Impaired left ventricular deformation and ventricular-arterial coupling in post-COVID-19: association with autonomic dysregulation.

Coronavirus disease-19 (COVID-19) has extended implications namely the long COVID-19 syndrome. We assessed over-time changes in left ventricular (LV) function, aortic stiffness, autonomic function, and ventricular-arterial coupling (VAC) in post-COVID-19 patients. We followed 34 post-COVID-19 subjects, up to 6 months post-hospital discharge. Subjects without COVID-19 served as control. We evaluated LV global longitudinal strain (LV-GLS), arterial stiffness [carotid-femoral pulse wave velocity (cf-PWV)], and heart rate variability -standard deviation of normal RR intervals (SDNN). VAC was estimated as the ratio of cf-PWV to LV-GLS. Post-COVID-19 individuals (1-month post-hospital discharge) presented with impaired LV-GLS [-18.4%(3.1) vs. -22.0%(2.7), P < 0.001], cf-PWV [12.1 m/s (3.2) vs. 9.6 m/s (1.9), P < 0.001], SDNN [111.3 ms (22.6) vs. 147.2 ms (14.0), P < 0.001], and VAC [-0.68 (0.22) vs. -0.44 (0.10), P < 0.001] compared to control. LV-GLS, SDNN, and VAC improved at the 6-month follow-up however they did not reach control levels. In post-COVID-19 subjects, SDNN and VAC were correlated at the 1-month (R = 0.499, P = 0.003) and 6-month (R = 0.372, P = 0.04) follow-up. Long COVID-19 syndrome was associated with impaired LV-GLS, SDNN, and VAC. Post-COVID-19 subjects presented with autonomic dysregulation associated with aortic stiffness, ventricular-arterial impairment, and LV dysfunction, even 6-months post-hospital discharge. These abnormalities may be related to the presence of long COVID-19 syndrome.

CYP1A2 polymorphisms modify the association of habitual coffee consumption with appetite, macronutrient intake, and body mass index: results from an observational cohort and a cross-over randomized study.

BACKGROUND/OBJECTIVES: Evidence regarding the influence of coffee on appetite and weight control is equivocal and the influence of covariates, such as genetic variation in caffeine metabolism, remains unknown. Herein, we addressed the novel hypothesis that genetic variation in CYP1A2, a gene responsible for more than 95% of caffeine metabolism, differentially impacts the association of coffee consumption with appetite and BMI among individuals with different genetic predispositions to obesity. SUBJECTS/METHODS: A cross-over randomized intervention study involving 18 volunteers assessed the effects of coffee consumption on dietary intake, appetite, and levels of the appetite-controlling hormones asprosin and leptin. Data on habitual coffee intake, BMI, and perceived appetite were obtained from an observational cohort of 284 volunteers using validated questionnaires. Participants were stratified according to a validated genetic risk score (GRS) for obesity and to the -163C > A (rs762551) polymorphism of CYP1A2 as rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers. RESULTS: Coffee consumption led to lower energy and dietary fat intake and circulating asprosin levels (P for interaction of rs762551 genotype*coffee consumption=0.056, 0.039, and 0.043, respectively) as compared to slow/intermediate metabolizers. High coffee consumption was more prevalent in rapid compared to slow metabolizers (P = 0.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption = 0.002 and 0.048, respectively). This differential association of rs762551 genotype and coffee consumption with BMI was more evident in individuals at higher genetic risk of obesity (mean adjusted difference in BMI = -5.82 kg/m2 for rapid versus slow/intermediate metabolizers who consumed more than 14 cups of coffee per week). CONCLUSIONS: CYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. This association is more evident in subjects with high genetic predisposition to obesity. ClinicalTrials.gov: registered Clinical Trial NCT04514588.

Dietary sodium estimation methods: accuracy and limitations of old and new methods in individuals at high cardiovascular risk.

OBJECTIVE: Accurate and easy to use methods for dietary Na intake estimation in population level are lacking. We aimed at (i) estimating the mean Na intake in the group level using a variety of dietary methods (DM) and urinary methods (UM) and correlating them with 24-h urine collection (24UCol) and (ii) improving the accuracy of the existing DM. DESIGN: The most common DM (three 24-h dietary recalls (24DR) and FFQ) and UM (24UCol and spot urine collection using common equations) were applied. To improve the existing: (i) 24DR, discretionary Na was quantified using salt-related questions or adding extra 15 % in total Na intake and (ii) FFQ, food items rich in Na and salt-related questions were added in the standard questionnaire (NaFFQ). SETTING: National and Kapodistrian University of Athens, Greece. PARTICIPANTS: Totally, 122 high cardiovascular risk subjects (56·0 ± 12·6 years; 55·7 % males). RESULTS: Mean 24 h Na excretion (24UNa) was 2810 ± 1304 mg/d. Spot urine methods overestimated the 24UNa (bias range: -1781 to -492 mg) and were moderately correlated to 24UCol (r = 0·469-0·596, P ≤ 0·01). DM underestimated the 24UNa (bias range: 877 to 1212 mg) and were weakly correlated with 24UCol. The improved DM underestimated the 24UNa (bias range: 877 to 923 mg). The NaFFQ presented the smallest bias (-290 ± 1336 mg) and the strongest correlation with 24UCol (r = 0·497, P ≤ 0·01), but wide limits of agreement in Bland-Altman plots (-2909 mg; 2329 mg), like all the other methods did. CONCLUSIONS: The existing methods exhibit poor accuracy. Further improvement of the newly developed NaFFQ could be promising for more accurate estimation of mean dietary Na intake in epidemiological studies. Additional validation studies are needed.

Medical education challenges and innovations during COVID-19 pandemic.

COVID-19 pandemic has undoubtedly disrupted the well-established, traditional structure of medical education. Τhe new limitations of physical presence have accelerated the development of an online learning environment, comprising both of asynchronous and synchronous distance education, and the introduction of novel ways of student assessment. At the same time, this prolonged crisis had serious implications on the lives of medical students including their psychological well-being and the impact on their academic trajectories. The new reality has, on many occasions, triggered the 'acting up' of medical students as frontline healthcare staff, which has been perceived by many of them as a positive learning and contributing experience, and has led to a variety of responses from the educational institutions. All things considered, the urgency for rapid and novel adaptations to the new circumstances has functioned as a springboard for remarkable innovations in medical education,including the promotion of a more "evidence-based" approach.

Experimental Devices Versus Hand-Sewn Anastomosis of the Aorta: A Systematic Review and Meta-Analysis.

BACKGROUND: To minimize complications associated with the construction of the hand-sewn aortic anastomosis, alternative experimental methods have been pursued. This study aimed to evaluate the efficacy of experimental anastomotic devices in relation to time and point of rupture of the anastomosis in comparison to the conventional technique. MATERIALS AND METHODS: An electronic search was performed using MEDLINE, Scopus, Science Direct, and Cochrane Library databases by two independent authors. Our exclusion criteria referred to studies reporting results solely from end-to-side anastomosis, results on vessels other than the aorta, studies that did not involve animal experiments, and non-English publications. The last search date was January 1, 2020. RESULTS: The meta-analysis included 22 studies with 34 anastomosis samples and a total of 316 animals. The pooled mean automated anastomosis time was 10.38 min, and the mean point of rupture was 32.7 N. In the subgroup analysis of automated anastomosis time by device category, the anastomotic stenting technique reported significantly lower anastomosis time but also showed significantly lower point of rupture. Comparing the efficacy of experimental devices and the hand-sewn technique, our pooled analysis showed that automated devices significantly decrease the time needed to perform the anastomosis (weighted mean difference -7.24 min). On the other hand, the automated anastomosis is also associated with decreased tensile strength (weighted mean difference -20.68 N). CONCLUSIONS: Although experimental devices seem to offer a faster anastomosis, they lack endurance when compared with the hand-sewn technique. Further research is needed for the development of an "ideal" anastomotic technique.

Esophageal defect repair by artificial scaffolds: a systematic review of experimental studies and proportional meta-analysis.

BACKGROUND: The traditional technique of gastrointestinal reconstruction of the esophagus after esophagectomy presents plenty of complications. Hence, tissue engineering has been introduced as an effective artificial alternative with potentially fewer complications. Three types of esophageal scaffolds have been used in experimental studies so far. The aim of our meta-analysis is to present the postoperative outcomes after esophageal replacement with artificial scaffolds and the investigation of possible factors that affect these outcomes. METHODS: The present proportional meta-analysis was designed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and A MeaSurement Tool to Assess systematic Reviews guidelines. We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, and Google Scholar databases from inception until February 2020. RESULTS: Overall, 32 studies were included that recruited 587 animals. The pooled morbidity after esophageal scaffold implantation was 53.4% (95% CI = 36.6-70.0%). The pooled survival interval was 111.1 days (95% CI = 65.5-156.8 days). Graft stenosis (46%), postoperative dysphagia (15%), and anastomotic leak (12%) were the most common complications after esophageal scaffold implantation. Animals that underwent an implantation of an artificial scaffold in the thoracic part of their esophagus presented higher survival rates than animals that underwent scaffold implantation in the cervical or abdominal part of their esophagus (P < 0.001 and P = 0.011, respectively). CONCLUSION: Tissue engineering seems to offer an effective alternative for the repair of esophageal defects in animal models. Nevertheless, issues like graft stenosis and lack of motility of the esophageal scaffolds need to be addressed in future experimental studies before scaffolds can be tested in human trials.

On the importance of the nonuniform aortic stiffening in the hemodynamics of physiological aging.

Mathematical models of the arterial tree constitute a valuable tool to investigate the hemodynamics of aging and pathology. Rendering such models as patient specific could allow for the assessment of central hemodynamic variables of clinical interest. However, this task is challenging, particularly with respect to the tuning of the local area compliance that varies significantly along the arterial tree. Accordingly, in this study, we demonstrate the importance of taking into account the differential effects of aging on the stiffness of central and peripheral arteries when simulating a person's hemodynamic profile. More specifically, we propose a simple method for effectively adapting the properties of a generic one-dimensional model of the arterial tree based on the subject's age and noninvasive measurements of aortic flow and brachial pressure. A key element for the success of the method is the implementation of different mechanisms of arterial stiffening for young and old individuals. The designed methodology was tested and validated against in vivo data from a population of n = 20 adults. Carotid-to-femoral pulse wave velocity was accurately predicted by the model (mean error = 0.14 m/s, SD = 0.77 m/s), with the greatest deviations being observed for older subjects. In regard to aortic pressure, model-derived systolic blood pressure and augmentation index were both in good agreement (mean difference of 2.3 mmHg and 4.25%, respectively) with the predictions of a widely used commercial device (Mobil-O-Graph). These preliminary results encourage us to further validate the method in larger samples and consider its potential as a noninvasive tool for hemodynamic monitoring.NEW & NOTEWORTHY We propose a technique for adapting the parameters of a validated one-dimensional model of the arterial tree using noninvasive measurements of aortic flow and brachial pressure. Emphasis is given on the adjustment of the arterial tree distensibility, which incorporates the nonuniform effects of aging on central and peripheral vessel elasticity. Our method could find application in the derivation of important hemodynamic indices, paving the way for novel diagnostic tools.

Α systematic review and meta-analysis of the efficacy of aortic anastomotic devices.

OBJECTIVE: One of the factors contributing to complications related to open repair of the aorta is the construction of a hand-sewn anastomosis. Aortic anastomotic devices (AADs), such as the intraluminal ringed graft (IRG), and the anastomotic stenting technique have been developed to perform a sutureless and less complicated anastomosis. This study performed a systematic review and meta-analysis of the literature reporting clinical use of AADs and aimed to assess, primarily, the effect of each device on 30-day overall and operation-related mortality and aortic cross-clamping time and, secondarily, the rate of successful two-sided application of the IRG device and the operation-related morbidity for each device. METHODS: An electronic search was performed using MEDLINE, Scopus, ScienceDirect, and Cochrane Library by two independent authors. Our exclusion criteria included studies incorporating fewer than three patients and studies reporting results solely from animals or in vitro testing, results solely from end-to-side anastomosis, and results solely from endarterectomy procedures. The last search date was February 1, 2018. RESULTS: A total of 41 studies were identified that reported outcomes for the use of three different device types: IRG, anastomotic stenting technique, and surgical staplers. The last two types were classified together as the non-IRG group. The meta-analysis included 27 studies with 50 cohorts incorporating 1260 patients. The median age of the incorporated patients was 61.4 years (range, 51-73 years), and 68.9% were male. The operations were performed for the treatment of acute aortic dissection in 82.3%. The pooled overall 30-day mortality rate varied by device type; IRG devices had a mean rate of all-cause mortality of 9.71%, whereas non-IRG devices were associated with a significantly (I2 = 15.78%; P for Cochrane Q test < .19) lower rate of death (1.47%). The pooled mean aortic cross-clamping time was 35.83 minutes. Metaregression showed that the performance of two-sided anastomosis with the IRG device significantly decreased the aortic cross-clamping time. However, a successful two-sided ringed anastomosis was performed in approximately half of the cases. CONCLUSIONS: Taking into account that the majority of operations were performed for the treatment of acute aortic dissection, AADs had a relatively low rate of 30-day mortality. Despite the observed heterogeneity in study protocols and the small sample size in the non-IRG group, the non-IRG group presented with the lowest 30-day mortality rate. Specific device-related complications between the different device types need further investigation.

Arterial stiffness and subclinical aortic damage of reclassified subjects as stage 1 hypertension according to the new 2017 ACC/AHA blood pressure guidelines.

Background: The 2017 ACC/AHA blood pressure (BP) guidelines generated controversies due to the new proposed BP cut-off values defining hypertension. We aimed to assess aortic stiffness of subjects who are reclassified as stage 1 hypertensive according to the new guidelines and compare them with the subjects of "elevated BP" category. Patients and methods. Data from the "Corinthia" study, an observational, cross-sectional survey of 2,043 participants were analyzed. Subjects were classified into 4 groups: group A: systolic pressure (SBP) 120-129 and diastolic pressure (DBP) < 80 mmHg, group B: SBP 130-139 or DBP 80-89 mmHg, group B1: SBP 130-139 and DBP < 80 mmHg and group B2: SBP 130-139 and DBP 80-89 mmHg. Aortic stiffness was assessed by carotid-to-femoral pulse wave velocity (PWV). A value of PWV > 10m/s was consider indicative of asymptomatic organ damage while values of PWV exceeded the 90 % percentile for each age group were consider as abnormal. Results: Groups B, B1 and B2 have significantly increased PWV compared to group A, independently from age and other risk factors (PWV: 9.2 ± 2.8 vs 9.4 ± 2.7 vs 8.6 ± 2.5 vs 8.1 ± 2.3 m/s, p < 0.01, respectively). The prevalence of PWV > 10 m/s and abnormal PWV values in group A was significantly lower than the corresponding prevalence in randomly selected, age-matched subjects from group B (13.5 % vs 24.4 %, p = 0.027 and 5.6 % vs 14.2 %, p = 0.022, respectively). Conclusions: The reclassified subjects as stage 1 hypertensive by the new guidelines have a significantly increased aortic stiffness and greater prevalence in asymptomatic aortic damage compared to subjects with elevated BP. This finding may indirectly explain the increased cardiovascular risk of this group.

The Hippocratic Doctrine of "the Acute Brain Suffering" as the Brain Stroke.

BACKGROUND: The ancient Greek term "apoplexy" as is repeatedly mentioned by the Hippocratic School of Medicine, included a cluster of diseases, mainly those concerning the central nervous system. The term was wrongfully infiltrated in Western European medicine as synonymous to what is called today a "stroke" of the brain. OBJECTIVE: While in "Corpus Hippocraticum" the definition of the stroke was rather ambiguous; our study aims to unveil those fragments referring to it, in order to compose the Hippocratic theory of what it stood for "Acute Brain Suffering" (Greek: Οξείες Οδύνες του Εγκεφάλου) during the Classical era of ancient Greece. METHOD: A bibliographic research of the "Hippocratic Collection" was conducted during our study in order to connect all fragments from the original ancient Greek text, and reconstruct the "Hippocratic Stroke Theory". Three editions have been used as reference. French edition by Littré, and two Greek ones by Kaktos and Pournaropoulos. RESULTS: The "Acute Brain Suffering" seems to be the entity we call "Stroke" in modern clinical practice. Edema (collection of fluids-humours theory) was considered to be the most significant element which though could have been addressed by a cranial decompression for the symptoms to improve. The symptoms in question were, acute brain pain, diplopia, vertigo, ataxia, saliva, and urine loss as well as feces incontinence. CONCLUSION: Both therapeutic approach and symptomatology exhibited significant similarities with the modern concept of the stroke. The Hippocratic School was a scientifically advanced sect of medicophilosophers who promoted global medicine.

3D Bioprinting Methods and Techniques: Applications on Artificial Blood Vessel Fabrication.

Three-dimensional (3D) printing has rapidly evolved, with major applications in the field of medicine. One of the greatest advances leading to 3D bioprinting was the development of biomaterials, cells and supporting components for the fabrication of functional living tissues. Several different methods and techniques of 3D bioprinting are briefly described in this review article, and applications of 3D printing for the fabrication of artificial blood vessels and grafts are presented. Advances in additive manufacturing techniques, medical imaging modalities, biomaterials and cellular engineering will lead to further developments in the fabrication of patient-specific vascular tissue constructs. Future multidisciplinary research and innovations are expected to further transform the fields of tissue engineering and regenerative medicine.

Novel Concept Enabling an Old Idea: A Flexible Electrode Array to Treat Neurogenic Erectile Dysfunction.

INTRODUCTION: Many studies have shown that electrostimulation of the cavernosal nerve can induce and maintain penile erection. Based on these discoveries, neurostimulation to activate the erectile response has been considered a potential solution to treat erectile dysfunction (ED). However, despite recognized potential, this technology has not been further developed. The barrier is the complex anatomy of the human cavernous nerve, which challenges the intraoperative identification of the cavernosal nerves for electrode placement. AIM: To overcome this major barrier, we proposed a practical solution: a 2-dimensional flexible electrode array that can cover the entire plexus area, ensuring that at least 1 of the electrodes will be in optimal contact with the cavernosal nerve, without the need of intraoperative identification. The present study aims to evaluate this concept intraoperatively. METHODS: 24 patients enrolled for open radical prostatectomy were recruited. During the surgical procedures, the electrode array was positioned on the pelvic plexus (on the prostatic apex or pelvic wall) and electrical stimulation was applied to induce penile erection. Penile erectile response was assessed by (i) visual change of penile tumescence and (ii) by a penile plethysmograph system. MAIN OUTCOME MEASURE: Ability and success rate of evoking penile response were measured by applying electrical stimulation using the developed electrode array. RESULTS: Electrical stimulation produced immediate penile response in all cases when tested before (on prostatic apex) or after prostate removal (on pelvic wall). Clear visual penile engorgement was observed in 75% of the cases, whereas 25% showed minimal to moderate penile tumescence. As expected, patients with lower International Index of Erectile Function-5 score presented a reduced response, whereas stimulation before prostate removal showed greater response than following removal. Interestingly, erectile response was potentiated by bilateral stimulation (circumference increase [mm]: 2.7 ± 1.02 vs. 8.2 ± 1.9, P = .01). CLINICAL IMPLICATIONS: These data bring sufficient proof of concept of a conceivable novel medical implant for the treatment of ED caused by mechanical nerve injury, such as prostatectomy and spinal cord injury. STRENGTH & LIMITATIONS: This is the first approach that can ensure the optimal site stimulation of the erectogenic neuronal path within the lower pelvic area and overcome the major barrier of individual anatomic variability. However, because this study was performed intraoperatively in an acute scenario, further studies are needed to evaluate its chronic efficacy for clinical practice. CONCLUSION: The flexible electrode array concept can ensure the electrostimulation of erectogenic neuronal path when positioned on the prostate apex or pelvic floor. Skoufias S, Sturny M, Fraga-Silva R, et al. Novel concept enabling an old idea: A flexible electrode array to treat neurogenic erectile dysfunction. J Sex Med 2018;15:1558-1569.

Total arterial compliance, estimated by a novel method, is better related to left ventricular mass compared to aortic pulse wave velocity: The SAFAR study.

AIM: The investigation of the association between total arterial compliance (CT)-estimated by a novel technique-with left ventricular mass (LVM) and hypertrophy (LVH). Our hypothesis was that CT may be better related to LVM compared to the gold-standard regional aortic stiffness. Within the frame of the ongoing cross-sectional study "SAFAR," 226 subjects with established hypertension or with suspected hypertension underwent blood pressure (BP) assessment, carotid-to-femoral pulse wave velocity (cf-PWV), and echocardiographic measurement of LVM. LVM index (LVMI) was calculated by the ratio of LVM to body surface area. CT was estimated by a previously proposed and validated formula: CT = 36.7 /cf-PWV2 [ml/mmHg]. LVMI was related to age (r = 0.207, p = 0.002), systolic BP (r = 0.248, p < 0.001), diastolic BP (r = 0.139, p = 0.04), mean BP (r = 0.212, p = 0.002), pulse pressure (r = 0.212, p = 0.002), heart rate (r = -0.172, p = 0.011), cf-PWV (r = 0.268, p < 0.001), and CT (r = -0.317, p < 0.001). The highest correlation was observed for CT that was significantly stronger than the respective correlation of cf-PWV (p < 0.001). In multivariate analysis, CT was a stronger determinant, compared to cf-PWV, of LVMI and LVH. It remains to be further explored whether CT has also a superior prognostic value beyond and above local or regional (segmental) estimates of pulse wave velocity.

Electromagnetic machines in cancer treatment: The "Priore affair".

In the 1960s and 1970s the Italian born scientist Antonio Priore, working in France, amazed the public and divided the scientific world with his invention, a machine which could cure a variety of illnesses, including cancer. Gaining the support of the French government and several scientific organizations, Priore received a great amount of money in funds to sustain his research. Without exposing his exact method, the scientific world questioned the legitimacy of Priore's research. For almost two decades scientists, institutes, journalists and cancer patients were implicated in a sensational case, known as the "Priore affair".

Instances of Biowarfare in World War I (1914-1918).

During World War I (WWI), also referred to as 'The Great War,' Germany implemented a pioneering biowarfare program as part of a broader military strategy to undermine Allied forces by targeting their logistical and supply capabilities. This initiative, unprecedented in its systematic and strategic application, utilized a variety of pathogens, primarily targeting animal populations, to disrupt support systems without contravening international laws, specifically the 1907 Hague Convention. The operations, shrouded in secrecy and largely led by the German General Staff, included sophisticated sabotage actions against both enemy and neutral states. The allegations and usage of bioweapons increased the interest of the Great Powers in further developing their own biowarfare program.