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This paper explores the unique nature and evolution of Euroscepticism in Iceland, which originates not from contemporary identity politics but from a deeply embedded national ideology prioritising sovereignty and democratic control over natural resources. Historically, Iceland's relationship with Europe has been defined by a dual imperative: seeking economic prosperity through integration mechanisms like the European Economic Area, while fiercely protecting its hard-won political autonomy by resisting full European Union membership. The study examines the multiparty political landscape, demonstrating how mainstream factions have traditionally navigated this ambivalence. Special emphasis is placed on the rise of populist and quasi-populist actors, notably the Centre Party and the People's Party. The Centre Party deploys a hard, historically grounded Euroscepticism framing the EU as a threat to Icelandic self-determination, whereas the People's Party utilizes a more reactive, welfare-centric critique. However, the trajectory of Icelandic Euroscepticism is not static. The paper argues that recent geopolitical shocks - including the complexities of Brexit, the COVID-19 pandemic, the war in Ukraine, and shifts in U.S. foreign policy - have tempered nationalist resistance, prompting a pragmatic re-evaluation of external alignments. Consequently, a 2024 coalition government has committed to holding a referendum on resuming the EU accession process, signalling a potential paradigm shift in Iceland's European orientation. Ultimately, this case study illuminates the complex interplay between nationalism, populism, and strategic pragmatism within a small-state setting. Icelanders have long hesitated to fully join the European Union, preferring to protect their hard-won independence and retain control over natural resources, particularly fisheries. To balance these concerns, Iceland cooperates economically with Europe through the European Economic Area (EEA) agreement but avoids the political oversight of full EU membership. Populist factions, particularly the Centre Party and People’s Party, have capitalised on this national pride. They strongly oppose integration, warning that it would surrender Icelandic sovereignty to foreign elites and bureaucrats. However, recent global shocks - including Brexit, the COVID-19 pandemic, and the war in Ukraine - have shifted this perspective. Recognising the need for collective security in a volatile world, a government coalition formed in late 2024 has pledged to hold a referendum on resuming EU accession talks.
Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome with debated optimal treatment in the setting of cardiogenic shock (CS). We report a case of a middle-aged woman presenting with out-of-hospital cardiac arrest due to extensive multivessel SCAD. Without evidence for transmural ischemia, we chose conservative treatment with single antiplatelet therapy and heparin. Due to deteriorating hemodynamics, a temporary left ventricular assist device (Impella) was implanted, stabilizing the patient. After weaning the device and initiating heart failure therapy, the patient recovered completely. This case highlights several important considerations for the management of SCAD patients with CS.
Cardiogenic shock secondary to acute myocardial infarction (AMI) is often complicated by acute kidney injury (AKI). Although percutaneous ventricular assist devices (pVADs) are used to treat organ failure in cardiogenic shock, it is difficult to predict whether AKI is reversible or not and how long treatment should be continued to improve renal function. A 57-year-old woman with AMI complicated by cardiogenic and anaphylactic shock developed persistent anuria and required dialysis. Despite initial mechanical support, she remained dependent on advanced circulatory assistance. She received prolonged pVADs (Impella CP® and Impella 5.5®) for over 4 months. Remarkably, urine output resumed after 2 months of anuria, allowing discontinuation of dialysis. She underwent successful left ventricular assist device (LVAD) implantation on Day 138 and remained dialysis-free thereafter. Cardiogenic shock complicated with AKI limits options for durable mechanical circulatory support. While dialysis-dependent renal dysfunction is considered a contraindication for LVAD implantation in our country, our case illustrates that recovery of renal function may still be achievable even after prolonged anuria. By maintaining renal perfusion with extended pVAD support, dialysis withdrawal was ultimately successful, enabling LVAD implantation. This case highlights that prolonged circulatory support may be a feasible bridge to durable LVAD or heart transplantation.
A solid pseudopapillary tumor (SPT) of the pancreas is a rare, low-grade epithelial-lined tumor that typically follows a benign course and is potentially curable with surgical excision. We describe a patient presenting to the emergency department with vague abdominal symptoms and moderate tenderness on deep palpation of the right hemiabdomen on exam ination. Computed tomography (CT) imaging showed evidence of an SPT in the tail of the pancreas. An SPT is a rare, low-grade tumor that typically has a benign prognosis and is potentially curable with surgical excision. SPT tumors can be found on CT imaging in the setting of trauma, and it should be in the differential in the setting of vague abdominal symptoms after abdominal trauma. We discuss the presentation, pathophysiology, prognosis, and management of SPTs based on a literature review.
Axial gout is an underrecognized manifestation of monosodium urate (MSU) crystal deposition and frequently mimics inflammatory, infectious, or mechanical spinal disorders, particularly without overt hyperuricaemia. We report a 29-year-old man with recurrent low back pain for over two years and recurrent nephrolithiasis who had undergone three extracorporeal shock wave lithotripsy sessions with only transient relief. Admission laboratory investigations showed normal serum urate (262 µmol/L, ~ 4.4 mg/dL) but markedly elevated C‑reactive protein (119 mg/L) and erythrocyte sedimentation rate (53 mm/h). Retrospective review of prior hospitalizations for ureteral stones revealed that routine serum urate measurements had never been elevated. Conventional imaging, including plain radiography and non‑contrast computed tomography, was inconclusive. Dual‑energy computed tomography (DECT) revealed MSU deposition in the L4/L5 and L5/S1 facet joints and sacral foramina, supporting the diagnosis of axial gout. The patient was treated with etoricoxib (60 mg daily) and febuxostat (20 mg daily). On telephone follow‑up on 27 May 2026 (the only follow‑up to date), he reported that the J stent had been removed and low back pain had completely resolved without recurrence. A single repeat laboratory test performed locally was reported as normal, though specific values were unavailable. A systematic literature review of 58 eligible articles revealed that the lumbar spine was most frequently involved (≈ 60%), DECT sensitivity ranged from 78% to 100%, and 77.5% of historically reported cases required surgical diagnosis, underscoring the underrecognition of axial gout in non-surgical settings. This case‑based review highlights that axial gout should be considered in young non‑hyperuricaemic patients with persistent axial pain, and that DECT is a valuable non‑invasive diagnostic tool when interpreted alongside clinical and laboratory features.
Children with cancers remain at a high risk of mortality due to infection, compounded by rising rates of multidrug-resistant Gram-negative bacteria (MDR-GNB), particularly in developing countries. This study aimed to determine the occurrence of bacteremia caused by MDR-GNB and identify the associated risk factors and the clinical outcomes. A retrospective cohort study was conducted using medical records from children with cancers aged 0-18 years at Dr. Sardjito Hospital, a tertiary care center in Indonesia, between 2020 and 2024. Patients with neutropenic fever and bacteremia were enrolled in the analysis. Multivariate logistic regression was used to analyze the associated factors of bacteremia caused by MDR-GNB, while Cox regression analysis was utilized to assess the outcomes of 30-days mortality rate. A total of 63 cases were included. MDR-GNB was identified in 28.6% (18/63) of patients, representing 52.9% (18/34) of all Gram-negative bacteremia. Most patients had hematologic malignancies (87.2%), with a median absolute neutrophil count (ANC) of 60 cells/mm³ (interquartile range: 0-320). The predominant pathogens were Escherichia coli (66.7%) and Klebsiella pneumoniae (16.7%). Multivariate analysis revealed that ANC <100 cells/mm³ (adjusted odds ratio [aOR], 5.8; 95% confidence interval [CI], 1.1-30.1; P=0.038) and cytostatic administration within the preceding week (aOR, 6.0; 95% CI, 1.04-35.1; P=0.045) were significant risk factors for MDR-GNB bacteremia. Furthermore, MDR-GNB infection was associated with a significantly increased risk of septic shock (hazard ratio [HR], 4.4; 95% CI, 1.2-15.4; P=0.021) and 30-day mortality (HR, 9.5; 95% CI, 2.4-37.6; P=0.001). Children with cancers and neutropenic fever should be carefully evaluated for MDR-GNB infection, particularly if the ANC was low and cytostatics were administered within the past week. Comprehensive strategies are essential to mitigate the risks of mortality among pediatric patients with MDR-GNB.
Imaging-based single-cell physiological profiling holds great potential for uncovering fundamental bacterial cold shock response (CSR) mechanisms, but its application is impeded by severe focus drift during rapid temperature downshifts required for CSR induction. Here, we introduce LUNA (Locking Under Nanoscale Accuracy), an innovative autofocusing method that leverages the coma pattern of detection light to characterize focus drift. LUNA improves the focusing precision down to 3 nm and extends the focusing range to at least 40 times the objective depth of focus. These advancements enable us to investigate the complete dynamics of bacterial single-cell CSR, revealing continuous cellular growth and division. We resolve a three-phase adaptation process characterized by distinct growth deceleration dynamics, and show that bacterial cells maintain robust size regulation and coordinate uniform adaptation to cold shock through synchronized growth and elapsed cycles. Notably, a model based on scattering theory reconciles the paradox between the growth lag of batch culture and continuous single-cell growth. These findings fundamentally transform our understanding of bacterial CSR and highlight LUNA's excellent potential for expanding state-of-the-art research in biology.
We present a multiscale, non-destructive analysis of non-poikilitic olivine in the shergottite NWA 7721 using dark-field X-ray microscopy, electron backscatter diffraction, and 2D micro-X-ray diffraction. We report striking bimodal microstructures within a single olivine crystal: fine Type 1 subgrains (around 5 μm), weakly oriented, and nearly strain-free; coarser Type 2 subgrains (>15 μm), aligned, and strongly strained. Layered DFXM data reveal slip-band features in Type 2 that are absent in Type 1. This bimodal microstructure, not observed in other Martian meteorites, including the paired NWA 1950 and ALH A77005, points to a heterogeneous response to impact at the crystallographic scale. We interpret Type 1 as shock-assisted recrystallites and Type 2 as relic partitioned from a highly deformed parental grain with a pre-existing fabric. The subsequent shock wave imposed a rapid load-release cycle that generated heterogeneous deformation within the crystal. Highly strained regions underwent recrystallization to form Type 1 subgrains, whereas less-strained domains retained deformation structures as Type 2. Grain-growth constraints limit the post-shock heating to ≈2.3 s, consistent with rapid quenching. Together, these observations illustrate a dynamic Martian crustal activity in the Late Amazonian and demonstrate DFXM, combined with EBSD and micro-XRD, as a promising tool for resolving complex fabrics in 3D.
We report a case demonstrating the evolution of diffusion lacunae (DL) into thrombus, supported by serial MRI and MR-pathologic correlation. A 36-year-old woman with a pregnancy achieved via frozen-thawed embryo transfer presented with complete placenta previa and vaginal bleeding. MRI at 27 weeks of gestation revealed an irregular intraplacental hypointense area on diffusion-weighted imaging corresponding to DL. Follow-up MRI at 32 weeks showed that the DL had become less discernible and appeared hyperintense, similar to the surrounding placenta. On the following day, the patient developed hemorrhagic shock and underwent emergency cesarean delivery, without evidence of placental adherence and decidual deficiency, indicating that the DL represented a placental lake rather than placental lacunae. Histopathologic examination demonstrated a paucity of chorionic villi and thrombus formation with lines of Zahn in the DL area. These findings provide direct evidence that DL may undergo thrombus formation over time, reflecting dynamic changes related to blood flow stasis within the placenta.
In the recent years, multiple myeloma (MM) has been associated with long-term survival. Life-threatening complications may occur in those patients leading to high risk of ICU admission. Within the same period, survival of critically ill patients with malignancy improved. The aim of this study was to evaluate severity and outcome in patients with MM admitted to ICU within the last 16 years. In this monocentric retrospective study, patients with MM admitted to ICU within two periods (2007-2015) and (2016-2023) around major therapeutic changes, were included. Patients from two periods were compared in terms of short and long terms outcomes. In the recent period, factors associated with mortality were assessed by multivariate analysis. During the first period (2007-2015), 199 patients were included and compared to 229 patients admitted within the second period (2016-2023). Median delay from MM diagnosis to ICU was 25.9 (2.2-70.6) months and 82 (19.2%) patients were newly diagnosed patients. MM classified as high risk concerned 119 (52%) or Stade III Salmon-Durie for 142 (71.4 %) patients. SOFA score on Day 1 was 5 (2-7). During ICU stay, 115 (26.9%) patients needed invasive mechanical ventilation, 105 (24.5%) patients received vasopressors and 97 (22.7%) had renal replacement therapy. Median length of ICU stay was 3 (2-6) days. Reason for ICU admission was different between the two periods: Shock was more frequent in the second period (29.7% vs 13.7%) whereas acute respiratory failure was more frequent in the first period (35.2% vs 46.7%) (p < 0.001). ICU and one-year mortality rates were respectively 12.1% (n = 50) and 40.6% (n = 170). Mortality rates, adjusted on age, comorbidities, more than 2 lines treatment, time between hospital and ICU admission >1 day, kidney amyloidosis, SOFA score at ICU admission and reason for ICU admission, were lower in the recent period compared to the first period (0.68 (0.49-0.95), p = 0.02). Survival in MM patients admitted to ICU improved in the recent years. Particularly, patients who were not previously heavily treated had better outcome and should be admitted to ICU.
Subclinical mastitis (SCM) is characterized as inflammation of mammary gland with absence of clinical signs. S. aureus, one of the principal causes of disease is known for production of various virulence factors, including enterotoxins, biofilm production and antibiotic resistant genes. Therefore, the present study was carried out with the objective of molecular characterization for various virulence associated genes, antibiogram profile, and MLST typing of S. aureus from milk samples from various districts of Haryana state of India. In our study, milk samples from 1154 quarters affected with subclinical mastitis (by CMT) subjected to isolation of Staphylococcus spp. yielded 519 isolates. Of them, 352 isolates were identified as S. aureus by targeting 23 S rRNA gene by PCR. Various genes possessed by these isolates were: (13.35%) mecA (methicillin resistant gene), (11.64%) biofilm formation gene icaD, (11.36%) biofilm formation gene icaA, and (9.37%) toxic shocks syndrome gene (tsst). Enterotoxin genes detected were: sec in (8.52%), sea in (8.23%), sed in (4.54%), seb in (2.84%) and see in (1.7%). Exfoliative genes etb and eta were detected in (3.97%) and (3.12%) isolates, respectively. Antimicrobial sensitivity assay revealed sensitivity in descending order to gentamicin, doxycycline, sulfisoxazole, neomycin, ceftriaxone, cefoperazone, chloramphenicol, ciprofloxacin, enrofloxacin, vancomycin, clindamycin, linezolid, cefoxitin and least susceptible to oxytetracycline. The finding of 'Multilocus Sequence Typing' (MLST) showed high diversity of sequence types and clonal complex of S. aureus isolates.
Hemostatic agents (bleeding-stopping agents) are pharmacological or biological substances used to induce hemostasis in cases of trauma, surgical interventions, or spontaneous bleeding. These agents act at various steps of primary and secondary hemostasis, promoting clot formation, reducing blood loss, and improving patient outcomes. This narrative review examines the current status of hemostatic agents and highlights major developments and gaps in the field. A systematic literature search was used to identify relevant articles. Consecutive trials in English between 2005 and 2025 investigating the indications and use of hemostatic agents were abstracted with a search in Google Scholar, PubMed, Scopus, Web of Science, and MEDLINE registries. Case reports, editorials, and expert opinions were excluded from the analysis. The use of tranexamic acid has recently been reintroduced, especially in trauma patients. It should be used in exsanguinating victims of trauma and resultant hemorrhagic shock. Prothrombin Complex Concentrates (PCC) have emerged as a favorable choice over Fresh Frozen Plasma (FFP) in bleeding due to vitamin K antagonists and other anticoagulants, and their use is increasing with studies. On the other hand, FFP is recommended when alternative treatment options are unavailable or in conjunction with first-choice agents, in narrowed indications due to possible complications. The evidence underscores that no single hemostatic agent is universally superior; optimal management requires individualized selection based on the mechanism of bleeding, underlying coagulopathy, and patient-specific factors. TXA has demonstrated consistent survival benefits in traumatic hemorrhage when administered early, yet its efficacy diminishes beyond the 3-hour window, emphasizing time-sensitivity in clinical decision-making. PCC offers practical advantages over FFP in anticoagulant reversal, including faster INR normalization, lower volume load, and no compatibility requirements, but its role in massive transfusion remains limited by the absence of factor V. FFP retains utility as an adjunct in complex coagulopathies and resource-limited settings. The integration of point-of-care viscoelastic testing (TEG/ROTEM) represents a significant advancement in guiding goal-directed hemostatic therapy and reducing unnecessary transfusions. Emerging agents and antidotes for DOAC reversal further expand the therapeutic landscape, though cost and availability remain barriers. Treatment with hemostatic agents can be lifesaving, especially after being adjusted for individual risks and benefits. Therefore, the selection of agents should be tailored on a case-by-case basis.
Severe dengue is a vascular immunopathology characterized by plasma leakage, thrombocytopenia, hemorrhage, and, in its most critical form, dengue shock syndrome. Although NS1-mediated endothelial injury, glycocalyx disruption, inflammatory myeloid activation, and coagulation/platelet abnormalities have all been implicated, it remains unclear which mechanisms are most consistently supported and whether they form a coherent functional architecture capable of explaining vascular decompensation. This review asks two linked questions: which dengue mechanisms are supported by the contemporary evidence base, and whether the strongest supported components are logically sufficient, when coupled, to generate a synthetic analog of connected endothelial-barrier failure. We conducted a PubMed-indexed systematic review of dengue mechanistic studies published from 2020 to 2025 under a dengue-only eligibility policy. Full texts were assigned to six mechanism families, graded on a five-tier evidence scale, and classified using predefined claim ceilings: C0 empirical restriction, C1_conditional regularity, or C2 exploratory evidence. Meta-analysis readiness was assessed using PICOS criteria. A constraint-first agent-based model (ABM) was then used as a permanent C2 logical sufficiency evaluator to test whether the three strongest evidence families could jointly generate a synthetic analogue of connected endothelial-barrier failure under explicit assumptions. Of 200 retrieved records, 59 were included after full-text adjudication. Three mechanism families reached C1_conditional evidence: NS1-linked vascular permeability (DENV-M01, n=23), endothelial glycocalyx/barrier disruption (DENV-M02, n=17), and myeloid effector activation (DENV-M03, n=12). Receptor gating, coagulopathy/platelet dysregulation, and therapeutic mechanistic targets remained C2 evidence-gap families. Two null randomized trials imposed C0 restrictions: rupatadine did not significantly reduce plasma leakage (RR = 0.68, 95% CI 0.41-1.12), and oseltamivir did not improve time to defervescence (MD =+ 0.1 days, p=0.055). No mechanism family was eligible for quantitative pooling because CI-bearing estimates were sparse and outcome definitions were insufficiently harmonized. In the ABM, the review-supported NS1-barrier-myeloid set generated a spatially connected endothelial-barrier failure analog. This analog emerged when upstream viral/NS1 pressure and myeloid collateral cost exceeded barrier reserve and repair capacity. The regime remained stable under changes in update rule, rule form, and spatial patch scale, indicating that it was not a single implementation artefact. Boundary location was more stable than local execution timing, whereas high heterogeneity intensity produced only bounded boundary displacement. Minimality ablation showed partial, not complete, minimality: upstream pressure and barrier fragility were load-bearing, whereas the myeloid arm was phase-dependent and counter-directional, consistent with a dual role in early containment and late collateral damage within the model. The current evidence supports a minimum-range organizational account of severe dengue vascular decompensation centered on the NS1-barrier-myeloid unit. This account is best interpreted as a competing-constraint model: viral/NS1 pressure, endothelial/glycocalyx barrier preservation, repair capacity, and myeloid effector control can become difficult to maintain within the same physiological window during progression toward vascular leakage. The ABM provides C2-level in silico support for logical sufficiency by showing that these review-supported components can generate a connected endothelial-barrier failure analog under explicit assumptions. It does not establish causal mechanistic validation, molecular equivalence, or patient-level prediction. Claim escalation now requires longitudinal cohorts measuring NS1/viraemia, endothelial barrier injury markers such as SDC1 or Ang-2, and myeloid effector proxies such as sTREM-1 or CXCL10, together with orthogonal functional perturbation assays reporting CI-bearing outcomes.
Candidemia is a major cause of hospital-acquired bloodstream infections and is associated with high mortality. This study evaluated clinical characteristics, pathogen distribution, antifungal susceptibility, and factors associated with 28-day outcome in patients with candidemia. We retrospectively analyzed 169 patients with confirmed candidemia at Guangdong Provincial People's Hospital from January 2021 to December 2023. Patients were classified as survivors (n = 81) or non-survivors (n = 88) according to 28-day outcome. Species distribution, time to positivity (TTP), antifungal susceptibility, clinical features, and prognostic factors were compared. Variables significant in univariate analysis were entered into a multivariable logistic regression model. Most patients were admitted to the intensive care unit (70.41%), and the 28-day mortality rate was 52.07%. The main causative species were Candida albicans (38.46%), Candida parapsilosis (27.22%), Candida glabrata (15.98%), and Candida tropicalis (15.98%). TTP differed significantly among species; C. tropicalis showed the shortest median TTP (18.73 h), whereas C. parapsilosis and C. glabrata showed longer TTPs (38.34 h and 37.15 h, respectively; P < 0.0001). C. tropicalis showed high resistance rates to fluconazole and voriconazole, at 33.33% and 37.04%, respectively. Univariate analysis showed that age, coronary heart disease, respiratory disease, concomitant bacterial bloodstream infections, septic shock, APACHE II score, catheter insertion, mechanical ventilation, glucocorticoid use, antifungal treatment within 48 h, and antifungal therapy duration ≥14 days were associated with 28-day mortality. Multivariate logistic regression further demonstrated that only antifungal therapy lasting ≥14 days emerged as an independent risk factor for 28-day mortality. Candidemia entails severe infection and poor prognosis, with C. albicans predominating. Clinicians should maintain vigilant monitoring and interventions targeting identified risks while tracking evolving resistance patterns.
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Emergency medical services (EMS) personnel are frequently exposed to challenging working conditions that may contribute to psychosocial risks. Understanding these risks is critical for improving occupational health and developing preventive strategies. This study aimed to identify psychosocial risk factors among EMS personnel in Artvin, Turkey. A descriptive cross-sectional design was employed. Data were collected from 68 participants using a sociodemographic characteristics form and the Copenhagen Psychosocial Questionnaire. Nonparametric statistical tests, including the Mann-Whitney U- and Kruskal-Wallis H-tests, were used to analyze differences across groups. Among the EMS personnel surveyed, 47.5% were found to be at high risk in at least one psychosocial domain. Statistically significant differences were observed based on gender and professional role. Specifically, female EMS workers reported higher levels of emotional demands (P = 0.013) and work-privacy conflict (P = 0.021) compared to males. Emergency medical technicians showed significantly higher stress scores compared to paramedics (P = 0.031), while personnel working 24-h shifts had elevated levels of exhaustion (P = 0.017). A moderate positive correlation was found between weekly working hours and stress levels (r = 0.284, P < 0.001). These findings highlight the need for tailored interventions based on specific risk factors. This study highlights the importance of addressing psychosocial risks in EMS settings. Factors such as professional role, working hours, and organizational support play a key role in shaping risk perception. Targeted interventions, including workload regulation, professional development, and supportive management strategies, are essential to enhance the well-being and resilience of EMS workers.
Accurate prediction of fluid responsiveness is essential in managing circulatory shock. While passive leg raising (PLR) is recommended in international guidelines, its diagnostic validity depends critically on the monitoring modality used to detect hemodynamic responses. In resource-limited settings, manual blood pressure measurement remains the predominant available technology, yet its adequacy for PLR interpretation has not been rigorously evaluated in an adequately powered study with an independent reference standard. To compare the diagnostic accuracy of manual pulse pressure change (ΔPP%) versus continuous flow monitoring (USCOM-1 A, ΔSV%) for predicting fluid responsiveness during PLR in intensive care unit (ICU) patients with undifferentiated shock, using echocardiographic cardiac output assessment as an independent reference standard. Prospective single-center diagnostic accuracy study enrolling consecutive ICU patients with undifferentiated shock at Sina Educational and Medical Center, Tehran, Iran (2020-2021). A standardized PLR protocol was performed with simultaneous blinded measurements by three independent operators: manual blood pressure via calibrated sphygmomanometer, continuous flow monitoring via USCOM-1 A, and echocardiographic velocity-time integral (VTI) measurement as the reference standard. Fluid responsiveness was defined as ≥ 15% cardiac output increase following 500 mL crystalloid challenge. Primary outcome was area under the receiver operating characteristic curve (AUC). The study followed Standards for Reporting Diagnostic Accuracy Studies (STARD) 2015 guidelines (Ethics approval: IR.SBMU.PHARMACY.REC.1399.316). Of 124 patients analyzed (mean age 58.1 ± 19.8 years, 65.3% female), 58 (46.8%) were fluid responders. Continuous flow monitoring demonstrated acceptable diagnostic accuracy (AUC 0.712, 95% confidence interval [CI] 0.622-0.802; sensitivity 81.0%; specificity 61.8%; negative predictive value [NPV] 79.2%). Manual pulse pressure demonstrated significantly inferior discrimination (AUC 0.601, 95%CI 0.502-0.700; DeLong test P = 0.029) with critically low sensitivity (32.8%) and clinically inadequate NPV (57.8%). Bootstrap-corrected performance estimates confirmed the robustness of findings (USCOM AUC 0.708; Manual pulse pressure [PP] AUC 0.596). Mean pulse pressure remained essentially unchanged during PLR (+ 0.4 ± 4.6 mmHg, P = 0.287) despite significant proportional increases in both systolic (+ 3.7%) and diastolic (+ 5.6%) pressures, and despite echocardiographically confirmed stroke volume augmentation (left ventricular outflow tract [LVOT] VTI + 15.9%). The correlation between ΔPP% and ΔSV% was weak (r = 0.39, R²=0.15). Baseline method comparison between USCOM-derived and echocardiography-derived cardiac output showed low paired bias, although the percentage error exceeded the conventional interchangeability threshold, supporting interpretation of USCOM as a directional flow-monitoring index rather than a fully interchangeable substitute for echocardiography. In this single-center study, manual pulse pressure demonstrated insufficient sensitivity (32.8%) and inadequate NPV (57.8%) for reliable fluid responsiveness prediction during PLR. Our findings suggest it should be interpreted with considerable caution, particularly when the test result is negative. Continuous flow monitoring provides superior and clinically acceptable diagnostic accuracy when available, although USCOM should be interpreted as a directional flow-monitoring index rather than a fully interchangeable substitute for echocardiographic cardiac output measurement. The proportional pressure increase phenomenon provides a mechanistic explanation for this diagnostic limitation. These findings require multicenter validation before definitive practice recommendations can be issued.
BRASH (Bradycardia, Renal failure, Atrioventricular nodal blockade, Shock, and Hyperkalemia) syndrome is a life-threatening clinical syndrome characterized by a vicious cycle in which hyperkalemia and AV nodal blocking medications synergistically produce profound bradycardia and hemodynamic instability. A 71-year-old male with stage IIIB chronic kidney disease (CKD), heart failure with improved ejection fraction, and coronary artery disease status post coronary artery bypass grafting, on carvedilol, losartan, and torsemide, was brought to the emergency room from a rehabilitation facility for a syncopal event and unresponsiveness. He had been recently hospitalized for multifocal pneumonia and respiratory syncytial virus infection, with suspected volume depletion and ongoing AV nodal blockade contributing to the development of BRASH syndrome. He was in respiratory distress, profound shock, and bradycardia with a heart rate of 30 BPM. Labs revealed severe acute kidney injury (creatinine 6.2 mg/dL), hyperkalemia (6.9 mmol/L), and metabolic acidosis (pH 7.19). Chest radiograph demonstrated pulmonary edema. His condition rapidly progressed to airway compromise requiring intubation, cardiogenic shock requiring vasopressors, and refractory bradycardia necessitating transvenous pacing after failure of atropine, dopamine, and transcutaneous pacing. He was admitted to the intensive care unit and promptly initiated on continuous renal replacement therapy (CRRT), resulting in correction of electrolyte and acid-base abnormalities with subsequent resolution of severe bradycardia, allowing discontinuation of transvenous pacing. Infectious workup remained negative, and echocardiography demonstrated preserved left ventricular systolic function. Following stabilization, he was successfully extubated and weaned off CRRT. His subsequent hospital course was complicated by recurrent oliguric renal failure requiring initiation of intermittent hemodialysis. Upon discharge, he remained hemodynamically stable with improved mental status and was planned for long-term hemodialysis and inpatient rehabilitation. The synergistic interaction of hyperkalemia and AV nodal blockade is the central pathophysiologic mechanism underlying BRASH syndrome. Common triggers include hypovolemia and medications that promote AV nodal blockade or hyperkalemia in vulnerable patients with advanced age, CKD, and heart failure. The resulting profound bradycardia further reduces cardiac output, worsening renal perfusion and perpetuating hemodynamic instability. Prognosis depends largely on early recognition and prompt intervention. This case highlights a severe presentation of BRASH syndrome in which timely initiation of CRRT corrected the underlying metabolic derangements, and transvenous pacing provided temporary hemodynamic support, ultimately leading to clinical recovery.