Patent foramen ovale closure in ischemic stroke patients with and without thrombophilia: a systematic review and meta-analyses.

Ischemic stroke patients with thrombophilia and patient foramen ovale (PFO) may have an increased risk of recurrent stroke and transient ischemic attack (TIA), and may benefit from PFO closure. However, screening for thrombophilia is not routinely performed and the impact of thrombophilia on prognosis after PFO closure is uncertain. We aim to compare the risk of recurrent stroke and TIA after PFO closure in patients with thrombophilia versus those without. We performed a systematic review and meta-analyses of the literature, with a comprehensive literature search performed on 12 January 2023. Studies comparing the outcomes of patients with and without thrombophilia after PFO closure were included. The primary outcome evaluated was a recurrence of acute cerebrovascular event (ACE), a composite of recurrent ischemic stroke and recurrent TIA. The secondary outcomes included recurrent ischemic stroke only or TIA only. A total of 8 cohort studies were included, with a total of 3514 patients. There was an increased risk of stroke/TIA in patients with thrombophilia compared to those without thrombophilia after PFO (OR: 1.42, 95% CI: 1.01-1.99, I2 = 50%). The association between risk of TIA only (OR: 1.36, 95% CI: 0.77-2.41, I2 = 0%) and stroke only (OR: 1.09, 95% CI: 0.54-2.21, I2 = 0%) with thrombophilia did not reach statistical significance. There is an increased risk of recurrent cerebral ischemia event in patients with thrombophilia compared to those without thrombophilia after PFO closure. Future large prospective studies are necessary to characterise the risk and benefits of PFO closure, as well as the appropriate medical treatment to reduce the risk of recurrent stroke and TIA in this high-risk population.

Polymorphisms of HLA genes and hypersensitivity to penicillin among patients in a Taiwanese population.

Penicillin allergy is a potentially life-threatening condition that is common among patients. However, the genetic associations with penicillin allergy are not yet recognized for prevention or diagnosis, particularly in East Asian populations. We conducted a retrospective case-control study using data from the Taiwan Precision Medicine Initiative and analysing DNA samples to identify eight major MHC Class I and Class II loci. We employed imputation methods for accurate HLA typing and enrolled 17,827 individuals who received penicillin. Logistic regression analyses were utilized to explore associations between HLA genotypes, comorbidities and allergy risk, while simultaneously conducting a subgroup analysis to explore the association between HLA genotypes, comorbidities and the severity of allergic reactions. Our study assigned 496 cases to the penicillin allergy group and 4960 controls to a matched group. The risk of penicillin allergy was significantly higher with HLA-DPB1*05:01 (OR = 1.36, p = .004) and HLA-DQB1*05:01 (OR = 1.54, p = .03), with adjusted p-values of .032 and .24, respectively. Urticaria was identified as a separate risk factor (OR = 1.73, p < .001). However, neither the HLA alleles nor the comorbidities had a significant relationship with the risk of severe penicillin-induced allergy. HLA-DPB1*05:01 was found to be significantly associated with penicillin allergy reactions among the Taiwanese population.

Validation of a Prediction Model for Acute Kidney Injury after Cardiac Surgery in a Retrospective Asian Cohort.

Background: The incidence of postoperative acute kidney injury (AKI) is relatively high in some Asian regions. The objective of this study was to examine the performance of an AKI prediction model developed based on data from a White-dominant population in a retrospective Asian cohort of patients undergoing cardiovascular surgery. Methods: We retrospectively identified 549 patients who underwent elective major cardiovascular surgery (coronary artery bypass graft, valve surgery, and aorta surgery), and excluded those who underwent a percutaneous cardiovascular procedure. Patients with a baseline estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were also excluded. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Performance of the prediction model for AKI was expressed as area under the receiver operating characteristic curve (AUC). Results: The prediction model had a good predictive accuracy for postoperative AKI (all AUC > 0.92). The AUC of the prediction model in subgroups of age (<65 years and ≥65 years), sex (male and female), hypertension, and diabetes were all >0.85 (all p values < 0.001). Conclusions: The model could be used to predict postoperative AKI in Asian patients undergoing cardiovascular surgery with a baseline eGFR ≥ 60 mL/min/1.73 m2.

Performance of Risk Scores in Predicting Infective Endocarditis in Patients with Staphylococcus aureus Bacteraemia in a Prospective Asian Cohort.

Background: Several risk scores have been derived to predict the risk of infective endocarditis (IE) amongst patients with Staphylococcus aureus bacteraemia (SAB), which helps to guide clinical management. Methods: We prospectively studied 634 patients admitted with SAB. The cohort was stratified into those with or without IE, and the PREDICT Day 1, Day 5 and VIRSTA scores were tabulated. Area under the receiver operating characteristic (AUC) curves were constructed to compare the performance of each score. Results: Of the 634 patients examined, 36 (5.7%) had IE. These patients were younger (51.6 ± 20.1 vs. 59.2 ± 18.0 years, p = 0.015), tended to have community acquisition of bacteraemia (41.7% vs. 17.9%, p < 0.001), and had persistent bacteraemia beyond 72 h (19.4% vs. 6.0%, p = 0.002). The VIRSTA score had the best performance in predicting IE (AUC 0.76, 95%CI 0.66-0.86) compared with PREDICT Day 1 and Day 5. A VIRSTA score of <3 had the best negative predictive value (97.5%), compared with PREDICT Day 1 (<4) and Day 5 (<2) (94.3% and 96.6%, respectively). Conclusions: Overall, the risk scores performed well in our Asian cohort. If applied, 23.5% of the cohort with a VIRSTA ≥ 3 would require TEE, and a score of <3 had an excellent negative predictive value.

Machine Learning Modeling to Predict Atrial Fibrillation Detection in Embolic Stroke of Undetermined Source Patients.

BACKGROUND: In patients with embolic stroke of undetermined source (ESUS), occult atrial fibrillation (AF) has been implicated as a key source of cardioembolism. However, only a minority acquire implantable cardiac loop recorders (ILRs) to detect occult paroxysmal AF, partly due to financial cost and procedural inconvenience. Without the initiation of appropriate anticoagulation, these patients are at risk of increased ischemic stroke recurrence. Hence, cost-effective and accurate methods of predicting AF in ESUS patients are highly sought after. OBJECTIVE: We aimed to incorporate clinical and echocardiography data into machine learning (ML) algorithms for AF prediction on ILRs in ESUS. METHODS: This was a single-center cohort study that included 157 consecutive patients diagnosed with ESUS from October 2014 to October 2017 who had ILR evaluation. We developed four ML models, with hyperparameters tuned, to predict AF detection on an ILR. RESULTS: The median age of the cohort was 67 (IQR 59-74) years old and the median monitoring duration was 1051 (IQR 478-1287) days. Of the 157 patients, 32 (20.4%) had occult AF detected on the ILR. Support vector machine predicted for AF with a 95% confidence interval area under the receiver operating characteristic curve (AUC) of 0.736-0.737, multilayer perceptron with an AUC of 0.697-0.708, XGBoost with an AUC of 0.697-0.697, and random forest with an AUC of 0.663-0.674. ML feature importance found that age, HDL-C, and admitting heart rate were important non-echocardiography variables, while peak mitral A-wave velocity and left atrial volume were important echocardiography parameters aiding this prediction. CONCLUSION: Machine learning modeling incorporating clinical and echocardiographic variables predicted AF in ESUS patients with moderate accuracy.

Atherosclerotic cardiovascular disease landscape in Singapore.

Cardiovascular disease (CVD) is the leading cause of death worldwide, accounting for over one-third of all deaths in Singapore. An analysis of age-standardized mortality rates (ASMR) for CVD in Singapore revealed a deceleration in the initial rapid decline in ASMR. A decrease in smoking prevalence may have contributed to the initial rapid decline in ASMR. Furthermore, other major risk factors, such as diabetes mellitus, hypertension, elevated low-density lipoprotein levels, and obesity, are steadily rising. Singapore's CVD economic burden is estimated to be 8.1 billion USD (11.5 billion SGD). The burden of CVD can only be reduced using individual and population-based approaches. Prevention programs must also be developed based on an understanding of risk trends. Therefore, this article attempts to capture the burden of CVD, trends in risk factor control, preventive care, disparities, and current unmet needs, particularly in atherosclerotic cardiovascular disease management in Singapore.

Structure-guided identification and characterization of potent inhibitors targeting PhoP and MtrA to combat mycobacteria.

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators PhoP and MtrA of mycobacteria. The constructed pharmacophore model Phar-PR-n4 identified effective inhibitors of formation of the PhoP-DNA complex: ST132 (IC50 = 29 ± 1.6 µM) and ST166 (IC50 = 18 ± 1.3 µM). ST166 (KD = 18.4 ± 4.3 µM) and ST132 (KD = 14.5 ± 0.1 µM) strongly targeted PhoP in a slow-on, slow-off manner. The inhibitory potency and binding affinity of ST166 and ST132 for MtrAC were comparable to those of PhoP. Structural analyses and molecular dynamics simulations revealed that ST166 and ST132 mainly interact with the α8-helix and C-terminal ß-hairpin of PhoP, with functionally essential residue hotspots for structure-based inhibitor optimization. Moreover, ST166 has in vitro antibacterial activity against Macrobacterium marinum. Thus, ST166, with its characteristic 1,2,5,6-tetrathiocane and terminal sulphonic groups, has excellent potential as a candidate for the development of novel antimicrobial agents to combat pathogenic mycobacteria.

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

Evaluation of the Lifetime Benefits of Metformin and SGLT2 Inhibitors in Type 2 Diabetes Mellitus Patients with Cardiovascular Disease: A Systematic Review and Two-Stage Meta-Analysis.

BACKGROUND: Metformin and sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular benefits but their comparative effects on mortality in type 2 diabetes mellitus (T2DM) patients with cardiovascular disease (CVD) are unknown. Hence, we evaluated and compared lifetime benefits arising from metformin or SGLT2 inhibitors in T2DM patients with CVD. MATERIALS AND METHODS: Studies published in the PubMed, EMBASE and CENTRAL databases before 28 October 2023 were retrieved. Treatment effects of metformin against US FDA-approved SGLT2 inhibitors in T2DM patients with CVD were evaluated and lifetime gains in event-free survival were estimated from our primary endpoints of all-cause and cardiovascular mortality. Risk ratios were derived to assess their impact on secondary outcomes such as major adverse cardiovascular events and hospitalizations for heart failure. RESULTS: Overall, 14 studies were included. Five studies published Kaplan-Meier curves for the primary outcome of all-cause mortality. Individual participant data were reconstructed from these Kaplan-Meier curves, from which we conducted our two-stage meta-analysis. Participants receiving metformin and SGLT2 inhibitors experienced a reduction in the risk for all-cause mortality as compared with those not taking metformin and placebo. However, participants receiving SGLT2 inhibitors had a higher all-cause mortality (hazard ratio 1.308, 95% confidence interval 1.103-1.550) versus metformin. Treatment with metformin was estimated to offer an additional 23.26 months of survival free from all-cause mortality versus 23.04 months with SGLT2 inhibitors. CONCLUSIONS: In patients with T2DM and CVD, metformin and SGLT2 inhibitors were associated with substantially lower all-cause mortality rates and slightly longer life expectancies than in patients without. Metformin presented an advantage over SGLT2 inhibitors in reducing all-cause mortality.

Association between holiday and weekend admissions and mortality outcomes among patients with acute myocardial infarction receiving percutaneous coronary intervention in Taiwan.

There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93-1.42 or aOR 1.23; 95% CI 0.96-1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90-1.58 or aOR 1.24; 95% CI 0.90-1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions.

Diabetic foot ulcers segmentation challenge report: Benchmark and analysis.

Monitoring the healing progress of diabetic foot ulcers is a challenging process. Accurate segmentation of foot ulcers can help podiatrists to quantitatively measure the size of wound regions to assist prediction of healing status. The main challenge in this field is the lack of publicly available manual delineation, which can be time consuming and laborious. Recently, methods based on deep learning have shown excellent results in automatic segmentation of medical images, however, they require large-scale datasets for training, and there is limited consensus on which methods perform the best. The 2022 Diabetic Foot Ulcers segmentation challenge was held in conjunction with the 2022 International Conference on Medical Image Computing and Computer Assisted Intervention, which sought to address these issues and stimulate progress in this research domain. A training set of 2000 images exhibiting diabetic foot ulcers was released with corresponding segmentation ground truth masks. Of the 72 (approved) requests from 47 countries, 26 teams used this data to develop fully automated systems to predict the true segmentation masks on a test set of 2000 images, with the corresponding ground truth segmentation masks kept private. Predictions from participating teams were scored and ranked according to their average Dice similarity coefficient of the ground truth masks and prediction masks. The winning team achieved a Dice of 0.7287 for diabetic foot ulcer segmentation. This challenge has now entered a live leaderboard stage where it serves as a challenging benchmark for diabetic foot ulcer segmentation.

MACE and Hyperthyroidism Treated With Medication, Radioactive Iodine, or Thyroidectomy.

Importance: Excessive thyroid hormones from hyperthyroidism increase cardiovascular risks. Among 3 available treatments for hyperthyroidism, comparisons of long-term outcomes associated with antithyroid drugs (ATDs), radioactive iodine (RAI), and surgery to treat newly diagnosed hyperthyroidism are lacking. Objective: To compare risks of major adverse cardiovascular events (MACE) and all-cause mortality among patients with hyperthyroidism treated with ATDs, RAI, or surgery. Design, Setting, and Participants: This nationwide cohort study used the Taiwan National Health Insurance Research Database. Patients aged 20 years or older with newly diagnosed hyperthyroidism between 2011 and 2020 were enrolled. Treatment groups were determined within 18 months from diagnosis, with follow-up until the development of MACE, death, or the end date of the database, whichever came first. Data were analyzed from October 2022 through December 2023. Exposures: The ATD group received ATDs only. RAI and surgery groups could receive ATDs before treatment. Anyone who underwent thyroid surgery without RAI was classified into the surgery group and vice versa. Main Outcomes and Measures: The primary outcomes included MACE (a composite outcome of acute myocardial infarction, stroke, heart failure, and cardiovascular mortality) and all-cause mortality. Results: Among 114 062 patients with newly diagnosed hyperthyroidism (mean [SD] age, 44.1 [13.6] years; 83 505 female [73.2%]), 107 052 patients (93.9%) received ATDs alone, 1238 patients (1.1%) received RAI, and 5772 patients (5.1%) underwent surgery during a mean (SD) follow-up of 4.4 (2.5) years. Patients undergoing surgery had a significantly lower risk of MACE (hazard ratio [HR] = 0.76; 95% CI, 0.59-0.98; P = .04), all-cause mortality (HR = 0.53; 95% CI, 0.41-0.68; P < .001), heart failure (HR = 0.33; 95% CI, 0.18-0.59; P < .001), and cardiovascular mortality (HR = 0.45; 95% CI, 0.26-0.79; P = .005) compared with patients receiving ATDs. Compared with ATDs, RAI was associated with lower MACE risk (HR = 0.45; 95% CI, 0.22-0.93; P = .03). Risks for acute myocardial infarction and stroke did not significantly differ between treatment groups. Conclusions and Relevance: In this study, surgery was associated with lower long-term risks of MACE and all-cause mortality, while RAI was associated with a lower MACE risk compared with ATDs.

Use of wearable technology in cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source: a systematic review.

INTRODUCTION: Prolonged cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source (ESUS) is necessary to identify atrial fibrillation (AF) that requires anticoagulation. Wearable devices may improve AF detection compared to conventional management. We aimed to review the evidence for the use of wearable devices in post-cryptogenic stroke and post-ESUS monitoring. METHODS: We performed a systematic search of PubMed, EMBASE, Scopus and clinicaltrials.gov on 21 July 2022, identifying all studies that investigated the use of wearable devices in patients with cryptogenic stroke or ESUS. The outcomes of AF detection were analysed. Literature reports on electrocardiogram (ECG)-based (external wearable, handheld, patch, mobile cardiac telemetry [MCT], smartwatch) and photoplethysmography (PPG)-based (smartwatch, smartphone) devices were summarised. RESULTS: A total of 27 relevant studies were included (two randomised controlled trials, seven prospective trials, 10 cohort studies, six case series and two case reports). Only four studies compared wearable technology to Holter monitoring or implantable loop recorder, and these studies showed no significant differences on meta-analysis (odds ratio 2.35, 95% confidence interval [CI] 0.74-7.48, I 2 = 70%). External wearable devices detected AF in 20.7% (95% CI 14.9-27.2, I 2 = 76%) of patients and MCT detected new AF in 9.6% (95% CI 7.4%-11.9%, I 2 = 56%) of patients. Other devices investigated included patch sensors, handheld ECG recorders and PPG-based smartphone apps, which demonstrated feasibility in the post-cryptogenic stroke and post-ESUS setting. CONCLUSION: Wearable devices that are ECG or PPG based are effective for paroxysmal AF detection after cryptogenic stroke and ESUS, but further studies are needed to establish how they compare with Holter monitors and implantable loop recorder.

The intersection of heart failure and cancer in women: a review.

Cancer and cardiovascular disease represent the two leading causes of morbidity and mortality worldwide. Women continue to enjoy a greater life expectancy than men. However, this comes at a cost with more women developing diabetes, hypertension and coronary artery disease as they age. These traditional cardiovascular risk factors not only increase their lifetime risk of heart failure but also their overall risk of cancer. In addition to this, many of the cancers with female preponderance are treated with potentially cardiotoxic therapies, adding to their increased risk of developing heart failure. As a result, we are faced with a higher risk population, potentially suffering from both cancer and heart failure simultaneously. This is of particular concern given the coexistence of heart failure and cancer can confer a worse prognosis than either a single diagnosis of heart failure or cancer alone. This review article explores the intersection of heart failure and cancer in women at multiple levels, including traditional cardiovascular risk factors, cardiovascular toxicity derived from antineoplastic and radiation therapy, shared pathophysiology and HF as an oncogenic process. This article further identifies opportunities and strategies for intervention and optimisation, whilst highlighting the need for contemporary guidelines to better inform clinical practice.

Left Ventricular Diastolic Dysfunction Is Associated with Poor Functional Outcomes after Endovascular Thrombectomy.

INTRODUCTION: With the advent of endovascular thrombectomy (ET), patients with acute ischaemic strokes (AIS) with large vessel occlusion (LVO) have seen vast improvements in treatment outcomes. Left ventricular diastolic dysfunction (LVDD) has been shown to herald poorer prognosis in conditions such as myocardial infarction. However, whether LVDD is related to functional recovery and outcomes in ischaemic stroke remains unclear. We studied LVDD for possible relation with clinical outcomes in patients with LVO AIS who underwent ET. METHODS: We studied a retrospective cohort of 261 LVO AIS patients who had undergone ET at a single comprehensive stroke centre and correlated LVDD to short-term mortality (in-hospital death) as well as good functional recovery defined as modified Rankin Scale of 0-2 at 3 months. RESULTS: The study population had a mean age of 65-years-old and were predominantly male (54.8%). All of the patients underwent ET with 206 (78.9%) achieving successful reperfusion. Despite this, 25 (9.6%) patients demised during the hospital admission and 149 (57.1%) did not have good function recovery at 3 months. LVDD was present in 82 (31.4%) patients and this finding indicated poorer outcomes in terms of functional recovery at 3 months (OR 2.18, 95% CI 1.04-4.54, p = 0.038) but was not associated with increased in-hospital mortality (OR 2.18, 95% CI 0.60-7.99, p = 0.240) after adjusting for various confounders. CONCLUSION: In addition to conventional echocardiographic indices such as left ventricular ejection fraction, LVDD may portend poorer outcomes after ET, and this relationship should be investigated further.

Erector spinae plane block reduces opioid consumption and improves incentive spirometry volume after cardiac surgery: A retrospective cohort study.

BACKGROUND: Effective postoperative pain management is vital in cardiac surgery to prevent opioid dependency and respiratory complications. Previous studies on the erector spinae plane (ESP) block have focused on single-shot applications or immediate postoperative outcomes. This study evaluates the efficacy of continuous ESP block vs conventional care in reducing opioid consumption and enhancing respiratory function recovery postcardiac surgery over 72 hours. METHODS: A retrospective study at a tertiary hospital (January 2021-July 2022) included 262 elective cardiac surgery patients. Fifty-three received a preoperative ESP block, matched 1:1 with a control group (n = 53). The ESP group received 0.5% ropivacaine intraoperatively and 0.16% ropivacaine every 4 hours postoperatively. Outcomes measured were cumulative oral morphine equivalent (OME) dose within 72 hours postextubation, daily maximum numerical rating scale (NRS) ≥3, incentive spirometry volume, and %baseline performance, stratified by surgery type (sternotomy or thoracotomy). RESULTS: Significant OME reduction was observed in the ESP group (sternotomy: median decrease of 113 mg, 95% CI: 60-157.5 mg, p < 0.001; thoracotomy: 172.5 mg, 95% CI: 45-285 mg, p = 0.010). The ESP group also had a lower risk of daily maximum NRS ≥3 (adjusted OR sternotomy: 0.22, p < 0.001; thoracotomy: 0.07, p < 0.001), a higher incentive spirometry volumes (sternotomy: mean increase of 149 mL, p = 0.019; thoracotomy: 521 mL, p = 0.017), and enhanced spirometry %baseline (sternotomy: mean increase of 11.5%, p = 0.014; thoracotomy: 26.5%, p < 0.001). CONCLUSION: Continuous ESP block was associated with a reduction of postoperative opioid requirements, lower instances of pain scores ≥3, and improve incentive spirometry performance following cardiac surgery. These benefits appear particularly prominent in thoracotomy patients. Further prospective studies with larger sample size are required to validate these findings.

Effects of integrated care with case management and nutritional counselling for frail older adults with nutritional risk in the primary care setting.

BACKGROUND: The effects of integrated care with case management and nutritional counselling for frail patients with nutritional risk are unclear. OBJECTIVES: To assess the impact of the integrated care model for frail patients with nutritional risk in the primary care setting. METHODS: This was a retrospective observational study. We enrolled 100 prefrail or frail patients according to Clinical Frailty Scale (CFS) aged ≥ 60 years with nutritional risk from the geriatric clinic. We implemented the frailty intervention model, including integrated care with comprehensive geriatric assessments (CGA), case management, and nutritional counselling by the dietitian. We obtained measures of CGA components, physical performance, body mass index (BMI), and daily caloric intake before and after the 2-month care program. We used the Wilcoxon signed-rank test to analyse differences after the care program and applied multiple linear regression to determine the predictive factors for CFS improvement. RESULTS: Among the 100 patients (mean age, 75.0 ±â€…7.2 years; females, 71.0%; frail patients, 26%), 93% improved their CFS status, and 91% achieved > 80% of recommended daily caloric intake after the care program. The Mini Nutritional Assessment Short-Form significantly improved after the program. BMI and daily caloric intake increased significantly after nutritional counselling. The post-test short physical performance battery (SPPB) significantly increased with a faster 4 m gait speed. Baseline poor CFS was a significant predictor for CFS improvement. CONCLUSIONS: Integrated care with case management and nutritional counselling for prefrail and frail patients with nutritional risk in the primary care setting may improve physical performance and nutritional status.

Frailty, a state of vulnerability in older adults, can lead to various health issues. Early intervention in poor nutrition can be beneficial in managing frailty. Integrated care with comprehensive assessments has demonstrated its effectiveness in managing frail older adults. However, there are limited models designed for primary care, and nutritional intervention alone may not be adequate. This retrospective observational study, conducted in a specialized primary care unit for geriatric patients, enrolled prefrail and frail individuals at nutritional risk. A multidisciplinary team implemented an integrated care model that included comprehensive geriatric assessments, case management, and nutritional counselling. After the care program, a significant majority of patients exhibited improved Clinical Frailty Scale status, along with a high proportion achieving 80% of their recommended daily caloric intake. The study also revealed improved physical performance measured by the Short Physical Performance Battery, and a faster 4 m gait speed. Additionally, both BMI and daily caloric intake significantly increased after nutritional counselling. These findings highlight the positive impact of integrated care, including comprehensive assessments, case management, and nutritional counselling, on the physical performance and nutritional status of prefrail and frail older adults.

A refined Uni-vector prime editing system improves genome editing outcomes in mammalian cells.

Prime editing is an advanced technology in CRISPR/Cas research with increasing numbers of improved methodologies. The original multi-vector method hampers the efficiency and precision of prime editing and also has inherent difficulty in generating homozygous mutations in mammalian cells. To overcome these technical issues, we developed a Uni-vector prime editing system, wherein the major components for prime editing were constructed in all-in-one plasmids, pPE3-pPuro and pePEmax-pPuro. The Uni-vector prime editing plasmids enhance the editing efficiency of prime editing and improved the generation of homozygous mutated mammalian cell lines. The editing efficiency is dependent of the transfection efficiency. Remarkably, the Uni-vector ePE5max system achieved an impressive editing rate approximately 79% in average, even in cell lines that are traditionally difficult to transfect, such as FaDu cell line. Furthermore, it resulted in a high frequency of homozygous knocked-in cells, with a rate of 99% in HeLa and 85% in FaDu cells. Together, our Uni-vector approach simplifies the delivery of editing components and improves the editing efficiency, especially in cells with low transfection efficiency. This approach presents an advancement in the field of prime editing.

Migraine and atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological factors between migraines and atrial fibrillation, we aimed to clarify the association between migraine and atrial fibrillation in this systematic review and meta-analysis. METHODS: A literature search was conducted in EMBASE, PubMed, Scopus and Cochrane electronic bibliographic databases from inception to 5 September 2022 with the following inclusion criteria: (a) cohort or cross-sectional studies; (b) studies that included only patients aged ≥18 years; and (c) studies that examined the association between atrial fibrillation and migraines. Exclusion criteria were case-control studies and the studies that included patients with previous diagnosis of atrial fibrillation or nonmigrainous headache. The Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS: Six studies were included, demonstrating a pooled prevalence of atrial fibrillation of 1.61% (95% confidence interval [CI] 0.51, 3.29) in migraine with aura and 1.32% (95% CI 0.17, 3.41) in migraine without aura. The overall prevalence of atrial fibrillation in migraine was 1.39% (95% CI 0.24, 3.46). CONCLUSION: In this systematic review and meta-analysis, the overall prevalence of atrial fibrillation in patients with migraine was low. Further studies are needed to clarify this relationship.

Intrinsic capacity and multimorbidity predicting incident disability-Insights from the I-Lan Longitudinal Aging Study.

OBJECTIVES: This longitudinal cohort study aimed to examine the effect of intrinsic capacity (IC) and multimorbidity on the development of new disabilities. METHODS: The study utilized data from 1,009 participants without disabilities from the I-Lan Longitudinal Aging Study. Multivariable logistic regressions were employed to assess the predictive capability of IC (ranging from 0 to 100) and multimorbidity for incident disability over a 7-year follow-up period. RESULTS: Both low IC (OR 4.9, 95 % CI 2.1-11.1, p < 0.001) and multimorbidity (OR 4.5, 95 % CI 2.2-9.2, p < 0.001) significantly predicted incident disability over the 7-year period. A one-point increase in IC reduced the risk of incident disability by 10 % (OR 0.9, 95 % CI 0.8-0.9, p < 0.001). Among IC subdomains, both better locomotion (OR 0.96, 95 % CI 0.94-0.99, p = 0.014) and psychology (OR 0.97, 95 %CI 0.94-1.00, p = 0.049) significantly reduced the risk of incident disability. Rapid declines in IC significantly predicted incident disability (OR 4.1, 95 % CI 1.8-9.3, p = 0.001), whereas the onset of new multimorbidity or changes in the number of chronic conditions did not demonstrate a significant association with incident disability. The interaction terms between IC and multimorbidity, both categorically (low IC * multimorbidity, p = 0.959) and numerically (IC (per point) * multimorbidity, p = 0.660) were all statistically insignificant. CONCLUSIONS: IC exhibited better predictive capacity for 7-year incident disability compared to multimorbidity, so health care services targeting older adults should adopt an integrated care approach that combines both function- and disease-centric strategies.