Resuscitation with macromolecular superoxide dismutase/catalase mimetic polynitroxylated PEGylated hemoglobin offers neuroprotection in guinea pigs after traumatic brain injury combined with hemorrhage shock.

BACKGROUND: Polynitroxylated PEGylated hemoglobin (PNPH, aka SanFlow) possesses superoxide dismutase/catalase mimetic activities that may directly protect the brain from oxidative stress. Stabilization of PNPH with bound carbon monoxide prevents methemoglobin formation during storage and permits it to serve as a carbon monoxide donor. We determined whether small volume transfusion of hyperoncotic PNPH is neuroprotective in a polytrauma model of traumatic brain injury (TBI) plus hemorrhagic shock. Guinea pigs were used because, like humans, they do not synthesize their own ascorbic acid, which is important in reducing methemoglobin. RESULTS: TBI was produced by controlled cortical impact and was followed by 20 mL/kg hemorrhage to a mean arterial pressure (MAP) of 40 mmHg. At 90 min, animals were resuscitated with 20 mL/kg lactated Ringer's solution or 10 mL/kg PNPH. Resuscitation with PNPH significantly augmented the early recovery of MAP after hemorrhagic shock by 10-18 mmHg; whole blood methemoglobin was only 1% higher and carboxyhemoglobin was 2% higher. At 9 days of recovery, unbiased stereology analysis revealed that, compared to animals resuscitated with lactated Ringer's solution, those treated with PNPH had significantly more viable neurons in the hippocampus CA1 + 2 region (59 ± 10% versus 87 ± 18% of sham and naïve mean value) and in the dentate gyrus (70 ± 21% versus 96 ± 24%; n = 12 per group). CONCLUSION: PNPH may serve as a small-volume resuscitation fluid for polytrauma involving TBI and hemorrhagic shock. The neuroprotection afforded by PNPH seen in other species was sustained in a species without endogenous ascorbic acid synthesis, thereby supporting potential translatability for human use.

The Relationship between Functional Outcome and Prehospital Time Interval in Patients with Cerebral Infarction.

BACKGROUND: When symptoms of cerebral infarction are recognized in a patient, he or she should be transported to a hospital and should be started on the appropriate treatments. The effectiveness of delayed treatment of cerebral infarction with respect to the initial diagnosis or perception of the disease is still unclear. METHODS: We retrospectively investigated whether the functional outcomes would improve if patients with cerebral infarction were transported to the hospital with minimum delay. One-hundred twenty-two patients who were transported to Mishuku Hospital from January 2012 to August 2015 were included. We conducted multiple regression analyses. The criterion variable included the BI at discharge, and the explanatory variables were age, sex, days of hospital stay, the Barthel Index (BI) on admission, time from symptom onset to hospital arrival, time from emergency medical service perception to hospital arrival, recombinant tissue plasminogen activator (rt-PA) treatment, and the occluded artery type. RESULTS: In all 122 cases, the BI at the time of discharge was not related to onset time (P = .453) but was significantly related to perception time (P = .026). BI scores at discharge were high for young patients (P = .002) and for patients with short hospital stays (P <.001). In the rt-PA group (52 cases), BI scores at discharge were also high when the perception time was short (P = .036). CONCLUSIONS: A short interval between perception and hospital arrival improves the functional outcomes for patients with cerebral infarction. Thus, patients with cerebral infarctions must be treated with minimal delay after diagnosis of the condition.

[Metastatic brain tumor from esophageal carcinoma:a report of three cases].

A metastatic brain tumor originating from esophageal carcinoma is very rare, accounting for only about 2% of all intracranial metastatic tumors. We review three cases of metastatic brain tumor from esophageal carcinoma and present one interesting case. A 60-year-old man was referred to our hospital with aphasia, 3 years after surgery for esophageal carcinoma. Magnetic resonance imaging demonstrated a 7-cm mass lesion with a cystic component in the left temporal lobe. Tumor resection was performed and an Ommaya reservoir system was placed. Histological analysis indicated squamous cell carcinoma, and metastatic brain tumor from esophageal carcinoma was diagnosed. After surgery, the cystic component was collapsed by drainage through the Ommaya reservoir, and cyberknife therapy was performed as an adjunctive therapy. Regrowth of the cystic component and exacerbation of cognitive dysfunction were identified 2 months later, so aspiration of cyst fluid through the Ommaya reservoir was continued. However, the cystic component regrew 5 months after the operation, and the patient died 1 month later. Metastatic brain tumors from primary esophageal carcinoma often have a cystic component, which makes treatment difficult. Control of cyst growth by aspiration using the Ommaya reservoir is effective for improvement of functional prognosis in such patients.

Anorexia Nervosa With Intermittent Fever Due to Diet-Induced Thermogenesis: A Case Report.

Diet-induced thermogenesis, influenced primarily by protein intake, generates energy from food. Herein, we present the case of anorexia nervosa in a 30-year-old woman, who developed intermittent fever while transitioning from continuous to intermittent tube feeding, with an increase in protein intake. Extensive investigations ruled out infection- or drug-related causes, indicating that intermittent fever resulted from diet-induced thermogenesis due to high protein administration. Recognizing the potential for diet-induced thermogenesis in cases of fever during tube feeding is crucial to avoid unnecessary antibiotic use and prevent the discontinuation of essential medications.

Diagnostic pitfalls associated with a large true posterior communicating artery aneurysm: a case report.

True posterior communicating artery (PCoA) aneurysm is an aneurysm that originates from the PCoA, and large or giant true PCoA aneurysms are rare. We report a case of a large true PCoA aneurysm successfully clipped after anterior clinoidectomy and discuss the diagnostic pitfalls associated with this rare clinical entity.

Delayed diagnosis of severe diabetic ketoacidosis associated with a sodium-glucose cotransporter 2 inhibitor: a case report.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are used to treat patients with type 2 diabetes mellitus but may induce diabetic ketoacidosis (DKA). Owing to their pharmacological mechanisms, they cause a different pathogenesis to that of typical DKA and require special attention in terms of blood glucose concentrations and acidosis. We describe a case of prolonged acidosis because of failure to immediately discover the use of an SGLT2 inhibitor. Compared with typical DKA, SGLT2 inhibitor-associated DKA requires earlier and longer glucose supplementation. SGLT2 inhibitors are specific aetiological factors in DKA, and their use should be suspected when the patient presents with mild hyperglycaemia or prolonged acidosis.

Case report: Severe respiratory failure caused by licorice.

Licorice, one of the most commonly used herbs, can cause hypokalemia, metabolic alkalosis, and apparent mineralocorticoid excess, also known as pseudoaldosteronism. Herein, we present a case of diaphragmatic dysfunction caused by licorice administration. An 80-year-old woman who had been taking dietary supplements and following a restricted diet for approximately 6 months was brought to the emergency department with impaired consciousness. Chronic respiratory acidosis was observed, and hypertension and hypokalemia became more prominent during hospitalization. History revealed that she was taking herbal medicines containing licorice. Based on the results of hormone tests, the patient was diagnosed with pseudoaldosteronism. Chest radiography and pulmonary function tests confirmed the clinical diagnosis of diaphragmatic dysfunction. The metabolic alkalosis resulting from licorice administration may have contributed to the impairment of the respiratory muscles. This case suggests that caution should be exercised when using licorice in patients with preexisting health or medical issues such as advanced age, malnutrition, and electrolyte imbalance.

Invasive candidiasis presenting bronchiectatic cavity as chest radiological findings: A case report.

Invasive candidiasis is rare but is associated with high mortality in immunocompromised or critically ill patients. Here, we present a case of a 55-year-old man with untreated diabetes who was diagnosed with coronavirus disease 2019 and subsequently developed invasive candidiasis. The patient presented with fever, tachycardia, and tachypnea. Chest computed tomography revealed multiple consolidations mainly distributed around the bronchovascular bundles with bronchiectatic cavity formation, which initially raised suspicion for invasive pulmonary aspergillosis. However, subsequent testing confirmed Candida albicans infection; hence, we changed the antifungal agents effective for invasive candidiasis. This improved the patient's respiratory status, and he was then successfully weaned from mechanical ventilation. This case report highlights the importance of considering invasive candidiasis in the differential diagnosis of patients with bronchiectatic cavities on chest computed tomography, particularly in immunocompromised or critically ill patients with risk factors for invasive candidiasis.

Characteristics of the patients consulted with emergency medicine physicians at a large-scale COVID-19 vaccination center: Prospective observational study.

OBJECTIVE: We aimed to clarify the characteristics of patients consulted by the medical staff with emergency medicine (EM) physicians after vaccination and EM physicians transferred to an outside hospital. DESIGN: The Japanese Self-Defense Force established a large-scale coronavirus disease 2019 (COVID-19) vaccination center. Overall, 1,306,928 citizens received the Moderna vaccine, which targeted the first and second vaccinations between May 24, 2021 and November 30, 2021. EM physicians were always available in the emergency room (ER). The medical staff could consult the patients with EM physicians; however, the criteria were ambiguous. We conducted signal detection analysis on the patients who experienced adverse events to detect characteristics. RESULTS: Of the 3,312 patients experienced adverse events after vaccination, the medical staff consulted 344 with EM physicians. The patients whose respiratory rate and systolic blood pressure (BP) were more than 18 per minute and 162 mmHg, respectively, were considerably consulted. In addition, the patients whose systolic BP was more than 186.5 mmHg were transferred to an outside hospital. No patients were seriously ill or died after being transferred to an outside hospital. CONCLUSIONS: The medical staff consulted the patients with a high respiratory rate or BP with EM physicians. In addition to BP, the respiratory rate would also be necessary as a finding that suggests a patient's severity after vaccination. Therefore, it appears safer that EM physicians are always available to ensure the recipients' safety when running a new large-scale vaccination center against unknown diseases, such as COVID-19.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunization Stress-Related Responses With COVID-19 mRNA Vaccine.

BACKGROUND: With the implementation of mass vaccination campaigns against COVID-19, the safety of vaccine needs to be evaluated. OBJECTIVE: We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunization stress-related responses (ISRR) with the Moderna COVID-19 vaccine. METHODS: This nested case-control study included recipients who received the Moderna vaccine at a mass vaccination center, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1 case: 4 controls) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR. RESULTS: Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2478 recipients (cases 2) showed 318 events of IHSR and 2558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and a history of allergy; for ISRR, the risk factors were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex. CONCLUSION: In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should be aware of the occurrence of ISRR. Although recipients with risk factors are associated with slightly increased risks of IHSR and ISRR, this is not of sufficient magnitude to warrant special measures regarding their vaccination.

Effects of Selective Serotonin Reuptake Inhibitors on Depression-Like Behavior in a Laser-Induced Shock Wave Model.

Primary blast injury can result in depression-like behavior in the long-term. However, the effects of the selective serotonin reuptake inhibitor (SSRI) on the depression induced by mild blast traumatic brain injury (bTBI) in the long-term remain unclear. We generated a mouse model of mild bTBI using laser-induced shock wave (LISW) and administered an SSRI to mice by oral gavage for 14 days after LISW exposure. This study aimed to investigate the mechanisms of SSRI-mediated alleviation of depression-like behavior induced by mild bTBI. Animals were divided into three groups: sham, LISW-Vehicle, and LISW-SSRI. LISW was applied to the head of anesthetized mice at 0.5 J/cm2. Twenty-eight days after the LISW, mice in the LISW-SSRI group exhibited reduced depression-like behavior, a significant increase in the number of cells co-stained for 5-bromo-2'-deoxyuridine (Brd-U) and doublecortin (DCX) in the dentate gyrus (DG) as well as increased brain-derived neurotrophic factor (BDNF) and serotonin levels in the hippocampus compared to the sham and LISW-Vehicle groups. Additionally, levels of phosphorylated cAMP response element binding protein (pCREB) in the DG were significantly decreased in the LISW-Vehicle group compared to that in the sham group. Importantly, pCREB levels were not significantly different between LISW-SSRI and sham groups suggesting that SSRI treatment may limit the downregulation of pCREB induced by mild bTBI. In conclusion, recovery from depression-like behavior after mild bTBI may be mediated by hippocampal neurogenesis induced by increased BDNF and serotonin levels as well as the inhibition of pCREB downregulation in the hippocampus.

A novel mouse model of mild traumatic brain injury using laser-induced shock waves.

Blast-induced mild traumatic brain injury (mild bTBI) has been a frequent battlefield injury in soldiers during the conflicts in Iraq and Afghanistan. Understanding the pathophysiology and determining effective treatments for mild bTBI has become an international problem in the field of neurotrauma research. Contributing to this problem is a lack of an experimental model that accurately mimics the characteristics of mild bTBI. To date, the "mild'' versions of common experimental models of TBI have simply been less severe degrees of traumatic injury; these animals do not necessarily exhibit the clinical characteristics of mild bTBI seen in humans. Therefore, our first objective was to develop a highly controlled mouse model of bTBI using laser-induced shockwaves (LISWs). We established the parameters necessary to cause a reproducible injury of very mild severity, the most important feature seen in clinical practice. We defined very mild bTBI as having no traumatic change on the head visible to the naked eye after the insult was applied using very mild shockwaves to the heads of mice. Our very mild bTBI mouse model exhibited neurobehavioral changes in the chronic phase, such as cognitive impairment and depression-like behavior. We also observed an increase in 5-bromo-2'-deoxyuridine-positive, proliferating cells in the dentate gyrus during the acute phase and a subsequent decrease during the chronic phase. This model appears to be an accurate representation of the damage occurring in actual mild bTBI patients. We also found that an increase in cell proliferation in the dentate gyrus during the acute phase is the most prominent feature after a TBI.

Poor prognostic factors in elderly patients aged 75 years old or older with mild traumatic brain injury.

The incidence of traumatic brain injury (TBI) in elderly patients is increasing. We retrospectively investigated the poor prognostic factors at discharge in elderly patients aged 75 years or older admitted to hospital with mild TBI. We continuously enrolled 83 patients aged 75 years or older with mild TBI, in a private general Japanese hospital. The Glasgow Coma Scale scores on admission were within the range of 13-15. Patients with good recovery or moderate disability were included in the "good outcome" group, and those with severe disability, in a persistent vegetative state, or who died were included in the "poor outcome" group. We performed statistical analyses using 8 parameters. We conducted a univariate analysis on each item. Next, we conducted a logistic regression analysis on variables where the p < 0.20 in the univariate analysis. Elderly patients had a poor prognosis when they had dementia (odds ratio [OR]: 20.357, 95% confidence interval [CI]: 2.075-199.683, p = 0.010), cancer (OR: 14.005, 95% CI: 1.262-154.444, p = 0.032), or a history of antithrombotic therapy before admission (OR: 6.673, 95% CI: 1.072-41.526, p = 0.042). When elderly patients aged 75 years or older with mild TBI have the 3 poor prognostic factors of dementia, cancer, or a history of antithrombotic therapy, their outcomes might be worse compared to other elderly patients. Elderly patients who have these factors should be carefully managed.

Fulminant pseudomembranous enterocolitis caused by Klebsiella oxytoca: an autopsy case report.

CASE: We describe a rare case of antibiotic-associated fulminant pseudomembranous enterocolitis caused by Klebsiella oxytoca. A 79-year-old man with a history of antibiotic therapy was admitted to our emergency department, complaining of consciousness disturbance. Initially, we suspected septic shock and diabetic ketoacidosis caused by intestinal infection. Although we administered sufficient extracellular fluid, his blood pressure was not elevated and his abdomen gradually swelled. OUTCOME: The patient died of shock and abdominal compartment syndrome. Autopsy revealed widespread jejunal necrosis in conjunction with colitis, suggesting fulminant pseudomembranous enterocolitis caused by K. oxytoca infection. CONCLUSION: As the clinical features of pseudomembranous enterocolitis caused by K. oxytoca resemble the features of colitis caused by Clostridium difficile, conservative therapy is applied first. However, fulminant pseudomembranous enterocolitis is a lethal disease, necessitating early operation for resection of the necrotic lesion. This report highlights the need for better surgical criteria at an early stage.

IgG4-Related Intracranial Hypertrophic Pachymeningitis : A Case Report and Review of the Literature.

Hypertrophic pachymeningitis is an uncommon disorder that causes a localized or diffuse thickening of the dura mater. Recently, the possibility that IgG4-related sclerosing disease may underlie some cases of intracranial hypertrophic pachymeningitis has been suggested. We herein report the tenth case of IgG4-related intracranial hypertrophic pachymeningitis and review the previous literature. A 45-year-old male presented with left-sided focal seizures with generalization. Magnetic resonance imaging (MRI) revealed a diffuse thickening and enhancement of the right convexity dura matter and falx with focal nodularity. The surgically resected specimens exhibited the proliferation of fibroblast-like spindle cells and an infiltration of mononuclear cells, including predominantly plasma cells. The ratio of IgG4-positive plasma cells to the overall IgG-positive cells was 45% in the area containing the highest infiltration of plasma cells. On the basis of the above findings, IgG4-related sclerosing disease arising from the dura mater was suspected. IgG4-related sclerosing disease should be added to the pachymeningitis spectrum.