Search Results (1,943)

Background/Objectives: Hypoalbuminaemia is a consistent predictor of mortality in sepsis; however, the temporal dynamics of albumin decline and its relationship with fluid exposure and early norepinephrine therapy remain incompletely characterised. Determining whether early norepinephrine use is associated with attenuation of albumin loss could inform fluid management strategies and identify therapeutic windows for combined vasopressor–albumin interventions. The study aimed to assess whether serum albumin trajectories in sepsis are associated with fluid exposure, modulated by early norepinephrine therapy, and related to 30-day mortality. Methods: We conducted a prospective longitudinal study of patients admitted to an intermediate care unit (IMCU) with community-acquired sepsis. Serum albumin concentrations, cumulative fluid balance (CFB), and vasopressor use were recorded during the first 5 days of hospitalisation. Longitudinal mixed-effects and segmented linear models assessed the association of CFB and vasopressor therapy with albumin trajectories. Lagged mediation modelling explored the potential mediating role of albumin in the association between fluid exposure and 30-day mortality. Results: A total of 389 patients with community-acquired sepsis were included. Thirty-day mortality was 18%. Mean serum albumin at baseline was 2.58 g/dL and declined early to 2.24 g/dL at 72 h. Serum albumin was inversely correlated with cumulative fluid balance over time (r ranging from −0.235 to −0.348; p < 0.001). In longitudinal models, each 1% increase in ΔCFB was associated with a −0.029 g/dL decrease in serum albumin (p < 0.001), supporting an independent effect of fluid exposure. Before norepinephrine initiation, the albumin slope was −0.043 g/dL per interval and was −0.008 g/dL after vasopressor initiation (interaction p = 0.012). Lower albumin concentrations at 72 h predicted 30-day mortality (OR 1.49 per 0.5 g/dL decrease), and serum albumin mediated 18.6% of the association between fluid exposure and mortality. Conclusions: Cumulative fluid exposure was associated with a progressive decline in serum albumin in patients with community-acquired sepsis. Early norepinephrine initiation was associated with attenuation of this trajectory, consistent with the hypothesis that vasopressor-guided haemodynamic stabilisation may limit fluid-associated albumin loss. Full article

Background: Frail patients undergoing hip and knee revision surgery represent a major anesthetic challenge because of advanced age and multiple comorbidities. Continuous spinal anesthesia (CSA) with titrated low-dose levobupivacaine may offer a potentially useful alternative to general anesthesia or single-shot spinal anesthesia in this high-risk population. Methods: A retrospective review was conducted of ASA II-III patients who underwent complex hip and knee revision surgeries between February and October 2024 under CSA. The technique was performed using a 25-gauge spinal catheter with incremental boluses of 0.25% levobupivacaine (2.5 mg). Hemodynamic parameters, including mean arterial pressure (MAP), stroke volume index (SVI), and cardiac index (CI), were continuously monitored using the EV1000 hemodynamic monitoring system. Postoperative complications were recorded. Results: 37 high-risk patients were included in the study. Catheter placement was successful in all patients, with no conversions to general anesthesia. MAP decreased by a mean of 14.6% after boluses (p < 0.05); 9 patients (24.3%) experienced reductions ≥ 20%, but all remained >65 mmHg and responded to fluid therapy. CI and SVI decreased by 10.1% and 10.5%, respectively (p < 0.05), without clinical instability. No major complications (neurological injury, infection, post-dural puncture headache) were observed. Conclusions: In this retrospective single-center experience, CSA with titrated low-dose levobupivacaine was feasible and associated with stable hemodynamic profiles and a low rate of complications in frail patients undergoing complex lower-limb revision surgery. However, given the absence of a control group and the limited sample size, these findings should be interpreted cautiously. Further prospective comparative studies are needed to better define the role of CSA in high-risk orthopedic patients. Full article

Aim: Percutaneous liver ablation is a challenging procedure and operator-dependent. During the time when transarterial liver oncological therapies are favored over percutaneous liver ablation, we discuss the challenges of liver ablation with bowel interposition within the needle tract. Materials and Methods: In this IRB-approved retrospective review, we analyzed 481 cases of percutaneous microwave ablation performed between 2012 and 2025 using the NeuWave microwave ablation system with 15 or 20 mm probes under non-contrast CT guidance, with needle trajectories planned based on ultrasound. Dissection techniques were not performed, as intraprocedural ultrasound and CT assessment suggested that the ablation zone would remain confined to hepatic parenchyma. Cases of bowel transgression or close proximity were identified on post-procedural CT imaging, with a follow-up duration of 3 months performed consistently across all cases. Results: Three cases (0.6%) of bowel transgression or close proximity to bowel loops during needle placement were identified. There was no evidence of transmural bowel perforation or clinically significant bowel injury on clinical or radiologic follow-up. Post-procedural imaging demonstrated no free intraperitoneal air or fluid collections. Conclusions: In cases where the ablation zone is confined to hepatic parenchyma, bowel proximity to or inadvertent traversal by the cooled antenna shaft may not result in clinically significant injury and can be managed conservatively in selected patients. Full article

Transarterial chemoembolization (TACE) is the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC), yet nearly half of treated patients fail to achieve durable benefit, and reliable biomarkers enabling early therapeutic stratification are still lacking. Treatment response is typically assessed by imaging one month after TACE and at three-month intervals, potentially delaying timely access to alternative therapies in non-responding patients. Circulating microRNAs (miRNAs) represent promising biomarkers due to their stability in body fluids and ease of detection. Here, we evaluated circulating miR-22 as an early predictor of TACE non-responder status and as a mechanistically relevant therapeutic target. Circulating miR-22 levels were measured by microarray and quantitative RT–PCR in three independent cohorts of early-to-intermediate-stage HCC patients undergoing TACE. Circulating miR-22 increased significantly in non-responders as early as 48 h after treatment, and fold changes consistently predicted treatment failure across two independent validation cohorts. Mechanistically, we identified the G2/M checkpoint kinase WEE1 as a direct functional target of miR-22. Modulation of the miR-22/WEE1 axis affected cell-cycle progression, proliferation, apoptosis, and DNA damage response in HCC cell lines and xenograft models. Under hypoxia-mimicking conditions combined with doxorubicin exposure, pharmacological inhibition of WEE1 induced mitotic catastrophe in highly proliferative miR-22-silenced cells. Collectively, these findings identify early post-TACE elevation of circulating miR-22 as a biomarker of non-response and highlight the miR-22/WEE1 axis as a potential target for precision treatment strategies in HCC. Full article

Background: Lumboperitoneal (LP) shunt surgery is an established treatment for idiopathic normal pressure hydrocephalus (iNPH). In Japan, patients undergoing LP shunt surgery are often hospitalized for several days to more than one week after surgery, even in uncomplicated cases, reflecting concerns regarding early complications, cerebrospinal fluid overdrainage, and discharge readiness in older adults. This study evaluated the feasibility and short-term safety of a perioperative optimization pathway for planned short-stay hospitalization after LP shunt surgery. Methods: This single-center retrospective before-and-after cohort study included 15 consecutive patients who underwent elective LP shunt surgery. Six patients were managed using a conventional hospitalization pathway, whereas nine patients were treated under a short-stay pathway targeting discharge after one postoperative night. Key perioperative modifications included a uniform higher initial programmable valve pressure (level 7), structured discharge education, scheduled postoperative analgesia, waterproof wound sealing permitting early showering, and early outpatient follow-up with head computed tomography for staged valve pressure adjustment. The primary outcome was 30-day safety, defined as readmission, reoperation, or major postoperative complications. Results: Baseline characteristics were generally comparable between groups, although the short-stay group was slightly older and had more frequent antithrombotic therapy. Mean hospital length of stay was shorter in the short-stay group than in the conventional group (3.7 ± 2.0 vs. 9.7 ± 0.8 days; median, 3 vs. 9.5 days). Orthostatic headache requiring valve adjustment occurred in three conventional cases but in none of the short-stay patients. No patients in the short-stay group required readmission or reoperation within 30 days. Conclusions: In this pilot before-and-after study, a short-stay LP shunt pathway incorporating perioperative optimization and individualized discharge decision-making was feasible and was not associated with an apparent increase in early adverse events. These findings should be interpreted as exploratory and may support further evaluation of short-stay management strategies for selected patients undergoing LP shunt surgery in Japan. Full article

Liver transplantation (LT) is the definitive treatment for patients with end-stage liver disease. Since its inception in the 1960s, transplant medicine has undergone substantial advances in surgical technique, immunosuppression, organ preservation, and organ allocation policies. According to the 2023 WHO census, approximately 47,180 LT procedures occur worldwide each year, with living donors contributing to up to 23% of cases. Additional milestones include the expansion of transplant eligibility to patients with hilar cholangiocarcinoma and advanced colorectal liver metastasis, the incorporation of viscoelastic testing into perioperative blood management algorithms, and the increasing use of mechanical circulatory support for pre-transplant optimization. In parallel, medical training has evolved to meet the complexities associated with these high-risk procedures. Structured fellowship programs now provide focused expertise, and guide investigations to resolve complex clinical dilemmas. Experience accumulated over decades has improved clinicians’ ability to manage the expanding spectrum of comorbidities seen in contemporary transplant candidates. Key perioperative challenges include accurate assessment of fluid status, optimization of intravascular volume, management of vasoplegia, intraoperative renal replacement therapy, treatment of right-ventricular failure, and the mitigation of severe lactic acidosis. As transplant recipients increasingly present at older ages and with multiple comorbidities, perioperative management has become more demanding. One emerging strategy for select high-risk patients involves performing concurrent surgical procedures within a single operative session. This narrative review focuses on the intraoperative management of five variables that proved challenging during the first case of concurrent liver transplantation and off-pump coronary artery bypass surgery in our institution. Full article

Background: Evaporative water loss from burn wounds is a major but often neglected component of early fluid requirements. Despite its physiological importance, no dedicated review has quantified acute post-burn evaporative water loss (TEWL) and its interaction with modern resuscitation strategies in over 40 years. Recent mass-casualty burn events in specialized centers have re-emphasized the clinical importance of accurate early fluid balance, which is particularly challenging. Methods: A scoping review (PRISMA-ScR) of historical quantitative studies and 23 contemporary (2015–2025) adult major-burn resuscitation cohorts was conducted. Expected TEWL was derived from Lamke benchmarks; interstitial edema was estimated from the only available regression of simultaneous fluid input and 24 h weight change. A novel TEWL/edema ratio was tested against resuscitation volume (mL/kg/%TBSA) and the established input/output (I/O) ratio. Results: In the acute phase, the median TEWL normalized to total body surface area was 71 mL/m²/h [52–79 mL/m²/h], allowing for calculation of the TEWL/edema ratio. The TEWL/edema ratio was inversely correlated with the resuscitation fluid dose (R² = 0.811) and the I/O ratio as well (R² = 0.86), crossing unity at 2.85 mL/kg/%TBSA. A ratio > 1 signals high evaporative drive and/or possible under-resuscitation; a ratio < 1 alerts to fluid creep before significant weight gain. Conclusions: The TEWL/edema ratio is the first physiology-grounded, easily calculable resuscitation endpoint that complements urine output by providing insight into whether administered fluid is lost as obligatory evaporation or sequestered as edema. Routine estimation of expected TEWL and early monitoring of the TEWL/edema ratio may help guide goal-directed burn resuscitation, especially when early excision is delayed or impossible. Given the substantial inter-individual variability, the ratio derived from aggregate data should not be interpreted as a patient-specific predictor. Full article

Purpose: No prior clinical studies have quantitatively evaluated the effect of low-dose radiation therapy (LDRT) on Alzheimer’s disease (AD) brain changes using multi-modal MRI. This study examined the feasibility of using conductivity, diffusion, and brain tissue volume measures to detect treatment effects in patients with AD receiving LDRT. Methods: Nine patients with mild AD were enrolled in three groups. Three patients in each group were assigned to the control group (0 cGy) and the treated groups [24 cGy/6 fractions (4 cGy for each fraction) and 300 cGy/6 fractions (50 cGy for each fraction)]. Conductivity, diffusivity, and brain tissue volume were acquired at baseline and 6 months post-treatment and were evaluated to assess within-group MRI changes and evaluate associations between MRI measures and Mini-Mental State Examination (MMSE) scores. Results: Region-of-interest (ROI) analyses identified substantial changes in high-frequency conductivity (HFC) (e.g., left insula), cerebrospinal fluid (CSF) volumes (e.g., anterior cingulate, limbic regions), and diffusion tensor imaging (DTI) metrics, such as axial diffusivity (AxD) and fractional anisotropy (FA), in fusiform, thalamic, hippocampal, and occipital areas. Correlation analysis showed strong associations between MRI measures and cognition, most notably HFC in the left fusiform gyrus (r = 0.843, p = 0.0043) after treatment. Diffusion indices across multiple regions also showed significant positive or negative correlations with MMSE. Conclusions: This exploratory clinical study demonstrates that LDRT induces measurable physiological and microstructural alterations in the brain detectable via conductivity and diffusion MRI. Conductivity emerged as the sensitive biomarker, showing strong cognitive correlations. These exploratory findings suggest that multi-modal quantitative MRI can serve as an effective tool for evaluating treatment response in clinical LDRT for AD. Full article

Hemorrhagic shock remains one of the leading causes of preventable death for both civilian and military trauma. Fluid resuscitation is the primary treatment but requires constant monitoring, particularly for volume non-responsive patients susceptible to fluid overload, pulmonary edema, and other life-threatening conditions. To overcome fluid non-responsiveness, vasoactive drugs or vasopressors can be necessary adjuvants to fluid therapy but require tedious titrations that can be difficult to manage during mass-casualty situations. This study developed and evaluated automated closed-loop vasopressor controllers for hemorrhage scenarios. Ten physiological closed-loop controller (PCLC) configurations with different underlying functionalities were tuned to be either more aggressive or conservative to reach the target mean arterial pressure. A hardware-in-loop test platform with fluid-pressure responsiveness, derived from animal data, tested each controller across three different starting pressure scenarios. The platform successfully differentiated controller designs based on performance metrics. While some configurations overshot the target and others could not reach the target pressure, strong-performing PCLCs consistently reached and maintained the target quickly. Three candidate PCLCs outperformed the rest and will be evaluated across wider scenarios to develop a robust controller design. This work accelerates PCLC-driven vasopressor administration development, providing a necessary fluid resuscitation adjuvant for precise hemodynamic management in hemorrhagic trauma. Full article

Non-coding RNAs (ncRNAs) have emerged as important regulators of gene expression and cellular homeostasis, and their dysregulation is now recognized as a hallmark of cancer. Over the past decades, extensive research has demonstrated that diverse ncRNA classes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other small ncRNA species, participate in complex regulatory networks that influence tumor initiation, progression, metastasis, and therapy response. Through mechanisms such as transcriptional regulation, post-transcriptional gene silencing, epigenetic modulation, and competitive endogenous RNA interactions, ncRNAs shape the molecular circuitry underlying cancer development. In addition to their functional roles in tumor biology, many ncRNAs are released into biological fluids and can be detected as circulating molecules in blood, urine, saliva, and other biofluids. Their remarkable stability in extracellular environments has generated considerable interest in their use as minimally invasive biomarkers in liquid biopsy applications. Emerging evidence has shown that circulating ncRNAs (c-ncRNAs) can support cancer detection, disease stratification, and treatment monitoring. This narrative review provides an integrated view that links ncRNA-mediated regulatory networks with their application as liquid biopsy biomarkers, positioning ncRNAs as comprehensive indicators of tumor conditions. Particular emphasis is placed on c-ncRNA biomarkers, the integration of multiple ncRNA classes, and multi-analyte biomarker strategies that combine ncRNAs with complementary circulating molecules such as cell-free DNA and protein markers. Finally, we discuss the technical and clinical challenges that currently limit the translation of ncRNA-based diagnostics into clinical practice and highlight future directions for advancing ncRNA-guided liquid biopsy approaches in precision oncology. Full article

Candida dubliniensis is an opportunistic yeast closely related to Candida albicans and an uncommon cause of central nervous system (CNS) infection. While isolates are often susceptible to azoles, reduced susceptibility or acquired resistance may occur, making species identification and antifungal susceptibility testing clinically relevant. We report a 3-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (ALL) in hematologic remission who developed chronic meningitis during maintenance chemotherapy. The initial presentation was non-specific (marked somnolence without fever or meningeal signs) and lumbar puncture performed to exclude CNS relapse revealed neutrophil-predominant pleocytosis and elevated protein; the cerebrospinal fluid (CSF) culture grew C. dubliniensis. Treatment with intravenous liposomal amphotericin B followed by prolonged fluconazole led to clinical improvement and sterile CSF. Six months later, progressive gait disturbance, limb pain, and episodic severe headaches recurred; repeat CSF cultures again yielded C. dubliniensis, with a changed susceptibility profile. Spine MRI demonstrated leptomeningeal enhancement involving the cauda equina nerve roots. Intravenous voriconazole with therapeutic drug monitoring was initiated and combined with intrathecal liposomal amphotericin B (seven doses, dose-escalated up to 3 mg), which was well tolerated and associated with rapid neurologic improvement, CSF sterilization, and radiologic resolution. At 12 months of follow-up, the patient remained infection-free and in leukemia remission. This case highlights that C. dubliniensis chronic meningitis may present subtly yet progress, requiring repeated CSF cultures with susceptibility testing; intrathecal liposomal amphotericin B can be a safe and effective adjunct to systemic therapy in refractory or recurrent disease. Full article

Creutzfeldt–Jakob disease (CJD) is a rare and still fatal neurodegenerative disorder caused by prion protein misfolding in the central nervous system. Accumulation of the pathogenic isoform leads to neuronal damage, spongiform degeneration, and rapidly progressive dementia. The disease is divided into sporadic, familial, iatrogenic, and variant forms, with sporadic cases accounting for the majority of cases. Diagnosis remains challenging and relies on a combination of clinical assessment, neuroimaging, and laboratory biomarkers. Key diagnostic methods include electroencephalography, Magnetic Resonance Imaging, and cerebrospinal fluid analysis for proteins as well as advanced amplification tests that improve diagnostic accuracy. Despite these advances, early detection remains challenging and misdiagnosis can occur. Currently, there is no effective disease-modifying therapy, and treatment is primarily supportive, focusing on symptom control and palliative care. Ongoing research aims to better understand the molecular mechanisms underlying prion propagation and develop targeted therapeutic strategies. This review summarizes current diagnostic methods and therapeutic approaches, focusing on molecular applications and their potential clinical implications. Full article

We report the case of a 68-year-old man presenting with rapidly progressive left cervical swelling, sialorrhea, and dysphagia. Imaging revealed a cervical fluid collection extending into the anterior mediastinum, initially suggestive of descending mediastinitis. Broad-spectrum antibiotic therapy was initiated, and surgical drainage was planned. Intraoperative exploration, however, revealed opalescent, milky fluid consistent with chyle, leading to a revised diagnosis of spontaneous chylocervical collection associated with chylothorax. Cultures were negative, and biochemical analysis confirmed markedly elevated triglyceride levels. Conservative management with total parenteral nutrition and a nil per os regimen achieved rapid resolution. Lymphangiography demonstrated normal thoracic duct anatomy without leakage. The patient was discharged in good condition, and follow-up imaging showed complete recovery. This case highlights the diagnostic challenge of differentiating chylous from infectious mediastinal collections, particularly when clinical presentation mimics descending mediastinitis. Accurate intraoperative assessment and multidisciplinary management are essential to avoid unnecessary invasive procedures. Rare etiologies such as idiopathic chylothorax should be considered in atypical presentations of cervical and mediastinal fluid collections. Full article

Background/Objectives: Wolfram syndrome type 1 (WS1) is a rare, progressive, multisystem neurodegenerative disorder characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. As survival has improved, an increasing number of affected women are reaching reproductive age. However, evidence on pregnancy and peripartum management in WS1 remains scarce, and practical guidance is limited. This case report describes the multidisciplinary management of pregnancy and delivery in a woman with genetically confirmed WS1 and highlights key considerations for peripartum care. Case Presentation: A woman with genetically confirmed WS1 and long-standing multisystem involvement, including diabetes mellitus, diabetes insipidus, neurogenic bladder requiring frequent self-catheterization, progressive neurologic manifestations, and severe sensory impairment, achieved pregnancy through assisted reproduction with oocyte donation and was closely monitored by a multidisciplinary team. Due to persistent breech presentation, a planned external cephalic version was performed at 37 + 5 weeks’ gestation with immediate availability for cesarean delivery. After unsuccessful attempts, cesarean delivery was performed under combined spinal–epidural anesthesia. Peripartum management focused on strict glycemic control, careful monitoring of fluid balance and urine output, neuraxial anesthesia with proactive hemodynamic management, precautions related to the cochlear implant, and tailored communication strategies. Postpartum recovery was favorable, although anemia on postoperative day 1 required transfusion of one unit of packed red blood cells and intravenous iron therapy. Discussion and Conclusions: Pregnancy in WS1 represents a high-risk clinical scenario because of the coexistence of endocrine, urologic, and neurologic comorbidities, while published evidence on peripartum management remains limited. This case supports an individualized, multidisciplinary approach to obstetric and anesthetic planning and the use of a practical framework to optimize peripartum management and enhance maternal–fetal safety in this rare condition. Full article

This manuscript shows a clinical case of interest that was brought to the Teaching Veterinary Clinical Complex, College of Veterinary Science and Animal Husbandry, Jabalpur, Madhya Pradesh. Based on the clinical findings, infection with canine parvovirus type 2 (CPV-2) was a first-line diagnosis and later confirmed by a rapid antigen detection kit. Disease prognosis is influenced by viral virulence and host response, with early therapeutic intervention being critical for survival. The dog was given intensive supportive management including fluid therapy, antibiotics, antiemetics, antidiarrheals, antacids, and vitamin supplementation for six days. The dog became progressively better clinically, the gastrointestinal signs resolved completely, and the dog recovered fully. Full article