Search Results (39)

Background: Hepatocellular carcinoma (HCC) is a major global health burden and a leading cause of cancer-related deaths. While aspirin has shown potential chemopreventive effects in chronic liver disease, its impact on clinical outcomes among patients hospitalized with HCC remains under-investigated. Methods: Using the National Inpatient Sample (NIS) from 2016 to 2022, we conducted a retrospective cohort study to evaluate the association between aspirin use and clinical outcomes in adult HCC hospitalizations. Patients were stratified based on documented aspirin use, and propensity score matching with inverse probability of treatment weighting (IPTW) was applied to minimize confounding. The primary outcome was in-hospital mortality; secondary outcomes included morbidity-related complications, hospital length of stay, and total charges. Results: Among 337,730 hospitalizations with HCC, 8.37% involved aspirin use. Aspirin users demonstrated significantly lower in-hospital mortality (5.2% vs. 10.09%), with an adjusted odds ratio (OR) of 0.58 (95% CI: 0.50–0.68; p < 0.001). Aspirin use was also associated with shorter hospital stays (5.42 vs. 6.39 days), lower total charges ($80,310 vs. $95,098), and reduced incidence of complications, including acute liver failure, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, sepsis, ICU admission, and acute kidney injury. Importantly, no statistically significant increase in gastrointestinal or variceal bleeding was observed among aspirin users. Conclusions: These findings suggest that aspirin use may reduce mortality, morbidity, and healthcare burden in patients hospitalized with HCC. Full article

Introduction: Sepsis-associated encephalopathy (SAE) is an acute brain dysfunction secondary to systemic infection, occurring without direct central nervous system involvement. Despite its clinical relevance, reliable biomarkers for diagnosing SAE and assessing its severity remain limited. This study aimed to evaluate the feasibility of amide proton transfer-weighted (APTw) chemical exchange saturation transfer (CEST) MRI as a non-invasive molecular imaging technique for detecting metabolic alterations related to neuroinflammation in SAE. Using a lipopolysaccharide (LPS)-induced rat model, we focused on hippocampal changes associated with neuronal inflammation. Materials and Methods: Twenty-one Sprague–Dawley rats (8 weeks old, male) were divided into three groups: control (CTRL, n = 7), LPS-induced sepsis at 5 mg/kg (LPS05, n = 7), and 10 mg/kg (LPS10, n = 7). Sepsis was induced via a single intraperitoneal injection of LPS. APTw imaging was performed using a 7 T preclinical MRI system, and signal quantification in the hippocampus was conducted using the magnetization transfer ratio asymmetry analysis. Results and Discussion: APTw imaging at 7 T demonstrated significantly elevated hippocampal APTw signals in SAE model rats (LPS05 and LPS10) compared to the control (CTRL) group: CTRL (−1.940 ± 0.207%) vs. LPS05 (−0.472 ± 0.485%) (p < 0.001) and CTRL vs. LPS10 (−0.491 ± 0.279%) (p < 0.001). However, no statistically significant difference was observed between the LPS05 and LPS10 groups (p = 0.994). These results suggest that APTw imaging can effectively detect neuroinflammation-related metabolic alterations in the hippocampus. Conclusion: Our findings support the feasibility of APTw CEST imaging as a non-invasive molecular MRI technique for SAE, with potential applications in diagnosis, disease monitoring, and therapeutic evaluation. Full article

Background: Cytokine release syndrome (CRS) is a life-threatening systemic inflammatory condition marked by excessive cytokine production, leading to multi-organ dysfunction. It is commonly associated with T-cell-engaging therapies such as chimeric antigen receptor (CAR) T cells, T-cell receptor bispecific molecules, and monoclonal antibodies. Carfilzomib, a proteasome inhibitor, is known to cause a range of adverse effects, primarily hematologic and cardiovascular. However, multiorgan failure grade 5 (fatal), resembling CRS has not been previously reported in association with Carfilzomib. Case Report: A 74-year-old male with relapsed multiple myeloma developed grade 5 multiorgan failure 60 min after the third dose of Carfilzomib, resulting in death within 24 h of symptom onset. The patient tolerated the first doses of Carfilzomib well with only fever and headache developing post infusion. Before the second dose, the patient developed worsening pancytopenia, prompting the discontinuation of Lenalidomide. After the second Carfilzomib infusion, he experienced fever and transient encephalopathy, which resolved with acetaminophen, corticosteroids, and supportive care. However, following the third dose, he rapidly deteriorated—developing fever, tachycardia, hypotension, hypoxia, and encephalopathy. Despite aggressive management with intravenous fluids, broad-spectrum antibiotics, corticosteroids, and tocilizumab, the patient progressed to refractory shock and multi-organ failure, culminating in death within 24 h. A comprehensive infectious workup was negative, ruling out sepsis and suggesting possible Carfilzomib-induced CRS. Conclusion: Grade 5 multiorgan failure with signs and symptoms similar with CRS following Carfilzomib administration is a rare but potentially fatal adverse drug reaction. Further research is needed to better define the risk factors and optimal management strategies for Carfilzomib-induced multiorgan failure and possible CRS. Full article

Background/Objectives: Idiopathic normal-pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence. Its pathophysiology involves impaired cerebrospinal fluid (CSF) absorption, and recent research has highlighted the role of the glymphatic and meningeal lymphatic systems in this process. However, the factors that trigger the clinical manifestations of iNPH in subclinical cases remain poorly understood. Case Presentation: Herein, we report two rare cases of iNPH in which clinical symptoms only became apparent following systemic infections. An 82-year-old man presented with transient neurological deficits during a course of sepsis caused by Klebsiella pneumoniae. Neuroimaging revealed periventricular changes and mild ventricular enlargement. Shunting and a tap test led to significant improvements to both his gait and cognition. An 80-year-old man with a history of progressive gait disturbance and cognitive decline developed worsening urinary incontinence and acute cerebral infarction caused by Staphylococcus haemolyticus bacteremia. Magnetic resonance imaging revealed a ventriculomegaly with features of disproportionally enlarged subarachnoid space hydrocephalus and a corona radiata infarct. Clinical improvement was achieved after a ventriculoperitoneal shunt was placed. Conclusions: Our two present cases suggest that systemic inflammatory states may act as catalysts for the manifestation of iNPH in patients with predisposing cerebral ischemia or subclinical abnormalities in CSF flow, highlighting the need for higher clinical awareness of iNPH in older patients who present with neurological deterioration during systemic infections. Early diagnosis and timely shunting after appropriate infection control may facilitate significant functional recovery in such patients. Full article

Sepsis is a syndrome of life-threatening acute organ dysfunction caused by a dysregulated host response to infection. Sepsis-associated encephalopathy (SAE) refers to the diffuse brain dysfunction observed in sepsis cases, clinically characterized by a spectrum of neuropsychiatric manifestations ranging from delirium to coma. SAE is independently associated with increased short-term mortality and long-term neurological abnormalities, with currently no effective preventive or treatment strategies. The pathogenesis is intricate, involving disruptions in neurotransmitters, blood–brain barrier (BBB) breakdown, abnormal brain signal transmission, and oxidative stress, among others. These mechanisms interact or act in conjunction, contributing to the complexity of SAE. Scholars worldwide have made significant strides in understanding the pathogenesis of SAE, offering new perspectives for diagnosis and treatment. This review synthesizes recent mechanistic breakthroughs and clinical evidence to guide future research directions, particularly in targeting BBB restoration and oxidative stress. Full article

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery and quality of life. As the aging population grows, the rising number of elderly surgical patients has made PND an urgent clinical challenge. Despite increasing research efforts, the pathophysiological mechanisms underlying PND remain inadequately characterized, underscoring the need for a more integrated framework to guide targeted interventions. To better understand the molecular mechanisms and therapeutic targets of PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, and white matter lesions as central to PND pathophysiology, with particular parallels to encephalocele- and sepsis-associated cognitive impairments. Among these, neuroinflammation, mediated by pathways such as the NLRP3 inflammasome and blood–brain barrier disruption, emerges as a pivotal driver, triggering cascades that exacerbate neuronal injury. Oxidative stress and mitochondrial dysfunction synergistically amplify these effects, while neurotransmitter imbalances and microvascular alterations, including white matter lesions, contribute to synaptic dysfunction and cognitive decline. Anesthetic agents modulate these interconnected pathways, exhibiting both protective and detrimental effects. Propofol and dexmedetomidine demonstrate neuroprotective properties by suppressing neuroinflammation and microglial activation, whereas inhalational anesthetics like sevoflurane intensify oxidative stress and inflammatory responses. Ketamine, with its anti-inflammatory potential, offers promise but requires further evaluation to determine its long-term safety and efficacy. By bridging molecular insights with clinical practice, this review highlights the critical role of personalized anesthetic strategies in mitigating PND and improving cognitive recovery in elderly surgical patients. It aims to inform future research and clinical decision-making to address this multifaceted challenge. Full article

Sepsis-associated encephalopathy (SAE) is linked to high mortality and impaired neurologic outcome. Brain ultrasonography (US) is a non-invasive tool for cerebral monitoring. A scoping review of the literature in three databases was performed to answer if brain perfusion is altered in sepsis, to determine the role of brain US in guiding resuscitation and its ability to predict the outcome. Randomized controlled trials, clinical trials, observational studies, and systematic reviews on adults with sepsis or septic shock in the ICU were included. A total of 625 articles were screened, and 34 included. There were 85% observational studies and 15% systematic reviews with or without meta-analysis. The majority of studies had a small sample size and used different metrics. The studies focused on cerebral blood flow (CBF) alterations reporting variable results (CBF increased, normal, or decreased). The findings showed a variable rate of cerebral autoregulation (CAR) impairment, with higher incidence in the early stages of sepsis and associations with poor neurological outcomes. However, the impact of CAR and CBF alterations on neurological outcomes and mortality was not clear. Very few studies were found on resuscitation. In conclusion, brain US can identify cerebral perfusions alterations and its usage in sepsis is promising. However, the current body of evidence for its usage is poor and lacks standardization. Full article

Neonatal encephalopathy represents a broad neurological syndrome which encompasses newborn foals presenting a variety of non-infectious neurologic signs and/or abnormal behaviors in the immediate postpartum period. It is recognized as the most predominant neurological disorder in neonatal foals. Prognostic factors can guide clinicians in medical decision-making, aiding in the establishment of survival probabilities. The aim of this work was to scrutinize the prognostic value of clinical and laboratorial findings upon admission and posterior comorbidities developed during hospitalization, assessing their influence on the outcome of foals with NE. For this purpose, the medical records of 61 neonatal foals with a primary diagnosis of NE were retrospectively analyzed. The overall survival rate was 57.4%. Most foals presented recumbency at admission, which was associated with higher mortality rates (p = 0.002). Hypothermic foals at admission were 4.85 times more likely to succumb (p = 0.015). The presence of hypoglycemia at admission was associated with higher mortality rates (p = 0.002). Foals with hypercreatinemia at admission had 6.67 times greater odds of dying. The development of seizures contributed to 4.14 greater odds of dying. Foals that developed comorbidities during hospitalization had 40.1 times greater odds of dying, with pneumonia and sepsis being the most relevant comorbidities. In foals with NE, rectal temperature, hematocrit, blood glucose, and creatinine concentrations are simple, quick-to-measure parameters that may have prognostic value during admission. Full article

Lung injury caused by respiratory infection is a major cause of hospitalization and mortality and a leading origin of sepsis. Sepsis-associated encephalopathy and delirium are frequent complications in patients with severe lung injury, yet the pathogenetic mechanisms remain unclear. Here, 70 female C57BL/6 mice were subjected to a single full-body-exposure with nebulized lipopolysaccharide (LPS). Neuromotor impairment was assessed repeatedly and brain, blood, and lung samples were analyzed at survival points of 24 h, 48 h, 72 h, and 96 h after exposure. qRT-PCR revealed increased mRNA-expression of TNFα and IL-1β 24 h and 48 h after LPS-exposure in the lung, concomitantly with increased amounts of proteins in bronchoalveolar lavage and interstitial lung edema. In the cerebral cortex, at 72 h and/or 96 h after LPS exposure, the inflammation- and activity-associated markers TLR4, GFAP, Gadd45b, c-Fos, and Arc were increased. Therefore, single exposure to nebulized LPS not only triggers an early inflammatory reaction in the lung but also induces a delayed neuroinflammatory response. The identified mechanisms provide new insights into the pathogenesis of sepsis-associated encephalopathy and might serve as targets for future therapeutic approaches. Full article

Introduction: Vitamin B1 deficiency poses a significant risk of impaired consciousness, with manifestations ranging from anorexia and fatigue to severe neurological and cardiovascular disturbances. Wernicke’s encephalopathy, a neurological disorder stemming from vitamin B1 deficiency, presents as the triad of ophthalmoplegia, altered mental state, and cerebellar ataxia. However, these symptoms are not consistently present, complicating the diagnosis. In addition, subclinical vitamin B1 deficiency can progress unnoticed until severe complications arise. Studies indicate a high rate of undiagnosed cases, emphasizing the need for early detection and intervention. Case presentation: We present the case of a 65-year-old man in whom hyperlactatemia was incidentally detected, leading to the diagnosis of vitamin B1 deficiency. The patient, presenting with vertigo and vomiting, had been eating boxed lunches bought from convenience stores following the death of his wife 3 years earlier. Vertigo gradually improved with rest, but the persistence of hyperlactatemia prompted further investigation, revealing low vitamin B1 levels and high pyruvate levels. Treatment with dietary adjustments and supplements significantly improved his symptoms. Discussion: In this case, hyperlactatemia was found in a vertigo patient, revealing asymptomatic vitamin B1 deficiency. Elevated lactate is often linked with conditions like sepsis but can also stem from overlooked factors such as low vitamin B1 levels due to poor diet habits like consuming fried foods. Conclusion: This case highlights the importance of considering vitamin B1 deficiency in patients with unexplained hyperlactatemia, even in high-income countries. Early detection can prevent progression to the severe complications associated with Wernicke’s encephalopathy. Proactive measurement of lactate levels in at-risk populations may facilitate early diagnosis and intervention, ultimately improving patient outcomes. Full article

Hemophagocytic lymphohistiocytosis (HLH) secondary to tick-borne infections is a rare but potentially life-threatening syndrome. We performed a scoping review according to PRISMA guidelines to systematically analyze the existing literature on the topic. A total of 98 patients were included, with a mean age of 43.7 years, of which 64% were men. Most cases, 31%, were reported from the USA. Immunosuppression was present in 21.4%, with the most common cause being previous solid organ transplantation. Constitutional symptoms were the most common, observed in 83.7% of the patients, while fever was reported in 70.4% of cases. Sepsis was present in 27.6%. The most common laboratory abnormalities in this cohort were thrombocytopenia in 81.6% of patients, while anemia, leukopenia, and leukocytosis were observed in 75.5%, 55.1%, and 10.2%, respectively. Liver enzyme elevation was noted in 63.3% of cases. The H-score was analyzed in 64 patients, with the mean value being 209, and bone marrow analysis was performed in 61.2% of patients. Ehrlichia spp. was the main isolated agent associated with HLH in 45.9%, followed by Rickettsia spp. in 14.3% and Anaplasma phagocytophilum in 12.2%. Notably, no patient with Powassan virus infection or Lyme borreliosis developed HLH. The most common complications were acute kidney injury (AKI) in 35.7% of patients, shock with multiple organ dysfunction in 22.5%, encephalopathy/seizure in 20.4%, respiratory failure in 16.3%, and cardiac complications in 7.1% of patients. Treatment included antibiotic therapy alone in 43.9%, while 5.1% of patients were treated with immunosuppressants alone. Treatment with both antibiotics and immunosuppressants was used in 51% of patients. Appropriate empiric antibiotics were used in 62.2%. In 43.9% of cases of HLH due to tick-borne disease, patients received only antimicrobial therapy, and 88.4% of those recovered completely without the need for immunosuppressive therapy. The mortality rate in our review was 16.3%, and patients who received inappropriate or delayed empiric therapy had a worse outcome. Hence, we suggest empiric antibiotic treatment in patients who are suspected of having HLH due to tick-borne disease or in whom diagnostic uncertainty persists due to diagnostic delay in order to minimize mortality. Full article

Hypoxic–ischemic encephalopathy (HIE) is one of the most common causes of childhood disability. Hypothermic therapy is currently the only approved neuroprotective approach. However, early diagnosis of HIE can be challenging, especially in the first hours after birth when the decision to use hypothermic therapy is critical. Distinguishing HIE from other neonatal conditions, such as sepsis, becomes a significant problem in diagnosis. This study explored the utility of a metabolomic-based approach employing the NeoBase 2 MSMS kit to diagnose HIE using dry blood stains in a Rice–Vannucci model of HIE in rats. We evaluated the diagnostic fidelity of this approach in a range between 3 and 6 h after the onset of HIE, including in the context of systemic inflammation and concomitant hypothermic therapy. Discriminant analysis revealed several metabolite patterns associated with HIE. A logistic regression model using glycine levels achieved high diagnostic fidelity with areas under the receiver operating characteristic curve of 0.94 at 3 h and 0.96 at 6 h after the onset of HIE. In addition, orthogonal partial least squares discriminant analysis, which included five metabolites, achieved 100% sensitivity and 80% specificity within 3 h of HIE. These results highlight the significant potential of the NeoBase 2 MSMS kit for the early diagnosis of HIE and could improve patient management and outcomes in this serious illness. Full article

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The 5-year survival rate for liver cancer in the US has improved from 3% four decades ago to 20% now. Transarterial chemoembolization (TACE) is the treatment of choice for stage B/intermediate-stage HCC. Complications of TACE include hepatic encephalopathy, liver failure, post-embolization syndrome, duodenal ulcers, liver abscesses, acute cholecystitis, and injury to the biliary tract. This study evaluates the 30-day readmission rate and predictors of readmission among patients with HCC undergoing TACE. Methods: The 2016–2018 Healthcare Cost and Utilization Project (HCUP) database, which includes the National Readmission Database (NRD), was used. All adult patients with HCC who underwent TACE were identified using the International Classification of Diseases (ICD-10). The rate of 30-day readmissions after TACE and the associated diagnoses were identified. Logistic regression was used to obtain adjusted odds ratios for variables associated with 30-day readmission. Results: A total of 566 patients underwent TACE between 2016–2018. Sixty-five patients were excluded due to death and unavailability of 30-day readmission data. The procedure was performed in large (80.4%), metro-teaching hospitals (94.5%). Mean patient age was 65.1 ± 9.9 years, and 74% of patients were male. Among the 501 patients, 81 (16.2%) were readmitted within 30 days. The mean age for readmitted patients was 63.2 ± 11.0 and 69.1% were male. The mean length of stay at readmission was 5.5 ± 7.3 days. A total of 7.4% of patients had neurological disorders, 17.3% had weight loss, 30.9% had fluid and electrolyte imbalance, and 21.0% had hepatic encephalopathy. The most common primary diagnoses at 30-day readmission were liver cell carcinoma, sepsis, and liver failure. Univariate analysis for variables associated with 30-day readmission included hepatic encephalopathy (OR 3.45; 95% CI 1.8–6.62; p = 0.0002), underlying neurological disorders (OR 3.28; 95% CI 1.16–9.3; p = 0.03), weight loss (OR 2.82; 95% CI 1.42–5.61; p = 0.003), and Medicaid status (OR 1.74; 95% CI 1.05–2.88; p = 0.03). Multivariable analysis showed hepatic encephalopathy (OR 2.91; 95% CI 1.4, 6.04; p = 0.04) and weight loss (OR 2.37; 95% CI 1.13–4.96; p = 0.02) were associated with hospital readmission. Conclusions: Weight loss and hepatic encephalopathy were predictors for 30-day readmission after a TACE procedure for HCC. Full article

Sepsis-associated encephalopathy (SAE) is a common brain dysfunction, which results in severe cognitive and neurological sequelae and an increased mortality rate in patients with sepsis. Depending on the stimulus, microglia (resident macrophages in the brain that are involved in SAE pathology and physiology) can adopt two polarization states (M1/M2), corresponding to altered microglial morphology, gene expression, and function. We systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE and demonstrated that microglia are closely related to SAE occurrence and development, and concomitant cognitive impairment. Finally, some potential therapeutic approaches that can prime microglia and neuroinflammation toward the beneficial restorative microglial phenotype in SAE were outlined. Full article

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The brain is one of the organs involved in sepsis, and sepsis-induced brain injury manifests as sepsis-associated encephalopathy (SAE). SAE may be present in up to 70% of septic patients. SAE has a very wide spectrum of clinical symptoms, ranging from mild behavioral changes through cognitive disorders to disorders of consciousness and coma. The presence of SAE increases mortality in the population of septic patients and may lead to chronic cognitive dysfunction in sepsis survivors. Therefore, therapeutic interventions with neuroprotective effects in sepsis are needed. Melatonin, a neurohormone responsible for the control of circadian rhythms, exerts many beneficial physiological effects. Its anti-inflammatory and antioxidant properties are well described. It is considered a potential therapeutic factor in sepsis, with positive results from studies on animal models and with encouraging results from the first human clinical trials. With its antioxidant and anti-inflammatory potential, it may also exert a neuroprotective effect in sepsis-associated encephalopathy. The review presents data on melatonin as a potential drug in SAE in the wider context of the pathophysiology of SAE and the specific actions of the pineal neurohormone. Full article