Should Glucokinase be Given a Chance in Diabetes Therapeutics? A Clinical-Pharmacological Review of Dorzagliatin and Lessons Learned So Far.

Despite advances in the management of type 2 diabetes mellitus (T2DM), one-third of patients with diabetes do not achieve the desired glycemic goal. Considering this inadequacy, many agents that activate glucokinase have been investigated over the last two decades but were withdrawn before submission for marketing permission. Dorzagliatin is the first glucokinase activator that has been granted approval for T2DM, only in China. As overstimulation of glucokinase is linked with pathophysiological disturbances such as fatty liver and cardiovascular issues and a loss of therapeutic efficacy with time. This review aims to highlight the benefits of glucokinase activators vis-à-vis the risks associated with chronic enzymatic activation. We discuss the multisystem disturbances expected with chronic activation of the enzyme, the lessons learned with glucokinase activators of the past, the major efficacy and safety findings with dorzagliatin and its pharmacological properties, and the status of other glucokinase activators in the pipeline. The approval of dorzagliatin in China was based on the SEED and the DAWN trials, the major pivotal phase III trials that enrolled patients with T2DM with a mean glycosylated hemoglobin of 8.3-8.4%, and a mean age of 53-54.5 years from multiple sites in China. Patients with uncontrolled diabetes, cardiac diseases, organ dysfunction, and a history of severe hypoglycemia were excluded. Both trials had a randomized double-blind placebo-controlled phase of 24 weeks followed by an open-label phase of 28 weeks with dorzagliatin. Drug-naïve patients with T2DM with a disease duration of 11.7 months were enrolled in the SEED trial while the DAWN trial involved patients with T2DM with a mean duration of 71.5 months and receiving background metformin therapy. Compared with placebo, the decline in glycosylated hemoglobin at 24 weeks was more with dorzagliatin with an estimated treatment difference of - 0.57% in the SEED trial and - 0.66% in the DAWN trial. The desired glycosylated hemoglobin (< 7%) was also attained at more than two times higher rates with dorzagliatin. The glycemic improvement was sustained in the SEED trial but decreased over 52 weeks in the DAWN trial. Hyperlipidemia was observed in 12-14% of patients taking dorzagliatin versus 9-11% of patients receiving a placebo. Additional adverse effects noticed over 52 weeks with dorzagliatin included an elevation in liver enzymes, hyperuricemia, hyperlacticacidemia, renal dysfunction, and cardiovascular disturbances. Considering the statistically significant improvement in glycosylated hemoglobin with dorzagliatin in patients with T2DM, the drug may be given a chance in treatment-naïve patients with a shorter disease history. However, with the waning therapeutic efficacy witnessed in patients with long-standing diabetes, which was also one of the potential concerns with previously tested molecules, extended studies involving patients with chronic and uncontrolled diabetes are needed to comment upon the long-term therapeutic performance of dorzagliatin. Likewise, evidence needs to be generated from other countries, patients with organ dysfunction, a history of severe hypoglycemia, cardiac diseases, and elderly patients before extending the use of dorzagliatin. Apart from monitoring lipid profiles, long-term safety studies of dorzagliatin should involve the assessment of serum uric acid, lactate, renal function, liver function, and cardiovascular parameters.

Traditional herbal medicine use doubled the risk of multi-organ dysfunction syndrome in children: A prospective cohort study.

BACKGROUND: Traditional herbal medicine (THM) is frequently used in pediatric populations in many low-income countries as a form of healthcare and has been associated with a range of adverse events, including liver toxicity, renal failure, and allergic reactions. Despite these concerns, its impact on multi-organ dysfunction syndrome (MODS) risk has not been thoroughly investigated. OBJECTIVE: This study aimed to investigate the incidence and predictors of MODS in a pediatric intensive care unit (PICU) in Ethiopia, with a focus on the association between THM use and the risk of MODS. METHODS: This was a single-center prospective cohort study conducted at a PICU in the university of Gondar Comprehensive Specialized hospital, Northwest Ethiopia. The study enrolled eligible patients aged one month to 18 years admitted to the PICU during the study period. Data on demographic characteristics, medical history, clinical and laboratory data, and outcome measures using standard case record forms, physical examination, and patient document reviews. The predictors of MODS were assessed using Cox proportional hazards models, with a focus on the association between traditional herbal medicine use and the risk of MODS. RESULTS: A total of 310 patients were included in the final analysis, with a median age of 48 months and a male-to-female ratio of 1.5:1. The proportion and incidence of MODS were 30.96% (95% CI:25.8, 36.6) and 7.71(95% CI: 6.10, 9.40) per 100-person-day observation respectively. Renal failure (17.74%), neurologic failure (15.16%), and heart failure (14.52%) were the leading organ failures identified. Nearly one-third of patients (32.9%) died in the PICU, of which 59.8% had MODS. The rate of mortality was higher in patients with MODS than in those without. The Cox proportional hazards model identified renal disease (AHR = 6.32 (95%CI: 3.17,12.61)), intake of traditional herbal medication (AHR = 2.45, 95% CI:1.29,4.65), modified Pediatric Index of Mortality 2 (mPIM 2) score (AHR = 1.54 (95% CI: 1.38,1.71), and critical illness diagnoses (AHR = 2.68 (95% CI: 1.77,4.07)) as predictors of MODS. CONCLUSION: The incidence of MODS was high. Renal disease, THM use, mPIM 2 scores, and critical illness diagnoses were independent predictors of MODS. A more than twofold increase in the risk of MODS was seen in patients who used TMH. Healthcare providers should be aware of risks associated with THM, and educate caregivers about the potential harms of these products. Future studies with larger sample sizes and more comprehensive outcome measures are needed.

Near-fatal cocaine intoxication in an infant with thrombotic microangiopathy associated with multiple organ failure.

OBJECTIVE: To report a pediatric case of drug-induced thrombotic microangiopathy caused by cocaine. CASE DESCRIPTION: We report a nine-month-old patient who developed thrombotic microangiopathies after extreme cocaine intoxication, multiple organ dysfunction syndrome with hemodynamic dysfunction, anuric renal failure, liver failure, encephalopathy, and myocardial injury, corresponding phenotypically to thrombocytopenia-associated multiple organ failure. The patient received continuous venous hemofiltration and therapeutic plasma exchange, recovering satisfactorily. She was discharged after 30 days of hospitalization under the guidance of the childcare service, and was healthy after one year of follow-up. Toxicological samples confirmed high levels of cocaine and derivatives in blood, urine and hair. COMMENTS: To our knowledge, this is the first reported pediatric case. There are particularities of cocaine intoxication pathophysiology that can trigger thrombotic microangiopathies because of vasoconstriction, direct endothelial injury, platelet activation, and increasing von Willebrand factor and fibrinogen levels. All of which results in a prothrombotic state, inflammatory dysregulation, and microvascular thrombi. The increasing use of cocaine, especially among young adults, puts children at high risk of toxicity, either by passive unintentional exposure, or abuse due to the increased availability in homes.

Multiorgan failure caused by Chinese herbal medicine Xanthii Fructus poisoning: a case report.

BACKGROUND: Xanthii Fructus was used in the treatment of rhinitis and related nasal disease. It is the most commonly used chemically active component in compounds formulated for the treatment of rhinitis. However, poisoning, resulting in serious consequences, can easily occur owing to cocklebur overdose, improper processing, or usage without processing. CASE PRESENTATION: We reported on a 55-year-old man who experienced allergic rhinitis for 2.5 years. He ingested unprocessed Xanthii Fructus for 2 months as treatment. However, he developed anorexia; nausea; abdominal pain; general weakness; hiccups; oliguria and anuria; significantly elevated serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels; and abnormalities in blood coagulation series. Nutritional support; daily drugs for liver protection, gastric protection, inflammation reduction; fresh plasma; and cryoprecipitate infusion were administered. Continuous venovenous hemodialysis (Prismaflex ST100) was also administered. However, the patient's multiple organ failure gradually worsened, ultimately leading to death. CONCLUSION: Xanthii Fructus poisoning affects multiple systems, and its clinical manifestations are complex. Therefore, it is easily misdiagnosed and missed. Along with careful inquiry of medical and medication history, early diagnosis and intervention are vital for a successful treatment. It is also important to educate people and create awareness about this poisoning. Therefore, this intractable case has great clinical significance.

Piperacillin-tazobactam induced immune hemolytic anemia led to increased renal impairment and eventual death from multiple organ failure in a patient with hypertensive nephropathy: case report and literature review.

BACKGROUND: Piperacillin is one of the most common drugs that cause drug-induced immune hemolytic anemia, but a complete description of the serological features and course of the disease is rare. This study completely describes the serological characteristics and course of a patient with hypertensive nephropathy who developed drug-induced immune hemolytic anemia and worsened renal function during repeated administration of piperacillin-tazobactam. CASE PRESENTATION: A 79-year-old male patient with hypertensive nephropathy who developed severe hemolytic anemia and worsened renal function during intravenous piperacillin-tazobactam anti-infective treatment due to lung infection. Serological tests showed that the result of the direct antiglobulin test for anti-IgG was positive (4 +) and anti-C3d was negative, and the irregular red blood cell antibody screening test was negative. Plasma samples collected at different times from 2 days before to 12 days after the discontinuation of piperacillin-tazobactam administration were incubated with piperacillin solution and red blood cells of O-type healthy blood donors at 37 °C, IgG piperacillin-dependent antibodies were detected, and the highest titer was 128. However, no tazobactam-dependent antibody was detected in any plasma samples. Therefore, the patient was diagnosed with piperacillin-induced immune hemolytic anemia. Although blood transfusion and continuous renal replacement therapy were given, the patient died of multiple organ failure 15 days after the administration of piperacillin-tazobactam was stopped. CONCLUSION: This is the first complete description of the disease course and serological changes of piperacillin-induced immune hemolytic anemia, which is bound to help deepen the understanding of drug-induced immune hemolytic anemia and draw profound lessons from it.

Four-week repeated exposure to tire-derived 6-PPD quinone causes multiple organ injury in male BALB/c mice.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ) is the ozonation product of tire antioxidant 6-PPD. 6-PPDQ can be detected in different environments, such as roadway runoff and dust. Although 6-PPDQ toxicity has been frequently assessed in aquatic organisms, the possible toxic effects of 6-PPDQ on mammals remain largely unclear. We here aimed to perform systematic assessment to evaluate 6-PPDQ toxicity on multiple organs in mice. Male BALB/c mice were intraperitoneally injected with 6-PPDQ for two exposure modes, single intraperitoneal injection and repeated intraperitoneal injection every four days for 28 days. Serum, liver, kidney, lung, spleen, testis, brain, and heart were collected for injury evaluation by organ index, histopathology analysis and biochemical parameters. In 0.4 and 4 mg/kg 6-PPDQ single injected mice, no significant changes in organ indexes and biochemical parameters were detected, and only moderate pathological changes were observed in organs of liver, kidney, lung, and brain. Very different from this, in 0.4 and 4 mg/kg 6-PPDQ repeated injected mice, we observed the obvious increase in organ indexes of liver, kidney, lung, testis, and brain, and the decrease in spleen index. Meanwhile, the significant pathological changes were formed in liver, kidney, lung, spleen, testis, and brain in 0.4 and 4 mg/kg 6-PPDQ repeated injected mice. Biochemical parameters of liver (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)) and kidney (urea and creatinine) were all significantly upregulated by repeated injection with 0.4 and 4 mg/kg 6-PPDQ. After repeated exposure, most of 6-PPDQ was accumulated in liver and lung of mice. Therefore, our results suggested the risk of repeated exposure to 6-PPDQ in inducing toxicity on multiple organs in mice.

[Cardiogenic shock due to phosphine poisoning]. / Cardiogene shock door intoxicatie met fosfinegas.

BACKGROUND: Toxic inhalations form a rare cause of poisoning in the Netherlands. The initial symptoms of toxic inhalations may appear similar to acute viral infections. In the maritime sector aluminum or zinc phosphide is used to overcome rodent infestations during transportation. CASE DESCRIPTION: Here we discuss two patients intoxicated with gaseous phosphide used as fumigant in the transport of grains. The exposure to phosphide gas resulted in respiratory and gastrointestinal tract symptoms. Upon admission one of the patients deteriorated resulting in respiratory insufficiency, multi-organ failure and cardiogenic shock. CONCLUSION: Phosphide gas poisoning forms a rare cause for transient acute heart and multiorgan failure largely due to mitochondria dysfunction. In the case of unexplained incapacitation of multiple patients and/or pets toxic inhalations should differentially diagnostically be considered.

Association of crystalloid fluid infusion with intravascular hemolysis and organ dysfunction in hematopoietic stem cell transplant patients.

Endothelial cell activation and injury is common after hematopoietic stem cell transplant (HSCT) and is associated with many post-transplant complications. An underexplored mechanism of endothelial cell damage in this population is the infusion of normal saline (NS, 0.9 % sodium chloride) and other crystalloids, as NS use is associated with adverse outcomes in other patient populations. We hypothesized that the infusion of unbalanced crystalloids during HSCT may lead to changes in biomarkers commonly associated with red blood cell (RBC) hemolysis in patients before and after infusion, and that markers of endothelial and end-organ damage during admission may be associated with markers of hemolysis and total crystalloid use. Samples were collected from 97 patients. From pre-fluid infusion to post-fluid infusion, mean haptoglobin decreased (11.7 ug/ml vs 8.4 ug/ml; p < 0.0001), hemopexin decreased (549 vs 512 µg/ml; p = 0.005), and red cell distribution width (RDW) decreased (15.7 vs 15.6; p = 0.0009). During admission (mean 19.4 days, SD 9.9), all markers of tissue and organ damage, including mean creatinine, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), total bilirubin, AST, and ALT, increased from admission to peak levels (p < 0.0001). On linear regression, fluid volume (ml/kg) of crystalloid infusion positively predicted post-fluid infusion cell-free hemoglobin (r(96) = 0.34, p < 0.0001), free heme (r(96) = 0.36, p < 0.0001), and peak LDH during admission (r(75) = 0.23, p = 0.041), and negatively predicted post-fluid infusion hemopexin (r(96) = - 0.34, p < 0.0001). Unbalanced crystalloids may contribute to hemolysis and endothelial damage in HSCT patients. Alternatives such as buffered crystalloid solutions (PlasmaLyte, Lactated Ringer's) may be worth investigating in this population.

MicroRNA-200b-3p as a biomarker for diagnosis and survival prognosis of multiple organ dysfunction syndrome caused by acute paraquat poisoning.

BACKGROUND: Acute paraquat poisoning-induced multiple organ dysfunction syndrome (MODS) leads to the high mortality. This study aimed to investigate the clinical significance of microRNA-200b-3p (miR-200b-3p), an upstream inhibitor of high-mobility group box 1 (HMGB1), in acute paraquat poisoning patients for the prediction of MODS and survival. METHODS: This study enrolled 80 patients with MODS induced by paraquat and 94 healthy volunteers. The interaction between miR-200b-3p and HMGB1 was identified by luciferase reporter assay. miR-200b-3p levels were measured by quantitative real-time (QRT) PCR. High-mobility group box 1 levels were measured by enzyme-linked immune sorbent assay (ELISA). Receiver operating characteristic analysis was used to evaluate the diagnostic value of miR-200b-3p in screening MODS patients. The relationship between miR-200b-3p and the 28-day survival of MODS patients was evaluated by Kaplan-Meier curves and log-rank test. Cox regression analysis was used to assess the prognostic value of miR-200b-3p. Correlation between miR-200b-3p and HMGB1 was confirmed by Pearson's correlation analysis. RESULTS: miR-200b-3p directly target HMGB1. miR-200b-3p, decreased in MODS patients, had high diagnostic value to screen MODS patients from healthy controls. Additionally, serum miR-200b-3p was decreased in non-survivors, and patients with low miR-200b-3p level had poor 28-day survival. Serum miR-200b-3p could independently predict the survival prognosis. Moreover, serum HMGB1 level was increased in MODS patients, and was negatively correlated with miR-200b-3p level. CONCLUSION: Decreased miR-200b-3p may function as a biomarker for the diagnosis and survival prognosis of MODS patients, and miR-200b-3p may be involved in the progression of acute paraquat-induced MODS via regulating inflammatory responses by targeting HMGB1.

A Fatal Colchicine Ingestion With Antemortem Blood Concentration.

ABSTRACT: Although there are multiple therapeutic uses for colchicine, it is particularly dangerous in the setting of overdose due to an irreversible mechanism of action combined with a narrow therapeutic window. Colchicine is an antimitotic agent that binds tubulin and inhibits microtubule polymerization. This produces a predictable sequence of toxicity beginning with gastrointestinal effects with progression to multiorgan system dysfunction. Unfortunately, there are no specific antidotes for colchicine toxicity after organ injury has occurred, which can lead to tragic consequences. Despite the recognized toxicity, it is exceedingly rare to find a case in the medical literature with a confirmed time of ingestion, amount ingested, data from longitudinal examinations, and laboratory assessments, with a quantitative blood colchicine concentration. We present a case of acute colchicine overdose of 18 mg (approximately 0.25 mg/kg) with subsequent multiorgan failure and death with an antemortem blood colchicine concentration of 14 ng/mL at 18.5 hours after ingestion.

PD-1/PD-L1 inhibitor ameliorates silica-induced pulmonary fibrosis by maintaining systemic immune homeostasis.

Pulmonary fibrosis induced by silica particles is defined as silicosis, which is an incurable disease. The pathogenesis of silicosis is not completely clear, but it's certain that immune system dysfunction is closely related to it. Immune checkpoint inhibitors (ICIs) are emerging immunotherapeutic agents that mainly target adaptive immune cells, and there is abundant evidence that ICIs are of great value in cancer treatment. However, whether these attractive agents can be implemented in silicosis treatment is unclear. In this study, we explored the efficacy of small molecule inhibitors targeted PD-1/PD-L1 and CTLA-4 on silica-induced pulmonary fibrosis in mice. ICIs were injected intraperitoneally into mice that received silica instillation twice a week. The mice were sacrificed 7 and 28 days after the injection. The lungs, spleen, hilar lymph nodes, thymus, and peripheral blood of mice were collected and subjected to histological examination, flow cytometry analysis, and mRNA and protein quantification. Our results demonstrated that silica exposure caused damage to multiple immune organs in mice, leading to an imbalance in systemic immune homeostasis. Specifically, proportions and subtypes of T and B cells were significantly altered, and the expressions of PD-1, PD-L1 and CTLA-4 were abnormal on these cells. Both PD-1/PD-L1 and CTLA-4 inhibitor administration modulated silica-induced immune system disruption, however, only PD-1/PD-L1 signaling inhibition showed significant amelioration of silicosis. Our findings confirmed for the first time the potential value of ICIs for the treatment of silica-induced pulmonary fibrosis, and this may provide new ideas for the treatment of other fibrosis-related diseases.

T cell activation and IFNγ modulate organ dysfunction in LPS-mediated inflammation.

LPS challenge is used to model inflammation-induced organ dysfunction. The effects of T cell activation on LPS-mediated organ dysfunction and immune responses are unknown. We studied these interactions through in vivo administration of anti-CD3ε (CD3) T cell activating antibody and LPS. Mortality in response to high-dose LPS (LPSHi; 600 µg) was 60%; similar mortality was observed with a 10-fold reduction in LPS dose (LPSLo; 60 µg) when administered with CD3 (CD3LPSLo). LPSHi and CD3LPSLo cohorts suffered severe organ dysfunction. CD3LPSLo led to increased IFNγ and IL12p70 produced by T cells and dendritic cells (cDCs) respectively. CD3LPSLo caused cDC expression of CD40 and MHCII and prevented PD1 expression in response to CD3. These interactions led to the generation of CD4 and CD8 cytolytic T cells. CD3LPSLo responded to IFNγ or IL12p40 blockade, in contrast to LPSHi. The combination of TCR activation and LPS (CD3LPSLo) dysregulated T cell activation and increased LPS-associated organ dysfunction and mortality through T cell and cDC interactions.

Effects of real-ambient PM2.5 exposure plus lipopolysaccharide on multiple organ damage in mice.

Background: The toxicological effects of fine particulate matter (PM2.5) on the cardiopulmonary and nervous systems have been studied widely, whereas the study of PM2.5 on systemic toxicity is not in-depth enough. Lipopolysaccharide (LPS) can cause multiple organ damage. The combined effects of co-exposure of PM2.5 plus LPS on the stomach, spleen, intestine, and kidney are still unclear. Purpose: This study was aimed to explore the toxicological effects of co-exposure of PM2.5 and LPS on the different organs of mice. Research Design and Study Sample Using a real-ambient PM2.5 exposure system and an intraperitoneal LPS injection mouse model, we investigated multiple organ damage effects on male BALB/c mice after co-exposure of PM2.5 plus LPS for 23 weeks in Linfen, a city with a high PM2.5 concentration in China. Data Collection: Eosin-hematoxylin staining, ELISA and the biochemical assay analysed the toxicological effects. Results: The pathological tissue injury on the four organs above appeared in mice co-exposed to PM2.5 plus LPS, accompanied by the body weight and stomach organ coefficient abnormality, and significant elevation of pro-inflammatory cytokines levels, oxidative stress in the spleen and kidney, and levels of kidney injury molecule (KIM-1) increase in the kidney. There were tissue differences in the pathological damage and toxicological effects on mice after co-exposure, in which the spleen and kidney were more sensitive to pollutants. In the PM2.5 + LPS group, the superoxide dismutase inhibition and catalase (CAT) activity promotion in the kidney or spleen of mice were significant relative to the PM2.5 group; the CAT and interleukin-6 (IL-6) levels in the spleen were raised considerably compared with the LPS group. Conclusions: These findings suggested the severity and sensitivity of multiple organ injuries in mice in response to PM2.5 plus LPS.

Multi-organ dysfunction as a presentation of calcium channel blocker intoxication.

SummaryWe report the case of a 73-year-old woman who intentionally ingested 400 mg of amlodipine in a suicidal attempt who initially presented with hypotension which persisted despite aggressive therapy with fluid resuscitation, multiple pressor support, high-dose insulin therapy and calcium infusion. Her haemodynamic instability evolved to include bradycardia requiring atropine and transcutaneous pacing. Eventually she required salvage therapy with intravenous lipid emulsion (ILE) therapy . Despite all aggressive therapy, she developed multi-organ failure resulting in death. The literature on high-dose insulin euglycaemic therapy (HIET) and ILE therapy shows mixed results with some showing significant improvement in haemodynamic status. In our case, it had no significant positive impact on the outcome.

Clinical implications of chemotherapeutic agent organ toxicity on perioperative care.

Cancer is the second most common cause of death in the United States and is a challenging disease to treat. The treatment options for various cancers include but are not limited to surgery, radiation, and chemotherapy. The mechanism behind chemotherapy is intended to promote cellular damage to cells that are proliferating uncontrollably. Unfortunately for the recipients, most chemotherapeutic agents cannot differentiate between malignant cells and healthy cells and tissues. Thus, chemotherapy-induced toxicities are often observed in once-healthy organs. These effects can be acute and self-limiting or chronic, appearing long after chemotherapy is completed. Cancer survivors can then present for non-cancer related surgeries later in life, due to this toxicity. Furthermore, the administration of chemotherapeutic agents can profoundly impact the anesthetic management of patients who are undergoing surgery. This review discusses how chemotherapy-induced organ toxicity can occur in multiple organ systems and what drugs should be avoided if prior toxicity exists in these organ systems.

Electronic cigarette aerosol increases the risk of organ dysfunction by enhancing oxidative stress and inflammation.

An electronic cigarette is a rechargeable device that produces an inhaled aerosol containing varying levels of nicotine, and inorganic and organic toxicants and carcinogenic compounds. The aerosol is generated by heating a solution of propylene glycol and glycerin with nicotine and flavoring ingredients at a high temperature. The e-cigarette was developed and marketed as a safer alternative to the regular cigarette which is known to be injurious to human health. However, published studies suggest that the aerosol of e-cigarette can also have adverse health effects. The main objective of this review is to briefly describe some consequences of e-cigarette smoking, and to present data showing that the resulting increased oxidative stress and inflammation are likely to be involved in effecting to lung damage. Other organs are also likely to be affected. The aerosol contains varying amounts of organic and inorganic toxicants as well as carcinogens, which might serve as the source of such deleterious events. In addition, the aerosol also contains nicotine, which is known to be addictive. E-cigarette smoking releases these toxicants into the air leading to inhalation by nonsmokers in residential or work place areas. Unlike regular tobacco smoke, the long-term consequences of direct and secondhand exposure to e-cigarette aerosol have not been extensively studied but based on available data, e-cigarette aerosol should be considered harmful to human health.

Multiple organ failure leading to death after ingestion of Caltha palustris: A case report.

RATIONALE: Studies have previously reported misidentifying Caltha palustris (C. palustris) as Ligularia fischeri and its subsequent ingestion leading to abdominal pain and gastrointestinal symptoms, which are alleviated immediately. Bradycardia and hypotension may persist for several days, and an infusion of dopamine can restore a healthy state without complications. We report a case of C. palustris poisoning with protein-losing enteropathy that has not been reported previously. The patient died of multiple organ failure, and exhibited more severe clinical deterioration than previous cases due to prolonged shock. PATIENT CONCERNS: A 70-year-old woman was admitted to the emergency department (ED) with complaints of epigastric pain, vomiting, and diarrhea after ingestion of a poisonous plant presumed to be C. palustris. The patient presented with bradycardia and hypotension after ED admission, and vasopressor infusion improved bradycardia but not hypotension, while the patient complained of severe epigastric pain. DIAGNOSES: Abdominal computed tomography showed luminal distention and edematous thickening of the entire stomach lining, as well as small and large intestinal wall edema, indicating severe gastritis and enterocolitis. The laboratory test results suggested severe hypoalbuminemia, while the arterial blood gas analyses showed a continuous increase in metabolic acidosis. INTERVENTIONS: As plant poisoning was suspected, activated charcoal was administered to the patient, followed by administration of vasopressors and other conservative therapies. Continuous renal replacement therapy (CRRT) was used for metabolic acidosis of increasing severity. OUTCOMES: Despite the administration of vasopressors and other conservative therapies, the state of shock persisted, and metabolic acidosis did not improve even after CRRT. Ultimately, the patient died of multiple organ failure. LESSONS: For many poisonous wild plants, the precise profile of toxic compounds and mechanisms of action remain to be identified; when there is insufficient literature reporting on suspected plant poisoning, the medical personnel providing the treatment should consider the various side effects that differ from the reported ones and the possibility of more severe clinical progress and poor prognosis.

Cefepime and diclofenac sodium combined treatment-potentiated multiple organ injury: Role of oxidative damage and disrupted lipid metabolism.

Concurrent exposure to antimicrobial and nonsteroidal anti-inflammatory drugs (NSAIDs) is usually inevitable in most infections and postsurgery. Consequently, the present study was designed to assess the intertwining impact of coadministration of cefepime (CP, a wide spectrum antibiotic) and diclofenac sodium (DF, an NSAID) on rat's liver, kidney, and testes. Rats received saline, CP (180 mg/kg/day, IM), DF (10 mg/kg/day, IM), or a combination of CP and DF. After 14 days, CP or DF induced tissue damage expressed by marked biochemical alterations in hepatic and renal function tests. Besides this, disrupted lipid metabolism and testosterone levels along with significant histological changes in hepatic, renal, and testicular tissues were noticed. A significant increase in malondialdehyde and decreases in superoxide dismutase and catalase activities alongside significant upregulated caspase 3 expression in tissues following CP or DF treatment suggested a bearable influence of oxidative stress, lipid peroxidation, and cell death. Accordingly, the simultaneous therapy of CP and DF evoked more obvious tissue damage than their individual treatment. Overall, data concluded that concurrent use of CP and DF in medical practice is a worrisome matter, so it should be done cautiously to avoid synergistic deleterious outcomes.