Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials.

AIMS/HYPOTHESIS: We conducted a systematic review and network meta-analysis to compare the efficacy and safety of s.c. administered tirzepatide vs s.c. administered semaglutide for adults of both sexes with type 2 diabetes mellitus. METHODS: We searched PubMed and Cochrane up to 11 November 2023 for RCTs with an intervention duration of at least 12 weeks assessing s.c. tirzepatide at maintenance doses of 5 mg, 10 mg or 15 mg once weekly, or s.c. semaglutide at maintenance doses of 0.5 mg, 1.0 mg or 2.0 mg once weekly, in adults with type 2 diabetes, regardless of background glucose-lowering treatment. Eligible trials compared any of the specified doses of tirzepatide and semaglutide against each other, placebo or other glucose-lowering drugs. Primary outcomes were changes in HbA1c and body weight from baseline. Secondary outcomes were achievement of HbA1c target of ≤48 mmol/mol (≤6.5%) or <53 mmol/mol (<7.0%), body weight loss of at least 10%, and safety outcomes including gastrointestinal adverse events and severe hypoglycaemia. We used version 2 of the Cochrane risk-of-bias tool (ROB 2) to assess the risk of bias, conducted frequentist random-effects network meta-analyses and evaluated confidence in effect estimates utilising the Confidence In Network Meta-Analysis (CINeMA) framework. RESULTS: A total of 28 trials with 23,622 participants (44.2% female) were included. Compared with placebo, tirzepatide 15 mg was the most efficacious treatment in reducing HbA1c (mean difference -21.61 mmol/mol [-1.96%]) followed by tirzepatide 10 mg (-20.19 mmol/mol [-1.84%]), semaglutide 2.0 mg (-17.74 mmol/mol [-1.59%]), tirzepatide 5 mg (-17.60 mmol/mol [-1.60%]), semaglutide 1.0 mg (-15.25 mmol/mol [-1.39%]) and semaglutide 0.5 mg (-12.00 mmol/mol [-1.09%]). In between-drug comparisons, all tirzepatide doses were comparable with semaglutide 2.0 mg and superior to semaglutide 1.0 mg and 0.5 mg. Compared with placebo, tirzepatide was more efficacious than semaglutide for reducing body weight, with reductions ranging from 9.57 kg (tirzepatide 15 mg) to 5.27 kg (tirzepatide 5 mg). Semaglutide had a less pronounced effect, with reductions ranging from 4.97 kg (semaglutide 2.0 mg) to 2.52 kg (semaglutide 0.5 mg). In between-drug comparisons, tirzepatide 15 mg, 10 mg and 5 mg demonstrated greater efficacy than semaglutide 2.0 mg, 1.0 mg and 0.5 mg, respectively. Both drugs increased incidence of gastrointestinal adverse events compared with placebo, while neither tirzepatide nor semaglutide increased the risk of serious adverse events or severe hypoglycaemia. CONCLUSIONS/INTERPRETATION: Our data show that s.c. tirzepatide had a more pronounced effect on HbA1c and weight reduction compared with s.c. semaglutide in people with type 2 diabetes. Both drugs, particularly higher doses of tirzepatide, increased gastrointestinal adverse events. REGISTRATION: PROSPERO registration no. CRD42022382594.

Assessment of Atherosclerosis in Ischemic Stroke by means of Ultrasound of Extracranial/Intracranial Circulation and Serum, Urine, and Tissue Biomarkers.

It is a common practice to take into consideration age, diabetes, smoking, treated and untreated systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol for the prediction of atherosclerosis and stroke. There are, however, ultrasound markers in use for the assessment of atherosclerosis and the evaluation of stroke risk. Two areas of investigation are of interest: the carotid artery and the intracranial arterial circulation. Again, within the domain of the carotid artery, two ultrasonic markers have attracted our attention: intima media thickness of the carotid artery and the presence of carotid plaque with its various focal characteristics. In the domain of intracranial circulation, the presence of arterial stenosis and the recruitment of collaterals are considered significant ultrasonic markers for the above-mentioned purpose. On the other hand, a series of serum, urine, and tissue biomarkers are found to be related to atherosclerotic disease. Future studies might address the issue of whether the addition of proven ultrasonic carotid indices to the aforementioned serum, urine, and tissue biomarkers could provide the vascular specialist with a better assessment of the atherosclerotic load and solidify their position as surrogate markers for the evaluation of atherosclerosis and stroke risk.

Stroke Units Necessity for Patients, Web-Based "SUN4P" Registry: Descriptive Characteristics of the Population.

The aim of this study was to present the descriptive characteristics of the Stroke Units Necessity for Patients (SUN4P) registry. METHODS: The study population derived from the web-based SUN4P registry included 823 patients with first-ever acute stroke. Descriptive statistics were used to present patients' characteristics. RESULTS: The vast majority of patients (80.4%) had an ischemic stroke, whereas 15.4% had a hemorrhagic stroke. Hypertension was the leading risk factor in both patients. The patients with ischemic stroke had higher prevalence of traditional cardiovascular risk factors such as diabetes mellitus, dyslipidemia and smoking and most commonly cryptogenic stroke (39%). National Institutes of Health Stroke Scale (NIHSS) was higher among patients with hemorrhagic in comparison to those with ischemic stroke (10.5 vs 6 respectively). Moreover, all patients had similar rate of disability prior to stroke, as shown by Modified Rankin Scale (mRS=0). CONCLUSIONS: These data are in accordance with current evidence and should be thoroughly assessed in order to ensure optimal therapeutic management of stroke patients.

Riedel's lobe of the liver: a case report.

Riedel lobe of the liver is a simple anatomical variation, a downward tongue-like projection of the anterior edge of the right lobe of the liver to the right of the gallbladder with its typical case to be rare.We report the case of a 71-year-old woman with typical feature of a nonpalpable Riedel's lobe of the liver, as an incidental finding who was referred for reported hypergammaglobulinemia (22.7% [9%-19%]). Both features were attributed to a chronic inflammation because of an abscess in the right iliopsoas caused by infection due to bilateral hip replacement which underwent revision surgery. This was confirmed by her medical history, the imaging findings combined with elevated C-reactive protein, and by cross-reaction weak positive autoantibodies.Generally, knowledge or suspicion of Riedel's lobe of the liver is important, as it does not always remain clinically latent, as in our case, and it can be complicated by its torsion or hepatic tumors.

Initially lymphocytic Sweet's syndrome in male patients with myelodysplasia: a distinguished clinicopathological entity? Case report and systematic review of the literature.

BACKGROUND: Sweet's syndrome (SS) is an acute febrile neutrophilic dermatosis. It can occur as an idiopathic, drug-induced or malignancy-associated entity. SS is also seen in patients with myelodysplastic syndrome (MDS) where it may present atypically, both clinically and histologically. In a few rare cases of MDS, lymphocytic infiltrates are the presenting feature of SS. METHODS: MEDLINE and Scopus were the data sources for our review. RESULTS: A clinicopathological subsetemerged of 12 male SS patients with MDS and a mean age of 67.3 years in which the initial SS lesions were lymphocytic infiltrates. However, from 0.5 to 8 years later, sequential biopsies revealed neutrophilic dermal infiltration typical of SS. CONCLUSION: Initially lymphocytic infiltrates in this subset could be attributed either to an early timing of the biopsy concerning the age of the lesion or to the dysgranulopoiesis syndrome. A possible relationship between the dysfunction of the receptor of the granulocyte-macrophage colony stimulating factor, the gene of which is located on the pseudoautosomal X-Y region, may exist in MDS patients with initially lymphocytic SS. This could explain the male gender of this subset and might establish initially lymphocytic SS as a distinguished clinicopathological entity for predicting the occurrence and even the prognosis of MDS.

The prognostic efficacy of myocardial perfusion imaging in optimally treated diabetic patients with no manifestations of coronary artery disease.

OBJECTIVE: This study investigates the efficacy of radionuclide myocardial perfusion imaging (MPI) in the evaluation of cardiac outcome in optimally treated diabetic patients without manifestations of coronary artery disease (CAD) in relation to the inherent clinical risk. METHODS: Follow-up data were collected from 86 diabetic patients who had undergone adenosine stressing MPI. These patients either had no symptoms or had noncardiac chest discomfort, had a normal resting electrocardiogram, had no known CAD or prior positive stress test results, and were receiving currently recommended therapy. Endpoints were cardiac death, myocardial infarction, new-onset heart failure, and CAD diagnosed by angiography at least 2 months from the MPI, irrespective of subsequent revascularization. RESULTS: Twenty-six (30%) diabetic patients had abnormal perfusion and the remaining had a normal scan. Over a median follow-up period of 32.5 months 14 cardiac events occurred. In patients with normal MPI, the annual cardiac event rate was 4.0% compared with 12.2% in those with abnormal MPI (P=0.008). In multivariate analysis, myocardial ischemia (hazard ratio 5.3; P=0.006), obesity (hazard ratio 6.8; P=0.005), the ALFEDIAM/SFC risk (hazard ratio 6.8; P=0.002), and type 2 diabetes (hazard ratio 5.3; P=0.035) were found to be independent predictors of cardiac events. The former two variables remained independent determinants of the outcome, together with peripheral arterial disease, when a different clinical risk classification system was applied. MPI provided incremental prognostic information over both clinical models formed. CONCLUSION: Adenosine MPI can effectively risk-stratify optimally treated diabetic patients without manifestations of CAD. In this subset, clinical variables can also determine the outcome independently, but MPI adds incremental predictability over them.