Search Results (558)

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of chromatin DNA, histones, and granular proteins released by neutrophils through a specialized form of cell death known as NETosis. While NETs contribute to the containment of pathogens, their excessive or dysregulated production in sepsis is associated with endothelial damage, immunothrombosis, and organ dysfunction. Several NET-associated biomarkers have been identified, including circulating cell-free DNA (cfDNA), histones, MPO-DNA complexes, and neutrophil elastase–DNA complexes, which correlate with the disease severity and prognosis. Therapeutic strategies targeting NETs are currently under investigation. Inhibition of NET formation using PAD4 inhibitors or ROS scavengers has shown protective effects in preclinical models. Conversely, DNase I therapy facilitates the degradation of extracellular DNA, reducing the NET-related cytotoxicity and thrombotic potential. Additionally, heparin and its derivatives have demonstrated the ability to neutralize NET-associated histones and mitigate coagulopathy. Novel approaches include targeting upstream signaling pathways, such as TLR9 and IL-8/CXCR2, offering further therapeutic promise. Full article

Systematic reviews are a cornerstone of evidence-based research, providing comprehensive summaries of existing studies to answer specific research questions. This article offers a detailed guide to conducting high-quality systematic reviews in biology, health and social sciences. It outlines key steps, including developing and registering a protocol, designing comprehensive search strategies, and selecting studies through a screening process. The article emphasizes the importance of accurate data extraction and the use of validated tools to assess the risk of bias across different study designs. Both meta-analysis (quantitative approach) and narrative synthesis (qualitative approach) are discussed in detail. The guide also highlights the use of frameworks, such as GRADE, to assess the certainty of evidence and provides recommendations for clear and transparent reporting in line with the PRISMA 2020 guidelines. This paper aims to adapt and translate evidence-based review principles, commonly applied in clinical research, into the context of biological sciences. By highlighting domain-specific methodologies, challenges, and resources, we provide tailored guidance for researchers in ecology, molecular biology, evolutionary biology, and related fields in order to conduct transparent and reproducible evidence syntheses. Full article

Background and Aims: Sepsis-associated acute kidney injury (S-AKI) is common and is associated with poor outcomes. This prospective observational study aimed to assess the predictive value of four novel biomarkers—syndecan-1 (SDC1), neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and presepsin (PSPN)—for renal outcomes and mortality in septic ICU patients. Methods: Serum biomarker levels were measured in serum samples collected at the time of sepsis diagnosis on the basis of the Sepsis-3 criteria. Acute kidney injury (AKI) was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, and patients were grouped by the presence of AKI, renal replacement therapy requirement (RRT), and intensive care unit (ICU) survival. Demographic, clinical, laboratory, and severity score data were compared between groups to evaluate the predictive performance of biomarkers and clinical parameters. Results: Of the 140 septic patients included, 55.0% developed AKI, 17.2% required RRT, and the ICU mortality rate was 50.0%. SDC1 was independently associated with both AKI (OR: 1.201; p = 0.024) and RRT initiation (OR: 1.260; p = 0.004). It also demonstrated the highest predictive performance for RRT (AUC: 0.715; p = 0.001) and a significant AUC for AKI evaluation (AUC: 0.659; p = 0.002). NGAL levels were significantly elevated in patients with AKI and higher SOFA scores but were not independently predictive. PENK and PSPN were not significantly associated with any renal outcome or mortality. The combined SOFA–SDC1 model improved discrimination for both AKI (AUC: 0.770) and RRT (AUC: 0.737), surpassing individual predictors. Conclusions: SDC1 emerged as the most reliable biomarker for assessing AKI and predicting the need for RRT, highlighting its potential role in early renal risk stratification among critically ill patients. Full article

Background/Objective: Sepsis is a leading cause of death in noncoronary intensive care units (ICUs). Fluids for intravascular resuscitation include crystalloids and colloids. There is extensive clinical evidence on colloid use, but large trials comparing gelatine with crystalloid regimens in ICU and septic patients are lacking. This study aimed to determine whether early, protocol-driven volume resuscitation using a gelatine-based regimen achieves hemodynamic stability (HDS) more rapidly than a crystalloid-based regimen in septic patients. Methods: This prospective, controlled, randomised, double-blind, multinational phase IV study compared two parallel groups of septic patients receiving a gelatine-based regimen (Gelaspan^® 4% and Sterofundin^® ISO, B. Braun Melsungen AG each, at a 1:1 ratio) or a crystalloid regimen (Sterofundin^® ISO). Primary endpoint was time to first HDS within 48 h after randomisation. Secondary endpoints included fluid overload, fluid balance, and patient outcomes. Results: 167 patients were randomised. HDS was achieved after 4.7 h in the gelatine group and after 5.8 h in the crystalloid group (p = 0.3716). The gelatine group had a more favourable fluid balance at 24 h (medians: 3463.00 mL vs. 4164.00 mL; p = 0.0395) and less fluid overload (medians: 4296.05 vs. 5218.75%; p = 0.0217). No differences were observed in serious adverse events or mortality. Conclusions: The study provided clinical evidence of balanced gelatine solution for volume resuscitation in septic patients, although it was terminated prematurely. The early and protocol-based administration of gelatine was safe and effective in the enrolled patient population. Time to HDS was not different between groups but the gelatine-based regimen led to better fluid balance and less fluid overload. Full article

Linezolid, an antimicrobial agent, has been linked to lactic acidosis, oxidative stress, and liver damage. Oxidative stress is considered to play a key role in this damage. Thiamine pyrophosphate (TPP), the active form of thiamine, may prevent lactate accumulation and enhance aerobic capacity. Therefore, this study aimed to evaluate the protective effect of TPP against possible linezolid-induced liver damage and lactic acidosis in rats. Twenty-four male Wistar albino rats were randomly assigned to four groups (n = 6): healthy control (HG), linezolid (LZD), thiamine plus linezolid (TLZD), and TPP plus linezolid (TPLZD). Thiamine and TPP (20 mg/kg, intraperitoneal (i.p.)) were administered once daily, while linezolid (125 mg/kg, per os (p.o.)) was given twice daily (250 mg/kg/day) for 28 days. Animals were euthanized under high-dose anesthesia (with 50 mg/kg, i.p. thiopental sodium). Liver tissues were analyzed for MDA, tGSH, SOD, and CAT, and examined histopathologically. Blood samples were collected prior to euthanasia to assess lactate, LDH, ALT, AST, and TPP levels. In the LZD group, MDA, lactate, ALT, AST, and LDH levels significantly increased, while tGSH, SOD, CAT, and TPP decreased (p < 0.001). Histopathology showed hydropic degeneration, necrosis, and mononuclear cell infiltration (p < 0.05). Thiamine did not prevent these alterations (p > 0.05), whereas TPP significantly prevented both biochemical and histopathological changes (p < 0.05), indicating its protective efficacy. TPP may offer significant protection against linezolid-induced hepatotoxicity and lactic acidosis. Full article

Background/Objectives: The Pleth Variability Index (PVI) is a non-invasive parameter used to guide fluid management by reflecting respiratory-induced variations in the plethysmographic waveform. While PVI’s reliability in various positions has been studied, data on its behavior in geriatric patients undergoing transurethral resection of the prostate (TUR-P) in the lithotomy position remain limited. This study aimed to evaluate the effect of the lithotomy position on PVI in geriatric versus non-geriatric patients under spinal anesthesia. Methods: This prospective observational study included 90 patients undergoing elective TUR-P in the lithotomy position under spinal anesthesia. Patients were divided into geriatric (≥65 years, n = 48) and non-geriatric (<65 years, n = 42) groups. PVI and Perfusion Index (PI) were recorded at baseline, in the supine position, and in the lithotomy position. Fluid and vasopressor requirements, along with hemodynamic parameters, were also analyzed. Results: PVI values at the 5th minute in the lithotomy position were significantly higher in the geriatric group compared to the non-geriatric group (p = 0.019). No significant differences were observed in PI values or intraoperative hypotension rates between the groups. Neurological comorbidities were more prevalent in the geriatric group (p = 0.025). Conclusions: PVI appears to be a more sensitive indicator of fluid responsiveness in elderly patients under spinal anesthesia in the lithotomy position. Its age-dependent variability suggests clinical utility in guiding fluid management in geriatric populations, while the stable hypotension rates support the effectiveness of PVI-guided goal-directed therapy. Full article

Background/Objectives: Hip fractures are highly prevalent worldwide, primarily affecting frail elderly patients. Frailty increases the risk of complications like postoperative delirium, which negatively impacts outcomes, including morbidity and mortality. Current recommendations favor a multidisciplinary approach and effective pain control, often using preoperative peripheral nerve blocks. We aimed to evaluate a multimodal approach’s efficacy in reducing postoperative delirium and complications in geriatric hip fracture patients. Methods: This study was conducted between March 2020 and June 2022. A total of 144 patients evaluated prior to the implementation of an optimized clinical pathway protocol (OCPP) were compared to 117 patients evaluated following its implementation. The protocol included early preoperative evaluation, streamlined medication adjustments, prompt surgical intervention and fascia iliaca compartment block (FICB) for analgesia. In addition, early patient mobilization and resumption of oral intake were promoted. The primary outcome was the incidence of delirium during hospitalization. Secondary outcomes were a composite of 30-day mortality or major complications, duration of stay, hospital readmission after discharge and 1-year mortality. Results: The OCPP intervention significantly reduced the incidence of postoperative delirium from 44% to 29% (a 33% relative reduction; p = 0.017), the rate of major complications or death was 14.5% in OCPP group and 25.7% in the control group (p = 0.02). Significantly more patients in the OCPP group were mobilized within 24 h (74.4% vs. 41.3% in the control group, p < 0.001). The median time to ambulation was also shorter in the OCPP group: 65 h (IQR: 39–115) compared to 72 h (IQR: 48–119.75) in the control group (p = 0.028). No differences were observed on hospital stay and 1-year mortality. Conclusions: Among patients undergoing hip fracture repair the implementation of a OCPP significantly reduced the incidence of postoperative delirium and the rate of major complications or death. This improvement was associated with significantly earlier patient mobilization and ambulation. The OCPP was not associated with a lower hospital stay and lower rate of one-year mortality. Full article

ABG analysis is the gold standard for assessing acid–base balance, oxygenation, and ventilation in critically ill patients, but it is invasive and associated with patient discomfort and potential complications. Venous blood gas (VBG) analysis offers a less invasive alternative, although its clinical utility remains debated. This review evaluates the current evidence on VBG analysis, exploring its correlation with ABG, clinical applications, and limitations. Studies show a strong correlation between ABG and VBG for pH and a good correlation for bicarbonate and base excess in most cases, while the correlation for pCO₂ remains controversial. Predictably, pO₂ values differ significantly due to oxygen consumption gradients between the arterial and venous blood. VBG analysis is especially valuable for initial assessments, monitoring therapeutic responses, and guiding resuscitation in intensive care settings. It is not merely an alternative to ABG but a complementary tool that can provide unique insights, such as mixed venous oxygen saturation (SvO₂) or indices that require combined ABG and VBG data, like the pCO₂ gap. This review highlights the diagnostic equivalence of VBG in appropriate contexts and advocates for its use when arterial sampling is unnecessary or impractical. Furthermore, VBG analysis could enhance patient care by enabling the timely, less invasive assessment of hemodynamic and metabolic conditions. Future research should focus on refining interpretation algorithms and expanding the clinical applications of VBG to fully realize its potential in critical care practice. Full article

Background and Objectives: Immunodeficiency associated with aging comorbidities increases the vulnerability of geriatric patients to sepsis. Early recognition and management of sepsis are essential in this population. This study evaluated the relationships between RDW, MPV, and MPV/PLT ratios and mortality in geriatric sepsis patients. Materials and Methods: This retrospective study was conducted between 2020 and 2024 in the Intensive Care Unit of the Department of Anesthesiology and Reanimation at a university hospital. Patients aged ≥ 65 years with a SOFA score of ≥2 were included. Demographic data (sex, age, height, weight, and BMI), hemogram parameters (RDW, MPV, and PLT), blood gas, and biochemical values were analyzed. Furthermore, their comorbidities; site of infection; ICU length of stay; vital signs; and SOFA, APACHE II, and SAPS II scores, recorded within the first 24 h following ICU admission, were evaluated. Statistical analysis was performed using the chi-square test, Student’s t-test, the Mann–Whitney U test, the Monte Carlo exact test, and ROC analysis. A p-value of <0.05 was considered statistically significant. Results: A total of 247 patients were included, with 46.2% (n = 114) classified as non-survivors during the 28-day follow-up period. Among them, 64.9% (n = 74) were male, with a mean age of 78.22 ± 8.53 years. Significant differences were also found in SOFA, APACHE-II, and SAPS-II scores between non-survivors and survivors (SOFA: 7.64 ± 3.16 vs. 6.78 ± 2.78, p = 0.023; APACHE-II: 21.31 ± 6.36 vs. 19.27 ± 5.88, p = 0.009; SAPS-II: 53.15 ± 16.04 vs. 46.93 ± 14.64, p = 0.002). On days 1, 3, and 5, the MPV/PLT ratio demonstrated a statistically significant predictive value for 28-day mortality. The optimal cut-off values were >0.03 on day 1 (AUC: 0.580, 95% CI: 0.516–0.642, sensitivity: 72.81%, specificity: 65.91%, p = 0.027), >0.04 on day 3 (AUC: 0.602, 95% CI: 0.538–0.663, sensitivity: 60.53%, specificity: 60.61%, p = 0.005), and >0.04 on day 5 (AUC: 0.618, 95% CI: 0.554–0.790, sensitivity: 66.14%, specificity: 62.88%, p = 0.001). Conclusions: The MPV and MPV/PLT ratios demonstrated statistically significant but limited predictive value for 28-day mortality in geriatric patients with sepsis. In contrast, the limited prognostic value of RDW may be related to variability in the inflammatory response and other underlying conditions. The correlations found between SOFA, APACHE II, and SAPS II scores highlight their importance in mortality risk prediction. Full article

Background: Down syndrome (DS) is associated with unique anatomical and physiological characteristics that complicate the perioperative management of infants undergoing cardiac surgery. While ventricular septal defect (VSD) repair is commonly performed in this population, detailed data comparing perioperative outcomes in DS versus non-syndromic infants remain limited. Methods: This retrospective matched study analysed 100 infants (50 with DS and 50 without DS) who underwent isolated VSD closure between January 2021 and January 2025. Patients were matched by age and surgical date. Intraoperative anesthetic management, complications, postoperative outcomes, and mortality were compared between groups. Results: DS patients had lower age, weight, and height at surgery. They required significantly smaller endotracheal tube sizes, more intubation and vascular access attempts. The DS group had significantly lower rates of extubation in the operating room and experienced longer durations of mechanical ventilation and ICU stay. However, no significant differences were observed in total hospital stay or mortality between groups. Conclusions: Although DS infants present with increased anesthetic complexity and respiratory challenges, they do not exhibit higher surgical mortality following isolated VSD closure. Tailored perioperative strategies may improve respiratory outcomes in this high-risk group. Full article

The present study aimed to investigate the electrophysiological correlates of face-identity recognition in newborn infants immediately after birth. Electroencephalographic acquisition was continuously recorded in 23 newborn infants (3 < age < 24 h of life) during the following visual task: presentation of a woman’s face for 60 s (“known face”); random presentation of 50 known faces, 50 novel women’s faces, and 50 chessboards (for 2 s each). The final sample included in ERP analyses was composed of 11 newborn infants (male/female: 6/5; age: 5 h 16′ ± 3 h 51′). A greater negative amplitude of the N290 and smaller P400 and LC2 were found in response to the known face compared with the novel one in the left hemisphere. A shorter N290 latency was detected during the known face presentation compared with the novel one, and a longer latency of the same component was observed during novel face presentation compared with the chessboard. These findings suggest that newborns process a face differently from an object at birth and that they can discriminate a new face from a familiar one previously viewed for one minute. Full article

Objective: This study aimed to investigate the cardioprotective effects of bosentan, an endothelin receptor antagonist, in a rat model of lung ischemia–reperfusion (I/R) injury, with a focus on myocardial tissue involvement. Methods: Twenty-four male Wistar rats were randomly assigned to four groups: sham, bosentan, I/R, and I/R + bosentan. Lung I/R injury was induced by hilar clamping for 45 min, followed by 60 min of reperfusion. Bosentan (30 mg/kg) was administered intraperitoneally 30 min prior to the procedure. Myocardial tissue was evaluated histopathologically for structural disorganization, inflammation, fibrosis, and edema. TGF-β1 protein levels in myocardial tissue were compared across the groups using β-actin as the loading control. ELISA was used to quantify ET-1, NF-κB, and p53 levels, while spectrophotometric analysis was employed to assess MDA levels and the activities of SOD and CAT enzymes in heart tissue. Results: The I/R group exhibited significant myocardial disorganization, inflammation, and interstitial edema compared to the sham and bosentan groups. Bosentan treatment markedly ameliorated these histopathological alterations. Additionally, the I/R group showed elevated levels of ET-1, NF-κB, p53, and MDA, along with reduced SOD and CAT activities; these changes were significantly attenuated by bosentan administration. Bosentan treatment significantly reduced myocardial ET-1 levels (from 136.88 ± 5.02 to 120.18 ± 2.67 nmol/g, p = 0.003), NF-κB levels (from 0.87 ± 0.04 to 0.51 ± 0.03 ng/mg, p = 0.002), and TGF-β1 expression (from 1.72 ± 0.10 to 0.91 ± 0.08 relative units, p = 0.001). Moreover, bosentan increased antioxidant enzyme activities, elevating SOD levels from 21.45 ± 1.23 to 32.67 ± 1.45 U/mg protein (p = 0.001) and CAT levels from 15.22 ± 0.98 to 25.36 ± 1.12 U/mg protein (p = 0.002). Conclusions: Bosentan exerts cardioprotective effects in rats subjected to lung I/R injury by reducing myocardial damage, inflammation, and oxidative stress. These findings suggest that bosentan may serve as a potential therapeutic agent for preventing remote organ injury associated with pulmonary I/R. Full article

Background and Objectives: Regional and systemic analgesic techniques, such as erector spinae plane (ESP) block and opioid administration, implemented during cancer surgery, have been shown to influence immune responses and potentially affect cancer outcomes. Surgical stress and analgesic techniques used in cancer surgery—such as regional nerve blocks or systemic opioids—not only affect pain control but also influence immune and inflammatory pathways that may impact cancer progression. To understand the biological consequences of these interventions, metabolomic profiling has emerged as a powerful approach for capturing systemic metabolic and immunological changes, which are particularly relevant in the oncologic perioperative setting. In this study, we examined the impact of the ESP on the metabolomic profile, as well as levels of VEGF, cortisol, and CRP, in addition to its analgesic effects in breast cancer surgery. Materials and Methods: Ninety patients were placed into three different analgesia groups (morphine, ESP, and control groups). Demographic data, ASA classification, comorbidities, surgery types, and pain scores were documented. Blood samples were taken at preoperative hour 0, postoperative hour 1, and postoperative hour 24 (T0, T1, and T24). VEGF, cortisol, and CRP levels were measured, and metabolomic analysis was performed. Results: Study groups were comparable regarding demographic findings, comorbidities, and surgery types (p > 0.05). NRS scores of group ESP were lowest in the first 12 h period (p < 0.01) and ESP block reduced opioid consumption (p < 0.01). VEGF and cortisol levels of group morphine were similar to ESP at T24 (p > 0.05). Group ESP had lower VEGF and cortisol levels than the control at T24 (p = 0.025, p = 0.041, respectively.). The CRP level of group morphine was higher than both ESP and control at T24 (p = 0.022). Metabolites involved in primary bile acid, steroid hormone biosynthesis, amino acid, and glutathione metabolism were changed in group ESP. Conclusions: Metabolites in bile acid biosynthesis and steroid hormone pathways, which play a key role in immune responses, were notably lower in the ESP group. Accordingly, VEGF and cortisol peaks were more moderate in group ESP. In conclusion, we think that ESP block, which provides adequate analgesia, is an acceptable approach in terms of modulating immune responses in breast cancer surgery. Full article

Innate immune cells appear to have an important implication in the resolution and/or the aggravation of the COVID-19 pathogenesis after infection with SARS-CoV-2. To better appreciate the role of these cells during COVID-19, changes in blood eosinophil, the neutrophil and monocyte count, and levels of surface protein markers have been reported. However, analyses at several timepoints of multiple surface markers on granulocytes and monocytes over a period of one month after a SARS-CoV-2 infection are missing. Therefore, in this study, we performed blood eosinophil, neutrophil, and monocyte phenotyping using a list of surface proteins and flow cytometry during a period of 30 days after the hospitalization of patients with severe SARS-CoV-2 infections. Blood cell counts were reported at seven different timepoints over the 30-day period as well as measures of multiple mediators in serum using a targeted multiplex assay approach. Our results indicate a 95% drop in the blood eosinophil count by D1, with eosinophils displaying a phenotype defined as CD69/CD63/CD125^high and CCR3/CD44^low during the early phases of hospitalization. Conversely, by D7 the neutrophil count increased significantly and displayed an immature, activated, and immunosuppressive phenotype (i.e., 3% of CD10/CD16^low and CD10^lowCD177^high, 6.7% of CD11b^highCD62L^low, and 1.6% of CD16^highCD62L^low), corroborated by enhanced serum proteins that are markers of neutrophil activation. Finally, our results suggest a rapid recruitment of non-classical monocytes leaving CD163/CD64^high and CD32^low monocytes in circulation during the very early phase. In conclusion, our study reveals potential very early roles for eosinophils and monocytes in the pathogenesis of COVID-19 with a likely reprogramming of eosinophils in the bone marrow. The exact roles of the pro-inflammatory neutrophils and the functions of the eosinophils and the monocytes, as well as these innate immune cell types, interplays need to be further investigated. Full article