Identification of Inflamed Atherosclerotic Lesions In Vivo Using PET-CT

Inflammation plays a major pathogenetic role in the development of atherosclerotic plaques and related thromboembolic events. The identification of vulnerable plaques is of the utmost importance, as this may allow the implementation of more effective preventive and therapeutic interventions. Fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be useful for tracing inflammation within plaques. However, its relationship to immunohistochemical findings in different territories of the peripheral circulation was not completely elucidated. We aimed to determine whether plaque inflammation could be measured by PET in combination with computer tomography (CT) using FDG and what is the relationship between FDG uptake and immunohistochemical findings in the removed atherosclerotic lesions of the femoral and carotid arteries. The study included 31 patients, 21 patients with high-grade stenosis of the internal carotid artery (ICA) and 10 patients with occlusion of the common femoral artery (CFA), all of whom underwent endarterectomy. Before endarterectomy in all patients, FDG-PET/CT imaging was performed. FDG uptake was measured as the maximum blood—normalized standardized uptake value, known as the target to background ratio (TBR max). TBR max amounted to 1.72?±?0.8, and in patients with ICA, stenosis was not significantly different from patients with CFA occlusion. Immunohistochemical and morphometric analyses of the plaques obtained at endarterectomy showed that the density of T lymphocytes and macrophages (number of cells per square millimeter) was significantly higher in subjects with stenosis of the ICA than in subjects with occlusion of the femoral arteries: lymphocytes, 1.26?±?0.21 vs. 0.77?±?0.29; p?=?0.02 and macrophages, 1.01?±?0.18 vs. 0.69?±?0.23; p?=?0.003. In the whole group of patients, the density of inflammatory cells significantly correlated with FDG uptake represented by PET-TBR max: T lymphocytes, r?=?0.60; p?<?0.01 and macrophages, r?=?0.65; p?<?0.01. The results of our study show that FDG uptake is related to the accumulation of inflammatory cells in atherosclerotic lesions. This finding suggests that FDG uptake reflects the severity of atherosclerotic vessel wall inflammation, and in stenotic lesions, it could be an indicator of their vulnerability. However, data from large outcome studies is needed to estimate the usefulness of this technique in identifying the most dangerous atherosclerotic lesions and vulnerable patients.     

Genetic Characterization of Circulating African Swine Fever Viruses in Nigeria (2007–2015)

Sequencing and analysis of three discrete genome regions of African swine fever viruses (ASFV) from archival samples collected in 2007–2011 and active and passive surveillance between 2012 and 2015 in Nigeria were carried out. Analysis was conducted by genotyping of three single‐copy African swine fever (ASF) genes. The E183L and B646L genes that encode structural proteins p54 and p72, respectively, were utilized to delineate genotypes before intragenotypic resolution by characterization of the tetrameric amino acid repeat region within the hypervariable central variable region of the B602L gene. The results showed no variation in the p72 and p54 gene regions sequenced. Phylogeny of p72 sequences revealed that all the Nigerian isolates belonged to genotype I, while that of the p54 recovered the Ia genotype. Analysis of B602L gene revealed the differences in the number of tetrameric repeats. Four new variants (Tet‐15, Tet‐17a, Tet‐17b and Tet‐48) were recovered, while a fifth variant (Tet‐20) was the most widely distributed in the country displacing Tet‐36 reported previously in 2003–2006. The viruses responsible for ASF outbreaks in Nigeria are from very closely related but mutated variants of the virus that have been circulating since 1997. A practical implication of the genetic variability of the Nigerian viral isolates in this study is the need for continuous sampling and analysis of circulating viruses, which will provide epidemiological information on the evolution of ASFV in the field versus new incursion for informed strategic control of the disease in the country.     

Increase in radiosensitivity of lung micrometastases by hyperbaric oxygen

Four-day-old artificial pulmonary micrometastases of two murine fibrosarcomas, designated FSA and NFSA, showed increased sensitivity to ionizing radiation by a factor of 1·13 when animals were exposed to hyperbaric oxygen breathing before and during irradiation, implying the presence of hypoxia in the micrometastases. At the time of irradiation the diameter of FSA and NFSA metastases was smaller than 200 and 100m, respectively, which, on the basis of oxygen diffusion, could not be responsible for hypoxia. It is assumed that hypoxia of micrometastases is passive, reflecting the radiobiological hypoxia of lung tissue that could exist under normal breathing conditions.     

Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity

The B cell-depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal IgM memory B cell expansions before and after therapy, by persistence of clonal expansions despite efficient peripheral B cell depletion, and by a lack of substantial changes in somatic hypermutation frequencies of IgM memory B cells. We infer from these data that the effectiveness of rituximab therapy depends on efficient depletion of noncirculating B cells and is associated with qualitative immunological changes that indicate reconfiguration of B cell memory through sustained reduction of autoreactive clonal expansions. These findings support the continued development of B cell-depleting therapies for autoimmune diseases.     

Comparison of survival between diabetic and non-diabetic patients on maintenance hemodialysis: a single-centre experience

We analyzed survival rates of 144 prevalent patients on maintenance hemodialysis from 1998 to 2003 at the Department of Nephrology and Dialysis, Rijeka University Hospital, Rijeka, Croatia, and evaluated risk factors predicting their survival. Included were only end-stage renal disease (ESRD) patients on maintenance hemodialysis treatment dialysed more than 6 months before entering the study and who were clinically stable. The patients were randomised in two groups according to the presence or absence of diabetic nephropathy as the cause of ESRD and followed-up. The patient's death as outcome measure was recorded. The survival rates were estimated by the Kaplan-Meier method. The major causes of death were cardiovascular disease in 40 (60.6%) patients. An acute myocardial infarction in 15 (22.7%) patients was the major single cause of death. We found a significantly lower survival of diabetic patients than non-diabetic patients (P=0.0013). The most important predictors of death among diabetic patients on maintenance hemodialysis were hyperglycaemia (P<0.001), ischemic heart disease (P=0.004), hypercholesterolemia (P=0.013), and low delivered dialysis dose (P=0.013). The survival of diabetic patients undergoing hemodialysis was much worse than survival of non-diabetic patients. The cardiovascular disease remained the major cause of death in both groups. Early detection of pre-existing cardiovascular risk factors and diseases, and treatment of infections leading to sepsis, are of great importance, as they may influence the survival rates. Intensive management of diabetic patients is essential.     

Late life depression: challenge or curse for the general practitioner (GP). A cohort study

The aim of this study was to examine specificity of GP's care for elderly depressed patients. Among 17,000 examinees (10 GP-Offices) were extracted 231 patients with diagnosis of depressive episode (F32) and 152 with diagnosis of recurrent depressive disorder (F33) classified according to ICD-10. Older than 65 years were 134 depressed patients. Data were tracked longitudinally and obtained retrospectively for a 1-year period from 1st January to 31st December 2008. Questionnaire was designed for this study to estimate the care delivered to depressed patients. Logistic regression analysis showed that GP more often diagnosed depression in older patients, provided medical care for them and changed their therapy. The main therapy for up to 80% of elderly with diagnosis of recurrent depressive disorder was combination of pharmacotherapy and GP's support and psychiatrist psychotherapy, while more than 20% of elderly with diagnosis of depressive episode took only pharmacotherapy. In comparison with younger age group, elderly less frequently received psychotherapy and GP's support. GP has an important role in older depressed patient care, so improvement efforts could focus on GP's clinical skills of depression treatment, as well as therapy effectiveness and depression outcome for understanding treatment specificity within elderly.     

Semaglutide delays 4-hour gastric emptying in women with polycystic ovary syndrome and obesity

Aim

To evaluate the effect of once-weekly subcutaneous semaglutide 1.0 mg on the late digestive period of gastric emptying (GE) after ingestion of a standardized solid test meal by using technetium scintigraphy, the reference method for this purpose.

Methods

We conducted a single-blind, placebo-controlled trial in 20 obese women with polycystic ovary syndrome (PCOS; mean [range] age 35 [32.3-40.8] years, body mass index 37 [30.7-39.8] kg/m²) randomized to subcutaneous semaglutide 1.0 mg once weekly or placebo for 12 weeks. GE was assessed after ingestion of [^99mTc] colloid in a pancake labelled with radiopharmaceutical by scintigraphy using sequential static imaging and dynamic acquisition at baseline and at Week 13. Estimation of GE was obtained by repeated imaging of remaining [^99mTc] activity at fixed time intervals over the course of 4 hours after ingestion.

Results

From baseline to the study end, semaglutide increased the estimated retention of gastric contents by 3.5% at 1 hour, 25.5% at 2 hours, 38.0% at 3 hours and 30.0% at 4 hours after ingestion of the radioactively labelled solid meal. Four hours after ingestion, semaglutide retained 37% of solid meal in the stomach compared to no gastric retention in the placebo group (P = 0.002). Time taken for half the radiolabelled meal to empty from the stomach was significantly longer in the semaglutide group than the placebo group (171 vs. 118 min; P < 0.001).

Conclusion

Semaglutide markedly delayed 4-hour GE in women with PCOS and obesity.