Artificial hallucination: GPT on LSD? Beutel, Gernot; Geerits, Eline; Kielstein, Jan T
Critical care (London, England),
04/2023, Letnik:
27, Številka:
1
Journal Article
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...their paper sparked an immediate interest to try this disruptive technology ourselves, using the identical prompt (command or action sentence used to communicate with ChatGPT) as Salvagno et al., ...referring to the discussion of the paper by Suverein et al. (1) Regarding the paper by Suverein et al. published in 2023, ChatGPT attempts to generate an output that is consistent with what would be expected based on the training dataset. Since the ChatGPT's knowledge cutoff date is September 2021 it is unable to discuss a research paper published in 2023. ...the results of LLMs should be evaluated by medical experts before they are used in research or clinical practice.
Substantial evidence suggests that chronic hyperuricemia is an independent risk factor for hypertension, metabolic syndrome, chronic kidney disease (CKD) and cardiovascular diseases. This highlights ...the need for greater attention to serum uric acid levels when profiling patients, and suggests that the threshold above which uricemia is considered abnormal is 6 mg/dl, in light of the available evidence. Another important question is whether lowering serum uric acid can improve cardiovascular and renal outcomes, and what therapeutic mechanism of action could provide more clinical benefits to patients; the available literature shows a trend toward improvement associated with administration of urate-lowering drugs, in particular for the xanthine oxidase inhibitors. The demonstrated efficacy of urate-lowering therapy on outcomes other than gout flares leads to the consideration that treatment may be beneficial even in the absence of overt gout when hyperuricemia accompanies other clinical conditions, such as urate deposition, advanced CKD or cardiovascular risk factors.
Extracorporeal blood purification systems represent a promising alternative for treatment of blood stream infections with multiresistant bacteria.
The aim of this study was to analyse the binding ...activity of S. aureus to Seraph affinity filters based on heparin coated beads and to identify effectors influencing this binding activity.
To test the binding activity, we used gfp-expressing S. aureus Newman strains inoculated either in 0.9% NaCl or in blood plasma and determined the number of unbound bacteria by FACS analyses after passing through Seraph affinity filters. The binding activity of S. aureus was clearly impaired in human plasma: while a percent removal of 42% was observed in 0.9% NaCl (p-value 0.0472) using Seraph mini columns, a percent removal of only 10% was achieved in human plasma (p-value 0.0934). The different composition of surface proteins in S. aureus caused by the loss of SarA, SigB, Lgt, and SaeS had no significant influence on its binding activity. In a clinically relevant approach using the Seraph® 100 Microbind® Affinity Filter and 1000 ml of human blood plasma from four different donors, the duration of treatment was shown to have a critical effect on the rate of bacterial reduction. Within the first four hours, the number of bacteria decreased continuously and the reduction in bacteria reached statistical significance after two hours of treatment (percentage reduction 64%, p-value 0.01165). The final reduction after four hours of treatment was close to 90% and is dependent on donor. The capacity of Seraph® 100 for S. aureus in human plasma was approximately 5 x 108 cells.
The Seraph affinity filter, based on heparin-coated beads, is a highly efficient method for reducing S. aureus in human blood plasma, with efficiency dependent on blood plasma composition and treatment duration.
Purpose of Review
In chronic kidney disease (CKD), plasma uric acid levels are increased because of the decrease in glomerular filtration rate. However, in addition to CKD, hyperuricemia is ...frequently associated with a number of other conditions such as hypertension, type 2 diabetes, obesity, and heart failure, overweight, and cardiovascular disease.
Recent Findings
It is now becoming increasingly clear that, in many clinical conditions, elevated levels of uric acid have a much greater role beyond just causing gout. The present review will summarize current knowledge on the relation between hyperuricemia, CKD, and existing comorbidities, as well as the mechanisms of uric acid–related renal damage. In addition, the role and evidence for urate-lowering therapy in prevention and cardiovascular protection in CKD patients is discussed with a focus on allopurinol and febuxostat. To date, several clinical studies have provided evidence that urate-lowering therapy may help to prevent and delay the decline of renal function in patients with CKD.
Summary
Use of a xanthine oxidase inhibitor should be considered in patients who are at high renal risk and/or with declining renal function in the presence of hyperuricemia with and without deposition, although additional studies are warranted to define treatment targets. Notwithstanding, the possibility to delay deterioration of renal function in patients with CKD merits consideration.
Placement of central venous catheters (CVC) into the internal jugular vein represents a routine clinical intervention. The periprocedural complication rate ranges from 5 to 20% and can be reduced by ...ultrasound guidance, training of residents and other measures. We aimed to proof that the average Seldinger needle is too long, increasing the risk of periprocedural injury, best epitomized in the stellate ganglion injury/irritation. The first part of the study was an online market analysis to investigate the standard needle length currently offered as part of the CVC placement sets. The second part of the study involved 35 hospitalized patients (14 female; median age 74.5 years). In those the distance between the skin and the internal jugular vein as well as the diameter of the internal jugular vein was measured by ultrasound in both, supine position as well as 45° semi-sitting position. In the third part of the study 80 body donors (45 female; median age 83.0 years) preserved by the ethanol/formaldehyde method were studied. In those the distance and angle between the typical landmark for insertion of the Seldinger needle for internal jugular vein catheter placement to the stellate ganglion was measured. The median interquartile range Seldinger needle length was 7 4.0-10.0 cm. In the examined patients the maximum distance between the skin and the internal jugular vein was 1.87 cm. The minimum distance was 0.46 cm and the median distance averaging supine and 45° position was 1.14 0.94-1.31 cm. Regarding the body donors the median distance from the insertion point of the internal jugular vein to the stellate ganglion was longer in men 5.5 4.95-6.35 cm than in women 5.2 4.7-5.9 (p = 0.031 unpaired t-test). With 7 cm average length the Seldinger needle currently sold as part of CVC sets is long enough to physically reach the stellate ganglion, not to mention more proximal structures. A shorter needle length would be sufficient to reach the internal jugular vein even in obese patients and with a small insertion angle while minimizing the possibility to cause severe injury as structures like the pleura and the stellate ganglion could not be reached by shorter needles.
Given the pathophysiological key role of the host response to an infection rather than the infection per se, an ideal therapeutic strategy would also target this response. This study was designed to ...demonstrate safety and feasibility of early therapeutic plasma exchange (TPE) in severely ill individuals with septic shock.
This was a prospective single center, open-label, nonrandomized pilot study enrolling 20 patients with early septic shock (onset < 12 h) requiring high doses of norepinephrine (NE; > 0.4 μg/kg/min) out of 231 screened septic patients. Clinical and biochemical data were obtained before and after TPE. Plasma samples were taken for ex-vivo stimulation of human umbilical vein endothelial cells (HUVECs) to analyze barrier function (immunocytochemistry and transendothelial electrical resistance (TER)). Cytokines were measured by cytometric bead array (CBA) and enzyme-linked immunosorbent assays (ELISAs). An immediate response was defined as > 20% NE reduction from baseline to the end of TPE.
TPE was well tolerated without the occurrence of any adverse events and was associated with a rapid reduction in NE (0.82 (0.61-1.17) vs. 0.56 (0.41-0.78) μg/kg/min, p = 0.002) to maintain mean arterial pressure (MAP) above 65 mmHg. The observed 28-day mortality was 65%. Key proinflammatory cytokines and permeability factors (e.g., interleukin (IL)-6, IL-1b, and angiopoietin-2) were significantly reduced after TPE, while the protective antipermeability factor angiopoietin-1 was not changed. Ex-vivo stimulation of HUVECs with plasma obtained before TPE induced substantial cellular hyperpermeability, which was completely abolished with plasma obtained after TPE.
Inclusion of early septic shock patients with high doses of vasopressors was feasible and TPE was safe. Rapid hemodynamic improvement and favorable changes in the cytokine profile in patients with septic shock were observed. It has yet to be determined whether early TPE also improves outcomes in this patient cohort. An appropriately powered multicenter randomized controlled trial is desirable.
Clinicaltrials.gov, NCT03065751 . Retrospectively registered on 28 February 2017.
The Seraph® 100 Microbind® Affinity adsorber (Exthera Medical, CA, USA) is an extracorporeal treatment currently being explored as an approach to improve the clinical course and outcome of critically ...ill patients with COVID-19. Bacteria and viruses bind to the immobilized heparin on the ultra-high molecular weight polyethylene beads of the Seraph® device in a manner similar to the interaction with heparan sulfate on the cell surface and are thereby removed from the bloodstream 3. While hemoperfusion with the Seraph® was executed either alone or in combination with a wide range of supportive treatments, including intermittent hemodialysis and continuous renal replacement therapy, N-protein concentration was consistently reduced when comparing pre- and post- Seraph treatment blood samples (Table 1).
Background. Late-onset chronic (low-grade) periprosthetic joint infections are often accompanied by unspecific symptoms, false-negative cultures or nonspecific low values of serum biomarkers. This ...may lead to the unintended implantation of a revision prosthesis into an infected surgical site with the risk of short-term failure developing again. Conversely, false diagnosis of joint infection may result in multistage revision procedures, which expose the patient to unnecessary surgical procedures and inappropriate antibiotic treatment. Here, we investigated whether circulating biomarkers can preoperatively distinguish between aseptic prosthesis loosening and low-grade joint infection, and which biomarker combinations are most accurate. Methods. Inclusion criteria for the study were indication for revision arthroplasty due to aseptic implant failure, acute high-grade infection, or (suspected) low-grade infection. C-reactive protein (CRP), procalcitonin, tumor necrosis factor α, interleukin 6 (IL-6), interleukin 10, and lipopolysaccharide binding protein were assessed preoperatively in the serum of 98 adult patients. Results. The classification tree method revealed IL-6 and CRP as the most suitable biomarker combination for the discrimination of aseptic loosening vs low-grade joint infection. The combination of IL-6 >5.12 pg/mL and CRP >0.3 mg/dL correctly identified 15 of 16 patients as having low-grade infection (94%) whereas just one patient was aseptic (6%). Conclusions. This is the first comprehensive prospective clinical study to our knowledge investigating the significance of a combined biomarker approach in differentiating between aseptic prosthesis loosening and low-grade joint infection. CRP plus IL-6 seems to be the most helpful combination for preoperative discrimination of aseptic loosening vs low-grade joint infection.
•Increasing prevalence of hyperuricaemia has been noted in many populations.•Uric acid is a potentially treatable predictive risk factor for cardiometabolic diseases.•Uric acid-lowering therapies ...improve outcomes in hypertension and kidney disease.•There may be benefit to lowering serum uric acid in other cardiometabolic diseases.
During the last century, there has been an increasing prevalence of hyperuricaemia noted in many populations. While uric acid is usually discussed in the context of gout, hyperuricaemia is also associated with hypertension, chronic kidney disease, hypertriglyceridaemia, obesity, atherosclerotic heart disease, metabolic syndrome, and type 2 diabetes. Here we review the connection between hyperuricaemia and cardiovascular, kidney and metabolic diseases. Contrary to the popular view that uric acid is an inert metabolite of purine metabolism, recent studies suggest serum uric acid may have a variety of pro-inflammatory, pro-oxidative and vasoconstrictive actions that may contribute to cardiometabolic diseases. Hyperuricaemia is a predictive factor for the development of hypertension, metabolic syndrome, type 2 diabetes, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, myocardial infarction, stroke, heart failure and chronic kidney disease. Treatment with uric acid-lowering therapies has also been found to improve outcomes in patients with hypertension and kidney disease, in some but not all studies. In conclusion, uric acid is emerging as a potentially treatable risk factor for cardiometabolic diseases, and more clinical trials investigating the potential benefit of lowering serum uric acid are recommended in individuals with hyperuricaemia with and without deposition and concomitant hypertension, metabolic syndrome or chronic kidney disease.
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