Acute quadruple extremity compartment syndrome due to angio-oedema after polypharmacy overdose including olmesartan medoxomil, telmisartan and vildagliptin.

This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.

Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: a Bayesian meta-analysis.

BACKGROUND: Tracheal intubation is a high-risk intervention commonly performed in critically ill patients. Due to its favorable cardiovascular profile, ketamine is considered less likely to compromise clinical outcomes. This meta-analysis aimed to assess whether ketamine, compared with other agents, reduces mortality in critically ill patients undergoing intubation. METHODS: We searched MEDLINE, Embase, and the Cochrane Library from inception until April 27, 2023, for randomized controlled trials and matched observational studies comparing ketamine with any control in critically ill patients as an induction agent. The primary outcome was mortality at the longest follow-up available, and the secondary outcomes included Sequential Organ Failure Assessment score, ventilator-free days at day 28, vasopressor-free days at day 28, post-induction mean arterial pressure, and successful intubation on the first attempt. For the primary outcome, we used a Bayesian random-effects meta-analysis on the risk ratio (RR) scale with a weakly informative neutral prior corresponding to a mean estimate of no difference with 95% probability; the estimated effect size will fall between a relative risk of 0.25 and 4. The RR and 95% credible interval (CrI) were used to estimate the probability of mortality reduction (RR < 1). The secondary outcomes were assessed with a frequentist random-effects model. We registered this study in Open Science Framework ( https://osf.io/2vf79/ ). RESULTS: We included seven randomized trials and one propensity-matched study totaling 2978 patients. Etomidate was the comparator in all the identified studies. The probability that ketamine reduced mortality was 83.2% (376/1475 [25%] vs. 411/1503 [27%]; RR, 0.93; 95% CrI, 0.79-1.08), which was confirmed by a subgroup analysis excluding studies with a high risk of bias. No significant difference was observed in any secondary outcomes. CONCLUSIONS: All of the included studies evaluated ketamine versus etomidate among critically ill adults requiring tracheal intubation. This meta-analysis showed a moderate probability that induction with ketamine is associated with a reduced risk of mortality.

A pitfall of cognitive bias during the pandemic: Two cases of Plasmodium falciparum malaria coinfected or misdiagnosed with COVID-19.

We report two the cases of patients with imported Plasmodium falciparum malaria during the COVID-19 pandemic. One was coinfected with COVID-19 and the other was misdiagnosed with COVID-19; either way, the diagnosis of malaria was delayed. These cases suggest that physicians should beware of cognitive biases during pandemics and carefully evaluate febrile patients. Malaria should be considered in any febrile patient returning from a malaria-endemic area.

Early diagnosis of Cryptococcus neoformans var. grubii meningitis using multiplex PCR assay in an immunocompetent patient.

Cryptococcosis is an invasive fungal infection that mainly affects the lungs and central nervous system. While patients with cell-mediated immunodeficiency are at high risk of developing cryptococcosis, there have been increasing reports of cryptococcosis in immunocompetent individuals with no underlying conditions. Herein, we report a case of cryptococcal meningitis in a 55-year-old apparently immunocompetent man with a history of heavy alcohol consumption. Although the patient was initially treated for tuberculous meningitis and varicella-zoster virus induced vasculopathy due to a history of exposure to tuberculosis and a presence of stroke, a multiplex polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) identified Cryptococcus species unexpectedly, enabling swift treatment and a favorable clinical outcome. The multiplex PCR assay, which can identify multiple pathogens simultaneously and instantly, may lead to early diagnosis and treatment by detecting unanticipated pathogens. Furthermore, the strain was identified through multilocus sequence typing (MLST) analysis as Cryptococcus neoformans var. grubii, Sequence Type 5, molecular type: VNI. Although simplified microbial identification techniques such as mass spectrometry have recently been developed, molecular biological assays are still essential for the accurate identification of infectious strains.

Pharmacokinetic and pharmacodynamic considerations in antimicrobial therapy for sepsis.

Introduction: Antimicrobial dose optimization for the treatment of sepsis remains challenging because of dynamic pharmacokinetic alterations and physiological/pathological responses of the host. Subtherapeutic plasma levels of antimicrobials are commonly observed in patients with sepsis, which potentially leads to both treatment failure and emergence of antimicrobial resistance. The knowledge of antimicrobial pharmacokinetics and pharmacodynamics is helpful in order to tailor antimicrobial dosing strategies.Areas covered: This narrative review summarizes pharmacokinetic alterations of antimicrobial agents and provides useful information on antimicrobial dose optimization. Literature was searched using PubMed database, focusing on pharmacokinetics and pharmacodynamics of antibacterial and antifungal agents in sepsis.Expert opinion: In patients with sepsis, increased volume of distribution and variable changes in renal clearance are the two major factors for antimicrobial pharmacokinetic alterations. Traditional 'one-dose-fits-all' dosing strategy is not suitable for patients with sepsis and hence individualized antimicrobial dosing adjustment is preferable. In general, the initial dose of hydrophilic antimicrobials such as ß-lactams, aminoglycosides, and vancomycin should be given at a high dose regardless of renal function. Improved methods of drug administration (e.g. extended/continuous infusion of ß-lactams) help to increase the chance of pharmacodynamic target attainment. The use of therapeutic drug monitoring should be considered where available.

Possible involvement of phospholipase A(2) and cyclooxygenase in stimulatory action of L-histidine on protein synthesis in L6 myotubes.

Effects of L-histidine and related compounds on protein synthesiswere studied in cultured L6 myotubes. L-Histidine specifically stimulated protein synthesis, whereas D-histidine, histamine, L-arginine and L-lysine did not. Inhibitors of phospholipase A(2), phospholipase C and cyclooxygenase intercepted the stimulatory action of L-histidine on protein synthesis, while inhibitors of protein kinase C and 5-lipoxygenase did not. These results suggest an involvement of phospholipase A(2) and cyclooxygenase in the stimulatory action of L-histidine on protein synthesis in L6 myotubes.