Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Purpose: This study identified factors predicting malignant upgrade for atypical ductal hyperplasia (ADH) diagnosed on core-needle biopsy (CNB) and developed a nomogram to facilitate evidence-based decision making. Methods: This retrospective analysis included women diagnosed with ADH at the National Cancer Centre Singapore (NCCS) in 2010–2015. Cox proportional hazards regression was used to identify clinical, radiological, and histological factors associated with malignant upgrade. A nomogram was constructed using variables with the strongest associations in multivariate analysis. Multivariable logistic regression coefficients were used to estimate the predicted probability of upgrade for each factor combination. Results: Between 2010 and 2015, 238,122 women underwent mammographic screening under the National Breast Cancer Screening Program. Among 29,564 women recalled, 5,971 CNBs were performed. Of these, 2,876 underwent CNBs at NCCS, with 88 patients (90 lesions) diagnosed with ADH and 26 lesions upgraded to breast malignancy on excision biopsy. In univariate analysis, factors associated with malignant upgrade were the presence of a mass on ultrasound (p = 0.018) or mammography (p = 0.026), microcalcifications (p = 0.047), diffuse microcalcification distribution (p = 0.034), mammographic parenchymal density (p = 0.008). and ≥ 3 separate ADH foci found on biopsy (p = 0.024). Mammographic parenchymal density (hazard ratio [HR], 0.04; 95% confidence interval [CI], 0.005–0.35; p = 0.014), presence of a mass on ultrasound (HR, 10.50; 95% CI, 9.21–25.2; p = 0.010), and number of ADH foci (HR, 1.877; 95% CI, 1.831–1.920; p = 0.002) remained significant in multivariate analysis and were included in the nomogram. Conclusion Our model provided good discrimination of breast cancer risk prediction (C-statistic of 0.81; 95% CI, 0.74–0.88) and selected for a subset of women at low risk (2.1%) of malignant upgrade, who may avoid surgical excision following a CNB diagnosis of ADH.

Kidney transplantation (KTP) lowers the mortality and morbidity of patients with end-stage renal disease. Post-transplantation infection and antibody mediated rejection (AMR) are the most common complications. Hepatitis B surface antigen (HBsAg) positive carrier donors and high anti A/B antibody titer ABO incompatible KTP could lead to recipient hepatitis B virus (HBV) infection and AMR. Here, we report a case of successful KTP in a 41-year-old male with a high titer of ABO incompatible and HBsAg positive donor. He underwent seven rounds of plasmapheresis, low dose intravenous immunoglobulin and rituximab treatment to inhibit antibody production and remove antibodies from the serum, after which he was administered anti-viral agent for HBV prophylaxis. The recipient maintained successful allograft function for 6 months after transplantation; therefore, we report that desensitization and anti-viral treatment achieved successful outcome in a 1:512 anti A/B antibody titer ABO incompatible and hepatitis B carrier donor KTP.
Adult ; Allografts ; Antibodies ; Antibody Formation ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; Humans ; Immunoglobulins ; Kidney Failure, Chronic ; Kidney Transplantation* ; Kidney* ; Male ; Mortality ; Plasmapheresis ; Rituximab ; Tissue Donors

Transplant renal artery stenosis (TRAS) is an important cause of hypertension, allograft dysfunction, and graft loss. Patient and allograft survival rates are lower in patients with TRAS. Causes of TRAS include acute rejection, cytomegalovirus infection, calcineurin inhibitor toxicity, atherosclerosis of recipient, and/or donor. Technical problems due to surgery are a common cause of early TRAS. A 62-year-old male in end stage renal disease received kidney transplant surgery. There was 5/6 mismatch of human leukocyte antigen and the panel reactive antibody of patient was class I 0% and class II 0%. End to side anastomosis was done between the graft's renal artery and the patient's common iliac artery. His serum creatinine was measured at 6.4 mg/dL before transplantation but his serum creatinine level did not fall below 2.6 mg/dL at 5 days postoperative. His blood pressures was 160/90~180/100 mmHg. There was a significant TRAS (about 80% luminal narrowing) at the arterial anastomosis site on the renal magnetic resonance angiography. We performed percutaneous transluminal angioplasty (PTA) for the stenotic lesion. The balloon angioplasty was done with a 5 mm balloon and low pressure (8 mmHg, nominal pressure was 10 mmHg) at the stenotic lesion. The arterial pressure gradient was 8 mmHg (recipient's common iliac arterial pressure, 147/73 mmHg; poststenotic segmental renal arterial pressure, 139/70 mmHg) just before the balloon angioplasty. After PTA, the arterial pressure gradient became 3 mmHg (recipient's common iliac arterial pressure, 157/66 mmHg; poststenotic segmental renal arterial pressure, 154/65 mmHg). The arterial size and blood flow recovered to within normal range and serum creatinine level was normal after PTA. PTA using low pressure and a small balloon was safe and effective modality in treating early TRAS.
Allografts ; Angioplasty ; Angioplasty, Balloon* ; Arterial Pressure ; Atherosclerosis ; Calcineurin ; Creatinine ; Cytomegalovirus Infections ; Humans ; Hypertension ; Iliac Artery ; Kidney ; Kidney Failure, Chronic ; Kidney Transplantation ; Leukocytes ; Magnetic Resonance Angiography ; Male ; Middle Aged ; Phenobarbital ; Reference Values ; Renal Artery Obstruction* ; Renal Artery* ; Survival Rate ; Tissue Donors ; Transplants

Thrombotic microangiopathy (TMA) is a serious complication of solid organ transplantation. Drug-induced TMA is typically caused by immunosuppressants, particularly calcineurin inhibitors. Withdrawing the causative drug can be one of the treatments for TMA. However, the more immunosuppressants are reduced, the more risk of rejection increases. Even if TMA is successfully resolved, the outcomes of patient and graft survival would be worse than expected. Therefore, it is necessary to maintain efficient and safe immunosuppression therapy. We report on a case of de novo TMA after kidney transplantation triggered by tacrolimus and reactivated by sirolimus. Belatacept, a novel CTLA4 Ig fusion protein, was administered for maintenance immunosuppressant with mycophenolate mofetil and prednisolon. The patient had excellent early graft outcome, and there have been no adverse events so far.
Abatacept ; Calcineurin ; Graft Survival ; Humans ; Immunosuppression* ; Immunosuppressive Agents ; Kidney Transplantation* ; Kidney* ; Organ Transplantation ; Sirolimus ; Tacrolimus ; Thrombotic Microangiopathies* ; Transplants

Transplant renal artery stenosis (TRAS) is a common surgical complication after kidney transplantation (KTP) and is the cause of allograft dysfunction. TRAS is a potentially curable cause of refractory hypertension and allograft dysfunction which accounts for approximately 1% to 5% of cases of post-transplant hypertension. Acute cellular rejection (ACR) is also common after KTP, which is the main cause of allograft dysfunction. Although the incidence of ACR has declined with the advent of new immunosuppressive drugs, it is still around 15% worldwide. Although each disease is frequently seen individually, seeing both together is rare. A 42-year-old man with end stage renal disease underwent KTP, and the donor was his younger brother. Four months after KTP, his serum creatinine was increased to 2.1 mg/dL, and renal biopsy showed interstitial lymphocytic infiltration and tubulitis. With the diagnosis of acute T-cell mediated rejection, steroid pulsing therapy was started, but it was resisted. Therefore thymoglobulin 60 mg (1 mg/kg/day) was administered for 6 days, but serum creatinine was 1.8 mg/dL. Abdomen magnetic resonance angiography showed TRAS, stenosis at the anastomosis site and lobar artery in the lower pole. Percutaneous transluminal angiography was performed successfully. After balloon angioplasty, the stenotic lesion showed a normal size and blood flow. The patient's renal function returned to normal levels and he is currently being followed up for 9 months.
Abdomen ; Adult ; Allografts ; Angiography ; Angioplasty, Balloon ; Arteries ; Biopsy ; Constriction, Pathologic ; Creatinine ; Diagnosis ; Humans ; Hypertension ; Incidence ; Kidney Failure, Chronic ; Kidney Transplantation ; Magnetic Resonance Angiography ; Renal Artery Obstruction* ; Renal Artery* ; Siblings ; T-Lymphocytes ; Tissue Donors ; Transplantation*