Search Results (1,270)

Background: Robot-assisted laparoscopic radical prostatectomy (RALP) requires prolonged steep Trendelenburg positioning, which increases intraocular and intracranial pressure. Although transient visual field defects have been documented after RALP using objective perimetric testing, data on patient-reported visual outcomes remain limited. We hypothesized that intraoperative optic nerve sheath diameter (ONSD) measurements and hemodynamic variables would be associated with postoperative patient-reported visual symptoms. Methods: This prospective, single-center observational cohort study enrolled consecutive adult patients undergoing RALP between March and September 2023 at Ospedale Santo Stefano, Prato, Italy. Patients with pre-existing glaucoma, ocular disease, or intracranial hypertension were excluded. Intraoperative ONSD was measured by transorbital ultrasound at three time points: before Trendelenburg (t1), 30 min after Trendelenburg (t2), and at end of Trendelenburg (t3). Postoperative visual symptoms were assessed at ≥1 month follow-up using the validated Catquest-9SF questionnaire. Rasch analysis converted ordinal responses to interval-level measures. Logistic regression explored associations between visual complaints and intraoperative predictors (Rasch scores, lowest mean arterial pressure [MAP], maximum ONSD). Results: Fifty-five patients were enrolled. Six patients (10.9%) reported new subjective visual symptoms at follow-up. Rasch-transformed scores were associated with the presence of these symptoms (coefficient 1.38; p < 0.05). Lowest intraoperative MAP (p = 0.081) and maximum ONSD (p = 0.811) did not reach statistical significance as independent factors. Conclusions: Patient-reported visual symptoms occurred in approximately 11% of patients after RALP. Postoperative Rasch-transformed visual function scores correlated with these complaints. While intraoperative ONSD was not associated with visual outcomes, the potential role of intraoperative hypotension requires further investigation in larger, powered cohorts. Full article

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have emerged as potent modulators of immune responses during sepsis, yet their roles remain complex, alternating between protective and permissive depending on timing, tissue compartment, and inflammatory context. This review presents a historical assessment of VIP and PACAP in sepsis research, highlighting the evolution of conceptual advances across five decades. Starting in the 1980s, early studies revealed that VIP levels rise during endotoxemia and correlated with hypotension and mortality, suggesting a deleterious role. By the 1990s, research pivoted toward understanding gut-derived VIP and its interaction with nitric oxide, culminating in the classification of VIP and PACAP as “macrophage deactivating factors” that downregulate TNFα and IL-6. The 2000s further clarified their cell-specific actions through VPAC1/2 and PAC1 receptors, showing anti-inflammatory effects on both innate and adaptive immune cells, while illuminating delivery challenges overcome by liposomal encapsulation. The 2010s expanded this narrative by dissecting receptor dynamics, gut barrier regulation, and VIP’s role in neuroimmune crosstalk and thrombo-inflammation. Most recently, studies in the 2020s provide a nuanced view of how VIP suppresses inflammatory damage but also enables pathogen persistence during live bacterial infection, implicating VIP signaling in trade-offs between tolerance and clearance. Across this chronological framework, VIP and PACAP have oscillated between friend, foe, and frenemy, underscoring the importance of context in leveraging their therapeutic potential in sepsis. Full article

Background: The optimal method of starting maintenance haemodialysis (HD) in patients with kidney failure is not known. We have compared early treatment characteristics, blood pressure trajectories, and selected dialysis-related safety events in patients who started HD using a stepped and phased approach, with those who received conventional care. Method: A single-centre cohort feasibility study was conducted. Participants with kidney failure, about to start maintenance HD, were enrolled prospectively (intervention arm). They started treatment on a novel regime comprising four pre-specified incremental steps (Phases 1 to 4) over 14 weeks. They were matched using propensity scores with historical controls: patients who had previously started HD on a three-times weekly basis from the outset (control arm). Results: The final cohort comprised 15 and 29 participants in the intervention and control arms respectively (1:2 ratio; one control excluded after matching). Intervention group participants were slightly older with a higher proportion of men. The rate of decline in blood pressure was slower in the intervention group. There were also signals for fewer events of intra-dialytic hypotension (211 vs. 379 per 100 person-year), infections not requiring admission (56 vs. 114 per 100 person-year) and loss of vascular access (56 vs. 79 per 100 person-year) in intervention group. There was a signal for higher incidence of severe hypertension (systolic BP ≥ 180 or diastolic BP ≥ 110 mmHg) in the intervention group. Hospitalisation rates were similar; there were no deaths and one non-fatal major cardiac event (MACE) in the intervention group, and one death and no MACE in the control group. Conclusions: Implementing a short transitional regime of incremental HD may be possible in clinical settings, potentially helping to reduce the gradient of physiological change and burden of early treatment. The findings of this feasibility study are exploratory, and fully powered randomised controlled trials are needed to establish the efficacy and safety of such a programme. Full article

Myocardial infarction remains a leading cause of mortality worldwide as the most severe clinical presentation of coronary artery disease, with an increasing trend in young adults. In the early phase of myocardial infarction, the mean blood pressure regulates the pressure distal to the occluded artery in the presence of well-developed collateral coronary circulation. Hypotensive medication administered after the myocardial infarction could compromise collateral recruitment and exacerbate myocardial ischemia. Collateral coronary circulation develops through angiogenic processes as a network of small blood vessels. After the myocardial infarction, the collateral arteries open and begin a process of arteriogenesis in order to mature into functional arteries. Although there are several well-known biochemical and molecular biomarkers for both myocardial infarction and angiogenesis, we need to associate these with arteriogenesis biomarkers in order to be able to fully determine the level of collateral coronary circulation development after myocardial infarction. In this review, we summarize some of the most important biomarkers that could provide insight into the collateral coronary arteriogenesis process. Our aim is to identify specific biomarkers that can be identified in the early processes of arteriogenesis after the myocardial event in order to quickly determine the best therapeutic strategy. Full article

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with blast TBI (bTBI) particularly affecting military personnel and individuals exposed to explosive environments, yet there are no available curative treatments to date. While adrenergic receptor antagonists have shown promise in reducing neuroinflammation and improving TBI mortality rates, systemic administration of these drugs can have deleterious effects including bradycardia and hypotension. Here, we introduce a polymeric nanoparticle system for the delivery of adrenergic receptor antagonists, which allows for size-based targeting of the injured blood–brain barrier (BBB). These nanoparticles consist of chitosan-coated polylactic co-glycolic acid encapsulating the β-adrenergic receptor antagonist propranolol and/or the α-adrenergic receptor antagonist phenoxybenzamine. Particles designed with a 200 nm hydrodynamic diameter showed a 20–24% increase in permeability on an in vitro contact co-culture BBB model exposed to a 23 or 35 PSI acoustic blast when compared to uninjured controls, whereas 100 nm particles show no difference, suggesting blast injury induces BBB damage that enables the accumulation of larger particles. Treatment of blast-injured human brain microvascular cells with our nanoformulation reduced extracellular inflammatory cytokine levels and reduced the expression of pro-inflammatory markers in microglia. Moreover, these particles mitigated the upregulation of extracellular TNFα induced by free phenoxybenzamine in injured and uninjured microglia, suggesting nanoparticle drug encapsulation can reduce adverse drug reactions in the brain. Together, these findings provide proof-of-concept for size-based targeting and the potential anti-inflammatory effects of CS-PLGA nanoparticles containing adrenergic receptor antagonists for treatment of TBI and bTBI. Full article

Patients with preload-dependent conditions are at high risk of hemodynamic instability from both hypovolemia and hypervolemia. In hypovolemic states, the presence of third spacing may be misleading and obscure true intravascular volume status. Therefore, management of critically ill patients should be guided by a thorough understanding of physiology and pathophysiology to appropriately address hemodynamic derangements. Overreliance on rigid protocols and protocol-driven care without adequate clinical judgment may, in some cases, adversely affect patient outcomes. Herein, we present a case of hypovolemia-induced hypotension in the setting of third spacing and concentric left ventricular hypertrophy. Full article

Background and Objectives: Gastrointestinal (GI) endoscopy requires safe and effective sedation. Remimazolam, an ultra-short-acting benzodiazepine, may offer advantages over traditional sedatives like midazolam and propofol, including rapid onset, short half-life, and a favorable safety profile. This study evaluates the feasibility, safety, and patient satisfaction of continuous remimazolam infusion administered by trained gastroenterologists for GI endoscopy. Materials and Methods: This prospective registry included patients with ASA physical status I and II undergoing standard endoscopic procedures. Continuous remimazolam sedation was administered, with boluses given as needed. Vital signs were monitored, and patient satisfaction was assessed before and after the procedure using standardized questionnaires. Results: A total of 159 procedures were performed in 141 patients. Sedation was successful in all patients, with a mean induction dose of 7.1 mg and total infusion of 15.1 mg. Recovery time averaged 3.3 min. Adverse events, including transient hypotension and hypoxia, occurred in 11.3% of patients but were easily managed. Most patients (97%) reported sufficient comfort, with an average satisfaction score of 8.1/10. Conclusions: Continuous remimazolam infusion administered by trained gastroenterologists is a safe and effective alternative to traditional propofol sedation for GI endoscopy. It offers stable sedation, rapid recovery and high patient satisfaction, potentially reducing anesthesiology workload and improving procedural efficiency. Further studies are needed to confirm these findings in broader patient populations. Full article

Background and Objectives: Systemic mastocytosis (SM) is a clonal mast cell disorder characterized by abnormal mast cell accumulation and activation in multiple organs, leading to mediator-related symptoms, including anaphylaxis. Drug hypersensitivity reactions (DHRs) are a major clinical challenge in SM, but their frequency and characteristics remain undefined. This study aimed to evaluate the frequency of drug allergy, identify high-risk drug groups, investigate reaction characteristics, and examine the relationship between drug reactions, baseline serum tryptase levels, and SM subtypes in patients with SM. Materials and Methods: We retrospectively analyzed 34 patients diagnosed with SM between 2009 and 2024 at Ege University Faculty of Medicine. Clinical features, SM subtypes, baseline serum tryptase levels, and DHR characteristics were recorded. Reactions to antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, anesthetics, radiocontrast media (RCM), and COVID-19 vaccines were graded using the Ring and Messmer anaphylaxis classification. Results: Among 34 patients, the mean age was 48.6 ± 13.3 years, 53% were male, and 10 (29.4%) had DHRs. The most common culprit drugs were NSAIDs (17.6%) and β-lactam antibiotics (14.7%). Anaphylaxis was the predominant reaction, frequently associated with hypotension. In 5 patients (14.7%), drug-induced anaphylaxis was the initial and only manifestation of SM. No hypersensitivity reactions occurred to quinolones, general anesthetics, or COVID-19 vaccines. Median baseline tryptase was 50.25 µg/L (min–max: 8.59–200.00) overall, and 41.85 µg/L (min–max: 19.00–200.00) among those with DHRs. Conclusions: Patients with SM are at increased risk of severe DHRs, particularly to NSAIDs and beta-lactam antibiotics. In some patients, drug allergy may be the first and only manifestation of SM. Measurement of baseline serum tryptase is essential in patients with drug-induced anaphylaxis. A comprehensive allergy assessment, including tolerance testing and individualized counseling, is crucial to ensure safe pharmacological management. Full article

Gamma-aminobutyric acid (GABA), a non-protein amino acid, functions as the chief inhibitory neurotransmitter in mammals and is associated with several health benefits, including hypotensive, diuretic, tranquilizing, and antidiabetic effects. Although cocoa has been identified as a potential source of GABA, information regarding its concentration in cocoa-derived materials remains limited. This study evaluated the GABA content of dried germinated cocoa beans and dried cocoa husks (shells) collected from different geographical regions in Thailand. GABA was extracted using solid–liquid extraction with deionized water, 70% ethanol (v/v), and 90% ethanol (v/v), and quantified by high-performance liquid chromatography coupled with diode array detection (HPLC/DAD). The results revealed that both germinated cocoa beans and cocoa husks contain considerable amounts of GABA. The highest GABA content in cocoa beans was detected in samples from Tak province (242 ± 18 mg/100 g), while cocoa husks from Nan province exhibited the highest GABA content (361 ± 11 mg/100 g), both obtained using 70% ethanol extraction. Among the solvents tested, 70% ethanol demonstrated superior extraction efficiency compared with deionized water and 90% ethanol. In conclusion, germinated cocoa beans and cocoa husks represent promising natural sources of GABA, and extraction with 70% ethanol provides an effective approach for maximizing GABA recovery for potential functional foods and bioactive product development. Full article

Hypersensitivity reactions to iodinated contrast media (ICM) are traditionally categorized as immediate or delayed reactions, involving IgE-mediated pathways, non–IgE-dependent mast cell or complement activation, or T cell–mediated immune mechanisms. However, we observed that some individuals develop systemic inflammatory responses that do not fit these established categories. We describe here a case series of three patients who developed cytokine release syndrome (CRS)-like reactions following iodinated contrast administration, which were initially difficult to distinguish from sepsis and were only recognized after recurrent episodes. Clinical presentation, laboratory findings, cytokine profiles, allergy investigations, and treatment outcomes were reviewed. All patients developed fever, rigors, and hypotension within 5 to 70 h after exposure, accompanied by leukocytosis and markedly elevated inflammatory markers despite negative microbiological investigations. Serum tryptase levels remained within the normal range with no significant rise, while cytokine analyses demonstrated elevations of pro-inflammatory interleukin-6 and other cytokines in patients 1 and 3 where samples were available. Standard corticosteroid premedication did not prevent recurrence, and one patient developed systemic symptoms following intradermal testing. All patients improved with high-dose systemic corticosteroids and supportive care. These findings suggest that ICM may induce a cytokine-mediated inflammatory phenotype distinct from classical hypersensitivity reactions, highlighting the importance of early clinical recognition to guide diagnosis and management. Full article

Background: Propofol is widely used for anesthesia in colorectal cancer surgery, but is frequently associated with hypotension and respiratory depression. Remimazolam, a novel ultra-short–acting benzodiazepine, may offer improved hemodynamic stability with similar anesthetic depth and recovery characteristics. However, evidence directly comparing remimazolam and propofol in the setting of colon cancer surgery remains limited. Therefore, the aim of this study was to systematically evaluate the efficacy, safety, perioperative hemodynamic stability, and recovery outcomes of remimazolam versus propofol in older adults undergoing colon cancer surgery. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials and comparative cohort studies evaluating remimazolam versus propofol in adult patients undergoing colon or colorectal cancer surgery. PubMed, Scopus, and Web of Science were searched from the start of each database to October 2025. Outcomes included perioperative hemodynamics (MAP and HR), recovery parameters, intraoperative remifentanil consumption, anesthesia duration, and adverse events. Random-effect models were used to calculate pooled mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Results: Six studies involving 542 patients (remimazolam n = 276; propofol n = 266) were included. Remimazolam produced significantly higher perioperative MAP (overall MD = 2.86 mmHg, 95% CI 1.52–4.21; p < 0.0001) and slightly higher HR (MD = 2.30 bpm, 0.08–4.52; p = 0.04). Differences were largest immediately after incision and at the end of surgery. No significant differences were found in PACU stay, overall recovery duration, remifentanil consumption, or anesthesia duration. Postoperative nausea and vomiting were comparable (RR = 0.93; p = 0.86), while respiratory depression was numerically lower with remimazolam (RR = 0.49; p = 0.17). Conclusions: Remimazolam provides anesthetic efficacy comparable to propofol in colon cancer surgery while offering modest, but clinically meaningful improvements in intraoperative hemodynamic stability. Recovery times, opioid requirements, and adverse-event rates were similar between agents. Remimazolam may be particularly advantageous for elderly or hemodynamically vulnerable patients undergoing major colorectal procedures. Larger, high-quality trials are warranted to clarify long-term and oncologic outcomes. Full article

Background/Objectives: The purpose of this study was to investigate the association between cardiovascular adverse drug events (ADEs) and the use of COVID-19 medicines. Methods: The analyses were conducted by leveraging pharmacovigilance data from the Food and Drug Authority (FDA) Adverse Event Reporting System (FAERS) and TriNetX electronic health records (EHRs). Transcriptomic data from human embryonic stem cell-derived cardiomyocytes (hESC-CMs) exposed to remdesivir were analyzed to provide supportive biological context for the observed cardiovascular safety signals. Results: Comparative analysis of three approved COVID-19 therapies revealed that COVID-19 patients treated with remdesivir had a higher risk of cardiovascular events than those treated with Paxlovid or REGEN-COV. FAERS analysis further indicated that bradycardia, hypotension, and cardiac arrest were the most frequently reported cardiovascular events associated with remdesivir, which was validated by propensity score-matched EHR data. These findings suggest an association between remdesivir exposure and increased cardiovascular ADEs relative to other COVID-19 therapies. Sex-stratified analysis using FAERS and EHR did not show strong sex-dependent patterns for remdesivir-associated cardiovascular ADEs. Age-stratified analyses of EHR data showed age-associated variation across the three cardiovascular ADEs. Bradycardia displayed a non-uniform pattern with higher prevalence in the youngest and oldest age groups, hypotension showed an overall age-associated increase, and cardiac arrest showed only a weak age-associated effect. Pathway enrichment analysis on transcriptomic data revealed that the “cGMP-PKG signaling pathway”, “dilated cardiomyopathy”, and “calcium signaling pathway” were enriched among genes up-regulated by remdesivir exposure. Conclusions: In summary, our integrated analysis of pharmacovigilance, EHR, and transcriptomic data provides convergent evidence for associations between remdesivir and cardiovascular ADEs and offers biological context into these associations. Full article

Background: Sepsis poses a major global challenge in critical care medicine. While
guideline-recommended interventions fail to reverse the core pathophysiological process
of sepsis: inflammation–immune imbalance. Ulinastatin mitigates inflammatory cytokine
storms. However, its impact on 28-day and 30-day survival rate in sepsis remains controversial,
and dose-dependent efficacy has not been systematically clarified. Methods:
This systematic review and meta-analysis adhered to the PRISMA guidelines. Randomized
controlled trials published from February 2016 to September 2025 were identified through
PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Adult patients (≥18 years)
with sepsis (Sepsis-3 criteria: SOFA ≥ 2 + suspected infection) were included. Primary outcomes
were 28-day and 30-day survival rates; secondary outcomes included inflammatory
markers and prognostic scores. Data were pooled using RevMan 5.4.1, with RR for binary
outcomes and mean difference for continuous variables. Heterogeneity was quantified
by the I2 statistic, and publication bias was assessed via funnel plots and Begg’s/Egger’s
tests. Results: In six included RCTs (n = 535), ulinastatin significantly improved survival
rates at both 28 days (RR = 1.14, 95% CI: 1.01–1.29) and 30 days (RR = 1.39, 95% CI:
1.20–1.60), with a statistically significant interaction between time points (p = 0.04). Exploratory
subgroup analyses suggested a “diminishing trend” with increasing daily doses,
with 400,000 units appearing optimal. Treatment for >5 days was associated with better
outcomes. The intervention also significantly lowered key inflammatory markers. Safety
reporting was limited. Safety data were limited to one study (n = 96), reporting mild adverse
events (rash, hypotension). Conclusions: A benefit has been shown with ulinastatin
at 400,000 units daily, but not with higher doses. Treatment beyond 5 days may improve
outcomes, though longer duration is not clearly better. Current evidence is limited by geographic
bias, small samples, and insufficient safety data. More high-quality, multinational
RCTs are needed to confirm the dose–response and long-term safety. Full article

Background/Objectives: Poincaré plot analysis represents a nonlinear approach to heart rate variability (HRV) assessment, but the physiological meaning of several derived parameters remains unclear. This study aimed to evaluate associations between selected Poincaré plot-derived parameters, conventional HRV indices, and cardiovascular autonomic reflex tests in a real-world clinical population. Methods: This observational study included 269 adult patients referred for evaluation of suspected autonomic dysfunction. All participants underwent short-term resting ECG, cardiovascular autonomic reflex testing, and 24 h Holter ECG monitoring. Poincaré plot-derived parameters were analyzed in relation to short- and long-term HRV measures using the Spearman correlation with false discovery rate correction, and group comparisons were performed based on reflex test results. Results: Several Poincaré plot-derived parameters showed strong correlations with long-term HRV indices. VLI and LA were primarily associated with global and long-term autonomic variability, whereas VAI and SA were more closely related to parasympathetic modulation. Associations with short-term HRV were generally weak. Lower values of selected parameters were observed in patients with abnormal parasympathetic reflex tests, while no significant differences were found in relation to orthostatic hypotension. Conclusions: Poincaré plot-derived parameters capture complementary aspects of autonomic regulation beyond conventional HRV indices and may enhance autonomic phenotyping in clinical settings. Full article

Background and Clinical Significance: Malignant glaucoma, also described as aqueous misdirection syndrome, most commonly occurs following trabeculectomy in patients with primary angle-closure glaucoma and a shallow anterior chamber. Management aims to restore normal anterior segment anatomy, re-establish aqueous flow from the posterior to the anterior chamber, and achieve adequate intraocular pressure control. This report presents a case of malignant glaucoma developing after trabeculectomy, with emphasis on current diagnostic and therapeutic approaches. Case Presentation: A patient with primary angle-closure glaucoma, pseudophakia of the right eye, and a patent laser peripheral iridotomy, receiving maximal tolerated topical antiglaucoma therapy, was referred to the Department of Ophthalmology due to uncontrolled intraocular pressure. The patient was scheduled for trabeculectomy of the right eye. In the immediate postoperative period, intraocular pressure was adequately controlled. However, on postoperative day five, a significant elevation in intraocular pressure was observed, accompanied by persistent shallowing of the anterior chamber. Topical and systemic hypotensive therapy, posterior capsulotomy and hyaloidotomy were performed without improvement of the local condition. The patient was qualified for irido-zonulectomy with pars plana vitrectomy. Following surgical intervention, normalization of intraocular pressure was achieved, and the anatomy of the anterior chamber was restored. Conclusions: Malignant glaucoma remains a challenging postoperative complication and is frequently refractory to conservative pharmacological and laser-based interventions. Early recognition and prompt surgical management, particularly irido-zonulectomy combined with pars plana vitrectomy, significantly increase the likelihood of anatomical and functional success. Full article