AI-enabled electrocardiography alert intervention and all-cause mortality: a pragmatic randomized clinical trial.

The early identification of vulnerable patients has the potential to improve outcomes but poses a substantial challenge in clinical practice. This study evaluated the ability of an artificial intelligence (AI)-enabled electrocardiogram (ECG) to identify hospitalized patients with a high risk of mortality in a multisite randomized controlled trial involving 39 physicians and 15,965 patients. The AI-ECG alert intervention included an AI report and warning messages delivered to the physicians, flagging patients predicted to be at high risk of mortality. The trial met its primary outcome, finding that implementation of the AI-ECG alert was associated with a significant reduction in all-cause mortality within 90 days: 3.6% patients in the intervention group died within 90 days, compared to 4.3% in the control group (4.3%) (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.70-0.99). A prespecified analysis showed that reduction in all-cause mortality associated with the AI-ECG alert was observed primarily in patients with high-risk ECGs (HR = 0.69, 95% CI = 0.53-0.90). In analyses of secondary outcomes, patients in the intervention group with high-risk ECGs received increased levels of intensive care compared to the control group; for the high-risk ECG group of patients, implementation of the AI-ECG alert was associated with a significant reduction in the risk of cardiac death (0.2% in the intervention arm versus 2.4% in the control arm, HR = 0.07, 95% CI = 0.01-0.56). While the precise means by which implementation of the AI-ECG alert led to decreased mortality are to be fully elucidated, these results indicate that such implementation assists in the detection of high-risk patients, prompting timely clinical care and reducing mortality. ClinicalTrials.gov registration: NCT05118035 .

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Opportunistic Screening for Asymptomatic Left Ventricular Dysfunction With the Use of Electrocardiographic Artificial Intelligence: A Cost-Effectiveness Approach.

BACKGROUND: The burden of asymptomatic left ventricular dysfunction (LVD) is greater than that of heart failure; however, a cost-effective tool for asymptomatic LVD screening has not been well validated. We aimed to prospectively validate an artificial intelligence (AI)-enabled electrocardiography (ECG) algorithm for asymptomatic LVD detection and evaluate its cost-effectiveness for opportunistic screening. METHODS: In this prospective observational study, patients undergoing ECG at outpatient clinics or health check-ups were enrolled in 2 hospitals in Taiwan. Patients were stratified into LVD (left ventricular ejection fraction ≤ 40%) risk groups according to a previously developed ECG algorithm. The performance of AI-ECG was used to conduct a cost-effectiveness analysis of LVD screening compared with no screening. Incremental cost-effectiveness ratio (ICER) and sensitivity analyses were used to examine the cost-effectiveness and robustness of the results. RESULTS: Among the 29,137 patients, the algorithm demonstrated areas under the receiver operating characteristic curves of 0.984 and 0.945 for detecting LVD within 28 days in the 2 hospital cohorts. For patients not initially scheduled for ECG, the algorithm predicted future echocardiograms (high-risk, 46.2%; medium-risk, 31.4%; low-risk, 14.6%) and LVD (high-risk, 26.2%; medium-risk, 3.4%; low-risk, 0.1%) at 12 months. Opportunistic screening with AI-ECG could result in a negative ICER of -$7,439 for patients aged 65 years, with consistent cost-savings across age groups and particularly in men. Approximately 91.5% of the cases were found to be cost-effective at the willingness-to-pay threshold of $30,000 in the probabilistic analysis. CONCLUSIONS: The use of AI-ECG for asymptomatic LVD risk stratification is promising, and opportunistic screening in outpatient clinics has the potential to reduce costs.

An Update on Recent Advances of Photodynamic Therapy for Primary Cutaneous Lymphomas.

Primary cutaneous lymphomas are rare non-Hodgkin lymphomas consisting of heterogeneous disease entities. Photodynamic therapy (PDT) utilizing photosensitizers irradiated with a specific wavelength of light in the presence of oxygen exerts promising anti-tumor effects on non-melanoma skin cancer, yet its application in primary cutaneous lymphomas remains less recognized. Despite many in vitro data showing PDT could effectively kill lymphoma cells, clinical evidence of PDT against primary cutaneous lymphomas is limited. Recently, a phase 3 "FLASH" randomized clinical trial demonstrated the efficacy of topical hypericin PDT for early-stage cutaneous T-cell lymphoma. An update on recent advances of photodynamic therapy in primary cutaneous lymphomas is provided.

Impact of temperature on infection with Japanese encephalitis virus of three potential urban vectors in Taiwan; Aedes albopictus, Armigeres subalbatus, and Culex quinquefasciatus.

Japanese encephalitis (JE) is an important mosquito-borne infectious disease in rural areas of Asia that is caused by Japanese encephalitis virus (JEV). Culex tritaeniorhynchus is the major vector of JEV, nevertheless there are other mosquitoes that may be able to transmit JEV. This study confirms that the midgut, head tissue, salivary glands, and reproductive tissue of Aedes albopictus, Armigeres subalbatus, and Culex quinquefasciatus are all able to be infected with JEV after a virus-containing blood meal was ingested by female mosquitoes. Even though the susceptibility to JEV of the different tissues varies, the virus-positive rate increased with the number of days after JEV infection. Moreover, once JEV escapes the midgut barrier, the oral transmission rates of JEV were 16%, 2%, and 21% for Ae. albopictus, Ar. subalbatus, and Cx. quinquefasciatus at 14 days after infection at 30 °C, respectively. There is no supporting evidence to suggest vertical transmission of JEV by the tested mosquitoes. Collectively, raising the temperature enhances JEV replication in the salivary gland of the three mosquito species, suggesting that global warming will enhance mosquito vector competence and that this is likely to lead to an increase in the probability of JEV transmission.

Artificial intelligence-enabled electrocardiogram screens low left ventricular ejection fraction with a degree of confidence.

Background: Artificial intelligence-enabled electrocardiogram has become a substitute tool for echocardiography in left ventricular ejection fraction estimation. However, the direct use of artificial intelligence-enabled electrocardiogram may be not trustable due to the uncertainty of the prediction. Objective: The study aimed to establish an artificial intelligence-enabled electrocardiogram with a degree of confidence to identify left ventricular dysfunction. Methods: The study collected 76,081 and 11,771 electrocardiograms from an academic medical center and a community hospital to establish and validate the deep learning model, respectively. The proposed deep learning model provided the point estimation of the actual ejection fraction and its standard deviation derived from the maximum probability density function of a normal distribution. The primary analysis focused on the accuracy of identifying patients with left ventricular dysfunction (ejection fraction ≤ 40%). Since the standard deviation was an uncertainty indicator in a normal distribution, we used it as a degree of confidence in the artificial intelligence-enabled electrocardiogram. We further explored the clinical application of estimated standard deviation and followed up on the new-onset left ventricular dysfunction in patients with initially normal ejection fraction. Results: The area under receiver operating characteristic curves (AUC) of detecting left ventricular dysfunction were 0.9549 and 0.9365 in internal and external validation sets. After excluding the cases with a lower degree of confidence, the artificial intelligence-enabled electrocardiogram performed better in the remaining cases in internal (AUC = 0.9759) and external (AUC = 0.9653) validation sets. For the application of future left ventricular dysfunction risk stratification in patients with initially normal ejection fraction, a 4.57-fold risk of future left ventricular dysfunction when the artificial intelligence-enabled electrocardiogram is positive in the internal validation set. The hazard ratio was increased to 8.67 after excluding the cases with a lower degree of confidence. This trend was also validated in the external validation set. Conclusion: The deep learning model with a degree of confidence can provide advanced improvements in identifying left ventricular dysfunction and serve as a decision support and management-guided screening tool for prognosis.

The safety and efficacy of the Mo.Ma system device for carotid artery stenting: A single-center experience from Taiwan.

Background: Proximal protection devices, such as the Mo.Ma system provides better neurological outcomes than the distal filter system in the carotid artery stenting (CAS) procedure. This study first evaluated the safety and efficacy of the Mo.Ma system during CAS in a single tertiary referral hospital from Taiwan. The outcomes of distal vs. proximal embolic protection devices were also studied. Methods: A total of 294 patients with carotid artery stenosis who underwent the CAS procedure were retrospectively included and divided into two groups: 152 patients in the distal filter system group and 142 patients in the Mo.Ma system. The outcomes of interest were compared between the two groups. The factors contributing to occlusion intolerance (OI) in the Mo.Ma system were evaluated. Results: The procedure success rates were more than 98% in both groups. No major stroke occurred in this study. The minor stroke rates were 2.8% (4/142) and 4.6% (7/152) in the Mo.Ma system and filter system, respectively (p = 0.419). Patients with hypoalbuminemia significantly predicted the risk of stroke with an odds ratio of 0.08 [95% confidence interval (CI), 0.01-0.68, p = 0.020] per 1 g/day of serum albumin in the filter group. A total of 12 patients developed OI in the Mo.Ma system (12/142, 8%). Low occlusion pressure predicted the occurrence of OI in the Mo.Ma group with the hazard ratios of 0.88 (95% CI: 0.82-0.96) and 0.90 (95% CI: 0.84-0.98) per 1 mmHg of occlusion systolic pressure (OSP) and diastolic pressure (ODP), respectively. We further indicated that patients with an OSP of ≥60 mmHg or an ODP of ≥44 mmHg could tolerate the procedure of occlusion time up to 400 s, while patients with an OSP of <49 mmHg or an ODP of <34 mmHg should undergo the procedure of occlusion time less than 300 s to prevent the occurrence of OI. Conclusion: We have demonstrated the safety and effectiveness of the Mo.Ma system during CAS in an Asia population. By reducing the occlusion time, our study indicated a lower risk of OI in the Mo.Ma system and proposed the optimal occlusion time according to occlusion pressure to prevent OI during the CAS procedure. Further large-scale and prospective studies are needed to verify our results.

Successful treatment of giant Bowen's disease with photodynamic therapy and subsequent imiquimod in a case with chronic arsenic exposure.

Multiple large lesions of Bowen's disease (BD) often appear in patients who have been under chronic exposure to arsenic. The treatment of such lesions is very challenging. Photodynamic therapy (PDT) has been considered a first-line effective treatment for BD. However, lesions larger than 2 cm are less responsive to PDT. We reported two giant BD lesions (> 10 cm in diameter), that were on a chronic arsenicosis patient's back, to be successfully treated with PDT and subsequent imiquimod occlusion overnight twice a week on the week after PDT. No recurrence was noted during the 12-month follow-up.

The cecropin-prophenoloxidase regulatory mechanism is a cross-species physiological function in mosquitoes.

This study's aim was to investigate whether the cecropin-prophenoloxidase regulatory mechanism is a cross-species physiological function among mosquitoes. BLAST and phylogenetic analysis revealed that three mosquito cecropin Bs, namely Aedes albopictus cecropin B (Aalcec B), Armigeres subalbatus cecropin B2 (Ascec B2), and Culex quinquefasciatus cecropin B1 (Cqcec B1), play crucial roles in cuticle formation during pupal development via the regulation of prophenoloxidase 3 (PPO 3). The effects of cecropin B knockdown were rescued in a cross-species manner by injecting synthetic cecropin B peptide into pupae. Further investigations showed that these three cecropin B peptides bind to TTGG(A/C)A motifs within each of the PPO 3 DNA fragments obtained from these three mosquitoes. These results suggest that Aalcec B, Ascec B2, and Cqcec B1 each play an important role as a transcription factor in cuticle formation and that similar cecropin-prophenoloxidase regulatory mechanisms exist in multiple mosquito species.

Annular infectious dermatoses.

Annular configuration is conspicuous in the clinical manifestation of many skin diseases and can be helpful for the diagnosis and differential diagnosis. Variations may include arciform, ring-form, annular, circinate, serpiginous, gyrated, polycyclic, targeted or figurate forms, in different colors, sizes, and numbers, with various textures and surfaces. In infectious dermatoses, the annular reactions can be specific or nonspecific, while the underlying mechanisms remain largely unknown. In the specific reactions caused by direct invasion of the pathogens, the contest between the centrifugal outspread of the infectious agents and the centripetal impedance of the host immune response is supposed to determine the final conformation. Examples include erythema infectiosum, orf, erythema multiforme, and pityriasis rosea of viral origin. Bacterial infections that may display annular lesions include erythrasma, erythema (chronicum) migrans of Lyme borreliosis, secondary syphilis, cutaneous tuberculosis, and leprosy. Superficial mycosis, such as dermatophytosis, candida intertrigo, tinea imbricata, and subcutaneous mycosis, such as chromoblastomycosis, and algae infection protothecosis, are characterized by annular progression of the skin lesions. The creeping serpiginous extension is an alarming sign for the diagnosis of cutaneous larva migrans. A better understanding of the virulence and pathogenicity of the pathogens and the way and type of immune response will help to clarify the pathogenesis.

A Deep-Learning Algorithm-Enhanced System Integrating Electrocardiograms and Chest X-rays for Diagnosing Aortic Dissection.

BACKGROUND: Chest pain is the most common symptom of aortic dissection (AD), but it is often confused with other prevalent cardiopulmonary diseases. We aimed to develop deep-learning models (DLMs) with electrocardiography (ECG) and chest x-ray (CXR) features to detect AD and evaluate their performance. METHODS: This study included 43,473 patients in the emergency department (ED) between July 2012 and December 2019 for retrospective DLM development. A development cohort including 49,071 ED records (120 AD type A and 64 AD type B) was used to train DLMs for ECG and CXR, and 9904 independent ED records (40 AD type A and 34 AD type B) were used to validate DLM performance. Human-machine competitions of ECG and CXR were conducted. Patient characteristics and laboratory results were used to enhance the diagnostic accuracy. The DLM-enabled AD diagnostic process was prospectively evaluated in 25,885 ED visits. RESULTS: The area under the curves (AUCs) of the ECG and CXR models were 0.918 and 0.857 for detecting AD in a human-machine competition, respectively, which were better than those of the participating physicians. In the validation cohort, the AUCs of the integrated model were 0.882, 0.960, and 0.813 in all AD, AD type A, and AD type B patients, respectively, with a sensitivity of 100.0% and a specificity of 81.7% for AD type A. In patients with chest pain and D-dimer tests, the DLM could predict more precisely, achieving a positive predictive value of 62.5% in the prospective evaluation. CONCLUSIONS: DLMs may serve as decision-supporting tools for identification of AD and facilitate differential diagnosis in patients with acute chest pain.

Lactic acidosis associated with standard dose linezolid in a kidney recipient with impaired renal function.

Severe lactic acidosis, a mitochondrial toxicity caused by the recommended standard dosage of linezolid (LZD), may occur in patients with impaired renal function. We describe an adult male who underwent kidney transplantation with stably impaired renal function, severe dyspnea, and abdominal discomfort. He received a standard oral dose of LZD (600 mg twice daily) and azithromycin for three weeks with a reduced immunosuppressant dose due to pulmonary non-tuberculosis mycobacterial infection. He was alert and afebrile, with a blood pressure of 140/60 mmHg. Pertinent laboratory data showed: pH 7.12, PaCO2 13.6 mmHg; HCO3- 4.3 mmol/L and serum lactate 18.4 mmol/L. His trough serum LZD concentration reached toxic levels (21.4 µg/mL). With hemodialysis, his clinical symptoms improved, with a decline in serum LZD (9.8µg/mL) and lactate (3.2 mmol/L). Chronic standard dose LZD in patients with impaired renal function can lead to life-threatening lactic acidosis, especially in coexisting conditions that reduce LZD metabolism.

Lactic acidosis associated with standard dose linezolid in a kidney recipient with impaired renal function

Abstract Severe lactic acidosis, a mitochondrial toxicity caused by the recommended standard dosage of linezolid (LZD), may occur in patients with impaired renal function. We describe an adult male who underwent kidney transplantation with stably impaired renal function, severe dyspnea, and abdominal discomfort. He received a standard oral dose of LZD (600 mg twice daily) and azithromycin for three weeks with a reduced immunosuppressant dose due to pulmonary non-tuberculosis mycobacterial infection. He was alert and afebrile, with a blood pressure of 140/60 mmHg. Pertinent laboratory data showed: pH 7.12, PaCO2 13.6 mmHg; HCO3- 4.3 mmol/L and serum lactate 18.4 mmol/L. His trough serum LZD concentration reached toxic levels (21.4 μg/mL). With hemodialysis, his clinical symptoms improved, with a decline in serum LZD (9.8μg/mL) and lactate (3.2 mmol/L). Chronic standard dose LZD in patients with impaired renal function can lead to life-threatening lactic acidosis, especially in coexisting conditions that reduce LZD metabolism.

Symptomatic Migraine with Prolonged Visual Aura and Unruptured Occipital Arteriovenous Malformation.

A 35 year-old woman had a two-year history of recurrent headache with clinical presentations of visual aura in her left visual field followed by right-sided throbbing headache. The patient suffered from a similar attack but her visual aura-like symptoms persisted for over 48 hours. The concurrent electroencephalogram demonstrated focal non-epileptiform rhythmic slow waves in the right occipital region. The magnetic resonance images showed prominent parenchymal edema in the right occipital area. The cerebral angiographic study proved a small cerebral arteriovenous malformation. This illustrated case showed that cerebral arteriovenous malformation produces headaches mimicking migraine with visual aura. The acute vascular flow change and the parenchymal edema trigger a prolonged visual aura with coinstantaneous evidence of cortical depression shown on the electroencephalogram. Keywords: Symptomatic migraine; Prolonged visual aura; Unruptured arteriovenous malformation.

Serum Sickness-Like Reactions After Pneumococcal Vaccination.

Serum sickness or serum sickness-like reactions (SSLRs) constitute a rare complication that manifests in individuals after receiving vaccinations. In this case report, we present a patient with typical symptoms of SSLRs after pneumococcal vaccination. The time course of this disease and our diagnostic process are documented in detail. The literature related to serum sickness and SSLRs is also reviewed.

Effects of piperonyl butoxide synergism and cuticular thickening on the contact irritancy response of field Aedes aegypti (Diptera: Culicidae) to deltamethrin.

BACKGROUND: Exploiting indoor-resting mosquitoes' innate behavioral responses to commonly used insecticide is crucial in vector control programs. Indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) treated with pyrethroids have become widely used for controlling dengue fever vectors. The present study tested the effects of piperonyl butoxide (PBO) synergism and cuticular thickening on the contact irritancy response of field A. aegypti (Diptera: Culicidae) to deltamethrin in Taiwan and Thailand. RESULTS: The escape response of field mosquitoes treated with PBO was significantly elicited, with an escape percentage increase between 2- and 10-fold. In addition, the escape time was significantly lower in PBO-pretreated mosquitoes compared with field mosquitoes treated with deltamethrin alone. PBO-pretreated mosquitoes from seven out of 11 field strains exhibited a knockdown percentage of 11.23-54.91%, significantly higher than that of mosquitoes in corresponding strains treated with deltamethrin only. The Annan, Zhongxi, Sanmin, and North strains exhibited weak knockdown responses (≤3.75%). The mortality of PBO-pretreated field mosquitoes increased 2- to 75-fold compared with those treated with deltamethrin alone (mortality: 0-6.70%). Furthermore, the effect of cuticular thickness on the escape response of field mosquitoes was significant, that is, the escape response marginally increased inversely to cuticular thickness. By contrast, cuticular thickness was not significantly associated with knockdown or mortality percentage. CONCLUSION: Irritant behavior in mosquitoes was significantly elicited by PBO synergism. PBO incorporating deltamethrin IRS or LLINs may be effective for controlling dengue fever vectors. © 2021 Society of Chemical Industry.

Biogeography and Ecology of Magnaporthales: A Case Study.

The order Magnaporthales belongs to Sordariomycetes, Ascomycota. Magnaporthales includes five families, namely Ceratosphaeriaceae, Pseudohalonectriaceae, Ophioceraceae, Pyriculariaceae, and Magnaporthaceae. Most Magnaporthales members are found in Poaceae plants and other monocotyledonous herbaceous plants ubiquitously as plant pathogens or endophytic fungi, and some members are found in decaying wood or dead grass as saprophytic fungi. Therefore, studying the biogeography and ecology of Magnaporthales is of great significance. Here, we described the biodiversity of endophytic Magnaporthales fungi from Poaceae at three latitudes in China and conducted a meta-analysis of the geography and ecology of Magnaporthales worldwide. We found that Magnaporthales is a dominant order in the endophytic fungi of Poaceae. More than half of the endophytic Magnaporthales fungi have a taxonomically uncertain placement. Notably, few endophytic fungi are grouped in the clusters with known saprophytic or pathogenic Magnaporthales fungi, indicating that they may have saprophytic and parasitic differentiation in nutritional modes and lifestyles. The meta-analysis revealed that most species of Magnaporthales have characteristic geographical, host, and tissue specificity. The geographical distribution of the three most studied genera, namely Gaeumannomyces, Magnaporthiopsis, and Pyricularia, in Magnaporthales may depend on the distribution of their hosts. Therefore, studies on the endophytic fungal Magnaporthales from monocotyledonous plants, including Poaceae, in middle and low latitudes will deepen our understanding of the biogeography and ecology of Magnaporthales.

Antidepressant-like effects of water extract of Cordyceps militaris (Linn.) Link by modulation of ROCK2/PTEN/Akt signaling in an unpredictable chronic mild stress-induced animal model.

ETHNOPHARMACOLOGY RELEVANCE: Cordyceps militaris (Linn.) Link (CM) is a medicinal mushroom traditionally used in tonics for treating several neurological disorders, including epilepsy and anxiety, in Asia. Reports have shown that CM has anti-inflammatory and anti-oxidative effects and may be beneficial for depression management. AIM OF THE STUDY: This study aimed to investigate the potential of CM as an antidepressant for a long-term unpredictable chronic mild stress (UCMS) rodent models and explore its underlying mechanisms. MATERIALS AND METHODS: Rats were orally administered with 125 (low, L), 250 (medium, M), and 500 (high, H) mg/kg bodyweight (bw) of the water extract of CM (WCM) for 35 consecutive days in the UCMS protocol. The levels of cerebral serotonin (5-HT), dopamine (DA), and metabolites in the frontal cortex of the rats were measured. Blood was collected to investigate the levels of proinflammatory cytokines, and the brain was dissected to assay the stress-associated ROCK2/PTEN/Akt signaling. RESULTS: All doses of the WCM prevented abnormal behaviors induced by UCMS, including anhedonia and hypoactivity. The LWCM treatment reduced the turnover rate of 5-HT, and all doses of the WCM reduced the turnover rate of DA in the frontal cortex. The LWCM also attenuated the elevation of serum IL-1ß induced by chronic stress. All doses of the WCM attenuated the ROCK2 protein hyperactivation, and the LWCM further increased the down-regulation of p-Akt/Akt signaling. CONCLUSION: The WCM has antidepressant-like effects, which may result from the regulation of the stress-related ROCK2/PTEN/Akt pathway. Therefore, the WCM may be developed and used for the complementary treatment of depression.