Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma-Brain Disjunction.

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models.

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial.

BACKGROUND: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. METHODS: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. FINDINGS: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). INTERPRETATION: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. FUNDING: National Institute of Neurological Disorders and Stroke and Genentech.

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial.

BACKGROUND: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. METHODS: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. FINDINGS: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22-3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31-0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64-0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37-3·91], p=0·771) was similar. INTERPRETATION: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. FUNDING: National Institute of Neurological Disorders and Stroke.

CGRP as a potential mediator for the sexually dimorphic responses to traumatic brain injury.

BACKGROUND: The outcomes of traumatic brain injury (TBI) exhibit variance contingent upon biological sex. Although female sex hormones exert neuroprotective effects, the administration of estrogen and progesterone has not yielded conclusive results. Hence, it is conceivable that additional mediators, distinct from female sex hormones, merit consideration due to their potential differential impact on TBI outcomes. Calcitonin gene-related peptide (CGRP) exhibits sexually dimorphic expression and demonstrates neuroprotective effects in acute brain injuries. In this study, we aimed to examine sex-based variations in TBI structural and functional outcomes with respect to CGRP expression. METHODS: Male and female Sprague Dawley rats were exposed to controlled cortical impact to induce severe TBI, followed by interventions with and without CGRP inhibition. In the acute phase of TBI, the study centered on elucidating the influence of CGRP on oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) and endothelial nitric oxide synthase (eNOS) signaling in the peri-impact tissue. Subsequently, during the chronic phase of TBI, the investigation expanded to evaluate CGRP expression in relation to lesion volume, microvascular dysfunction, and white matter injury, as well as working and spatial memory, anxiety-like, and depression-like behaviors in subjects of both sexes. RESULTS: Female rats exhibited elevated levels of CGRP in the peri-impact brain tissue during both baseline conditions and in the acute and chronic phases of TBI, in comparison to age-matched male counterparts. Enhanced CGRP levels in specific brain sub-regions among female rats correlated with superior structural and functional outcomes following TBI compared to their male counterparts. CGRP inhibition induced heightened oxidative stress and a reduction in the expression of Nrf2 and eNOS in both male and female rats, with the observed alteration being more pronounced in females than in males. CONCLUSIONS: This study marks the inaugural identification of CGRP as a downstream mediator contributing to the sexually dimorphic response observed in TBI outcomes.

Investigating sex disparities in traumatic brain injury (TBI) is crucial for the advancement of precision therapeutics. Despite the neuroprotective effects demonstrated by female sex hormones, the administration of estrogen and progesterone has not produced conclusive results. Therefore, it is conceivable that additional mediators, separate from female sex hormones, warrant consideration due to their potential differential influence on TBI outcomes. In this study, we examined sex-related variations in calcitonin gene-related peptide (CGRP) expression in peri-impact brain tissue and investigated its potential implications on associated TBI outcomes. CGRP exhibits sexually dimorphic expression and exerts a multifaceted influence on diverse physiological processes that contribute to the pathophysiology of TBI. Our findings reveal that female rats exhibit heightened CGRP levels at both baseline and post-TBI within specific brain sub-regions, thereby contributing to superior structural and functional outcomes compared to their age-matched male counterparts. Additionally, we identified substantial sex-based variations in mechanisms modulated by CGRP pertaining to oxidative stress and microvascular dysfunction. The disparities in CGRP levels may be crucial for comprehending the advantageous outcomes noted in female TBI. Therefore, elucidating the sex-related distinctions in CGRP within TBI brains could pave the way for improved management and treatment strategies for TBI in both male and female individuals.

Brain temperature measurement: A study of in vitro accuracy and stability of smart catheter temperature sensors.

The injured brain is vulnerable to increases in temperature after severe head injury. Therefore, accurate and reliable measurement of brain temperature is important to optimize patient outcome. In this work, we have fabricated, optimized and characterized temperature sensors for use with a micromachined smart catheter for multimodal intracranial monitoring. Developed temperature sensors have resistance of 100.79 ± 1.19Ω and sensitivity of 67.95 mV/°C in the operating range from15-50°C, and time constant of 180 ms. Under the optimized excitation current of 500 µA, adequate signal-to-noise ratio was achieved without causing self-heating, and changes in immersion depth did not introduce clinically significant errors of measurements (<0.01°C). We evaluated the accuracy and long-term drift (5 days) of twenty temperature sensors in comparison to two types of commercial temperature probes (USB Reference Thermometer, NIST-traceable bulk probe with 0.05°C accuracy; and IT-21, type T type clinical microprobe with guaranteed 0.1°C accuracy) under controlled laboratory conditions. These in vitro experimental data showed that the temperature measurement performance of our sensors was accurate and reliable over the course of 5 days. The smart catheter temperature sensors provided accuracy and long-term stability comparable to those of commercial tissue-implantable microprobes, and therefore provide a means for temperature measurement in a microfabricated, multimodal cerebral monitoring device.

Micromachined lab-on-a-tube sensors for simultaneous brain temperature and cerebral blood flow measurements.

This work describes the development of a micromachined lab-on-a-tube device for simultaneous measurement of brain temperature and regional cerebral blood flow. The device consists of two micromachined gold resistance temperature detectors with a 4-wire configuration. One is used as a temperature sensor and the other as a flow sensor. The temperature sensor operates with AC excitation current of 500 µA and updates its outputs at a rate of 5 Hz. The flow sensor employs a periodic heating and cooling technique under constant-temperature mode and updates its outputs at a rate of 0.1 Hz. The temperature sensor is also used to compensate for temperature changes during the heating period of the flow sensor to improve the accuracy of flow measurements. To prevent thermal and electronic crosstalk between the sensors, the temperature sensor is located outside the "thermal influence" region of the flow sensor and the sensors are separated into two different layers with a thin-film Copper shield. We evaluated the sensors for accuracy, crosstalk and long-term drift in human blood-stained cerebrospinal fluid. These in vitro experiments showed that simultaneous temperature and flow measurements with a single lab-on-a-tube device are accurate and reliable over the course of 5 days. It has a resolution of 0.013 °C and 0.18 ml/100 g/min; and achieves an accuracy of 0.1 °C and 5 ml/100 g/min for temperature and flow sensors respectively. The prototype device and techniques developed here establish a foundation for a multi-sensor lab-on-a-tube, enabling versatile multimodality monitoring applications.

Ketamine for empiric treatment of cortical spreading depolarization after subdural hematoma evacuation.

BACKGROUND: It is widely known that some patients surgically treated for subdural hematoma (SDH) experience neurologic deficits not clearly explained by the acute brain injury or known sequelae like seizures. There is increasing evidence that cortical spreading depolarization (CSD) may be the cause. A recent article demonstrated that CSD occurred at a rate of 15 % and was associated with neurological deterioration in a subset of patients following chronic subdural hematoma evacuation. Furthermore, CSD can lead to ischemia leading to worsening neurologic deficits. CSD is usually detected on electrocorticography (ECoG) and needs cortical strip electrode placement with equipment and expertise that may not be readily available. CASE DESCRIPTION: We report three cases of patients with subdural hematoma (SDH) not undergoing ECoG in whom CSD was suspected to be the cause of their neurologic deficits post evacuation. Extensive workup including neuroimaging and electroencephalography (EEG) were inconclusive. Patients were subsequently treated with ketamine infusion and had resultant neurological recovery. CONCLUSIONS: Ketamine infusion can help reverse neurologic deficits in patients with SDH in whom the deficits are not explained by neuroimaging or electrographic seizure. CSD is a known phenomenon that can result in neurological injury and must remain in the differential diagnosis of such patients. Though only limited cases are discussed (n = 3), this small case series provides the basis for conducting clinical trials evaluating the efficacy of ketamine in improving functional outcome in brain-injured patients demonstrating evidence of CSD.

Antioxidant efficacy of curcuminoids from turmeric ( Curcuma longa L.) powder in broiler chickens fed diets containing aflatoxin B1.

A 3-week-feeding study (1-21 d post-hatch) was conducted to evaluate the efficacy of total curcuminoids (TCMN), as an antioxidant, to ameliorate the adverse effects of aflatoxin B1 (AFB1) in broiler chickens. Turmeric powder (Curcuma longa L.) that contained 2.55 % TCMN was used as a source of TCMN. Six cage replicates of five chicks each were assigned to each of six dietary treatments, which included: basal diet; basal diet supplemented with 444 mg/kg TCMN; basal diet supplemented with 1.0 mg/kg AFB1; basal diet supplemented with 74 mg/kg TCMN and 1.0 mg/kg AFB1; basal diet supplemented with 222 mg/kg TCMN and 1.0 mg/kg AFB1; basal diet supplemented with 444 mg/kg TCMN and 1.0 mg/kg AFB1. The addition of 74 and 222 mg/kg TCMN to the AFB1 diet significantly (P < 0.05) improved weight gain and feed efficiency. Increase (P < 0.05) in relative liver weight in birds fed AFB1 was significantly reduced (P < 0.05) with the addition of 74, 222 and 444 mg/kg TCMN to the AFB1 diet. The inclusion of 222 mg/kg TCMN ameliorated the adverse effects of AFB1 on serum chemistry in terms of total protein, albumin and gamma-glutamyl transferase activity. The decreased antioxidant functions due to AFB1 were also alleviated by the inclusion of 222 mg/kg TCMN. It is concluded that the addition of 222 mg/kg TCMN to the 1.0 mg/kg AFB1 diet demonstrated maximum antioxidant activity against AFB1.

Occurrence of aflatoxins in rice and in cassava (Manihot esculenta) products (meal, bread) produced in Guyana.

A survey was conducted on Guyana's main staple foods, rice, cassava meal and cassava bread to determine the presence and concentration of aflatoxins (AFs) using enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC) with fluorescence detection for concurrence. Aflatoxins are secondary metabolites of the fungus Aspergillus and can be a health risk to humans and animals. Results were compared with European Union Commission (EUC) maximum levels of total aflatoxins of 10 µg/kg. Various types of rice (paddy, steamed paddy, cargo rice, white rice and parboiled rice) were randomly collected either directly from the field and rice mills in Guyana during the November 2015/March 2016 season. Of the total 186 composite samples of rice fractions collected from field and mills, 10% (19) had AF concentrations greater than the maximum EUC level of 10 µg/kg. Fifteen samples had aflatoxin concentrations ranging from 10 to 171 µg/kg, mean 54.4 µg/kg; four samples were outliers. Since Guyanese consume mainly white and parboiled rice, composite samples were taken along the marketing chain at points of sale to determine the presence of AFs. Of the sixty samples of white rice collected, 6.7% (4) had AF concentrations greater than the EUC regulatory limits ranging from 31.9 to 131 µg/kg, mean 80.8 µg/kg. For the 57 samples of parboiled rice, 3.5% (2) samples exceeded the limit with values of 72.6 and 407 µg/kg. Forty (40) samples each of cassava meal and cassava bread were analysed fresh and after 2 months of storage, and no sample exceeded the ELISA detection limit of 0.5 µg/kg.

Cerebrospinal fluid macrophage migration inhibitory factor: a potential predictor of cerebral vasospasm and clinical outcome after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: In patients with aneurysmal subarachnoid hemorrhage (aSAH), poor outcomes have been shown to be correlated with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). The identification of novel biomarkers may aid in the prediction of which patients are vulnerable to developing vasospasm, cerebral ischemia, and neurological deterioration. METHODS: In this prospective clinical study at North Shore University Hospital, patients with aSAH or normal pressure hydrocephalus (NPH) with external ventricular drains were enrolled. The concentration of macrophage migration inhibitory factor (MIF) in CSF was assessed for correlation with CV or DCI, the primary outcome measures. RESULTS: Twenty-five patients were enrolled in the aSAH group and 9 were enrolled in the NPH group. There was a significant increase in aggregate CSF MIF concentration in patients with aSAH versus those with NPH (24.4 ± 19.2 vs 2.3 ± 1.1 ng/ml, p < 0.0002). Incidence of the day of peak MIF concentration significantly correlated with the onset of clinical vasospasm (rho = 0.778, p < 0.0010). MIF concentrations were significantly elevated in patients with versus those without evidence of DCI (18.7 ± 4.93 vs 8.86 ± 1.28 ng/ml, respectively, p < 0.0025). There was a significant difference in MIF concentrations between patients with infection versus those without infection (16.43 ± 4.21 vs 8.5 ± 1.22 ng/ml, respectively, p < 0.0119). CONCLUSIONS: Preliminary evidence from this study suggests that CSF concentrations of MIF are correlated with CV and DCI. These results, however, could be confounded in the presence of clinical infection. A study with a larger patient sample size is necessary to corroborate these findings.

Individual and combined effects of ochratoxin A and Salmonella enterica serovar Gallinarum infection on pathological changes in broiler chickens.

A study was conducted to evaluate the individual and combined effects of ochratoxin A (OA) and Salmonella enterica serovar Gallinarum (S. Gallinarum) on gross and histopathological changes in broiler chickens. One hundred and seventy-six 1-day-old broiler chicks were divided into two groups of 88 chicks each; one group was fed a control mash diet, and the other group was fed a mash diet containing 2 parts/10(6) OA. On day 14, each group was further subdivided into two groups, with one group inoculated with S. Gallinarum intraperitoneally (1.25 x 10(10) colony-forming units/0.5 ml) whereas the other group was not inoculated with S. Gallinarum. Four birds from each group were sacrificed on 1, 2, 3, 5, 7, 10, 14 and 21 days post inoculation to record pathological changes in different organs. Gross and microscopic changes in OA-fed birds indicated the kidneys and bursa of Fabricius as the primary organs to be affected by this toxin. Gross and microscopic changes due to S. Gallinarum infection indicated the liver and spleen as the primary organs affected by this infection. The effects of OA on the kidney and bursa of Fabricius were enhanced following S. Gallinarum infection. Degenerative changes and interstitial nephritis in the kidneys, and lymphocyte depletion from bursal follicles were more pronounced and were observed earlier in the combination group. In conclusion, data indicate that birds fed OA and infected with S. Gallinarum will demonstrate increased pathology compared with birds fed OA alone or those infected with S. Gallinarum but not fed OA.

Aflatoxin B(1) adsorption by natural and copper modified montmorillonite.

Adsorption of aflatoxin B(1) (AFB1) by natural montmorillonite (MONT) and montmorillonite modified with copper ions (Cu-MONT) was investigated. Both MONTs were characterized using the X-ray powder diffraction (XRPD) analysis, thermal analysis (DTA/TGA) and scanning electron miscroscopy/electron dispersive spectroscopy (SEM/EDS). The results of XRPD and SEM/EDS analyses of Cu-MONT suggested partial ion exchange of native inorganic cations in MONT with copper occurred. Investigation of AFB1 adsorption by MONT and Cu-MONT, at pH 3, 7 or 9, showed that adsorption of this toxin by both MONTs was high (over 93%). Since AFB1 is nonionizable, no differences in AFB1 adsorption by both MONTs, at different pHs, were observed, as expected. Futhermore, it was determined that adsorption of AFB1 by both MONTs followed a non-linear (Langmuir) type of isotherm, at pH 3. The calculated maximum adsorbed amounts of AFB1 by MONT (40.982mg/g) and Cu-MONT (66.225mg/g), derived from Langmuir plots of isotherms, indicate that Cu-MONT was much effective in adsorbing AFB1. Since, the main cation in an exchangeable position in MONT is calcium, and in Cu-MONT both calcium and copper, the fact that ion exchange of inorganic cations in MONT with copper increases adsorption of AFB1 suggests that additional interactions between AFB1 and copper ions in Cu-MONT caused greater adsorption.

Electroencephalogram Abnormalities During Positional Changes in Brain Sagging Syndrome.

PURPOSE: Brain sagging after craniotomy and clipping of a ruptured aneurysm is a rare complication. Clinical and electrographic changes in patients with a final diagnosis of intracranial hypotension are not well described, and can be mistaken on rare occasions for other entities such as nonconvulsive status epilepticus. There may be resulting delay in the diagnosis and treatment of this potentially life-threatening disorder. METHODS: Case report and imaging. RESULTS: We present a case of intracranial hypotension in which concerning continuous electroencephalogram (cEEG) and quantitative EEG (qEEG) findings were noted during active sagging of the brain, which resolved with supine positioning. During upright seating, cEEG showed high-amplitude bilateral rhythmic 2-Hz slow-wave activity, and bilateral increase of spectral delta power on qEEG, in association with neurologic decline in function. When placed in supine position, the cEEG and qEEG abnormalities resolved in conjunction with the recovery of neurologic function. CONCLUSIONS: Brain sagging can be diagnosed using simple maneuvers such as supine positioning. This case report describes changes seen in cEEG and qEEG monitoring that accompany these maneuvers, which may provide further evidence for the diagnosis of brain sagging. Thus, cEEG and qEEG monitoring may have a role in the early detection and treatment of brain sagging.

Can Procalcitonin Be Used as a Reliable Marker for Infectious Fever in Patients with Intracranial Hemorrhage?

OBJECTIVE: To determine whether procalcitonin (PCT) levels are different in infected versus noninfected febrile patients with intracranial hemorrhage (ICH). METHODS: This prospective observational study included 104 patients with ICH and fever >38.3°C admitted to the intensive care unit of a tertiary care hospital. PCT was measured on day 1 (PCT 1) of fever and 48-72 hours later (PCT 2). Patients were determined to have an infection (pneumonia, urinary tract infection, or bacteremia) based on cultures, imaging, and clinical impression of treating clinicians. RESULTS: Analysis of variance indicated significant mean differences in patients with no, probable, and definite infection (F2,103 = 3.12, P = 0.048) between PCT 1 and PCT 2 (F2,72 = 4.64, P = 0.013). Patients with probable infection had the highest PCT 1 (mean = 0.47, SD = 0.93), and patients with definite infection had higher PCT 2 (mean = 0.62, SD = 0.85). Additional analyses of univariable mean differences showed mean PCT 1 that was significantly higher in the probable infection group compared with the no infection group. Mean PCT was significantly higher at both time points in the definite infection group compared with the no infection group. There were no significant differences between the probable and definite infection groups. CONCLUSIONS: PCT levels were higher in patients with ICH and infections and may be a useful marker to differentiate between infectious and noninfectious etiologies of fevers in these patients. Further studies, including randomized controlled trials, will help in establishing the utility of this marker in optimal management of febrile patients with ICH.

Changes in renal gene expression associated with induced ochratoxicosis in chickens: activation and deactivation of transcripts after varying durations of exposure.

Exposure to ochratoxin A (OTA) can lead to changes in global gene expression. This study investigated the individual expression of genes turned on and off in renal cells of chicks after different durations of exposure to dietary OTA. One hundred and eighty day-old male broiler chicks (Ross 308) were randomly assigned to a 3 × 3 factorial arrangement of treatments (3 levels of OTA: 0, 1 and 2 mg OTA/kg diet and 3 time periods: 7, 14 and 21 d). Birds were allocated to 36 pens (4 replicate pens of 5 birds each per treatment). For RNA-Sequencing analysis (RNA-Seq), kidney samples were collected weekly from 3 controls and 3 chicks fed 1 mg OTA/kg. Birds fed 2 mg OTA/kg diet were not chosen for analysis because their reduced feed intake could affect gene expression. The libraries were constructed by Illumina's TruSeq RNA protocol. NextGENe software was used for alignment and transcript quantification. Reads per kilobase of target per million tiled reads (RPKM) were used in the Binary test analysis (P < 0.05). The highest RPKM values were used as criterion for the selection of the genes described. A total of 27,638,976 50-bp RNA-Seq reads were produced over the 3 time periods. Transcripts (40,782) were assembled de novo and annotated by homology to either G. gallus or H. sapiens. The genes activated at 7 d were IL9 and TULP1, at 14 d was GHSR and at 21 d were GRK6 and GAPDH. Unlike all other genes, LOC396365 was activated during all time periods. In contrast, the genes deactivated at 7 d were SPAG4 and LOC100857131, at 14 d were LOC771469, NKX2-1, NKX2-8, FOXO1, MyHC and CLDN18 and at 21 d was XPC. The B-G gene was turned off at 7 and 21 d. All of these genes were involved in kidney toxicity. Therefore, the turning on and off responses of these genes may contribute to carcinogenic and tumorigenic effects of OTA in birds.

Rates of iatrogenic ventriculitis before and after the use of an alcohol-impregnated external ventricular drain port cap.

Iatrogenic ventriculitis is a potential complication of ventriculostomy drain placement. In this study, an alcohol-impregnated external ventricular drain port cap was added to a standardized ventriculostomy placement bundle. Rates of ventriculitis were reduced postintervention, but this finding did not reach statistical significance.

Lactobacillus acidophilus bacteraemia after use of a probiotic in a patient with AIDS and Hodgkin's disease.

We report the case of a patient who developed bacteraemia and septic pulmonary emboli with Lactobacillus acidophilus after taking a probiotic containing this organism.

Ventriculoperitoneal Shunt Infection with Mycobacterium abscessus: A Rare Cause of Ventriculitis.

BACKGROUND: Mycobacterium abscessus is a rapidly growing atypical mycobacterium implicated in chronic lung disease, otitis media, surgical site infections, and disseminated cutaneous diseases. It is typically seen in patients with some degree of immunosuppression. Only 1 previous case has been reported in the setting of ventriculoperitoneal (VP) shunt infection. We report a case of M abscessus as the causative organism in a VP shunt infection in an immunocompetent adult. CASE DESCRIPTION: A 67-year-old woman required VP shunt placement after aneurysmal subarachnoid hemorrhage complicated by hydrocephalus. Her course was complicated by repeat hospitalization for 2 shunt infections, the second of which did not respond to standard antibiotic therapy. Cultures repeatedly grew M abscessus. The patient continued to decline and eventually died after transfer to the palliative care service. CONCLUSIONS: Nontuberculous mycobacteria are rare, atypical organisms in the setting of VP shunt infection. Patients with ventriculitis secondary to atypical mycobacteria may exhibit drug-resistant cerebrospinal fluid pleocytosis in the face of standard antibiotic regimens.

A comparison of the test tube and the dialysis tubing in vitro methods for estimating the bioavailability of phosphorus in feed ingredients for swine.

The validity of a simplified in vitro test tube (TT) method was compared with a more complicated dialysis tubing (DT) method to estimate the percentage of available phosphorus (P) in 41 plant origin and five animal origin feed ingredients for swine. The TT method using 1.0 or 0.25 g samples was compared with the DT method using 1.0 g samples at two pancreatic incubation times (2 vs 4 h) in a 3 x 2 factorial arrangement of treatments. Each DT and TT method treatment was replicated three and six times, respectively. Both methods utilize three enzymatic digestions: (i) predigestion with endoxylanase and beta-glucanase for 1 h, (ii) pepsin digestion for 2 h, and (iii) pancreatin digestion for 2 or 4 h. For the TT method, the entire procedure was conducted in a 50 mL conical centrifuge tube and replicated six times. For the DT method, the first two digestions were conducted in a 10 mL plastic syringe before the contents were quantitatively transferred into a segment of DT for the pancreatic digestion. The percentages of hydrolyzed P for plant origin ingredients measured by the DT method using 1.0 g samples and the TT method using 0.25 g samples were highly correlated (r = 0.94-0.97, P < 0.001) with each other and with published in vivo available P values for swine. Repeatabilities for these two methods ranged from 99.64 to 99.86%. The TT method using 1.0 g samples, however, did not provide valid estimates of P availability for all ingredients. For animal origin ingredients, neither method was significantly correlated (r = 0.1-0.6, P >or = 0.4) with published in vivo available P values. In conclusion, the accuracy and validity of the TT method using 0.25 g samples with a 2 h pancreatic digestion time was equal to or superior to the DT method using 1.0 g samples with a 4 h pancreatic digestion time for estimating P availability in plant origin feed ingredients.