Sepsis-3: new edition — old problems. analysis from the perspective of general pathology

Sepsis-3 Guidelines defines sepsis as an organ dysfunction caused by dysregulated host response to infection. To record organ dysfunction, the SOFA/quick SOFA scales were recommended. In fact, in medical practice, sepsis is considered nothing more than a critical infection that requires intensive care. Therefore, sepsis is pathogenetically a nonhomogeneous condition manifested by diverse nosologies and syndromes. Unlike the previous two editions, Sepsis-1 and Sepsis-2 Guidelines, the formal criteria provided in the Sepsis-3 are closer to the de facto position, describe more specific, but less sensitive features to predict mortality. However, the initial, latent manifestations of critical conditions, which can be relatively effectively controlled by intensive therapy, remain outside the Sepsis-3 criteria. Not all signs of multiple organ dysfunctions (according to the Sepsis-3 criteria) will require intensive care. Hence, obviously the presence or absence of formal criteria of Sepsis-3 will not be always taken into account while verifying sepsis. The only relatively pathogenetically homogeneous definition in Sepsis-3 is “septic shock”. However, it also does not fully consider the staging (according to the degree of compensation of hemodynamic disturbances) and the phasing (according to the severity of the proinflammatory response) of the dynamics of the shock condition. From our point of view, a positive result of the Sepsis-3 consensus would be in transition of the systemic inflammatory response syndrome (SIRS) from the main to additional (optional) verifying sepsis criteria. We also believe that the weak side of the Sepsis-3 Guidelines is in underestimated mechanisms of systemic inflammation as a general pathological process in the genesis of developing critical conditions of various origins. From the perspective of general pathology, sepsis is a combination of the three common fundamental pathological processes: classical (canonical) and systemic inflammation (SI), as well as chronic systemic low-grade inflammation (parainflammation), the latter can be considered as an unfavorable background for development of the former two processes. All three processes are characterized by any SIR signs and require to be differentiated on the basis of integral criteria, which reflect specific blocks of the SI complex process. The pathogenesis of the SARS-CoV-2 infection (COVID-19) is a relevant example underlying inevitability of such approach. The systemic microvascular vasculitis, and its main clinical manifestations such as systemic microcirculatory disorders in the form of shockogenic conditions is the SI pathogenetic basis. Apparently, one of the modalities for further evolution of critical care medicine will be coupled to development of a more multilayered but effective methods for assessing pathogenesis of critical states and more differentiated methods of pathogenetic therapy. Therefore, it will require to modernize a number of fundamental premises in our knowledge about pathobiology, pathophysiology, and general pathology.

Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction with Acute Kidney injury caused by Cardiogenic Shock, Is it Really Safe?; A Case Report

Background ST-elevation myocardial infarction (STEMI) is a life-threatening condition. Timely treatment with Percutaneous Coronary Intervention (PCI) is a recommended management of STEMI. However, in STEMI condition accompanied by complications such as prolonged shock condition and become Acute Kidney Injury (AKI), it is still a question of whether to be treated conservatively or invasively. If PPCI was an option, how to prevent the worsening outcome is still an issue Case Illustration A 53 years old, woman, was referred from a private hospital with STEMI inferior Killip IV onset 5 hours with typical chest pain and azotemia with creatinine serum was 3.4 mg/dl; eGFR 15 ml/m/1.73m2. In the emergency room, she got hydration, inotropic, and planned for PPCI. After the PPCI procedure, she was fallen into the altered mental status and then referred to our hospital. The GCS was E4V4M6; blood pressure was 118/62 mmHg (on dobutamine 10 mcg/kg BW/minutes and NE 0.3 mcg/kg BW/minutes), heart rate was 130 bpm, respiration rate was 20 times per minute, peripheral saturation was 98% on NRBM 10 liters per minute. The laboratorium result in our hospital showed a creatinine level was 1.6 mg/dl. We treated this patient for 9 days, with optimal medicamentosa and fluid therapy. There is an improvement in clinical presentation and physical examination on the last day of treatment, with urine output 1900 cc/24 hours, creatinin serum 0.8 mg/dl, and eGFR 84 ml/min/1.73m2. Conclusion Acute renal failure is a frequent complication in STEMI, leading to higher mortality, morbidity, and intrahospital complications. PPCI is a reperfusion strategy recommended by the guideline in the setting of myocardial infarction with cardiogenic shock. Proper management to prevent worsening of renal function in this condition is very important.

Surface Forming Criteria of Ti-6AL-4V Titanium Alloy under Laser Loading

In order to study the spallation phenomenon of titanium alloy under the shock of nanosecond laser, the Neodymium-Yttrium-Aluminum Garnet laser was used to carry out laser shock experiments on the surface of titanium alloy. By observing and measuring the surface morphology of the target material, the forming factors and the changes of the surface morphology under different parameter settings, the forming criteria of the titanium alloy were obtained. The results show that under the single variable method, the change of laser energy can affect the target shape variable, and there is a positive correlation between them. When the thickness was greater than or equal to 0.08 mm, no obvious cracks were found in the targets. Moreover, the number of impact times was the key factor for the target deformation; with the growth of impact times, the target deformation gradually became larger until the crack appeared. The larger the diameter of the spot, the more likely the target was to undergo plastic deformation. The surface of titanium alloy with a thickness of 0.08 mm appeared to rebound under specific laser shock condition. The changes in the back of the target material were observed in real time through a high-speed camera, and the plasma induced by the laser was observed in the process. This study is based on the results of previous studies to obtain the titanium alloy forming criteria, which provides a basis for the setting of laser parameters and the thickness of the target when the nanosecond laser impacts the Ti-6AL-4V target.

Chronology and Element Distribution of Shock-deformed Regions in Zircon from the Chicxulub Impact Structure

<p>Zircon is ubiquitously used to nail down the geological events for both terrestrial and extraterrestrial materials. The U-Pb system and other trace elements in zircon plausibly remain stable and robust in normal metamorphic processes on Earth, while under the extremely shock condition, trace element behaviors in zircon could be unstable and differential due to the generated extraordinary deformations and thermal annealing. Since the systematic deformations in zircon recovered from the Chicxulub impact structure, such as planar fractures (PFs), reidite and granular zircon, the phenomenon of partially or completely age resetting are discovered in zircons from impact melt, breccia, ejecta and meteorites. In effect, element migration during the shock or post-shock setting is the most critical question, which may yield age resetting in nature. The enrichment of elements in shock-deformed zircon regions (PFs and reidite) are revealed, such as Y, Al, Ca, U, Th and Pb. Due to the limitation of resolution and lack of typical shock deformations, the straightforward correlations among deformations, element migration and chronology in zircon by traditional means have not been illustrated clearly so far. Here we systematically analyzed the correlations between shock deformations (from low to high degree: PFs, reidite and granular zircon) and element distribution in zircon by high-resolution Nano-SIMS mapping data. This can be used to interpret the chronology of shock products both from terrestrial and extraterrestrial bodies.</p>

IL-1, IL-6, TNF-α, and MIF in relative adrenal insufficiency in septic shock: a piglet model

BACKGROUND Inflammatory mediators released during septic shock are involved in the mechanism of adrenal insufficiency. This study investigated the role of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, and macrophage migration inhibitory factor (MIF) in septic shock with relative adrenal insufficiency (RAI). METHODS We conducted a 6-month experimental study in 20 piglets. Following endotoxin administration, their hemodynamics were monitored and blood samples were drawn to test the levels of cytokines IL-1, IL-6, TNF-α, and MIF every 15 min until septic shock onset as well as during a corticotropin stimulation test. Septic shock was managed by administering fluid resuscitation, inotropic drugs, and hydrocortisone. At the end of the study, the piglet models were classified as either RAI or non-RAI. Immunohistochemistry staining was performed on the hypothalamus of the RAI group. RESULTS The level of IL-6 at 45 min was higher in the RAI group than the non-RAI group (p = 0.008), and that of IL-1 was similar in the two groups during septic shock. The RAI group had higher TNF-α levels at 15 min (p = 0.002) and at 30 min (p = 0.007) than the non-RAI group, and the MIF level during septic shock was higher in the RAI group (p = 0.003) than the non-RAI group. CONCLUSIONS Cytokine-induced inflammatory process of adrenal gland reflected in TNF-α level in 15 min and 30 min, IL-6 in 45 min, and MIF in septic shock condition but not in IL-1.

Transcriptomic response of an Antarctic yeast Rhodotorula sp. USM-PSY62 to temperature changes

Rhodotorula sp. (USM-PSY62) is a psychrophilic yeast isolated from Antarctic sea ice and it grows optimally at 15 °C. This study was set up to observe how USM-PSY62 adapted to fluctuations in temperature. During cold adaptation, an elevated transcription of the CorA magnesium transporter gene in USM-PSY62 indicated a higher requirement for magnesium ions in order to gain additional enzyme cofactors or maintain cytoplasmic fluidity. The HepA homologue coding for DNA/RNA helicase was also over-expressed in cold condition possibly to reorganize secondary structures of DNA and RNA. An up-regulation of the catalase gene was also observed reflecting an increment in the concentration of reactive oxygen species and fluctuations in the associated antioxidant system. The YOP1 gene, which encodes a membrane protein associated with protein transport and membrane traffic, was the most down-regulated under cold shock condition. The genes responsible for the structural maintenance of chromosome (SMC) were also down-regulated when the temperature was shifted to 0 °C. Upon cold shock, the gene for heat shock factor protein 1 (HSF1) was also down-regulated. Hsf1 is a transcriptional regulator which regulate the heat shock responses. Although USM-PSY62 showed some common adaptive strategies as in several other psychrophilic organisms, new mechanisms were also uncovered.

I told you it was safe: Associations between intolerance of uncertainty and different types of uncertainty during instructed threat of shock

Background and Objectives. Intolerance of Uncertainty (IU) is a dispositional tendency to find uncertainty aversive. There is a lack of research on how IU modulates physiological responding to different types of uncertainty. Methods. Here, we conducted exploratory secondary analyses on an existing data set (n = 45) to examine whether IU is related to a particular type of uncertainty during instructed threat of shock (i.e. certain shock, certain safety from shock, outcome uncertainty of shock, temporal uncertainty of shock). Results. Analyses revealed that IU was associated with larger auditory startle blink during the anticipatory period for the certain safety from shock condition, relative to the certain shock condition. Limitations. The sample was relatively small. Conclusions. Individuals higher in IU may be more inclined to generalize threat to safety cues in the context of instructed threat of shock with multiple types of uncertainty