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Paper-based point-of-care testing for diagnosis of dengue infections

Choi JR, Hu J, Wang S, Yang H, Wan Abas WA, Pingguan-Murphy B, et al.

Crit Rev Biotechnol, 2017 Feb;37(1):100-111.
PMID: 26912259

Dengue endemic is a serious healthcare concern in tropical and subtropical countries. Although well-established laboratory tests can provide early diagnosis of acute dengue infections, access to these tests is limited in developing countries, presenting an urgent need to develop simple, rapid, and robust diagnostic tools. Point-of-care (POC) devices, particularly paper-based POC devices, are typically rapid, cost-effective and user-friendly, and they can be used as diagnostic tools for the prompt diagnosis of dengue at POC settings. Here, we review the importance of rapid dengue diagnosis, current dengue diagnostic methods, and the development of paper-based POC devices for diagnosis of dengue infections at the POC.
An integrated paper-based sample-to-answer biosensor for nucleic acid testing at the point of care

Choi JR, Hu J, Tang R, Gong Y, Feng S, Ren H, et al.

Lab Chip, 2016 Feb 7;16(3):611-21.
PMID: 26759062 DOI: 10.1039/c5lc01388g

With advances in point-of-care testing (POCT), lateral flow assays (LFAs) have been explored for nucleic acid detection. However, biological samples generally contain complex compositions and low amounts of target nucleic acids, and currently require laborious off-chip nucleic acid extraction and amplification processes (e.g., tube-based extraction and polymerase chain reaction (PCR)) prior to detection. To the best of our knowledge, even though the integration of DNA extraction and amplification into a paper-based biosensor has been reported, a combination of LFA with the aforementioned steps for simple colorimetric readout has not yet been demonstrated. Here, we demonstrate for the first time an integrated paper-based biosensor incorporating nucleic acid extraction, amplification and visual detection or quantification using a smartphone. A handheld battery-powered heating device was specially developed for nucleic acid amplification in POC settings, which is coupled with this simple assay for rapid target detection. The biosensor can successfully detect Escherichia coli (as a model analyte) in spiked drinking water, milk, blood, and spinach with a detection limit of as low as 10-1000 CFU mL(-1), and Streptococcus pneumonia in clinical blood samples, highlighting its potential use in medical diagnostics, food safety analysis and environmental monitoring. As compared to the lengthy conventional assay, which requires more than 5 hours for the entire sample-to-answer process, it takes about 1 hour for our integrated biosensor. The integrated biosensor holds great potential for detection of various target analytes for wide applications in the near future.
Complications constitute a major risk factor for mortality in hepatitis B virus-related acute-on-chronic liver failure patients: a multi-national study from the Asia-Pacific region

Chen T, Yang Z, Choudhury AK, Al Mahtab M, Li J, Chen Y, et al.

Hepatol Int, 2019 Nov;13(6):695-705.
PMID: 31650510 DOI: 10.1007/s12072-019-09992-x

BACKGROUND AND AIM: Cirrhosis is a controversial determinant of mortality in HBV-related acute-on-chronic liver failure (HBV-ACLF). The present study aimed to explore the effects of cirrhosis and the associated risk factors, especially its complications, on the outcome of HBV-ACLF.
METHODS: A prospective-retrospective cohort of 985 patients was identified from the APASL-ACLF Research Consortium (AARC) database and the Chinese Study Group. Complications of ACLF (ascites, infection, hepatorenal syndrome, hepatic encephalopathy, upper gastrointestinal bleeding) as well as cirrhosis and the current main prognostic models were measured for their predictive ability for 28- or 90-day mortality.
RESULTS: A total of 709 patients with HBV-ACLF as defined by the AARC criteria were enrolled. Among these HBV-ACLF patients, the cirrhotic group showed significantly higher mortality and complications than the non-cirrhotic group. A total of 36.1% and 40.1% of patients met the European Association for the Study of Liver (EASL)-Chronic Liver Failure consortium (CLIF-C) criteria in the non-cirrhotic and cirrhotic groups, respectively; these patients had significantly higher rates of mortality and complications than those who did not satisfy the CLIF-C criteria. Furthermore, among patients who did not meet the CLIF-C criteria, the cirrhotic group exhibited higher mortality and complication rates than the non-cirrhotic group, without significant differences in organ failure. The Tongji prognostic predictor model score (TPPMs), which set the number of complications as one of the determinants, showed comparable or superior ability to the Chinese Group on the Study of Severe Hepatitis B-ACLF score (COSSH-ACLFs), APASL-ACLF Research Consortium score (AARC-ACLFs), CLIF-C organ failure score (CLIF-C OFs), CLIF-C-ACLF score (CLIF-C-ACLFs), Model for End-Stage Liver Disease score (MELDs) and MELD-sodium score (MELD-Nas) in HBV-ACLF patients, especially in cirrhotic HBV--ACLF patients. Patients with two (OR 4.70, 1.88) or three (OR 8.27, 2.65) complications had a significantly higher risk of 28- or 90-day mortality, respectively.
CONCLUSION: The presence of complications is a major risk factor for mortality in HBV-ACLF patients. TPPM possesses high predictive ability in HBV-ACLF patients, especially in cirrhotic HBV-ACLF patients.
Identifying KCNJ5 Mutation in Aldosterone-Producing Adenoma Patients With Baseline Characteristics Using Machine Learning Technology

Chen LC, Huang WC, Peng KY, Chen YY, Li SC, Syed Mohammed Nazri SK, et al.

JACC Asia, 2023 Aug;3(4):664-675.
PMID: 37614534 DOI: 10.1016/j.jacasi.2023.03.010

BACKGROUND: Primary aldosteronism is characterized by inappropriate aldosterone production, and unilateral aldosterone-producing adenoma (uPA) is a common type of PA. KCNJ5 mutation is a protective factor in uPA; however, there is no preoperative approach to detect KCNJ5 mutation in patients with uPA.
OBJECTIVES: This study aimed to provide a personalized surgical recommendation that enables more confidence in advising patients to pursue surgical treatment.
METHODS: We enrolled 328 patients with uPA harboring KCNJ5 mutations (n = 158) or not (n = 170) who had undergone adrenalectomy. Eighty-seven features were collected, including demographics, various blood and urine test results, and clinical comorbidities. We designed 2 versions of the prediction model: one for institutes with complete blood tests (full version), and the other for institutes that may not be equipped with comprehensive testing facilities (condensed version).
RESULTS: The results show that in the full version, the Light Gradient Boosting Machine outperformed other classifiers, achieving area under the curve and accuracy values of 0.905 and 0.864, respectively. The Light Gradient Boosting Machine also showed excellent performance in the condensed version, achieving area under the curve and accuracy values of 0.867 and 0.803, respectively.
CONCLUSIONS: We simplified the preoperative diagnosis of KCNJ5 mutations successfully using machine learning. The proposed lightweight tool that requires only baseline characteristics and blood/urine test results can be widely applied and can aid personalized prediction during preoperative counseling for patients with uPA.
The prevalence and clinical correlates of suicide attempts in patients with bipolar disorder misdiagnosed with major depressive disorder: Results from a national survey in China

Chen L, Xu YY, Lin JY, Ji ZP, Yang F, Tan S, et al.

Asian J Psychiatr, 2024 Mar;93:103958.
PMID: 38364597 DOI: 10.1016/j.ajp.2024.103958

BACKGROUND AND AIM: Suicide is nearly always associated with underlying mental disorders. Risk factors for suicide attempts (SAs) in patients with bipolar disorder (BD) misdiagnosed with major depressive disorder (MDD) remain unelucidated. This study was to evaluate the prevalence and clinical risk factors of SAs in Chinese patients with BD misdiagnosed with MDD.
METHODS: A total of 1487 patients with MDD from 13 mental health institutions in China were enrolled. Mini International Neuropsychiatric Interview (MINI) was used to identify patients with BD who are misdiagnosed as MDD. The general sociodemographic and clinical data of the patients were collected and MINI suicide module was used to identify patients with SAs in these misdiagnosed patients.
RESULTS: In China, 20.6% of patients with BD were incorrectly diagnosed as having MDD. Among these misdiagnosed patients, 26.5% had attempted suicide. These patients tended to be older, had a higher number of hospitalizations, and were more likely to experience frequent and seasonal depressive episodes with atypical features, psychotic symptoms, and suicidal thoughts. Frequent depressive episodes and suicidal thoughts during depression were identified as independent risk factors for SAs. Additionally, significant sociodemographic and clinical differences were found between individuals misdiagnosed with MDD in BD and patients with MDD who have attempted suicide.
CONCLUSIONS: This study highlights the importance of accurate diagnosis in individuals with BD and provide valuable insights for the targeted identification and intervention of individuals with BD misdiagnosed as having MDD and those with genuine MDD, particularly in relation to suicidal behavior.
Effects of R-salbutamol on the inflammatory response and acute lung injury in endotoxemic mice

Beng H, Hu J, Wang S, Liang X, Qin H, Tan W

Int Immunopharmacol, 2023 Aug;121:110482.
PMID: 37364330 DOI: 10.1016/j.intimp.2023.110482

Salbutamol, which consists of an R-isomer and S-isomer, is an effective and widely used β2 adrenoreceptor agonist that may possess anti-inflammatory properties in addition to its bronchodilator activity. Whether the salbutamol R-isomer has advantages over its racemic mixture and effectiveness in treating endotoxemia and endotoxin-induced lung injury has not been well studied. In this study, we investigated the preventive and therapeutic effects of R-salbutamol (R-sal), S-salbutamol (S-sal), and their racemic mixture (Rac-sal) on a mouse model of lipopolysaccharide (LPS)-induced endotoxemia. Dexamethasone (Dex) was used for comparison. The results showed that R-sal markedly improved the 7-day survival rate of endotoxic mice when administered before and after LPS treatment. Dex was toxic and accelerated the death of endotoxic mice when administered before LPS injection. Histological examination of the lungs revealed that the LPS challenge resulted in acute lung damage, including inflammatory cell infiltration, thickened alveolar septa, and congestion. R-sal pre-treatment effectively inhibited these changes, accompanied by markedly reduced lung myeloperoxidase levels, serum cytokine levels, and lactate release, significant restoration of lymphocyte count, and reduction of monocyte count. This may have occurred through inhibition of M1 macrophage inflammatory responses by enhancement of β-arrestin2 expression and suppression of NF-κB activation. Rac-sal exhibited diminished effects compared to that of R-sal, while S-sal showed enhanced release of some inflammatory cytokines. In addition, R-sal pre-treatment showed a better improvement in prognostic pulmonary function on day 4 compared to that by Rac-sal. Collectively, our results indicate the potential benefits of R-sal in regulating inflammatory responses to endotoxemia and endotoxin-induced lung injury.
Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy

Anand L, Choudhury A, Bihari C, Sharma BC, Kumar M, Maiwall R, et al.

Hepatology, 2019 08;70(2):587-596.
PMID: 30113706 DOI: 10.1002/hep.30205

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.