Non-Conventional Prognostic Markers in Life-Threatening COVID-19 Cases-When Less Is More.

Background/Objectives: In this study, we aimed to compare the predictive power of non-conventional (neutrophil/lymphocyte ratio-NLR; platelet/lymphocyte ratio-PLR) and conventional markers (C-reactive protein-CRP; procalcitonin-PCT; interleukin-6-IL-6) in terms of disease progression and mortality in severe SARS-CoV-2 patients. Methods: In this prospective observatory study, blood samples were collected daily, focusing on the established inflammatory markers. Critically ill COVID-19 patients who required ICU admission were included. Patient treatment followed established COVID-19 protocols, and the data analysis was performed using SPSS with non-normal distribution methods. The study cohort primarily included patients infected with the delta variant. Results: A mortality rate of 76.6% was observed among 167 patients during the study period. Significant differences in conventional and non-conventional markers between survivor and non-survivor groups were observed. The PCT levels were significantly elevated (p < 0.005) in the deceased group. Among the non-conventional markers, the NLR was consistently higher in non-survivors and emerged as a significant predictor of mortality, whereas the PLR was not elevated among the non-survivors. ROC analyses indicated that PCT and the NLR were the markers with the highest predictive power for mortality. The multivariate logistic regression analysis identified NLR, PCT, CRP, and IL-6 as significant predictors of mortality across different days. The NLR showed a consistent, though not always statistically significant, association with increased mortality risk, particularly on Days 2 and 5. Conclusions: The NLR's accessibility and simplicity of determination make it a valuable and practical tool for monitoring inflammatory processes in viral infections. Our findings suggest that incorporating NLR analysis into routine clinical practice could enhance the early identification of high-risk patients, thereby improving patient management and outcomes.

Indications for Sleeve Gastrectomy-Is It Worth Waiting for Comorbidities to Develop?

(1) Background and Objectives: Morbid obesity significantly increases the prevalence of comorbidities, such as heart disease, restrictive lung disease, stroke, diabetes mellitus and more. (2) Methods: Patients undergoing gastric sleeve surgery were divided into three groups with BMI between 30-34.9 kg/m2 (Group I), 35-39.9 kg/m2 (Group II), and over 40 kg/m2 (Group III). Preoperative examinations included cardiac ultrasound, respiratory function and laboratory tests, and preoperative comorbidities were also recorded. Following a one-year follow-up, we compared the rate of weight loss in the three groups at six months and one year following surgery, specifically, the effect of surgery on preoperative comorbidities at one year. (3) Results: The weight loss surgeries performed were successful in all three groups. Preoperative laboratory examinations, an echocardiogram and respiratory function results showed no clinically significant difference, except moderate elevations in blood lipid levels. Hypertension was the most common comorbidity. (4) Conclusions: In our patient population, hypertension and diabetes were the only comorbidities with a high prevalence. It can be explained by the relatively younger age among the patients (mean age 44.5 years) and the fact that they had not yet developed the pathological consequences of severe obesity. Consequently, while performing the surgery at a relatively younger age, it seems far more likely that the patient will return to a more active and productive life and enjoy a better quality of life. Additionally, the perioperative risk is lower, and the burden upon health systems and health expenditure is reduced by preventing comorbidities, in particular, multimorbidity. On this basis, it may be advisable to direct patients who do not exhaust the classical indications for bariatric surgery toward the surgical solution at a younger age. Our results suggest it is not worth waiting for comorbidities, especially multimorbidity, to appear.

Acquired Hemophilia A after SARS-CoV-2 Infection: A Case Report and an Updated Systematic Review.

The role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been implicated in the pathogenesis of acquired hemophilia A (AHA). The aim of this study is to report our case and to summarize clinical studies on de novo AHA after SARS-CoV-2 infection. We performed a systematic search on the association of SARS-CoV-2 with AHA in four medical databases up to 28 May 2023. Eligible studies should include de novo AHA patients who had SARS-CoV-2 infection before or concomitant with the diagnosis of AHA. Findings were synthesized narratively. In addition, we report the case of a 62-year-old female patient, who presented to our clinic with left flank pain 2 weeks after SARS-CoV-2 infection. Clinical investigations confirmed AHA and imaging studies revealed retroperitoneal bleeding. Her hemostasis was successfully secured with bypassing agents; however, despite immunosuppressive therapy, high inhibitor titer persisted. In the systematic review, we identified only 12 relevant cases with a questionable cause-effect relationship between SARS-CoV-2 infection and AHA. Based on the qualitative analysis of the relevant publications, current clinical evidence is insufficient to support a cause-effect relationship. The analysis of data from ongoing AHA registries can serve further evidence.

Serum Total Antioxidant Capacity (TAC) and TAC/Lymphocyte Ratio as Promising Predictive Markers in COVID-19.

SARS-CoV-2 infection might cause a critical disease, and patients' follow-up is based on multiple parameters. Oxidative stress is one of the key factors in the pathogenesis of COVID-19 suggesting that its level could be a prognostic marker. Therefore, we elucidated the predictive value of the serum non-enzymatic total antioxidant capacity (TAC) and that of the newly introduced TAC/lymphocyte ratio in COVID-19. We included 61 COVID-19 (n = 27 ward, n = 34 intensive care unit, ICU) patients and 29 controls in our study. Serum TAC on admission was measured by an enhanced chemiluminescence (ECL) microplate assay previously validated by our research group. TAC levels were higher (p < 0.01) in ICU (median: 407.88 µmol/L) than in ward patients (315.44 µmol/L) and controls (296.60 µmol/L). Besides the classical parameters, both the TAC/lymphocyte ratio and TAC had significant predictive values regarding the severity (AUC-ROC for the TAC/lymphocyte ratio: 0.811; for TAC: 0.728) and acute kidney injury (AUC-ROC for the TAC/lymphocyte ratio: 0.747; for TAC: 0.733) in COVID-19. Moreover, the TAC/lymphocyte ratio had significant predictive value regarding mortality (AUC-ROC: 0.752). Serum TAC and the TAC/lymphocyte ratio might offer valuable information regarding the severity of COVID-19. TAC measured by our ECL microplate assay serves as a promising marker for the prediction of systemic inflammatory diseases.

Can we predict critical care mortality with non-conventional inflammatory markers in SARS-CoV-2 infected patients?

BACKGROUND: Severe COVID-19 disease is associated with multiple organ involvement,then failure and often fatal outcomes.In addition,inflammatory mechanisms and cytokine storms,documented in many COVID-19 patients,are responsible for the progression of the disease and high mortality rates.Inflammatory parameters,such as procalcitonin(PCT) and C-reactive protein(CRP), are widely used in clinical practice. OBJECTIVE: To evaluate the predictive power of non-conventional inflammatory markers regarding mortality risk. METHODS: In our prospective study 52 patients were followed for 5 days after admission to an intensive care unit immediately with severe SARS-CoV-2 infection.We compared leukocyte-,platelet antisedimentation rate (LAR, PAR),neutrophil lymphocyte ratio(NLR), CRP, PCT levels. RESULTS: In non-surviving(NSU) patients LAR remained largely constant from D1 to D4 with a statistically significant drop(p < 0.05) only seen on D5.The NSU group showed statistically significant(p < 0.05) elevated LAR medians on D4 and D5, compared to the SU group.NLR values were continually higher in the non-survivor group.The difference between the SU and NSU groups were statistically significant on every examined day.PAR, CRP and PCT levels didn't show any significant differences between the SU and NSU groups. CONCLUSIONS: In conclusion, this study suggests that LAR and NLR are especially worthy of further investigation as prognostic markers.LAR might be of particular relevance as it is not routinely obtained in current clinical practice.It would seem beneficial to include LAR in data sets to train prognostic artificial intelligence.

Plasma Levels and Renal Handling of Amino Acids Contribute to Determination of Risk of Mortality or Feed of Ventilation in Patients with COVID-19.

COVID-19 infection may lead to serious complications, e.g., need for mechanical ventilation or death in some cases. A retrospective analysis of patients referred to our COVID Emergency Department, indiscriminately, was performed. A routine lab analysis measured amino acids in plasma and urine of patients. Data of surviving and deceased patients and those requiring or not requiring mechanical ventilation were compared, and logistic regression analyses have been performed. Deceased patients were older, had higher blood glucose, potassium, AST, LDH, troponin, d-dimer, hsCRP, procalcitonin, interleukin-6 levels (p < 0.05 for all). They had lower plasma serine, glycine, threonine, tryptophan levels (p < 0.01), higher tyrosine and phenylalanine levels (p < 0.05), and higher fractional excretion of arginine, methionine, and proline (p < 0.05) than survivors. In a regression model, age, severity score of COVID-pneumonia, plasma levels of threonine and phenylalanine were predictors of in-hospital mortality. There was a difference in ventilated vs. non-ventilated patients in CT-scores, glucose, and renal function (p < 0.001). Using logistic regression, CT-score, troponin, plasma level, and fractional excretion of glycine were predictors of ventilation. Plasma levels and renal excretion of certain amino acids are associated with the outcome of COVID-19 infection beside other parameters such as the CT-score or age.

Changes of pituitary adenylate cyclase activating polypeptide (PACAP) level in polytrauma patients in the early post-traumatic period.

In polytrauma patients who survive the primary insult, the imbalance between the pro- and anti-inflammatory processes seems to be responsible for life-threatening complications such as sepsis or multiple organ dysfunction syndrome. Measurement of C-reactive protein (CRP) and procalcitonin (PCT) is a standard way for differentiating between infectious (bacterial) and non-infectious inflammation. Monitoring of immune cell functions, like leukocyte anti-sedimentation rate (LAR) can also be useful to diagnose infectious complications. Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with well-known immunomodulatory and anti-inflammatory effects. The aim of our study was to determine the changes of PACAP38 levels in polytrauma patients in the early post-traumatic period in intensive care unit and analyse possible correlation of its level with conventional (CRP, PCT) and unconventional (LAR) laboratory parameters. Twenty polytrauma patients were enrolled. Blood samples were taken daily for five days. We observed significant correlation between PACAP38 and CRP levels on day 4 and 5 as well as between PACAP38 and LAR levels all of the days. This could be due to the anti-inflammatory and cytoprotective functions of PACAP38 as part of an endogenous response to the trauma induced systemic inflammatory response syndrome. These significant correlations could have clinical importance in monitoring the dynamic balance of pro- and anti-inflammatory processes in case of polytraumatic patients.

Lack of early platelet and leukocyte activation can indicate complications after major burn injury.

BACKGROUND: Major burn injury causes massive tissue destruction consequently enhanced platelet function and leukocyte-mediated inflammatory response. METHODS: In a prospective, observational study 23 consecutive patients with more than 20% body surface burn injury were followed for five days (T1-T5) after admission to a university intensive care (ICU). Platelet and leukocyte antisedimentation rate (PAR and LAR) was measured by one-hour gravity sedimentation. It detects the percentage of total platelet and leukocyte number crossed the half line of blood sample column, therefore, they can be regarded as cells of decreased specific gravity. We aimed to investigate the time course of PAR and LAR after burn injury, as the trend of platelet and the leukocyte activation in the early post-burn period. RESULTS: Daily mean PAR and LAR values continuously increased in the observation period (T1 to T5). Daily mean PAR and LAR were lower in ICU non-survivors (n = 7) compared to survivors (n = 16) between T2 and T4 (p < 0.05 and p < 0.01). PAR values of septic patients (n = 10) were lower than that of non-septic ones (n = 13, p < 0.01 at T5). CONCLUSIONS: Both PAR and LAR, as novel bedside test can predict septic complications and unfavorable outcome after major burn injury. Further studies with higher sample size are warranted.

Changes of para-, meta- and ortho-tyrosine over time in burned patients.

PURPOSE: Serious burn injury leads to oxidative stress resulting in production of meta- and ortho-tyrosine, while para-tyrosine is the physiological isoform. Our aim was to investigate the metabolism of these tyrosine isoforms following major burn injury. METHODS: Fifteen patients requiring intensive care were followed for 5 consecutive days after major burn injury. Serum and urine concentrations of para-, meta-, and ortho-tyrosine were measured with high performance liquid chromatography. Fifteen healthy matching individuals were invited as control group. RESULTS: Median serum concentration of normal isoform para-tyrosine decreased in burned patients between days 2 and 5 (p < 0.01). Mean meta-, and ortho-tyrosine levels were significantly higher in patients compared to controls in the same time period (p < 0.05). Renal excretion of para-tyrosine increased significantly in our observation period (p < 0.01). CONCLUSIONS: Pathologic isoforms of tyrosine accumulate in serum meanwhile the level of normal isoform decreases possibly due to belated enhanced renal excretion or, to decreased synthesis after major burn injury.

Can leukocyte antisedimentation rate (LAR) predict septic complications and critical care survival early in polytrauma and burn victims?

BACKGROUND: In polytrauma and burn injury Systemic Inflammatory Response Syndrome (SIRS) develops. SIRS is presented in many hospitalized patients, including those who never develop infection or sepsis. Both in SIRS and sepsis the leukocyte activation occurs. In acute phase reaction leukocytes' upward flotation i.e. leukocyte antisedimentation rate (LAR) can indicate infectious origin. OBJECTIVE: To evaluate the predictive power of LAR, serum C-reactive protein (CRP) and procalcitonin (PCT) levels regarding mortality risk and development of septic complications. METHODS: In a prospective, observational study, 36 patients were followed for 5 days (T1-T5) after admission to a critical care unit immediately with severe polytrauma or burn injury. Eleven patients developed septic complications, their LAR, CRP and PCT levels were analyzed before and after 3 days of sepsis was declared. RESULTS: Ten patients died due to septic complications. In survivors LAR at T1 (p < 0.001) and T2 (p < 0.001) as well as CRP at T1 (p < 0.05) were significantly higher compared to controls and non survivors. In septic patients LAR (p < 0.05) and CRP (p < 0.05) showed a significant drop one day before sepsis was declared. PCT levels failed to predict this. CONCLUSIONS: Drop in LAR and CRP levels may be warning signs regarding the onset of septic complications after severe polytrauma and burn injury.