Early reduction in albuminuria is associated with a steeper 'dip' in initial estimated glomerular filtration rate but favourable long-term kidney outcomes in people with diabetes receiving sodium-glucose cotransporter-2 inhibitors.

AIM: To assess if early change in albuminuria was linked to an initial change in estimated glomerular filtration rate (eGFR) and long-term kidney outcomes in people with type 2 diabetes (T2D) receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors. METHODS: Using a medical database from a multicentre healthcare institute in Taiwan, we retrospectively enrolled 8310 people receiving SGLT2 inhibitors from 1 June 2016 to 31 December 2021. We compared the risks of initial eGFR decline, major adverse renal events (MARE; >50% eGFR reduction or development of end-stage kidney disease), major adverse cardiovascular events (MACE), or hospitalization for heart failure (HHF) using a Cox proportional hazards model. RESULTS: In all, 36.8% (n = 3062) experienced a >30% decrease, 21.0% (n = 1743) experienced a 0%-30% decrease, 14.4% (n = 1199) experienced a 0%-30% increase, and 27.7% (n = 2306) experienced a >30% increase in urine albumin-to-creatine ratio (UACR) after 3 months of SGLT2 inhibitor treatment. Greater acute eGFR decline at 3 months correlated with greater UACR reduction: -3.6 ± 10.9, -2.0 ± 9.5, -1.1 ± 8.6, and -0.3 ± 9.7 mL/min/1.73 m2 for the respective UACR change groups (p < 0.001). Over a median of 29.0 months, >30% UACR decline was associated with a higher risk of >30% initial eGFR decline (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.61-4.47]), a lower risk of MARE (HR 0.66, 95% CI 0.48-0.89), and a comparable risk of MACE or HHF after multivariate adjustment (p < 0.05). The nonlinear analysis showed early UACR decline was linked to a lower risk of MARE but a higher risk of initial steep eGFR decline of >30%. CONCLUSION: Physicians should be vigilant for the potential adverse effects of abrupt eGFR dipping associated with a profound reduction in UACR, despite the favourable long-term kidney outcomes in the population with T2D receiving SGLT2 inhibitor treatment.

Stepwise construction of a metallocatenane based on non-labile bis(terpyridine)-CdII complexes.

A series of metalloligands bearing homoleptic 2,2':6',2''-terpyridine (tpy)-CdII complexes has been successfully synthesized. The formation of ML1 was accomplished through a sequence of Suzuki-Miyaura coupling and complexation reactions, offering an alternative method to produce tpy-based metalloligands under relatively mild conditions. Moreover, the metallomacrocycle C1 and metallocatenane C2 were self-assembled from heteroleptic complexation reactions involving ML1 and suitable counterparts.

Long-term outcomes of active vaccination against de novo hepatitis B among pediatric recipients of living donor liver transplantations with anti-HBc (+) grafts: a retrospective case-control study.

BACKGROUND: Active vaccination has been utilized to prevent de novo hepatitis B virus infection (DNHB) in anti-HBc (+) grafts after liver transplantation (LT). However, the long-term efficacy of active vaccination and graft/patient outcomes of anti-HBc (+) grafts have yet to be comprehensively investigated. MATERIALS AND METHODS: Among 204 pediatric patients enrolled in the study, 82 recipients received anti-HBc (+) grafts. For DNHB prevention, active vaccination was repeatedly administered prior to transplant. Anti-viral therapy was given to patients with pre-transplant anti-HBs<1000 IU/ ml (non-robust response) for 2 years and discontinued when post-transplant patients achieved anti-HBs>1000 IU/mL, while anti-viral therapy was not given in patients with an anti-HBs titer over 1000 IU/mL. The primary outcome was to investigate the long-term efficacy of active vaccination, while the secondary outcomes included the graft and patient survival rates. RESULTS: Among the 82 anti-HBc (+) transplant patients, 68% of recipients achieved a robust immune response, thus not requiring antiviral therapy. Two patients (2.4%) developed DNHB infection, one of which was due to an escape mutant. With a median follow-up of 150 months, the overall 10-year patient and graft survival rates were significantly worse in recipients of anti-HBc (+) grafts than those of anti-HBc (-) grafts (85.2% vs 93.4%, P=0.026; 85.1% vs 93.4%, P=0.034, respectively). Additionally, the 10-year patient and graft outcomes of the anti-HBc (+) graft recipients were significantly worse than those of the anti-HBc (-) graft recipients after excluding early mortality and non-graft mortality values (90.8% vs 96.6%, P=0.036; 93.0% vs 98.3%, P=0.011, respectively). CONCLUSION: Our long-term follow-up study demonstrates that active vaccination is a simple, cost-effective strategy against DNHB infection in anti-HBc (+) graft patients, whereby the need for life-long antiviral therapy is removed. Notably, both the anti-HBc (+) grafts and patients exhibited inferior long-term survival rates, although the exact mechanisms remain unclear.

Number of Premature Ventricular Complexes Predicts Long-Term Outcomes in Patients with Persistent Atrial Fibrillation.

BACKGROUND: Premature ventricular complexes (PVCs) are common electrocardiographic abnormalities and may be a prognosticator in predicting mortality in patients with structurally normal hearts or chronic heart diseases. Whether PVC burden was associated with mortality in patients with chronic atrial fibrillation (AF) remained unknown. We investigated the prognostic value of PVC burden in patients with persistent AF. METHODS: A retrospective analysis of 24 h Holter recordings of 1767 patients with persistent AF was conducted. Clinical characteristics, 24 h average heart rate (HR), and PVC measures, including 24 h PVC burden and the presence of consecutive PVCs (including any PVC couplet, triplet, or non-sustained ventricular tachycardia) were examined for the prediction of all-cause and cardiovascular mortality using the Cox proportional hazards model. RESULTS: After a median follow-up time of 30 months, 286 (16%) patients died and 1481 (84%) patients survived. Multivariate analysis revealed that age, heart failure, stroke, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, digoxin, oral anticoagulant use, and estimated glomerular filtration rate were significant baseline predictors of all-cause mortality and cardiovascular mortality. Twenty-four-hour PVC burden and the presence of consecutive PVCs were significantly associated with all-cause and cardiovascular mortality after adjusting for significant clinical factors. When compared to the first quartile of PVC burden (<0.003%/day), the highest quartile (>0.3%/day) was significantly associated with an increased risk of all-cause mortality (hazard ratio, 2.46; 95% CI, 1.77-3.42) and cardiovascular mortality (hazard ratio: 2.67; 95% CI, 1.76-4.06). CONCLUSIONS: Twenty-four-hour PVC burden is independently associated with all-cause and cardiovascular mortality in patients with persistent AF.

High-order layered self-assembled multicavity metal--organic capsules and anti-cooperative host-multi-guest chemistry.

The construction and application of metal-organic cages with accessible internal cavities have witnessed rapid development, however, the precise synthesis of complex metal-organic capsules with multiple cavities and achievement of multi-guest encapsulation, and further in-depth comprehension of host-multi-guest recognition remain a great challenge. Just like building LEGO blocks, herein, we have constructed a series of high-order layered metal-organic architectures of generation n (n = 1/2/3/4 is also the number of cavities) by multi-component coordination-driven self-assembly using porphyrin-containing tetrapodal ligands (like plates), multiple parallel-podal ligands (like clamps) and metal ions (like nodes). Importantly, these high-order assembled structures possessed different numbers of rigid and separate cavities formed by overlapped porphyrin planes with specific gaps. The host-guest experiments and convincing characterization proved that these capsules G2-G4 could serve as host structures to achieve multi-guest recognition and unprecedentedly encapsulate up to four C60 molecules. More interestingly, these capsules revealed negative cooperation behavior in the process of multi-guest recognition, which provides a new platform to further study complicated host-multi-guest interaction in the field of supramolecular chemistry.

Applying machine learning to construct an association model for lung cancer and environmental hormone high-risk factors and nursing assessment reconstruction.

INTRODUCTION: To utilize machine learning techniques to develop an association model linking lung cancer and environmental hormones to enhance the understanding of potential lung cancer risk factors and refine current nursing assessments for lung cancer. DESIGN: This study is exploratory in nature. In Stage 1, data were sourced from a biological database, and machine learning methods, including logistic regression and neural-like networks, were employed to construct an association model. Results indicate significant associations between lung cancer and blood cadmium, urine cadmium, urine cadmium/creatinine, and di(2-ethylhexyl) phthalate. In Stage 2, 128 lung adenocarcinoma patients were recruited through convenience sampling, and the model was validated using a questionnaire assessing daily living habits and exposure to environmental hormones. RESULTS: Analysis reveals correlations between the living habits of patients with lung adenocarcinoma and exposure to blood cadmium, urine cadmium, urine cadmium/creatinine, polyaromatic hydrocarbons, diethyl phthalate, and di(2-ethylhexyl) phthalate. CONCLUSIONS: According to the World Health Organization's global statistics, lung cancer claims approximately 1.8 million lives annually, with more than 50% of patients having no history of smoking or non-traditional risk factors. Environmental hormones have garnered significant attention in recent years in pathogen exploration. However, current nursing assessments for lung cancer risk have not incorporated environmental hormone-related factors. This study proposes reconstructing existing lung cancer nursing assessments with a comprehensive evaluation of lung cancer risks. CLINICAL RELEVANCE: The findings underscore the importance of future studies advocating for public screening of environmental hormone toxins to increase the sample size and validate the model externally. The developed association model lays the groundwork for advancing cancer risk nursing assessments.

Clinical Outcomes in Type 2 Diabetes Patients After Acute Myocardial Infarction: A Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs. Non-Users.

To compare clinical outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (AMI) using sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. non-use of SGLT2i. A national cohort study based on the Taiwan National Health Insurance Research Database enrolled 944 patients with T2D who had experienced AMI and were treated with SGLT2i and 8,941 patients who did not receive SGLT2i, respectively, from May 1, 2016, to December 31, 2019. We used propensity score matching to balance covariates across study groups. The follow-up period was from the index date to the independent occurrence of the study outcomes, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. The SGLT2i group exhibited a significantly lower incidence of cardiovascular death (0.865% per year vs. 2.048% per year; hazard ratio (HR): 0.42; 95% confidence interval (CI): 0.24-0.76; P = 0.0042), heart failure hospitalization (1.987% per year vs. 3.395% per year; HR: 0.59; 95% CI: 0.39-0.89; P = 0.0126), and all-cause mortality (3.406% per year vs. 4.981% per year, HR: 0.69; 95% CI: 0.50-0.95; P = 0.0225) compared with the non-SGLT2i group. There were no significant differences between the two groups in the incidence of AMI, ischemic stroke, coronary revascularization, major adverse cardiovascular events, composite renal outcomes, or lower limb amputation. These findings suggest that the use of SGLT2i may have favorable effects on clinical outcomes in patients with T2D after AMI.

Enhanced reliability and time efficiency of deep learning-based posterior tibial slope measurement over manual techniques.

PURPOSE: Multifaceted factors contribute to inferior outcomes following anterior cruciate ligament (ACL) reconstruction surgery. A particular focus is placed on the posterior tibial slope (PTS). This study introduces the integration of machine learning and artificial intelligence (AI) for efficient measurements of tibial slopes on magnetic resonance imaging images as a promising solution. This advancement aims to enhance risk stratification, diagnostic insights, intervention prognosis and surgical planning for ACL injuries. METHODS: Images and demographic information from 120 patients who underwent ACL reconstruction surgery were used for this study. An AI-driven model was developed to measure the posterior lateral tibial slope using the YOLOv8 algorithm. The accuracy of the lateral tibial slope, medial tibial slope and tibial longitudinal axis measurements was assessed, and the results reached high levels of reliability. This study employed machine learning and AI techniques to provide objective, consistent and efficient measurements of tibial slopes on MR images. RESULTS: Three distinct models were developed to derive AI-based measurements. The study results revealed a substantial correlation between the measurements obtained from the AI models and those obtained by the orthopaedic surgeon across three parameters: lateral tibial slope, medial tibial slope and tibial longitudinal axis. Specifically, the Pearson correlation coefficients were 0.673, 0.850 and 0.839, respectively. The Spearman rank correlation coefficients were 0.736, 0.861 and 0.738, respectively. Additionally, the interclass correlation coefficients were 0.63, 0.84 and 0.84, respectively. CONCLUSION: This study establishes that the deep learning-based method for measuring posterior tibial slopes strongly correlates with the evaluations of expert orthopaedic surgeons. The time efficiency and consistency of this technique suggest its utility in clinical practice, promising to enhance workflow, risk assessment and the customization of patient treatment plans. LEVEL OF EVIDENCE: Level III, cross-sectional diagnostic study.

Correlation between higher lateral tibial slope and inferior long term subjective outcomes following single bundle anterior cruciate ligament reconstruction.

BACKGROUND: The impact of anatomical factors, such as the lateral tibial slope (LTS), on outcomes following anterior cruciate ligament (ACL) reconstruction is an area of growing interest. This study was led by the observation that patients with a higher LTS may have different recovery trajectories. HYPOTHESIS/PURPOSE: The purpose of this study was to investigate the correlation between a higher LTS and long term subjective outcomes following single-bundle ACL reconstruction. STUDY DESIGN: This study was designed as a retrospective cohort study. METHODS: The study comprised 138 patients who underwent single-bundle ACL reconstruction. The LTS was measured on preoperative radiographs. Patient-reported outcome measures (PROMs) were collected, which included the Lysholm Knee Score, UCLA Activity Score, IKDC Score, and Tegner Activity Score, over a mean follow-up duration of 137 months. RESULTS: A significant negative correlation was found between LTS and all measured PROMs (p < 0.001). The established cut-off value of LTS distinguishing between "Good" and "Fair" Lysholm scores was 8.35 degrees. Female patients have statistically significant higher LTS and lower PROMs scores than male. Patients with LTS greater than or equal to 8.35 had significantly lower PROMs, indicative of poorer functional and subjective outcomes. CONCLUSION: Our findings suggest that a higher LTS is associated with inferior subjective outcomes following single-bundle ACL reconstruction in long term. The LTS cut-off value of 8.35 degrees could potentially be used as a reference in preoperative planning and patient counseling. CLINICAL RELEVANCE: Understanding the relationship between LTS and ACL reconstruction outcomes could inform surgical planning and postoperative management. These findings highlight the need to consider anatomical variances, such as LTS, when assessing patient-specific risks and recovery expectations, contributing to the advancement of personalized care in sports medicine.

Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain.

Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

Development of a simulation system for femoroacetabular impingement detection based on 3D images.

Image-based criteria have been adopted to diagnose femoroacetabular impingement (FAI). However, the overlapping property of the two-dimensional X-ray outlines and static and supine posture of taking computed tomography (CT) and magnetic resonance imaging images potentially affect the accuracy of the criteria. This study developed a CT image-based dynamic criterion to effectively simulate FAI, thereby providing a basis for physicians to perform pre-operative planning for arthroscopic surgery. Post-operative CT images of 20 patients with satisfactory surgical results were collected, and 10 sets of models were used to define the flexion rotation centre (FRC) of the three-dimensional FAI model. First, let these 10 groups of models simulate the FAI detection action and find the best centre offset, and then FRC is the result of averaging these 10 groups of best displacements. The model was validated in 10 additional patients. Finally, through the adjustment basis of FRC, the remaining 10 sets of models can find out the potential position of FAI during the dynamic simulation process. Rotational collisions detected using FRC indicate that the patient's post-operative flexion angle may reach 120° or greater, which is close to the actual result. The recommended surgical range of the diagnostic system (average length of 6.4 mm, width of 4.1 mm and depth of 3.2 mm) is smaller than the actual surgical results, which prevents the doctor from performing excessive resection operations, which may preserve more bones. The FRC diagnostic system detects the distribution of FAI in a simple manner. It can be used as a pre-operative diagnosis reference for clinicians, hoping to improve the effect and accuracy of debridement surgery.

Initial eGFR Changes with SGLT2 Inhibitor in Patients With Type 2 Diabetes and Associations With the Risk of Abnormal Serum Potassium Level.

BACKGROUND: Both high and low levels of serum potassium measurements are linked with a higher risk of adverse clinical events among patients with type 2 diabetes. The study was aimed at evaluating the implications of the various degrees of initial estimated glomerular filtration rate (eGFR) change on subsequent serum potassium homeostasis following sodium-glucose cotransporter-2 inhibitor (SGLT2i) initiation among patients with type 2 diabetes. METHODS AND RESULTS: We used medical data from a multicenter health care provider in Taiwan and recruited 5529 patients with type 2 diabetes with baseline/follow-up eGFR data available after 4 to 12 weeks of SGLT2i treatment from June 1, 2016, to December 31, 2018. SGLT2i treatment was associated with an initial mean (SEM) eGFR decline of -3.5 (0.2) mL/min per 1.73 m2 in overall study participants. A total of 36.7% (n=2028) of patients experienced no eGFR decline, and 57.9% (n=3201) and 5.4% (n=300) of patients experienced an eGFR decline of 0% to 30% and >30%, respectively. Patients with an initial eGFR decline of >30% were associated with higher variability in consequent serum potassium measurement when compared with those without an initial eGFR decline. Participants with a pronounced eGFR decline of >30% were associated with a higher risk of hyperkalemia ≥5.5 (adjusted hazard ratio,4.59 [95% CI, 2.28-9.26]) or use of potassium binder (adjusted hazard ratio, 2.65 [95% CI, 1.78-3.95]) as well as hypokalemia events <3.0 mmol/L (adjusted hazard ratio, 3.21 [95% CI, 1.90-5.42]) or use of potassium supplement (adjusted hazard ratio, 1.87 [95% CI, 1.37-2.56]) following SGLT2i treatment after multivariate adjustment. CONCLUSIONS: Physicians should be aware that the eGFR trough occurs shortly, and consequent serum potassium changes following SGLT2i initiation.

Prognostic factors and treatment responses among patients with gross residual disease in differentiated thyroid cancer.

BACKGROUND: Various postoperative staging systems were developed to assess the outcome of differentiated thyroid cancer from initial risk after surgery to dynamic changing prognosis during follow-up. The objective of our retrospective cohort study was to identify risk factors contributing to macroscopic positive surgical margin (R2 resection) and parameters in discriminating the treatment responses and prognosis among R2 patients. METHODS: In total, 242 differentiated thyroid cancer patients with extrathyroidal extension who underwent a thyroidectomy at Kaohsiung Chang Gung Memorial Hospital between January 2013 and July 2018, were included. The patients were grouped according to the presence or absence of gross residual disease (R2). The R2 patients were further classified into two categories according to their treatment response into excellent and nonexcellent groups. The parameters and treatment outcomes were compared between these groups. RESULTS: The mean follow-up time was 45.3 months. Two hundred seven (85.5%) patients had either surgery-free or microscopic margins (R0/R1), while 35 (14.5%) had R2 resection. In the R2 group (n = 35), 15 (42.9%) patients achieved an excellent response, while 20 (57.1%) achieved a nonexcellent response. Statistically significant differences were observed in the extent of neck dissection, TSH-Tg level, post-RAI Tg level, nodal status, and recurrence between the two groups. The Kaplan-Meier curves for 5-year local and distant recurrence-free survival of R0/R1 versus R2 patients were 90.0% versus 66.3%, and 98.4% versus 90.7%, respectively ( p < 0.001). Among the R2 patients, the excellent responders had a higher local recurrence-free survival than nonexcellent responders (93.3% vs. 45.1%, p = 0.008). CONCLUSION: There are significant disparities in recurrence-free survival among R2 patients with different treatment responses. The nodal status of papillary thyroid cancer and thyroglobulin level after thyroidectomy and RAI were factors contributing to difference in their treatment responses.

SGLT2 inhibitors vs. GLP-1 receptor agonists and clinical outcomes in patients with diabetes with/without atrial fibrillation.

CONTEXT: The coexistence of diabetes mellitus and atrial fibrillation (AF) is associated with substantial risks of adverse cardiovascular events. OBJECTIVE: The relevant outcomes associated with the use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus glucagon-like peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D) with/without concomitant AF remained unknown. METHODS: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, there were 344,392 and 31,351 patients with T2D without AF, and 11,462 and 816 T2D patients with AF treated with SGLT2i and GLP-1RA from May 1, 2016, to December 31, 2019. Patients were followed from the drug-index date until the occurrence of study events, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. We used propensity score stabilized weight to balance covariates across two medication groups. RESULTS: The incidence rate of all study outcomes in patients with concomitant AF was much higher than in those without concomitant AF. For the AF cohort, SGLT2i vs. GLP-1RA was associated with a lower risk of hospitalization for heart failure (2.32 vs. 4.74 events per 100 person-years; hazard ratio (HR):0.48 [95% confidential interval (CI):0.36-0.66]), with no benefit seen for the non-AF cohort (P for homogeneity < 0.01). SGLT2i vs. GLP-1RA was associated with a lower risk of composite kidney outcomes both in the AF (0.38 vs. 0.79 events per 100 person-years; HR:0.47; [95%CI:0.23-0.96]) and non-AF cohorts (0.09 vs. 0.18 events per 100 person-years; HR:0.53; [95%CI:0.43-0.64]). There were no significant differences in the risk of major adverse cardiovascular events and all-cause mortality in those who received SGLT2i compared to GLP-1RA for the AF or non-AF cohorts. CONCLUSION: Considering the high risk of developing HF and/or high prevalence of concomitant HF in patients with diabetes, whether SGLT2i should be the preferred treatment to GLP-1RA for such a high-risk population requires further investigation.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis-a nationwide cohort study.

BACKGROUND: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. METHODS: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. RESULTS: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052-1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454-0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529-0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478-0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231-1.880), ICH (aHR 2.045, 95% CI 1.329-3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB. CONCLUSIONS: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Clinical significance of regional constructive and wasted work in patients receiving cardiac resynchronization therapy.

Background: Previous studies have shown that global constructive work (CW) and wasted work (WW) predict response to cardiac resynchronization therapy (CRT). This study evaluated the predictive value of regional CW and WW for reverse remodeling and clinical outcomes after CRT. Methods: We performed a prospective study involving 134 CRT candidates with left bundle branch block and left ventricular ejection fraction ≤35%. Global and regional CW and WW were calculated using pressure-strain loop analysis. CRT response was defined by reverse remodeling as a reduction of ≥15% in left ventricular end-systolic volume after six months. Results: At six-month follow-up, 92 (69%) patients responded to CRT. Of the regional CW and WW measures, lateral wall (LW) CW and septal WW were most strongly and significantly correlated with reverse remodeling. At multivariate analysis, LW CW and septal WW were both independent determinants of reverse remodeling. When LW CW and septal WW were included in the model, global CW and WW were not independently associated with reverse remodeling. LW CW and septal WW predicted reverse remodeling with an area under the curve (AUC) of 0.783 (95% CI: 0.700-0.866) and 0.737 (95% CI: 0.644-0.831), respectively. Using both variables increased the AUC to 0.832 (95% CI: 0.755-0.908). Both LW CW ≤878 mmHg% (HR 2.01; 95% CI: 1.07-3.79) and septal WW ≤181 mmHg% (HR 2.60; 95% CI: 1.38-4.90) were significant predictors of combined death and HF hospitalization at two-year follow-up. Conclusion: LW CW and septal WW before CRT are important determinants of reverse remodeling and clinical outcomes.

Early Surgery for Infective Endocarditis Complicated With Neurologic Injury.

OBJECTIVES: To estimate the association between early surgery and the risk of mortality in patients with left-sided infective endocarditis in the context of stroke. DESIGN: Retrospective cohort study. SETTING: This study was a multiinstitution study based on the Chang Gung Research Database, which contains electronic medical records from 7 hospitals in northern and southern Taiwan; these include 2 medical centers, 2 regional hospitals, and 3 district hospitals. PARTICIPANTS: Patients with active left-sided infective endocarditis who underwent valve surgery between September 2002 and December 2018. INTERVENTIONS: The authors divided patients into 2 groups, with versus without preoperative neurologic complications, had undergone early (within 7 d) or later surgery, and with brain ischemia or hemorrhage. MEASUREMENTS AND MAIN RESULTS: Three hundred ninety-two patients with a median time from diagnosis to surgery of 6 days were included. No significant differences in postoperative stroke, in-hospital mortality, or follow-up outcomes were observed between the patients with and without neurologic complications. Among the patients with preoperative neurologic complications, patients who underwent early surgery had a lower 30-day postoperative mortality rate (13.1% v 25.8%; hazard ratio, 0.21; 95% CI 0.07-0.67). In the subgroup analysis of the comparison between brain ischemia and hemorrhage groups, there was no significant between-group difference in the in-hospital outcomes or outcomes after discharge. CONCLUSIONS: Early cardiac surgery may be associated with more favorable clinical outcomes in patients with preoperative neurologic complications. Thus, preoperative neurologic complications should not delay surgical interventions.

Effects of mitral valve disease etiology on the outcomes of mechanical and biological valve replacement: retrospective cohort study.

INTRODUCTION: The choice of an artificial mitral valve (MV) is a crucial clinical decision that affects the long-term survival and quality of life of patients. However, current guidelines recommend selecting MV based on patient age and life expectancy at the time of mitral valve replacement (MVR), without considering the etiology of MV disease. This study aimed to investigate whether MV disease etiology should be considered when choosing a valve for MVR and to evaluate the impact of MV disease etiology on long-term patient survival. METHODS: Using data (2002-2018) from Taiwan's National Health Insurance Research Database, the authors conducted a nationwide retrospective cohort study to compare the biological and mechanical valves in terms of all-cause mortality as the primary outcome. The inverse probability of the treatment weighting method was used to reduce the effects of the confounding factors. The following etiologies were assessed: infective endocarditis, rheumatic heart disease, ischemic mitral regurgitation, and degenerative mitral regurgitation. RESULTS: In patients aged below 70 years, it was observed that mechanical valves demonstrated an association with benefits compared to biological valves in the context of survival. In patients with infective endocarditis aged below 72 years, mechanical valves were associated with survival benefits, but not in those with stroke during hospitalization. These valves were also found to be linked with survival advantages for patients with rheumatic heart disease aged below 60 years and for those with degenerative mitral regurgitation aged below 72 years. However, no age-dependent effects of valve type on all-cause mortality were observed in patients with ischemic mitral regurgitation. CONCLUSION: The etiology of MV disease appears to be important in the selection of a suitable MV and determination of a cutoff age for mechanical and biological MVR.

Feasibility of new-generation endocytoscopy for the real-time diagnosis of ampullary lesions: A pilot study (with video).

BACKGROUND AND AIM: An early and accurate diagnosis of ampullary neoplasia is crucial; however, sampling bias is still a major concern. New-generation endocytoscopy enables real-time visualization of cellular structures and enables an accurate pathological prediction; however, its feasibility for small ampullary lesions has never been investigated. METHODS: We developed a novel endocytoscopic (EC) classification system for ampullary lesions after an expert review and agreement from five experienced endoscopists and one pathologist. We then consecutively enrolled a total of 43 patients with an enlarged ampulla (< 3 cm), all of whom received an endocytoscopic examination. The feasibility of endocytoscopy was evaluated, and the performance of the EC classification system was then correlated with the final histopathology. RESULTS: In five cases (11.6%), the endocytoscope could not approach the ampulla, and these cases were defined as technical failure. Among the remaining 38 patients, 8 had histopathology-confirmed adenocarcinoma, 15 had adenoma, and 15 had non-neoplastic lesions. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification system to diagnose ampullary neoplasias were 95.7%, 86.7%, 91.7%, 92.9%, and 92.1%, respectively. Moreover, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification to diagnose ampullary cancer were 62.5%, 100%, 100%, 90.9%, and 92.1%, respectively. One case with intra-ampullary papillary-tubular carcinoma was classified as having a non-neoplastic lesion by endocytoscopy. CONCLUSIONS: Endocytoscopy and the novel EC classification system demonstrated good feasibility to discriminate ampullary neoplasias from non-neoplastic lesions and may be useful for optical biopsies of clinically suspicious ampullary lesions.