The landscape of etiological patterns of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in Thailand.

Thailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER-LC consortium-based population study covering all high-incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011-2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06-2.11 to 2.91; 95% CI: 1.82-4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64-0.96) and iCCA (HR 0.84; 95% CI: 0.70-0.99). Risk factor co-exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer-term survivors, including behavioral changes to reduce exposures.

Effect of Corticosteroid on Immunogenicity of SARS-CoV-2 Vaccines in Patients With Solid Cancer.

PURPOSE: Corticosteroids are known to diminish immune response ability, which is generally used in routine premedication for chemotherapy. The intersecting of timeframe between the corticosteroid's duration of action and peak COVID-19 vaccine efficacy could impair vaccine immunogenicity. Thus, inquiring about corticosteroids affecting the efficacy of vaccines to promote effective immunity in this population is needed. METHODS: This was a prospective longitudinal observational cohort study that enrolled patients with solid cancer classified into dexamethasone- and nondexamethasone-receiving groups. All participants were immunized with two doses of ChAdOx1 nCoV-19 or CoronaVac vaccines. This study's purpose was to compare corticosteroid's effect on immunogenicity responses to the SARS-CoV-2 S protein in patients with cancer after two doses of COVID-19 vaccine in the dexamethasone and nondexamethasone group. Secondary outcomes included the postimmunization anti-spike (S) immunoglobin G (IgG) seroconversion rate, the association of corticosteroid dosage, time duration, and immunogenicity level. RESULTS: Among the 161 enrolled patients with solid cancer, 71 and 90 were in the dexamethasone and nondexamethasone groups, respectively. The median anti-S IgG titer after COVID-19 vaccination in the dexamethasone group was lower than that in the nondexamethasone group with a statistically significant difference (47.22 v 141.09 U/mL, P = .035). The anti-S IgG seroconversion rate was also significantly lower in the dexamethasone group than in the nondexamethasone group (93.83% v 80.95%, P = .023). The lowest median anti-SARS-CoV-2 IgG titer level at 7.89 AU/mL was observed in patients with the highest dose of steroid group (≥37 mg of dexamethasone cumulative dose throughout the course of chemotherapy [per course]) and patients who were injected with COVID-19 vaccines on the same day of receiving dexamethasone, 25.41 AU/mL. CONCLUSION: Patients with solid cancer vaccinated against COVID-19 disease while receiving dexamethasone had lower immunogenicity responses than those who got vaccines without dexamethasone. The direct association between the immunogenicity level and steroid dosage, as well as length of duration from vaccination to dexamethasone, was observed.

Pan-viral serology uncovers distinct virome patterns as risk predictors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

This study evaluates the pan-serological profiles of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) compared to several diseased and non-diseased control populations to identify risk factors and biomarkers of liver cancer. We used phage immunoprecipitation sequencing, an anti-viral antibody screening method using a synthetic-phage-displayed human virome epitope library, to screen patient serum samples for exposure to over 1,280 strains of pathogenic and non-pathogenic viruses. Using machine learning methods to develop an HCC or iCCA viral score, we discovered that both viral scores were positively associated with several liver function markers in two separate at-risk populations independent of viral hepatitis status. The HCC score predicted all-cause mortality over 8 years in patients with chronic liver disease at risk of HCC, while the viral hepatitis status was not predictive of survival. These results suggest that non-hepatitis viral infections may contribute to HCC and iCCA development and could be biomarkers in at-risk populations.

Efficacy of Andrographis paniculata extract treatment in mild to moderate COVID-19 patients being treated with favipiravir: A double-blind, randomized, placebo-controlled study (APFaVi trial).

BACKGROUND: While favipiravir had been the standard anti-SARS-CoV-3 drug for COVID-19 treatment in Thailand, the efficacy of favipiravir treatment is controversial. Andrographis paniculata extract (APE) inhibits viral entry, exhibits immunomodulatory effects, and proposes to have the potential for early-stage COVID-19 treatment. METHODS: A randomized, double-blind, placebo-controlled trial was performed in Thailand during June - September 2021. Non-severe COVID-19 patients were randomized 1:1 to groups receiving 180 mg/day of APE plus favipiravir (APE-FPV group) or placebo plus favipiravir (placebo-FPV group). Efficacy in preventing disease progression to severe COVID-19 was assessed on day 4, using World Health Organization Clinical Progression Scale (WHOCPS) score and visual analog scale (VAS) for acute respiratory tract infection symptoms. RESULTS: Of 146 patients, there were 73 patients in each group. Non-deterioration of WHOCPS scores on day 4 was 98.63% versus 97.26% of patients in the APE-FPV and placebo-FPV groups (p = 1.000). No difference in supplemental oxygen, hospitalization, and death was shown in both groups. The oxygen supplemental was 4.11% in the placebo-FPV group. The interleukin (IL)-1ß was significantly lower in the APE than in the placebo-FPV group throughout the study. We found no difference in virologic outcomes between groups and no substantial adverse events. CONCLUSIONS: APE treatment did not demonstrate additional clinical and virological benefits in patients with mild to moderate COVID-19 being treated with favipiravir. Early reduction of IL-1ß with APE may be advantageous in preventing cytokine storms in severe COVID-19 and requires further study.

Efficacy of combination therapy of fluvoxamine and favipiravir vs favipiravir monotherapy to prevent severe COVID-19 among mild to moderate COVID-19 patients: Open-label randomized controlled trial (EFFaCo study).

OBJECTIVES: Fluvoxamine (FVX) is an antidepressant proposed to its immunomodulatory effects in preventing deterioration in mild and moderate COVID-19. METHODS: An open-label, 1:1 randomized controlled trial was assigned either combination therapy 50 mg twice daily of FVX for 10 days and favipiravir (FPV) or FPV alone to assess the efficacy in preventing disease progression in mild to moderate COVID-19 on the 5th day. RESULTS: In total, 134 patients with mild COVID-19 received FPV and 132 received FVX/FPV, 31 patients with moderate COVID-19 received FPV/dexamethasone (FPV/Dex), and 30 received FVX/FPV/Dex. The intention-to-treat (ITT) analysis showed no difference of no clinical deterioration on the 5th day in both mild COVID-19 (100% in FPV vs 97% in FVX/FPV) and moderate COVID-19 (83.9% in FPV/Dex vs 86.7% in FVX/FPV/Dex). However, there was a low rate of oxygen supplemental, hospitalization, or intensive care in both groups and zero death in all groups. No significant difference in oxygen supplemental, hospitalization, radiological, virological, or biochemical outcomes, and the immunomodulatory effect was observed between the group. CONCLUSION: The combined fluvoxamine treatment did not add benefit in preventing deterioration in patients with mild to moderate COVID-19 without the immunomodulatory effect observed, although it demonstrated low hospitalization rates, oxygen supplemental, intensive care needed, and zero mortality. TRIAL REGISTRATION: Thai clinical trials registry (TCTR) no. 20210615002.

Benefits and harms of gastric suction or lavage at birth for gastrointestinal outcomes: A systematic review and meta-analysis.

The benefits of routine gastric suctioning or lavage in neonates remain uncertain, despite the common practice worldwide. To investigate the potential advantages and harms, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effects of these procedures in healthy or meconium-stained neonates at birth. We systematically searched PubMed, Scopus, Embase, Ovid, and the Cochrane Library databases from inception to February 9, 2023. We included only RCTs assessing the outcomes of gastric suction or lavage in neonates at birth. We calculated risk ratio (RR) and weighted mean differences with 95% confidence intervals (CIs) using a random-effects model. The primary outcomes were gastrointestinal symptoms including vomiting, retching, feeding intolerance, and secondary aspiration. The secondary outcomes included time to initiation of breastfeeding and potential adverse procedure-related events. Twelve RCTs with a total of 4,122 neonates were analyzed. All the studies compared neonates who received gastric suction or lavage with those who received usual care. Gastrointestinal symptoms were significantly reduced in neonates receiving gastric suction or gastric lavage compared with the control group (RR, 0.75; 95% CI, 0.63-0.89). Gastric lavage was beneficial for infants with meconium-stained amniotic fluid (RR 0.71; 95% CI, 0.60-0.84), while gastric suction had no significant benefit in reducing gastrointestinal symptoms in infants without meconium-stained amniotic fluid (RR 0.91; 95% CI, 0.61-1.37). Our findings suggest that gastric suction or lavage may reduce gastrointestinal symptoms in neonates; however, these procedures may only benefit infants born with meconium-stained amniotic fluid. Vigorous newborns without meconium-stained amniotic fluid may not benefit from these procedures. Furthermore, gastric suction may lead to adverse outcomes such as apnea and bradycardia. Registration: This study was registered in the PROSPERO International prospective register of systematic reviews in health and social care (CRD42023247780).

Gut dysbiosis in Thai intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

Primary liver cancer (PLC), which includes intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC), has the highest incidence of all cancer types in Thailand. Known etiological factors, such as viral hepatitis and chronic liver disease do not fully account for the country's unusually high incidence. However, the gut-liver axis, which contributes to carcinogenesis and disease progression, is influenced by the gut microbiome. To investigate this relationship, fecal matter from 44 Thai PLC patients and 76 healthy controls were subjected to whole-genome metagenomic shotgun sequencing and then analyzed by marker gene-based and assembly based methods. Results revealed greater gut microbiome heterogeneity in iCCA compared to HCC and healthy controls. Two Veillonella species were found to be more abundant in iCCA samples and could distinguish iCCA from HCC and healthy controls. Conversely, Ruminococcus gnavus was depleted in iCCA patients and could distinguish HCC from iCCA samples. High Veillonella genus counts in the iCCA group were associated with enriched amino acid biosynthesis and glycolysis pathways, while enriched phospholipid and thiamine metabolism pathways characterized the HCC group with high Blautia genus counts. These findings reveal distinct landscapes of gut dysbiosis among Thai iCCA and HCC patients and warrant further investigation as potential biomarkers.

The Real-World Clinical Outcomes of Favipiravir Treatment with Telemedicine Monitoring in Preventing Disease Progression in Mild to Moderate COVID-19 Patients; A Retrospective Cohort Study.

Background: Favipiravir has complex pharmacokinetics, and varied efficacy has been reported in treating COVID-19. Telehealth and telemonitoring are disruptive challenges used for COVID-19 care during pandemics. Objective: This study aimed to assess the outcome of favipiravir treatment to prevent clinical deterioration in mild to moderate COVID-19 cases with adjunctive telemonitoring during the COVID-19 surge. Methods: This was a retrospective observational study of PCR-confirmed mild to moderate COVID-19 cases subjected to home isolation. Chest computed tomography (CT) was performed in all cases, and favipiravir was administrated. Results: This study involved 88 PCR-confirmed COVID-19 cases. In addition, 42/42 (100%) cases were Alpha variants. COVID-19 pneumonia was found in 71.5% of the cases, according to chest X-rays and chest CT on the first visit. Favipiravir started 4 days after symptoms, which was part of the standard of care. The 12.5% of the patients required supplemental oxygen and intensive care unit admission rate was 1.1%; 1.1% required mechanical ventilation, and the rate of all-cause mortality was 1.1%, with a value of 0% of severe COVID-19 deaths. All mild illness cases showed no clinical deterioration or requirement for supplemental oxygen. No significant deterioration in either obesity or diabetes mellitus was observed. Conclusions: Favipiravir treatment for mild to moderate COVID-19 cases in outpatient settings, coupled with telemonitoring, was both safe and effective in preventing clinical deterioration, including the need for oxygen supplementation. This approach proved valuable during surges of COVID-19 cases.

Immunogenicity and reactogenicity of heterologous prime-boost vaccination with inactivated COVID-19 and ChAdOx1 nCoV-19 (AZD1222) vaccines, a quasi-experimental study.

The global supply of COVID-19 vaccines has been limited, and concerns have arisen about vaccine supply chain disruptions in developing countries. Heterologous prime-boost vaccination, which involves using different vaccines for the first and second doses, has been proposed to enhance the immune response. We aimed to compare the immunogenicity and safety of a heterologous prime-boost vaccination using an inactivated COVID-19 vaccine and AZD1222 vaccine with that of a homologous vaccination using AZD1222. This pilot involved 164 healthy volunteers without prior SARS-CoV-2 infection aged 18 years or older assigned to receive either the heterologous or homologous vaccination. The results showed that the heterologous approach was safe and well-tolerated, although the reactogenicity of the heterologous approach was higher. At 4 weeks after receiving the booster dose, the heterologous approach elicited a non-inferior immune response compared to the homologous approach in neutralizing antibody and cell-mediated immune response. The percentage of inhibition was 83.88 (79.72-88.03) in the heterologous and 79.88 (75.50-84.25) in the homologous group, a mean difference of 4.60 (-1.67-10.88). The geometric mean of interferon-gamma was 1072.53 mIU/mL (799.29-1439.18) in the heterologous group and 867.67 mIU/mL (671.94-1120.40) in the homologous group, a GMR of 1.24 (0.82-1.85). However, the binding antibody test of the heterologous group was inferior to the homologous group. Our findings suggest that the use of heterologous prime-boost vaccination with different types of COVID-19 vaccines is a viable strategy, especially in settings where vaccine supply is limited or where vaccine distribution is challenging.

Difference in Immunogenic Responses to COVID-19 Vaccines in Patients With Cancer Receiving Chemotherapy Versus Nonchemotherapy Treatment.

PURPOSE: The COVID-19 pandemic has affected public health worldwide. The efficacy and safety of COVID-19 vaccines have been evaluated in the general population; however, data on patients with malignancies are limited. METHODS: This prospective longitudinal observational cohort study was conducted between June and July 2021. Enrolled adult patients with cancer were divided into chemotherapy and nonchemotherapy groups. All participants were immunized with two doses of the ChAdOx1 nCoV-19 or CoronaVac COVID-19 vaccines. The primary outcome was a comparison of the immunogenicity (as assessed by spike protein [anti-S] immunoglobulin G [IgG] antibody titers) of two doses of COVID-19 vaccine in the chemotherapy and nonchemotherapy groups. The secondary outcomes included the anti-S IgG seroconversion rate and vaccine safety in both groups. RESULTS: Among the 173 enrolled patients with solid cancer, after COVID-19 vaccination, the chemotherapy group had a significantly lower median anti-S IgG titer than the nonchemotherapy group (26 v 237 U/mL, P < .001). A statistically significant difference in anti-S IgG titer was found between groups vaccinated with CoronaVac (7 v 90 U/mL, P < .001), but no difference was found in those vaccinated with ChAdOx1 nCoV-19 (818 v 1061 U/mL, P = .075). The anti-S IgG seroconversion rate was significantly lower in the chemotherapy group than that in the nonchemotherapy group (78.9% v 96.5%, P = .001). No new or serious vaccine-related adverse events were reported. CONCLUSION: Patients with solid cancer receiving a COVID-19 vaccine while undergoing chemotherapy had lower immunogenicity responses to vaccination than those who were vaccinated while undergoing nonchemotherapy treatment. No statistically significant difference was observed in the COVID-19 vaccine safety profiles between groups.

Pharmacokinetic Comparison of Favipiravir Oral Solution and Tablet Formulations in Healthy Thai Volunteers.

This study compared the pharmacokinetics and safety of favipiravir oral solution with those of tablet formulations, which were agents repurposed to treat nonsevere coronavirus disease 2019 in Thailand. In an open-label, single-dose, randomized, crossover study, 24 healthy subjects under fasting conditions were randomly assigned to a single dose of 200 mg of favipiravir, either as an oral solution of 200 mg/15 mL (test product) or a tablet (reference product), separated by a 7-day washout period. Fifteen plasma samples were collected over 12 hours after drug administration. Plasma favipiravir levels were quantified using in-house developed ultra-high-performance liquid chromatography-tandem mass spectrometry. The test/reference geometric mean ratio along with 90%CI for the maximum plasma concentration, area under the concentration-time curve (AUC) to the time of the last quantifiable concentration, and AUC after single-dose administration, extrapolated to infinity were 115.3% (90%CI, 107.7%-123.3%), 100.4% (90%CI, 96.9%-104.0%), and 100.4% (90%CI, 96.8%-104.2%), respectively. These results were within the predefined acceptance criteria for bioequivalence (80.0%-125.0%). No adverse events were observed in either group. The oral solution formulation could offer the advantage of easier swallowing in broader patient groups.

SARS-CoV-2 seroprevalence among cancer patients and household caregivers in a cancer hospital: Cross-sectional survey after the second COVID-19 wave in Thailand.

Objectives: Patients with cancer may be at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and experience more severe outcomes. Low vaccine coverage in the early phase of the coronavirus disease 2019 (COVID-19) pandemic meant that personal and social measures to reduce viral spread were the only methods of lowering the risk of infection among cancer patients. This study explored the prevalence of SARS-CoV-2 antibodies in cancer patients and caregivers in a cancer hospital after the second COVID-19 outbreak in Thailand. Study design: Cross-sectional study. Methods: A SARS-CoV-2 seroprevalence cross-sectional survey was conducted among 200 cancer patients and 200 household caregivers in a tertiary cancer care hospital in Bangkok, Thailand. The survey took place between 4 March and May 31, 2021 - a time period covering the end of the second COVID-19 wave and the early phase of the third wave in Thailand. Results: Rigorous personal and social measures to reduce viral spread among cancer patients and caregivers lead to an extremely low prevalence of SARS-CoV2 infection (0% among cancer patients and 1% among household caregivers). Conclusion: This study demonstrates the importance of social distancing and personal hygiene measures for the prevention of SARS-CoV-2 infection, even when vaccine coverage is low.

Safety after BBIBP-CorV (Sinopharm) COVID-19 Vaccine in Adolescents Aged 10-17 Years in Thailand.

Coronavirus disease 2019 affected child health and impacted learning because of the resulting onsite school closures. This prospective cohort study included children aged 10-17 who received two 4 µg doses of BBIBP-CorV administered intramuscularly 21-28 days apart. To assess vaccine safety, 36,808 participants were then followed with paper- and web-based online questionnaire surveys that captured local and systemic reactogenicities following vaccine administration on days 1, 7, and 30. Among participants, 76% (27,880) reported reactogenicity within the first 24 h and 7 days following the first dose. Half (51.41%) of participants experienced pain at the injection site; the majority of cases were mild in severity. Injection site tenderness (37.93%) was another common local reaction. Fatigue (37.89%), myalgia (33.56%), and headache (26.76%) were the most common systemic reactions. On days 2-7 after the first dose, 25.85% of participants experienced adverse reactions. Following the second dose, reactogenicity was 7.6% and 1.09% within 24 h and between days 2-7. The majority of reactions were of mild to moderate severity. We report that two doses of the BBIBP-CorV caused mild to moderate side effects in adolescents in Thailand. The findings confirm the vaccine's safety profile in this age group.

Bilateral Proptosis as an Unusual Presentation of Adult-Onset Alveolar-Type Rhabdomyosarcoma of Ethmoid Sinus: A Case Report.

Rhabdomyosarcoma (RMS) exhibits varying degrees of clinical manifestations, and one of the determining factors is its primary site of origin. Ocular proptosis is an infrequent presentation of parameningeal RMS. The growing tumor in spacious environments such as air-filled sinuses can obscure its early detection, leading to late disease intervention. Among the four subtypes (embryonal, leiomyomatous, sclerosing and spindle cell, and alveolar), the predominant type of RMS in the paranasal sinuses is alveolar. The incidence in adult-onset RMS is relatively low compared with those of children. We herein present a rare case of a 23-year-old man with an unusual presentation of bilateral proptosis from alveolar RMS of the ethmoid sinus. In contrast to our patient, most reported cases of ocular involvement in RMS turned out to be unilateral and responded poorly to treatment. Despite the aggressive behavior of the adult-onset alveolar subtype in comparable reports, our case shows an excellent outcome. Negative FOXO1 fusion status has been recognized in recent studies as a molecular feature inclined toward a favorable outcome in alveolar RMS. The integration of molecular prognostic factors to risk stratification could be advantageous in determining different prognoses and proper management for an individual patient.

Unusual Presentation of Bilateral Chylothorax and Chylous Ascites with Pancreatic Adenocarcinoma: A Case Report.

Chylothorax is a lymphatic fluid, which is contained in the pleural cavity. Chylothorax has a typical milky white fluid appearance and is diagnosed by triglyceride concentrations >110 mg/dL. The combination of chylothorax with chylous ascites is a rare condition that is difficult to manage. We present a case of a 60-year-old man who presented with dyspnea for 1 week and generalized abdominal distention. He was diagnosed with advanced-stage pancreatic adenocarcinoma and received palliative chemotherapy. On follow-up examination, he showed decreased breathing sounds in both lungs and marked ascites. Chest radiography showed bilateral pleural effusion, which was more prominent in the left hemithorax than the right hemithorax. Thoracocentesis and abdominal paracentesis were performed, and the finding of pleural and ascites fluid was compatible with bilateral chylothorax and chylous ascites. Although the patient was receiving dietary modification, he still required repeated thoracentesis. Bilateral chest tube insertion with medical pleurodesis with talc successfully treated his chylothorax. This treatment should be considered as an option for malignancy-associated chylothorax besides systemic cancer treatment to improve patients' quality of life.

Immunogenicity evaluation of ChAdox1 nCov-19 (AZD1222) vaccine in solid cancer patients in Chulabhorn Hospital.

INTRODUCTION: Cancer patients are more vulnerable to coronavirus disease 2019 (COVID-19) owing to their compromised immune status. However, data regarding COVID-19 vaccine safety and immune response in cancer patients are scarce. METHOD: This prospective, age- and sex-matched, single-center cohort study included 61 cancer patients and 122 healthy control participants. Seropositivity was defined as anti-S IgG titer >0.8 units/ml. Primary end point was seroconversion rate of immunoglobulin (Ig)G antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein (anti-S IgG) in cancer patients vs. healthy control participants following the second dose of COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). RESULTS: After the second-dose vaccination, there was no difference in seropositivity rate between groups (57 [93.44%] patients with cancer vs. 121 [99.18%] control participants; geometric mean ratio [GMR]: 0.39; 95%CI: 0.01-10.46; p-value = 0.571). In contrast, after the first-dose vaccination, the seropositivity rate was significantly lower in the cancer patients than in the control participants (50/61 [81.97%] vs. 121/122 [99.18%]; GMR: 0.07; 95%CI: 0.01-0.71; p = 0.025). The median anti-S IgG titer after the first-and second dose vaccination were not significantly different between groups. Female sex was significantly associated with a higher anti-S IgG titer. 5FU- and taxane-based chemotherapy regimens were associated with a lower IgG titer. Side effects of vaccination were tolerable. CONCLUSIONS: The anti-S IgG seropositivity rate after completing the second vaccine dose did not differ between the cancer patients and control participants. However, the anti-S IgG seropositivity rate after the first-dose vaccination was lower in cancer patients.

Safety and Immunogenicity of the BBIBP-CorV Vaccine in Adolescents Aged 12 to 17 Years in the Thai Population: An Immunobridging Study.

Adolescents can develop a severe form of Coronavirus disease 2019 (COVID-19), especially with underlying comorbidities. No study has examined the efficacy or effectiveness of inactivated COVID-19 vaccines in adolescents. This single-center, prospective cohort study was performed to evaluate the safety and effectiveness of an inactivated COVID-19 vaccine in adolescents using the immunobridging approach at Chulabhorn Hospital. The key eligibility criterion was a healthy clinical condition or stable pre-existing comorbidity. The anti-receptor-binding domain (anti-RBD) antibody concentration at 4 weeks after dose 2 of the vaccine was compared between participants aged 12 to 17 years and those aged 18 to 30 years. Safety profiles included adverse events within 7 days after each dose of the vaccine and any adverse events through 1 month after dose 2 of the vaccine. In the adolescent and adult cohorts, the geometric mean concentration of anti-RBD antibody was 102.9 binding antibody unit (BAU)/mL (95% CI, 91.0−116.4) and 36.9 BAU/mL (95% CI, 30.9−44.0), respectively. The geometric mean ratio of the adolescent cohort was 2.79 (95% CI, 2.25−3.46, p < 0.0001) compared with the adult cohort, meeting the non-inferiority criterion. The reactogenicity was slightly lower in the adolescent than in the adult cohort. No serious adverse events occurred. The inactivated COVID-19 vaccine appears safe and effective in adolescents.

Oral vitamin A supplementation in preterm infants to improve health outcomes: A systematic review and meta-analysis.

OBJECTIVE: To determine the effects of oral vitamin A supplementation on clinical outcomes in preterm infants. DESIGN: We conducted the meta-analysis by searching PubMed/Medline, Scopus, Embase, CINAHL, and the Cochrane Library databases from inception to 12 August 2021, including reference lists of retrieved articles. Only randomized controlled trials (RCTs) evaluating the effects of oral vitamin A on premature babies were included. We used a random-effects model to calculate risk ratios (RRs) and weighted mean differences (MDs) with 95% confidence intervals (CIs). We used the GRADE approach to grade evidence quality and assess how oral vitamin A supplementation affects clinical outcomes. MAIN OUTCOMES MEASURES: The primary outcomes were respiratory outcomes, including the length of respiratory support, the need for oxygen at 36 weeks postmenstrual age (PMA), and moderate-to-severe bronchopulmonary dysplasia (BPD) at 36 weeks PMA. Secondary outcomes were hospitalization time, vitamin A status, mortality, other related outcomes, and potential adverse drug-related events. RESULTS: We included four RCTs, with 800 patients total. In all trials, oral vitamin A treatment was compared to a placebo. Oral vitamin A supplementation did not significantly affect mechanical ventilation duration (MD, -1.07 days; 95% CI, -2.98 to 0.83 days), oxygen requirement at 36 weeks PMA (RR, 0.65; 95% CI, 0.33 to 1.31), or moderate-to-severe BPD at 36 weeks PMA (RR, 0.53; 95% CI, 0.07 to 4.17). However, oral vitamin A supplementation yielded a slightly shorter noninvasive ventilation duration (MD, -0.96 days; 95% CI, -1.59 to -0.33 days). CONCLUSIONS: Administering oral vitamin A to preterm newborns did not alter the mechanical ventilation duration, oxygen needed at 36 weeks PMA, moderate-to-severe BPD at 36 weeks PMA, death, or short-term benefits. However, oral vitamin A supplementation may slightly affect the duration of noninvasive respiratory support without adverse drug-related events.

Duration of Hepatitis B Vaccine-Induced Protection among Medical Students and Healthcare Workers following Primary Vaccination in Infancy and Rate of Immunity Decline.

Since the introduction of hepatitis B virus (HBV) vaccines, the numbers of HBV infections and complications have significantly decreased. However, the evidence on whether primary vaccination of infants confers lifelong immunity varies. We aimed to assess long-term immunity among healthcare workers and medical students, and the rate of decline of HBV surface antigen antibodies (anti-HBs). Hepatitis B status among participants born after 1 January 1992 was reviewed at Chulabhorn Royal Academy, Thailand. Participants were stratified by intervals since primary vaccination. HBV immunity was determined and analyzed as anti-HBs decline rate in participants with multiple follow-ups. A total of 464 participants were analyzed, with a median age of 23. Protective immunity against HBV (anti-HBs ≥ 10 mIU/mL) at 16-20, 21-25 and 26-28 years post-primary vaccination was 28%, 51.7% and 60%, respectively. The overall declining rate of anti-HBs was -42.39 mIU/mL per year. Participants with anti-HBs levels of >100-1000 mIU/mL at baseline had a faster decline rate than those with anti-HBs levels of 10-100 mIU/mL. Primary vaccination may not provide lifelong protection since HBV immunity deteriorates over time. Individuals with higher initial HBV immunity levels may experience a faster decline rate.

Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine.

BACKGROUND & AIMS: Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. METHODS: We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. RESULTS: The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. CONCLUSION: There is great variability in CHB disease progression rates even among "lower-risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.