shared-decision making) and direct breastfeeding (37% prohibited/discouraged, 15% encouraged, and 48% based on shared-decision making). Among presumed uninfected dyads, 59% of hospitals discharged at least some mother-infant dyads early. We found variation in practices by U.S. census region. CONCLUSION: Approaches to newborn care and breastfeeding support for mother-infant dyads with positive SARS-CoV-2 testing differed across U.S. birth hospitals during the COVID-19 pandemic. Early discharge of presumed uninfected mother-infant dyads was common.

Sleep impairments and quality of life in Thai adolescents with systemic lupus erythematosus.

PURPOSE: Adolescents with systemic lupus erythematosus (SLE) are susceptible to sleep impairments. We aimed to determine the prevalence and factors related to sleep impairments, and the associations of sleep impairments with health-related quality of life (HRQOL) in Thai adolescents with SLE. METHODS: Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire for Adolescents (PHQA), and Pediatric Quality of Life Inventory™ 4.0 Core Scales were administered to 57 participants with SLE aged 13-18 years to evaluate sleep, depression, and HRQOL, respectively. Participants were divided into "good sleep" (PSQI scores <5) and "poor sleep" groups (PSQI scores ≥5). Participants with body mass index (BMI) >23 kg/m2 were classified into the high BMI group. FINDINGS: Eighteen participants (31.6%) were in the poor sleep group. High BMI and PHQA scores were associated with sleep impairments with the odds ratio of 8.00 (95% CI 1.50-42.64; p = 0.02), and 1.25 (95% CI 1.01-1.54; p = 0.04), respectively. In terms of HRQOL, adolescents with SLE had the highest scores in social functioning and the lowest scores in school functioning. Good sleepers had better scores than poor sleepers across all sub-categories except for social functioning, and the difference was significant in emotional functioning (90% (IQR 75-100) vs. 70% (IQR 55-85); p = 0.03). CONCLUSIONS: A substantial number of adolescents with SLE had sleep impairments, which decreased HRQOL, particularly in emotional functioning. Sleep impairments were associated with obesity and depression. IMPLICATIONS: Proactive management in addressing weight, mood, and sleep problems should be included in the multidisciplinary care of adolescents with SLE to improve their health and well-being.

Efficacy of antimalarial agents to prevent the progression of discoid lupus erythematosus to systemic lupus erythematosus: A retrospective cross-sectional study.

BACKGROUND: Discoid Lupus Erythematosus (DLE) patients have the potential to developing Systemic Lupus Erythematosus (SLE) at a later time. The prescription of antimalarial agents might be beneficial to prevent this progression but the validated data is still lacking. OBJECTIVE: Our study aimed to explore whether antimalarial agent could slow progression to SLE in DLE patients, adjusting for other potential confounders. METHODS: We retrospectively studied 65 patients who were diagnosed as DLE and attended the outpatient clinic at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between January 1, 2017 and December 31, 2020. We reviewed medical records including history of DLE, SLE signs and symptoms, laboratory findings and treatment options. RESULTS: Over a total of 458.73 person years (PY), 19 patients (29.23%) eventually progressed to SLE within approximately 1 year. Of these, 15 patients had widespread lesions whereas only 4 patients presented with localized form. The prescription of antimalarial drug was associated with delayed SLE progression in our cohort. Other parameters such as generalized form (IRR 6.243 (95% CI 1.450-26.872); P = 0.014), joint involvement (IRR 5.005 (95% CI 1.931-12.969); P = 0.001) and LE specific skin lesions (IRR 3.799 (95% CI 1.220-11.825); P = 0.021) were considered as strong risk factors in SLE development. CONCLUSIONS: Our study suggested that an antimalarial drug could postpone the SLE development in DLE patients.

Drug-drug Interactions Among Thai Transgender Women Living with Human Immunodeficiency Undergoing Feminizing Hormone Therapy and Antiretroviral Therapy: The iFACT Study.

BACKGROUND: Drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are a major concern among transgender women (TGW), which may lead to suboptimal ART adherence and inappropriate FHT dosage. To evaluate potential drug-drug interactions between FHT and ART, we performed intensive measurements of the pharmacokinetic (PK) parameters of blood tenofovir (TFV), efavirenz (EFV), and estradiol (E2). METHODS: Twenty TGW with newly diagnosed human immunodeficiency virus (HIV) infection were enrolled. FHT (E2 valerate 2 mg/d and cyproterone acetate 25 mg/d) was prescribed at baseline until week 5 and restarted at week 8. ART (TFV disoproxil fumarate/emtricitabine/EFV at 300/200/600 mg) was initiated at week 3. The E2 PK parameters were measured intensively at weeks 3 (without ART) and 5 (with ART), and TFV and EFV PK parameters were measured intensively at weeks 5 (with FHT) and 8 (without FHT). RESULTS: The median (interquartile range) age and body mass index were 25.5 (22.5-31.0) years and 20.6 (19.3-23.1) kg/m2, respectively. The differences in geometric mean ratios between weeks 3 and 5 were as follows for E2 area under the curve, maximum concentration, and concentration at 24 hours (C24), respectively: 0.72 (90% confidence interval, .64-.81; P < .001), 0.81 (.72-.92; P = .006), and 0.64 (.50-.83; P = .004). The differences in geometric mean ratios between weeks 5 and 8 were as follows for TFV AUC, TFV C24, and EFV C24: 0.86 (90% confidence interval, .80-.93; P = .002), 0.83 (.75-.93; P = .006), and 0.91 (.85-.97; P = .02). CONCLUSIONS: Among HIV-positive TGW, E2 PK parameters were significantly lower in the presence of TFV disoproxil fumarate/emtricitabine/EFV, and some TFV and EFV PK parameters were lower in the presence of FHT. Further studies should determine whether these reductions are clinically significant and whether they occur with other FHT or ART regimens.