Comparing clinical outcomes in patients with type 2 diabetes mellitus after ischaemic stroke: Sodium-glucose cotransporter 2 inhibitors users versus non-users. A propensity score matching National Cohort Study.

AIM: This nationwide cohort study evaluated the impact of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on patients with type 2 diabetes mellitus (T2DM) after ischaemic stroke (IS), aiming to compare clinical outcomes between SGLT2i-treated patients and those not receiving SGLT2i. MATERIALS AND METHODS: Utilizing Taiwan's National Health Insurance Research Database, we identified 707 patients with T2DM treated with SGLT2i and 27 514 patients not treated with SGLT2i after an IS, respectively, from 1 May 2016 to 31 December 2019. Propensity score matching was applied to balance baseline characteristics. The follow-up period extended from the index date (3 months after the index acute IS) until the independent occurrence of the study outcomes, 6 months after discontinuation of the index drug, or the end of the study period (31 December 2020), whichever came first. RESULTS: After propensity score matching, compared with the non-SGLT2i group (n = 2813), the SGLT2i group (n = 707) exhibited significantly lower recurrent IS rates (3.605% per year vs. 5.897% per year; hazard ratio: 0.55; 95% confidence interval: 0.34-0.88; p = 0.0131) and a significant reduction in all-cause mortality (5.396% per year vs. 7.489% per year; hazard ratio: 0.58; 95% confidence interval: 0.39-0.85; p = 0.0058). No significant differences were observed in the rates of acute myocardial infarction, cardiovascular death, heart failure hospitalization, or lower limb amputation. CONCLUSIONS: Our findings indicate significantly lower risks of recurrent IS and all-cause mortality among patients with T2DM receiving SGLT2i treatment. Further studies are required to validate these results and investigate the underlying mechanisms behind the observed effects.

The results of preventing postoperative achilles tendon adhesion using cross-linked and non-cross-linked hyaluronic acid, a study with rat model.

BACKGROUND: There are many adhesion barrier materials, cross-linked or non-cross-linked hyaluronic acid (HA), used during surgeries. PURPOSE: This study investigates the efficacy of cross-linked and non-cross-linked HA in preventing Achilles tendon adhesions. We hypothesized that non-cross-linked HA may be more effective than cross-linked HA in preventing Achilles tendon adhesions following injury and repair. METHODS: Twenty male Sprague Dawley rats, totaling 40 legs, underwent Achilles tendon transection and repair. Following the surgery, they were treated simultaneously with cross-linked and non-cross-linked HA formulations. The rats were divided into four groups: a positive control group, a group treated with BMC non-cross-linked HA gel, a group treated with DEFEHERE cross-linked HA gel, and a group treated with ANIKA cross-linked HA gel. Four weeks after surgery, macroscopic evaluation of peritendinous adhesion and histological analysis were conducted to assess the effectiveness of the treatments. RESULTS: Non-cross-linked BMC HA demonstrated superior efficacy in preventing tendon adhesions compared to cross-linked HA and control groups. Histological analysis confirmed reduced adhesion severity in the non-cross-linked HA group (P < 0.05). The findings support the potential of non-cross-linked HA as a treatment to inhibit tendon adhesions. Further research, including clinical trials, is warranted to validate these results in human subjects. CONCLUSIONS: Non-cross-linked BMC HA had significantly lower tendon adhesions parameters and better healing scores in histological analysis than cross-linked HA and control group did. Non-cross-linked HA holds promise as a potential treatment to inhibit the formation of such adhesions.

Single-bundle ACL combined with ALL reconstruction yields comparable outcomes in patients with varied anatomical risk factors for ACL graft failure.

BACKGROUND: Anterior cruciate ligament (ACL) graft failure is influenced by factors such as meniscal tears and tibial plateau slope. Combined anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstruction has reduced failure rates; however, its efficacy in high-risk patients remains unclear. This study hypothesized that combined ACL and ALL reconstruction would yield similar clinical outcomes in patients with varying risks of ACL failure. PATIENTS AND METHODS: A total of 76 patients who underwent primary single-bundle ACL reconstruction combined with ALL reconstruction between June 2018 and June 2021 were included. The medial tibial slope (MTS), lateral tibial slope (LTS), and anterior tibial translation (ATT) were measured using magnetic resonance imaging and plain radiography of the knee joint. The meniscal lesions were assessed during surgery. Preoperative clinical assessments and final follow-up were conducted using patient-reported outcome measurements (PROMs), including the International Knee Documentation Committee (IKDC) evaluation, Lysholm knee scoring scale, and Tegner Activity scale. PROMs were collected at least two years postoperatively. RESULTS: The average follow-up was 32.5 ± 7.4 months. There were no significant differences in postoperative IKDC score, Lysholm score, or Tegner activity score between patients with or without medial meniscus injury (p = 0.155, 0.914, and 0.042, respectively), with or without lateral meniscus injury (p = 0.737, 0.569, and 0.942, respectively), medial tibial slope > 12° or ≤ 12° (p = 0.290, 0.496, and 0.988, respectively), or lateral tibial slope > 7.4° or ≤ 7.4° (p = 0.213, 0.625, and 0.922, respectively). No significant correlations were found between anterior tibial translation and postoperative IKDC (R = -0.058, p = 0.365), Lysholm (R = -0.017, p = 0.459), or Tegner activity scores (R = -0.147, p = 0.189). CONCLUSION: Our study demonstrates that single-bundle ACL reconstruction combined with ALL reconstruction provides reliable and comparable clinical outcomes in patients with high-risk factors for ACL graft failure, such as increased tibial slope or meniscal injury. Our results suggest that the indications for ALL reconstruction may be expanded to include patients with a high tibial slope or meniscal injury, because these factors have been shown to contribute to increased rotational instability and high rates of ACL graft failure. Future prospective randomized controlled trials with large patient cohorts and long follow-up periods are needed to validate these findings and establish clear guidelines for patient selection and surgical decision-making. LEVEL OF EVIDENCE: Level 3.

Association between antithrombotic drug regimen changes and clinical outcomes after stroke in atrial fibrillation.

BACKGROUND: The impact of post-stroke antithrombotic regimen in atrial fibrillation is uncertain. OBJECTIVE: This study aimed to describe antithrombotic therapy prescribing patterns after ischemic stroke and the impact on outcomes. METHODS: A total of 23,165 patients with atrial fibrillation experiencing ischemic stroke were identified. Subsequent post-stroke events included recurrent ischemic stroke, intracranial hemorrhage, major bleeding, mortality, and composite outcomes. RESULTS: Of those who were nonanticoagulated before a stroke, 33.5% remained nonanticoagulated and 39.2% were prescribed only antiplatelet agents (APs) after a stroke. Compared with non-vitamin K antagonist oral anticoagulants (NOACs) after stroke, there was a significant increase in ischemic stroke and mortality in nonanticoagulated patients (adjusted hazard ratio [aHR], 2.09 and 3.92) and AP users (aHR, 1.32 and 1.28). Post-stroke warfarin was associated with a significantly increased risk of major bleeding compared with NOACs (aHR, 1.23). Of 769 patients receiving NOACs before stroke and continuing NOACs after stroke, those switching to a different NOAC were associated with significantly higher risk of ischemic stroke (aHR, 2.07) and composite outcomes (aHR, 1.36-1.85) with no difference in intracranial hemorrhage, major bleeding, or mortality compared with those receiving the same NOAC after stroke. Of patients receiving NOACs before stroke, the risks of clinical events were similar between patients taking NOACs alone and those taking NOAC plus AP after stroke. CONCLUSION: NOAC alone after stroke was associated with a better clinical outcome compared with nonanticoagulation, AP, or warfarin. Of patients already taking NOACs before stroke, the addition of AP did not confer additional benefits compared with NOACs alone. A change of NOAC types after stroke was associated with a 2-fold higher risk of ischemic stroke and composite outcomes.

Correlation of medial tibial slope and lateral tibial slope measured on radiographs and magnetic resonance imaging in patients with anterior cruciate ligament injury.

OBJECTIVES: The study aimed to investigate the correlation between medial tibial slope (MTS) and lateral tibial slope (LTS) on magnetic resonance imaging (MRI), MTS measured by different imaging, and the intra- and interobserver reliability of measurements between reviewers with gaps of experience over 10 years. PATIENTS AND METHODS: This retrospective study included 97 patients (93 males, 4 females; mean age: 30.8±8.3 years; range, 17 to 49 years) with anterior cruciate ligament (ACL) injuries who subsequently underwent double-bundle ACL reconstruction by a single surgeon between January 2005 and December 2014. The MTS was measured on lateral knee radiographs, and MTS and LTS were measured on MRIs. Three different reviewers, including a postgraduate year doctor, an orthopedic resident, and an attending orthopedic surgeon, performed the measurements. Each reviewer measured the slope of the same image three times. The correlations of MTS on radiographs and MTS/LTS on MRIs were calculated. Intra- and interobserver reliability were evaluated. RESULTS: The average MTS and LTS measured on MRI were not significantly different (6.4° and 6.9°, respectively; p=0.268) and exhibited a moderate positive correlation (r=0.544, p<0.001). The average MTS on radiographs was significantly greater than that on MRI (10.5° and 6.4°, respectively; p<0.001) with a low positive correlation (r=0.480, p<0.001). The intraobserver reliability of the postgraduate year doctor, the orthopedic resident, and the attending orthopedic surgeon were moderate to excellent. The interobserver reliability of MTS on radiographs was excellent (intraclass correlation coefficient [ICC]=0.925; p<0.001). The interobserver reliability of MTS on MRI as well as LTS on MRI was good (ICC=0.755 and 820, respectively; all p values <0.001). CONCLUSION: Average MTS and LTS measured on MRI in patients with ACL injury exhibited a moderate positive correlation. The average MTS measured on radiographs was significantly greater than that on MRI with a low positive correlation.

SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.

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.

Double-bundle ACL combined with ALL reconstruction for patients at high risk of ACL failure: clinical and radiological results.

BACKGROUND: We investigated whether double-bundle (DB) anterior cruciate ligament (ACL) reconstruction (ACLR) combined with anterolateral ligament reconstruction (ALLR) improved clinical and radiological outcomes in patients at high risk of ACL failure. The primary outcome was graft failure, and secondary outcomes included knee stability and patient-reported outcome measures (PROMs). PATIENTS AND METHODS: Fifty-two patients who underwent DB ACLR combined with ALLR were included in this retrospective cohort study. Preoperative risk factors, including femorotibial angle (FTA), lateral tibial slope (LTS), medial tibial slope (MTS), and meniscal tears, were assessed using X-ray and magnetic resonance imaging (MRI). The grade of post-operative pivot shift, Lysholm score, and Tegner activity score were used to assess clinical outcomes. The minimum follow up duration was 2 years. RESULTS: The cohort (mean age, 26.1 ± 9.4 years; 51.9% male) had a mean follow-up duration of 28.9 ± 3.4 months. Preoperatively, 57.8% had lateral meniscus (LM) tears, and 61.0% had a grade 2-3 pivot shift. Postoperatively, no graft failures or revision cases occurred during follow-up. Approximately 90.4% of the patients exhibited a negative pivot shift (p < 0.001), with Lysholm and Tegner activity scores of 92.5 ± 6.1 and 5.1 ± 2.0. The medial meniscus (MM) tear group had a significantly smaller FTA than the intact group (p = 0.043). No significant differences in PROMs were found between the LM tear and intact LM groups or between the high and low MTS or LTS groups (p = n.s.). CONCLUSION: DB ACLR combined with ALLR had satisfactory clinical outcomes in patients at high risk of ACL failure, with no graft failures observed during a mean follow-up duration of 2.4 years. The technique effectively reduced the postoperative pivot shift, regardless of preoperative risk factors. STUDY DESIGN: Level IV, retrospective therapeutic case-series. TRAIL REGISTRATION: ethical approval number, 202300134B0; ethical committee, the Institutional Review Board of Chang Gung Medical Foundation.

Use of fluoroquinolones and the risk of aortic and mitral regurgitation: A nationwide case-crossover study.

BACKGROUND: Recently, there have been conflicting results reporting an increased risk of AR or MR associated with oral fluoroquinolones (FQs).This study investigated whether the use of FQs increases the risk of mitral regurgitation (MR) or aortic regurgitation (AR). METHODS: A retrospective cohort study was conducted by using the Taiwan National Health Insurance research database. A unidirectional case-crossover design without selecting controls from an external population was adopted in this study. A total of 26,650 adult patients with new onset of AR or MR between January 1, 2000, and December 31, 2012, were identified. The risk of outcomes was compared between the hazard period and one of the randomly selected referent periods of the same individuals. RESULTS: Before exclusion of pneumonia diagnosed within 2 months before the index date, patients who took FQs had a significantly greater risk of AR or MR (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.30-1.77), any AR (combined AR and MR) (aOR 1.50, 95% CI 1.10-2.04), and any MR (combined AR and MR) (aOR 1.37, 95% CI 1.16-1.62). After exclusion of pneumonia, FQs exposure remained significantly associated with a greater risk of MR (aOR 1.38, 95% CI 1.17-1.62) and any MR (aOR 1.25, 95% CI 1.05-1.48). CONCLUSIONS: The findings suggested that patients treated with FQs could be warned about the potential risk for MR even after considering the possibility of protopathic bias. Reducing unnecessary FQs prescriptions may be considered to reduce the risk of valvular heart disease.

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.

Human TMEFF1 is a restriction factor for herpes simplex virus in the brain.

Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained1,2. Here, we report on two unrelated people who had HSE as children and are homozygous for rare deleterious variants of TMEFF1, which encodes a cell membrane protein that is preferentially expressed by brain cortical neurons. TMEFF1 interacts with the cell-surface HSV-1 receptor NECTIN-1, impairing HSV-1 glycoprotein D- and NECTIN-1-mediated fusion of the virus and the cell membrane, blocking viral entry. Genetic TMEFF1 deficiency allows HSV-1 to rapidly enter cortical neurons that are either patient specific or derived from CRISPR-Cas9-engineered human pluripotent stem cells, thereby enhancing HSV-1 translocation to the nucleus and subsequent replication. This cellular phenotype can be rescued by pretreatment with type I interferon (IFN) or the expression of exogenous wild-type TMEFF1. Moreover, ectopic expression of full-length TMEFF1 or its amino-terminal extracellular domain, but not its carboxy-terminal intracellular domain, impairs HSV-1 entry into NECTIN-1-expressing cells other than neurons, increasing their resistance to HSV-1 infection. Human TMEFF1 is therefore a host restriction factor for HSV-1 entry into cortical neurons. Its constitutively high abundance in cortical neurons protects these cells from HSV-1 infection, whereas inherited TMEFF1 deficiency renders them susceptible to this virus and can therefore underlie HSE.

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.

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.

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.

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.

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.

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.

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.