Improving iPSC Differentiation Using a Nanodot Platform.

Differentiation of induced pluripotent stem cells (iPSCs) is an extremely complex process that has proven difficult to study. In this research, we utilized nanotopography to elucidate details regarding iPSC differentiation by developing a nanodot platform consisting of nanodot arrays of increasing diameter. Subjecting iPSCs cultured on the nanodot platform to a cardiomyocyte (CM) differentiation protocol revealed several significant gene expression profiles that were associated with poor differentiation. The observed expression trends were used to select existing small-molecule drugs capable of modulating differentiation efficiency. BRD K98 was repurposed to inhibit CM differentiation, while iPSCs treated with NSC-663284, carmofur, and KPT-330 all exhibited significant increases in not only CM marker expression but also spontaneous beating, suggesting improved CM differentiation. In addition, quantitative polymerase chain reaction was performed to determine the gene regulation responsible for modulating differentiation efficiency. Multiple genes involved in extracellular matrix remodeling were correlated with a CM differentiation efficiency, while genes involved in the cell cycle exhibited contrasting expression trends that warrant further studies. The results suggest that expression profiles determined via short time-series expression miner analysis of nanodot-cultured iPSC differentiation can not only reveal drugs capable of enhancing differentiation efficiency but also highlight crucial sets of genes related to processes such as extracellular matrix remodeling and the cell cycle that can be targeted for further investigation. Our findings confirm that the nanodot platform can be used to reveal complex mechanisms behind iPSC differentiation and could be an indispensable tool for optimizing iPSC technology for clinical applications.

Fatality Rates After Infection With the Omicron Variant (B.1.1.529): How Deadly has it been? A Systematic Review and Meta-Analysis.

Background: Since late 2019, the global community has been gripped by the uncertainty surrounding the SARS-CoV-2 pandemic. In November 2021, the emergence of the Omicron variant in South Africa added a new dimension. This study aims to assess the disease's severity and determine the extent to which vaccinations contribute to reducing mortality rates. Methods: A systematic review and meta-analysis of the epidemiological implications of the omicron variant of SARS-CoV-2 were performed, incorporating an analysis of articles from November 2021that address mortality rates. Results: The analysis incorporated data from 3,214,869 patients infected with omicron, as presented in 270 articles. A total of 6,782 deaths from the virus were recorded (0.21%). In the analysed articles, the pooled mortality rate was 0.003 and the pooled in-house mortality rate was 0.036. Vaccination is an effective step in preventing death (odds ratio: 0.391, p < 0.01). Conclusion: The mortality rates for the omicron variant are lower than for the preceding delta variant. mRNA vaccination affords secure and effective protection against severe disease and death from omicron.

Improvement of clinical wound microcirculation diagnosis using an object tracking-based laser speckle contrast imaging system.

Wound monitoring is crucial for effective healing, as nonhealing wounds can lead to tissue ulceration and necrosis. Evaluating wound recovery involves observing changes in angiogenesis. Laser speckle contrast imaging (LSCI) is vital for wound assessment due to its rapid imaging, high resolution, wide coverage, and noncontact properties. When using LSCI equipment, regions of interest (ROIs) must be delineated in lesion areas in images for quantitative analysis. However, patients with serious wounds cannot maintain constant postures because the affected areas are often associated with discomfort and pain. This leads to deviations between the drawn ROI and actual wound position when using LSCI for wound assessment, affecting the reliability of relevant assessments. To address these issues, we used the channel and spatial reliability tracker object tracking algorithm to develop an automatic ROI tracking function for LSCI systems. This algorithm is used to track and correct artificial movements in blood flow images, address the ROI position offset caused by the movement of the affected body part, increase the blood flow analysis accuracy, and improve the clinical applicability of LSCI systems. ROI tracking experiments were performed by simulating wounds, and the results showed that the intraclass correlation coefficient (ICC) ranged from 0.134 to 0.976. Furthermore, the object within the ROI affected tracking performance. Clinical assessments across wound types showed ICCs ranging from 0.798 to 0.917 for acute wounds and 0.628-0.849 for chronic wounds. We also discuss factors affecting tracking performance and propose strategies to enhance implementation effectiveness.

Prehospital ultrasound scanning for abdominal free fluid detection in trauma patients: a systematic review and meta-analysis.

INTRODUCTION: Focused assessment with sonography for trauma helps detect abdominal free fluid. Prehospital ultrasound scanning is also important because the early diagnosis of hemoperitoneum may reduce the time to definitive treatment in the hospital. This study investigated whether prehospital ultrasound scanning can help detect abdominal free fluid. MATERIALS AND METHODS: In this systematic review, relevant databases were searched for studies investigating prehospital ultrasound examinations for abdominal free fluid in trauma patients. The prehospital ultrasound results were compared with computed tomography, surgery, or hospital ultrasound examination data. The pooled sensitivity and specificity values were analyzed using forest plots. The overall predictive power was calculated by the summary receiver operating characteristic curve. The quality of the included studies was assessed using the quality assessment of diagnostic accuracy studies tool. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was performed to assess the certainty of evidence. RESULT: This meta-analysis comprised six studies that included 1356 patients. The pooled sensitivity and specificity values were 0.596 (95% confidence interval [CI] = 0.345-0.822) and 0.970 (95% CI = 0.953-0.983), respectively. The pooled area under the summary receiver operating characteristic curve was 0.998. The quality assessment tool showed favorable results. In the GRADE analysis, the quality of evidence was very low for sensitivity and high for specificity when prehospital ultrasound was used for hemoperitoneum diagnosis. CONCLUSION: The specificity of abdominal free fluid detection using prehospital ultrasound examinations in trauma patients was very high.

The Coronary Reperfusion Effect and Safety of Prehospital P2Y12 Inhibitor in Primary-PCI STEMI Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The concept of early administration of P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) is widely accepted, but whether prehospital administration results in greater coronary reperfusion remains unclear. Our study aims to analyze the benefit and safety of prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor administration. METHOD: Three databases (PubMed, EMBASE, and Cochrane Library) were searched from database inception to June 2023. We included all types of studies except for conference publications, abstract presentations, reviews, and case reports. The primary outcomes were pre-PCI TIMI flow grade 2-3 (TIMI = Thrombolysis in Myocardial Infarction) and major bleeding. The secondary outcomes included post-PCI TIMI flow grade 2-3, major adverse cardiac events (MACE), recurrent myocardial infarction (MI), and short-term (30-day) mortality. RESULT: Eight individual studies with a total of 10823 patients were included in our meta-analysis. Compared with in-hospital P2Y12 inhibitor, prehospital P2Y12 inhibitor were associated with significantly higher rates of pre-PCI TIMI flow grade 2-3 (OR 1.32, 95% CI: 1.09-1.61, p = 0.005) and post-PCI TIMI flow grade 2-3 (OR 1.43, 95% CI: 1.04-1.97, p = 0.03), and a significantly lower risk of recurrent MI (OR 0.69, 95% CI: 0.49-0.96, p = 0.03). There were no significant difference in the risk of major bleeding (OR 1.00, 95% CI: 0.75-1.32, p = 0.98), MACE (OR 0.94, 95% CI: 0.70-1.25, p = 0.65), or short-term mortality (OR 0.87, 95% CI: 0.50-1.51, p = 0.61). CONCLUSION: Prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor is associated with a significantly higher rate of pre-PCI and post-PCI TIMI flow grade 2-3, a reduced risk of recurrent MI, and no increase in major bleeding in STEMI patients undergoing primary PCI.

Designing 3D-Printed Mesh-Covered Fluid Collecting Racks (MFCRs) to Prevent Moisture-Related COVID-19 Sampling Interruptions in Taiwan.

Background: A sampling platform (or table) set at the patient's side in a zero-exposure screening center (booth) might be used for specimen collection during public health crises such as the COVID-19 pandemic. However, repeated sanitization causes moisture problems. Such moisture problems would not only be noted by patients but also interrupt the sampling process. In this study, we aimed to develop 3D-printed mesh-covered fluid collecting racks (MFCRs) to address surface moisture problems to determine whether MFCRs can shorten the sampling time. Methods: This was an observational, descriptive, and cross-sectional study. We observed the reasons for sampling interruptions related to surface moisture problems among patients who used MFCRs or did not (April 28-30, 2022). We used a 3D printer to make an MFCR, which measured 14.5 cm in width and length and 1.0 cm in height. The MFCR allows the ethanol to drain through the mesh into the fluid collection rack below to leave a relatively dry surface on the mesh. Finally, we calculated the median time to finish sampling between MFCRs and non-MFCRs. Results: A total of 400 patients were randomly observed (using MFCRs, n = 200; non-MFCRs, n = 200). Patients in the non-MFCR group were more likely to interrupt the sampling process (n = 39, 19.5%) by noting surface moisture problems than those in the MFCR group (n = 3, 1.5%). Two of the major interruptions, "asking questions about the moist surface" (from 12% to 1%) and "slowing down their actions" (from 4.5% to 0.5%), were obviously improved by using MFCRs. Overall, the median sampling time was significantly shorter (p < 0.001) in the group using MFCRs (0.6 min) than in the group using non-MFCRs (1.5 min). The MFCRs shortened the sampling time by 60%, which might be associated with decreasing interruptions caused by surface moisture problems. Conclusions: The 3D printed MFCRs are suitable for handling surface moisture problems caused by repeated sanitizations. More importantly, the MFCRs might be associated with decreasing interruptions caused by moisture problems.

The adjusted impact of different severities of acute exacerbations and medications on the risk of developing dementia in COPD patients.

BACKGROUND: Although a relationship between chronic obstructive pulmonary disease (COPD) and dementia has been reported, the initial severity upon emergency department (ED) visits and the medications used have not been well evaluated as risk factors for increased dementia occurrence. We aimed to analyze the risks of dementia development over 5 years among patients with COPD compared to matched controls (primary) and the impact of different severities of acute exacerbations (AEs) of COPD and medications on the risk of dementia development among COPD patients (secondary). METHOD: This study used the Taiwanese government deidentified health care database. We enrolled patients during the 10-year study period (January 1, 2000, to December 31, 2010), and each patient was followed up for 5 years. Once these patients received a diagnosis of dementia or died, they were no longer followed up. The study group included 51,318 patients who were diagnosed with COPD and 51,318 matched (in terms of age, sex, and the number of hospital visits) non-COPD patients from the remaining patients as the control group. Each patient was followed up for 5 years to analyze the risk of dementia with Cox regression analysis. Data on medications (antibiotics, bronchodilators, corticosteroids) and severity at the initial ED visit (ED treatment only, hospital admission, or ICU admission) were collected for both groups, as well as demographics and baseline comorbidities, which were considered confounding factors. RESULTS: In the study and control groups, 1,025 (2.0%) and 423 (0.8%) patients suffered from dementia, respectively. The unadjusted HR for dementia was 2.51 (95% CI: 2.24-2.81) in the study group. Bronchodilator treatment was associated with the HRs, especially among those who received long-term (> 1 month) treatment (HR = 2.10, 95% CI: 1.91-2.45). Furthermore, among 3,451 AE of COPD patients who initially visited the ED, patients who required ICU admission (n = 164, 4.7%) had a higher risk of dementia occurrence (HR = 11.05, 95% CI: 7.77-15.71). CONCLUSION: Bronchodilator administration might be associated with a decreased risk of dementia development. More importantly, patients who suffered AEs of COPD and initially visited the ED and required ICU admission had a higher risk of developing dementia.

Guidelines for COVID-19 Laboratory Testing for Emergency Departments From the New Diagnostic Technology Team of the Taiwan Society of Emergency Medicine.

COVID-19 tests have different turnaround times (TATs), accuracy levels, and limitations, which emergency physicians should be aware of. Nucleic acid amplification tests (NAATs) can be divided into standard high throughput tests and rapid molecular diagnostic tests at the point of care (POC). The standard NAAT has the advantages of high throughput and high accuracy with a TAT of 3-4 hours. The POC molecular test has the same advantages of high accuracy as standard high throughput PCR, but can be done in 13-45 minutes. Roche cobas Liat is the most commonly used machine in Taiwan, displaying 99%-100% sensitivity and 100% specificity, respectively. Abbott ID NOW is an isothermal PCR-based POC machine with a sensitivity of 79% and a specificity of 100%. A high rate of false positives and false negatives is associated with rapid antigen testing. Antibody testing is mostly used as part of public health surveys and for testing for immunity.

The Impact of Do-Not-Resuscitate Order in the Emergency Department on Respiratory Failure after ICU Admission.

(1) Background: It has been hypothesized that a discrepancy exists in the understanding of a do-not-resuscitate (DNR) order among physicians. We hypothesized that a DNR order signed in the emergency department (ED) could influence the patients' prognosis after intensive care unit (ICU) admission. (2) Methods: We included patients older than 17 years, who visited the emergency department for non-traumatic disease, who had respiratory failure, required ventilator support, and were admitted to the ICU between January 2010 and December 2016. The associations between DNR and mortality, hospital length of stay (LOS), and medical fees were analyzed. Prolonged hospital LOS was defined as hospital stay ≥75th percentile (≥26 days for the study). Patients were classified as those who did and did not sign a DNR order. A 1:4 propensity score matching was conducted for demographics, comorbidities, and etiology. (3) Results: The study enrolled a total of 1510 patients who signed a DNR and 6040 patients who did not sign a DNR. The 30-day mortality rates were 47.4% and 28.0% among patients who did and did not sign a DNR, respectively. A DNR order was associated with mortality after adjusting for confounding factors (hazard ratio, 1.9; confidence interval, 1.70−2.03). It was also a risk factor for prolonged hospital LOS in survivors (odds ratio, 1.2; confidence interval, 1.02−1.44). Survivors who signed a DNR order were charged higher medical fees than those who did not sign a DNR (217,159 vs. 245,795 New Taiwan Dollars, p < 0.001). (4) Conclusions: Signing a DNR order in the ED increased the ICU mortality rate among patients who had respiratory failure and needed ventilator support. It increased the risk of prolonged hospital LOS among survivors. Finally, signing a DNR order was associated with high medical fees among survivors.

Assessment of Brain Functional Activity Using a Miniaturized Head-Mounted Scanning Photoacoustic Imaging System in Awake and Freely Moving Rats.

Understanding the relationship between brain function and natural behavior remains a significant challenge in neuroscience because there are very few convincing imaging/recording tools available for the evaluation of awake and freely moving animals. Here, we employed a miniaturized head-mounted scanning photoacoustic imaging (hmPAI) system to image real-time cortical dynamics. A compact photoacoustic (PA) probe based on four in-house optical fiber pads and a single custom-made 48-MHz focused ultrasound transducer was designed to enable focused dark-field PA imaging, and miniature linear motors were included to enable two-dimensional (2D) scanning. The total dimensions and weight of the proposed hmPAI system are only approximately 50 × 64 × 48 mm and 58.7 g (excluding cables). Our ex vivo phantom experimental tests revealed that a spatial resolution of approximately 0.225 mm could be achieved at a depth of 9 mm. Our in vivo results further revealed that the diameters of cortical vessels draining into the superior sagittal sinus (SSS) could be clearly imaged and continuously observed in both anesthetized rats and awake, freely moving rats. Statistical analysis showed that the full width at half maximum (FWHM) of the PA A-line signals (relative to the blood vessel diameter) was significantly increased in the selected SSS-drained cortical vessels of awake rats (0.58 ± 0.17 mm) compared with those of anesthetized rats (0.31 ± 0.09 mm) (p < 0.01, paired t-test). In addition, the number of pixels in PA B-scan images (relative to the cerebral blood volume (CBV)) was also significantly increased in the selected SSS-drained blood vessels of awake rats (107.66 ± 23.02 pixels) compared with those of anesthetized rats (81.99 ± 21.52 pixels) (p < 0.01, paired t-test). This outcome may result from a more active brain in awake rats than in anesthetized rats, which caused cerebral blood vessels to transport more blood to meet the increased nutrient demand of the tissue, resulting in an obvious increase in blood vessel volume. This hmPAI system was further validated for utility in the brains of awake and freely moving rats, showing that their natural behavior was unimpaired during vascular imaging, thereby providing novel opportunities for studies of behavior, cognition, and preclinical models of brain diseases.

The effect of the head-up position on cardiopulmonary resuscitation: a systematic review and meta-analysis.

OBJECTIVE: Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. METHODS: Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). RESULTS: Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11-13.64; p < 0.01; I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84-13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD - 13.66; 95% CI - 18.6 to -8.71; p < 0.01; I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD - 1.63; 95% CI - 10.77-7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31-2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression-decompression (ACD) and impedance threshold (ITD) devices. CONCLUSION: In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

Comparative effectiveness of ultrasound-guided and anatomic landmark percutaneous dilatational tracheostomy: A systematic review and meta-analysis.

INTRODUCTION: Ultrasound-guided tracheostomy (UGT) and bronchoscope-guided tracheostomy (BGT) have been well compared. However, the differences in benefits between UGT and landmark tracheostomy (LT) have not been addressed and, in particular, lack a detailed meta-analysis. We aimed to compare the first-pass success, complication rate, major bleeding rate, and tracheostomy procedure time between UGT and LT. METHODS: In a systematic review, relevant databases were searched for studies comparing UGT with LT in intubated patients. The primary outcome was the odds ratio (OR) of first-pass success. The secondary outcomes were the OR of complications, OR of major bleeding, and standardized mean difference (SMD) of the total tracheostomy procedure time. RESULTS: The meta-analysis included three randomized controlled studies (RCTs) and one nonrandomized controlled study (NRS), comprising 474 patients in total. Compared with LT, UGT increased first-pass success (OR: 4.287; 95% confidence interval [CI]: 2.308 to 7.964) and decreased complications (OR: 0.422; 95% CI: 0.249 to 0.718). However, compared with LT, UGT did not significantly reduce major bleeding (OR: 0.374; 95% CI: 0.112 to 1.251) or the total tracheostomy placement time (SMD: -0.335; 95% CI: -0.842 to 0.172). CONCLUSIONS: Compared with LT, real-time UGT increases first-pass success and decreases complications. However, UGT was not associated with a significant reduction in the major bleeding rate. The total tracheostomy placement time comparison between UGI and LT was inconclusive.

Development of an Electrochemical Immunosensor for Detection of Cardiac Troponin I at the Point-of-Care.

Cardiac troponin I (cTnI) plays an important role in the assessment of various cardiac diseases. However, accurate detection of cTnI at the point-of-care (POC) remains unfeasible. In this study, we report the development of an electrochemical immunosensor designed for rapid and accurate cTnI detection in pre-hospital settings. Rapid cTnI analysis of whole blood samples was then performed. cTnI measurements were highly correlated with the results of the standard clinical laboratory method for cTnI detection. The results of this study suggest that the proposed POC immunosensor can deliver fast and accurate cTnI analysis in pre-hospital settings to achieve rapid diagnosis and guide patient management.

AMBtalk: A Cardiovascular IoT Device for Ambulance Applications.

Acute Coronary Syndrome (ACS) and other heart emergency events require immediate chest pain identification in the ambulance. Specifically, early identification and triage is required so that patients with chest pain can be quickly sent to a hospital with appropriate care facilities for treatment. In the traditional approach, ambulance personnel often use symptom checklists to examine the patient and make a quick decision for the target hospital. However, not every hospital has specialist facilities to handle such emergency cases. If the result of the subsequent cardiac enzyme test performed at the target hospital strongly suggests the occurrence of myocardial infarction, the patient may need to be sent to another hospital with specialist facilities, such as Percutaneous Coronary Intervention. The standard procedure is time consuming, which may result in delayed treatment and reduce patent survival rate. To resolve this issue, we propose AMBtalk (Ambulance Talk) for accurate, early ACS identification in an ambulance. AMBtalk provides real-time connection to hospital resources, which reduces the elapsed time for treatment, and therefore, improves the patient survival rate. The key to success for AMBtalk is the development of the AllCheck® Internet of Things (IoT) device, which can accurately and quickly provide cardiovascular parameter values for early ACS identification. The interactions between the AllCheck® IoT device, the emergency medical service center, the ambulance personnel and the hospital are achieved through the AMBtalk IoT server in the cloud network. AllCheck® outperforms the existing cardiovascular IoT device solutions for ambulance applications. The testing results of the AllCheck® device show 99% correlation with the results of the hospital reports. Due to its excellent performance in quick ACS identification, the AllCheck® device was awarded the 17th Taiwan Innovators Award in 2020.