Adrenal function in relation to cytokines and outcome in non-critically ill patients with COVID-19.

PURPOSE: We aimed to identify whether hypothalamic-pituitary-adrenal (HPA) axis dysfunction is related to deterioration in a percentage of patients who progress to severe COVID-19. METHODS: In this cohort observational study, we evaluated HPA axis activation by measuring cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate (DHEA-S) levels, whole blood expression levels of the key glucocorticoid receptor, GCR-α, and the glucocorticoid-induced leucine zipper (GILZ), and cytokines, as markers of the inflammatory phase, in 149 patients with respiratory infection admitted in the ward, without known adrenal disease and/or confounding medications (glucocorticoids). One hundred and four (104) patients were SARS-CoV-2 positive (C +) and controls consisted of 45 SARS-CoV-2-negative patients (NC). RESULTS: No differences in cortisol levels were observed between the C + and the NC patients. Cortisol levels correlated with ACTH (r = 0.284, p = 0.001) and IL-6 (r = 0.289, p = 0.04). In C + patients, cortisol levels mainly correlated with IL-6 levels (r = 0.28; p = 0.017). GCR-α expression was significantly higher in C + patients compared to NC. Patients with higher cortisol levels were more likely to progress to respiratory function deterioration or die. Both GCR-α and GILZ expression were significantly higher in C + non-survivors. CONCLUSION: Our findings indicate that cortisol serves as an indicator of disease severity. GILZ expression appears to be a more effective marker of mortality prediction in moderate COVID-19 cases. However, routine measurement of GILZ levels is currently unavailable. Elevated levels of cortisol may be indicative of patients with moderate COVID-19 who are at a higher risk of deterioration. This information can aid in identifying individuals who require early medical attention.

Accuracy of T2 magnetic resonance assays as point-of-care methods in the intensive care unit.

BACKGROUND: Novel molecular diagnostic methods are being evaluated in order to expedite pathogen identification in patients with bacteraemia. AIMS: To evaluate the feasibility and diagnostic accuracy of the T2 magnetic resonance (T2MR) assays - T2 Bacteria (T2B) and T2 Resistance (T2R) - as point-of-care tests in the intensive care unit compared with blood-culture-based tests. METHODS: Prospective cross-sectional study of consecutive patients with suspected bacteraemia. Diagnostic accuracy was evaluated using blood culture as the reference method. FINDINGS: In total, 208 cases were included in the study. The mean time from sampling to report was lower for the T2MR assays compared with blood-culture-based methods (P<0.001). The rate of invalid reports was 6.73% for the T2B assay and 9.9% for the T2R assay. For the T2B assay, overall positive percentage agreement (PPA) was 84.6% [95% confidence interval (CI) 71.9-93.1%], negative percentage agreement (NPA) was 64.3% (95% CI 55.4-72.6%), positive predictive value (PPV) was 48.9% (95% CI 42.5-55.3%) and negative predictive value (NPV) was 91.2% (95% CI 84.4-95.2%). Cohen's kappa coefficient was 0.402. For the T2R assay, overall PPA was 80% (95% CI 51.9-95.7%), NPA was 69.2% (95% CI 54.9-81.3%), PPV was 42.9% (95% CI 31.7-54.8%) and NPV was 92.3% (95% CI 81.1-97.1%). Cohen's kappa coefficient was 0.376. CONCLUSION: T2MR assays have high NPV for rapid exclusion of bacteraemia, and could potentially assist with antimicrobial stewardship when applied as point-of-care diagnostic tests in the intensive care unit.

Ghrelin alterations during experimental and human sepsis.

BACKGROUND: Ghrelin is a hormone mainly produced by cells of the gastric mucosa, which has been shown to possess anti-inflammatory and immunomodulatory properties. The objective of the study was to investigate ghrelin levels during sepsis, as well as in an experimental sepsis model. METHODS: All consecutive admissions to the ICU of a tertiary hospital in Athens, Greece were screened for eligibility during the study. Thirty four non-septic patients upon ICU admission who subsequently developed sepsis were enrolled. Clinical data and scores were recorded, and blood samples were obtained at baseline (upon ICU admission), and at sepsis development. Total and active ghrelin, leptin, and cytokines were measured. Moreover, lipopolysaccharide (LPS) was administered to mice in order to induce endotoxemia and at specified time points, blood and tissue samples were collected. RESULTS: In patients, serum total and active ghrelin concentrations were significantly elevated in sepsis compared to baseline (553.8 ±â€¯213.4 vs 193.5 ±â€¯123.2, p < 0.001; 254.3 ±â€¯70.6 vs 56.49 ±â€¯16.3, p < 0.001). Active ghrelin levels at the sepsis stage were inversely correlated with SOFA score and length of stay in the ICU (p = 0.023 and p = 0.027 respectively). In the mouse endotoxemia model ghrelin levels were elevated following LPS treatment, and the same trend was observed for leptin, TNFα and IL-6. Ghrelin administration managed to reduce IL-6 levels in mouse serum and in BALF. Pulmonary expression of ghrelin and its receptor GHSR1a was found decreased in LPS-treated mice. CONCLUSIONS: In a well-defined cohort of ICU patients, we have demonstrated that active and total ghrelin increase in sepsis. The same is true for the experimental sepsis model used in the study. The inverse correlation of active ghrelin levels with SOFA score and length of ICU stay among septic patients is indicative of a potential protective role of active ghrelin during the septic process.

Elevated soluble endothelial protein C receptor levels at ICU admission are associated with sepsis development.

BACKGROUND: The endothelial protein C receptor (EPCR) is a protein that regulates the protein C anticoagulant and anti-inflammatory pathways. A soluble form of EPCR (sEPCR) circulates in plasma and inhibits activated protein C (APC) activities. The clinical impact of sEPCR and its involvement in the septic process is under investigation. In this study, we assessed the role of sEPCR levels as an early indicator of sepsis development. METHODS: Plasma sEPCR levels were measured in 59 critically-ill non-septic patients at the time of admission to the intensive care unit (ICU). Multiple logistic regression analysis was performed to identify potential risk factors for sepsis development and Cox-Regression models were fitted for variables to examine their relationship with time to sepsis development. RESULTS: Thirty patients subsequently developed sepsis and 29 did not. At ICU admission, sequential organ failure assessment (SOFA) scores were significantly higher in the subsequent sepsis group as compared to the non sepsis group (mean ± SD: 6.4±2.7 and 5±2.3, respectively, P=0.037). sEPCR levels were also higher in the patients who subsequently developed sepsis compared to the patients who did not (median and interquartile range: 173.4 [104.5-223.5] ng/mL vs. 98.3 [69.8-147.7] ng/mL, respectively; P=0.004). Cox regression analysis identified sEPCR as the only parameter related to sepsis development with time (relative risk: 1.078, 95% confidence interval: 1.016-1.144, by 10 units; P=0.013). CONCLUSION: Upon ICU admission, sEPCR levels in initially non-septic critically-ill patients appear elevated in the subjects who will subsequently become septic.

Meniere's disease: Still a mystery disease with difficult differential diagnosis.

One hundred and forty-six years after its first description, the differential diagnosis of Meniere's disease remains very challenging. The aim of the present study is to review the current knowledge on the advantages and disadvantages of the new diagnostic methods for Meniere's disease. The importance of accurate diagnosis for primary healthcare systems is also discussed. An extensive search of the literature was performed in Medline and other available database sources. Information from electronic links and related books were also included. Controlled clinical studies, prospective cohort studies, retrospective cohort studies, cross-sectional studies, case reports, written guidelines, systematic reviews, and books were selected. The typical clinical triad of symptoms from the vestibular and cochlear systems (recurrent vertigo, fluctuating sensorineural hearing loss and tinnitus) is usually the key for clinical diagnosis. Glycerol dehydration test and electrocochleography are the main diagnostic tests in current practice, while vestibular evoked myogenic potentials may be used in disease staging. Imagine techniques are not specific enough to set alone the diagnosis of Meniere's disease, although they may be necessary to exclude other pathologies. Recently developed 3D MRI protocols can delineate the perilymphatic/endolymphatic spaces of the inner ear and aid diagnosis. Meniere's disease is a continuous problem for the patients and affects their quality of life. Taking into account the frequent nature of the disease in certain countries, efforts for reliable diagnosis, prompt referral, and successful management are undoubtedly cost-effective for healthcare systems.

Facile synthesis of polyester-PEG triblock copolymers and preparation of amphiphilic nanoparticles as drug carriers.

Novel amphiphilic triblock copolymers of poly(propylene succinate) (PPSu) and poly(ethylene glycol) (PEG) with different hydrophobic/hydrophilic ratios were synthesized using a facile one-pot procedure. The molecular weight of the copolymers was adjusted by varying the molecular weight of PPSu while keeping that of PEG constant. The copolymers exhibited glass transition temperatures between -36.0 and -38°C and single melting points around 44°C. WAXD data indicated that both blocks of the copolymers could crystallize. The mPEG-PPSu copolymers exhibited low in vitro toxicity against HUVEC cells. The synthesized copolymers were used to prepare core-shell nanoparticles with hydrophobic PPSu and hydrophilic PEG forming the core and shell, respectively. The drug loading efficiency and drug release properties of the mPEG-PPSu nanoparticles were investigated using two model drugs: the hydrophilic Ropinirole and the hydrophobic Tibolone. The mean size of the drug-loaded mPEG-PPSu nanoparticles ranged between 150 and 300nm and increased with the molecular weight of the PPSu block. The drug loading efficiency of the nanoparticles was found to be dependent upon drug hydrophilicity and was much higher for the hydrophobic Tibolone. Drug release characteristics also depended on drug hydrophilicity: the hydrophilic Ropinirole was released at a much higher rate than the hydrophobic Tibolone. Contrary to Ropinirole, the profiles of Tibolone exhibited an early phase of burst release followed by a phase of slow release. By varying the composition (mPEG/PPSu ratio) of mPEG-PPSU copolymers, nanoparticles of different sizes and drug loading capacities can be synthesized exhibiting different drug release characteristics. Based on the results obtained, the proposed mPEG-PPSu copolymers can be useful in various controlled drug delivery applications, especially those involving relatively hydrophobic drugs.

Inflammatory cytokines in insulin-treated patients with type 2 diabetes.

OBJECTIVE: An association between type 2 diabetes mellitus and inflammation has been described in several studies. The aim of this study was to search for the presence of low-grade inflammation in a special group of insulin-treated patients with type 2 diabetes, and to investigate a possible correlation between inflammation and obesity, glucose homeostasis and insulin requirement (IU insulin/kg body weight, BW). METHODS: We studied 85 subjects with type 2 diabetes that were receiving insulin treatment (group A) and 32 receiving sulfonylurea treatment (group B), and 57 subjects without diabetes (group C). Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), and the soluble TNF-alpha receptors sTNFR-60 and sTNFR-80 were measured in serum samples taken from all patients. RESULTS: The mean serum cytokine levels in group A vs. group B were: IL-6, 8.54+/-11 vs. 2.71+/-1.9 pg/ml (p=0.000); TNF-alpha, 14.33+/-24 vs. 5.12+/-15 pg/ml (p=0.016); sTNFR60, 3.9+/-2.8 vs. 2.36+/-1.4 ng/ml (p=0.000); and sTNFR80, 11.9+/-7 vs. 9.4+/-6 ng/ml (p=0.080). The mean serum cytokine levels in group A vs. group C were: IL-6, 8.54+/-11 vs. 4.74+/-7 pg/ml (p=0.017); TNF-alpha, 14.33+/-24 vs. 5.94+/-3.4 pg/ml (p=0.003); sTNFR60, 3.9+/-2.8 vs. 2.54+/-1.4 ng/ml (p=0.000); and sTNFR80, 11.9+/-7 vs. 10.85+/-8 ng/ml (p=0.470). A positive association between waist circumference and IL-6 (r=0.165, p=0.030) and sTNFR-60 (r=0.276, p=0.000) was detected. A significant correlation coefficient was observed between haemoglobin A1c (HbA1c) and both IL-6 (r=0.278, p=0.000) and sTNFR-60 (r=0.293, p=0.000), when the groups were studied as one. No correlation between inflammation and units of insulin/kg BW was found. In conclusion, low-grade chronic inflammation, as estimated by the relative levels of inflammatory cytokines, was present in patients with type 2 diabetes that were receiving insulin treatment, with significantly higher cytokine levels recorded compared to sulfonylurea-treated patients. In addition, an association between inflammation and both obesity and glucose homeostasis was detected.

Low bit-rate efficient compression for seismic data.

Compression is a relatively new introduced technique for seismic data operations. The main drive behind the use of data compression in seismic data is the very large size of seismic data acquired. Some of the most recent acquired marine seismic data sets exceed 10 Tbytes, and in fact there are currently seismic surveys planned with a volume of around 120 Tbytes. Thus, the need to compress these very large seismic data files is imperative. Nevertheless, seismic data are quite different from the typical images used in image processing and multimedia applications. Some of their major differences are the data dynamic range exceeding 100 dB in theory, very often it is data with extensive oscillatory nature, the x and y directions represent different physical meaning, and there is significant amount of coherent noise which is often present in seismic data. Up to now some of the algorithms used for seismic data compression were based on some form of wavelet or local cosine transform, while using a uniform or quasiuniform quantization scheme and they finally employ a Huffman coding scheme. Using this family of compression algorithms we achieve compression results which are acceptable to geophysicists, only at low to moderate compression ratios. For higher compression ratios or higher decibel quality, significant compression artifacts are introduced in the reconstructed images, even with high-dimensional transforms. The objective of this paper is to achieve higher compression ratio, than achieved with the wavelet/uniform quantization/Huffman coding family of compression schemes, with a comparable level of residual noise. The goal is to achieve above 40 dB in the decompressed seismic data sets. Several established compression algorithms are reviewed, and some new compression algorithms are introduced. All of these compression techniques are applied to a good representation of seismic data sets, and their results are documented in this paper. One of the conclusions is that adaptive multiscale local cosine transform with different windows sizes performs well on all the seismic data sets and outperforms the other methods from the SNR point of view. All the described methods cover wide range of different data sets. Each data set will have his own best performed method chosen from this collection. The results were performed on four different seismic data sets. Special emphasis was given to achieve faster processing speed which is another critical issue that is examined in the paper. Some of these algorithms are also suitable for multimedia type compression.

Instantaneous axis of rotation as a function of the three columns of the spine.

A knowledge of the rotatory motion of the vertebral bodies is needed to understand the normal biomechanical behavior of the spine. The aims of this investigation were 1) to define the instantaneous axis of rotation of the lumbar spine in rotation; and 2) to study the effect of the loss of the anulus, facet joints, and ligamentous structures on the location of the instantaneous axis of rotation. The instantaneous axis of rotation was found in 10 human cadaver thoracolumbar spines by the method of Reuleaux from superimposed serial photographs. Long-segment specimens were tested to minimize the effect of the imposed axis of the testing device. The instantaneous axis of rotation was consistently posterior to the anulus in the intact spine. With isolated destruction of the columns of the spine, the instantaneous axis of rotation migrated to the remaining intact structures. Anterior releases enhance derotation by removing the primary rotatory stabilizer. Ultimate control of a rotatory deformity or instability lies in the recognition that the anterior structures have a mechanical advantage in resisting torsion.

The effect of the three columns of the spine on the instantaneous axis of rotation in flexion and extension.

Instrumentation designed for stabilization and correction of spinal deformities must limit the amount of motion in flexion and extension. In flexion or extension, the vertebral bodies move about a specific point called the instantaneous axis of rotation. The ability of the implant to limit this motion is a function of its relation to the axis of rotation of the spine. The goal of this study was threefold: 1) to define the instantaneous axis of rotation of the spine in flexion and extension; 2) to study the effect of the loss of the three columns of the spine on the location of the instantaneous axis of rotation; and 3) to determine how the above parameters relate to the choice of anterior or posterior instrumentation. Ten human cadaver spines were subjected to compressive loads in flexion and extension. The columns of the spine were then destroyed in sequence at L3. The instantaneous axis of rotation for each vertebral body was found by the method of Reuleaux, and the effect of the compromise of the columns on the location of the instantaneous axis of rotation was noted. Understanding the exact location of the instantaneous axis of rotation after a specific injury would allow the clinician to objectively choose the best surgical approach and the appropriate instrumentation.

Identification of chlorite and serpentine in cosmetic or pharmaceutical talc.

Chlorite is the most common accessory mineral group found in high purity talc ore used in cosmetic or pharmaceutical consumer talcum products. X-ray diffraction and wet chemical analytical data obtained on geologic samples representing commercial talc ore deposits of high purity and on processed samples representing talc found in consumer talcum products indicate that clinochlore and penninite are the two chlorite minerals most commonly found in all talc samples irrespective of origin or source, but sheridanite is also found in some samples representing talc deposits that are associated with serpentinite rocks. The chlorite minerals exhibit certain well-defined X-ray diffraction characteristics which differentiate them from each other as well as from those of serpentine minerals, including the hazardous chrysotile asbestos.