Clinical characteristics and outcomes of critically ill patients with COVID-19 in Kobe, Japan: a single-center, retrospective, observational study.

PURPOSE: Coronavirus disease 2019 (COVID-19) has placed a great burden on critical care services worldwide. Data regarding critically ill COVID-19 patients and their demand of critical care services outside of initial COVID-19 epicenters are lacking. This study described clinical characteristics and outcomes of critically ill COVID-19 patients and the capacity of a COVID-19-dedicated intensive care unit (ICU) in Kobe, Japan. METHODS: This retrospective observational study included critically ill COVID-19 patients admitted to a 14-bed COVID-19-dedicated ICU in Kobe between March 3, 2020 and June 21, 2020. Clinical and daily ICU occupancy data were obtained from electrical medical records. The last follow-up day was June 28, 2020. RESULTS: Of 32 patients included, the median hospital follow-up period was 27 (interquartile range 19-50) days. The median age was 68 (57-76) years; 23 (72%) were men and 25 (78%) had at least one comorbidity. Nineteen (59%) patients received invasive mechanical ventilation for a median duration of 14 (8-27) days. Until all patients were discharged from the ICU on June 5, 2020, the median daily ICU occupancy was 50% (36-71%). As of June 28, 2020, six (19%) died during hospitalization. Of 26 (81%) survivors, 23 (72%) were discharged from the hospital and three (9%) remained in the hospital. CONCLUSION: During the first months of the outbreak in Kobe, most critically ill patients were men aged ≥ 60 years with at least one comorbidity and on mechanical ventilation; the ICU capacity was not strained, and the case-fatality rate was 19%.

Contamination of Blood Cultures From Arterial Catheters and Peripheral Venipuncture in Critically Ill Patients: A Prospective Multicenter Diagnostic Study.

BACKGROUND: Collecting blood cultures from indwelling arterial catheters is an attractive option in critically ill adult patients when peripheral venipuncture is difficult. However, whether the contamination proportion of blood cultures from arterial catheters is acceptable compared with that from venipuncture is inconclusive. RESEARCH QUESTION: Is contamination of blood cultures from arterial catheters noninferior to that from venipuncture in critically ill adult patients with suspected bloodstream infection? STUDY DESIGN AND METHODS: In this multicenter prospective diagnostic study conducted at five hospitals, we enrolled episodes of paired blood culture collection, each set consisting of blood drawn from an arterial catheter and another by venipuncture, were obtained from critically ill adult patients with cilinical indication. The primary measure was the proportion of contamination, defined as the number of false-positive results relative to the total number of procedures done. The reference standard for true bloodstream infection was blinded assessment by infectious disease specialists. We examined the noninferiority hypothesis that the contamination proportion of blood cultures from arterial catheters did not exceed that from venipuncture by 2.0%. RESULTS: Of 1,655 episodes of blood culture from December 2018 to July 2021, 590 paired blood culture episodes were enrolled, and 41 of the 590 episodes (6.9%) produced a true bloodstream infection. In blood cultures from arterial catheters, 33 of 590 (6.0%) were positive, and two of 590 (0.3%) were contaminated; in venipuncture, 36 of 590 (6.1%) were positive, and four of 590 (0.7%) were contaminated. The estimated difference in contamination proportion (arterial catheter - venipuncture) was -0.3% (upper limit of one-sided 95% CI, +0.3%). The upper limit of the 95% CI did not exceed the predefined margin of +2.0%, establishing noninferiority (P for noninferiority < .001). INTERPRETATION: Obtaining blood cultures from arterial catheters is an acceptable alternative to venipuncture in critically ill patients. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Center (UMIN-CTR); No.: UMIN000035392; URL: https://center6.umin.ac.jp/.

Incidence of Adverse Events Associated With the In-Hospital Transport of Critically Ill Patients.

IMPORTANCE: Despite various reports on the incidence of adverse events related to the in-hospital transport of critically ill patients, there is little verification of the correlation between the occurrence of adverse events and the use of checklists. The risk factors for the occurrence of adverse events during transport based on the use of checklists have not been well studied. Understanding them can contribute to making patient transport safer. OBJECTIVES: We aimed to investigate the frequency of adverse events and risk factors related to the in-hospital transport of critically ill patients in a hospital that uses a checklist for transporting patients. DESIGN SETTING AND PARTICIPANTS: This single-center, prospective, observational study was conducted between February 1, 2020, and July 31, 2020, at Kobe City Medical Center General Hospital, Japan. Patients greater than or equal to 18 years old who were admitted to the ICU and were transported for examination or procedures were included. MAIN OUTCOMES AND MEASURES: The transport member recorded patient information and any adverse events that occurred and filled out an information collection form. We then applied multivariate analysis to identify risk factors. RESULTS: A total of 117 transports for 117 patients were evaluated in this study. Twenty-two adverse events occurred in 20 transports (17.1%). There were nine transports (7.7%) in which the patients required treatment, all of which were related to patient instability. Multivariate logistic regression analysis showed that the use of sedative drugs was related to adverse events (odds ratio, 2.9; 95% CI, 1.0-8.5; p = 0.04). We were not able to show a relationship of either the severity of the illness or body mass index with the occurrence of adverse events. CONCLUSIONS AND RELEVANCE: This study revealed that the frequency of adverse events related to the in-hospital transportation of critically ill patients based on the use of a checklist was 17.1% and that the use of sedatives was associated with adverse events.

Patient-centered outcomes at hospital discharge in mechanically ventilated COVID-19 patients in Kobe, Japan: A single-center retrospective cohort study.

BACKGROUND: Apart from saving the lives of coronavirus disease (COVID-19) patients on mechanical ventilation (MV), recovery from the sequelae of prolonged MV (PMV) is an emerging issue.c METHODS: We conducted a retrospective study among consecutive adult COVID-19 patients admitted to an intensive care unit (ICU) in Kobe, Japan, between March 3, 2020, and January 31, 2021, and received invasive MV. Clinical outcomes included in-hospital mortality and recovery from COVID-19 in survivors regarding organ dysfunction, respiratory symptoms, and functional status at discharge. We compared survivors' outcomes with MV durations of >14 days and ≤14 days. RESULTS: We included 85 patients with a median age of 69 years (interquartile range, 64-75 years); 76 (89%) patients had at least 1 comorbidity, 72 (85%) were non-frail, and 79 (93%) were functionally independent before COVID-19 infection. Eighteen patients (21%) died during hospitalization. At discharge, 59/67 survivors (88%) no longer required respiratory support, 50 (75%) complained of dyspnea, and 40 (60%) were functionally independent. Of the survivors, 23 patients receiving MV for >14 days had a worse recovery from COVID-19 at discharge compared with those on MV for ≤14 days, as observed using the Barthel index (median: 35 [5-65] vs. 100 [85-100]), ICU mobility scale (8 [5-9] vs. 10 [10-10]), and functional oral intake scale (3 [1-7] vs. 7 [7-7]) (P < 0.0001). CONCLUSION: Although four-fifths of the patients survived and >50% of survivors demonstrated clinically important recovery in organ function and functional status during hospitalization, PMV was related to poor recovery from COVID-19 at discharge.

Nephrotic range proteinuria and metabolic alkalosis in Takayasu arteritis.

Nephrotic range proteinuria and metabolic alkalosis are unusual findings in large vessel vasculitis. In this case, renovascular hypertension with unilateral renal artery stenosis in Takayasu arteritis was complicated by nephrotic range proteinuria. Symptoms resolved after angioplasty, although non-nephrotic proteinuria persisted. The renal pathology of Takayasu arteritis included focal glomerulosclerosis.

Residue-specific millisecond to microsecond fluctuations in bacteriorhodopsin induced by disrupted or disorganized two-dimensional crystalline lattice, through modified lipid-helix and helix-helix interactions, as revealed by 13C NMR.

We have recorded 13C NMR spectra of [3-13C]-, [1-13C]Ala-, and [1-13C]Val-labeled bacteriorhodopsin (bR), W80L and W12L mutants and bacterio-opsin (bO) from retinal-deficient E1001 strain, in order to examine the possibility of their millisecond to microsecond local fluctuations with correlation time in the order of 10(-4) to 10(-5) s, induced or prevented by disruption or assembly of two-dimensional (2D) crystalline lattice, respectively, at ambient temperature. The presence of disrupted or disorganized 2D lattice for W12L, W80L and bO from E1001 strain was readily visualized by increased relative proportions of surrounding lipids per protein, together with their broadened 13C NMR signals of transmembrane alpha-helices and loops in [3-13C]Ala-labeled proteins, with reference to those of wild-type. In contrast, 13C CP-MAS NMR spectra of [1-13C]Ala- and Val-labeled these mutants were almost completely suppressed, owing to the presence of fluctuations with time scale of 10(-4) s interfered with magic angle spinning. In particular, 13C NMR signals of [1-13C]Ala-labeled transmembrane alpha-helices of wild-type were almost completely suppressed at the interface between the surface and inner part (up to 8.7 A deep from the surface) with reference to those of the similarly suppressed peaks by Mn(2+)-induced accelerated spin-spin relaxation rate. Such fluctuation-induced suppression of 13C NMR peaks from the interfacial regions, however, was less significant for [1-13C]Val-labeled proteins, because fluctuation motions in Val residues with bulky side-chains at the C(alpha) moiety were modified to those of longer correlation time (>10(-4) s), if any, by residue-specific manner. To support this view, we found that such suppressed 13C NMR signals of [1-13C]Ala-labeled peaks in the wild-type were recovered for D85N and bO in which correlation times of fluctuations were shifted to the order of 10(-5) s due to modified helix-helix interactions as previously pointed out [Biochemistry, 39 (2000) 14472; J. Biochem. (Tokyo) 127 (2000) 861].

Effect of As2O3 on cell cycle progression and cyclins D1 and B1 expression in two glioblastoma cell lines differing in p53 status.

Recent clinical studies have demonstrated that As2O3 is an effective drug in the treatment of acute promyelocytic leukemia (APL) by inducing apoptosis and inhibiting the proliferation of leukemia cells both in vitro and in vivo. As a novel anticancer agent for the treatment of solid cancer, As2O3 is promising, but no experimental investigations of its efficacy on glioblastoma have been conducted at concentrations that may be achieved clinically. In addition, the cell proliferation and cell cycle regulating mechanism of As2O3 has not yet to be clarified, especially in solid cancers. We investigated the effect of As2O3 on proliferation and cell cycle regulation with change in cyclins in two human glioblastoma cell lines differing in p53 status (U87MG-wt; T98G-mutated). Sensitivity to As2O3 varied depending on the dose with the IC50 of the U87MG and T98G cells being 1.78 and 3.55 microM, respectively. Analysis by laser scanning cytometry (LSC) indicated that As2O3 inhibited the proliferation of the two cell lines via cell cycle arrest both at the G1 and G2 phases. To address the mechanism of the antiproliferative effect of As2O3, we examined its effect on cell cycle-related proteins by means of LSC, confocal microscopy and Western blot analysis. As2O3 induced an increase in p53 level and a decrease in level of cyclin B1 combined with cell arrest at G2/M in both cell lines. Cell arrest in G1, however, was associated with a decline in cyclin D1 expression only in the wt U87MG cells. As2O3 also induced apoptosis of U87MG cells as evidenced by the presence of cells with fractional DNA content ( cell populations). The present evidence that As2O3 at relatively low concentration effectively inhibited proliferation of U87MG and T98G cells in vitro, suggests that the drug may be considered for in vivo testing on animal models and possibly clinical trials on glioma patients.

Ultrastructural analysis of brain tumors using collagen gel culture.

In an attempt to investigate the tumor type-specific ultrastructure of cultured brain tumors, a collagen gel culture was utilized instead of the conventional monolayer culture. To avoid intermingling of the normal brain cells, tumors with a clear margin and a portion typical of invasive tumors were sampled. The tumors were minced, and small fragments were prepared and embedded in the collagen gel in an aseptic manner. Tumors were observed on a daily basis under a phase contrast microscope. When sprouting of the tumor cells from a tumor fragment was confirmed, the samples were fixed with 2.5% glutaraldehyde and then processed for electron microscopy. Ultrastructurally, meningioma has been shown to form a whorl-like structure. The cell processes have a complex interrelationship, but this phenomenon cannot be regarded as the so-called interdigitation. A basement membrane was formed surrounding the tumor cell processes facing the collagen gel in two ependymomas. Lipid droplets were contained in great numbers inside a chordoma cell. These findings suggest the usefulness of collagen gel culture in analyzing the tumor type-specific ultrastructure of cultured brain tumors, and possibly in studying cellular differentiation.

Blood tumor permeability of experimental brain tumor: an electron microscopic study using lanthanum.

In an attempt to assess the permeability of microvessels in the experimental brain tumor model, lanthanum ion (La3+) was used as a low-molecular weight electron microscopic probe. Rat glioma 9 L and adenocarcinoma ACL15 were transplanted to the brain and subflank of rats. The rats were then anesthetized sequentially perfused with saline, saline plus La3+ followed by a fixative in phosphate buffer. The brain and subcutaneous tumors were removed, further fixed, and processed for electron microscopy. La3 did not pass through the tight junctions of the normal cerebral endothelium. Similarly, La3+ did not penetrate the endothelial cell wall of the microvessels in the transplanted brain tumors. In contrast, extravasation of La3+ from the microvessels in the transplanted subcutaneous tumors was observed. The electron microscopy examination results indicate that the vesicular transport was a predominant mechanism in the penetration of La3+ through the endothelial cell wall. Since most chemotherapeutic agents similar as La3+ are of low molecular weight, we can suggest from the results of our present study that the blood tumor permeability of the anti-cancer agents in the rat model of brain glioma transplantation differs from that in the rat model of subcutaneous glioma transportation. In other words, our results indicate that when the subcutaneous glioma transplantation model is used in sensitivity tests of anti-cancer agents, it will possibly be very difficult to predict the anti-neoplastic effect in vivo.

Cycloheximide induces apoptosis of astrocytes.

Cultured rat astrocytes were incubated in the presence of cycloheximide (CHX; 20 microg/mL), a potent neuroprotective agent. Then cells were subjected to DNA gel electrophoresis. Electrophoresis showed DNA ladder formation, which is characteristic of apoptosis. Inhibitors of interleukin-1beta-converting enzyme (ICE) and caspase 32(CPP32), which play critical roles in certain apoptotic pathways, did not block the cycloheximide-induced apoptosis of cultured astrocytes. This observation indicates that the role of ICE and CPP32 is not significant in the CHX-induced astrocyte apoptosis process. When the blood-brain barrier was disrupted in the rat, the number of brain cells undergoing apoptosis was significantly higher after cycloheximide administration, in contrast to controls. Of the cells that produced glial fibrillary acidic protein, some were observed to undergo apoptosis. Although CHX has been shown to be useful as a neuroprotective agent against ischemic neuronal death, astroglial toxicity may be problematic, depending on CHX concentration. Therefore, a prudent use of this compound is recommended.