Obesity, often linked to high-fat (HF) diets and sedentary lifestyles, exacerbates metabolic syndrome and diabetes, significantly heightening risks for cerebrocardiovascular disease and cancer. Decreased plasma adiponectin (Ad) levels in obesity contribute to insulin resistance and diabetes. Importantly, J-DOIT3 showed that the average HDL cholesterol level was significantly higher in the intensive-therapy group compared to the conventional-therapy group, likely due to increased physical activity. This could independently protect against risk factors. Therefore, targeting AdipoRs emerged as a promising therapeutic strategy. Activation of AdipoRs, akin to caloric restriction and exercise, shows potential not only to alleviate non-communicable diseases but also to extend lifespan in HF diet-induced obesity.

Background: Osteoarthritis (OA) remains one of the leading causes of disability among adults worldwide, significantly limiting mobility and quality of life. Although pharmacological management offers temporary symptom relief, long-term efficacy remains suboptimal. Objective: This study aimed to evaluate the effectiveness of an intensive physical rehabilitation therapy program compared to conventional physiotherapy in improving knee joint function, reducing pain, and enhancing overall mobility among patients with knee OA. Methods: A randomized controlled trial was conducted among 180 adults (aged 40–75 years) diagnosed with moderate knee OA (Kellgren–Lawrence grades II–III). Participants were randomized into two groups: the Intensive Physical Rehabilitation Therapy (IPRT) group (n=90) received a structured 12-week intervention involving progressive resistance exercise, manual therapy, and proprioceptive training, while the Control group (n=90) received standard hospital-based physiotherapy. Primary outcomes were pain intensity (VAS) and joint function (WOMAC). Secondary outcomes included quadriceps strength, range of motion (ROM), and quality of life (SF-36). Statistical analysis used paired and independent t-tests with p<0.05 considered significant. Results: After 12 weeks, the IPRT group demonstrated a significant reduction in pain (mean ΔVAS = –3.6 ± 0.9 vs –1.8 ± 0.7; p<0.001), improved joint function (ΔWOMAC = –21.3 ± 5.8 vs –10.4 ± 4.1; p<0.001), and increased quadriceps strength (Δ = +4.2 ± 0.8 kg; p<0.01). Improvement in SF-36 physical function subscale was also greater in the IPRT group (p<0.05). No adverse events were reported. Conclusion: Intensive physical rehabilitation significantly enhances knee joint function and pain reduction compared to standard physiotherapy

BackgroundAcute myocardial infarction in the elderly often leads to significant left ventricular structural remodeling, which adversely affects prognosis. This study aims to evaluate the effects of intensive rosuvastatin therapy on markers of ventricular remodeling and cardiac function following percutaneous coronary intervention (PCI) in elderly patients with ST-segment elevation myocardial infarction (STEMI).MethodsThis study enrolled 100 patients aged ≥60 years with STEMI who underwent emergency PCI. The patients were randomly assigned to either an intensive therapy group (n = 50), receiving rosuvastatin 20 mg/day, or a control group (n = 50), receiving 10 mg/day. Differences in lipid profiles, serum inflammatory markers, fibrosis indicators, and echocardiographic parameters were compared between the two groups before treatment and after 8 weeks of therapy.ResultsAfter 8 weeks of treatment, the intensive group showed significantly reduced serum inflammatory levels compared to the control group, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) (P < 0.05). Markers of ventricular remodeling also improved in the intensive group, with lower levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3, and matrix metalloproteinase-9 (MMP-9) compared to the control group (P < 0.05), while levels of tissue inhibitor of metalloproteinases-4 (TIMP-4) were significantly higher (P < 0.05). Additionally, after treatment, the intensive group demonstrated significantly higher levels of left ventricular ejection fraction (LVEF), stroke volume, and peak systolic velocity at the lateral mitral annulus (TDI s′-l) compared to the control group (P < 0.05). Conversely, the left ventricular end-systolic diameter (LVESD) and left ventricular end-systolic volume (LVESV) were significantly lower in the intensive group than in the control group (P < 0.05).ConclusionIn elderly patients with STEMI, high-dose rosuvastatin demonstrates superior therapeutic efficacy compared to conventional-dose therapy in alleviating inflammatory responses, improving ventricular remodeling, and enhancing cardiac function.Clinical Trial Registration[www.chictr.org.cn], identifier [ChiCTR2200066956].

Background The optimal management of symptomatic vertebral artery in-stent restenosis or occlusion (SVISRO) after stent-assisted angioplasty (SAA) at the vertebral artery origin remains unclear. This study aimed to investigate the efficacy of vertebral artery reconstruction surgery (VRS) surgery among SVISRO patients. Methods A retrospective study was conducted to analyze the clinical data for SVISRO patients admitted to the Third Affiliated Hospital of Sun Yat-sen University between May 2011 and November 2021. The stroke recurrence and stroke-free rates during the follow-up (FU) period and the patients’ neurological statuses at the last FU were compared between a VRS group and an intensive medical therapy (IMT) group. Results Sixty-two SVISRO patients with an average age of 60.1 ± 8.3 years and an average FU duration of 67.6 ± 32.5 months were studied. The VRS group had significantly fewer stroke recurrences than the IMT group did (5.7% vs. 25.9%, p = 0.034). A 154-month stroke-free rate of 73.8% (95% CI, 24.5% to 93.7%) was observed in the VRS group, whereas the IMT group had a stroke-free rate of 33.9% (95% CI, 17.3% to 75.0%). The hazard ratio (log-rank) between the two groups was 0.234 (95% CI, 0.063–0.871; p = 0.048). The modified Rankin scale score for the VRS group was significantly better than that for the IMT group at the final FU (p = 0.032). Conclusions In patients with SVISRO secondary to SAA, VRS targeting the extracranial vertebral artery (V1-V2) appears to reduce stroke recurrence, increase the stroke-free rate and improve neurological status.

Recurrence of hypertriglyceridaemia-associated acute pancreatitis (HTG-AP) is common. Uncontrolled HTG after hospital discharge is an important risk factor for recurrence. However, the optimal triglyceride (TG) goal of lipid-lowering therapy for outpatients remains unclear. The efficacy and safety of intensive TG-lowering therapy on reducing recurrence of HTG-AP trial aims to determine whether intensive TG-lowering therapy (with a TG goal of <150 mg/dL (equal to 1.7 mmol/L)), compared with usual care (with a TG goal of <500 mg/dL (equal to 5.65 mmol/L)), can reduce recurrence in patients after a first episode of HTG-AP. This is an investigator-initiated, multicentre, open-label, parallel, superiority, randomised, controlled trial. Adult patients who have been successfully treated and discharged from their index episode of HTG-AP will be screened for eligibility after a 4-week to 3-month run-in period in the outpatient setting, and then patients with the fasting serum TG levels ≥150 mg/dL at baseline are eligible. During the study period, a total of 256 study participants will be randomised to receive either intensive TG-lowering therapy or usual care. In the intensive TG-lowering therapy group, the goal of TG levels is lower than 150 mg/dL, which will be monitored at 1 month, 3 months, 6 months, 12 months and 18 months after randomisation. In the usual care group, the goal of TG levels is lower than 500 mg/dL according to the current guidelines. Lifestyle suggestions and TG-lowering agents are the main strategies to manage the lipid level. The primary endpoint is the incidence of recurrent episodes of HTG-AP at 18 months after randomisation. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University (No. 2023101-3). Ethics approval of each participating centre is required before initiation of enrolment. The results of this study will be published in peer-reviewed journals and reported at international conferences. ChiCTR2300073483 (Chinese Clinical Trial Registry) PROTOCOL VERSION: V.4.0 (2024).

To determine the effectiveness of tyrosine kinase inhibitor (TKI) plus reduced-intensity therapy in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL), this retrospective study compared treatment outcomes and induction mortality according to backbone regimen intensity. The data of 132 patients diagnosed with Ph-positive ALL were retrospectively collected from five centers. Patients received imatinib plus intensive chemotherapy (modified VPD, KALLA1407, or hyper-CVAD) or reduced-intensity chemotherapy (EWALL) for curative purposes. This study analyzed 117 patients, of which 35,22,46, and 14 received modified VPD, KALLA1407, hyper-CVAD, and EWALL, respectively. All patients used imatinib as a TKI. The median age of the patients who received reduced-intensity chemotherapy was 64.4 years, while that of the patients with intensive regimens was 47.5 years. There was no induction death in the reduced-intensity group, while nine patients died in the intensive therapy group. Major molecular response achievement tended to be higher in the intensive chemotherapy group than in the reduced-intensity group. More patients in the intensive chemotherapy group received allogeneic stem cell transplantation (allo-SCT). There was no statistically significant difference in long-term survival between the two groups in terms of relapse-free survival and overall survival rates. When imatinib plus reduced-intensity therapy was used as a frontline treatment, there was no inferiority in obtaining complete remission compared to imatinib plus intensive chemotherapy or significant difference in long-term survival. Since imatinib plus reduced-intensity therapy has limitations in obtaining a deep molecular response, proceeding to allo-SCT should be considered.

This study aimed to investigate the efficacy of early intensive statin therapy following intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS). AIS patients who received IVT and statin therapy were included from multicenter registry databases. The primary endpoint was functional independence, defined by a modified Rankin Scale (mRS) score of 0-2 at 90 days. Propensity score matching (PSM) analyses were employed. A total of 21,349 patients were included in this study, with a mean age of 68.5 ± 12.6 years, of whom 13,578 (63.6%) were male. The baseline NIHSS score was 4 (IQR 2-8). A total of 9532 patients (44.6%) received intensive statin therapy. In the PSM analysis, the proportion of patients with mRS scores of 0-2 was significantly higher in the intensive statin therapy group (OR = 1.095, 95% CI 1.022-1.173, p = 0.010). Statin type modified the effect of intensive statin therapy on functional independence (p-value for interaction = 0.030). Treatment effects favoring the intensive approach were observed in patients receiving atorvastatin (OR = 1.134, 95% CI 1.051-1.224, p = 0.001). Early intensive statin therapy following IVT leads to a significant but modest improvement in neurological outcomes, particularly in patients treated with atorvastatin as part of the intensive regimen.

Introduction. Blood pressure optimization during and after reperfusion in patients with acute ischemic stroke can reduce the risk of hemorrhagic complications and improve functional recovery. Several randomized controlled trials of different target blood pressure values have been published with varying results.The objective was to evaluate the effect of intensive hypotensive therapy in the first day after intravenous thrombolysis on outcomes of acute ischemic stroke and incidence of complications.Materials and methods. A single-center open label randomized controlled trial was conducted. Patients older than 18 years with acute ischemic stroke who underwent reperfusion were included. Patients were randomized into 2 groups: with a target systolic blood pressure of 161–185 mm Hg on the first day (control group) versus &lt; 160 mm Hg (intensive hypotensive therapy group). The primary end points were mortality and modified Rankin Scale score at day 90 from the onset of stroke.Results. The final analysis included 69 patients. In the intensive hypotensive therapy group, mortality rate did not differ from the control group: OR 1.1 [95% CI 0.3 to 4.8] (p = 0.896). The median modified Rankin scale score at day 90 in the control group was 2 (1; 3.8) versus 2 (1; 3.5) in the intensive hypotensive therapy group (p = 0.812).Conclusion. Intensive hypotensive therapy at the first day after intravenous thrombolysis in acute ischemic stroke patients with target values of systolic blood pressure &lt; 160 mm Hg compared to conventional values of 161–185 mm Hg neither improved functional outcome nor decreased mortality and complications rate on day 90 from the onset of stroke.

Patient Characteristics and Treatment Outcomes of TP53 Mutated Myeloid Neoplasms : A Single Cancer Center Experience from the MENA Region

TP53 mutations (TP53m) define the most treatment-refractory acute myeloid leukemia (AML) subtype. Optimal treatment approaches have not been established in this setting. We reviewed our institutional experience to identify therapy sequencing, treatment response, and survival patterns in these patients. This study was a single-center, retrospective cohort analysis. Our cohort includes 86 TP53m and 337 TP53 wild-type (TP53wt) adult AML patients. TP53m AML patients presented with lower bone marrow and peripheral blasts; none presented with hyperleukocytosis. Patients who received intensive treatment up front demonstrated superior overall survival (OS) over those receiving first-line non-intensive therapy (2-year OS 22% versus 7%; p = 0.02). However, the complete remission (CR) rates among the first-line intensive and non-intensive therapy groups were comparable (21.9% and 29.4%, respectively, p = 0.49). The improved OS is therefore attributed to superior cumulative CR in the intensive group. First-line intensively treated patients were more likely to receive and respond to salvage, leading to a cumulative CR rate of 65.7% (versus 29.4%, p = 0.003). Achieving CR at any point is strongly associated with superior survival outcomes with 2-year OS of 31% versus 0% for those not achieving CR ever (p < 0.01). We find that TP53m AML rarely presents with oncological emergencies, suggesting that clinical trial enrollment is feasible in this group. Additionally, in our cohort, intensive induction therapies lead to superior survival outcomes attributed to successful salvage therapy. These data suggest that strategic therapy sequencing and salvage therapy may be important in optimizing outcomes for TP53m AML patients.

BackgroundWe investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients.MethodsThis was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0 mg/dL and < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL and < 7.0 mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment.ResultsThree hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23 mg/dL at baseline and 6.13 mg/dL at 52 weeks. In the Intensive therapy group, mean serum UA was 8.15 mg/dL at baseline and 5.25 mg/dL at 52 weeks. There was no significant difference in changes in log ACR at 52 weeks between the Intensive therapy and the Standard therapy groups.ConclusionThis study did not reveal the benefit of Intensive ULT to improve albuminuria levels.(UMIN000026741 and jRCTs051180146).

Background: Stroke is a leading cause of disability worldwide, often resulting in spasticity that significantly impairs the functional recovery of individuals. The comparative efficacy of intensive physical therapy and electrical stimulation in mitigating post-stroke spasticity remains a critical area of research. Understanding the impacts of these treatments can guide clinicians in optimizing rehabilitation strategies for stroke survivors. Objective: The study aimed to compare the effectiveness of intensive physical therapy and electrical stimulation in reducing spasticity among stroke patients, with an emphasis on how these interventions influence muscle tone and functional outcomes. Methods: This quasi-experimental trial was conducted at Nishtar Hospital, Multan, over six months, involving 30 participants aged 50-65 years who had experienced a stroke. Participants were randomly assigned to receive either intensive physical therapy or electrical stimulation. Baseline and post-treatment assessments of spasticity were conducted using the Modified Ashworth Scale (MAS). Data were analyzed using SPSS version 25, focusing on changes in MAS scores before and after the interventions. Results: Both interventions showed significant improvements in spasticity levels. The intensive physical therapy group exhibited notable reductions in MAS scores across various joints: shoulder flexors (from 3.13 ± 0.51 to 1.20 ± 0.41), shoulder extensors (from 3.00 ± 0.65 to 1.20 ± 0.67), and hip abduction (from 3.00 ± 0.65 to 1.33 ± 0.72). The electrical stimulation group also demonstrated significant improvements, with MAS scores in wrist flexion (from 2.73 ± 0.70 to 1.33 ± 0.61) and hip extension (from 2.80 ± 0.67 to 1.26 ± 0.45) showing notable reductions. However, no statistically significant differences were observed between the two groups in terms of overall effectiveness in reducing spasticity (p &gt; 0.05). Conclusion: Both intensive physical therapy and electrical stimulation are effective in reducing post-stroke spasticity, with no significant difference in their overall efficacy. This suggests that either treatment can be considered as part of a comprehensive rehabilitation strategy for stroke survivors, depending on individual patient needs, preferences, and specific functional goals.

Effects of intensive blood pressure control on left ventricular hypertrophy in aortic valve disease

Cumulative HbA1c exposure as a CVD risk in patients with type 2 diabetes: A post hoc analysis of ACCORD trial

As many people with type 1 diabetes find it hard to reach the recommended glycemic goals, even with CGM, this study aims to determine if a closer, digitally supported collaboration on interpreting CGM data together with a diabetes nurse can improve glycemic control. A total of 120 individuals, 18 years and older and with HbA1c ≥ 58 mmol/mol will be included in the study at 8 different sites in Sweden and Norway. To be included, the participants must use a CGM or isCGM and be able to upload the data to the appropriate online service for their clinic and sensor. Both those with insulin pumps and insulin pens will be included in the study. Participants will be randomized into two different groups, that is, the intensive therapy group and the control group. The intensive therapy group will upload their glucose data weekly for the first 4 months and have telephone contact with their diabetes care team to receive support in interpreting CGM data and taking appropriate actions if their mean blood glucose level is above 8.4 mmol/L. After the 4-month-long intensive treatment phase, both randomized groups will have the same number of clinical visits and receive the same type of diabetes support. It is of great importance to find new ways to help people with type 1 diabetes manage their condition as well as they can to help them achieve better glycemic control so that hopefully more people can achieve the recommended glycemic goals, which are associated with fewer diabetes complications. If it is shown that people with type 1 diabetes achieve better glycemic control with intensive therapy, then this can be incorporated into clinical praxis as an option for those not currently reaching the recommended glycemic goals. https://clinicaltrials.gov/study/NCT03474393?locStr=Uddevalla,%20Sweden&country=Sweden&distance=50&cond=Diabetes&aggFilters=ages:adult%20older&state=V%C3%A4stra%20G%C3%B6taland%20County&city=Uddevalla&page=4&rank=34, identifier 03474393.

This study compared the outcomes between intensive and nonintensive insulin regimens and assessed the predictive factors for failing to achieve the glycated hemoglobin (A1C) goals in type-2-diabetes-mellitus (T2DM) patients requiring insulin therapy. A single-center, retrospective assessment of the medical records of 125 T2DM patients undergoing intensive (46 patients) and nonintensive insulin therapy (79 patients) were conducted. No significant differences were found when the intensive and nonintensive insulin therapy groups were compared in terms of the percentage decreases of glucose and A1C levels. The mean A1C levels of the nonintensive and intensive groups declined from 11.15% and 11.30% to 7.97% and 8.06%, respectively. Both intensive and nonintensive insulin therapies improved the baseline glycemic parameters but being overweight or obese and/or being reluctant to dietary recommendations led to treatment failures regardless of the insulin regimen.

Aims: Physicians determine the treatment regimen for metastatic colorectal cancer on a case-by-case bases, according to the individual disease characteristics. We retrospectively compared the baseline characteristics and efficacies of first-line treatment among patients with metastatic colorectal cancer who received intensive therapy involving fluoropyrimidine plus oxaliplatin and/or irinotecan, potentially with molecularly targeted agents as well, versus less intensive fluoropyrimidine and/or bevacizumab therapy. Materials & methods: Data were collected from a medical claims database. The efficacy outcomes were: time to treatment failure, time to first subsequent therapy and overall survival. Results: The less intensive therapy group (n=633) had higher median age, lower daily activity levels and shorter time to treatment failure, time to first subsequent therapy and overall survival than the intensive therapy group (n=3829). Combination therapy with molecularly targeted agents and bevacizumab improved treatment efficacy outcomes in the intensive and less intensive groups, respectively. Conclusion: Patient age and daily activity levels were important factors for determining treatment intensity.

Objective: The equivocal benefit of intensive blood pressure lowering in patients with diabetes may be partially due to the neglected residual cardiovascular risk. However, it remains uncertain whether residual cholesterol (RC) level affect the benefit of intensive blood pressure lowering in patients with diabetes. We aimed to determine whether the treatment difference of intensive versus standard blood pressure therapy on risk of cardiovascular events (CVD) in the ACCORD-BP trial depended on baseline RC level. Design and method: Participants in the ACCORD-BP trail were divided into two groups based on baseline RC levels (low RC: &lt; 31 mg/dL and high RC: 31mg/dL and higher). We report the primary outcomes identical to those used in the original ACCORD trial, which included nonfatal myocardial infarction, nonfatal stroke, and/or incident cardiovascular death. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) estimated from stratified Cox regression models were used to quantify the association between intensive therapy and incident CVD for the 2 different baseline RC groups. Results: The incident rate was significantly lower in the intensive-therapy group as compared with standard-therapy group in the low RC group (log-rank P = 0.029) but not in the high RC group (log-rank P = 0.74). Compared with standard therapy, intensive therapy was associated with a lower risk of incident CVD among participants with low RC (aHR: 0.71; 95% CI: 0.53 to 0.94), but not among participants with high RC (aHR: 1.04; 95% CI: 0.80 to 1.35). The same pattern was observed for nonfatal stroke (aHR [95% CI] in participants with low RC: 0.48 [0.25-0.93]; aHR [95% CI] in participants with high RC: 0.76 [0.41-1.41]). Subgroup analyses revealed that the protective effect of intensive therapy against CVD events among the low RC group was not influenced by sex, previous CVD at baseline, assignment to intensive glycemic control, systolic or diastolic blood pressure at baseline, and baseline low-density lipoprotein cholesterol levels. Conclusions: Intensive blood pressure lowering therapy was effective at preventing incident CVD events in the ACCORD-BP trial participants with low baseline RC level but not in those with high RC level.

The influence of exercise training versus intensive insulin therapy on insulin resistance development in type 1 diabetes

BackgroundWe examined the retinal microvascular changes and associated factors in type 2 diabetes mellitus (T2DM) before and after intensive insulin therapy.MethodsThis prospective observational study recruited patients with T2DM and divided them into intensive insulin therapy and oral hypoglycemic agent groups. All patients enrolled in this study had diabetes without retinopathy or non-proliferative diabetic retinopathy. Optical coherence tomography angiography (OCTA) was used in all patients before treatment and at 1, 3, and 6 months after treatment. Vessel density (VD) and thickness changes in the macular and optic disc areas were assessed.ResultsThe study included 36 eyes in the intensive insulin therapy group and 36 in the oral hypoglycemic agent group. One month after treatment, VD in the deep capillary plexus (DCP) and peripapillary capillary VD (ppVD) were significantly decreased by intensification (P = 0.009, 0.000). At three months after treatment, decreases in VD induced by intensification were found in the superficial capillary plexus (SCP), DCP, foveal density in a 300-μm-wide region around the foveal avascular area (FD-300), and ppVD (P = 0.032, 0.000, 0.039, 0.000). Six months after treatment, decreases in VD by intensification were observed in the DCP and ppVD groups (P = 0.000, 0.000). Vessel density showed no significant change in the oral hypoglycemic agent group after treatment. The amount of DCP-VD reduction was correlated with macular thickening (r = 0.348, P = 0.038; r = 0.693, P = 0.000 and r = 0.417, P = 0.011, respectively) after intensive insulin therapy.ConclusionsInsulin-intensive treatment caused a transient reduction in vessel density in the macular and optic disc areas. DCP-VD and ppVD were more susceptible at an earlier stage. Retinal microvasculature monitoring using OCTA is vital for patients with type 2 diabetes receiving intensive insulin therapy.