Final infarct size (FIS) and microvascular obstruction (MVO) are associated with heart failure hospitalisations and mortality in patients with acute myocardial infarction (AMI). Interventions beyond primary percutaneous coronary intervention (PCI) to reduce FIS are needed. Supersaturated oxygen (SSO₂) therapy demonstrated reduced FIS in clinical trials.

We aimed to investigate whether routine use of SSO₂ reduces FIS and MVO in clinical practice.

Intracoronary SSO₂ was delivered for 60 minutes after successful primary PCI in patients with anterior AMI. Results from 20 SSO₂ patients were compared with those from 20 similar non-SSO₂ AMI patients. Multimodal imaging including single-photon emission computed tomography (SPECT), fibroblast activation protein inhibitor positron emission tomography (FAPI-PET), and cardiac magnetic resonance imaging (CMR) was performed to assess left ventricular function, FIS, area at risk, extent of myocardial fibroblast activation, myocardial salvage, and MVO.

The two groups did not significantly differ regarding sex, age, weight, hypertension, dyslipidaemia, smoking and diabetes status, prehospital cardiac arrest, door-to-balloon time, Thrombolysis in Myocardial Infarction flow before and after PCI, or renal function (p>0.1 for each) and had comparable area at risk by CMR and FAPI-PET. SSO₂ patients showed lower FIS determined by CMR (SSO₂: 20% vs non-SSO₂: 32%; p<0.001) and SPECT (SSO₂: 16% vs non-SSO₂: 29%; p=0.014). Myocardial salvage was higher in SSO₂ patients (50% vs 28%; p=0.002). MVO occurred less often and was less extreme under SSO₂ therapy.

SSO₂ therapy was associated with significantly reduced microvascular obstruction and FIS in patients with anterior AMI in clinical routine practice.

To understand clinical and health economic outcomes in patients receiving standard-of-care (SOC), out-of-hospital management for recently diagnosed heart failure (HF) in the US.

Systematic literature review with a subsequent pooled rates analysis.

Researchers reviewed randomized controlled trials (RCTs) indexed in PubMed and EMBASE between 2008 and 2023. RCTs were selected as the data sources because of the standardized reporting on outcomes and prospective data. Studies included in the analysis reported on US patients recently diagnosed with HF who underwent watchful waiting after discharge. The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with details reported in the PROSPERO study protocol (No. CRD42023410084). The pooled estimates of all-cause and HF-specific hospital readmissions, length of hospital stay, emergency department visits, and mortality at 3, 6, and 12 months were calculated using R software's meta and metafor packages.

There were 31 studies that met the inclusion criteria and reported data for 6916 patients with HF receiving SOC. The proportions of patients with a readmission and an emergency department visit at 3 months were 32.55% (95% CI, 24.03%-41.63%) and 13.83% (95% CI, 8.21%-20.49%), respectively. Mortality over the same period was 3.46%. Quality-of-life and cost data were heterogeneous and infrequently reported, preventing pooled analyses of these data. Length of stay had a pooled value of 7.12 days (95% CI, 5.78-8.46).

HF with SOC monitoring is associated with substantial health care burden. Improvements in SOC monitoring, potentially through remote monitoring and management, could be beneficial to patients, clinicians, and payers.

Acute ischemic stroke (AIS) remains a leading cause of disability and death globally, with limited effective neuroprotective strategies beyond reperfusion therapies. Despite advances in reperfusion treatments, many patients still experience poor outcomes, highlighting the urgent need for additional therapeutic approaches. We investigated whether intra-arterial local therapeutic hypothermia (IA-LTH) combined with endovascular treatment could improve outcomes in patients with AIS.

We conducted a multicenter, randomized trial with blinded outcome assessment (ISOLATION trial), where outcome assessors and patients were blinded to treatment allocation while procedural staff could not be blinded, to test the effectiveness of IA-LTH for neuroprotection in AIS (registration number: ChiCTR2300074990). Between September 2023 and January 2024, we recruited 100 patients with anterior circulation large vessel occlusion within 24 h of stroke onset from 18 stroke centers in China. Participants were randomly assigned (1:1) to receive either IA-LTH plus standard care (including endovascular treatment and guideline-recommended medical therapy; intervention; n = 50) or standard care alone (control; n = 50). The IA-LTH group received intra-arterial infusion of 4 °C saline during and following endovascular treatment. Primary outcome was favorable functional outcome (modified Rankin Scale 0-2) at 90 days. Using intention-to-treat analysis, among participants (median age 69 years, 64% [64/100] male, median National Institutes of Health Stroke Scale score 14), the primary outcome did not reach statistical significance, with favorable outcome achieved in 58.0% (29/50) of the IA-LTH group versus 40.0% (20/50) of controls (adjusted relative risk [aRR] of 1.47 (95% CI [0.99, 2.16]; P = 0.055)). This lack of statistical significance is primarily due to the limited sample size of this pilot study, which was designed to assess feasibility and safety rather than provide definitive efficacy evidence. Safety outcomes, including rates of symptomatic intracranial hemorrhage (8.0% [4/50] versus 16.0% [8/50]) and mortality (20.0% [10/50] versus 22.0% [11/50]), were not significantly different between groups. The main limitations include the insufficient sample size of this pilot study which limited statistical power to detect differences in the primary outcome, the inability to adjust for potentially important confounders beyond age and ASPECTS due to the small sample size, and the higher incidence of pulmonary infections in the IA-LTH group that may have resulted from hypothermia-induced immune suppression or sedation-related factors.

This pilot study provides preliminary insights suggesting that IA-LTH combined with endovascular therapy may be feasible and safe, with potential to improve functional outcomes in patients with AIS. The primary outcome did not reach statistical significance. However, the observed numerical differences suggest that IA-LTH warrants further investigation in larger trials.

Chinese Clinical Trial Registry (ChiCTR) ChiCTR2300074990.

This double-blinded randomised clinical trial aimed to compare the efficacy of lignocaine, diclofenac sodium and ketorolac tromethamine as supplemental intraligamentary injections for intra-appointment pain in normotensive and hypertensive patients with moderate to severe symptomatic irreversible pulpitis.

Ethical clearance was obtained, and the trial was registered on the Clinical Trial Registry India (CTRI/2020/09/027635; Registered on 07/09/2020). A total of 198 patients were divided into two groups-hypertensive group (Group 1; n=99) and normotensive (healthy) group (Group 2; n=99). After computerised randomisation and double blinding, participants were subdivided into three subgroups-1A/2A: lignocaine (n=33), 1B/2B: diclofenac sodium (n=33) and 1C/2C: ketorolac tromethamine (n=33). The preoperative visual analogue scale (VAS) scores was recorded. For the hypertensive group, blood pressure was recorded, and inferior alveolar nerve block (IANB) comprising 1.8ml of 2% lignocaine without adrenaline was administered. For the normotensive group, IANB with 1.8ml of 2% lignocaine with adrenaline was administered. A supplemental intraligamentary injection comprising one of the experimental drugs was injected to both the groups. Endodontic access was gained, and the intraoperative VAS score was recorded. As part of the statistical analysis, paired t-tests, Tukey's post hoc test and ANOVA were performed using SPSS software version 20.

Supplemental intraligamentary injections of diclofenac sodium and ketorolac tromethamine showed a statistically significant difference (p<0.05) compared to lignocaine in the reduction of intraoperative pain with no side effects in hypertensive and healthy individuals.

Supplemental injections of both NSAIDs performed better than lignocaine in reducing intraoperative pain among healthy and hypertensive individuals. (EEJ-2023-06-076).

While several studies have assessed the potential effect of intermittent fasting on reducing cardiovascular risks, the findings are inconclusive.

To compare the relative effectiveness of intermittent fasting methods in reducing key cardiovascular risks.

Studies were searched from Medline, Embase, Cochrane Library Central and Global Health to identify studies that enrolled adults (≥ 18 years) to intermittent fasting methods and reported effects on one of the six specified cardiovascular risk factors. We performed a random-effects network meta-analysis using a frequentist framework. Outcomes were reported as mean differences (MD) with their corresponding 95% confidence intervals (CI).

Fifty-six studies were included in the analysis. With high certainty of evidence, modified alternate-day fasting was found to be the most effective intervention compared to a usual diet in reducing body weight (MD= -5.18 kg; 95% CI: -7.04, -3.32), waist circumference (-3.55 cm; -5.66, -1.45), systolic blood pressure (-7.24 mmHg; -11.90, -2.58), diastolic blood pressure (-4.70 mmHg; -8.46, -0.95). With high certainty, time-restricted eating was the most effective intervention compared to usual diet in reducing fat-free mass (-0.82 kg; -1.46, -0.17), waist circumference (-3.00 cm; -4.50, -1.51), diastolic blood pressure (-3.24 mmHg; -4.69, -1.79) and fasting plasma glucose (-3.74 mg/dL; -6.01, -1.46).

Modified alternate-day fasting, and time-restricted eating appear to be promising approaches for reducing most cardiovascular risk factors. These intermittent fasting methods may be considered as potential components of lifestyle interventions aimed at managing cardiovascular disease risk factors. However, further long-term randomised controlled trials comparing intermittent fasting methods are needed to confirm their efficacy and assess their safety over time.

Aging is a biological process that occurs in every living organism and affects all bodily systems. Many chronic diseases, such as cardiovascular diseases, diabetes, and neurodegenerative diseases of the central nervous system, are perceived as an integral part of the aging process and are even referred to as "aging-related diseases." These diseases develop over long periods of time and are typically treated only after they have already manifested or been diagnosed, primarily with medications, and they cannot be completely cured. In recent decades, a growing perspective views the mechanisms of aging themselves as a pathological process that facilitates the development of diseases. Consequently, intervening in these mechanisms may, if not prevent, at least significantly delay their progression. This raises the question: 'Should medicine regard the aging process itself as a disease and even define aging as a disease?' The answer to this question is complex, particularly given the necessity of a clearly defined and agreed-upon medical indication for any medical treatment. This article explores this issue by reviewing well-known biological mechanisms of aging, the relationship between aging and chronic diseases, the existing potential to treat aging directly, and the challenges associated with considering aging as a disease.

We have read 'NSBBs, EBL or Combined Therapy for High-Risk Varices: Systematic Review and Meta-Analysis' and provided objective comments on it.

Ischaemic stroke is a leading cause of disability and death worldwide, but limited treatment options are available to improve its outcomes. Some studies have explored transcranial laser therapy in people with acute ischaemic stroke, but the benefits and harms of this treatment are unclear.

The primary objective was to assess the benefits and harms of transcranial laser therapy for improving functional outcomes after acute ischaemic stroke. The secondary objective was to assess the equity of transcranial laser therapy in people with acute ischaemic stroke.

We searched CENTRAL, MEDLINE, Embase, ISI Science Citation Index, CINAHL, PEDro (Physiotherapy Evidence Database), REHABDATA, and four ongoing trials registries. We also searched reference lists and databases of conference abstracts for other studies, including any that are ongoing or unpublished. The latest search date was 3 August 2024 for all databases except CenterWatch, which we searched on 1 November 2024.

We included randomised controlled trials (RCTs) comparing transcranial laser therapy with sham treatment or no treatment in people with acute ischaemic stroke, with or without standard treatment in both groups.

The critical outcomes were unfavourable functional outcome, defined as a score of 3 to 6 on the modified Rankin Scale (mRS), and all-cause mortality. The important outcomes were improvement of stroke severity measured on the National Institutes of Health Stroke Scale (NIHSS), serious adverse events, and adverse events.

We used the Cochrane risk of bias tool (RoB 2) to assess the risk of bias for all outcomes in all RCTs.

We planned to use risk ratios (RRs) with 95% confidence intervals (CIs) to compare all outcomes. However, for improvement of stroke severity, we extracted odds ratios (ORs) and 95% CIs from the original studies because the raw data were unavailable. Our meta-analyses used fixed-effect modelling. To assess statistical heterogeneity, we used the I² statistic. We used the GRADE approach to assess the certainty of the evidence.

We included four RCTs enrolling a total of 1420 people with acute ischaemic stroke. The studies were published between 2007 and 2014. All were multicentre studies, based in Europe, North America, South America, Asia, or more than one of these continents. All studies included people older than 40 years (mean age 68.3 years), and 59.6% of participants were men. All studies enrolled participants within 24 hours after onset of stroke symptoms, all used a transcranial laser of 808-nm wavelength, and all compared transcranial laser therapy with sham treatment.

Critical outcomes Transcranial laser therapy results in little to no difference in unfavourable functional outcome at 90 days compared with sham treatment (RR 0.93, 95% CI 0.85 to 1.02; I² = 10%; 3 studies, 1408 participants; high-certainty evidence). Transcranial laser therapy may result in little to no difference in all-cause mortality at 90 days compared with sham treatment (RR 0.96, 95% CI 0.72 to 1.28; I² = 0%; 4 studies, 1420 participants; low-certainty evidence). Important outcomes Transcranial laser therapy may result in little to no difference in improvement of stroke severity at 90 days compared with sham treatment (OR 1.14, 95% CI 0.92 to 1.42; I² = 73%; 3 studies, 1408 participants; low-certainty evidence). Transcranial laser therapy may lead to a slight reduction in serious adverse events at 90 days compared with sham treatment (RR 0.83, 95% CI 0.71 to 0.96; I² = 0%; 4 studies, 1420 participants; low-certainty evidence). Transcranial laser therapy likely results in little to no difference in adverse events at 90 days compared with sham treatment (RR 1.01, 95% CI 0.97 to 1.06; I² = 8%; 3 studies, 1300 participants; moderate-certainty evidence). After excluding the only study with high risk of bias judgements, the findings of sensitivity analyses for unfavourable functional outcome, improvement of stroke severity, and serious adverse events were consistent with the findings of the main analyses. For serious adverse events, we excluded the only study (630 participants) with positive findings, and the pooled effect estimate of the remaining three studies indicated little or no difference between the intervention and control groups.

The current evidence shows no clear benefit or harm associated with transcranial laser therapy in people with acute ischaemic stroke. Our results suggest transcranial laser therapy compared with sham treatment results in little to no difference in unfavourable functional outcome and may result in little to no difference in all-cause mortality at 90 days. The evidence regarding adverse events was of low-to-moderate certainty. More high-quality trials are needed to further evaluate the role of transcranial laser therapy in people with acute ischaemic stroke, to inform the optimal treatment regimen, and to identify people who might benefit most from the therapy.

This review was supported by the National Natural Science Foundation of China (grant numbers 82171285; 82371323); the Science and Technology Department of Sichuan Province (grant numbers 2024YFHZ0330; 2023NSFSC1558); the 1·3·5 project for disciplines of excellence-Clinical Research Fund, West China Hospital, Sichuan University (grant numbers 2024HXFH022; 2024HXFH023); and the Postdoctor Research Fund of West China Hospital, Sichuan University (grant number 2024HXBH139).

Protocol available via DOI: 10.1002/14651858.CD012426.

BackgroundWhile PCSK9 inhibition has proven safe and effective, there is limited research on using intravascular ultrasound (IVUS) to assess the impact of atorvastatin combined with PCSK9 inhibitors on borderline coronary lesions.MethodsFrom June 2022 to June 2025, a detailed analysis of biochemical markers, coronary angiography (CAG), and IVUS was conducted on 69 patients with borderline coronary lesions after different treatments.ResultsOf the 69 patients enrolled, 60 completed the 48-week study. All groups showed significant low-density lipoprotein cholesterol (LDL-C) reductions, with Group C (Alirocumab + Atorvastatin) having the largest decrease from 3.64 to 1.48 (P < .001). At 48 weeks, arterial lumen volumes increased in all groups, but Group C's was significantly larger than Groups A (Alirocumab + placebo) and B (Atorvastatin + placebo) (P = .038). Group C also had a greater reduction in plaque volume compared to Groups A and B (P = .041).ConclusionAlirocumab and Atorvastatin together significantly lowered LDL-C levels and improved the vascular environment, notably reversing plaque in patients with borderline coronary lesions.

Background: Severe maternal hypertension is linked to adverse perinatal outcomes. Both nifedipine and hydralazine are commonly used antihypertensive agents in this setting. Methods: A comprehensive literature search was conducted in PubMed, Cochrane Library, and EMBASE from inception to April 2024 to identify randomized controlled trials comparing oral or sublingual nifedipine with intravenous hydralazine for the management of severe hypertension, with or without preeclampsia/eclampsia. A random-effects meta-analysis was performed using RevMan. Results: Seven randomized controlled trials were included. The pooled analysis demonstrated no significant difference between the two agents regarding time to achieve optimal blood pressure control (MD = -1.08 min, 95% CI = -6.66 to 4.49), caesarean delivery (OR = 0.62, 95% CI = 0.38 to 1.03), neonatal birth weight (MD = 57.65 g, 95% CI = -209.09 to -324.40), NICU admissions (OR = 0.90, 95% CI = 0.41 to 1.98), and 5-min APGAR scores (MD = 0.1, 95% CI = -0.20 to 0.39). However, patients receiving nifedipine had significantly lower odds of experiencing medication-related adverse events (OR = 0.62, 95% CI = 0.40 to 0.97). Conclusions: Nifedipine and intravenous hydralazine showed comparable efficacy in achieving optimal blood pressure control and similar maternal and neonatal outcomes. However, nifedipine was associated with significantly fewer maternal adverse effects, indicating superior tolerability.