Sepsis is a life-threatening organ dysfunction caused by the dysregulation of the host’s response to an infection, where the dominant mechanism is tissue hypoperfusion. Currently, the marker used to define tissue disorders is lactate levels, which may be elevated in other disease states as well. Renin is an essential hormone for the proper functioning of the renin-angiotensin-aldosterone (RASS) system. It is secreted in the glomerular apparatus in response to hypoperfusion. This study aimed to assess the usefulness of renin as a marker of tissue hypoperfusion in patients with sepsis and septic shock. A final group of 48 patients treated for sepsis and septic shock in the intensive care unit was included. Blood samples for renin quantification were collected in the morning as a part of routine blood analysis on the first, third, and fifth days. Sepsis was diagnosed in 19 patients (39.6%), and septic shock was diagnosed in 29 patients (60.4%). There was no significant difference in renin concentration between patients who received and did not receive continuous renal replacement therapy (CRRT) on any study day. Therefore, all samples were analyzed together in subsequent analyses. There was a significant difference in renin concentration between sepsis survivors and non-survivors on the third (31.5 and 119.9 pg/mL, respectively) and fifth (18.2 and 106.7 pg/mL, respectively) days. As a survival marker, renin was characterized by 69% and 71% overall accuracy if determined on the third and fifth days, respectively. There was a significant difference in renin concentration between sepsis and septic shock patients on the first (45.8 and 103.4 pg/mL, respectively) and third (24.7 and 102.1 pg/mL, respectively) days. At an optimal cut-off of 87 pg/mL, renin had very good specificity and a positive likelihood ratio. Renin was a strong predictor of mortality in patients with sepsis and septic shock. Further, the level of renin in patients with septic shock was significantly higher than in patients with sepsis. In combination with the assessment of lactate concentration, renin seems to be the optimal parameter for monitoring tissue hypoperfusion and could be helpful for septic shock diagnosis, as well as for identifying candidate patients for CRRT.

Sepsis-associated liver dysfunction (SALD) is associated with a poor prognosis and increased mortality in the intensive care unit. Bilirubin is one of the components of Sequential Organ Failure Assessment used in Sepsis-3 criteria. Hyperbilirubinemia is a late and non-specific symptom of liver dysfunction. This study aimed to identify plasma biomarkers that could be used for an early diagnosis of SALD. This prospective, observational study was conducted on a group of 79 patients with sepsis and septic shock treated in the ICU. Plasma biomarkers—prothrombin time, INR, antithrombin III, bilirubin, aspartate transaminase (AST), alanine transaminase, alkaline phosphatase, gamma glutamyl transferase, albumin, endothelin-1, hepcidin, plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex, and interferon-gamma inducible protein (10 kDa) were analysed. Plasma samples were obtained within 24 h after having developed sepsis/septic shock. Enrolled patients were followed for 14 days for developing SALD and 28 days for overall survival. A total of 24 patients (30.4%) developed SALD. PAI-1 with a cut-off value of 48.7 ng/mL was shown to be a predictor of SALD (AUC = 0.671, sensitivity 87.3%, and specificity 50.0%) and of 28-day survival in patients with sepsis/septic shock (p = 0.001). Measuring PAI-1 serum levels at the onset of sepsis and septic shock may be useful in predicting the development of SALD. This should be verified in multicenter prospective clinical trials.

Background: Prolonged support of organ functions without therapeutic benefit represents a serious problem of therapy in intensive care units (ICUs). This kind of treatment, called “futile therapy”, prolongs the process of dying and should be avoided. In Poland, the guidelines and protocol defining the best clinical practice for the avoidance of futile therapy in ICUs was published in 2014. The aim of study was to analyse the protocols concerning futile therapy in the general ICU in the University Hospital in Wrocław, Poland during the years 2015–2018.Methods: The content of protocols was analysed. The protocols contained information on clinical problems, ethical and social aspects, data on communication with relatives, and therapeutic procedures regarded as futile and consequently withheld or withdrawn.Results: During the study 1660 patients were treated in the ICU, of whom 557 patients died. Protocols regarding futile therapy were analysed in 146 patients. The diagnosis before starting the protocol was multiorgan failure (56%), permanent CNS injury (39%), respiratory failure (3%), and circulatory failure (2%). The withholding of therapeutic procedures was preferred, and the cases of withdrawal were rare. All patients with protocols died during hospital stay, 81.5% of them in the ICU.Conclusions: The protocols concerning futile therapy were instituted in 1 in 10 patients treated in the ICU in Wrocław, which comprised was nearly one-fifth of all ICU deaths. The withholding of futile therapeutic procedures was preferred in comparison to withdrawing. Communication with relatives was essential to the process of avoiding futile therapy.

Acute kidney injury (AKI) is one of the most common organ failures. An early diagnosis of AKI using specific biomarkers is essential for effective treatment. This study determined the serum concentrations of selected amino acids and amines using targeted liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in patients with AKI during sepsis and septic shock treated in the Intensive Care Unit (ICU). A sample of 41 patients was divided into 2 groups: (1) patients with sepsis and septic shock along required continuous renal replacement therapy (CRRT) due to AKI (n=13), and (2) patients with sepsis and septic shock but without AKI (n=28). LC-MS/MS was used to measure a serum concentration of 6 amino acids and amines: arginine, ornithine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), dimethylamine (DMA), and citrulline. There was a statistically significantly higher median DMA level in AKI patients compared to those without AKI (8.1 vs 5.2 umol/L; P=0.022). The results for the remaining molecules showed no significant differences (P>0.05). Patients with DMA ≥14.95 umol/L (n=5; 100%) and treated with CRRT presented DMA level below the cut-off point (n=7; 20%). Subjects with creatinine levels ≥1.19 mg/dL (n=11; 28%) and treated with CRRT presented creatinine levels below the cut-off point (n=1; 3%). In patients with sepsis, increased serum levels of DMA were significantly associated with AKI requiring CRRT. It remains unclear whether increased DMA concentrations are secondary to sepsis-induced AKI or are a cause.

SARS-CoV-2 is a virus that causes severe respiratory distress syndrome. The pathophysiology of COVID-19 is related to the renin–angiotensin system (RAS). SARS-CoV-2, a vector of COVID-19, uses angiotensin-converting enzyme 2 (ACE-2), which is highly expressed in human lung tissue, nasal cavity, and oral mucosa, to gain access into human cells. After entering the cell, SARS-CoV-2 inhibits ACE-2, thus favouring the ACE/Ang II/angiotensin II type 1 receptor (AT1R) axis, which plays a role in the development of acute lung injury (ALI). This study aimed to analyse the influence of angiotensin 1 receptor (AT1R) levels in the serum on the course of the severity of symptoms in healthcare professionals who had a SARS-CoV-2 infection. This prospective observational study was conducted on a group of 82 participants. The study group included physicians and nurses who had a COVID-19 infection confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2. The control group consisted of healthy medical professionals who had not had a SARS-CoV-2 infection or who had no symptoms of COVID-19 and who tested negative for SARS-CoV-2 on the day of examination. We analysed the correlation between AT1R concentration and the severity of COVID-19, as well as with sex, age, blood group, and comorbidities. There were no statistically significant differences in the mean values of AT1R concentration in the recovered individuals and the non-COVID-19 subjects (3.29 vs. 3.76 ng/mL; p = 0.32). The ROC curve for the AT1R assay showed an optimal cut-off point of 1.33 (AUC = 0.44; 95% CI = 0.32–0.57; p = 0.37). There was also no correlation between AT1R concentration and the severity of symptoms associated with COVID-19. Blood type analysis showed statistically significantly lower levels of AT1R in COVID-19-recovered participants with blood group A than in those with blood group O. In conclusion, AT1R concentration does not affect the severity of symptoms associated with COVID-19 among healthcare professionals.

Serum procalcitonin (PCT) is a sensitive biomarker used for the diagnosis of infection and sepsis. PCT has also some toxic effects. It is not a proinflammatory stimulus, but may augment the inflammatory processes. High levels of PCT in sepsis may lead to hepatocyte necrosis and, as a result, to liver failure. The pathomechanism of the toxic effect of PCT is still unknown. The influence of liver function on PCT levels has not been studied yet. It is not sure whether the liver dysfunction affects the diagnostic and prognostic value of serum PCT levels. In patients with acute liver failure, the usefulness of PCT-level determination remains controversial. Recent studies have shown a potential diagnostic benefit of PCT as a marker of infection in chronic liver diseases. In both groups there is still no consensus on the optimal cut-off value of PCT levels in order to exclude infection. In patients with liver disease, the serum PCT levels should be interpreted with caution, taking into consideration other factors affecting the PCT threshold. Serum procalcitonin (PCT) is a sensitive biomarker used for the diagnosis of infection and sepsis. PCT has also some toxic effects. It is not a proinflammatory stimulus, but may augment the inflammatory processes. High levels of PCT in sepsis may lead to hepatocyte necrosis and, as a result, to liver failure. The pathomechanism of the toxic effect of PCT is still unknown. The influence of liver function on PCT levels has not been studied yet. It is not sure whether the liver dysfunction affects the diagnostic and prognostic value of serum PCT levels. In patients with acute liver failure, the usefulness of PCT-level determination remains controversial. Recent studies have shown a potential diagnostic benefit of PCT as a marker of infection in chronic liver diseases. In both groups there is still no consensus on the optimal cut-off value of PCT levels in order to exclude infection. In patients with liver disease, the serum PCT levels should be interpreted with caution, taking into consideration other factors affecting the PCT threshold.