Prevalence and incidence of anal high-grade squamous intraepithelial lesions in a cohort of cisgender men and transgender women who have sex with men diagnosed and treated during acute HIV acquisition in Bangkok, Thailand.

INTRODUCTION: Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. METHODS: Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits. RESULTS: A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48). CONCLUSIONS: With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.

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.

Immunogenicity and safety of heterologous versus homologous prime-boost schedules with inactivated and adenoviral vectored SARS-CoV-2 vaccines - A prospective multi-center study.

Background: During the peak of Coronavirus disease (COVID-19) pandemic in Thailand when the emergence of delta variant reduced the efficacy of inactivated vaccine, Thailand had abundance of inactivated vaccine but mRNA vaccine was not available and the supply of adenoviral-vectored vaccine was limited. The heterologous vaccination using CoronaVac and ChAdOx1-nCoV-19 vaccines was applied. We aim to compare the immunogenicity of immune response of primary vaccination with homologous ChAdOx1 nCoV-19 and heterologous vaccination with CoronaVac and ChAdOx1 nCoV-19. Methods: A total of 430 adults, scheduled to receive ChAdOx1-nCoV-19 as their second dose of primary COVID-19 vaccination, were enrolled. Participants were classified into two groups based on the first dose vaccine as CoronaVac (heterologous group) or ChAdOx1 nCoV-19 (homologous group). The primary outcome was antibodies to the SARS-CoV-2 spike protein receptor binding domain (anti-RBD) titres at 28 days after the second dose of vaccination. Secondary outcomes were anti-RBD titres at 90 days, surrogate viral neutralizing test (sVNT) at 28 and 90 days, and adverse events. Findings: In 358 participants with correct vaccine interval, the anti-RBD geometric mean titre ratio for the heterologous versus homologous group was 0.55 (95%CI; 0.44-0.067); p < 0.001 at day 28, and 0.80 (95%CI; 0.65-1.00); P = 0.05 at day 90. Median sVNT neutralizing activity was not significantly different in the heterologous versus homologous group at 28 days (93.5 vs 92.7 %); p = 0.13, but significantly higher in the heterologous group at day 90 (82.9 vs 76.4 %); p = 0.01. Interpretation: The homologous vaccination resulted in higher anti-RBD titres at 28 days after vaccination, but titres in the homologous group showed more rapid decline at 90 days. In the sVNT assay, median neutralization was similar at 28 days, but was longer-lasting and higher in the heterologous group at 90 days. Funding: This research received funding from the Royal College of Physicians of Thailand special grant 2021 for research initiative during COVID-19 pandemic.

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.

EUS-guided radiofrequency ablation plus chemotherapy versus chemotherapy alone for pancreatic cancer (ERAP): An observational open-label pilot study.

Background: No study has compared EUS-guided radiofrequency ablation (EUS-RFA) plus systemic chemotherapy (CMT) with CMT alone for unresectable pancreatic ductal adenocarcinoma. Methods: This study compared the results of treatment in patients receiving EUS-RFA plus concomitant CMT (group A; n = 14) with those receiving CMT (group B; n = 14) as a pilot study. Results: From July 2017 to August 2018, 4 and 2 patients from groups A and B, respectively, withdrew from the study because of progression of the disease. In total, 10 and 12 patients from groups A and B, respectively, completed the study. All 30 EUS-RFA procedures were successful. Mean maximal tumor diameter before treatment of group A (n = 10) versus B (n = 12) was 62.2 ± 21.0 versus 50.5 ± 22.0 mm, respectively (P = not significant). After treatment, no statistically significant difference in mean maximal tumor diameter was found between both groups. However, in group B, mean maximal tumor diameter was significantly increased from 50.5 ± 22.0 to 56.3 ± 18.7 mm, respectively (P = 0.017). Tumor necrosis occurred in group A versus B at 10 of 10 (100%) versus 6 of 12 (50%) patients, respectively (P = 0.014). After treatment, group A patients could reduce the mean narcotic pain drug dosage at 26.5 mg of morphine equivalent per day (from 63.6 to 37.1 mg, P = 0.022), whereas group B patients could not reduce the dosage of pain-controlled medication. No statistically significant difference in 6-month mortality rate was found. In group A, 1 procedure-related nonsevere adverse event (n = 1 of 30 [3.3%]) occurred in 1 patient (n = 1 of 14 [7.1%]). Conclusions: In this study, the mean tumor diameter of group B was significantly increased after the treatment. Group A had a significantly higher rate of necrosis of tumor and required less narcotic.

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.

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.

Artificial intelligence assists operators in real-time detection of focal liver lesions during ultrasound: A randomized controlled study.

PURPOSE: Detection of hepatocellular carcinoma (HCC) is crucial during surveillance by ultrasound. We previously developed an artificial intelligence (AI) system based on convolutional neural network for detection of focal liver lesions (FLLs) in ultrasound. The primary aim of this study was to evaluate whether the AI system can assist non-expert operators to detect FLLs in real-time, during ultrasound examinations. METHOD: This single-center prospective randomized controlled study evaluated the AI system in assisting non-expert and expert operators. Patients with and without FLLs were enrolled and had ultrasound performed twice, with and without AI assistance. McNemar's test was used to compare paired FLL detection rates and false positives between groups with and without AI assistance. RESULTS: 260 patients with 271 FLLs and 244 patients with 240 FLLs were enrolled into the groups of non-expert and expert operators, respectively. In non-experts, FLL detection rate in the AI assistance group was significantly higher than the no AI assistance group (36.9 % vs 21.4 %, p < 0.001). In experts, FLL detection rates were not significantly different between the groups with and without AI assistance (66.7 % vs 63.3 %, p = 0.32). False positive detection rates in the groups with and without AI assistance were not significantly different in both non-experts (14.2 % vs 9.2 %, p = 0.08) and experts (8.6 % vs 9.0 %, p = 0.85). CONCLUSIONS: The AI system resulted in significant increase in detection of FLLs during ultrasound examinations by non-experts. Our findings may support future use of the AI system in resource-limited settings where ultrasound examinations are performed by non-experts. The study protocol was registered under the Thai Clinical Trial Registry (TCTR20201230003), which is part of the WHO ICTRP Registry Network. The registry can be accessed via the following URL: https://trialsearch.who.int/Trial2.aspx?TrialID=TCTR20201230003.

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.

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

BACKGROUND: Although results from studies of first-trimester influenza vaccination and congenital heart defects (CHDs) have been reassuring, data are limited for specific CHDs. METHODS: We assessed associations between reported maternal influenza vaccination, 1 month before pregnancy (B1) through end of third pregnancy month (P3), and specific CHDs using data from a multisite, population-based case-control study. Analysis included 2,982 case children diagnosed with a simple CHD (no other cardiac involvement with or without extracardiac defects) and 4,937 control children without a birth defect with estimated delivery dates during 2006-2011. For defects with ≥5 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; and maternal age at delivery, race/ethnicity, low folate intake, and smoking and alcohol use during B1P3. RESULTS: Overall, 124 (4.2%) simple CHD case mothers and 197 (4.0%) control mothers reported influenza vaccination from 1 month before through the third pregnancy month. The aOR for any simple CHD was 0.97 (95% CI: 0.76-1.23). Adjusted ORs for specific simple CHDs ranged from 0.62 for hypoplastic left heart syndrome to 2.34 for total anomalous pulmonary venous return (TAPVR). All adjusted CIs included the null except for TAPVR. CONCLUSIONS: Although we cannot fully exclude that exposure misclassification may have masked risks for some CHDs, findings add to existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. The TAPVR result may be due to chance, but it may help inform future studies.

Factors Associated with Morbidity and Mortality Among Sexually Active Asian Adolescents and Young Adults with Perinatally Acquired HIV.

We assessed morbidity and mortality among Thai and Vietnamese adolescents and young adults with perinatally acquired human immunodeficiency virus (PHIV) compared with matched HIV-negative peers, 12-24 years of age. Data on serious adverse events (SAEs) were prospectively collected between 2013 and 2018 according to U.S. NIH Division of AIDS criteria. Of 288 youth, 142 had PHIV and 146 were HIV negative. At enrollment, the overall median age was 19 (interquartile range [IQR] 17-20) years, 67% were female, and 95% were Thai. Almost all PHIV youth (99%) were receiving antiretroviral therapy; 50% self-reported adherence ≥95%. Median CD4 was 579 (IQR 404-800) cells/mm3, and 24% had HIV-RNA ≥1,000 copies/mL. During follow-up, 31 (22%) PHIV youth and 9 (6%) HIV-negative youth had at least one SAE. The overall crude SAE rate was 4.66 (3.42-6.35) per 100 person-years (PY); 7.22 (5.08-10.26) per 100 PY among youth with PHIV and 2.10 (1.09-4.03) per 100 PY in HIV-negative youth (p < .001). All seven deaths that occurred were among those with PHIV and primarily due to opportunistic infections (e.g., pneumocystis pneumonia, tuberculous meningitis). In multivariate analyses, having PHIV, being <20 years of age, and having anogenital high-risk human papillomavirus (HPV) infection with types 16 and/or 18 increased risk of SAEs. Among PHIV youth, CD4 count <350 cells/mm3, HIV-RNA ≥1,000 copies/mL, advanced WHO stages, and having anogenital HPV 16 and/or 18 infection predicted higher incidence of SAEs; no prior use of alcohol was protective. These data emphasize the need for tailored interventions for adolescents with PHIV to prevent long-term morbidity and mortality.

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.).

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.

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.

A Comparison of Polyetheretherketone and Titanium-Coated Polyetheretherketone in Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Randomized Clinical Trial.

OBJECTIVE: To compare patient-reported outcomes and radiographic outcomes between using polyetheretherketone (PEEK) and titanium-coated PEEK (TiPEEK) as an interbody cage in patients who underwent minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: Eighty-Six patients who underwent 1-2 levels of MIS-TLIF were randomly allocated to receive a TiPEEK or PEEK cage. Patient-reported outcomes were recorded using visual analog scale, Oswestry Disability Index, and EuroQoL-5D-5L. Postoperative radiographs and computed tomography were assessed for spinal fusion and cage subsidence. RESULTS: The eligible 82 patients (41 patients, 49 operated levels in TiPEEK group and 41 patients, 50 operated levels in PEEK group) were included in the final analysis. Over total follow-up, the mean difference in visual analog scale back and leg pain scores between TiPEEK versus PEEK group was -0.04 (95% confidence interval [CI], -0.5 to 0.4; P = 0.85) and -0.12 (95% CI, -0.6 to 0.3; P = 0.62), respectively. The mean difference in Oswestry Disability Index scores was -0.71 (95% CI, -3.8 to 2.4; P = 0.65), and the mean difference in EQ-5D-5 L was 0.03 (95% CI, -0.01 to 0.06; P = 0.11) in TiPEEK group versus PEEK group as a reference. TiPEEK showed significantly higher fusion rates than PEEK at 6-month (91.8% vs. 76%; P = 0.03), but no difference at 12-month postoperation. There was no significant difference in cage subsidence rates between the 2 groups. CONCLUSIONS: The patient-reported outcomes showed significant improvements at 6- and 12-month postoperation following MIS-TLIF; the differences in those with TiPEEK versus PEEK cages were minimal with tight CIs. Fusion rates in both groups were ≥90%, with TiPEEK cages showing higher fusion rates at 6 months after the procedure.

Factors Predicting 30-Day Grade IIIa-V Clavien-Dindo Classification Complications and Delayed Chemotherapy Initiation after Cytoreductive Surgery for Advanced-Stage Ovarian Cancer: A Prospective Cohort Study.

Objective: The aim of this study was to evaluate factors associated with 30-day postoperative Clavien−Dindo classification (CDC) grade IIIa or greater complications and delayed initiation of chemotherapy after cytoreductive surgery (CRS) for primary advanced-stage epithelial ovarian cancer (AEOC). Methods: This was a prospective study involving 300 patients who underwent primary or interval CRS for AEOC between February 2018 and September 2020. Postoperative complications were graded according to the CDC. Logistic regression analysis was used to evaluate factors predicting CDC grade ≥IIIa and time to chemotherapy (TTC) >42 days. Results: Interval CRS was performed in 255 (85%) patients. CDC grade ≥IIIa occurred in 51 (17%) patients. In multivariable analysis, age (p = 0.036), cardiovascular comorbidity (p < 0.001), diaphragmatic surgery (p < 0.001), intraoperative urinary tract injury (p = 0.017), and upper-abdominal visceral injury (e.g., pancreas, stomach, liver, or spleen) (p = 0.012) were associated with CDC grade ≥IIIa. In 26% of cases, TTC was >42 days (median (IQR) 39 (29−50) days) in patients with CDC grade ≥IIIa versus 33 (25−41) days in patients without CDC grade ≥ IIIa (p = 0.008). The adjusted odds ratio of developing TTC >42 days was significantly higher in patients associated with WHO performance grade ≥2 (p = 0.045), intraoperative bowel injury (p = 0.043), upper-abdominal visceral injury (p = 0.008), and postoperative CDC grade ≥IIIa (p = 0.032). Conclusions: Patients with advanced age, with cardiovascular comorbidity, and who required diaphragmatic surgery had an increased adjusted odds ratio of developing CDC grade ≥IIIa complications. CDC grade ≥IIIa complications were independently associated with TTC >42 days. Proper patient selection and prevention of intraoperative injury are essential in order to prevent postoperative complications and delayed initiation of chemotherapy.

Indirect Effects on Adjacent Segments After Minimally Invasive Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: To compare radiographic parameters at adjacent segments before and after minimally invasive transforaminal lumbar interbody fusion and assess relationships of radiographic changes between adjacent segments and fused level. METHODS: Study participants included 44 patients who underwent minimally invasive transforaminal lumbar interbody fusion at L4-5 level. Radiographic parameters at adjacent segments (L3-4 and L5-S1) and clinical parameters were reviewed. RESULTS: Postoperative dural sac area significantly increased in upper (mean change 8.05 mm2, P < 0.001) and lower (14.08 mm2, P < 0.001) adjacent segments. Significant increases in SAPD were seen in upper (0.85 mm, P < 0.001) and lower (0.66 mm, P < 0.001) adjacent segments. Ligamentum flavum thickness significantly decreased in lower adjacent segments (-0.37 mm, P = 0.006). For every 1-mm increase in fused level disc height, lower SAPD increased 0.22 mm (P = 0.04), and lower segmental angle increased 0.91° (P = 0.04). For every 1° increase in fused level segmental angle, lower dural sac area increased 1.25 mm2 (P = 0.03), and lower SAPD increased 0.12 mm (P = 0.003). The 6- and 12-month postoperative visual analog scale back and leg scores significantly decreased compared with preoperatively (back: mean change -5.98 and -6.05, P < 0.001; leg: -6.86 and -6.89, P < 0.001). CONCLUSIONS: Performing minimally invasive transforaminal lumbar interbody fusion at the symptomatic index level does not worsen canal dimension of asymptomatic adjacent segments during short-term follow-up. It might be possible to improve canal dimension at adjacent segments by changing disc height or lordosis at the fused level via adjusting size and position of the interbody cage.

Immunogenicity of ChAdOx1-nCoV-19 vaccine in solid malignancy patients by treatment regimen versus healthy controls: A prospective, multicenter observational study.

Background: Limited data exists regarding the efficacy of ChAdOx1-nCoV-19 vaccine against Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) in solid cancer patients. We aimed to assess the immunogenicity of the ChAdOx1-nCoV-19 vaccine and the impact of different anticancer therapies for solid malignancies on immune response. Methods: This prospective, longitudinal observational study of immunogenicity following ChAdOx1-nCoV-19 vaccination among 385 solid cancer patients on active cancer treatment was conducted in two oncology centers. Participants received the first dose between June 18 and July 27, 2021 and the second dose at 8-10 weeks later. Blood samples were evaluated for total immunoglobulins against the receptor-binding of SARS-CoV-2 spike protein (anti-RBD total-Ig) before, and 4-week after the first- and second-doses. The primary endpoint was the geometric mean titers (GMT) of antibody among solid cancer patients compared to healthy controls and the impact of different cancer treatment types. Findings: Among solid cancer patients, the antibody level increased more slowly to significantly lower levels than achieved in healthy controls. The GMT at 4-weeks post-vaccination in cancer vs. healthy were 224.5 U/ml (95%CI 176.4-285.6) vs. 877.1 U/ml (95%CI 763.5-1008), p<0.0001), respectively. For different types of cancer treatments, chemotherapy agents, especially anthracyclines (GMR 0.004; 95%CI 0.002-0.008), paclitaxel (GMR 0.268; 95%CI 0.123-0.581), oxaliplatin (GMR 0.340; 95%CI 0.165-0.484), and immunotherapy (GMR 0.203; 95%CI 0.109-0.381) showed significantly lower antibody response. Anti-HER2, endocrine therapy and 5-fluouracil or gemcitabine, however, had less impact on the immune response. Interpretation: Suboptimal and heterogeneous immunologic responses were observed in cancer patients being treated with different systemic treatments. Immunotherapy or chemotherapy significantly suppressed the antibody response. Funding: Quality Improvement Fund, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society and Center of Excellence in Clinical Virology at Chulalongkorn University and Chulalongkorn Medical Oncology Research Fund.

Grip strength after hamate hook excision and reconstruction surgery: A biomechanical cadaveric study.

Fractures of the hamate hook are common among professional athletes. The recommended treatment for this is hamate hook excision. The purpose of this study is to evaluate the hand grip strength after hamate hook resection at different levels. Six cadaver forearm flexor digitorum profundus tendons were loaded with 5- to 15-kilograms force and grip strength was subsequently measured. The same measurements were performed in five hamate hook conditions: normal, one-third, two-thirds, total hamate excision, and after perihamate ligament reconstruction. Multilevel mixed-effect models were used to calculate the scaling ratios after each surgical intervention and compared them to a normal hamate hook. A 25%, 36%, 47% reduction, and 7% increase (107% of baseline) in grip strength was found after one-third, two-thirds, total bone was resected, and after perihamate ligament reconstruction, respectively. The study shows an association between grip strength reduction and the level of hamate hook resection. Perihamate ligament reconstruction is recommended as it restores grip strength to normal.

Factors predicting postoperative morbidity after cytoreductive surgery for ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: Advances in ovarian cancer cytoreductive surgery have enabled more extensive procedures to achieve maximal cytoreduction but with a consequent increase in postoperative morbidity and mortality. The aim of this study was to evaluate factors for postoperative morbidity after extensive cytoreductive surgery for primary epithelial ovarian cancer (EOC), particularly those which may be modifiable. METHODS: Electronic databases were searched. Meta-analysis was conducted using random-effects models. RESULTS: Fifteen relevant studies, involving 15,325 ovarian cancer patients, were included in this review. Severe 30-day postoperative complications occurred in 2,357 (15.4%) patients. The postoperative mortality rate was 1.92%. Meta-analysis demonstrated that patient with following risk factors; age (p<0.001), Eastern Cooperative Oncology Group score >0 (p=0.001), albumin level <3.5 g/dL (p<0.001), presence of ascites on CT scan (p=0.013), stage IV disease (p<0.001) and extensive surgical procedure (p<0.001) has a significantly increase risk of developing postoperative complications. Surgical procedures including peritonectomy (p=0.012), splenectomy (p<0.001) and colon surgery (p<0.001) were significant predictors for postoperative complications. Moreover, we found that patients who received neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) had a lower risk of developing severe complications compared to those who underwent primary debulking surgery (PDS) (p<0.001). CONCLUSION: Our study demonstrated that patient performance status and hypoalbuminemia were the only significant adjustable preoperative risk factors associated with postoperative complications. Patients who underwent NACT-IDS had a lower risk of developing severe complications compared to PDS. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) Identifier: CRD42021282770.