Abstract
Brain hypoxia can occur after non-traumatic subarachnoid hemorrhage (SAH), even when levels of intracranial pressure (ICP) remain normal. Brain tissue oxygenation (PbtO
2
) can be measured ...as a part of a neurological multimodal neuromonitoring. Low PbtO
2
has been associated with poor neurologic recovery. There is scarce data on the impact of PbtO
2
guided-therapy on patients’ outcome. This single-center cohort study (June 2014–March 2020) included all patients admitted to the ICU after SAH who required multimodal monitoring. Patients with imminent brain death were excluded. Our primary goal was to assess the impact of PbtO
2
-guided therapy on neurological outcome. Secondary outcome included the association of brain hypoxia with outcome. Of the 163 patients that underwent ICP monitoring, 62 were monitored with PbtO
2
and 54 (87%) had at least one episode of brain hypoxia. In patients that required treatment based on neuromonitoring strategies, PbtO
2
-guided therapy (OR 0.33 CI 95% 0.12–0.89) compared to ICP-guided therapy had a protective effect on neurological outcome at 6 months. In this cohort of SAH patients, PbtO
2
-guided therapy might be associated with improved long-term neurological outcome, only when compared to ICP-guided therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neurological outcome and mortality of patients suffering from poor grade subarachnoid hemorrhage (SAH) may have changed over time. Several factors, including patients' characteristics, the presence ...of hydrocephalus and intraparenchymal hematoma, might also contribute to this effect. The aim of this study was to assess the temporal changes in mortality and neurologic outcome in SAH patients and identify their predictors.
We performed a single center retrospective cohort study from 2004 to 2018. All non-traumatic SAH patients with poor grade on admission (WFNS score of 4 or 5) who remained at least 24 h in the hospital were included. Time course was analyzed into four groups according to the years of admission (2004-2007; 2008-2011; 2012-2015 and 2016-2018).
A total of 353 patients were included in this study: 202 patients died (57 %) and 260 (74 %) had unfavorable neurological outcome (UO) at 3 months. Mortality tended to decrease in in 2008-2011 and 2016-2018 periods (HR 0.55 0.34-0.89 and HR 0.33 0.20-0.53, respectively, when compared to 2004-2007). The proportion of patients with UO remained high and did not vary significantly over time. Patients with WFNS 5 had higher mortality (68 % vs. 34 %, p = 0.001) and more frequent UO (83 % vs. 54 %, p = 0.001) than those with WFNS 4. In the multivariable analysis, WFNS 5 was independently associated with mortality (HR 2.12 1.43-3.14) and UO (OR 3.23 1.67-6.25). The presence of hydrocephalus was associated with a lower risk of mortality (HR 0.60 0.43-0.84).
Both hospital mortality and UO remained high in poor grade SAH patients. Patients with WFNS 5 on admission had worse prognosis than others; this should be taken into consideration for future clinical studies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Serum lactate dehydrogenase (LDH) levels are often elevated in cardiovascular diseases. Their prognostic role after subarachnoid hemorrhage (SAH) remains poorly evaluated.
This is a retrospective ...single-center study of patients with non-traumatic SAH admitted to the intensive care unit (ICU) of an University Hospital from 2007 to 2022. Exclusion criteria were pregnancy and incomplete medical records or follow-up data. Baseline information, clinical data, radiologic data, the occurrence of neurological complications as well as serum LDH levels during the first 14 days of ICU stay were collected. Unfavorable neurological outcome (UO) at 3 months was defined as a Glasgow Outcome Scale of 1-3.
Five hundred and forty-seven patients were included; median serum LDH values on admission and the highest LDH values during the ICU stay were 192 160-230 IU/L and 263 202-351 IU/L, respectively. The highest LDH value was recorded after a median of 4 2-10 days after ICU admission. LDH levels on admission were significantly higher in patients with UO. When compared with patients with favorable outcome (FO), patients with UO had higher serum LDH values over time. In the multivariate logistic regression model, the highest LDH value over the ICU stay (OR 1.004 95% CI 1.002 - 1.006) was independently associated with the occurrence of UO; the area under the receiving operator (AUROC) curve for the highest LDH value over the ICU stay showed a moderate accuracy to predict UO (AUC 0.76 95% CI 0.72-0.80; p < 0.001), with an optimal threshold of > 272 IU/L (69% sensitivity and 74% specificity).
The results in this study suggest that high serum LDH levels are associated with the occurrence of UO in SAH patients. As a readily and available biomarker, serum LDH levels should be evaluated to help with the prognostication of SAH patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Blood lactate concentrations are often used to assess global tissue perfusion in critically ill patients; however, there are scarce data on lactate concentrations after subarachnoid hemorrhage (SAH). ...We aimed to assess the prognostic role of serial blood lactate measurements on hospital mortality and neurological outcomes at 3 months after SAH. We reviewed all SAH patients admitted to the intensive care unit from 2007 to 2019 and recorded the highest daily arterial lactate concentration for the first 6 days. Patients with no lactate concentration were excluded. Hyperlactatemia was defined as a blood lactate concentration >2.0 mmol/L. A total of 456 patients were included: 158 (35%) patients died in hospital and 209 (46%) had an unfavorable outcome (UO) at 3 months. The median highest lactate concentration was 2.7 (1.8-3.9) mmol/L. Non-survivors and patients with UO had significantly higher lactate concentrations compared to other patients. Hyperlactatemia increased the chance of dying (OR 4.19 (95% CI 2.38-7.39)) and of having UO in 3 months (OR 4.16 (95% CI 2.52-6.88)) after adjusting for confounding factors. Therefore, initial blood lactate concentrations have prognostic implications in patients with SAH; their role in conjunction with other prognostic indicators should be evaluated in prospective studies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Alkaline phosphatase (ALP) levels are often elevated in cerebrovascular and cardiovascular disease. Their prognostic role after subarachnoid hemorrhage (SAH) remains to be elucidated.
We performed a ...retrospective single center study of patients with non-traumatic SAH admitted to the intensive care unit (ICU) of Erasme Hospital (Brussels, Belgium) from 2006 to 2019. Exclusion criteria were previous history of liver cirrhosis or malignancies and early death (i.e. within 24 h from ICU admission). Baseline information, clinical data, radiologic data were collected, the occurrence of DCI as well as serum ALP levels during the first 12 days of ICU stay. Unfavorable neurological outcome (UO) at 3 months was defined as a Glasgow Outcome Scale of 1–3.
Six hundred and fifty patients were included; ALP levels increased from baseline after day 6 from admission, in particular among patients with an initial poor clinical status. There was no difference in the ALP levels between patients with or without DCI over time. Patients with UO had higher ALP levels over time than others; however, in the multivariable analysis, nor ALP levels on admission or the highest ALP value during the ICU stay were independently associated with UO.
The results of this study suggested that ALP levels had no prognostic role in SAH patients. Other possible prognostic biomarkers should be evaluated in this setting.
•We have evaluated the role of the alkaline phosphatase in the course of one type of cerebrovascular disease.•Alkaline phosphatase is not associated with poor outcomes in this analysis.•Alkaline phosphatase is increased during the first twelve days in the intensive care unit.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We addressed elevated C-reactive protein level (eCRP) specificity comparing, for the first time, eCRP (i.e., serum CRP > 3 and ≤10 mg/L) in patients with major depressive disorder (MDD), bipolar ...disorder (BD), or obsessive–compulsive disorder (OCD). We also assessed to what extent multiple variables that can potentially increase inflammation may have influenced eCRP in our sample.
We performed a retrospective, observational, cross-sectional study using information documented in the electronic medical records (EMRs) of patients hospitalized for a 4-week psychiatric rehabilitation program. We collected all information according to the standardized procedures of the hospital's clinical practice and applied a logistic regression model (α = 0.05).
We included 388 inpatients, that is, 156 (40.2%) with MDD, 135 (34.8%) with BD, and 97 (25.0%) with OCD, and found considerable eCRP rates among them (36.5%, 47.4%, and 29.9% in MDD, BD, and OCD, respectively) but without significant differences across groups. In the whole sample, eCRP variations were only partially attributable (approximately for one-third) to potential confounders. All groups presented considerable rates of cardiovascular risk factors, and we classified most patients as having medium or high CRP-based cardiovascular risk.
This first study comparing eCRP in MDD, BD, and OCD suggests that eCRP may be a transdiagnostic feature of different psychiatric disorders, and other mechanisms beyond the effects of multiple confounders may explain the presence of eCRP in a substantial portion of psychiatric patients. Therefore, we encourage the routine measurement of CRP in psychiatric clinical practice.
•Patients with MDD, BD or OCD had elevated C-reactive protein levels (eCRP).•eCRP may be a transdiagnostic feature across different psychiatric disorders.•Multiple confounders explained only partially the eCRP variations in the sample.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Donkeys reared in Central Italy are highly exposed to tick-borne pathogens.•High levels of exposure to piroplasms were detected.•A lesser extent of exposure to Anaplasma phagocytophilum was ...found.•No evidences of Borrelia burgdorferi infection were found.•A molecular characterization of Theileria equi strains was obtained.
Donkeys, owing to the frequent outdoor activity, are exposed to a high risk of infection with tick-borne pathogens. This work aimed to detect exposure to Theileria equi, Babesia caballi, Anaplasma phagocytophilum and Borrelia burgdorferi s.l. of donkeys reared in Central Italy.
For this purpose 122 adult donkeys were selected within 11 herds and submitted to blood collection. IgG antibodies to T. equi, B. caballi, A. phagocytophilum and B. burgdorferi s.l. were detected by IFAT. Conventional PCRs targeting the genes MSP2 and the flagellin were used for the detection of A. phagocytophilum and B. burgdorferi s.l. respectively and a Real Time PCR Sybr Green was used to detect Babesia/Theileria spp…. The species identity was determined by amplicons sequencing.
Forty eight (39.3%) and 58 (47.5%) animals tested positive for T. equi and B. caballi antibodies, respectively; nine animals (7.4%) were found positive for antibodies against A. phagocytophilum whereas negative results were obtained for B. burgdorferi s.l. Twenty-six (21.3%) animals showed antibodies for both T. equi and B. caballi. Twenty-three (18.8%) donkeys were positive to Babesia/Theileria spp. PCR assay. Out of 21 sequenced amplicons, 20 were identified as T. equi, belonging to three main groups designated A, B and D and one as B. caballi group A. Neither A. phagocytophilum nor B. burgdorferi PCR results were positive.
The study showed a high exposure of donkeys to tick-borne pathogens and provides information on the genetic identity of the T. equi strains circulating in Central Italy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Nucleophosmin (NPM1) is the most frequently mutated gene in Acute Myeloid Leukemia (AML) patients and mutations lead to its aberrant cytoplasmatic accumulation in leukemic cells. Its C-terminal ...domain (CTD) is endowed with a globular structure consisting of a three-helix bundle in the wild type form that is disrupted by AML mutations. Our recent results demonstrate, unexpectedly and unequivocally, that regions of the CTD of NPM1 are prone to aggregate to amyloid states. Here we present novel studies, at solution as well as fibrillar states of a nonapeptide covering the 264–272 region of NPM1: this small fragment is the most amyloidogenic stretch of the entire protein and its conformational and aggregation properties were investigated through Circular Dichroism, Fluorescence spectroscopies, amyloid seeding assay (ASA), isothermal titration calorimetry (ITC) and electrospray ionization (ESI) mass analyses. Structural features of fibrils were investigated by means of Scanning Electron Microscopy (SEM) and Wide-Angle X-ray Scattering (WAXS).
This study deepens the amyloid fibrillization process of a short stretch of the CTD likely involved in the propagative mechanism for NPMc+ cytoplasmatic accumulation in leukemogenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Nucleophosmin (NPM1) is a multifunctional protein involved in a variety of biological processes including the pathogenesis of several human malignancies and is the most frequently mutated gene in ...Acute Myeloid Leukemia (AML). To deepen the role of protein regions in its biological activities, lately we reported on the structural behavior of dissected C-terminal domain (CTD) helical fragments. Unexpectedly the H2 (residues 264–277) and H3 AML-mutated regions showed a remarkable tendency to form amyloid-like assemblies with fibrillar morphology and β-sheet structure that resulted as toxic when exposed to human neuroblastoma cells. More recently NPM1 was found to be highly expressed and toxic in neurons of mouse models of Huntington's disease (HD). Here we investigate the role of each residue in the β-strand aggregation process of H2 region of NPM1 by performing a systematic alanine scan of its sequence and structural and kinetic analyses of aggregation of derived peptides by means of Circular Dichorism (CD) and Thioflavin T (Th-T) assay. These solution state investigations pointed out the crucial role exerted by the basic amyloidogenic stretch of H2 (264–271) and to shed light on the initial and main interactions involved in fibril formation we performed studies on fibrils deriving from the related Ala peptides through the analysis of fibrils with birefringence of polarized optical microscopy and wide-angle X-ray scattering (WAXS). This analysis suggested that the presence of branched Ile269 conferred preferential packing patterns that, instead, appeared geometrically hampered by the aromatic side-chain of Phe268. Present investigations could be useful to deepen the knowledge of AML molecular mechanisms and the role of cytoplasmatic aggregates of NPM1c+.
•In this study the role of dissected C-terminal domain (CTD) helical fragments of Nucleophosmin protein was investigated.•We deepened the tendency of H2 region of to form assemblies with fibrillar morphology through an alanine scan, structural and kinetic analyses.•CD, Th-T, FT-IR experiments and birefringence of polarized optical microscopy and WAXS assays were employed in this study•Our study pointed out that the basic amyloidogenic stretch and that Ile269 conferred packing patterns to the fiber.•Present findings deepen the knowledge of AML molecular mechanisms and the role of cytoplasmatic aggregates of NPM1c +.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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