Experience of Carbon Monoxide Poisoning Treated With Hyperbaric Oxygen Therapy and Steroid Pulse Therapy
This case suggests that the combination of steroid pulse therapy (SPT) and hyperbaric oxygen therapy (HBOT) may be effective for treating severe CO poisoning. The combined therapy not only improved acute neurological recovery but also appeared to prevent the development of delayed neurological sequelae (DNS).
KEY FINDINGS: This case suggests that the combination of steroid pulse therapy (SPT) and hyperbaric oxygen therapy (HBOT) may be effective for treating severe CO poisoning. The combined therapy not only improved acute neurological recovery but also appeared to prevent the development of delayed neurological sequelae (DNS). This is a single case report, and further research is needed to validate these findings.
BACKGROUND: Carbon monoxide (CO) poisoning is a significant concern in emergency medicine, often leading to delayed neurological sequelae (DNS) such as memory impairment, disorientation, apraxia, agnosia, gait disturbances, and Parkinson-like symptoms. While hyperbaric oxygen therapy (HBOT) is a recognized treatment for preventing DNS, there is no established treatment for the acute neurological symptoms of severe CO poisoning. This case report explores a combined therapeutic approach.
DETAILS: This is a case report about a 50-year-old man who was admitted to the hospital with severe CO poisoning, presenting with a Glasgow Coma Scale score of 3. His carboxyhemoglobin level was 51.2%. The patient was treated in the intensive care unit with a combination of hyperbaric oxygen therapy (HBOT) and steroid pulse therapy (SPT). The patient's level of consciousness improved significantly within three days of starting the combined therapy. He was discharged from the hospital after 14 days and had no complications, including DNS, during a follow-up period of 49 days.
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Source: Kano, S., Miyake, T., Asano, H.,s et al. (2025). Experience of Carbon Monoxide Poisoning Treated With Hyperbaric Oxygen Therapy and Steroid Pulse Therapy: A Case Report. International Journal of Emergency Medicine. 2025; Published: August 18, 2025. DOI: 10.1186/s12245-025-00966-5.
T-Wave Morphology Variation Improves Risk Stratification in Type 2 Long-QT Syndrome Beyond QTc Duration
This study demonstrates that the TMV index provides prognostic information beyond QTc duration in patients with LQT2. More negative TMV values were independently associated with an increased lifetime risk of cardiac events, whereas T-wave amplitude and the morphology combination score were not predictive of outcomes. TMV may enhance ECG-based risk stratification, particularly in patients with borderline or prolonged QTc intervals, pending validation in larger prospective multicenter studies.
KEY FINDINGS: This study demonstrates that quantitative assessment of T-wave morphology using the TMV index provides prognostic information beyond conventional QTc duration in patients with LQT2. More negative TMV values, reflecting greater T-wave morphological distortion and broader repolarization, were independently associated with a markedly higher lifetime risk of cardiac events after adjustment for established clinical and electrocardiographic risk markers. In contrast, traditional morphology metrics such as T-wave amplitude and the morphology combination score did not independently predict outcomes. These findings suggest that TMV may serve as a complementary ECG biomarker to improve risk stratification, particularly among patients with borderline or prolonged QTc intervals. Because this was a relatively small, exploratory cohort, larger prospective multicenter studies are required before routine clinical implementation.
BACKGROUND: Risk stratification in patients with genotype-confirmed type 2 long-QT syndrome (LQT2) remains challenging because corrected QT (QTc) duration alone does not fully capture arrhythmic risk. A substantial proportion of genetically affected individuals have borderline or normal QTc intervals despite remaining susceptible to cardiac events. This study evaluated whether a novel electrocardiographic marker, the T-wave morphology variation (TMV) index, could provide incremental prognostic information by quantifying T-wave morphology abnormalities relative to a large population-based reference.
DETAILS: This combined retrospective and prospective cohort study included 54 genotype-confirmed patients with LQT2 recruited from three tertiary cardiogenetic centers in Sweden. T-wave morphology was analyzed from resting 12-lead ECGs using a dynamic time-warping algorithm that generated the TMV index by comparing each patient's T wave with sex-, heart rate-, and lead-matched reference waveforms derived from 23,962 healthy participants in the UK Biobank. The primary outcome was the first lifetime cardiac event, defined as syncope or ventricular arrhythmia, while ventricular arrhythmia alone served as the secondary endpoint. Cox proportional hazards models evaluated the association between TMV and clinical outcomes after adjustment for QTc, sex, and the morphology combination score (MCS). Among the 54 patients, 32 experienced at least one cardiac event, including 28 with syncope and 11 with documented ventricular arrhythmia. A TMV threshold of <=-18.41 ms (25th percentile) identified patients at substantially higher risk of cardiac events. Low TMV was associated with a significantly increased risk of cardiac events in univariate analysis (HR, 3.505 [95% CI, 1.673-7.341]; P<0.001). The association remained significant after adjustment for QTc (HR, 2.92 [95% CI, 1.111-7.676]; P=0.03), QTc plus sex (HR, 3.375 [95% CI, 1.256-9.067]; P=0.016), and QTc, sex, plus MCS (HR, 4.061 [95% CI, 1.369-12.046]; P=0.012). Patients with TMV <=-18.41 ms experienced cardiac events more frequently than those with higher TMV (93% vs 43%), while ventricular arrhythmias occurred in 43% versus 10%, respectively. TMV also predicted ventricular arrhythmias in univariate analysis (HR, 4.978 [95% CI, 1.4-17.705]; P=0.013), although this association did not remain statistically significant after multivariable adjustment. Neither T-wave amplitude nor MCS independently predicted cardiac events in this cohort.
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Source: Gomez, N., Ramirez, J., Savelev, A. A., et al. Risk Stratification of Patients With Type 2 Long-QT Syndrome Through Analysis of T-Wave Morphology. Journal of the American Heart Association. 2026; 15(3). Published: June 23, 2026. DOI: 10.1161/JAHA.125.048388.
Comparative Effectiveness and Safety of Pharmacological Treatments for Rapid Tranquilisation in Emergency Settings
This IPD network meta-analysis suggests that antipsychoticbenzodiazepine combinations may offer the greatest efficacy for rapid tranquilisation in emergency settings. However, the very low certainty of evidence and study heterogeneity underscore the need for individualized treatment decisions and further high-quality randomized trials.
Summary
An Individual Participant Data Network Meta-analysis
[Posted 17/Jul/2026]
AUDIENCE: Emergency Medicine, Psychiatry
KEY FINDINGS: This IPD network meta-analysis suggests that antipsychotic–benzodiazepine combinations may provide the most effective pharmacologic option for rapid tranquilisation in emergency settings, particularly compared with haloperidol monotherapy. While other antipsychotics and benzodiazepines also demonstrated favorable efficacy, haloperidol alone appeared less effective and was associated with extrapyramidal adverse effects. Given the very low certainty of evidence and the heterogeneity across studies, treatment selection should be individualized, and additional large pragmatic randomized trials are needed to strengthen the evidence base.
BACKGROUND: Psychomotor agitation is a frequent medical emergency requiring rapid pharmacologic intervention when nonpharmacologic de-escalation is insufficient. Although multiple parenteral agents are available, including antipsychotics, benzodiazepines, and combination regimens, treatment recommendations vary across clinical guidelines and practice settings. This systematic review and individual participant data (IPD) network meta-analysis evaluated the comparative effectiveness and safety of pharmacologic agents used for rapid tranquilisation in psychiatric and general emergency settings.
DETAILS: This systematic review included randomized controlled trials comparing intramuscular or intravenous pharmacologic treatments for rapid tranquilisation in patients with psychomotor agitation. Literature searches were conducted from database inception through November 14, 2025. A total of 18 trials involving 3,411 participants across eight regions met the inclusion criteria, with 13 trials (2,705 participants) providing individual participant data for the primary analysis. Participants had a mean age of 36.0 years (SD 11.7), 58.3% were men, and 68.2% presented with severe agitation at baseline. The primary outcome was achievement of sedation within 15-30 minutes after treatment. Bayesian one-stage random-effects IPD network meta-regression was used to compare treatment classes while accounting for agitation severity and other prognostic factors. Safety outcomes were assessed using aggregate data. Baseline agitation severity significantly influenced treatment response. In patients with moderate agitation, the likelihood of achieving sedation within 15-30 minutes, compared with haloperidol monotherapy, was greatest with antipsychotic-benzodiazepine combinations (OR 12.93, 95% CrI 3.00-50.91; RR 1.58), followed by benzodiazepines (OR 5.52, 95% CrI 1.37-21.02; RR 1.49) and other antipsychotics (OR 4.54, 95% CrI 1.35-14.45; RR 1.45). Among patients with severe agitation, antipsychotic-benzodiazepine combinations remained more effective than haloperidol monotherapy (OR 4.86, 95% CrI 1.28-17.54; RR 1.73), whereas the comparative effectiveness of benzodiazepines (OR 2.09, 95% CrI 0.58-6.99; RR 1.38) and other antipsychotics (OR 1.70, 95% CrI 0.62-4.59; RR 1.28) was less certain. Most participants (>90%) achieved sedation within 45-240 minutes irrespective of treatment. Antipsychotic-benzodiazepine combinations demonstrated the greatest advantage during the first 10 minutes after administration, although early time-point data were limited. Haloperidol monotherapy was associated with extrapyramidal adverse effects, whereas benzodiazepines were linked to cardiorespiratory depression. Sensitivity analyses suggested ketamine ranked as the most effective treatment; however, this finding was derived from a single study without individual participant data. Overall confidence in the evidence for the primary outcome was rated as very low.
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Source: Siafis, S., Philipona, F., Nomura, N., et al. Comparative Effectiveness and Safety of Pharmacological Treatments for Rapid Tranquilisation in Emergency Settings: A Systematic Review and Individual Participant Data Network Meta-Analysis. The Lancet Psychiatry. 2026; 13(7): 567-580. Published: July, 2026. DOI: 10.1016/S2215-0366(26)00097-0.
Gadolinium-Based Contrast Agents: Reassessing Safety Beyond Nephrogenic Systemic Fibrosis
This review highlights that gadolinium-based contrast agents continue to play a critical role in diagnostic MRI, but their use should be guided by careful patient selection and individualized risk assessment. Although the risk of nephrogenic systemic fibrosis has declined considerably, further research is needed to clarify the clinical significance of gadolinium retention and its long-term safety.
KEY FINDINGS: This review emphasizes that GBCAs remain indispensable for diagnostic MRI but should be used following an individualized benefit-risk assessment, particularly in patients with chronic kidney disease or acute kidney injury. Although modern practice has substantially reduced the incidence of NSF, uncertainties remain regarding gadolinium retention, long-term toxicity, and persistent symptoms after exposure. Continued research into the mechanisms of gadolinium-associated injury, along with transparent patient counseling and evidence-based imaging policies, will be essential to optimize both patient safety and diagnostic care.
BACKGROUND: Gadolinium-based contrast agents (GBCAs) have been widely used to enhance magnetic resonance imaging (MRI) since the 1980s because of their favorable diagnostic performance and generally low incidence of acute adverse reactions. However, concerns regarding nephrogenic systemic fibrosis (NSF), gadolinium retention, and potential long-term toxicity have prompted ongoing debate about their safety, particularly in patients with kidney disease. This review examines current evidence on GBCA-associated complications, mechanisms of toxicity, and considerations for balancing diagnostic benefits with potential risks.
DETAILS: This narrative review synthesizes published evidence on the clinical safety of GBCAs, including acute hypersensitivity reactions, nephrotoxicity, NSF, gadolinium retention, and emerging concepts such as gadolinium-associated symptoms. The authors discuss differences between linear and macrocyclic GBCAs, proposed mechanisms of tissue deposition and fibrosis, the role of kidney dysfunction in gadolinium elimination, current American College of Radiology (ACR) recommendations, and unresolved questions regarding long-term toxicity. Experimental and clinical data addressing tissue retention, dialysis, and mechanistic pathways underlying gadolinium-induced injury are also reviewed. The review highlights that the incidence of NSF has declined substantially following the adoption of risk-based prescribing practices and updated clinical guidelines. Nevertheless, available evidence indicates that gadolinium retention can occur in multiple tissues, including the brain, even in individuals without severe renal impairment. The authors emphasize that tissue retention and toxicity are not fully explained by current GBCA classifications and that macrocyclic agents, although generally considered more stable, do not completely eliminate potential risk. Evidence reviewed also suggests that gadolinium may contribute to acute kidney injury, persistent tissue deposition, rare cases of encephalopathy, and symptoms associated with gadolinium exposure. Current data do not establish a definitive exposure threshold for toxicity, and the benefit of prophylactic hemodialysis after GBCA administration remains uncertain. While observational studies have estimated the risk of NSF with group II agents to be below 0.07%, the review notes that the true absolute risk remains difficult to define because of limitations in available evidence and confounding factors.
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Promising Drug Candidates and Emerging Therapeutic Strategies Against Candida auris
Emerging therapies for Candida auris extend beyond conventional antifungal agents and include repurposed drugs, novel antifungal compounds, vaccines, antimicrobial peptides, and nanotechnology-based approaches. While further clinical validation is needed, these strategies may help address the growing challenge of multidrug-resistant C. auris infections.
KEY FINDINGS: This review underscores the expanding pipeline of therapeutic strategies targeting Candida auris, ranging from repurposed medications and next-generation antifungal agents to vaccines, antimicrobial peptides, nanoparticle formulations, and innovative environmental control measures. Although no single therapy has emerged as a definitive solution, compounds such as ibrexafungerp (SCY-078), ATI-2307, and fosmanogepix, together with drug repurposing and bioinspired approaches, represent promising avenues for addressing multidrug-resistant C. auris infections. Continued translational research and clinical evaluation remain essential to establish safe and effective treatment options for this increasingly important fungal pathogen.
BACKGROUND: Candida auris has rapidly emerged as a multidrug-resistant fungal pathogen of global concern since its first identification in 2009. The organism is associated with healthcare-associated outbreaks, high transmissibility, frequent misidentification, and severe invasive infections, with reported mortality rates ranging from 35% to 72%. Resistance to currently available antifungal agents further complicates treatment, with approximately 90% of isolates resistant to fluconazole, around 30% resistant to amphotericin B, and fewer than 5% resistant to echinocandins. These challenges have accelerated efforts to identify novel antifungal therapies and alternative treatment strategies.
DETAILS: This publication is a comprehensive narrative review that summarizes advances in antifungal research targeting C. auris over the preceding decade. The authors evaluated emerging therapeutic approaches from a medicinal chemistry perspective, including drug repurposing, combination therapy, novel antifungal agents, natural products, metal-based compounds, nanoparticles, vaccines, antimicrobial peptides, and environmental decontamination strategies. The review also examined chemical and physicochemical characteristics of promising compounds, including lipophilicity and topological polar surface area, to identify structural features that may facilitate future antifungal drug development. The review highlights several promising therapeutic candidates with activity against multidrug-resistant C. auris. Drug repurposing identified multiple agents with antifungal or antibiofilm activity, including sertraline, miltefosine, iodoquinol, octenidine dihydrochloride, taurolidine, and bensulfuron methyl. Miltefosine demonstrated fungicidal and antibiofilm activity, while encapsulation within alginate nanoparticles reduced toxicity and improved survival in an infected Galleria mellonella model. The NDV-3A vaccine generated cross-reactive antibodies against C. auris and protected neutropenic mice, with additive efficacy when combined with micafungin.
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Among novel antifungal agents, SCY-078 (ibrexafungerp), an orally available 1,3-ß-D-glucan synthesis inhibitor, demonstrated potent activity against C. auris, with an MIC90 of 1 mg/L and MIC50 and MIC90 values of 0.5 µg/mL and 1 µg/mL, respectively, across 100 isolates representing the four major clades. More than 150 strains with diverse resistance profiles were subsequently shown to be uniformly susceptible to SCY-078, and the agent remained active against pan-resistant isolates while also exhibiting antibiofilm activity.
Additional investigational therapies also demonstrated encouraging preclinical activity. The arylamidine T-2307 (ATI-2307) exhibited in vitro MIC values ranging from 0.125 to 4 µg/mL and improved survival while reducing kidney fungal burden in murine infection models following 3 mg/kg once-daily subcutaneous treatment. Other experimental approaches included antimicrobial peptides, ceragenins, fluorinated hydrazone derivatives, and novel chemical scaffolds designed to overcome existing resistance mechanisms.
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Source: Billamboz, M., Fatima, Z., Hameed, S., et al. Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris. Microorganisms. 2021; 9(3): 634. Published: March 18, 2021. DOI: 10.3390/microorganisms9030634.
Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts
Early initiation of a 5-day oral ensitrelvir regimen within 72 hours after symptom onset in an index patient significantly reduced the risk of developing Covid-19 among household contacts while maintaining a safety profile comparable to placebo. Clinical benefit was observed across major patient subgroups, including individuals at increased risk for severe disease, and treatment was associated with reduced household transmission. These findings support ensitrelvir as an effective postexposure prophylactic option for household contacts and suggest potential utility in other high-risk exposure settings where rapid outbreak control is needed.
KEY FINDINGS: Early initiation of a 5-day oral ensitrelvir regimen within 72 hours after symptom onset in an index patient significantly reduced the risk of developing Covid-19 among household contacts while maintaining a safety profile comparable to placebo. Clinical benefit was observed across major patient subgroups, including individuals at increased risk for severe disease, and treatment was associated with reduced household transmission. These findings support ensitrelvir as an effective postexposure prophylactic option for household contacts and suggest potential utility in other high-risk exposure settings where rapid outbreak control is needed.
BACKGROUND: Household transmission remains a major contributor to the spread of SARS-CoV-2, particularly among individuals at increased risk for severe Covid-19. Although vaccination and prior infection have reduced disease severity, waning immunity and emerging variants continue to sustain transmission. Previous trials evaluating oral antiviral agents for postexposure prophylaxis in household contacts have not demonstrated significant protection, highlighting the need for effective preventive therapies. This phase 3 trial evaluated whether oral ensitrelvir, a SARS-CoV-2 3C-like protease inhibitor, could prevent Covid-19 among household contacts exposed to an infected index patient.
DETAILS: This phase 3, double-blind, randomized, placebo-controlled trial was conducted between June 2023 and mid-September 2024 across the United States, Argentina, Japan, South Africa, and Vietnam. Eligible household contacts were 12 years of age or older, had a negative SARS-CoV-2 test at enrollment, and were randomized within 72 hours after symptom onset in the index patient. Participants received either ensitrelvir 375 mg on day 1 followed by 125 mg once daily on days 2-5 or matching placebo. The primary endpoint was laboratory-confirmed Covid-19 by day 10 in the modified intention-to-treat population, defined as RT-PCR positivity accompanied by at least one prespecified Covid-19 symptom lasting 48 hours or longer. Secondary endpoints included laboratory-confirmed SARS-CoV-2 infection regardless of symptoms, subgroup analyses, and safety outcomes. Overall, 2,387 household contacts were randomized, including 1,030 participants in the ensitrelvir group and 1,011 in the placebo group within the modified intention-to-treat population. The mean participant age was 42.4 years, 71.1% were enrolled within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. By day 10, laboratory-confirmed Covid-19 occurred in 2.9% of participants receiving ensitrelvir compared with 9.0% receiving placebo, corresponding to a risk ratio of 0.33 (95% CI, 0.22-0.49; P<0.001) and an approximate 67% relative risk reduction in the modified intention-to-treat population. In the intention-to-treat population, Covid-19 developed in 4.4% and 10.2% of participants, respectively (risk ratio, 0.43; 95% CI, 0.32-0.59; P<0.001). Laboratory-confirmed SARS-CoV-2 infection irrespective of symptoms was also lower with ensitrelvir (14.0% vs. 21.5%; risk ratio, 0.66; 95% CI, 0.55-0.79). Subgroup analyses demonstrated generally consistent efficacy across age groups and participants with risk factors for severe disease. Among participants with risk factors, Covid-19 developed in 2.4% of the ensitrelvir group compared with 9.9% of the placebo group. Ensitrelvir was also associated with a 34% relative reduction in household SARS-CoV-2 transmission. Adverse events occurred at similar frequencies in the ensitrelvir and placebo groups (15.1% vs. 15.5%), with serious adverse events reported in 0.2% of participants in each group. No Covid-19-related hospitalizations or deaths occurred. Transient reductions in high-density lipoprotein concentrations were observed with ensitrelvir but returned toward baseline by day 15 and were not associated with clinical events.
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