Graft flow assessment and early coronary artery bypass graft failure: a computed tomography analysis

Open in a separate window OBJECTIVESWe evaluated graft patency by computed tomography and explored the determinants of intraoperative mean graft flow (MGF) and its contribution to predict early graft occlusion.METHODSOne hundred and forty-eight patients under a single surgeon were prospectively enrolled. Arterial and endoscopically harvested venous conduits were used. Intraoperative graft characteristics and flows were collected. Graft patency was blindly evaluated by a follow-up computed tomography at 11.4 weeks (median).RESULTSGraft occlusion rate was 5.2% (n = 22 of 422; 8% venous and 3% arterial). Thirteen were performed on non-significant proximal stenosis while 9 on occluded or >70% stenosed arteries. Arterial and venous graft MGF were lower in females (P_arterial = 0.010, P_venous = 0.009), with median differences of 10 and 13.5 ml/min, respectively. Arterial and venous MGF were associated positively with target vessel diameter ≥1.75 mm (P_arterial = 0.025; P_venous = 0.002) and negatively with pulsatility index (P_arterial < 0.001; P_venous < 0.001). MGF was an independent predictor of graft occlusion, adjusting for EuroSCORE-II, pulsatility index, graft size and graft type (arterial/venous). An MGF cut-off of 26.5 ml/min for arterial (sensitivity 83.3%, specificity 80%) and 36.5 ml/min for venous grafts (sensitivity 75%, specificity 62%) performed well in predicting early graft occlusion.CONCLUSIONSWe demonstrate that MGF absolute values are influenced by coronary size, gender and graft type. Intraoperative MGF of >26.5 ml/min for arterial and >36.5 ml/min for venous grafts is the most reliable independent predictor of early graft patency. Modern-era coronary artery bypass graft is associated with low early graft failure rates when transit time flow measurement is used to provide effective intraoperative quality assurance.     

COVID-19 Vaccination in Patients with Chronic Liver Disease

Vaccination against SARS-CoV-2 has become a central public health issue, primarily for vulnerable populations such as individuals with Chronic Liver Disease (CLD). Increased COVID-19-related mortality and disease severity has been noted in this subgroup of patients. Severe COVID-19 tends to further deregulate liver function in patients with chronic liver failure or cirrhosis and even reactivate hepatitis in people living with HBV or HCV. In addition, impaired hepatic function leads to several limitations in possible therapeutic interventions. Chronic hepatic dysregulation, along with the underlying cirrhosis-associated immune dysfunction (CAID), leads to a decreased immune response to vaccination that, in turn, may result in reduced efficacy rates and lowered lasting protection. According to current guidelines, timely vaccination and frequent booster shot administration are deemed necessary in this context. Vaccination-related adverse events are mostly mild in nature and similar to those reported in the general population, whereas the incidence of liver injury following vaccination is relatively rare. We aimed to review available evidence and recommendations associated with COVID-19 vaccination in patients with chronic liver disease, and provide insight to current issues and future directions.     

Oral Antiviral Treatment for COVID-19: A Comprehensive Review on Nirmatrelvir/Ritonavir

Despite the rapid development of efficient and safe vaccines against COVID-19, the need to confine the pandemic and treat infected individuals on an outpatient basis has led to the approval of oral antiviral agents. Taking into account the viral kinetic pattern of SARS-CoV-2, it is of high importance to intervene at the early stages of the disease. A protease inhibitor called nirmatrelvir coupled with ritonavir (NMV/r), which acts as a CYP3A inhibitor, delivered as an oral formulation, has shown much promise in preventing disease progression in high-risk patients with no need for supplemental oxygen administration. Real-world data seem to confirm the drug combination’s efficacy and safety against all viral variants of concern in adult populations. Although, not fully clarified, viral rebound and recurrence of COVID-19 symptoms have been described following treatment; however, more data on potential resistance issues concerning the Mpro gene, which acts as the drug’s therapeutic target, are needed. NMV/r has been a gamechanger in the fight against the pandemic by preventing hospitalizations and halting disease severity; therefore, more research on future development and greater awareness on its use are warranted.     

Investigating the efficacy of monovalent and tetravalent dengue vaccine formulations against DENV-4 challenge in AG129 mice

Dengue (DEN) is the most important mosquito-borne viral disease, with a major impact on global health and economics, caused by four serologically and distinct viruses termed DENV-1 to DENV-4. Currently, there is no licensed vaccine to prevent DEN. We have developed a live attenuated tetravalent DENV vaccine candidate (TDV) (formally known as DENVax) that has shown promise in preclinical and clinical studies and elicits neutralizing antibody responses to all four DENVs. As these responses are lowest to DENV-4 we have used the AG129 mouse model to investigate the immunogenicity of monovalent TDV-4 or tetravalent TDV vaccines, and their efficacy against lethal DENV-4 challenge. Since the common backbone of TDV is based on an attenuated DENV-2 strain (TDV-2) we also tested the efficacy of TDV-2 against DENV-4 challenge. Single doses of the tetravalent or monovalent vaccines elicited neutralizing antibodies, anti-NS1 antibodies, and cellular responses to both envelope and nonstructural proteins. All vaccinated animals were protected against challenge at 60 days post-immunization, whereas all control animals died. Investigation of DENV-4 viremias post-challenge showed that only the control animals had high viremias on day 3 post-challenge, whereas vaccinated mice had no detectable viremia. Overall, these data highlight the excellent immunogenicity and efficacy profile of our candidate dengue vaccine in AG129 mice.     

Evidence for association between endothelial nitric oxide synthase gene polymorphism (G894T) and inflammatory markers: the ATTICA study

Background

We evaluated the effect of the point mutation of guanine to thymine at nucleotide position 894 (G894T) of the endothelial nitric oxide synthase (eNOS) gene on inflammatory and oxidative stress markers.

Methods

We studied genetic information from 270 men (18-87 years old) and 325 women (18-89 years old). Participants without any clinical evidence of cardiovascular or other atherosclerotic disease were randomly selected from the general population according to the age-sex distribution of Athens greater area. Genomic DNA was extracted from 2 to 5 mL of fresh or frozen whole blood using standard methods.

Results

The DNA analysis showed that 10.6% of the participants were Asp-homozygotes (Asp/Asp), 40% heterozygotes (Asp/Glu) and 49.4% Glu-homozygotes (Glu/Glu). Compared to Asp/Glu and Glu/Glu, Asp/Asp had higher levels of fibrinogen (332 ± 46 or 329 ± 33 vs 319 ± 29 mg/dL, P = .029), white blood cells (6.9 ± 0.6 or 6.5 ± 0.3 vs 6.1 ± 0.9 × 10³ counts, P = .044), and oxidized low-density lipoprotein cholesterol (68 ± 21 or 61 ± 22 vs 59 ± 20 mg/dL, P = .039), after controlling for several potential confounders. An insignificant association was found between homocysteine (P = .08), C-reactive protein (P = .096), and the distribution of G894T polymorphism (P < .1). No association between the distribution of the polymorphism and hypertension status of the participants was observed.

Conclusions

Our results imply that G894T polymorphism of the endothelial nitric oxide synthase gene is associated with elevated levels of inflammatory and oxidative stress markers, which may partially explain the increased prevalence of G894T polymorphism among patients with cardiovascular disease.     

Immune-mediated liver injury following COVID-19 vaccination

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination protocols. All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations, e.g., BNT162b2, mRNA-1273, and ChAdOx1-S, can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration. Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination. The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies. Novel vaccine delivery platforms, e.g., mRNA-containing lipid nanoparticles and adenoviral vectors, contribute to the inflammatory background that leads to an exaggerated immune response, while patterns of molecular mimicry between the spike (S) protein and prominent liver antigens may account for the autoimmune presentation. Immune mediators triggered by vaccination or vaccine ingredients per se, including autoreactive antibodies, cytokines, and cytotoxic T-cell populations, may inflict hepatocellular damage through well-established pathways. We aim to review available data associated with immune-mediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.     

Mapping frailty in people living with HIV: A nationwide study in Greece

Objectives

Frailty is known to affect people living with HIV prematurely, compared to the ageing seronegative population. In this cross-sectional study, we aimed to assess frailty prevalence in people living with HIV in Greece and find associations of frailty criteria with clinical data.

Methods

Demographic and clinical data were collected from 477 participants in six HIV clinics. Fried's frailty phenotype was used to assess frailty prevalence, and participants were classified as frail, pre-frail or robust. Associations of several factors with overall frailty phenotype, as well as with frailty criteria, were explored.

Results

The median age was 43 years old (IQR = 51.5) and 444/477 (93%) were men. Most of the participants (429/477, 93.5%) had an undetectable HIV viral load, and a CD4 cell count over 500 cells/μl (366/477, 76.7%). Frailty assessment classified 285/477 (62.1%) as robust, 155/477 (33.8%) as pre-frail and 19/477 (4.1%) as frail. Weakness in grip strength was the most prevalent criterion (128/477, 26.8%), followed by exhaustion (46/477, 9.6%). Lower CD4 cell count, history of AIDS diagnosis, CNS disorders, psychiatric diagnoses, and polypharmacy were strongly associated with frailty.

Conclusions

Although the prevalence of frailty in people living with HIV in Greece is uncommon, when combined with pre-frailty over a third of people are affected, which requires attention in clinical practice. The physical and psychological aspects of frailty highlight the need for a holistic approach to prevent or counteract it. The diverse associations of frailty criteria with HIV-related and non-HIV-related factors suggest a possible variation in people's different healthcare needs.     

One-year outcomes of resveratrol supplement with aflibercept versus aflibercept monotherapy in wet age-related macular degeneration

AIM: To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration (AMD). METHODS: Fifty naïve and previously untreated patients suffering from wet AMD, were randomly assigned in two subgroups of 25 patients each. All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept (IAIs) followed by injections “according to need”, while in one group the patients also received daily two tablets of resveratrol oral supplement. Prior to treatment initiation, a complete ophthalmological examination, including best corrected visual acuity (BCVA) and contrast sensitivity evaluation, optical coherence tomography (OCT) scans, fundus autofluorescence (FAF), fluorescein angiography, indocyanine green angiography, and OCT angiography (OCTA), was performed to every participant, while all of them completed the Hospital Anxiety and Depression Scale (HADS) questionnaire, in order to assess their quality of life (QoL) status. The patients were assessed monthly for 1y with FAF, and OCT or OCTA; the main endpoints were the number IAIs, the changes in BCVA, in contrast sensitivity, and in patients'' QoL status. RESULTS: No significant differences were present between the groups regarding the baseline demographic and clinical data. Over the 12-month period, a similar number of IAIs was applied in both groups (4.52±1.00 vs 4.28±0.90, P=0.38), while the rest of the clinical data also did not differ significantly after the completion of the study period. However, for HADS Depression (11.88±2.51 vs 8.28±1.54, P<0.001) and HADS Anxiety (11.92±2.52 vs 7.76±1.51, P<0.001) questionnaires values, the score was significantly better in patients who received resveratrol supplements. Moreover, a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity (0.17±0.19 vs 0.35±0.24, P=0.005), HADS Depression (0.08±1.38 vs -3.88±1.48, P<0.001), and HADS Anxiety (0.36±1.98 vs -5.12±2.70, P<0.001) scores, in favour of the patients treated with resveratrol supplements. CONCLUSION: The resveratrol oral supplement is a complementary treatment in cases of wet AMD, highlighting its effectiveness in improving patients'' QoL status.     

Somatic SNCA Copy Number Variants in Multiple System Atrophy are Related to Pathology and Inclusions

Background

Somatic α-synuclein (SNCA) copy number variants (CNVs, specifically gains) occur in multiple system atrophy (MSA) and Parkinson's disease brains.

Objective

The aim was to compare somatic SNCA CNVs in MSA subtypes (striatonigral degeneration [SND] and olivopontocerebellar atrophy [OPCA]) and correlate with inclusions.

Methods

We combined fluorescent in situ hybridization with immunofluorescence for α-synuclein and in some cases oligodendrocyte marker tubulin polymerization promoting protein (TPPP).

Results

We analyzed one to three brain regions from 24 MSA cases (13 SND, 11 OPCA). In a region preferentially affected in one subtype (putamen in SND, cerebellum in OPCA), mosaicism was higher in that subtype, and cells with CNVs were 4.2 times more likely to have inclusions. In the substantia nigra, nonpigmented cells with CNVs and TPPP were about six times more likely to have inclusions.

Conclusions

The correlation between SNCA CNVs and pathology (at a regional level) and inclusions (at a single-cell level) suggests a role for somatic SNCA CNVs in MSA pathogenesis. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.