A novel IKZF1 variant in a family with autosomal dominant CVID: A case for expanding exon coverage in inborn errors of immunity.

Common variable immune deficiency (CVID) is a heterogenous group of disorders characterized by varying degrees of hypogammaglobulinemia, recurrent infections, and autoimmunity. Currently, pathogenic variants are identified in approximately 20-30% of CVID cases. Here we report a 3-generation family with autosomal dominant Common Variable Immunodeficiency (CVID) diagnosed in 9 affected individuals. Although primary immune deficiency panels and exome sequencing were non-diagnostic, whole genome sequencing revealed a novel, pathogenic c.499C > T: p.His167Tyr variant in IKZF1, a critical regulator of B cell development. Functional testing done through pericentromeric heterochromatin localization and light shift chemiluminescent electrophoretic mobility shift assay confirmed the variant's deleterious effect via a haploinsufficiency mechanism. Our findings expand the spectrum of known IKZF1 mutations and contribute to a more comprehensive understanding of CVID's genetic heterogeneity. Furthermore, this case underscores the importance of considering whole genome sequencing for comprehensive genetic diagnosis when concern for a monogenic inborn errors of immunity is high.

Targeted phasing of 2-200 kilobase DNA fragments with a short-read sequencer and a single-tube linked-read library method.

In the human genome, heterozygous sites refer to genomic positions with a different allele or nucleotide variant on the maternal and paternal chromosomes. Resolving these allelic differences by chromosomal copy, also known as phasing, is achievable on a short-read sequencer when using a library preparation method that captures long-range genomic information. TELL-Seq is a library preparation that captures long-range genomic information with the aid of molecular identifiers (barcodes). The same barcode is used to tag the reads derived from the same long DNA fragment within a range of up to 200 kilobases (kb), generating linked-reads. This strategy can be used to phase an entire genome. Here, we introduce a TELL-Seq protocol developed for targeted applications, enabling the phasing of enriched loci of varying sizes, purity levels, and heterozygosity. To validate this protocol, we phased 2-200 kb loci enriched with different methods: CRISPR/Cas9-mediated excision coupled with pulse-field electrophoresis for the longest fragments, CRISPR/Cas9-mediated protection from exonuclease digestion for mid-size fragments, and long PCR for the shortest fragments. All selected loci have known clinical relevance: BRCA1, BRCA2, MLH1, MSH2, MSH6, APC, PMS2, SCN5A-SCN10A, and PKI3CA. Collectively, the analyses show that TELL-Seq can accurately phase 2-200 kb targets using a short-read sequencer.

A Guideline for Open-Source Tools to Make Medical Imaging Data Ready for Artificial Intelligence Applications: A Society of Imaging Informatics in Medicine (SIIM) Survey.

In recent years, the role of Artificial Intelligence (AI) in medical imaging has become increasingly prominent, with the majority of AI applications approved by the FDA being in imaging and radiology in 2023. The surge in AI model development to tackle clinical challenges underscores the necessity for preparing high-quality medical imaging data. Proper data preparation is crucial as it fosters the creation of standardized and reproducible AI models while minimizing biases. Data curation transforms raw data into a valuable, organized, and dependable resource and is a fundamental process to the success of machine learning and analytical projects. Considering the plethora of available tools for data curation in different stages, it is crucial to stay informed about the most relevant tools within specific research areas. In the current work, we propose a descriptive outline for different steps of data curation while we furnish compilations of tools collected from a survey applied among members of the Society of Imaging Informatics (SIIM) for each of these stages. This collection has the potential to enhance the decision-making process for researchers as they select the most appropriate tool for their specific tasks.

Multi-harmonic near-infrared-ultraviolet dual-comb spectrometer.

Dual-comb spectroscopy in the ultraviolet (UV) and visible would enable broad bandwidth electronic spectroscopy with unprecedented frequency resolution. However, there are significant challenges in generation, detection, and processing of dual-comb data that have restricted its progress in this spectral region. In this work, we leverage robust 1550 nm few-cycle pulses to generate frequency combs in the UV-visible. We combine these combs with a wavelength multiplexed dual-comb spectrometer and simultaneously retrieve 100 MHz comb-mode-resolved spectra over three distinct harmonics at 386, 500, and 760 nm. The experiments highlight the path to continuous dual-comb coverage spanning 200-750 nm, offering extensive access to electronic transitions in atoms, molecules, and solids.

Population Pharmacokinetics of Sacituzumab Govitecan in Patients with Metastatic Triple-Negative Breast Cancer and Other Solid Tumors.

BACKGROUND AND OBJECTIVE: Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an antibody with affinity for Trop-2 coupled to SN-38 via hydrolyzable linker. SG is approved for patients with metastatic triple-negative breast cancer (mTNBC) who have received two or more prior chemotherapies (at least one in a metastatic setting) and for patients with pretreated hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. METHODS: In these analyses, the pharmacokinetics of SG, free SN-38, and total antibody (tAB) were characterized using data from 529 patients with mTNBC or other solid tumors across two large clinical trials (NCT01631552; ASCENT, NCT02574455). Three population pharmacokinetic models were constructed using non-linear mixed-effects modeling; clinically relevant covariates were evaluated to assess their impact on exposure. Models for SG and tAB were developed independently whereas free SN-38 was sequentially generated via a first-order release process from SG. RESULTS: Pharmacokinetics of the three analytes were each described by a two-compartment model with estimated body weight-based scaling exponents for clearance and volume. Typical parameter estimates for clearance and steady-state volume of distribution were 0.133 L/h and 3.68 L for SG and 0.0164 L/h and 4.26 L for tAB, respectively. Mild-to-moderate renal impairment, mild hepatic impairment, age, sex, baseline albumin level, tumor type, UGT1A1 genotype, or Trop-2 expression did not have a clinically relevant impact on exposure for any of the three analytes. CONCLUSIONS: These analyses support the approved SG dosing regimen of 10 mg/kg as intravenous infusion on days 1 and 8 of 21-day cycles and did not identify a need for dose adjustment based on evaluated covariates or disease characteristics.

Assessing the Performance of Artificial Intelligence Models: Insights from the American Society of Functional Neuroradiology Artificial Intelligence Competition.

BACKGROUND AND PURPOSE: Artificial intelligence (AI) models in radiology are frequently developed and validated using datasets from a single institution and are rarely tested on independent, external datasets, raising questions about their generalizability and applicability in clinical practice. The American Society of Functional Neuroradiology (ASFNR) organized a multi-center AI competition to evaluate the proficiency of developed models in identifying various pathologies on NCCT, assessing age-based normality and estimating medical urgency. MATERIALS AND METHODS: In total, 1201 anonymized, full-head NCCT clinical scans from five institutions were pooled to form the dataset. The dataset encompassed normal studies as well as pathologies including acute ischemic stroke, intracranial hemorrhage, traumatic brain injury, and mass effect (detection of these-task 1). NCCTs were also assessed to determine if findings were consistent with expected brain changes for the patient's age (task 2: age-based normality assessment) and to identify any abnormalities requiring immediate medical attention (task 3: evaluation of findings for urgent intervention). Five neuroradiologists labeled each NCCT, with consensus interpretations serving as the ground truth. The competition was announced online, inviting academic institutions and companies. Independent central analysis assessed each model's performance. Accuracy, sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curves were generated for each AI model, along with the area under the ROC curve (AUROC). RESULTS: 1177 studies were processed by four teams. The median age of patients was 62, with an interquartile range of 33. 19 teams from various academic institutions registered for the competition. Of these, four teams submitted their final results. No commercial entities participated in the competition. For task 1, AUROCs ranged from 0.49 to 0.59. For task 2, two teams completed the task with AUROC values of 0.57 and 0.52. For task 3, teams had little to no agreement with the ground truth. CONCLUSIONS: To assess the performance of AI models in real-world clinical scenarios, we analyzed their performance in the ASFNR AI Competition. The first ASFNR Competition underscored the gap between expectation and reality; the models largely fell short in their assessments. As the integration of AI tools into clinical workflows increases, neuroradiologists must carefully recognize the capabilities, constraints, and consistency of these technologies. Before institutions adopt these algorithms, thorough validation is essential to ensure acceptable levels of performance in clinical settings.ABBREVIATIONS: AI = artificial intelligence; ASFNR = American Society of Functional Neuroradiology; AUROC = area under the receiver operating characteristic curve; DICOM = Digital Imaging and Communications in Medicine; GEE = generalized estimation equation; IQR = interquartile range; NPV = negative predictive value; PPV = positive predictive value; ROC = receiver operating characteristic; TBI = traumatic brain injury.

Enhancing regional control in p16-negative oropharyngeal cancer: A propensity score-matched analysis of upfront neck dissection and definitive chemoradiotherapy.

BACKGROUND: The presence of p16 and neck disease is important predictors of prognosis for oropharyngeal squamous cell carcinoma (OPSCC). Patients who are p16-negative and have clinically node-positive (cN+) disease generally have worse oncologic outcomes. This study aimed to investigate whether upfront neck dissection (UFND) could provide potential benefits for patients with cN+ p16-negative OPSCC. METHODS: Through this retrospective study, 76 patients with cN+ p16-negative OPSCC were analyzed, those who received either definite concurrent chemoradiotherapy (CCRT group) or UFND followed by chemoradiotherapy (UFND group). The primary endpoints were regional recurrence-free survival (RRFS), disease-specific survival (DSS), and overall survival (OS). Factors associated with survival were evaluated by univariate and multivariate analysis. Survival between the two groups was compared by propensity score-matched analysis. RESULTS: Matched 23 patients in each group through propensity analysis, the UFND group showed a significantly better 5-year RRFS (94.1% vs 61.0%, p = 0.011) compared to the CCRT group. Univariate analysis revealed that UFND was the sole factor associated with regional control (hazard ratio [HR] = 0.110; 95% CI, 0.014-0.879; p = 0.037). Furthermore, the study found that the CCRT group was associated with a higher dose of radiotherapy and exhibited a significantly higher risk of mortality due to pneumonia. CONCLUSION: The study indicated that UFND followed by CCRT may be a potential treatment option for patients with cN+ p16-negative OPSCC, as it can reduce the risk of regional recurrence. Additionally, the study highlights that definite CCRT is connected to a larger dose of radiotherapy and a higher risk of fatal pneumonia. These findings could be beneficial in informing clinical decision-making and improving treatment outcomes for patients with OPSCC.

The association of patient and disease characteristics with the overtreatment of low-risk prostate cancer from 2010 to 2016.

BACKGROUND: Although active surveillance is the preferred management for low-risk prostate cancer (PCa), some men remain at risk of overtreatment with definitive local therapy. We hypothesized that baseline characteristics may be associated with overtreatment and represent a potential source of health disparities. We therefore examined the associations of patient and disease characteristics with the surgical overtreatment of low-risk PCa. METHODS: We identified men aged 45-75 years with cT1 cN0 cM0 prostate adenocarcinoma with biopsy Gleason score 6 and PSA < 10 ng/ml from 2010-2016 in the National Cancer Database (NCDB) and who underwent radical prostatectomy (RP). We evaluated the associations of baseline characteristics with clinically insignificant PCa (iPCa) at RP (i.e., "overtreatment"), defined as organ-confined (i.e., pT2) Gleason 3 + 3 disease, using multivariable logistic regression. RESULTS: We identified 36,088 men with low-risk PCa who underwent RP. The unadjusted rate of iPCa decreased during the study period, from 54.7% in 2010 to 40.0% in 2016. In multivariable analyses adjusting for baseline characteristics, older age (OR 0.98, 95% CI 0.97-0.98), later year of diagnosis (OR 0.62, 95% CI 0.57-0.67 for 2016 vs. 2010), Black race (OR 0.85, 95% CI 0.79-0.91), treatment at an academic/research program (OR 0.82, 95% CI 0.73-0.91), higher PSA (OR 0.91, 95% CI 0.90-0.92), and higher number of positive biopsy cores (OR 0.87, 95% CI 0.86-0.88) were independently associated with a lower risk of overtreatment (iPCa) at RP. Conversely, a greater number of biopsy cores sampled (OR 1.01, 95% CI 1.01-1.02) was independently associated with an increased risk of overtreatment (iPCa) at RP. CONCLUSIONS: We observed an ~27% reduction in rates of overtreatment of men with low-risk PCa over the study period. Several patient, disease, and structural characteristics are associated with detection of iPCa at RP and can inform the management of men with low-risk PCa to reduce potential overtreatment.

The Association of a Peritoneal Interposition Flap With Lymphocele Formation After Pelvic Lymph Node Dissection During Robotic-assisted Laparoscopic Radical Prostatectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the association of a peritoneal interposition flap (PIF) with lymphocele formation following robotic-assisted laparoscopic radical prostatectomy (RALP) with pelvic lymph node dissection. METHODS: We conducted a systematic search of MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials through August 30, 2023, to identify randomized and nonrandomized studies comparing RALP with pelvic lymph node dissection with and without PIF. A random effects meta-analysis was then performed to evaluate the associations of PIF with 90-day postoperative outcomes. RESULTS: Five randomized controlled trials (RCTs) and four observational studies, including a total of 2941 patients, were included. The use of PIF was associated with a reduced risk of 90-day symptomatic lymphocele formation after RALP when examining only RCTs (pooled odds ratios [OR] 0.44, 95% CI 0.28-0.69; I2 =3%) and both RCTs and observational studies (OR 0.35, 95% CI 0.22-0.56; I2 =17%). Similarly, use of PIF was associated with a reduced risk of 90-day any lymphocele formation (OR 0.40, 95% CI 0.28-0.56, I2 =39%). There were no statistically significant differences in postoperative complications between the two groups (OR 0.89; 95% CI 0.69-1.14; I2 =20%). CONCLUSION: Use of the PIF is associated with an approximately 50% reduced risk of symptomatic and any lymphocele formation within 90-days of surgery, and it is not associated with an increase in postoperative complications.

How Can We Identify Extraprostatic Extension (EPE) Before Surgery? The Use of a Preoperative Prostate MRI EPE Scoring System to Assess Postprostatectomy Locally Advanced Prostate Cancer.

Background: Distinguishing between organ-confined disease and extraprostatic extension (EPE) is crucial for the treatment of patients with prostate cancer. EPE is associated with an increased risk of biochemical recurrence, positive surgical margins, and metastatic disease. An MRI-based EPE scoring system was developed by Mehralivand in 2019; however, it has not been adopted in the Urology community. The purpose of this study is to evaluate the association of MRI-based EPE scoring with the pathologic EPE (pEPE) after radical prostatectomy. Methods: We conducted a retrospective review on a prospectively collected database of male patients who underwent a prostate MRI with EPE scoring by a trained genitourinary radiologist and subsequent robotic radical prostatectomy at our institution from September 2020 to December 2022. The associations between MRI EPE (mEPE) score and the presence of EPE on surgical pathology (pEPE) were examined using multivariable logistic regression. Results: A total of 194 patients met inclusion criteria with a median age of 63 years and prostate specific antigen (PSA) 7 ng/mL. Among those with mEPE score 3, 96% had pEPE. Those patients with an mEPE score ≥2 had an increased risk of pEPE compared with those with mEPE score 0 (odds ratio 3.79; 95% confidence interval 1.28-11.3) Furthermore, those with an mEPE score 3 were significantly more likely to have pEPE compared with those with mEPE score 0, 1 and 2 independently. Conclusion: MRI EPE is a straightforward tool that strongly correlates with the presence of pEPE. If validated prospectively, this scoring system could assist in counseling patients regarding nerve-sparing approach.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

Continuity corrected score confidence interval for the difference in proportions in paired data.

For paired binary data, the hybrid method and the score method are often recommended for use to calculate the confidence interval for risk difference. These asymptotic intervals do not control the coverage probability. We propose to develop a new score interval with continuity correction to further improve the performance of the existing intervals. The traditional correction value may be too large which leads to a wide interval. For that reason, we propose three different correction values to identify the optimal correction interval with balanced coverage probability and interval width. From simulation studies, we find that a small correction value for the score interval has good performance. In addition, we derive the non-iterative solutions for the developed continuity correction score intervals.

Efficient and Accurate Computed Tomography-Based Stone Volume Determination: Development of an Automated Artificial Intelligence Algorithm.

PURPOSE: Given the shortcomings of current stone burden characterization (maximum diameter or ellipsoid formulas), we sought to investigate the diagnostic accuracy and precision of a University of California, Irvine-developed artificial intelligence (AI) algorithm for determining stone volume determination. MATERIALS AND METHODS: A total of 322 noncontrast CT scans were retrospectively obtained from patients with a diagnosis of urolithiasis. The largest stone in each noncontrast CT scan was designated the "index stone." The 3D volume of the index stone using 3D Slicer technology was determined by a validated reviewer; this was considered the "ground truth" volume. The AI-calculated index stone volume was subsequently compared with ground truth volume as well with the scalene, prolate, and oblate ellipsoid formulas estimated volumes. RESULTS: There was a nearly perfect correlation between the AI-determined volume and the ground truth (R=0.98). While the AI algorithm was efficient for determining the stone volume for all sizes, its accuracy improved with larger stone size. Moreover, the AI stone volume produced an excellent 3D pixel overlap with the ground truth (Dice score=0.90). In comparison, the ellipsoid formula-based volumes performed less well (R range: 0.79-0.82) than the AI algorithm; for the ellipsoid formulas, the accuracy decreased as the stone size increased (mean overestimation: 27%-89%). Lastly, for all stone sizes, the maximum linear stone measurement had the poorest correlation with the ground truth (R range: 0.41-0.82). CONCLUSIONS: The University of California, Irvine AI algorithm is an accurate, precise, and time-efficient tool for determining stone volume. Expanding the clinical availability of this program could enable urologists to establish better guidelines for both the metabolic and surgical management of their urolithiasis patients.

Practical Use of Self-Adjusted Nitrous Oxide During Transrectal Prostate Biopsy: A Double-Blind Randomized Controlled Trial.

PURPOSE: Transrectal prostate biopsy is a common ambulatory procedure that can result in pain and anxiety for some men. Low-dose, adjustable nitrous oxide is increasingly being used to improve experience of care for patients undergoing painful procedures. This study seeks to evaluate the efficacy and safety of low-dose (<45%) nitrous oxide, which has not been previously established for transrectal prostate biopsies. MATERIALS AND METHODS: A single-institution, prospective, double-blind, randomized, controlled trial was conducted on patients undergoing transrectal prostate biopsies. Patients were randomized to receive either self-adjusted nitrous oxide or oxygen, in addition to routine periprostatic bupivacaine block. Nitrous oxide at levels between 20% and 45% were adjusted to patients' desired effect. Patients completed a visual analog scale for anxiety, State Trait Anxiety Inventory, and a visual analog scale for pain immediately before and after biopsy. The blinded operating urologist evaluated ease of procedure. Periprocedural vitals and complications were assessed. Patients were allowed to drive home independently. RESULTS: A total of 133 patients received either nitrous oxide (66) or oxygen (67). There was no statistically significant difference in the primary anxiety end point of State Trait Anxiety Inventory or the visual analog scale for anxiety scores between the nitrous oxide and oxygen groups. However, patients in the nitrous oxide group reported significantly lower visual analog scale for pain scores compared to the oxygen group (P = .026). The operating urologists' rating of tolerance of the procedure was better in the nitrous oxide group (P = .03). There were no differences in biopsy performance time. Complications were similarly low between the 2 groups. CONCLUSIONS: Patient-adjusted nitrous oxide at levels of 20% to 45% is a safe adjunct during transrectal prostate biopsy. Although there was not an observed difference in the primary end point of anxiety, nitrous oxide was associated with lower patient-reported pain scores.

Recapitulation of anti-aging phenotypes by global overexpression of PTEN in mice.

The PTEN gene negatively regulates the oncogenic PI3K-AKT pathway by encoding a lipid and protein phosphatase that dephosphorylates lipid phosphatidylinositol-3,4,5-triphosphate (PIP3) resulting in the inhibition of PI3K and downstream inhibition of AKT. Overexpression of PTEN in mice leads to a longer lifespan compared to control littermates, although the mechanism is unknown. Here, we provide evidence that young adult PTENOE mice exhibit many characteristics shared by other slow-aging mouse models, including those with mutations that affect GH/IGF1 pathways, calorie-restricted mice, and mice treated with anti-aging drugs. PTENOE white adipose tissue (WAT) has increased UCP1, a protein linked to increased thermogenesis. WAT of PTENOE mice also shows a change in polarization of fat-associated macrophages, with elevated levels of arginase 1 (Arg1, characteristic of M2 macrophages) and decreased production of inducible nitric oxide synthase (iNOS, characteristic of M1 macrophages). Muscle and hippocampus showed increased expression of the myokine FNDC5, and higher levels of its cleavage product irisin in plasma, which has been linked to increased conversion of WAT to more thermogenic beige/brown adipose tissue. PTENOE mice also have an increase, in plasma and liver, of GPLD1, which is known to improve cognition in mice. Hippocampus of the PTENOE mice has elevation of both BDNF and DCX, indices of brain resilience and neurogenesis. These changes in fat, macrophages, liver, muscle, hippocampus, and plasma may be considered "aging rate indicators" in that they seem to be consistently changed across many of the long-lived mouse models and may help to extend lifespan by delaying many forms of late-life illness. Our new findings show that PTENOE mice can be added to the group of long-lived mice that share this multi-tissue suite of biochemical characteristics.

Topics Included in Health Literacy Studies in Asia: A Systematic Review.

The study aimed to review general and specific health literacy studies in different countries in Asia to understand the progress of health literacy researches in the region. English-published studies with quantitative measurements of health literacy were collected through a systematic search in PubMed, Cochrane Library, Embase, and Web of Science, without publication dates limitation. A total of 156 articles on general health literacy, oral, mental, disease-specific health literacy, and eHealth literacy were collected. General health literacy was the most covered topic in 89 articles, followed by eHealth Literacy. Health literacy studies have been conducted in 16 countries and have been increasingly concerned in most of the countries in Asia. China had the largest number of articles, followed by Taiwan. Four studies had participants from more than one country. Education, age, health status, incomes, and living/residential area were significantly associated with health literacy levels in 156 studies, with the prevalence of 55.8%, 28.2%, 20.5%, 17.9%, and 10.9%, respectively. Lower health literacy was related to poorer health outcomes or lower quality of life in 71 studies.