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Search Results (186)

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18 pages, 3680 KB  
Article
Polymicrobial Infection (Gram-Positive and Gram-Negative) Exacerbates Systemic Inflammatory Response Syndrome in a Conscious Swine Extremity Trauma Model
by Catharina C. Gaeth, Travis R. Madaris, Jamila M. Duarte, Amber M. Powers, Christina M. Sandoval, Stefanie M. Shiels and Randolph Stone
Pathophysiology 2025, 32(4), 59; https://doi.org/10.3390/pathophysiology32040059 - 4 Nov 2025
Viewed by 240
Abstract
Background/Objectives: Extremity trauma represents a significant proportion of battlefield injuries and is prevalent in polytraumatized patients from accidents. Delayed antibiotic treatment and surgical intervention can lead to wound infections, contributing to preventable mortality. This preliminary study aimed to develop a conscious swine [...] Read more.
Background/Objectives: Extremity trauma represents a significant proportion of battlefield injuries and is prevalent in polytraumatized patients from accidents. Delayed antibiotic treatment and surgical intervention can lead to wound infections, contributing to preventable mortality. This preliminary study aimed to develop a conscious swine model of complex extremity trauma that induces systemic inflammatory response syndrome (SIRS). Methods: All surgical procedures were conducted under anesthesia with sufficient analgesia. All swine were instrumented with a telemetry device and catheters at least 3 days prior to any injury. In phase 1 of model development, a complex extremity injury was performed that consisted of skin and muscle loss, bone defect, severe hemorrhage, and 2 h tourniquet application. In phase 2, multi-drug resistant Gram-positive and Gram-negative bacteria were inoculated topically at the injury site to exacerbate pathophysiological changes towards SIRS. Post-injury, conscious animals were assessed a minimum of twice daily, including pain assessment, neurological response, and vital signs. Blood samples were collected for microbiological testing, complete blood cell counts, and biochemical analysis. Results: After establishing SIRS criteria for Sinclair swine, we developed a model of severe extremity trauma leading to SIRS. During phase 1, resuscitative fluids were reduced and discontinued, with animals surviving 24 h and maintaining SIRS for up to 4 h post-recovery. Phase 2 showed that Gram-negative and Gram-positive pathogens can exacerbate and prolong SIRS. After 72 h, localized infection at the injury site was observed in all animals. Conclusions: We established a new swine model of complex extremity trauma with SIRS. Our model is consistent, reproducible, and relevant to prolonged care scenarios, providing a platform for future research into the evaluation of preventative and therapeutic strategies. Full article
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15 pages, 258 KB  
Review
Comparative Analysis of Recent Burn Guidelines Regarding Specific Aspects of Anesthesia and Intensive Care
by Rolf K. Gigengack, Joeri Slob, J. Seppe H. A. Koopman, Cornelis H. Van der Vlies and Stephan A. Loer
Eur. Burn J. 2025, 6(4), 57; https://doi.org/10.3390/ebj6040057 - 29 Oct 2025
Viewed by 272
Abstract
Background: Critical care for patients with severe burn injuries is challenging, particularly in the first 24–48 h. Multiple guidelines exist but their recommendations vary in content and in the level of detail. Methods: This narrative review analyzed recent (last 10 years) adult burn [...] Read more.
Background: Critical care for patients with severe burn injuries is challenging, particularly in the first 24–48 h. Multiple guidelines exist but their recommendations vary in content and in the level of detail. Methods: This narrative review analyzed recent (last 10 years) adult burn guidelines in English, Dutch and German, sourced from PubMed, Medline and official burn society publications. The review focused on airway management, mechanical ventilation, fluid resuscitation, pain management and procedural sedation. Results: All guidelines emphasize early airway assessment and timely intubation in patients at risk for loss of airway patency; however, a strategy for analyzing patients at risk is lacking. Lung-protective ventilation strategy is generally recommended. Fluid resuscitation is the cornerstone during the first phase, though recommendations for thresholds, volume and adjuncts differ. (Chronic) pain management should be multimodal, combining pharmacologic and non-pharmacologic approaches, but specifics on choice of modality are limited, also, there is no uniform strategy for procedural sedation management. Conclusion: Current guidelines offer broadly consistent recommendations for initial burn care but differ in specifics, reflecting evidence gaps. Future guidelines should address advances in airway management, fluid resuscitation endpoints, volume and adjuncts, and give a more detailed (chronic) pain strategy to improve standardization and outcomes. Full article
17 pages, 1178 KB  
Article
Hemodynamic Heterogeneity in Community-Acquired Sepsis at Intermediate Care Admission: A Prospective Pilot Study Using Impedance Cardiography
by Gianni Turcato, Arian Zaboli, Lucia Filippi, Fabrizio Lucente, Michael Maggi, Alessandro Cipriano, Massimo Marchetti, Daniela Milazzo, Christian J. Wiedermann and Lorenzo Ghiadoni
Healthcare 2025, 13(21), 2686; https://doi.org/10.3390/healthcare13212686 - 23 Oct 2025
Viewed by 274
Abstract
Background: Sepsis is a heterogeneous syndrome in which patients with similar clinical presentations at admission may exhibit markedly different treatment responses and outcomes, suggesting that comparable macroscopic features can conceal profoundly distinct perfusion and hemodynamic states. Aim: This study aimed to [...] Read more.
Background: Sepsis is a heterogeneous syndrome in which patients with similar clinical presentations at admission may exhibit markedly different treatment responses and outcomes, suggesting that comparable macroscopic features can conceal profoundly distinct perfusion and hemodynamic states. Aim: This study aimed to characterize the hemodynamic profile of patients with community-acquired sepsis, assess its correlation with macro-hemodynamic indices, compare fluid responders with non-responders, and explore the prognostic value of early identification of a feature consistent with distributive shock. Methods: A prospective observational pilot study was conducted in the Intermediate Medical Care Unit (IMCU) of Ospedale Alto Vicentino (Santorso, Italy), September 2024–May 2025. 115 consecutive adults with community-acquired sepsis underwent NICaS® bioimpedance assessment at IMCU admission. Sepsis was diagnosed at IMCU admission as suspected/confirmed infection plus an acute increase in total Sequential Organ Failure Assessment (SOFA) ≥ 2 points. Hemodynamic indices were analyzed in relation to the Sequential Organ Failure Assessment (SOFA) score and mean arterial pressure (MAP), fluid responsiveness, and 30-day mortality. Results: Hemodynamics were heterogeneous across patients and within SOFA strata. SOFA showed no correlation with SV, SI, CO, or CI; weak inverse associations for TPR (r = −0.198, p = 0.034) and TPRI (r = −0.241, p = 0.009) were observed. MAP did not correlate with SV, SI, CO, or CI, but correlated positively with TPR (r = 0.461) and TPRI (r = 0.547) and with CPI (ρ = 0.550), all p < 0.001. A distributive profile was present in 21.7% (25/115), increasing with higher SOFA (p = 0.033); only 20% of those with this profile had MAP < 65 mmHg at admission. Fluid non-responders (27.8%) had lower resistance and higher CI (4.1 vs. 3.4 L/min/m2; p = 0.015). The distributive profile was not associated with 30-day mortality (log-rank p = 0.808). Conclusions: In IMCU patients with community-acquired sepsis, macro-indices (SOFA, MAP) correlate poorly with the underlying hemodynamic state. Early noninvasive profiling reveals within-SOFA circulatory heterogeneity and may support operational, individualized resuscitation strategies; these pilot findings are hypothesis-generating and warrant prospective interventional testing. Full article
(This article belongs to the Special Issue New Tools and Technologies in Emergency Medicine and Critical Care)
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20 pages, 1246 KB  
Review
Fluid Therapy in Acute Pancreatitis—Current Knowledge and Future Perspectives
by Miłosz Caban, Hubert Zatorski and Ewa Małecka-Wojciesko
Pharmaceuticals 2025, 18(11), 1601; https://doi.org/10.3390/ph18111601 - 23 Oct 2025
Viewed by 1728
Abstract
Acute pancreatitis (AP) is one of the most frequent diseases requiring hospitalization in gastroenterology or intensive care unit departments. Its incidence and hospitalization rates have steadily increased over the last few years, contributing to high costs of medical care. This disease is associated [...] Read more.
Acute pancreatitis (AP) is one of the most frequent diseases requiring hospitalization in gastroenterology or intensive care unit departments. Its incidence and hospitalization rates have steadily increased over the last few years, contributing to high costs of medical care. This disease is associated with relevant mortality and morbidity rates. Fluid therapy in the first 48–72 h has an important role in the clinical course and complications; however, it has been raising numerous controversies recently. We present a review article summarizing the current knowledge about fluid therapy in AP. The demonstrated results are based on the most recent clinical studies published in the last five years. Data confirms that the therapy should be individualized along with the amount of fluids adapted to body mass, concomitant diseases, critical signs, and laboratory markers. A relevant issue in the context of fluid therapy of AP is fluid resuscitation that should be implemented in some patients upon hospital admission to maintain organ perfusion and substrate delivery. Ringer’s lactate should be preferred in the vast majority of AP cases over normal saline solution. Its use is associated with lowered risk of intensive care unit admission and local complications development, reduced hospital stay, and decreased mortality. Colloids, mainly hydroxyethyl starch, should not be recommended. Moderate-rate fluid infusion seems to be an advantage over high-rate infusion. Relying on presented results, fluid therapy has a key therapeutic role in AP management. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
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8 pages, 828 KB  
Case Report
Expanding the Limits of Burn Care: Survival After a 92% Total Body Surface Area Burn
by Rafael Rocha, Odete Martinho, Filipe Marques da Costa, Gaizka Ribeiro, Fátima Xambre and Miguel Ribeiro de Andrade
Eur. Burn J. 2025, 6(4), 56; https://doi.org/10.3390/ebj6040056 - 20 Oct 2025
Viewed by 491
Abstract
Introduction: Massive burns, particularly those exceeding 90% total body surface area (TBSA), represent one of the most demanding challenges in critical care and reconstructive surgery. Advances in resuscitation, early excision, and wound coverage techniques have improved survival rates, but despite these advances, [...] Read more.
Introduction: Massive burns, particularly those exceeding 90% total body surface area (TBSA), represent one of the most demanding challenges in critical care and reconstructive surgery. Advances in resuscitation, early excision, and wound coverage techniques have improved survival rates, but despite these advances, mortality remains high, and standardized treatment protocols are lacking. Case Report: We report a case which demonstrates survival and meaningful recovery in an extreme case of massive burns. A 57-year-old woman sustained 92% TBSA burns following a gas explosion at her home. She developed burn shock requiring aggressive fluid resuscitation and vasopressor support. Due to extensive burns and limited donor sites, staged debridement with temporary allograft coverage was performed, followed by Meek micrografting for definitive wound closure. After 197 days in the Burn Unit and an additional three months of rehabilitation, she regained functional independence. Conclusions: While historically considered non-survivable, burns exceeding 90% TBSA are increasingly being successfully treated with multimodal strategies. This case highlights the importance of multidisciplinary care in redefining survival expectations for massive burn patients. As burn care continues to evolve, further research is needed to refine treatment strategies, enhance long-term functional outcomes and standardize protocols for these complex cases. Full article
(This article belongs to the Special Issue Controversial Issues in Intensive Care-Related Burn Injuries)
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13 pages, 735 KB  
Article
Pleth Variability Index or Inferior Vena Cava Collapsibility Index? Prospective Observational Study in Volume Control and Follow-Up Acute Kidney Injury
by Ecem Ermete Güler, Ejder Saylav Bora, Hüseyin Acar, Süleyman Kırık, Burak Acar and Şakir Hakan Aksu
Medicina 2025, 61(10), 1868; https://doi.org/10.3390/medicina61101868 - 17 Oct 2025
Viewed by 424
Abstract
Background and Objective: Acute kidney injury (AKI) is a serious condition requiring prompt fluid resuscitation, yet both under- and over-treatment carry risks. Accurate volume assessment is essential, especially in emergency settings. The Inferior Vena Cava Collapsibility Index (IVCCI) is commonly used but [...] Read more.
Background and Objective: Acute kidney injury (AKI) is a serious condition requiring prompt fluid resuscitation, yet both under- and over-treatment carry risks. Accurate volume assessment is essential, especially in emergency settings. The Inferior Vena Cava Collapsibility Index (IVCCI) is commonly used but has limitations. The Pleth Variability Index (PVI) offers a non-invasive alternative, though its role in AKI remains unclear. To compare the efficacy of the Pleth Variability Index (PVI) and Inferior Vena Cava Collapsibility Index (IVCCI) in assessing fluid responsiveness and predicting in-hospital mortality in patients with acute kidney injury. Materials and Methods: This prospective observational study enrolled 50 adult AKI patients presenting to a tertiary emergency department. All patients received sequential fluid resuscitation with 1000 mL and 2000 mL of isotonic saline. PVI, IVCCI, mean arterial pressure (MAP), peripheral oxygen saturation (SpO2, perfusion index (PI), and shock index (SI) were recorded at baseline and after each fluid bolus. Changes in these parameters were analyzed to assess their utility in fluid responsiveness. Additionally, the prognostic value of baseline PVI for in-hospital mortality was investigated. Results: PVI demonstrated a significant and dose-responsive decrease following fluid administration, outperforming IVCCI, MAP, PI, SpO2, and SI in sensitivity (p < 0.001). Baseline PVI values were significantly associated with mortality (AUC: 0.821, p < 0.001), whereas post-resuscitation PVI values showed no prognostic significance. IVCCI and PI showed comparable reliability but were less sensitive to incremental volume changes. Conclusions: PVI is a sensitive, non-invasive marker of fluid responsiveness in non-intubated AKI patients and may also serve as an early prognostic indicator. Its use in emergency departments could support fluid management decisions, but further large-scale, multicenter studies are needed to validate these findings. Full article
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16 pages, 726 KB  
Review
Non-Invasive Hemodynamic Monitoring in Critically Ill Patients: A Guide for Emergency Physicians
by Michela Beltrame, Mattia Bellan, Filippo Patrucco and Francesco Gavelli
J. Clin. Med. 2025, 14(19), 7002; https://doi.org/10.3390/jcm14197002 - 3 Oct 2025
Viewed by 2105
Abstract
Hemodynamic monitoring is fundamental in the management of critically ill patients with acute circulatory failure. The invasiveness of conventional devices, however, often limits their applicability in the emergency department (ED). Recent advances have introduced non-invasive modalities (including echocardiography, bioreactance, and plethysmography) that extend [...] Read more.
Hemodynamic monitoring is fundamental in the management of critically ill patients with acute circulatory failure. The invasiveness of conventional devices, however, often limits their applicability in the emergency department (ED). Recent advances have introduced non-invasive modalities (including echocardiography, bioreactance, and plethysmography) that extend the use of hemodynamic assessment beyond the intensive care unit. Among various available techniques, bedside ultrasound (Point-of-Care Ultrasound, POCUS) emerges as a particularly versatile tool for rapid and comprehensive assessment of cardiac function and volume status. When integrated with continuous technologies such as bioreactance or pulse contour analysis, it allows for the adoption of more dynamic and personalized fluid management strategies. Currently, a multimodal and patient-centered approach represents the most effective paradigm for non-invasive hemodynamic evaluation in the emergency setting. This strategy enhances diagnostic accuracy and enables timely interventions guided by pathophysiological principles. Despite the inherent limitations of each technique, their integration provides emergency physicians with real-time information, with potential benefits on clinical outcomes and resource utilization. This review aims to outline the pathophysiological rationale for adopting non-invasive monitoring in the ED and to critically evaluate the advantages and limitations of each technique, providing emergency physicians with a concise framework to guide clinical practice. Full article
(This article belongs to the Section Emergency Medicine)
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19 pages, 2611 KB  
Review
Interventional Management of Acute Pancreatitis and Its Complications
by Muaaz Masood, Amar Vedamurthy, Rajesh Krishnamoorthi, Shayan Irani, Mehran Fotoohi and Richard Kozarek
J. Clin. Med. 2025, 14(18), 6683; https://doi.org/10.3390/jcm14186683 - 22 Sep 2025
Viewed by 2940
Abstract
Acute pancreatitis (AP) is the most common cause of gastrointestinal-related hospitalizations in the United States, with gallstone disease and alcohol as the leading etiologies. Management is determined by disease severity, classified as interstitial edematous pancreatitis or necrotizing pancreatitis, with severity further stratified based [...] Read more.
Acute pancreatitis (AP) is the most common cause of gastrointestinal-related hospitalizations in the United States, with gallstone disease and alcohol as the leading etiologies. Management is determined by disease severity, classified as interstitial edematous pancreatitis or necrotizing pancreatitis, with severity further stratified based on local complications and systemic organ dysfunction. Regardless of etiology, initial treatment involves aggressive intravenous fluid resuscitation with Lactated Ringer’s solution, pain and nausea control, early oral feeding in 24 to 48 h, and etiology-directed interventions when indicated. In gallstone pancreatitis, early endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy is indicated in the presence of concomitant cholangitis or persistent biliary obstruction, with subsequent laparoscopic cholecystectomy as standard of care for stone clearance. The role of interventional therapy in uncomplicated AP is limited in the acute phase, except for biliary decompression or enteral feeding support with nasojejunal tube placement. However, in severe AP with complications, interventional radiology (IR) and endoscopic approaches play a pivotal role. IR facilitates early percutaneous drainage of symptomatic, acute fluid collections and infected necrosis, particularly in non-endoscopically accessible retroperitoneal or dependent collections, improving outcomes with a step-up approach. IR-guided angiographic embolization is the preferred modality for hemorrhagic complications, including pseudoaneurysms. In the delayed phase, walled-off necrosis (WON) and pancreatic pseudocysts are managed with endoscopic ultrasound (EUS)-guided drainage, with direct endoscopic necrosectomy (DEN) reserved for infected necrosis. Dual-modality drainage (DMD), combining percutaneous and endoscopic drainage, is increasingly utilized in extensive or complex collections, reflecting a collaborative effort between gastroenterology and interventional radiology comparable to that which exists between IR and surgery in institutions that perform video assisted retroperitoneal debridement (VARD). Peripancreatic fluid collections may fistulize into adjacent structures, including the stomach, small intestine, or colon, requiring transpapillary stenting with or without additional closure of the gut leak with over-the-scope clips (OTSC) or suturing devices. Additionally, endoscopic management of pancreatic duct disruptions with transpapillary or transmural stenting plays a key role in cases of disconnected pancreatic duct syndrome (DPDS). Comparative outcomes across interventional techniques—including retroperitoneal, laparoscopic, open surgery, and endoscopic drainage—highlight a shift toward minimally invasive approaches, with decreased morbidity and reduced hospital stay. The integration of endoscopic and interventional radiology-guided techniques has transformed the management of AP complications and multidisciplinary collaboration is essential for optimal patient outcomes. Full article
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24 pages, 3144 KB  
Systematic Review
Fluid Resuscitation with Lactated Ringer vs. Normal Saline in Acute Pancreatitis: A Systematic Review and Meta-Analysis of Clinical Trials
by Freiser Eceomo Cruz Mosquera, Elizabeth Camacho Benítez, Mariatta Catalina Ceballos Benavides, Julián Esteban Castillo Muñoz, Carlos Andrés Castañeda and Yamil Liscano
Diseases 2025, 13(9), 300; https://doi.org/10.3390/diseases13090300 - 10 Sep 2025
Viewed by 1807
Abstract
Background: Initial fluid therapy in acute pancreatitis is critical for modulating the systemic inflammatory response. The choice between Lactated Ringer and normal saline remains debated, given their potentially divergent impacts on disease progression and clinically relevant outcomes. The objective of this meta-analysis is [...] Read more.
Background: Initial fluid therapy in acute pancreatitis is critical for modulating the systemic inflammatory response. The choice between Lactated Ringer and normal saline remains debated, given their potentially divergent impacts on disease progression and clinically relevant outcomes. The objective of this meta-analysis is to determine the effectiveness of one solution versus the other in patients with AP. Methods: A systematic review of randomized clinical trials published between 2000 and 2024 was conducted through an exhaustive search in databases such as PubMed, ScienceDirect, LILACS, SCOPUS, Web of Science, Springer, Scielo, and Cochrane. The review protocol adhered to the recommendations established by PRISMA. The methodological quality of the selected studies was assessed using the Jadad scale, while statistical analyses were performed with RevMan 5.4® and Jamovi 2.3.28® software. Results: Five trials with 299 patients showed that, in patients with AP, Lactated Ringer significantly reduced ICU admission (RR: 0.39; 95% CI: 0.18–0.85; p = 0.02) and the progression of pancreatitis (RR: 0.63; 95% CI: 0.40–0.98; p = 0.04). There was no significant difference in mortality or hospital stay (SMD: −0.89; 95% CI: −2.26 to 0.48; p = 0.23). No clear effects were observed on SIRS at 24, 48, and 72 h. CRP at 48 h was significantly lower with lactate (SMD: −3.91; 95% CI: −4.66 to −3.17; p < 0.00001), but not at 72 h. Conclusions: The administration of Lactated Ringer in acute pancreatitis shows clinical and anti-inflammatory benefits, but the evidence is mostly of low quality. Full article
(This article belongs to the Section Gastroenterology)
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27 pages, 1574 KB  
Review
A Comprehensive Review of Fluid Resuscitation Strategies in Traumatic Brain Injury
by Mairi Ziaka, Wolf Hautz and Aristomenis Exadaktylos
J. Clin. Med. 2025, 14(17), 6289; https://doi.org/10.3390/jcm14176289 - 5 Sep 2025
Viewed by 3615
Abstract
The current management of severe traumatic brain injury (TBI) focuses on maintaining cerebral perfusion pressure (CPP) to prevent or minimize secondary brain injury, limit cerebral edema, optimize oxygen delivery to the brain, and reduce primary neuronal damage by addressing contributing risk factors such [...] Read more.
The current management of severe traumatic brain injury (TBI) focuses on maintaining cerebral perfusion pressure (CPP) to prevent or minimize secondary brain injury, limit cerebral edema, optimize oxygen delivery to the brain, and reduce primary neuronal damage by addressing contributing risk factors such as hypotension and hypoxia. Hypotension and cardiac dysfunction are common in patients with severe TBI, often requiring treatment with intravenous fluids and vasopressors. The primary categories of resuscitation fluids include crystalloids, colloids (such as albumin), and blood products. Fluid osmolarity is a critical consideration in TBI patients, as hypotonic fluids, such as balanced crystalloids, may increase the risk of cerebral edema development and worsening. Hyperosmolar therapy is a common therapeutic approach in patients with intracranial hypertension; however, its use as a resuscitation fluid is not associated with benefits in patients with TBI and is not recommended. Given the contradictory results of trials on blood transfusion strategies in patients with TBI, the transfusion approach should be tailored to individual systemic and cerebral physiological parameters. The evaluation of recent randomized clinical trials will provide insight into whether a liberal or restrictive transfusion strategy is preferred for this patient population. Hemodynamic and multimodal neurological monitoring to assess cerebral oxygenation, autoregulation, and metabolism are essential tools for detecting early hemodynamic alterations and cerebral injury, guiding resuscitation management, and contributing to improved outcomes. Full article
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16 pages, 3954 KB  
Article
Targeting Kupffer Cell Enolase 1 Attenuates Liver Inflammation and Injury in Hemorrhagic Shock
by Zhijian Hu, Jingsong Li, Naureen Rashid, Asha Jacob and Ping Wang
Int. J. Mol. Sci. 2025, 26(17), 8340; https://doi.org/10.3390/ijms26178340 - 28 Aug 2025
Viewed by 765
Abstract
Hemorrhagic shock (HS) is a type of hypovolemic shock and is a leading cause of mortality worldwide. Enolase 1 (ENO1), a key enzyme in glycolysis, has been implicated in the pathogenesis of inflammatory disorders. We hypothesize that Kupffer cell (KC) ENO1 contributes to [...] Read more.
Hemorrhagic shock (HS) is a type of hypovolemic shock and is a leading cause of mortality worldwide. Enolase 1 (ENO1), a key enzyme in glycolysis, has been implicated in the pathogenesis of inflammatory disorders. We hypothesize that Kupffer cell (KC) ENO1 contributes to liver inflammation and that inhibiting ENO1 with ENOblock protects the liver from HS-induced injury. HS was induced in mice by lowering mean arterial pressure to 25 mmHg for 90 min, followed by fluid resuscitation. Twenty-four hours later, KCs were isolated. To mimic HS in vitro, KCs were isolated from healthy mice and exposed to hypoxia/reoxygenation (H/R). Hypoxic KCs were treated with ENOblock during reoxygenation, and cytokines (IL-1β, TNF-α, IL-6) were measured. In mice subjected to HS and treated with ENOblock, the liver was harvested. In KCs isolated from HS mice as well as in H/R exposed KCs, ENO1 mRNA and protein expression were significantly increased. In KCs exposed to H/R as well as in liver tissues from HS mice, cytokine mRNA and protein levels (IL-1β, TNF-α, IL-6) were increased; however, ENOblock treatment significantly decreased these parameters. HS also markedly increased ENO1 activity and cleaved caspase-1 in KCs, while these parameters were significantly attenuated by ENOblock treatment. These findings suggest that targeting ENO1 in KCs could be a promising therapeutic strategy for mitigating HS-induced liver injury. Full article
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9 pages, 479 KB  
Article
Impact of Change in Neonatal Resuscitation Program Guidelines for Infants Born Through Meconium-Stained Amniotic Fluid
by Hamza Abbasi, James Shelton, Praveen Chandrasekharan and Munmun Rawat
Children 2025, 12(8), 1072; https://doi.org/10.3390/children12081072 - 15 Aug 2025
Viewed by 2753
Abstract
Background: In 2016, the neonatal resuscitation program (NRP) changed its recommendation to perform endotracheal suctioning in non-vigorous neonates born through meconium-stained amniotic fluid (MSAF). The objective of this study is to compare outcomes in non-vigorous neonates born through MSAF before and after [...] Read more.
Background: In 2016, the neonatal resuscitation program (NRP) changed its recommendation to perform endotracheal suctioning in non-vigorous neonates born through meconium-stained amniotic fluid (MSAF). The objective of this study is to compare outcomes in non-vigorous neonates born through MSAF before and after the change in the NRP’s recommendations. Methods: This is a retrospective cohort study in a single center assessing all neonates ≥34 weeks of gestation with MSAF in 2010–2015 (pre-implementation of new guidelines) and 2017–2022 (post-implementation of new guidelines). Results: Neonates receiving tracheal suctioning were more likely to be diagnosed with MAS (29.3% vs. 19.7%; p = 0.03) and PPHN (8.9% vs. 2.5%; p = 0.003) and more likely to receive surfactant (7.6% vs. 3.2%; p = 0.03). Conclusions: In our institution, non-vigorous neonates born via MSAF after the change in NRP guidelines were less likely to be diagnosed with MAS and PPHN and were less likely to receive surfactant. Our study supports current NRP guidelines. Full article
(This article belongs to the Special Issue New Insights in Neonatal Resuscitation)
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14 pages, 1836 KB  
Article
Machine Learning Prediction of Mean Arterial Pressure from the Photoplethysmography Waveform During Hemorrhagic Shock and Fluid Resuscitation
by Jose M. Gonzalez, Saul J. Vega, Shakayla V. Mosely, Stefany V. Pascua, Tina M. Rodgers and Eric J. Snider
Sensors 2025, 25(16), 5035; https://doi.org/10.3390/s25165035 - 13 Aug 2025
Viewed by 786
Abstract
We aimed to evaluate the non-invasive photoplethysmography waveform as a means to predict mean arterial pressure using artificial intelligence models. This was performed using datasets captured in large animal hemorrhage and resuscitation studies. An initial deep learning model trained using a subset of [...] Read more.
We aimed to evaluate the non-invasive photoplethysmography waveform as a means to predict mean arterial pressure using artificial intelligence models. This was performed using datasets captured in large animal hemorrhage and resuscitation studies. An initial deep learning model trained using a subset of large animal data and was then evaluated for real-time blood pressure prediction. With the successful proof-of-concept experiment, we further tested different feature extraction approaches as well as different machine learning and deep learning methodologies to examine how various combinations of these methods can improve the accuracy of mean arterial pressure predictions from a non-invasive photoplethysmography sensor. Different combinations of feature extraction and artificial intelligence models successfully predicted mean arterial pressure throughout the study. Overall, manual feature extraction fed into a long short-term memory network tracked the mean arterial pressure through hemorrhage and resuscitation with the highest accuracy. Full article
(This article belongs to the Special Issue AI on Biomedical Signal Sensing and Processing for Health Monitoring)
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33 pages, 1782 KB  
Review
Synthalin, Buformin, Phenformin, and Metformin: A Century of Intestinal “Glucose Excretion” as Oral Antidiabetic Strategy in Overweight/Obese Patients
by Giuliano Pasquale Ramadori
Livers 2025, 5(3), 35; https://doi.org/10.3390/livers5030035 - 31 Jul 2025
Viewed by 2019
Abstract
After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have [...] Read more.
After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article
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15 pages, 1173 KB  
Article
Efficacy and Safety of a Balanced Gelatine Solution for Fluid Resuscitation in Sepsis: A Prospective, Randomised, Controlled, Double-Blind Trial-GENIUS Trial
by Gernot Marx, Jan Benes, Ricard Ferrer, Dietmar Fries, Johannes Ehler, Rolf Dembinski, Peter Rosenberger, Kai Zacharowski, Manuel Sanchez, Karim Asehnoune, Bernd Bachmann-Mennenga, Carole Ichai and Tim-Philipp Simon
J. Clin. Med. 2025, 14(15), 5323; https://doi.org/10.3390/jcm14155323 - 28 Jul 2025
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Abstract
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 [...] Read more.
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
(This article belongs to the Section Hematology)
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