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БЕРЕМЕННОСТЬД-ДИМЕРБЕРЕМЕННОСТИ ОСЛОЖНЕНИЯГЕМОСТАЗПОСЛЕРОДОВОЙ ПЕРИОДБИОЛОГИЧЕСКИЕ МАРКЕРЫПРОГНОЗИРОВАНИЕПРЕНАТАЛЬНАЯ ДИАГНОСТИКАД-димер является важным показателем активации системы гемостаза, увеличивающимся в течение физиологически протекающей беременности. В статье рассматриваются вопросы референсных значений Д-димера при беременности и в послеродовом периоде

Fractional spinal anesthesia and systemic hemodynamics in frail elderly hip fracture patients [version 3; peer review: 1 approved, 2 approved with reservations]

Background: Systemic haemodynamic effects of intrathecal anaesthesia in an aging and frail population has not been well investigated. We examined the systemic haemodynamics of fractional spinal anaesthesia following intermittent microdosing of a local anaesthetic and an opioid. Methods: We included 15 patients aged over 65 with significant comorbidities, planned for hip fracture repair. Patients received a spinal catheter and cardiac output monitoring using the LiDCOplus system. All measurements were performed prior to start of surgery. Invasive mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), heart rate and stroke volume index (SVI) were registered. Two doses of bupivacaine 2.25 mg and fentanyl 15 µg were administered with 25-minute intervals. Hypotension was defined as a fall in MAP by >30% or a MAP <65 mmHg. Results: The incidence of hypotension was 30%. Hypotensive patients (n=5) were treated with low doses of norepinephrine (0.01-0.12 µg/kg/min). MAP showed a maximum reduction of 17% at 10 minutes following the first dose. CI, systemic vascular resistance index and stroke volume index decreased by 10%, 6%, and 7%, respectively, while heart rate was unchanged over time. After the second dose, none of the systemic haemodynamic variables were affected. Conclusions: Fractional spinal anaesthesia administered prior to surgery induced a minor to moderate fall in MAP, mainly caused by a reduction in cardiac output, induced by systemic venodilation, causing a fall in venous return. Our results are contrary to the widely held belief that hypotension is mainly the result of a reduction of systemic vascular resistance

Studies in patients with septic shock and subarachnoid haemorrhage.

In this thesis, strain echocardiography by two-dimensional speckle tracking imaging (2D-STI), was used for the evaluation of left ventricular (LV) and right ventricular (RV) function in critically ill patients with septic shock and subarachnoid haemorrhage. The aims were to: 1) investigate the value of strain echocardiography for the early detection of LV and RV dysfunction not diagnosed with conventional echocardiography in severe sepsis and septic shock, 2) to study the effects of norepinephrine on RV systolic function and pulmonary haemodynamics in patients with norepinephrine-dependent septic shock 3) evaluate the use of strain echocardiography for detection of myocardial injury in patients with subarachnoid haemorrhage (SAH) and 4) study the impact of general anaesthesia and positive pressure ventilation (PPV) on RV and LV myocardial longitudinal strain. The main findings were that LV and RV systolic performances, as detected by 2D-STI, were impaired to a greater extent in septic patients with preserved ejection fraction, when compared to critically ill, non-septic patients with preserved ejection fraction. In septic shock, norepinephrine-induced increases in mean arterial pressure (MAP), improves RV performance without affecting pulmonary vascular resistance (PVR). The diagnostic performance of global LV strain and regional LV strain to detect myocardial injury in patients with subarachnoid haemorrhage is not superior to that of conventional echocardiography. Finally, general anaesthesia with positive pressure ventilation decreases absolute values of LV and RV longitudinal strain in patients with no heart disease. In conclusion, strain imaging is useful in the early detection of myocardial dysfunction in sepsis and evaluation of the vasopressor therapy. It does not have better diagnostic performance in detecting global or regional systolic dysfunction in patients with (SAH) than conventional echocardiography. The impact of anaesthesia and PPV should be taken into consideration when strain imaging is used in ICU patients

Strain echocardiography identifies impaired longitudinal systolic function in patients with septic shock and preserved ejection fraction

Background: Myocardial dysfunction is recognized in sepsis. We hypothesized that mechanical left (LV) and right (RV) ventricular function analysed using 2-dimensional speckle-tracking echocardiography in a cohort of early severe sepsis or septic shock patients, would be different to that of a group of critically ill, non-septic patients. Methods: Critically ill adult patients with early, severe sepsis/septic shock (n = 48) and major trauma patients with no sepsis (n = 24) were included retrospectively, as well as healthy controls (n = 16). Standard echocardiographic examinations, including right (RV) left (LV) volumes and mitral, aortic and pulmonary vein Doppler flow profiles, were retrospectively identified and the studies were then reanalysed for assessment of myocardial strain using speckle-tracking echocardiography. Endocardial tracing of the LV was performed in apical four-chamber (4-Ch), two-chamber (2-Ch), apical long-axis (3-Ch) and apical views of RV determining the longitudinal LV and RV free wall strain in each subject. Results: In septic patients, heart rate was significantly higher (p = 0.009) and systolic (p &lt; 0.001) and mean arterial pressures (p &lt; 0.001), as well as systemic vascular resistance (p &lt; 0.001) were significantly lower when compared to the non-septic trauma group. Ninety-three per cent of the septic patients and 50 % of the trauma patients were treated with norepinephrine (p &lt; 0.001). LV ejection fraction (LVEF) was lower in the septic patients (p = 0.019). In septic patients with preserved LVEF (&gt;50 %, n = 34), seventeen patients (50 %) had a depressed LV global longitudinal function, defined as a LV global strain &gt; -15 %, compared to two patients (8.7 %) in the non-septic group (p = 0.0014). In septic patients with preserved LVEF, LV global and RV free wall strain were 14 % (p = 0.014) and 17 % lower (p = 0.008), respectively, compared to the non-septic group with preserved LVEF. There were no significant differences between groups with respect to LV end-diastolic or end-systolic volumes, stroke volume, or cardiac output. There were no signs of diastolic dysfunction from the mitral or pulmonary vein Doppler profiles in the septic patients. Conclusions: LV and RV systolic function is impaired in critically ill patients with early septic shock and preserved LVEF, as detected by Speckle-tracking 2D echocardiography. Strain imaging may be useful in the early detection of myocardial dysfunction in sepsis

Radiological appearance and lung function six months after invasive ventilation in ICU for COVID-19 pneumonia: An observational follow-up study.

BackgroundRespiratory functional sequelae in COVID-19 patients admitted to the intensive care unit for invasive ventilation are sparsely reported. The aim of this study was to investigate the radiological lung appearance, lung function and their association at 6 months after hospital discharge. It was hypothesized that the degree of pathological morphology on CT scans would correlate with lung function at the time of follow-up.Methods and findingsIn this single-centre prospective observational study, 86 from 154 patients admitted to ICU due to COVID-19 between March 2020 and May 2021 were followed up at 6 months post discharge with computed tomography (CT) of the chest and pulmonary function tests (PFTs). The PFT results were expressed as z-scores calculated as the difference between the measured and predicted values divided by the standard deviation obtained from a reference population. Correlations were evaluated by Spearman's rho including the 95% confidence interval. Pathological changes on CT were found in 78/85 participants with fibrous parenchymal bands being the most prevalent finding (91%) followed by traction bronchiectasis (64%) and ground glass opacities (41%). Sixty-five participants performed PFTs, and a restrictive pattern was the most prevalent abnormality (34%). Diffusing capacity of the lung for carbon monoxide (DLCO) was reduced in 66% of participants. The CT severity score weakly correlated with forced vital capacity (FVC) z-score (0.295, p = 0.006), DLCO z-score (-0.231, p = 0.032) and alveolar volume (VA) z-score (0.253, p = 0.019).ConclusionsMost patients showed persistent radiological abnormalities on CT and reduced lung volumes, impaired diffusion capacity and patterns of restrictive lung function at 6 months post discharge from the ICU. The correlations between abnormalities on CT and lung function tests were weak. Further, studies with a long-term follow-up of lung function in this group of patients are needed

Design, physico-chemical characterization and in vitro biological activity of organogold(III) glycoconjugates

To develop new metal-based glycoconjugates as potential anticancer agents, four organometallic gold(iii)-dithiocarbamato glycoconjugates of the type [AuIII(2-Bnpy)(SSC-Inp-GlcN)](PF6) (2-Bnpy: 2-benzylpyridine; Inp: isonipecotic moiety; GlcN: amino-glucose scaffold; Au3-Au6) and the corresponding model non-glycosylated counterparts [AuIII(2-Bnpy)(SSC-Inp-R)](PF6) (R: OEt (Au1), NH2 (Au2)) have been generated and characterized by means of several analytical techniques (elemental analysis, FT-IR, 1H-/13C-NMR, ESI-MS, UV-Vis, X-ray crystallography). Their stability under physiologically-relevant conditions (PBS solution) and n-octanol/PBS distribution coefficient (D7.4) have also been evaluated. Gold(iii) glycoconjugates showed an antiproliferative effect against ovarian carcinoma A2780 cells, with GI50 values in the low micromolar range. Remarkably, their cell growth inhibitory effect increases upon the addition of a glucose transporter 1 (GLUT1) inhibitor, thus ruling out the involvement of GLUT1 in their transport inside the cell. Additional mechanistic studies have been carried out in A2780 cells, supporting the hypothesis of a facilitated diffusion mechanism (possibly mediated by glucose transporters other than GLUT1), and revealing their capability to act as topoisomerase I and II inhibitors and to disrupt mitochondrial membrane integrity, leading to the generation of ROS, thus resulting in the promotion of oxidative stress and, eventually, cell death

Data_Sheet_1_Sex difference in circulating soluble form of ACE2 protein in moderate and severe COVID-19 and healthy controls.PDF

IntroductionMembrane-bound angiotensin-converting enzyme-2 (ACE2) in epithelial cells is the main receptor for SARS-CoV-2. The extracellular portion of ACE2 may be shedded to plasma in which process ADAM17 (a disintegrin and metalloproteinase 17) is important. Results on the relationship between circulating levels of the soluble form of ACE2 (sACE2) and disease severity are inconclusive. This study investigates if sACE2 concentration correlates with COVID-19 severity, and whether this is affected by sex.Materials and methodsSoluble form of ACE2 was analyzed in three groups: 104 patients (23 women and 81 men) with severe COVID-19 admitted to an intensive care unit (ICU), patients with moderate COVID-19 who required hospital care (n = 19, 4 women and 15 men), and age and sex matched healthy controls (n = 20, 4 women and 16 men). Blood samples were collected at hospital admission between 18 March 2020, and 3 May 2021, and at follow-up between 27 October 2020, and 19 October 2021. Circulating sACE2 (μg/L) was measured in EDTA plasma with a sensitive enzyme-linked immunosorbent assay. Additionally, CRP, ferritin, and lymphocyte count were analyzed during hospital stay.ResultsIn total, 23 patients (22%) died in the ICU. When comparing healthy controls [mean age 58.1 (SD 11.4) years] and patients with moderate COVID-19 [mean age 61.0 (SD 13.2) years] with patients in the ICU [mean age 63.6 (SD 11.6) years], we found that sACE2 concentration decreased (70% reduction) with disease severity in men (p = 0.002) but increased 3.7-fold with severity in women (p = 0.043), suggesting a sex-related difference in how COVID-19 severity is related to sACE2 concentration. Moreover, we identified a relationship between inflammatory biomarkers and sACE2 concentration during the intensive care treatment, such that higher CRP and higher ferritin concentration correlated with lower sACE2 concentration in men.ConclusionThe decrease in sACE2 concentration, selectively in men, in severe COVID-19 is of pathophysiological interest since men are affected more severely by the disease compared to women. Additionally, the inflammatory biomarkers, CRP and ferritin, correlated inversely with sACE2 concentration, suggesting a role in severe disease. Our findings imply that sACE2 is a possible biomarker of disease severity in a sex-specific manner.</p

Cerebrospinal fluid biomarkers of synaptic dysfunction are altered in Parkinson's disease and related disorders

Background: Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects. Objective: To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders. Methods: Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n1 = 51, n2 = 101), corticobasal degeneration (CBD) (n1 = 11, n2 = 3), progressive supranuclear palsy (PSP) (n1 = 22, n2 = 21), multiple system atrophy (MSA) (n1 = 31, n2 = 26), and healthy control (HC) (n1 = 48, n2 = 30) participants, as well as Alzheimer's disease (AD) (n2 = 23) patients in the second cohort. Results: Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P &lt; 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P &lt; 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021). Conclusions: These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD.