MR‐proADM as marker of endotheliitis predicts COVID‐19 severity García de Guadiana‐Romualdo, Luis; Calvo Nieves, María Dolores; Rodríguez Mulero, María Dolores ...
European journal of clinical investigation,
20/May , Letnik:
51, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Background
Early identification of patients at high risk of progression to severe COVID‐19 constituted an unsolved challenge. Although growing evidence demonstrates a direct association between ...endotheliitis and severe COVID‐19, the role of endothelial damage biomarkers has been scarcely studied. We investigated the relationship between circulating mid‐regional proadrenomedullin (MR‐proADM) levels, a biomarker of endothelial dysfunction, and prognosis of SARS‐CoV‐2‐infected patients.
Methods
Prospective observational study enrolling adult patients with confirmed COVID‐19. On admission to emergency department, a blood sample was drawn for laboratory test analysis. Primary and secondary endpoints were 28‐day all‐cause mortality and severe COVID‐19 progression. Area under the curve (AUC) and multivariate regression analysis were employed to assess the association of the biomarker with the established endpoints.
Results
A total of 99 patients were enrolled. During hospitalization, 25 (25.3%) cases progressed to severe disease and the 28‐day mortality rate was of 14.1%. MR‐proADM showed the highest AUC to predict 28‐day mortality (0.905; CI 95%: 0.829‐0.955; P < .001) and progression to severe disease (0.829; CI 95%: 0.740‐0.897; P < .001), respectively. MR‐proADM plasma levels above optimal cut‐off (1.01 nmol/L) showed the strongest independent association with 28‐day mortality risk (hazard ratio HR: 10.470, 95% CI: 2.066‐53.049; P < .005) and with progression to severe disease (HR: 6.803, 95% CI: 1.458‐31.750; P = .015).
Conclusion
Mid‐regional proadrenomedullin was the biomarker with highest performance for prognosis of death and progression to severe disease in COVID‐19 patients and represents a promising predictor for both outcomes, which might constitute a potential tool in the assessment of prognosis in early stages of this disease.
Heart transplant recipients (HTr) have a higher probability of suffer from severe coronavirus disease-2019 (COVID-19) in comparison to general population, but their risk has changed over the course ...of the pandemic in relation to various factors. We conducted a prospective study including all HTr at risk of COVID-19 in a tertiary center between February 2020 and October 2022. The aim was to analyze how the prognosis (incidence of pneumonia and mortality) of COVID-19 in HTr has evolved over time, contextualizing variants, vaccination, and other treatments.
Of 308 HTr included, 124 got the infection (39.2%). COVID and non-COVID HTr had similar baseline characteristics. COVID-19 patients with pneumonia had a poorer prognosis than those with less severe presentations, with a higher rate of hospitalization (93.3 vs. 14.1%, p < .001) and death (41.0 vs. 1.2%, p < .001). Multivariate analysis identified age ≥60 years (odds ratio OR 3.65, 95% confidence interval CI 1.16-11.49, p = .027), and chronic kidney disease ≥3a (OR 4.95, 95% CI 1.39-17.54, p = .014) as predictors of pneumonia. Two-dose vaccination (OR 0.20, CI 95% 0.05-0.72, p = .02) and early remdesivir administration (OR 0.17, CI 0.03-0.90, p = .037) were protective factors. Over the course of the pandemic considering three periods in the follow-up (prevaccination February-December 2020, postvaccination January-December 2021, and post early remdesivir indication January-October 2022), we observed a reduction in pneumonia incidence from 62% to 19% (p < .001); and mortality (from 23% to 4%, p < .001).
The prognosis of COVID-19 in HTr has improved over time, likely due to vaccination and early administration of remdesivir.
The deposition and manipulation of human remains in natural caves are well known for the Neolithic of Southern Iberia. The cultural meaning of these practices is however still largely unclear. Cueva ...de los Marmoles (CM, Priego-Córdoba) is one of the most important cave contexts from Southern Spain, which returned a large number of commingled skeletal remains suggesting its funerary use from the Neolithic to the Late Bronze Age. Here we discuss CM from a chronological and cultural perspective based on new radiocarbon, anthropological, and taphonomic analyses. These include the estimation of the minimum number of individuals, the exploration of fragmentation patterns characterizing different skeletal regions, and the macroscopic and microscopic analysis of modifications to the remains of possible anthropic origin. Radiocarbon data point to a funerary use of CM between the 5
th
-2
nd
millennium cal. BCE. MNI estimates reveal the presence of at least 12 individuals (seven adults and five nonadults). The low representation of elements from hands and feet suggests that individuals were placed in the cave while partially decomposed. Anthropic traces on the remains (e.g. fresh fractures, marrow canal modifications, and scraping marks) hint at their intentional fragmentation, cleaning from residual soft tissues, and in some cases reutilization. These practices are well-exemplified by the recovery of one "skull cup" and of two long bones used as tools. These data align with those from other cave contexts from the same geographic region, suggesting the presence, especially during the Neolithic period, of shared ideologies centered on the human body.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Wild edible plants have played an important role in traditional diets, including the Mediterranean diet. Many of these plants have acquired an undervalued status, since they are under-appreciated in ...terms of their nutritional, organoleptic qualities, or their seasonality. However, some of these species are still used in local gastronomy for their aromatic and taste characteristics. This study has investigated the quantitative and qualitative aromatic characteristics of seven undervalued wild plants that determine their organoleptic characteristics. Volatiles of the fresh leaves of each species have been determined by head-space solid-phase microextraction, a sensitive and solvent-free technique, coupled with gas chromatography and mass spectrometry. A total of 37 compounds with remarkable quantitative and qualitative differences were identified. In general, benzenoids and monoterpenoids were the most abundant groups, while branched unsaturated hydrocarbons, fatty alcohols, and sesquiterpenoids were the minor groups. Benzyl nitrile, benzyl isothiocyanate, p-cymene, and 2-hexenal were the main individual volatiles, while benzyl alcohol, eugenol, and α-copaene were the differentiating aromas. The results display that the undervalued species studied could be a suitable choice to include as new environmentally friendly crops, providing a double benefit to producers, because they are a possible way to achieve sustainable production systems, and they are an alternative for consumers, because these plants provide flavors that have high organoleptic qualities.
Hydrocephalic hyh mutant mice undergo a programmed loss of the neuroepithelium/ependyma followed by a reaction of periventricular astrocytes, which form a new cell layer covering the denuded ...ventricular surface. We present a comparative morphological and functional study of the newly formed layer of astrocytes and the multiciliated ependyma of hyh mice. Transmission electron microscopy, immunocytochemistry for junction proteins (N-cadherin, connexin 43) and proteins involved in permeability (aquaporin 4) and endocytosis (caveolin-1, EEA1) were used. Horseradish peroxidase (HRP) and lanthanum nitrate were used to trace the intracellular and paracellular transport routes. The astrocyte layer shares several cytological features with the normal multiciliated ependyma, such as numerous microvilli projected into the ventricle, extensive cell–cell interdigitations and connexin 43-based gap junctions, suggesting that these astrocytes are coupled to play an unknown function as a cell layer. The ependyma and the astrocyte layers also share transport properties: (1) high expression of aquaporin 4, caveolin-1 and the endosome marker EEA1; (2) internalization into endocytic vesicles and early endosomes of HRP injected into the ventricle; (3) and a similar paracellular route of molecules moving between CSF, the subependymal neuropile and the pericapillary space, as shown by lanthanum nitrate and HRP. A parallel analysis performed in human hydrocephalic foetuses indicated that a similar phenomenon would occur in humans. We suggest that in foetal-onset hydrocephalus, the astrocyte assembly at the denuded ventricular walls functions as a CSF–brain barrier involved in water and solute transport, thus contributing to re-establish lost functions at the brain parenchyma–CSF interphase.
Objective
To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic‐clonic seizures (GTCS).
...Methods
This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure‐free rate after 3, 6, and 12 months and tolerability throughout the follow‐up.
Results
A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1‐57) with a median dose of 4 mg (range = 2‐10). The retention rates at 3, 6, and 12 months and last follow‐up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log‐rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3‐26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure‐free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow‐up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1‐8.33, P = .046).
Significance
PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.
Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined.
This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective ...observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020.
We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p < 0.0001); ECOG 3-4 (OR, 2.56, 95% CI 1.4-4.7, p = 0.003); neutropenia (< 0.5 × 10
/L) (OR 2.8, 95% CI 1.3-6.1, p = 0.01); and a C-reactive protein (CRP) > 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1).
In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.
•Endotheliopathy is a pathological feature associated with thromboinflammation.•Endothelial biomarkers may help the stratification of risk in COVID-19.•Disruption of the adrenomedullin system ...contributes to endothelial dysfunction.•MR-proADM might be useful for early risk stratification of COVID-19.
Thromboinflammation, resulting from a complex interaction between thrombocytopathy, coagulopathy, and endotheliopathy, contributes to increased mortality in COVID-19 patients. MR-proADM, as a surrogate of adrenomedullin system disruption, leading to endothelial damage, has been reported as a promising biomarker for short-term prognosis. We evaluated the role of MR-proADM in the mid-term mortality in COVID-19 patients.
A prospective, observational study enrolling COVID-19 patients from August to October 2020. A blood sample for laboratory test analysis was drawn on arrival in the emergency department. The primary endpoint was 90-day mortality. The area under the curve (AUC) and Cox regression analyses were used to assess discriminatory ability and association with the endpoint.
A total of 359 patients were enrolled, and the 90-day mortality rate was 8.9%. ROC AUC for MR-proADM predicting 90-day mortality was 0.832. An optimal cutoff of 0.80 nmol/L showed a sensitivity of 96.9% and a specificity of 58.4%, with a negative predictive value of 99.5%. Circulating MR-proADM levels (inverse transformed), after adjusting by a propensity score including eleven potential confounders, were an independent predictor of 90-day mortality (HR: 0.162 95% CI: 0.043-0.480)
Our data confirm that MR-proADM has a role in the mid-term prognosis of COVID-19 patients and might assist physicians with risk stratification.
The adenoma detection rate (ADR) is the most important marker of colonoscopy quality. Devices to improve adenoma detection have been developed, such as the Endocuff and transparent cap. The aim of ...the current study was to examine whether there was a difference in ADR between Endocuff-assisted (EAC) and cap-assisted colonoscopy (CAC).
A randomized prospective trial was conducted. Eligible patients included adults ≥ 18 years referred because of symptoms, surveillance, or colonoscopies as part of the Bowel Cancer Screening Programme (BCSP). The primary outcome measure was ADR. Secondary outcomes included mean number of adenomas, mean number of polyps, polyp detection rate, cecal intubation rate, and time to cecal intubation. Procedural measures, device removal rate, and adverse events were also recorded.
A total of 711 patients (51.1 % men; median age 63 years) were included, of whom 357 patients were randomized to EAC and 354 patients to CAC. In the intention-to-treat analysis, the ADR was similar in both groups: EAC 50.4 % (95 % confidence interval CI 45.1 - 55.7) vs. CAC 50.6 % (95 %CI 45.2 - 55.9). Similar results were obtained in the per-protocol analysis: EAC 51.6 % (95 %CI 46.2 - 57) vs. CAC 51.4 % (95 %CI 46 - 56.8). There were no differences between the two devices in ADR according to the mean number of adenomas and polyps per procedure, polyp detection rate, cecal intubation rate, and time to cecal intubation. Device removal rate and adverse events were also similar.
In this randomized study, no differences in ADR were found between Endocuff- and cap-assisted colonoscopy.
Jujube fruit (Ziziphus jujuba Mill.) has been a food source since ancient times. In Spain, it is considered a marginal crop, and jujube fruits are of low economic importance. Its consumption is bound ...to local marketplaces. However, jujube is a good alternative crop due to its climatic adaptation and low-input conditions. We aimed to evaluate the morphological, physicochemical, and bioactive compounds of jujube fruits grown under low-input conditions (wild and organic farming) in the Mediterranean basin, specifically in Marjal de los Moros, Valencia, Spain. The organic system produces higher protein, fiber, ash, and carbohydrate concentrations from small-caliber fruit cultivars. Potassium and phosphorus are the major mineral elements in jujube. The fruits’ total polyphenols range from 480.83 to 630.81 mg EGA·100 gsup.−1 fw in organic conditions and 520.71 mg EGA·100 gsup.−1 fw in wild conditions. Low-input conditions influence the production of glucose (sweet fruits) and bioactive compounds, as well as mineral concentrations. A strong relationship exists between vitamin C levels and the potassium concentration. Jujube fruits are classified as “vitamin C-rich”. A 20 g serving of fruit can provide the regular vitamin C requirements of an adult person. The environmental and nutritional opportunities offered by jujubes are in line with different SDGs.
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