The effect of topiramate on energy balance in obese men: a 6-month double-blind randomized placebo-controlled study with a 6-month open-label extension

Objective Topiramate (TPM) has been reported to reduce body weight beyond a placebo in the treatment of obese participants, but the effect of this agent on components of energy balance has not yet been established in humans. Thus, the aim of this study was to study the impact of TPM on food preferences, measures of satiety, food intake, resting metabolic rate (RMR), and 24-h energy expenditure. Methods The study design consisted of a 6-month, single-center, randomized, double-blind, parallel group, placebo-controlled trial with a 6-month open-label extension. The study included 68 sedentary men with abdominal obesity (waist circumference ≥100 cm), of between 25 and 55 years of age, with a dyslipidemic profile and a body mass index (BMI) ≥27 and ≤40 kg/m². Results Treatment with TPM produced significant changes in anthropometric variables and body composition compared with placebo. However, at the end of the 1-year study, the placebo/TPM group showed similar weight loss and reduction in body fatness compared with the TPM/TPM group. For instance, at the end of the 12-month intervention, mean percentage of body weight loss from baseline was about −5% in both groups (−4 kg fat loss). Topiramate treatment reduced energy intake, be it in the context of an ad libitum buffet-type meal or under free living conditions. The 24-h daily energy expenditure (DEE) assessed by whole-body indirect calorimetry adjusted for body weight and age was not altered by TPM treatment. Conclusion Topiramate treatment produced significantly greater weight loss than placebo and the majority of this loss was explained by a decrease in body fat stores. Most of the weight loss effect produced by TPM therapy was observed within a period of 6 months. Finally, TPM treatment had an impact on energy balance through a reduction in food intake that appears to have created an energy deficit of about 30,000–40,000 kcal compared with treatment with the placebo over 6 months.     

Hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis

Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma (HCC), but in non-alcoholic fatty liver disease (NAFLD), up to 50% of patients with HCC had no clinical or histological evidence of cirrhosis. It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis, and each patient should be evaluated on a case-by-case basis based on the profile of specific risk factors identified. For HCC screening in NAFLD, a valid precision-based screening is needed. Currently, when evaluating this population of patients, the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program. Hence, the objective of the present study is to review the epidemiology, the pathophysiology, the histopathological aspects, the current recommendations, and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.     

STAR procedure becomes SAFER: First-in-man case series of a new antegrade dissection re-entry technique

Introduction

Antegrade dissection and re-entry (ADR) is an integral part of the hybrid algorithm, which has allowed for improved outcomes in chronic total occlusion (CTO) coronary intervention (PCI).

Methods

A new ADR method, Subintimal Antegrade FEnestration and Re-entry (SAFER), is described. The results of a first-in-man series are presented.

Results

SAFER was performed on seven consecutive patients with angiographic and clinical success in all patients.

Conclusions

This first-in-man study has shown that the SAFER technique is feasible and effective with the possibility of improving the antegrade PCI CTO success rate.     

Higher accuracy of surgical over core needle biopsy for the diagnosis of lymphoproliferative disorders

Introduction

The diagnosis of lymphoproliferative disorders (LPDs) is based on histological evaluation of representative tissue samples. Despite surgical excision biopsies (SEBs) are reference procedures for such diagnoses, lymph node core needle biopsies (LNCBs) are increasingly performed. The diagnostic yield of LNCB is, however, debated and few studies have compared the reproducibility of LNCB and SEB findings.

Methods

To address the diagnostic value of LNCB and SEB, the present study considered a retrospective series of 43 paired LNCB/SEB samples. After histological revision, concordance rates between matched LNCB/SEB samples were evaluated, assuming SEB as gold standard procedure. The actionability of LNCB and SEB-based diagnoses (i.e., relevance for planning further medical interventions) was also assessed.

Results

Overall, LNCB provided actionable diagnoses in 39/43 (90.7%) cases, but a consistent subset of them (7/39 [17.9%]) turned out to be wrong at SEB. The cumulative diagnostic inaccuracy of LNCB (i.e., inadequate samples plus wrong diagnoses) was 25.6% and the mean diagnostic delay in such cases was 54.2 days.

Conclusions

Although limited by selection biases due to its retrospective nature, this study highlights the intrinsic limitations of LNCB for the diagnosis of LPDs. SEB remains the gold standard procedure and should be performed in all suitable cases.     

Biomarkers of mitochondrial dysfunction and inflammaging in older adults and blood pressure variability

GeroScience - Most physiopathological mechanisms underlying blood pressure variability (BPV) are implicated in aging. Vascular aging is associated with chronic low-grade inflammation occurring in...     

Assessing the impact of transcatheter aortic valve replacement on myocardial work indices and left ventricular diastolic function in aortic valve stenosis patients

Background

Aortic valve stenosis (AS) is the most common valvular heart disease worldwide. When timely intervention is performed, aortic valve replacement can improve patients' quality and duration of life. Load-independent left ventricular (LV) functional assessments, such as myocardial work indices (MWIs) and LV diastolic function parameters, could help clinicians decide on the optimal timing of intervention.

Aims

To evaluate the reliability of MWI in AS patients and the changes in MWI and LV diastolic function after transcatheter aortic valve replacement (TAVR).

Methods

We enrolled 53 consecutive patients with severe AS undergoing TAVR admitted between March 2021 and November 2021. MWIs and LV diastolic function were assessed before and after TAVR for each patient.

Results

All MWIs and LV diastolic function indices improved after TAVR. The degree of MWIs improvement was higher in patients with lower prior-TAVR MWI values, while the more severe the impairment of diastolic function, the greater the post-TAVR benefit.

Conclusion

The introduction of myocardial work parameters into the routine assessment of patients with AS could improve our understanding of cardiac performance and aid in identifying the optimal timing for surgical or percutaneous treatment.     

Dopamine Receptors in Parkinson's Disease: A Meta-Analysis of Imaging Studies

Dopamine receptors are abundant along the central nigrostriatal tract and are expressed as 5 subtypes in two receptor families. In PD, compensatory changes in dopamine receptors emerge as a consequence of the loss of dopamine nerve terminals or dopaminergic pharmacotherapy. We performed a systematic review and meta-analysis of the available PET and single-photon emission computed tomography studies that have investigated dopamine receptors in PD, PSP and MSA. The inclusion criteria were studies including human PET or single-photon emission computed tomography imaging; dopamine receptor tracers (D1-like or D2-like) and idiopathic PD, PSP, or MSA patients compared with healthy controls. The 67 included D2-like studies had 1925 patients. Data were insufficient for an analysis of D1-like studies. PD patients had higher striatal binding early in the disease, but after a disease duration of 4.36 years, PD patients had lower binding values than healthy controls. Striatal D2R binding was highest in unmedicated early PD patients and in the striatum contralateral to the predominant motor symptoms. PSP and MSA-P patients had lower striatal D2R binding than PD patients (14.2% and 21.8%, respectively). There is initial upregulation of striatal D2Rs in PD, which downregulate on average 4 years after motor symptom onset, possibly because of agonist-induced effects. The consistent upregulation of D2Rs in the PD striatum contralateral to the predominant motor symptoms indicates that receptor changes are driven by neurodegeneration and loss of striatal neuropil. Both PSP and MSA patients have clearly lower striatal D2R binding values than PD patients, which offers an opportunity for differential diagnostics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society