Ultrasound-guided central venous catheterization around the neck: Systematic review and network meta-analysis.

BACKGROUND: Ultrasound-guided central venous catheterization (CVC) has become the standard of care. However, providers use a variety of approaches, encompassing the internal jugular vein (IJV), supraclavicular subclavian vein (SupraSCV), infraclavicular subclavian vein (InfraSCV), proximal axillary vein (ProxiAV), distal axillary vein (DistalAV), and femoral vein. OBJECTIVE: This review aimed to compare the first-pass success rate and arterial puncture rate for different approaches to ultrasound-guided CVC above the diaphragm. METHODS: In May 2023, Embase, MEDLINE, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform were searched for randomized controlled trials (RCTs) comparing the 5 CVC approaches. The Confidence in Network Meta-Analysis tool was used to assess confidence. Thirteen RCTs (4418 participants and 13 comparisons) were included in this review. RESULTS: The SupraSCV approach likely increased the proportion of first-attempt successes compared to the other 4 approaches. The SupraSCV first-attempt success demonstrated risk ratios (RRs) > 1.21 with a lower 95% confidence interval (CI) exceeding 1. Compared to the IJV, the SupraSCV approach likely increased the first-attempt success proportion (RR 1.22; 95% confidence interval [CI] 1.06-1.40, moderate confidence), whereas the DistalAV approach reduced it (RR 0.72; 95% CI 0.59-0.87, high confidence). Artery puncture had little to no difference across all approaches (low to high confidence). CONCLUSION: Considering first-attempt success and mechanical complications, the SupraSCV may emerge as the preferred approach, while DistalAV might be the least preferable approach. Nevertheless, head-to-head studies comparing the approaches with the greatest first attempt success should be undertaken.

Progressive disruption of neurodevelopment by mid-gestation exposure to lipopolysaccharides and the ameliorating effect of continuous alpha-glycosyl isoquercitrin treatment.

We investigated the effect of lipopolysaccharide (LPS)-induced maternal immune activation used as a model for producing neurodevelopmental disorders on hippocampal neurogenesis and behaviors in rat offspring by exploring the antioxidant effects of alpha-glycosyl isoquercitrin (AGIQ). Pregnant Sprague-Dawley rats were intraperitoneally injected with LPS (50 µg/kg body weight) at gestational days 15 and 16. AGIQ was administered in the diet to dams at 0.5% (w/w) from gestational day 10 until weaning at postnatal day 21 and then to offspring until adulthood at postnatal day 77. During postnatal life, offspring of LPS-injected animals did not show neuroinflammation or oxidative stress in the brain. At weaning, LPS decreased the numbers of type-2b neural progenitor cells (NPCs) and PCNA+ proliferating cells in the subgranular zone, FOS-expressing granule cells, and GAD67+ hilar interneurons in the dentate gyrus. In adulthood, LPS decreased type-1 neural stem cells, type-2a NPCs, and GAD67+ hilar interneurons, and downregulated Dpysl3, Sst, Fos, Mapk1, Mapk3, Grin2a, Grin2b, Bdnf, and Ntrk2. In adults, LPS suppressed locomotor activity in the open field test and suppressed fear memory acquisition and fear extinction learning in the contextual fear conditioning test. These results indicate that mid-gestation LPS injections disrupt programming of normal neurodevelopment resulting in progressive suppression of hippocampal neurogenesis and synaptic plasticity of newborn granule cells by suppressing GABAergic and glutamatergic neurotransmitter signals and BDNF/TrkB signaling to result in adult-stage behavioral deficits. AGIQ ameliorated most aberrations in hippocampal neurogenesis and synaptic plasticity, as well as behavioral deficits. Effective amelioration by continuous AGIQ treatment starting before LPS injections may reflect both anti-inflammatory and anti-oxidative stress effects during gestation and neuroprotective effects of continuous exposure through adulthood.

Efficacy of different anticoagulant doses for patients with COVID-19: a systematic review and network meta-analysis.

PURPOSE: As no reported randomized control trials (RCTs) directly compare the three administration doses of anticoagulants (prophylactic dose, treatment dose, and no treatment), the most recommended dose to be administered to patients with coronavirus disease 2019 (COVID-19) remains unclear. The purpose of this study was to examine the effects of anticoagulant doses administered to patients with COVID-19, using a network meta-analysis (NMA) including high-quality studies. METHODS: All eligible trials from the Cochrane Central Register of Controlled Trials, MEDLINE, and Clinicaltrials.gov were included. We included RCTs and observational studies adjusted for covariates for patients aged ≥ 18 years and hospitalized due to objectively confirmed COVID-19. The main study outcome was mortality. RESULTS: In patients with moderate COVID-19, the prophylactic (relative risk (RR) 0.64 [95% confidence interval (CI) 0.52-0.80]) and treatment dose (RR 0.57 [95% CI 0.45-0.72] were associated with a lower risk of short-term mortality than that with no anticoagulant treatment. However, the prophylactic and treatment dose groups were not significantly different. The hierarchy for efficacy in reducing short-term mortality was treatment dose (P score 92.4) > prophylactic dose (57.6) > no treatment (0.0). In patients with severe COVID-19, due to the absence of trials with the no-treatment group, NMA could not be conducted. However, pairwise comparison did not show a significant difference between the prophylactic and treatment dose groups. CONCLUSIONS: Treatment and prophylactic doses of anticoagulants showed similar effects on mortality; however, the treatment dose is preferred over the prophylactic dose for patients with both moderate and severe COVID-19. TRIAL REGISTRATION NUMBER AND REGISTRATION DATES: PROSPERO (registration number: CRD42021245308, 05/21/2021).

Gene expression profiles of multiple brain regions in rats differ between developmental and postpubertal exposure to valproic acid.

We have previously reported that the valproic acid (VPA)-induced disruption pattern of hippocampal adult neurogenesis differs between developmental and 28-day postpubertal exposure. In the present study, we performed brain region-specific global gene expression profiling to compare the profiles of VPA-induced neurotoxicity between developmental and postpubertal exposure. Offspring exposed to VPA at 0, 667, and 2000 parts per million (ppm) via maternal drinking water from gestational day 6 until weaning (postnatal day 21) were examined, along with male rats orally administered VPA at 0, 200, and 900 mg/kg body weight for 28 days starting at 5 weeks old. Four brain regions-the hippocampal dentate gyrus, corpus callosum, cerebral cortex, and cerebellar vermis-were subjected to expression microarray analysis. Profiled data suggested a region-specific pattern of effects after developmental VPA exposure, and a common pattern of effects among brain regions after postpubertal VPA exposure. Developmental VPA exposure typically led to the altered expression of genes related to nervous system development (Msx1, Xcl1, Foxj1, Prdm16, C3, and Kif11) in the hippocampus, and those related to nervous system development (Neurod1) and gliogenesis (Notch1 and Sox9) in the corpus callosum. Postpubertal VPA exposure led to the altered expression of genes related to neuronal differentiation and projection (Cd47, Cyr61, Dbi, Adamts1, and Btg2) in multiple brain regions. These findings suggested that neurotoxic patterns of VPA might be different between developmental and postpubertal exposure, which was consistent with our previous study. Of note, the hippocampal dentate gyrus might be a sensitive target of developmental neurotoxicants after puberty.

Oral exposure to aluminum chloride for 28 days suppresses neural stem cell proliferation and increases mature granule cells in adult hippocampal neurogenesis of young-adult rats.

Aluminum (Al), a common light metal, affects the developing nervous system. Developmental exposure to Al chloride (AlCl3 ) induces aberrant neurogenesis by targeting neural stem cells (NSCs) and/or neural progenitor cells (NPCs) in the dentate gyrus (DG) of rats and mice. To investigate whether hippocampal neurogenesis is similarly affected by AlCl3 exposure in a general toxicity study, AlCl3 was orally administered to 5-week-old Sprague Dawley rats at dosages of 0, 4000, or 8000 ppm in drinking water for 28 days. AlCl3 downregulated Sox2 transcript level in the DG at the highest dosage and produced a dose-dependent decrease of SOX2+ cells without altering numbers of GFAP+ or TBR2+ cells in the subgranular zone, suggesting that AlCl3 decreases Type 2a NPCs. High-dose exposure downregulated Pcna, upregulated Pvalb, and altered expression of genes suggestive of oxidative stress induction (upregulation of Nos2 and downregulation of antioxidant enzyme genes), indicating suppressed proliferation and differentiation of Type 1 NSCs. AlCl3 doses also increased mature granule cells in the DG. Upregulation of Reln may have contributed to an increase of granule cells to compensate for the decrease of Type 2a NPCs. Moreover, upregulation of Calb2, Gria2, Mapk3, and Tgfb3, as well as increased numbers of activated astrocytes in the DG hilus, may represent ameliorating responses against suppressed neurogenesis. These results suggest that 28-day exposure of young-adult rats to AlCl3 differentially targeted NPCs and mature granule cells in hippocampal neurogenesis, yielding a different pattern of disrupted neurogenesis from developmental exposure.

Efficacy of non-invasive and invasive respiratory management strategies in adult patients with acute hypoxaemic respiratory failure: a systematic review and network meta-analysis.

BACKGROUND: Although non-invasive respiratory management strategies have been implemented to avoid intubation, patients with de novo acute hypoxaemic respiratory failure (AHRF) are high risk of treatment failure. In the previous meta-analyses, the effect of non-invasive ventilation was not evaluated according to ventilation modes in those patients. Furthermore, no meta-analyses comparing non-invasive respiratory management strategies with invasive mechanical ventilation (IMV) have been reported. We performed a network meta-analysis to compare the efficacy of non-invasive ventilation according to ventilation modes with high-flow nasal oxygen (HFNO), standard oxygen therapy (SOT), and IMV in adult patients with AHRF. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Ichushi databases were searched. Studies including adults with AHRF and randomized controlled trials (RCTs) comparing two different respiratory management strategies (continuous positive airway pressure (CPAP), pressure support ventilation (PSV), HFNO, SOT, or IMV) were reviewed. RESULTS: We included 25 RCTs (3,302 participants: 27 comparisons). Using SOT as the reference, CPAP (risk ratio [RR] 0.55; 95% confidence interval [CI] 0.31-0.95; very low certainty) was associated significantly with a lower risk of mortality. Compared with SOT, PSV (RR 0.81; 95% CI 0.62-1.06; low certainty) and HFNO (RR 0.90; 95% CI 0.65-1.25; very low certainty) were not associated with a significantly lower risk of mortality. Compared with IMV, no non-invasive respiratory management was associated with a significantly lower risk of mortality, although all certainties of evidence were very low. The probability of being best in reducing short-term mortality among all possible interventions was higher for CPAP, followed by PSV and HFNO; IMV and SOT were tied for the worst (surface under the cumulative ranking curve value: 93.2, 65.0, 44.1, 23.9, and 23.9, respectively). CONCLUSIONS: When performing non-invasive ventilation among patients with de novo AHRF, it is important to avoid excessive tidal volume and lung injury. Although pressure support is needed for some of these patients, it should be applied with caution because this may lead to excessive tidal volume and lung injury. Trial registration protocols.io (Protocol integer ID 49375, April 23, 2021). https://doi.org/10.17504/protocols.io.buf7ntrn .

Post-extubation oxygenation strategies in acute respiratory failure: a systematic review and network meta-analysis.

BACKGROUND: High-flow nasal cannula oxygenation (HFNC) and noninvasive positive-pressure ventilation (NPPV) possibly decrease tracheal reintubation rates better than conventional oxygen therapy (COT); however, few large-scale studies have compared HFNC and NPPV. We conducted a network meta-analysis (NMA) to compare the effectiveness of three post-extubation respiratory support devices (HFNC, NPPV, and COT) in reducing the mortality and reintubation risk. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Ichushi databases were searched. COT, NPPV, and HFNC use were assessed in patients who were aged ≥ 16 years, underwent invasive mechanical ventilation for > 12 h for acute respiratory failure, and were scheduled for extubation after spontaneous breathing trials. The GRADE Working Group Approach was performed using a frequentist-based approach with multivariate random-effect meta-analysis. Short-term mortality and reintubation and post-extubation respiratory failure rates were compared. RESULTS: After evaluating 4631 records, 15 studies and 2600 patients were included. The main cause of acute hypoxic respiratory failure was pneumonia. Although NPPV/HFNC use did not significantly lower the mortality risk (relative risk [95% confidence interval] 0.75 [0.53-1.06] and 0.92 [0.67-1.27]; low and moderate certainty, respectively), HFNC use significantly lowered the reintubation risk (0.54 [0.32-0.89]; high certainty) compared to COT use. The associations of mortality with NPPV and HFNC use with respect to either outcome did not differ significantly (short-term mortality and reintubation, relative risk [95% confidence interval] 0.81 [0.61-1.08] and 1.02 [0.53-1.97]; moderate and very low certainty, respectively). CONCLUSION: NPPV or HFNC use may not reduce the risk of short-term mortality; however, they may reduce the risk of endotracheal reintubation. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: PROSPERO (registration number: CRD42020139112, 01/21/2020).

Identification of gene targets of developmental neurotoxicity focusing on DNA hypermethylation involved in irreversible disruption of hippocampal neurogenesis in rats.

We have previously found that maternal exposure to 6-propyl-2-thiouracil (PTU), valproic acid (VPA), or glycidol (GLY) has a sustained or late effect on hippocampal neurogenesis at the adult stage in rat offspring. Herein, we searched for genes with hypermethylated promoter region and downregulated transcript level to reveal irreversible markers of developmental neurotoxicity. The hippocampal dentate gyrus of male rat offspring exposed maternally to PTU, VPA, or GLY was subjected to Methyl-Seq and RNA-Seq analyses on postnatal day (PND) 21. Among the genes identified, 170 were selected for further validation analysis of gene expression on PND 21 and PND 77 by real-time reverse transcription-PCR. PTU and GLY downregulated many genes on PND 21, reflecting diverse effects on neurogenesis. Furthermore, genes showing sustained downregulation were found after PTU or VPA exposure, reflecting a sustained or late effect on neurogenesis by these compounds. In contrast, such genes were not observed with GLY, probably because of the reversible nature of the effects. Among the genes showing sustained downregulation, Creb, Arc, and Hes5 were concurrently downregulated by PTU, suggesting an association with neuronal mismigration, suppressed synaptic plasticity, and reduction in neural stem and progenitor cells. Epha7 and Pvalb were also concurrently downregulated by PTU, suggesting an association with the reduction in late-stage progenitor cells. VPA induced sustained downregulation of Vgf and Dpysl4, which may be related to the aberrations in synaptic plasticity. The genes showing sustained downregulation may be irreversible markers of developmental neurotoxicity.

Downregulation of low-density lipoprotein receptor class A domain-containing protein 4 (Ldlrad4) in the liver of rats treated with nongenotoxic hepatocarcinogen to induce transforming growth factor ß signaling promoting cell proliferation and suppressing apoptosis in early hepatocarcinogenesis.

We previously found downregulation of low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4), a negative regulator of transforming growth factor (TGF)-ß signaling, in glutathione S-transferase placental form (GST-P) expressing (+ ) pre-neoplastic lesions produced by treatment with nongenotoxic hepatocarcinogens for up to 90 days in rats. Here, we investigated the relationship between LDLRAD4 downregulation and TGFß signaling in nongenotoxic hepatocarcinogenesis. The transcripts of Tgfb and Hb-egf increased after ≥28 days of treatment. After 84 or 90 days, Snai1 increased transcripts and the subpopulation of GST-P+ foci downregulating LDLRAD4 co-expressed TGFß1, phosphorylated EGFR, or phosphorylated AKT2, and downregulated PTEN, showing higher incidences than those in GST-P+ foci expressing LDLRAD4. The subpopulation of GST-P+ foci downregulating LDLRAD4 also co-expressed caveolin-1 or TACE/ADAM17, suggesting that disruptive activation of TGFß signaling through a loss of LDLRAD4 enhances EGFR and PTEN/AKT-dependent pathways via caveolin-1-dependent activation of TACE/ADAM17 during nongenotoxic hepatocarcinogenesis. The numbers of c-MYC+ cells and PCNA+ cells were higher in LDLRAD4-downregulated GST-P+ foci than in LDLRAD4-expressing GST-P+ foci, suggesting a preferential proliferation of pre-neoplastic cells by LDLRAD4 downregulation. Nongenotoxic hepatocarcinogens markedly downregulated Nox4 after 28 days and later decreased cleaved caspase 3+ cells in LDLRAD4-downregulated GST-P+ foci, suggesting an attenuation of apoptosis by LDLRAD4 downregulation through activation of the EGFR pathway. At the late hepatocarcinogenesis stage in a two-stage model, LDLRAD4 downregulation was higher in adenoma and carcinoma than in pre-neoplastic cell foci, suggesting a role of LDLRAD4 downregulation in tumor development. Our results suggest that nongenotoxic hepatocarcinogens cause disruptive activation of TGFß signaling through downregulating LDLRAD4 toward carcinogenesis in the rat liver.

Continuous exposure to α-glycosyl isoquercitrin from developmental stages to adulthood is necessary for facilitating fear extinction learning in rats.

We previously reported that exposure to α-glycosyl isoquercitrin (AGIQ) from the fetal stage to adulthood facilitated fear extinction learning in rats. The present study investigated the specific AGIQ exposure period sufficient for inducing this behavioral effect. Rats were dietarily exposed to 0.5% AGIQ from the postweaning stage to adulthood (PW-AGIQ), the fetal stage to postweaning stage (DEV-AGIQ), or the fetal stage to adulthood (WP-AGIQ). Fear memory, anxiety-like behavior, and object recognition memory were assessed during adulthood. Fear extinction learning was exclusively facilitated in the WP-AGIQ rats. Synaptic plasticity-related genes showed a similar pattern of constitutive expression changes in the hippocampal dentate gyrus and prelimbic medial prefrontal cortex (mPFC) between the DEV-AGIQ and WP-AGIQ rats. However, WP-AGIQ rats revealed more genes constitutively upregulated in the infralimbic mPFC and amygdala than DEV-AGIQ rats, as well as FOS-immunoreactive(+) neurons constitutively increased in the infralimbic cortex. Ninety minutes after the last fear extinction trial, many synaptic plasticity-related genes (encoding Ephs/Ephrins, glutamate receptors/transporters, and immediate-early gene proteins and their regulator, extracellular signal-regulated kinase 2 [ERK2]) were upregulated in the dentate gyrus and amygdala in WP-AGIQ rats. Additionally, WP-AGIQ rats exhibited increased phosphorylated ERK1/2+ neurons in both the prelimbic and infralimbic cortices. These results suggest that AGIQ exposure from the fetal stage to adulthood is necessary for facilitating fear extinction learning. Furthermore, constitutive and learning-dependent upregulation of synaptic plasticity-related genes/molecules may be differentially involved in brain regions that regulate fear memory. Thus, new learning-related neural circuits for facilitating fear extinction can be established in the mPFC.

High-flow nasal cannula therapy reduced the respiratory rate and respiratory distress in a standard model simulator and in patients with hypoxemic respiratory failure.

High-flow nasal cannula (HFNC) therapy has been increasingly applied to treat patients with severe hypoxemic respiratory failure. We investigated whether vital signs reflect the reduction of work of breathing in a simulator study and a clinical study. In the simulator study, a standard model high-fidelity human patient simulator (HPS) directly received 35 L/minute of 100% O2 via the HFNC. In the clinical study, the medical records of patients with hypoxemic respiratory failure who received HFNC therapy between January 2013 and May 2015 were retrospectively reviewed. Statistical analysis was performed using a one-way repeated analysis of variance followed by Bonferroni post-hoc testing. In the HPS, HFNC therapy significantly reduced the partial pressure of alveolar CO2, respiratory rate, and tidal volume (p < 0.001), and all values returned to baseline following HFNC therapy termination (p < 0.001). In the clinical study including 48 patients, the respiratory rate was significantly reduced from 27 ± 9 (baseline) to 24 ± 8 (3 hours), 24 ± 8 (5 hours), and 24 ± 8.0 (6 hours) (p < 0.05). The heart rate also decreased significantly (p < 0.05). Our results suggested that HFNC therapy reduced work of breathing and assessing vital signs can be important.

Ultrasound-guided identification of the cricothyroid membrane in a patient with a difficult airway: a case report.

BACKGROUND: Surgical cricothyroidotomy is considered to be the last resort for management of the difficult airway. A major point for a successful surgical cricothyroidotomy is to identify the location of the cricothyroid membrane. CASE PRESENTATION: We encountered a patient with progressive respiratory distress who was anticipated to have a difficult airway due to a large neck abscess. We prepared for both awake intubation and surgical cricothyroidotomy. The cricothyroid membrane could not be identified by palpation, but was readily identified using ultrasound. CONCLUSION: Ultrasound-guided identification of the cricothyroid membrane may be useful in a patient with a difficult airway due to neck swelling.

Emergency resuscitative thoracotomy in severe trauma: Analysis of the nation-wide registry data in Japan.

Aim: Emergency resuscitative thoracotomy is a potentially lifesaving procedure for patients with cardiac pulmonary arrest and profound circulatory failure resulting from a severe injury. However, survival rate post-emergency resuscitative thoracotomy shows considerable variation, with many studies constrained by limited sample sizes and ambiguous criteria for inclusion. Herein, we assessed the outcomes of emergency resuscitative thoracotomy and identified predictors of futility using Japan Trauma Data Bank data. Methods: Data of patients aged ≥18 years between 2004 and 2019 were analyzed. The primary outcome measure was survival at discharge. Descriptive statistics were used to compare the survivor and nonsurvivor groups. A multivariable logistic regression analysis was conducted to identify predictors of survival in patients undergoing emergency resuscitative thoracotomy while adjusting for confounding factors. Results: Among patients who underwent emergency resuscitative thoracotomy, 684/5062 (13.5%) survived. Age <65 years (adjusted odds ratio, 1.351; 95% confidence interval, 1.130-1.615; p < 0.001), absence of cardiac pulmonary arrest on emergency department arrival (adjusted odds ratio, 1.694; 95% confidence interval, 1.280-2.243; p < 0.01), Injury Severity Score <16 (adjusted odds ratio, 2.195; 95% confidence interval, 1.611-2.992; p < 0.01), and penetrating injury (adjusted odds ratio, 1.834; 95% confidence interval, 1.384-2.431; p < 0.01) were identified as factors associated with survival at discharge. Conclusion: The survival rate for emergency resuscitative thoracotomy in Japan stands at approximately 13.5%. Factors contributing to survival include younger age, absence of cardiopulmonary arrest at emergency department arrival, lack of severe trauma, and sustaining penetrating injuries.

A case report of undetected cardiac arrest in a patient with an insertable cardiac monitor.

Insertable cardiac monitors (ICMs) are small electrocardiographs implanted subcutaneously to automatically record electrocardiograms when arrhythmia is detected in patients with syncope. If the ICM misses a significant arrhythmia, it may delay the diagnosis of arrhythmogenic syncope and put the patient at risk. Herein, we describe a case of undetected cardiac arrest in a patient with ICM. An 87-year-old man with syncope was admitted to the hospital. After 8 days of monitoring, the cause could not be determined, and an ICM was implanted. Nine hours after implantation, the patient experienced cardiopulmonary arrest. Despite a body surface electrocardiogram showing ventricular flatline and fibrillation, the ICM failed to record. The cause of failure to record was considered to be the fluctuation in the R-wave amplitude of the ICM and noise oversensing. In conclusion, albeit infrequently, ICMs might overlook life-threatening arrhythmias. Even in cases where the ICM fails to detect an arrhythmia matching the symptoms, it may not be feasible to entirely rule out the presence of arrhythmias. Learning objective: Insertable cardiac monitors (ICMs) are used to diagnose arrhythmogenic syncope. However, extremely infrequently, ICM may fail to record life-threatening arrhythmias. Failure to capture arrhythmias can happen due to an unfortunate combination of factors such as a low amplitude of the recorded R wave and noise. Even in cases where the ICM does not detect an arrhythmia that matches the symptoms, it may not be feasible to completely exclude the presence of arrhythmias.

External validation of the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 pneumonia managed on high-flow nasal cannula therapy: a multicenter retrospective observational study in Japan.

BACKGROUND: The HACOR score for predicting treatment failure includes vital signs and acid-base balance factors, whereas the ROX index only considers the respiratory rate, oxygen saturation, and fraction of inspired oxygen (FiO2). We aimed to externally validate the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 (COVID-19) on high-flow nasal cannula (HFNC) therapy in Japan. METHODS: This retrospective, observational, multicenter study included patients, aged ≥ 18 years, diagnosed with COVID-19 and treated with HFNC therapy between January 16, 2020, and March 31, 2022. The HACOR score and ROX index were calculated at 2, 6, 12, 24, and 48 h after stating HFNC therapy. The primary outcome was treatment failure (requirement for intubation or occurrence of death within 7 days). We calculated the area under the receiver operating characteristic curve (AUROC) and assessed the diagnostic performance of these indicators. The 2-h time-point prediction was considered the primary analysis and that of other time-points as the secondary analysis. We also assessed 2-h time-point sensitivity and specificity using previously reported cutoff values (HACOR score > 5, ROX index < 2.85). RESULTS: We analyzed 300 patients from 9 institutions (median age, 60 years; median SpO2/FiO2 ratio at the start of HFNC therapy, 121). Within 7 days of HFNC therapy, treatment failure occurred in 127 (42%) patients. The HACOR score and ROX index at the 2-h time-point exhibited AUROC discrimination values of 0.63 and 0.57 (P = 0.24), respectively. These values varied with temporal changes-0.58 and 0.62 at 6 h, 0.70 and 0.68 at 12 h, 0.68 and 0.69 at 24 h, and 0.75 and 0.75 at 48 h, respectively. The 2-h time-point sensitivity and specificity were 18% and 91% for the HACOR score, respectively, and 3% and 100% for the ROX index, respectively. Visual calibration assessment revealed well calibrated HACOR score, but not ROX index. CONCLUSIONS: In COVID-19 patients receiving HFNC therapy in Japan, the predictive performance of the HACOR score and ROX index at the 2-h time-point may be inadequate. Furthermore, clinicians should be mindful of time-point scores owing to the variation of the models' predictive performance with the time-point. Trial registration UMIN (registration number: UMIN000050024, January 13, 2023).

Steroid Pulse Therapy as a Treatment for Patients With COVID-19 Pneumonia at an Intensive Care Unit: A Single-Center Retrospective Observational Study.

BACKGROUND: Evidence supporting the use of steroid pulse therapy in severely ill patients with coronavirus disease 2019 (COVID-19) pneumonia is lacking. Few studies have evaluated the efficacy of high-dose (1000 mg/day) methylprednisolone (mPSL), which is commonly used in Japan. AIM: This study aimed to compare the clinical outcomes with and without steroid pulse therapy (mPSL 1000 or 500 mg/day for three days) in patients with COVID-19 pneumonia, admitted to an intensive care unit (ICU). METHODS: Study design was retrospective observational study. The inclusion criterion was severe to critically ill adult patients with COVID-19 pneumonia requiring ICU admission. The exclusion criteria were as follows: patients (1) with a "Do not attempt to resuscitate" order; (2) with a "Do not intubate" order; or (3) admitted to the ICU owing to other infectious diseases were excluded. Treatment strategy was as follows: Patients were divided into two groups: steroid pulse therapy (Group P) and steroids without pulse therapy (Group NP). Group P received mPSL 1000 or 500 mg/day on ICU days 1-3, and Group NP received dexamethasone 6.6 mg or mPSL 1 or 2 mg/kg/day. The primary outcome was 28-day mortality. RESULTS: We enrolled 82 patients. Out of 70 who met the inclusion criteria, 48 and 22 were included in Groups P and NP, respectively. No difference in 28-day survival was observed between the Groups P and NP (log-rank P=0.11). After adjusting for covariates (age, sex, interleukin-6 level, and acute physiology and chronic health evaluation II score on ICU admission) using a multivariate Cox proportional hazard model, treatment with steroid pulse therapy significantly improved 28-day mortality (hazard ratio, 0.14; 95% confidence interval, 0.02-0.86; P=0.03). CONCLUSION: Steroid pulse therapy may improve the 28-day mortality in patients with COVID-19 pneumonia in the ICU.

Efficacy and safety of supraclavicular versus infraclavicular approach for subclavian vein catheterisation: An updated systematic review and meta-analysis of randomised controlled trials.

Background and Aims: Subclavian vein catheterisation (SVC) is more effective than internal jugular or femoral catheterisation and is linked to a lesser incidence of infection and patient discomfort. Whether the supraclavicular (SC) or infraclavicular (IC) approach is more effective for SVC is unclear in the previous systematic review. This updated review is designed to search the efficacy and safety of both approaches adopting the Grading of Recommendations Assessment, Development and Evaluation approach. Methods: In May 2022, we explored the databases of Embase, MEDLINE, CENTRAL, ClinicalTrials.gov and WHO-ICTRP for randomised controlled trials to compare the two approaches. Results: Seventeen trials (2482 cases) were included. In the primary outcomes, the SC approach likely reduces the failure proportion (relative risk [RR], 0.63; 95% confidence interval [CI], 0.47-0.86; I2 = 5%) and the incidence of malposition (RR, 0.23; 95% CI, 0.13-0.39; I2 = 0%) with moderate evidence and may slightly reduce the incidence of arterial puncture and pneumothorax (RR, 0.59; 95% CI, 0.29-1.22; I2 = 0%) with low evidence. In the secondary outcomes, the SC approach may decrease the access time and may increase the first-attempt success proportion. Conclusion: The SC approach for SVC should be selected after considering the clinician's expertise.

A case of hemorrhagic shock in a patient with neurofibromatosis type 1.

Complications of neurofibromatosis type 1 include fatal bleeding events due to vascular fragility. In this case of hemorrhagic shock due to a neurofibroma, the bleeding was controlled using an occlusion balloon and endovascular treatment which stabilized the patient. Systemic vascular investigation for bleeding sites is important to prevent fatal outcomes.

Efficacy of Remifentanil in Patients Undergoing Cardiac Surgery: A Systematic Review and Network Meta-Analysis.

Remifentanil, characterized by its ultra-short action duration and nonorgan-dependent metabolism, is applied in postcardiac surgery settings worldwide. While previous studies have compared its efficacy with that of other opioids, it has never been compared to a single specific opioid. Here, we evaluated whether remifentanil shortens mechanical ventilation (MV) times in patients after cardiac surgery. We identified randomized controlled trials that compared various opioids in adults (≥18 years) admitted to the intensive care unit after cardiac surgery. The primary outcome was the duration of MV, expressed as the mean difference (MD) in minutes, with a 95% confidence interval (CI). A 60-min reduction was considered significant based on prior research. Data were sourced from MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the World Health Organization International Clinical Trials Platforms Search Portal, and ClinicalTrials.gov, and a frequentist network meta-analysis was conducted. The eight identified studies indicate no differences in the duration of MV between remifentanil and fentanyl (MD 0.09 min; 95%CI -36.89-37.08), morphine (MD -19 min; 95%CI -55.86-16.21), or sufentanil (MD -2.44 min; 95%CI -67.52-62.55). Our study revealed that remifentanil did not reduce MV times in patients after cardiac surgery. The study protocol was registered with the Open Science Forum (https://osf.io/) (DOI 10.17605/OSF.IO/YAHW2).