Multisystem inflammatory syndrome and lymphohistiocytic myocarditis after Covid-19 vaccine in a middle-aged woman.

We describe a 51-year-old otherwise healthy woman hospitalized for hypotension, fever, and weakness 4 days after the second-dose Covid-19 mRNA vaccine. Elevated inflammatory markers, natriuretic peptide levels and troponin levels, and slightly reduced left ventricular ejection fraction of 50% were noted. We also found the multiple organ damage, including mucocutaneous, gastrointestinal, and neurologic systems. In addition, we revealed the positive results for anti-nucleocapsid SARS-CoV-2 IgG, albeit negative for SARS-CoV-2 polymerase chain reaction testing, suggesting the prior asymptomatic Covid-19 infection. We finally diagnosed her as multisystem inflammatory syndrome after vaccination. Of note, we obtained myocardial specimen from the patients and demonstrated the lymphohistiocytic myocarditis, which is a rare form of myocarditis.

Diabetic ketoacidosis after the second dose of SARS-CoV-2 mRNA vaccination in a patient with pembrolizumab-induced fulminant type 1 diabetes.

We report a case of 77-year-old woman with fulminant type 1 diabetes (T1D) who developed diabetic ketoacidosis (DKA) after the second dose of SARS-CoV-2 vaccine tozinameran. The patient had been diagnosed as having T1D associated with an immune-related adverse event caused by pembrolizumab at the age of 75. After the second dose of tozinameran, she developed DKA and needed intravenous insulin infusion and mechanical ventilation. Although the direct causal relationship between the vaccination and the DKA episode could not be proven in this case, published literatures had suggested the possibility of developing DKA after SARS-CoV-2 vaccination in patients with T1D. As the magnitude of the risk of the combination of the known adverse drug reactions of SARS-CoV-2 mRNA vaccine and T1D patients' vulnerability to sick-day conditions is not yet thoroughly assessed, future studies such as a non-interventional study with adequate sample size would be required to address this issue.

Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital.

BACKGROUND: Caffeine (0.1 g) is used as a central nervous system stimulant and as a nontoxic phenotyping probe for cytochrome P450 1A2. However, an increasing number of suicide attempts by caffeine overdose have been recently reported. CASE PRESENTATION: A 25-year-old woman (body weight, 43 kg) who intentionally took an overdose of 5.9 g caffeine as a suicide attempt was emergently admitted to Kyoto Medical Center. The plasma concentrations of caffeine and its primary metabolite, N-demethylated paraxanthine, in the current case were 100 and 7.3 µg/mL, 81 and 9.9 µg/mL, 63 and 12 µg/mL, and 21 and 14 µg/mL, at 12, 20, 30, and 56 h after oral overdose, respectively. The observed apparent terminal elimination half-life of caffeine during days 1 and 2 of hospitalization was 27 h, which is several times longer than the reported normal value. This finding implied nonlinearity of caffeine pharmacokinetics over such a wide dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic model founded on a normal dose of 100 mg. Low serum potassium levels (2.9 and 3.5 mM) on days 1 and 2 may have been caused by the caffeine overdose in the current case. CONCLUSIONS: The patient underwent infusion with bicarbonate Ringer's solution and potassium chloride and was discharged on the third day of hospitalization despite taking a potentially lethal dose of caffeine. The virtual plasma exposures of caffeine estimated using the current simplified PBPK model were higher than the measured values. The present results based on drug monitoring data and additional pharmacokinetic predictions could serve as a useful guide in cases of caffeine overdose.

Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital.

BACKGROUND: Loxoprofen is a propionic acid derivative and is the most widely prescribed non-steroidal anti-inflammatory drug in Japan. Loxoprofen is generally considered to be relatively nontoxic. CASE PRESENTATION: A 33-year-old man (body weight, 55 kg) who intentionally took an overdose of 100 tablets of loxoprofen (6000 mg) as a suicide attempt was emergently admitted to Kyoto Medical Center. On arrival, the patient was suffering disorders of consciousness. His plasma concentrations of loxoprofen and its reduced trans-alcohol metabolite were 52 and 24 µg/mL, 3.7 and 2.3 µg/mL, 0.81 and 0.54 µg/mL, and 0.015 and 0.011 µg/mL, respectively, at 4, 26, 50, and 121 h after the oral overdose. The observed apparent terminal elimination half-life of loxoprofen during days 1 and 2 of hospitalization was in the range 6-12 h, which is several times longer than the reported normal value. This finding implied nonlinearity of loxoprofen pharmacokinetics over the current 100-fold dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic (PBPK) model founded on data from a normal dose of 60 mg. The reasons for the delayed eliminations from plasma of loxoprofen and its trans-alcohol metabolite in this case are uncertain, but slight renal impairment (low eGFR values) developed on the second and third hospital days and could be a causal factor. CONCLUSIONS: Because the patient's level of consciousness had gradually improved, he was discharged on the fourth day of hospitalization. The virtual plasma exposures of loxoprofen and its reduced trans-alcohol metabolite estimated using the current simplified PBPK model were lower than the measured values in the overdose case. The present results based on drug monitoring data and pharmacokinetic predictions could serve as a useful guide in cases of loxoprofen overdose.

Pharmacokinetic modeling of over-the-counter drug diphenhydramine self-administered in overdoses in Japanese patients admitted to hospital.

BACKGROUND: Although the over-the-counter H1 receptor antagonist diphenhydramine is not a common drug of abuse, it was recently recognized as one of the substances causing acute poisoning in patients attempting suicide that led to admissions to our hospital emergency room. CASE PRESENTATION: Two patients [women aged 21 and 27 years (cases 1 and 2)] were emergently admitted after intentionally taking overdoses of 900 and 1200 mg diphenhydramine, respectively. The plasma diphenhydramine concentrations in case 1 were 977 and 425 ng/mL at 2.5 and 11.5 h after single oral overdose, and those in case 2 were 1320 and 475 ng/mL at 3 and 18 h after administration, respectively. We set up a simplified physiologically based pharmacokinetic (PBPK) model that was established using the reported pharmacokinetic data for a microdose of diphenhydramine. The two virtual plasma concentrations and the area under the curve (AUC) values extrapolated using the PBPK model were consistent with the observed overdose data. This finding implied linearity of pharmacokinetics over a wide dosage range for diphenhydramine. CONCLUSIONS: The determined plasma concentrations of diphenhydramine of around 1000 ng/mL at ~ 3 h after orally administered overdoses in cases 1 and 2 may not have been high enough to cause hepatic impairment because levels of aspartate aminotransferase and alanine aminotransferase were normal; however, there was an increase in total bilirubin in case 1. Nonetheless, high virtual liver exposures of diphenhydramine were estimated by the current PBPK model. The present results based on drug monitoring data and pharmacokinetic predictions could serve as a useful guide when setting the duration of treatment in cases of diphenhydramine overdose.

Interleukin-18 levels and mouse Leydig cell apoptosis during lipopolysaccharide-induced acute inflammatory conditions.

Interleukin (IL)-18 is an inflammasome-mediated cytokine produced by germ cells, Leydig cells, and resident macrophages that is indispensable in the maintenance of homeostasis in the testis. We previously demonstrated that endogenous IL-18 induces testicular germ cell apoptosis during acute inflammation when plasma IL-18 levels are very high. However, the impact of acute inflammation and IL-18 on Leydig cells remained unclear. TM3 cells, a mouse Leydig cell line, and RAW264.7 cells, a mouse macrophage cell line, were stimulated with lipopolysaccharide (LPS) or recombinant IL-18 (rIL-18). We assessed the expression of inflammatory cytokines, caspase cleavage, and markers of apoptotic pathways. In Leydig cells, caspase 3 cleavage was increased and death-receptor-mediated apoptotic pathways were activated after LPS stimulation. However, LPS stimulation did not increase IL-18 expression in the Leydig cell line. When high-dose rIL-18 was administered to the Leydig cell line to mimic levels seem after inflammation, rIL-18 upregulated Tnf-α mRNA, Fadd mRNA, and Fas protein, promoted cleavage of caspase-8 and caspase-3, and induced apoptosis. Low-dose rIL-18 did not stimulate apoptosis. To determine if the high level of IL-18 seen in the testes after inflammation was derived from immune cells, we examined IL-18 protein expression in a macrophage cell line, RAW264.7. In contrast to the TM3 cells, IL-18 was significantly increased in RAW264.7 cells after LPS stimulation. These results suggest that high-dose IL-18 derived from macrophages is harmful to Leydig cells. Reducing the overexpression of IL-18 could be a new therapeutic approach to prevent Leydig cell apoptosis as a result of acute inflammation.

Cerebral oxygenation monitoring during resuscitation by emergency medical technicians: a prospective multicenter observational study.

AIM: To assess the feasibility and predictive ability of regional cerebral oxygen saturation monitoring during cardiopulmonary resuscitation by emergency medical technicians. METHODS: This prospective observational study included 33 cardiac arrest patients who received cardiopulmonary resuscitation in a prehospital setting. Patients were connected to a near-infrared spectrometer through two disposable probes immediately after entering the ambulance. The monitor, which showed regional cerebral oxygen saturation readings, was obscured by covering it with a sheet of paper. Regional cerebral oxygen saturation was measured continuously until hospital arrival. Outcome variables included the prehospital return of spontaneous circulation, survival to hospital admission, and survival at 90 days. RESULTS: For patients who survived >90 days after hospital admission (n = 2), the mean regional cerebral oxygen saturation values upon ambulance and hospital arrival were 24% and 60%, respectively; for patients who did not survive (n = 31), the mean regional cerebral oxygen saturation values were 15% and 17%, respectively. Regional cerebral oxygen saturation values increased to a greater extent between ambulance arrival and hospital arrival in patients who survived >90 days (median, 36%; interquartile range, 32-40%) than in those who did not survive (0; 0-6%; P = 0.07). Additionally, regional cerebral oxygen saturation values were not related to the prehospital return of spontaneous circulation or survival to hospital admission. CONCLUSION: Regional cerebral oxygen saturation could be monitored during resuscitation by emergency medical technicians, and it can be used during physiological monitor-guided cardiopulmonary resuscitation.

Verbal Communication of an Orally Intubated Patient in the Intensive Care Unit: A Case Report.

BACKGROUND: Effective interaction with orally intubated patients is important for critical care rehabilitation. An electrolarynx (EL) has reportedly proven useful for facilitating verbal communication during oral intubation. The EL allows patients to express their wishes instantly. Nevertheless, this method is not commonly applied, probably because articulation is often unsatisfactory. Here, we report a case of successful EL-based communication during early mobilization and describe the key factors involved in this success. CASE: An 82-year-old man, who was intubated and undergoing mechanical ventilation for the treatment of acute respiratory failure caused by severe pneumonia, was referred to the rehabilitation department for early mobilization. The patient tried to speak during the spontaneous awakening trials and breathing trials for weaning off mechanical ventilation. However, he was frustrated by communication difficulties and consequently exhibited negative behavior toward physical therapy. We attempted to use an EL to facilitate communication, but initially the patient failed to achieve intelligible articulation. We eventually established that the intubation tube should be located at the corner of the mouth to minimize the restriction of tongue movement. Intelligible sounds were recognized and successful communication between the patient and staff was subsequently achieved. DISCUSSION: The use of an EL is worthy of consideration during early mobilization of orally intubated patients. To achieve successful communication with an EL, both patient selection (Richmond Agitation-Sedation Scale score of 0 or -1) and the proper placement of the intubation tube are necessary to ensure intelligible articulation.

Different Patterns in Abdominal Stab Wound in the Self-Inflicted and Assaulted Patients: An Observational Analysis of Single Center Experience.

Patterns of penetrating abdominal stab wounds (ASW) may be different according to the mechanism of injury. The purpose of this study was to review and characterize penetrating abdominal stab wounds in self-inflicted wound patients and assaulted patients. We retrospectively analyzed patients with ASW who were admitted to our emergency department from 2007 to 2015. The patients were divided into two groups: self-inflicted wound group and assaulted group. There were 46 stabbing cases in 45 different patients (25 males, 21 females; average age 47 y, range 21 to 85 y). Thirty-three patients were in the self-inflicted wound group and 13 patients were in the assaulted group. Although injury sites were concentrated around the periumbilical and epigastric regions in the self-inflicted wound group, the left lateral abdomen was a favorite site in the assaulted group. The peritoneum was violated in the 17 patients in the self-inflicted wound group and 11 patients in the assaulted group. Both the self-inflicted wound group and assaulted group included patients with previous psychological disorders (28 and 5 patients, respectively). The mean Revised Trauma Score, Probability of Survival, Injury Severity Score and the Acute Physiology and Chronic Health Evaluation II scores were not significantly different between the groups although the Injury Severity Score tended to be higher in the assaulted group. The rate of the peritoneal violation was significantly higher in the assaulted group than in the self-inflicted wound group. We also should be aware of more likelihood of patients with psychological disorders among those with assault wounds.

IL18 production and IL18 promoter polymorphisms correlate with mortality in ICU patients.

BACKGROUND: Single nucleotide polymorphisms in the promoter of interleukin (IL)-18 (-607C/A and -137G/C) may affect the clinical course of inflammatory diseases. This study examined the relationship between the plasma IL18 levels, IL18 promoter polymorphism, and outcomes in the intensive care unit (ICU) setting. PATIENTS AND METHODS: Plasma IL18 levels, IL18 promoter genotype, clinical variables, including APACHE II score, and mortality were examined in 70 ICU patients. RESULTS: Plasma IL18 levels were significantly higher in patients who did not survive the ICU stay than in patients who survived, and were correlated with APACHE II score. When examined by IL18 promoter genotype, only patients with the -607CA genotype exhibited differences in IL18 expression between survivors and non-survivors. CONCLUSION: Plasma IL18 levels may predict outcome in patients with sepsis. IL18 promoter polymorphism, especially at -607, may increase IL18 production in some patients and might be useful in predicting the outcome of patients with sepsis in the ICU.

Supplementation of parenteral nutrition with fish oil attenuates acute lung injury in a rat model.

Fish oil rich in n-3 polyunsaturated fatty acids has diverse immunomodulatory properties and attenuates acute lung injury when administered in enternal nutrition. However, enteral nutrition is not always feasible. Therefore, we investigated the ability of parenteral nutrition supplemented with fish oil to ameliorate acute lung injury. Rats were infused with parenteral nutrition solutions (without lipids, with soybean oil, or with soybean oil and fish oil) for three days. Lipopolysaccharide (15 mg/kg) was then administered intratracheally to induce acute lung injury, characterized by impaired lung function, polymorphonuclear leukocyte recruitment, parenchymal tissue damage, and upregulation of mRNAs for inflammatory mediators. Administration of parenteral nutrition supplemented with fish oil prior to lung insult improved gas exchange and inhibited neutrophil recruitment and upregulation of mRNAs for inflammatory mediators. Parenteral nutrition supplemented with fish oil also prolonged survival. To investigate the underlying mechanisms, leukotriene B4 and leukotriene B5 secretion was measured in neutrophils from the peritoneal cavity. The neutrophils from rats treated with fish oil-rich parenteral nutrition released significantly more leukotriene B5, an anti-inflammatory eicosanoid, than neutrophils isolated from rats given standard parenteral nutrition. Parenteral nutrition with fish oil significantly reduced lipopolysaccharide-induced lung injury in rats in part by promoting the synthesis of anti-inflammatory eicosanoids.

Application of a first impression triage in the Japan railway west disaster.

On April 25, 2005, a Japanese express train derailed into a building, resulting in 107 deaths and 549 injuries. We used "First Impression Triage (FIT)", our new triage strategy based on general inspection and palpation without counting pulse/respiratory rates, and determined the feasibility of FIT in the chaotic situation of treating a large number of injured people in a brief time period. The subjects included 39 patients who required hospitalization among 113 victims transferred to our hospital. After initial assessment with FIT by an emergency physician, patients were retrospectively reassessed with the preexisting the modified Simple Triage and Rapid Treatment (START) methodology, based on Injury Severity Score, probability of survival, and ICU stay. FIT resulted in shorter waiting time for triage. FIT designations comprised 11 red (immediate), 28 yellow (delayed), while START assigned six to red and 32 to yellow. There were no statistical differences between FIT and START in the accuracy rate calculated by means of probability of survival and ICU stay. Overall validity and reliability of FIT determined by outcome assessment were similar to those of START. FIT would be a simple and accurate technique to quickly triage a large number of patients.

Successful treatment of a 14-year-old patient with intestinal malrotation with laparoscopic Ladd procedure: case report and literature review.

Midgut malrotation is an anomaly of intestinal rotation that occurs during fetal development and usually presents in the neonatal period. We present a rare case of malrotation in a 14-year-old patient who presented with cramping, generalized right abdominal pain, and vomiting for a duration of one day. A computed tomography abdominal scan and upper gastrointestinal contrast studies showed malrotation of the small bowel without volvulus. Laparoscopy revealed typical Ladd's bands and a distended flabby third and fourth duodenal portion extrinsically obstructing the misplaced duodeno-jejunal junction. The Ladd procedure, including widening of the mesenteric base and appendectomy, was performed. Symptoms completely resolved in a half-year follow up period. Patients with midgut malrotation may present with vague abdominal pain, intestinal obstruction, or intestinal ischemia. The laparoscopic Ladd procedure is feasible and safe, and it appears to be as effective as the standard open Ladd procedure in the diagnosis and treatment of teenage or adult patients with intestinal malrotation.

The effects of n-3 polyunsaturated fatty acid-rich total parenteral nutrition on neutrophil apoptosis in a rat endotoxemia.

Although recruited neutrophils function as first-line defense to remove bacteria, delayed apoptosis is implicated in persistent inflammation leading to organ injury. Leukotrien B4, n-6 polyunsaturated fatty acids (PUFAs) product, is one of the mediators that delay neutrophil apoptosis. The mechanism of the beneficial effects of supplementation of fish oil-based long-chain n-3 PUFAs in parenteral nutrition for critically ill patients has not been fully understood. One possible mechanism is the less inflammatory n-3 PUFAs products can compete with proinflammatory n-6 PUFAs products for access to the enzymes. The aim of this study was to determine whether n-3 PUFA rich parenteral nutrition may alter the composition of fatty acids in the neutrophil membrane and restore delay of neutrophil apoptosis during endotoxin-induced systemic inflammation in rats. The animals in group 1 were treated with 20% Hicaliq NC-N in Neoparen-2 for three days. The animals in group 2 (referred to as n-6 PUFA-rich parenteral nutrition) were given parenteral nutrition solutions containing 20% soybean oil in Neoparen-2 (n-6/n-3 = 10). The animals in group 3 (referred to as n-3 PUFA-rich parenteral nutrition) were administered parenteral nutrition consisting of 10% soybean oil and 10% fish oil emulsion (n-6/n-3 = 1.3). The n-3/n-6 ratio of the neutrophil membrane was significantly increased in group 3 and was associated with restored lipopolysaccharide-delayed-apoptosis of neutrophils in bone marrow cells and increased production of leukotriene B5 from peritoneal neutrophils stimulated by lipopolysaccharide. Our preliminary results showed that n-3 PUFA-rich parenteral nutrition regulated neutrophil apoptosis and prevented synthesis of pro-inflammatory eicosanoids, explaining the protective effects seen in the clinical setting.

A secure "double-check" technique of bedside post pyloric feeding tube placement using transnasal endoscopy.

Enteral feeding has become an important means of providing nutritional support to seriously ill patients. Placement of the feeding tube through the pyloric ring and past the ligament of Treitz into the proximal jejunum is critical to reduce the risk of gastroesophageal regurgitation and microaspiration. We started utilizing transnasal endoscopy for intestinal feeding tube placement, placing enteral tubes for 40 patients between March 2008 and February 2009. Although we achieved a high success rate comparable to previous reports, we experienced several cases of failure, which was corrected with repeated endoscopy. Based on these experiences, we modified our method by adding a "double-check" transnasal endoscopy through the other nasal passage. After April 2010, we have placed the feeding tube by "double-check" method for all patients (more than 40 patients) who required transnasal endoscopic feeding tube placement. We have not experienced any misplacement in all these patients after 24 h later with 100% successful rate since the introduction of "double-check" procedure. We describe our experience with "double-check" transnasal endoscopic feeding tube placement, which we found to be a helpful adjunct, for patients in intensive care unit.

[A case of cardiac arrests before and after emergent exploratory laparotomy for panperitonitis].

We report a case of cardiac arrest before and after emergent exploratory laparotomy for panperitonitis in an 84-year-old woman with a history of hypertension, gastric ulcer, uterine myoma and dementia. She complained of lower abdominal pain, and suffered from septic shock and DIC. The first cardiac arrest occurred after anesthesia induction. Following resuscitation, a left hemicolectomy and colostomy were performed. The second cardiac arrest occurred immediately after the operation. Cardiac arrest in this case may have been due to preexisting cardiac dysfunction enhanced by septic shock. Prompt preoperative evaluation of cardiac function is necessary for successful circulatory management during anesthesia induction for surgical patients in septic shock.