Trans unsaturated fatty acids are components of atheromatous plaque

Wstęp. Przeprowadzono badania chromatograficzne blaszek miażdżycowych pobranych od 21 pacjentów w Klinice Chirurgii Naczyniowej PAM w Szczecinie, których operowano z powodu powikłań zaawansowanej miażdżycy tętnic brzusznych i udowych. Cel pracy. Celem analizy było ustalenie czy izomery trans nienasyconych kwasów tłuszczowych (występujące w utwardzonych tłuszczach spożywczych pochodzenia roślinnego) są istotnymi składnikami blaszki miażdżycowej. Materiał i metody. Kwasy tłuszczowe ekstrahowano mieszaniną Folcha, zmydlano metanolowym 2-procentowym roztworem KOH i metylowano 14-procentowym BF3 w metanolu, otrzymując estry metylowe kwasów tłuszczowych. Analizę badanego materiału przeprowadzono przy użyciu chromatografu gazowego Perkin-Elmer 8500, stosując program Chromed PI. Oceny zależności pomiędzy otrzymanymi parametrami dokonano na podstawie współczynnika korelacji rang Spearmana, przyjmując za istotne statystycznie wartości p < 0,05. Wyniki. W badanym materiale stwierdzono obecność różnych izomerów kwasów tłuszczowych, w tym także charakterystycznych dla utwardzanych tłuszczów roślinnych (zwłaszcza margaryn). Kwas elaidynowy (trans 9 C18:1) okazał się dominującym trans izomerem wśród jednonienasyconych kwasów tłuszczowych. Głównym reprezentantem wielonienasyconych kwasów tłuszczowych był jeden ze sprzężonych dienów kwasu linolowego: cis 9 trans 11 C18:2. Wnioski. Wyniki badań wskazują na zależność pomiędzy występowaniem w diecie izomerów trans nienasyconych kwasów tłuszczowych a ich udziałem w metabolizmie blaszki miażdżycowej, a nawet w ewentualnym indukowaniu procesu aterogenezy.Background. Chromatographic studies on fatty acid composition of atheromatous plaques obtained from 21 patients treated surgically in the Department of Vascular Surgery (Pomeranian Academy of Medicine, Szczecin, Poland) for complications of atherosclerosis of abdominal aorta, iliac or femoral arteries, were carried out. Aim of the study. The aim of the study was to assess if the trans unsaturated fatty acids (occurring in hardened fats of plant origin) are substantial components of the atheromatous plaques. Material and methods. Fatty acids were extracted using Folch mixture, saponified in 2% KOH solution and methylated with 14% solution of BF3 in methanol, obtaining fatty acid methyl esters. The analysis of obtained material was carried out with a gas chromatograph Perkin-Elmer 8500, applying Chromed PI software. Correlations between obtained parameters were calculated using the Spearman&#8217;s correlation coefficient, taking p < 0.05 as statistically significant. Results. The presence of varied isomers of fatty acids in the analysed material (among them typical for the hardened plant fats) was established. Elaidic acid (trans-9 C18:1) served as a major trans isomer among monounsaturated fatty acids. The main representative of polyunsaturated fatty acids was one of conjugated diens of linoleic acid: cis-9, trans-11 C18:2. Conclusions. The results of the study show the relationship between trans unsaturated fatty acids content in the diet and their importance in the metabolism of atheromatous plaque and possible induction of atherogenesis

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Multi-organ trauma with rupture and Stanford type B dissection of thoracic aorta. Management sequence. Current possibilities of medical treatment

A case of a 46-year-old car driver struck with great force by a tram through the driver’s door is presented. The main trauma consisted in chest injury with multi-rib fracture along with rupture and dissection of the thoracic aorta. Immediate medical rescue actions consisted only in procedures necessary to support vital functions; the patient survived owing to being promptly transported to the Emergency Department to undergo thoracotomy and laparotomy with massive blood transfusion. Polytrauma angio-CT scan revealed a posttraumatic thoracic aorta lesion which in turn was treated by deployment of an endovascular thoracic stent graft. This way, the immediate risk of death was averted, and the remaining traumatic lesions and conditions could be treated. Patient was discharged to a Rehabilitation Center on the 49th day of treatment. The authors stress that trauma resulting from accidents with this particular mechanism, i.e. lateral car crash on the driver’s side with the driver’s door being staved in by the tram, should be managed by immediate transport of the patient to the Emergency Center. In such cases early drainage of the pleural cavity can deteriorate patient’s status by increasing the bleeding from the ruptured aorta

Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass

Objective: The human acellular vessel (HAV) was evaluated for surgical bypass in a phase II study. The primary results at 24 months after implantation have been reported, and the patients will be evaluated for ≤10 years. Methods: In the present report, we have described the 6-year results of a prospective, open-label, single-treatment arm, multicenter study. Patients with advanced peripheral artery disease (PAD) requiring above-the-knee femoropopliteal bypass surgery without available autologous graft options had undergone implantation with the HAV, a bioengineered human tissue replacement blood vessel. The patients who completed the 24-month primary portion of the study will be evaluated for ≤10 years after implantation. The present mid-term analysis was performed at the 6-year milestone (72 months) for patients followed up for 24 to 72 months. Results: HAVs were implanted in 20 patients at three sites in Poland. Seven patients had discontinued the study before completing the 2-year portion of the study: four after graft occlusion had occurred and three who had died of causes deemed unrelated to the conduit, with the HAV reported as functional at their last visit. The primary results at 24 months showed primary, primary assisted, and secondary patency rates of 58%, 58%, and 74%, respectively. One vessel had developed a pseudoaneurysm deemed possibly iatrogenic; no other signs of structural failure were reported. No rejections or infections of the HAV occurred, and no patient had required amputation of the implanted limb. Of the 20 patients, 13 had completed the primary portion of the study; however, 1 patient had died shortly after 24 months. Of the remaining 12 patients, 3 died of causes unrelated to the HAV. One patient had required thrombectomy twice, with secondary patency achieved. No other interventions were recorded between 24 and 72 months. At 72 months, five patients had a patent HAV, including four patients with primary patency. For the entire study population from day 1 to month 72, the overall primary, primary assisted, and secondary patency rate estimated using Kaplan-Meier analysis was 44%, 45%, and 60% respectively, with censoring for death. No patient had experienced rejection or infection of the HAV, and no patient had required amputation of the implanted limb. Conclusions: The infection-resistant, off-the-shelf HAV could provide a durable alternative conduit in the arterial circuit setting to restore the lower extremity blood supply in patients with PAD, with remodeling into the recipient’s own vessel over time. The HAV is currently being evaluated in seven clinical trials to treat PAD, vascular trauma, and as a hemodialysis access conduit. : Clinical Relevance: Patients with peripheral artery disease who require surgical revascularization need options when autologous grafts are not available. The human acellular vessel (HAV) has been demonstrated to have characteristics similar to those of autologous vessels in terms of resistance to infection, mechanics, and a very low risk of rejection. Safety and performance were evaluated for ≤6 years after implantation of an HAV in a femoropopliteal position. Overall, the secondary patency rate estimated using the Kaplan-Meier method was 60% at 72 months, with 45% primary patency. No infection or rejection episodes had occurred with the HAV conduits. These data have demonstrated the durability of the HAV and suggest the occurrence of cellular remodeling by the host

The burden of metabolic risk factors in North Africa and the Middle East, 1990–2019: findings from the Global Burden of Disease StudyResearch in context

Summary: Background: The objective of this study is to investigate the trends of exposure and burden attributable to the four main metabolic risk factors, including high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high body-mass index (BMI), and high low-density lipoproteins cholesterol (LDL) in North Africa and the Middle East from 1990 to 2019. Methods: The data were retrieved from Global Burden of Disease Study 2019. Summary exposure value (SEV) was used for risk factor exposure. Burden attributable to each risk factor was incorporated in the population attributable fraction to estimate the total attributable deaths and disability-adjusted life-years (DALYs). Findings: While age-standardized death rate (ASDR) attributable to high-LDL and high-SBP decreased by 26.5% (18.6–35.2) and 23.4% (15.9–31.5) over 1990–2019, respectively, high-BMI with 5.1% (−9.0–25.9) and high-FPG with 21.4% (7.0–37.4) change, grew in ASDR. Moreover, age-standardized DALY rate attributed to high-LDL and high-SBP declined by 30.2% (20.9–39.0) and 25.2% (16.8–33.9), respectively. The attributable age-standardized DALY rate of high-BMI with 8.3% (−6.5–28.8) and high-FPG with 27.0% (14.3–40.8) increase, had a growing trend. Age-standardized SEVs of high-FPG, high-BMI, high-SBP, and high-LDL increased by 92.4% (82.8–103.3), 76.0% (58.9–99.3), 10.4% (3.8–18.0), and 5.5% (4.3–7.1), respectively. Interpretation: The burden attributed to high-SBP and high-LDL decreased during the 1990–2019 period in the region, while the attributable burden of high-FPG and high-BMI increased. Alarmingly, exposure to all four risk factors increased in the past three decades. There has been significant heterogeneity among the countries in the region regarding the trends of exposure and attributable burden. Urgent action is required at the individual, community, and national levels in terms of introducing effective strategies for prevention and treatment that account for local and socioeconomic factors. Funding: Bill &amp; Melinda Gates Foundation

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

International audienceLife-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Age–sex differences in the global burden of lower respiratory infections and risk factors, 1990–2019: results from the Global Burden of Disease Study 2019

Background: The global burden of lower respiratory infections (LRI) and corresponding risk factors in children older than five years and adults has not been studied as comprehensively as in children under five years old. We assessed the burden and trends of LRI and risk factors across all age groups by sex for 204 countries and territories. Methods: We used clinician-diagnosed pneumonia or bronchiolitis as our case definition for lower respiratory infections. We included ICD9 codes 073.0-073.6, 079.82, 466-469, 480-489, 513.0, and 770.0 and ICD10 codes A48.1, J09-J22, J85.1, P23-P23.9, and U04. We used the Cause of Death Ensemble modelling strategy to analyse 23,109 site-years of vital registration data, 825 site-years of sample vital registration data, 1766 site-years of verbal autopsy data, and 681 site-years of mortality surveillance data. We used DisMod-MR 2.1, a Bayesian meta-regression tool, to analyse age-sex-specific incidence and prevalence data identified via systematic review, population-based surveys, and claims and inpatient data. Additionally, we estimated age-sex-specific LRI mortality that is attributable to the independent effects of 14 risk factors.Results: Globally, we estimated LRI episodes of 257 million (95% UI 240–275) for males and 232 million (217–248) for females in 2019. In the same year, LRI accounted for 1.3 million (1.2–1.4) deaths among males and 1.2 million (1.1–1.3) deaths among females. Age-standardised incidence and mortality rates were 1.2 times and 1.3 times greater in males than in females in 2019. Between 1990 and 2019, LRI incidence and mortality rates declined at different rates across age groups while an increase in LRI episodes and deaths was estimated among all adult age groups, with males aged 70 years and older experiencing the highest increase in LRI episodes (126.0% [121.4–131.1]) and deaths (100.0% [83.4–115.9]). During the same period, LRI episodes and deaths in children younger than 15 years were estimated to have decreased, and the greatest decline was observed for mortality among males under the age of five (70.7% [61.8–77.3]). The leading risk factors for LRI mortality varied across age groups and sex. More than half of global LRI deaths among males and females younger than five years were attributable to child wasting, and more than a quarter of LRI deaths among those aged 5–14 years were attributable to household air pollution in 2019. For males aged 15–49, 50–69, and 70 years and older, 20.4 (15.4-25.2), 30.5% (24.1–36.9), and 21.9% (16.8–27.3), respectively, of estimated LRI deaths were attributable to smoking in the same year. For females aged 15–49 and 50–69 years, 21.1% (14.5–27.9) and 7.9% (5.5–10.5) of estimated LRI deaths were attributable to household air pollution in 2019. For females aged 70 years and older, the leading risk factor, ambient particulate matter, was responsible for 11.7% (8.2–15.8) of LRI deaths in the same year.Interpretation: The patterns and progress in reducing the burden of LRI and key risk factors varied across age groups and sexes.. The progress seen in under five children was clearly a result of targeted interventions, such as vaccination and reduction of exposure to risk factors. Similar interventions for other age groups could contribute to achieving multiple Sustainable Development Goals targets, including promoting well-being at all ages and reducing inequalities. Interventions, including addressing risk factors such as child wasting, smoking, ambient particulate matter pollution, and household air pollution, would mean preventable deaths and millions of lives saved, as well as reduced health disparities

Age–sex differences in the global burden of lower respiratory infections and risk factors, 1990–2019: results from the Global Burden of Disease Study 2019

Summary Background The global burden of lower respiratory infections (LRIs) and corresponding risk factors in children older than 5 years and adults has not been studied as comprehensively as it has been in children younger than 5 years. We assessed the burden and trends of LRIs and risk factors across all age groups by sex, for 204 countries and territories. Methods In this analysis of data for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we used clinician-diagnosed pneumonia or bronchiolitis as our case definition for LRIs. We included International Classification of Diseases 9th edition codes 079.6, 466–469, 470.0, 480–482.8, 483.0–483.9, 484.1–484.2, 484.6–484.7, and 487–489 and International Classification of Diseases 10th edition codes A48.1, A70, B97.4–B97.6, J09–J15.8, J16–J16.9, J20–J21.9, J91.0, P23.0–P23.4, and U04–U04.9. We used the Cause of Death Ensemble modelling strategy to analyse 23 109 site-years of vital registration data, 825 site-years of sample vital registration data, 1766 site-years of verbal autopsy data, and 681 site-years of mortality surveillance data. We used DisMod-MR 2.1, a Bayesian meta-regression tool, to analyse age–sex-specific incidence and prevalence data identified via systematic reviews of the literature, population-based survey data, and claims and inpatient data. Additionally, we estimated age–sex-specific LRI mortality that is attributable to the independent effects of 14 risk factors. Findings Globally, in 2019, we estimated that there were 257 million (95% uncertainty interval [UI] 240–275) LRI incident episodes in males and 232 million (217–248) in females. In the same year, LRIs accounted for 1·30 million (95% UI 1·18–1·42) male deaths and 1·20 million (1·07–1·33) female deaths. Age-standardised incidence and mortality rates were 1·17 times (95% UI 1·16–1·18) and 1·31 times (95% UI 1·23–1·41) greater in males than in females in 2019. Between 1990 and 2019, LRI incidence and mortality rates declined at different rates across age groups and an increase in LRI episodes and deaths was estimated among all adult age groups, with males aged 70 years and older having the highest increase in LRI episodes (126·0% [95% UI 121·4–131·1]) and deaths (100·0% [83·4–115·9]). During the same period, LRI episodes and deaths in children younger than 15 years were estimated to have decreased, and the greatest decline was observed for LRI deaths in males younger than 5 years (–70·7% [–77·2 to –61·8]). The leading risk factors for LRI mortality varied across age groups and sex. More than half of global LRI deaths in children younger than 5 years were attributable to child wasting (population attributable fraction [PAF] 53·0% [95% UI 37·7–61·8] in males and 56·4% [40·7–65·1] in females), and more than a quarter of LRI deaths among those aged 5–14 years were attributable to household air pollution (PAF 26·0% [95% UI 16·6–35·5] for males and PAF 25·8% [16·3–35·4] for females). PAFs of male LRI deaths attributed to smoking were 20·4% (95% UI 15·4–25·2) in those aged 15–49 years, 30·5% (24·1–36·9) in those aged 50–69 years, and 21·9% (16·8–27·3) in those aged 70 years and older. PAFs of female LRI deaths attributed to household air pollution were 21·1% (95% UI 14·5–27·9) in those aged 15–49 years and 18·2% (12·5–24·5) in those aged 50–69 years. For females aged 70 years and older, the leading risk factor, ambient particulate matter, was responsible for 11·7% (95% UI 8·2–15·8) of LRI deaths. Interpretation The patterns and progress in reducing the burden of LRIs and key risk factors for mortality varied across age groups and sexes. The progress seen in children younger than 5 years was clearly a result of targeted interventions, such as vaccination and reduction of exposure to risk factors. Similar interventions for other age groups could contribute to the achievement of multiple Sustainable Development Goals targets, including promoting wellbeing at all ages and reducing health inequalities. Interventions, including addressing risk factors such as child wasting, smoking, ambient particulate matter pollution, and household air pollution, would prevent deaths and reduce health disparities