Assessment of the prognosis, frequency, and isolated bacteria in ventilator-associated pneumonia among patients with severe coronavirus disease 2019 pneumonia: A single-center retrospective observational study.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) due to severe coronavirus disease 2019 (COVID-19) pneumonia is associated with a high incidence of ventilator-associated pneumonia (VAP). We aimed to evaluate the epidemiology of VAP associated with severe COVID-19 pneumonia. METHODS: This retrospective observational study recruited patients with COVID-19-associated ARDS admitted to our center from April 1, 2020, to September 30, 2021. The primary outcome was the survival-to-discharge rate. The secondary outcomes were the VAP rate, time to VAP, length of ICU stay, length of ventilator support, and isolated bacteria. RESULTS: Sixty-eight patients were included in this study; 23 developed VAP. The survival-to-discharge rate was 60.9 % in the VAP group and 84.4 % in the non-VAP group. The median time to VAP onset was 16 days. The median duration of ventilator support and of ICU stay were higher in the VAP group than in the non-VAP group. The VAP rate was 33.8 %. The most common isolated species was Stenotrophomonas maltophilia. On admission, carbapenems were used in a maximum number of cases (75 %). Furthermore, the median body mass index (BMI) was lower and the median sequential organ failure assessment (SOFA) score on admission was higher in the VAP group than in the non-VAP group. CONCLUSIONS: The survival-to-discharge rate in VAP patients was low. Moreover, VAP patients tended to have long ICU stays, low BMI, and high SOFA scores on admission. Unusually, S. maltophilia was the most common isolated bacteria, which may be related to the frequent use of carbapenems.

Genotypic Shift and Diversification of MRSA Blood Stream Isolates in a University Hospital Setting: Evidence from a 12-Year Observational Study.

There have been few reports regarding the long-term trends in the genotypes of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates. Therefore, this study was performed to investigate the longitudinal trends in the genotypes of MRSA bloodstream isolates obtained from hospitalized patients during a 12-year study period from 2010 to 2021 at a tertiary care university hospital. Over the 12-year period from 2010 to 2021, we conducted a genetic investigation focusing on 245 MRSA strains isolated from the blood of hospitalized patients. The genotypes of the MRSA bloodstream isolates were determined by Staphylococcal Cassette Chromosome mec (SCCmec) typing, accessory gene regulator (agr) typing, PCR-based ORF typing (POT), and multilocus sequence typing (MLST). Strains with the same POT type detected in two or more isolates were designated as epidemic clones, while strains without a common POT type were classified as sporadic clones. Until 2015, isolates with SCCmec II/agr II were prevalent, but isolates with SCCmec IV/agr III increased from 2016. A total of 128 strains (52%) were identified as epidemic clones, while 117 strains (48%) were classified as sporadic clones. The detection rate of sporadic clones increased significantly since 2016 (p < 0.05). The epidemic clones were classified into three clusters, with MRSA of clonal complex (CC) 1 being prominent after 2016. This study showed that the genotypes of MRSA bloodstream isolates underwent a shift from SCCmec II/agr II type to SCCmec IV/agr III type, with a notable increase in MRSA of CC1, after 2016. There was a significant increase in the proportion of sporadic strains among the isolates, suggesting the diversification of genotypes.

CG02N Analyzer Accurately Measures Fibrinogen Level in Whole Blood in the Presence of Low- or High-Dose Heparin.

Rapid fibrinogen (Fbg) evaluation is important in patients with massive bleeding during severe trauma and those undergoing major surgery. However, there are only a few studies on the point-of-care Fbg analyzer. In this study, we aimed to investigate the accuracy of Fbg level measured using CG02N, with whole blood contained in lithium-heparinized syringes with two different concentrations of heparin. Blood samples were collected in lithium-heparinized tubes, namely PREZA-PAK®II (low-dose heparin group [LG], 7 IU/mL) and Pro-Vent® Plus (high-dose heparin group [HG], 70.5 IU/mL). The Fbg levels in LG and HG were compared with those of citrated plasma Fbg (standard-Fbg). Strong correlations with respect to the Fbg level were observed between standard-Fbg and LG or HG (r = 0.968, p < 0.0001; r = 0.970, p < 0.0001, respectively). We demonstrated that the Fbg level in whole-blood samples was accurately assessed by CG02N and not affected by low- or high-dose heparin.

Case report of pharmacokinetic analysis of continuous intravenous infusion of fentanyl in a patient with severe burn: burn shock stage complicates pain management.

BACKGROUND: Fentanyl is widely used as an analgesic and sedative for patients with severe burn injuries in intensive care units. However, pharmacokinetic (PK) data for fentanyl, particularly for continuous intravenous infusion during the acute phase of burn injuries, are limited. Here, we report the clinical course and changes in blood fentanyl concentrations during the acute phase in a patient with severe burns treated with continuous intravenous infusion of fentanyl. CASE PRESENTATION: A woman in her 40s, with burns caused by a gas cylinder explosion, was transported to our hospital. The patient had burn wounds on face, neck, shoulders, and all four extremities, with a total burn area of 39.0%. For pain relief, the patient received a continuous infusion of 0.01 mg/mL fentanyl (20-30 µg/h) with a target blood concentration of 1.0-1.5 ng/mL, but continued to suffer from pain due to burning during the acute phase. We measured the blood fentanyl concentrations and found that all concentrations obtained during the acute phase were subtherapeutic. Notably, during the burn shock stage, blood concentrations of fentanyl were 0.50 ng/mL on day 1 and 0.66 ng/mL on day 2, indicating that the blood concentration did not rise sufficiently for the dosage. From days 0 to 2, the patient was administered a massive fluid load for burn shock. After the burn shock stage resolved, fentanyl concentrations gradually approached the target range, and the pain rating scale improved, even though the fentanyl administration rate remained unchanged (30 µg/h). CONCLUSIONS: Major changes in the fluid volumes of body compartments that occur with large burns might increase the volume of fentanyl distribution, thereby lowering its concentration when a standard dose is administered. Our findings indicate that the PK of fentanyl in patients with severe burns can be substantially affected, especially during the shock phase, implying the importance of titrating analgesics for clinical efficacy in the acute phase.

Daily combined measurement of platelet count and presepsin concentration can predict in-hospital death of patients with severe coronavirus disease 2019 (COVID-19).

The purpose of this study was to classify patients with severe COVID-19 into more detailed risk groups using coagulation/fibrinolysis, inflammation/immune response, and alveolar/myocardial damage biomarkers, as well as to identify prognostic markers for these patients. These biomarkers were measured every day for eight intensive care unit days in 54 adult patients with severe COVID-19. The patients were classified into survivor (n = 40) and non-survivor (n = 14) groups. Univariate and multivariate analyses showed that the combined measurement of platelet count and presepsin concentrations may be the most valuable for predicting in-hospital death, and receiver operating characteristic curve analysis further confirmed this result (area under the curve = 0.832). Patients were consequently classified into three groups (high-, medium-, and low-risk) on the basis of their cutoff values (platelet count 53 × 103/µL, presepsin 714 pg/mL). The Kaplan-Meier curve for 90-day survival by each group showed that the 90-day mortality rate significantly increased as risk level increased (P < 0.01 by the log-rank test). Daily combined measurement of platelet count and presepsin concentration may be useful for predicting in-hospital death and classifying patients with severe COVID-19 into more detailed risk groups.

Spinal mechanism underlying the antiallodynic effect of gabapentin studied in the mouse spinal nerve ligation model.

We studied the antiallodynic effect of gabapentin (GBP) in the mouse model of neuropathic pain, aiming at clarifying the underlying mechanism. The L5 spinal nerve ligation induced tactile allodynia, an increase of CD11b expression, and an increase in the protein expression level of the voltage-dependent Ca(2+) channel α(2)/δ-1 subunit in the spinal dorsal horn on the injured side. The chronic intrathecal administration of GBP (100 µg/body per day) as well as ω-conotoxin MVIIA, an N-type Ca(2+)-channel blocker, completely suppressed allodynia, but did not attenuate the CD11b expression. The antiallodynic effect of GBP lasted for several days after the termination of the drug, while that of ω-conotoxin MVIIA disappeared immediately after the termination. GBP suppressed the elevation of the protein level of the α(2)/δ-1 subunit in the spinal dorsal horn, although it did not affect its mRNA level in the L5 DRG. These results suggest that GBP inhibits the development of allodynia by suppressing the up-regulation of N-type Ca(2+) channels, through normalization of the protein level of the α(2)/δ-1 subunit at the primary afferent nerve terminal via the inhibition of its anterograde transport. In addition, we propose that the nerve injury enhances the expression level of α(2)/δ-1 in the downstream of the activation of microglia.

Relationship between serum zinc level and sepsis-induced coagulopathy.

BACKGROUND: We investigated whether a decrease in the serum zinc level (SZL) among patients with sepsis admitted to the intensive care unit (ICU) was related to sepsis-induced coagulopathy. METHODS: All patients (≥20 years) with a diagnosis of sepsis defined by Sepsis-3 criteria, presenting to the ICU between June 2016 and July 2017, were enrolled. Demographic characteristics and the Sequential Organ Failure Assessment (SOFA) and Japanese Association of Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scores were recorded. Blood samples were collected upon admission and analyzed for SZL. RESULTS: One hundred patients with sepsis (median age, 70 years) were enrolled. Patients with SOFA scores ≥8 had a significantly lower SZL compared to those with SOFA scores <8 (p < 0.001). The SZL in the DIC group (JAAM DIC score ≥4) was significantly lower than that in the non-DIC group (JAAM DIC score <4) (p < 0.001). Analysis of receiver operating characteristic (ROC) curves for prediction of sepsis-induced DIC based on SZL in patients with sepsis showed a cut-off value of 25 µg/dL for zinc level and a sensitivity of 63% and a specificity of 72% with AUC of 0.7 (p = 0.0065). CONCLUSION: We observed that SZL reflects organ failure, particularly coagulopathy, in patients with sepsis.

SARS-CoV-2 is localized in cardiomyocytes: a postmortem biopsy case.

A 72-year-old patient was admitted to the intensive care unit due to acute respiratory distress syndrome caused by COVID-19. On day 20, the patient experienced shock. The electrocardiogram showed ST segment elevation in leads V3-V6 and severe left ventricular dysfunction with an ejection fraction of 35%-40%. The left ventricle showed basal hypokinesis and apical akinesis, while the creatine kinase level was normal, indicating Takotsubo cardiomyopathy. On day 24, the patient died of multiple organ failure. In post-mortem biopsy, SARS-CoV-2 antigen was detected in cardiomyocytes by immunostaining. Moreover, SARS-CoV-2 RNA was detected in heart tissue. We need to further analyse the direct link between SARS-CoV-2 and cardiomyocytes.

Efficacy of direct hemoperfusion with a polymyxin B-immobilized fiber column in miliary tuberculosis.

Case: A 75-year-old woman presented with a 10-day history of intermittent fever, general fatigue, and progressive dyspnea. Although she had a low PaO2/FIO2 ratio, the cause of acute respiratory distress syndrome was not clear until day 9 in hospital. Outcome: We treated the patient with direct hemoperfusion with a polymyxin B-immobilized fiber column incidentally; the PaO2/FIO2 ratio improved following this therapy. Acid-fast bacilli, which were not seen in the sputum on admission, were detected in cultures from sputum, urine, bone marrow, liver biopsy, and blood samples, with a real-time polymerase chain reaction assay confirming tuberculosis. She was immediately transferred to a specialized tuberculosis hospital, and after a 3-month treatment, was discharged. Conclusion: Treatment with polymyxin B-immobilized fiber column may provide good results for pulmonary oxygenation in acute respiratory distress syndrome caused by tuberculosis.

Augmented renal clearance in Japanese intensive care unit patients: a prospective study.

BACKGROUND: Augmented renal clearance (ARC) of circulating solutes and drugs has been recently often reported in intensive care unit (ICU) patients. However, only few studies on ARC have been reported in Japan. The aims of this pilot study were to determine the prevalence and risk factors for ARC in Japanese ICU patients with normal serum creatinine levels and to evaluate the association between ARC and estimated glomerular filtration rate (eGFR) calculated using the Japanese equation. METHODS: We conducted a prospective observational study from May 2015 to April 2016 at the emergency ICU of a tertiary university hospital; 111 patients were enrolled (mean age, 67 years; interquartile range, 53-77 years). We measured 8-h creatinine clearance (CLCR) within 24 h after admission, and ARC was defined as body surface area-adjusted CLCR ≥ 130 mL/min/1.73 m2. Multiple logistic regression analysis was performed to identify the risk factors for ARC. Moreover, a receiver operating curve (ROC) analysis, including area under the receiver operating curve (AUROC) was performed to examine eGFR accuracy and other significant variables in predicting ARC. RESULTS: In total, 43 patients (38.7 %) manifested ARC. Multiple logistic regression analysis was performed for age, body weight, body height, history of diabetes mellitus, Acute Physiology and Chronic Health Evaluation II scores, admission categories of post-operative patients without sepsis and trauma, and serum albumin, and only age was identified as an independent risk factor for ARC (odds ratio, 0.95; 95 % confidence interval [CI], 0.91-0.98). Moreover, the AUROC of ARC for age and eGFR was 0.81 (95 % CI, 0.72-0.89) and 0.81 (95 % CI, 0.73-0.89), respectively. The optimal cutoff values for detecting ARC were age and eGFR of ≤63 years (sensitivity, 72.1 %; specificity, 82.4 %) and ≥76 mL/min/1.73 m2 (sensitivity, 81.4 %; specificity, 72.1 %), respectively. CONCLUSIONS: ARC is common in Japanese ICU patients, and age was an independent risk factor for ARC. In addition, age and eGFR calculated using the Japanese equation were suggested to be useful screening tools for identifying Japanese patients with ARC.

Effects of T-82, a novel acetylcholinesterase inhibitor, on impaired learning and memory in passive avoidance task in rats.

Effects of 2-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dihydro-9-methoxy-1H-pyrrolo[3,4-b]quinolin-1-one hemifumarate (T-82), a new quinoline derivative, on drug- and basal forebrain lesion-induced amnesia models were examined in rats. Scopolamine (0.5 mg/kg, i.p.) and cycloheximide (1.5 mg/kg, s.c.) shortened the step-through latency in the passive avoidance task. T-82 significantly ameliorated amnesia induced by scopolamine or cycloheximide at the dose of 0.03, 0.1 and 0.3 mg/kg, p.o., and 0.3 and 1.0 mg/kg, p.o., respectively. Basal forebrain lesions with ibotenic acid shortened the step-through latency in passive avoidance task. An acute (0.1 and 0.3 mg/kg, p.o.) or subacute (0.03-0.3 mg/kg, p.o., for 7 days) treatment of T-82 significantly reversed the shortened latency. These results suggest that T-82 may ameliorate the impairment of memory induced by acetylcholinergic dysfunction.

New mu-opioid receptor agonists with phenoxyacetic acid moiety.

New muq-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, 12-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of delta- and kappa-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a peripheral analgesic activity in vivo screening on rat.