Prevalence and Risk Factor Analysis of Post-Intensive Care Syndrome in Patients with COVID-19 Requiring Mechanical Ventilation: A Multicenter Prospective Observational Study.

INTRODUCTION: Post-intensive care syndrome (PICS) is an emerging problem in critically ill patients and the prevalence and risk factors are unclear in patients with severe coronavirus disease 2019 (COVID-19). This multicenter prospective observational study aimed to investigate the prevalence and risk factors of PICS in ventilated patients with COVID-19 after ICU discharge. METHODS: Questionnaires were administered twice in surviving patients with COVID-19 who had required mechanical ventilation, concerning Barthel Index, Short-Memory Questionnaire, and Hospital Anxiety and Depression Scale scores. The risk factors for PICS were examined using a multivariate logistic regression analysis. RESULTS: The first and second PICS surveys were obtained at 5.5 and 13.5 months (mean) after ICU discharge, with 251 and 209 patients completing the questionnaires and with a prevalence of PICS of 58.6% and 60.8%, respectively, along with the highest percentages of cognitive impairment. Delirium (with an odds ratio of (OR) 2.34, 95% CI 1.1-4.9, and p = 0.03) and the duration of mechanical ventilation (with an OR of 1.29, 95% CI 1.05-1.58, and p = 0.02) were independently identified as the risk factors for PICS in the first PICS survey. CONCLUSION: Approximately 60% of the ventilated patients with COVID-19 experienced persistent PICS, especially delirium, and required longer mechanical ventilation.

Two cases of cryptogenic life-threatening hemoptysis - identification and management of bleeding point.

Cases: Case 1: A 63-year-old woman was referred for coughing blood. Although cardiorespiratory dynamics were stabilized by artificial respiration under sedation, severely poor ventilation developed from asphyxia associated with massive respiratory tract hemorrhage. One-lung ventilation was temporarily secured by endotracheal tube insertion into the left main bronchus just prior to cardiopulmonary arrest.Case 2: A 72-year-old man was referred for massive hemoptysis after coughing, then intubated and placed on a respirator. During angiography, blood clots collected with bronchoscopy confirmed extravascular leakage into the right main bronchus. Outcomes: Both showed no hemoptysis recurrence after bronchial artery embolization and were discharged. Case 1 required intensive treatment for 6 days, including artificial respiratory management. Conclusion: Emergency one-lung ventilation was required for asphyxia in Case 1, and we had difficulties with bleeding point identification and hemostatic therapy. From that experience, we noted hemoptysis during angiography using bronchoscopy in Case 2, enabling prompt bronchial artery embolization.

[Histamine formation in Japanese marine fish species and the effect of frozen storage].

To investigate histamine formation in Japanese marine fish, model samples were made from fish meat mixed with intestines of commercial 73 fish species. After the samples were stored at 25℃ for 12 hr, histamine was detected in 35 fish species at 50 mg/kg or more. These fish species might potentially be related to histamine poisoning. In addition, the effect of frozen storage at -45℃ on histamine formation was examined. Although histamine was formed in some fish species, and Photobacterium damselae and Photobacterium iliopiscarium were isolated from the frozen samples, the amount of histamine formed in the model samples was reduced in all tested fish species after frozen storage. Therefore frozen storage of fish may be effective to control histamine formation, even though histamine forming bacteria survived under these conditions.

Usefulness of procalcitonin serum level for the discrimination of severe sepsis from sepsis: a multicenter prospective study.

Procalcitonin serum level has been recommended as a new marker of bacterial infectious diseases. The aim of this prospective, multicenter study was to determine the clinical usefulness of procalcitonin in differentiating patients with sepsis from those with severe sepsis. Eighty-two patients were enrolled: 20 without systemic inflammatory response syndrome (SIRS), 9 with SIRS, 34 with sepsis, and 19 with severe sepsis. The patients with severe sepsis had significantly higher procalcitonin levels (median, 36.1 ng/ml) than those with sepsis (median, 0.6 ng/ml). With a procalcitonin cutoff value of 2.0 ng/ml, sensitivity for the detection of severe sepsis and specificity for the detection of sepsis were 94.7% and 78.1%, respectively. A good correlation was found between the serum procalcitonin level and the Sepsis-Related Organ Failure Assessment (SOFA) score (r = 0.680), although no correlation was found between the C-reactive protein (CRP) level and the SOFA score. In conclusion, the procalcitonin serum level may be useful not only for aiding the diagnosis of sepsis but also for discriminating between sepsis and severe sepsis.

Hyperbaric oxygen therapy for interstitial cystitis resistant to conventional treatments.

We treated two cases of interstitial cystitis (IC) that were resistant to some conventional therapies with hyperbaric oxygen (HBO). Both patients underwent 20 sessions of 100% oxygen inhalation (2.0 atmosphere absolute for 60 min/day x 5 days/week for 4 weeks) in a hyperbaric chamber. The period of follow up was 12 months for case 1 and 9 months for case 2. After a course of HBO, the bladder mucosal ulcer (Hunner's ulcer) disappeared, and changes from baseline in pain and urinary frequency was constitutively inhibited. There were no adverse events during the 20 treatment sessions. One woman (case 1) had mild Eustachian tube dysfunction, resulting in a transient hearing impairment. HBO seems to be an option for treatment of IC resistant to conventional therapies.

Neutrophil elastase as a predicting factor for development of acute lung injury.

OBJECTIVE: To determine whether the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) associated with systemic inflammatory response syndrome (SIRS) can be predicted by the plasma neutrophil elastase level. PATIENTS AND METHODS: Patients were sequentially enrolled after obtaining informed consent. Twenty-three adult patients with SIRS were classified into the following groups; SIRS alone (5 patients), Group A of ALI/ARDS with SIRS (9 patients) that did not require mechanical ventilation, and Group B of ALI/ARDS with SIRS (9 patients) that required mechanical ventilation. Blood samples were obtained after the diagnosis of SIRS, and the sequential sampling was performed. RESULTS: The plasma neutrophil elastase level was significantly elevated in all patient groups as compared with healthy controls (43.7+/-5.4 ng/ml). The elastase levels in SIRS alone, Group A of ALI/ARDS, and Group B of ALI/ARDS were 126.9+/-11.0 ng/ml, 316.2+/-68.9 ng/ml, and 458.4+/-132.8 ng/ml, respectively. The elastase level in ALI/ARDS with SIRS was significantly greater than that in SIRS alone. The maximal level in 13 of 18 patients with ALI/ARDS with SIRS was more than 220 ng/ml. The level in all patients with SIRS alone was consistently less than 220 ng/ml over the study period. The serum levels of inflammatory cytokines were elevated in these patients, but no statistical significance was detected among the groups. CONCLUSION: The critical level of plasma neutrophil elastase is 220 ng/ml, and the SIRS patients with more than 220 ng/ml neutrophil elastase are highly likely to develop ALI/ARDS.

Multicenter prospective study of procalcitonin as an indicator of sepsis.

The clinical significance of serum procalcitonin (PCT) for discriminating between bacterial infectious disease and nonbacterial infectious disease (such as systemic inflammatory response syndrome (SIRS)), was compared with the significance of endotoxin, beta-D: -glucan, interleukin (IL)-6, and C-reactive protein (CRP) in a multicenter prospective study. The concentrations of PCT in patients with systemic bacterial infection and those with localized bacterial infection were significantly higher than the concentrations in patients with nonbacterial infection or noninfectious diseases. In addition, PCT, endotoxin, IL-6, and CRP concentrations were significantly higher in patients with bacterial infectious disease than in those with nonbacterial infectious disease (P<0.001, P<0.005, P<0.001, and P<0.001, respectively). The cutoff value of PCT for the discrimination of bacterial and nonbacterial infectious diseases was determined to be 0.5 ng/ml, which was associated with a sensitivity of 64.4% and specificity of 86.0%. Areas under the receiver operating characteristic curves (POCs) were 0.84 for PCT, 0.60 for endotoxin, 0.77 for IL-6, and 0.78 for CRP in the combined group of patients with bacterial infectious disease and those with nonbacterial infectious disease, and the area under the ROC for PCT was significantly higher than that for endotoxin (P<0.001). In patients diagnosed with bacteremia based on clinical findings, the positive rate of diagnosis with PCT was 70.2%, while that of blood culture was 42.6%. PCT is thus essential for discriminating bacterial infection from SIRS, and is superior in this respect to conventional serum markers and blood culture.

Effect of enteral nutrition of monoacetoacetin on bacterial translocation in burned rats.

BACKGROUND: Bacterial translocation (BT) occurs under stress, and enteral nutrition is said to be effective in counteracting this effect. The usefulness of i.v. nutrition of monoacetoacetine (MA) under stress has been reported previously, and we studied the effect of enteral nutrition of MA as it is related to BT. METHODS: Rats were given 13.6% MA or 15% glucose (Glu) via gastrostomy, and after 4 days a 30% full-thickness burn was made. Before and after administration of the burn, we measured serum cytokines; amounts of bacteria in the mesenteric lymph node (MLN), liver, and spleen (estimation of BT); mucosal thickness of the terminal ileum; and body weight changes. To confirm the effectiveness of MA in the small intestine, we estimated succinyl-CoA:3-oxoacid CoA-transferase (SCOT) expression in the terminal ileum by immunohistochemical staining and Western blot analysis. RESULTS: At 6 hours after burn, all cytokines were lower, and BT in the MLN was inhibited significantly in the MA group. Ileal mucosal thickness was not significantly different, but mucosa was more edematous in the Glu group. At 3 days after burn injury, BT was significantly inhibited in the MLN and liver, and the ileal mucosa was significantly thicker in the MA group. Body weight loss after burn injury was significantly smaller in the MA group. SCOT expression was the strongest at 6 hours after burn injury by Western blot analysis but not by immunohistochemical staining. CONCLUSIONS: Enteral nutrition of MA may be useful for the inhibition of intestinal mucosal atrophy and the prevention of multiple organ dysfunction syndrome caused by the inhibition of BT and subsequent overproduction of cytokines.

2-Hydroxypenta-2,4-dienoate metabolic pathway genes in a strong polychlorinated biphenyl degrader, Rhodococcus sp. strain RHA1.

A gram-positive polychlorinated biphenyl (PCB) degrader, Rhodococcus sp. strain RHA1, metabolizes biphenyl through the 2-hydroxypenta-2,4-dienoate (HPD) and benzoate metabolic pathways. The HPD metabolic pathway genes, the HPD hydratase (bphE1), 4-hydroxy-2-oxovalerate aldolase (bphF1), and acetaldehyde dehydrogenase (acylating) (bphG) genes, were cloned from RHA1. The deduced amino acid sequences of bphGF1E1 have 30 to 58% identity with those of the HPD metabolic pathway genes of gram-negative bacteria. The order of these genes, bphG-bphF1-bphE1, differs from that of the HPD metabolic pathway genes, bphE-bphG-bphF, in gram-negative degraders of PCB, phenol, and toluene. Reverse transcription-PCR experiments indicated that the bphGF1E1 genes are inducibly cotranscribed in cells grown on biphenyl and ethylbenzene. Primer extension analysis revealed that the transcriptional initiation site exists within the bphR gene located adjacent to and upstream of bphG, which is deduced to code a transcriptional regulator. The respective enzyme activities of bphGF1E1 gene products were detected in Rhodococcus erythropolis IAM1399 carrying a bphGF1E1 plasmid. The insertional inactivation of the bphE1, bphF1, and bphG genes resulted in the loss of the corresponding enzyme activities and diminished growth on both biphenyl and ethylbenzene. Severe growth interference was observed during growth on biphenyl. The growth defects were partially restored by the introduction of plasmids containing the respective intact genes. These results indicated that the cloned bphGF1E1 genes are not only responsible for the primary metabolism of HPD during growth on both biphenyl and ethylbenzene but are also involved in preventing the accumulation of unexpected toxic metabolites, which interfere with the growth of RHA1.

Comparison of protein chemical and physicochemical properties of rapeseed cruciferin with those of soybean glycinin.

Rapeseeds contain cruciferin (11S globulin), napin (2S albumin), and oleosin (oil body protein) as major seed proteins. The effects of oil expression and drying conditions on the extraction of these proteins from rapeseed meal were examined. The conditions strongly affected the extraction of oleosin and only weakly affected the extraction of cruciferin and napin. The protein chemical and physicochemical properties of cruciferin, the major protein present, were compared with those of glycinin (soybean 11S globulin) under various conditions. In general, cruciferin exhibited higher surface hydrophobicity, lower thermal stability, and lower and higher solubility at mu= 0.5 and mu = 0.08, respectively, than did glycinin. At the pHs (6.0, 7.6, and 9.0) and ionic strengths (mu= 0.08 and 0.5) examined, the emulsifying ability of cruciferin was worse than that of glycinin, except at mu= 0.08 and pH 7.6. The emulsifying abilities of cruciferin and glycinin did not correlate with thermal stability and surface hydrophobicity. Higher protein concentration, higher heating temperature, higher pH, and lower ionic strength were observed to produce harder gels from cruciferin. Gel hardness partly correlated with the structural stability of cruciferin.