The epigenetically regulated PP1α expression by KDM1A may contribute to oxycodone conditioned place preference in mice.

The lysine-specific demethylase 1 (KDM1A) is reported to be a regulator in learning and memory. However, the effect of KDM1A in oxycodone rewarding memory has yet to be studied. In our study, rewarding memory was assessed by using conditioned place preference (CPP) in male mice. Next generation sequencing and chromatin immunoprecipitation-PCR were used to explore the molecular mechanisms. Oxycodone significantly decreased PP1α mRNA and protein levels in hippocampal neurons. Oxycodone significantly increased KDM1A and H3K4me1 levels, while significantly decreased H3K4me2 levels in a time- and dose-dependent manner. Behavioral data demonstrated that intraperitoneal injection of ORY-1001 (KDM1A inhibitor) or intra-hippocampal injection of KDM1A siRNA/shRNA blocked the acquisition and expression of oxycodone CPP and facilitated the extinction of oxycodone CPP. The decrease of PP1α was markedly blocked by the injection of ORY-1001 or KDM1A siRNA/shRNA. Oxycodone-induced enhanced binding of CoRest with KDM1A and binding of CoRest with the PP1α promoter was blocked by ORY-1001. The level of H3K4me2 demethylation was also decreased by the treatment. The results suggest that oxycodone-induced upregulation of KDM1A via demethylation of H3K4me2 promotes the binding of CoRest with the PP1α promoter, and the subsequent decrease in PP1α expression in hippocampal neurons may contribute to oxycodone reward.

Cost-effectiveness of immune checkpoint inhibitors in treating metastatic urothelial cancer.

Objectives: Immune checkpoint inhibitor (ICI) is an important treatment option for metastatic urothelial carcinoma (mUC) patients. A lot of clinical evidence proved the survival benefits of ICI, but cost-effectiveness of the treatment remains unclear. This study evaluates the cost-effectiveness of the ICIs treatment in different sequences among mUC patients. Methods: We retrospectively analyzed mUC patients who had been treated at our hospital between January 2016 and December 2020. These patients received chemotherapy with or without ICI treatment (Pembrolizumab, Atezolizumab, Nivolumab, Durvalumab, or Avelumab). The patients were divided into three different groups: receiving chemotherapy alone, receiving a combination of first-line ICI and chemotherapy (ICI combination therapy), and receiving chemotherapy as the first-line treatment followed by second-line ICI therapy (Subsequent ICI therapy). The primary endpoint was cost per life day, while lifetime medical costs and overall survival were also evaluated. Results: The 74 enrolled patients had a median age of 67.0 years, with 62.2% being male. Of these patients, 23 had received chemotherapy only, while the remaining patients had received combined therapy with ICI in either first-line or as subsequent agents (37 patients had ever received atezolizumab, 18 pembrolizumab, 1 Durvalumab, 1 Nivolumab, and 1 Avelumab separately.). Fifty-five patients (74.3%, 55/74) received cisplatin amongst all the patients who underwent chemotherapy. Median overall survival was 27.5 months (95% CI, 5.2-49.9) in the first-line ICI combination therapy group, and 8.9 months (95% CI, 7.1-10.8) in the chemotherapy only. Median overall survival for the subsequent ICI therapy group was not reached. The median lifetime cost after metastatic UC diagnosis was USD 31,221. The subsequent ICI therapy group had significantly higher costs when compared with the ICI combination therapy group (155.8 USD per day, [IQR 99.0 to 220.5] v 97.8 USD per day, [IQR 60.8 to 159.19], p = 0.026). Higher insurance reimbursement expenses for the subsequent ICI therapy group were observed when compared with the ICI combination therapy group. Conclusion: Our real-world data suggests that first line use of ICI combined with chemotherapy demonstrates better cost-effectiveness and similar survival outcomes for mUC patients, when compared with subsequent ICI therapy after chemotherapy.

Effects of Hericium erinaceus polysaccharide in porcine IPEC-J2 intestinal epithelial cells against apoptosis induced by oxidative stress.

This study was intended to investigate whether Hericium erinaceus polysaccharides (HEP) prevent oxidative stress and apoptosis of intestinal porcine epithelial cells from jejunum (IPEC-J2 cells) induced by hydrogen peroxide (H2O2). Crude HEP were extracted and purified by chromatography. The ultraviolet and infrared spectra and monosaccharide composition of HEP were analyzed. Reactive oxygen species (ROS) generation was quantified by flow cytometry method, and lactate dehydrogenase (LDH) and malondialdehyde (MDA) production were determined by TBARS. Also, apoptosis was analyzed by flow cytometry method and the apoptosis-related regulatory molecules were determined by microplate or western blotting method. Our results showed that pretreatment of IPEC-J2 cells with HEP significantly scavenged ROS and reduced LDH and MDA production. HEP also reduced apoptosis and kept polarity of the mitochondrial membrane potential. Moreover, HEP increased the content of caspase-3 and PARP, and protein expression of Bcl-2, while inhibited Bax and Bad and reduced the content of caspase-9 and release of CytC. Meanwhile, HEP inhibited the protein expression of TNFR1, FAS, and FASL, and decreased the content of caspase-8. The results indicated that HEP had a protective effect against oxidative stress in IPEC-J2 cells and the underlying mechanism was reducing apoptosis via mitochondrial and death receptor pathways.

Ankle-brachial index associates with arteriovenous fistula stenosis.

BACKGROUND: Arteriovenous fistula (AVF) stenosis is associated with pre-existing arterial atherosclerosis of AVF and results in significant morbidity and hospitalization for hemodialysis patients. The ankle brachial index (ABI) is a noninvasive method of assessing atherosclerosis. This study was to examine whether ABI is a significant predictor for AVF stenosis. METHODS: This was a retrospective, longitudinal cohort study. Patients with hemodialysis between 1 January 2016 and 31 December 2022 were reviewed. ABI was assessed in January 2016. AVF stenosis was diagnosed by fistulography. RESULTS: A total of 82 patients were included. Forty-two patients experienced AVF stenosis. The univariate logistic regression analysis showed that AVF stenosis was associated with age (OR: 1.045, p = 0.033), DM status (OR: 5.529, p = 0.013), 7-year averaged cholesterol level (OR: 1.018, p = 0.034), 7-year averaged triglyceride level (OR: 1.007, p = 0.017), and ABI (OR: 0.011, p < 0.001). In multivariate logistic regression analysis, ABI was a strong predictor for AVF stenosis (OR: 0.036, p = 0.023). Then, a cut-off point of ABI with optimal sensitivity and specificity for AVF stenosis was 1.01. An analysis of time to events with adjustment for other variables showed that patients with ABI < 1.01 were significantly associated with AVF stenosis (HR: 3.859, p < 0.001). CONCLUSIONS: ABI below 1.01 was associated with AVF stenosis. This finding may be useful in tailoring surveillance programs for monitoring AVF function.

Malfunction endostapler trapped on renal vein - Nightmare scenario for surgeon.

The utilization of endostapler devices has become standard practice for renal vein ligation during laparoscopic nephroureterectomy. While exceptionally rare, malfunctions can occur in these devices. In the video, we present a malfunctioning endostapler that became trapped on the renal vein. Fortunately, this catastrophic event was successfully managed without conversion to open surgery or massive blood loss and was recorded on video. We propose a structured management flow chart for addressing GIA malfunction, aiming to assist surgeons in navigating through this potentially life-threatening situation.

Effectiveness of Chewing Gum on Nausea and Vomiting Following Postprocedure: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to evaluate the effectiveness of chewing gum in reducing postprocedure nausea and vomiting. DESIGN: A systematic review and meta-analysis. METHODS: A systematic literature search was performed on MEDLINE Complete, EMBASE, CINAHL, PubMed, Web of Science, Academic Search Complete, and Cochrane Library databases from their inception to October 2, 2022. Methodological quality was assessed using the revised Cochrane Risk of Bias 2.0 tool for randomized trials. A meta-analysis was performed using a fixed-effects model to calculate pooled effects with Review Manager 5.4.1. FINDINGS: Twelve randomized trials encompassing 1,458 participants were pooled. The chewing gum intervention was effective in reducing vomiting (P = .007; risk ratio = 0.55; 95% Cl = 0.35-0.85), but not nausea (P = .14; risk ratio = 0.84; 95% Cl = 0.66-1.06). Thirty-minute sessions of gum chewing were significantly more effective in reducing vomiting than 15-minute sessions (P = .04; risk ratio = 0.31; 95% Cl = 0.1-0.93). CONCLUSIONS: The results indicate that repeated gum chewing sessions of at least 30 minutes may act as a nonpharmacological intervention for reducing vomiting. However, further studies are necessary to determine the outcomes of chewing gum interventions.

Successful rescue pneumovesicoscopic surgery for post-Deflux® vesicoureteral junction obstruction.

BACKGROUND: Vesicoureteral junction (VUJ) obstruction after Deflux® subureteral injection for vesicoureteral reflux (VUR) is rare and minimally invasive management has not been reported. This work investigated the patients who underwent Deflux® injection for VUR and identified those with subsequent VUJ obstruction. METHODS: Medical records of matched patients from October 2003 to March 2022 were reviewed, and parameters were retrospectively studied. All patients underwent Deflux® injection. The injection was performed under general anesthesia using the same manner. For patients complicated with VUJ obstruction, the symptoms, signs, management, images, renal ultrasounds, Tc-99m dimercaptosuccinic acid renal scintigraphy, histology of VUJ region, and outcomes were documented and reported. VUJ stenosis was diagnosed by performing renal ultrasound and magnetic resonance imaging. RESULTS: Totally 407 patients (554 ureterorenal units) received Dx/HA injections for VUR. VUJ obstruction was found in three patients (four ureterorenal units). Originally, three were grade V VUR, and one was grade IV. The repeated injection was not a risk factor for VUJ obstruction. The overall incidence of VUJ obstruction post-Dx/HA injection was 0.7% by ureter. The incidences were 0%, 0.75%, and 2.25% for grade I-III, IV, and V VUR, respectively. After the initial conversion case of pneumovesicoscopic ureteral reimplantation, the procedure was performed smoothly and successfully in the two following cases. CONCLUSIONS: Pneumovesicoscopic ureteral reimplantation offers an alternative for VUJ obstruction following Dx/HA injection for VUR. Fibrosis and foreign-body reaction may influence the feasibility. High-grade VUR and young age of injection were related to VUJ obstruction.

Is Thrombocytopenia an In-Hospital Mortality Risk Factor among Patients with Acute Ischemic Stroke? A Propensity Score-Matched Analysis from the MIMIC-IV Database.

(1) Background: We aimed to evaluate the aspect of thrombocytopenia in patients with acute ischemic stroke (AIS); (2) Methods: Patients with AIS were recruited in the Medical Information Mart for Intensive Care IV database from 2008 to 2019. The thrombocytopenia was defined as a platelet blood count of less than 150 K/µL. We compared the patient characteristics and clinical outcomes using propensity score matching (PSM); (3) Results: Thrombocytopenia affected 151 out of the 1236 patients (12.2%). Patients with thrombocytopenia were older (70.5 ± 12.8 vs. 68.4 ± 14.4; SMD = 0.154) and had a higher Charlson comorbidity index (7.3 ± 2.5 vs. 6.7 ± 2.7; SMD = 0.228) and acute physiology score III (44.8 ± 21.0 vs. 38.2 ± 19.1; SMD = 0.328) than those without thrombocytopenia. The risk of in-hospital mortality did not increase linearly or nonlinearly with a lower platelet count (overall p value = 0.794; nonlinear p value = 0.646). After PSM, 147 pairs remained. Thrombocytopenia was not linked with in-hospital mortality (HR: 1.06, 95% CIs: 0.60-1.88); (4) Conclusions: We described the clinical characteristics of patients admitted for thrombocytopenia and AIS who did not receive reperfusion therapy; additionally, we found that thrombocytopenia was not an independent short-term risk factor of in-hospital mortality.

Endovascular therapy for acute ischemic stroke in patients with active malignancy: a meta-analysis with trial sequential analysis.

BACKGROUND: Active malignancy has a poorer prognosis and more deaths in patients with acute ischemic stroke (AIS). The outcomes of endovascular therapy (EVT) remain controversial in patients with AIS and active malignancy. METHODS: We searched PubMed, Cochrane, and Embase for articles published up to June 1, 2022. The primary outcome was good functional outcome at 3 months and successful reperfusion between patients with cancer and AIS and control patients. The secondary and safety outcomes included mortality at 3 months, in-hospital mortality, symptomatic intracerebral hemorrhage (sICH), any ICH, and subarachnoid hemorrhage (SAH). RESULTS: Twelve studies involving 5944 patients with AIS secondary to EVT were included (389 patients having active malignancy). The OR of good functional outcome at 3 months was 0.53 (95% CI 0.41 to 0.67) between the two groups. The OR of successful reperfusion between the two groups was 0.90 (95% CI 0.63 to 1.30). Compared with patients without cancers, those with cancers had a higher risk of mortality at 3 months (OR 3.64; 95% CI 2.35 to 6.27) and in-hospital mortality (OR 3.46; 95% CI 1.71 to 7.01). Despite a higher point estimate regarding any ICH (OR 1.41; 95% CI 1.01 to 1.96) and SAH (OR 2.53; 95% CI 1.10 to 5.81), sICH (OR 0.85; 95% CI 0.51 to 1.42) was not significant. CONCLUSION: Although a quarter of patients with active malignancy and AIS regained functional independence, physicians and patients should consider whether to apply EVT in patients with active malignancy.

The Role of Nondiabetic Hyperglycemia in Critically Ill Patients with Acute Ischemic Stroke.

In this study, we aim to elucidate the association between nondiabetic hyperglycemia and the short-term prognosis of critically ill patients with acute ischemic stroke. We extracted data using the Medical Information Mart for Intensive Care IV from 2008 to 2019. The primary outcomes were set as intensive care units (ICU) and in-hospital mortality. We developed a Cox proportional hazards model to determine the nonlinear association between serum glucose levels and primary outcomes. Of the 1086 patients included, 236 patients had hyperglycemia. Patients with hyperglycemia were associated with higher ages, female gender, higher Charlson Comorbidity Index scores, and higher Acute Physiology Score III scores. After propensity score matching, 222 pairs remained. The hyperglycemia group had a significantly higher ICU mortality (17.6% vs. 10.8%; p = 0.041). Meanwhile, no significant differences in ICU length of stay (5.2 vs. 5.2; p = 0.910), in-hospital mortality (26.6% vs. 18.9%, p = 0.054), and hospital length of stay (10.0 vs. 9.1; p = 0.404) were observed between the two groups. The Kaplan-Meier curves for ICU and in-hospital survival before matching suggested significant differences; however, after matching, they failed to prove any disparity. Non-diabetic patients with acute ischemic stroke have poor clinical characteristic while encountering hyperglycemic events; therefore, careful monitoring in the acute phase is still required.

[Health Risk Assessment and Environmental Benchmark of Heavy Metals in Cultivated Land in Mountainous Area of Northwest Guizhou Province].

An extensive investigation of heavy metal (Cd, Hg, As, Pb, and Cr) levels in 137 pairs of soil-maize/rice samples was conducted in cultivated land from a typical karst mountain area in the Northwest of Guizhou Province. A health risk assessment model was used to assess the health risks of those areas, and the environmental benchmarks of heavy metals in soils were evaluated using the species sensitivity distribution (SSD) model. The results showed that the soils of maize and rice were polluted by heavy metals. Cd was the primary pollutant, with an exceeding rate ranging from 87% to 445%. The contaminated level of maize fields was higher than those of rice fields. In contrast, only 3.51% and 13.4% of Cd content in maize kernels and rice grains exceeded the national threshold, and the Cd heavy metal accumulation ability of rice was higher than that of maize. The carcinogenic and non-carcinogenic risks of heavy metals for adults and children in the study area were at a low level. The carcinogenic risk of rice consumption was slightly higher than that of maize, and the health risk to children was higher than that to adults. The results derived from the SSD method showed that the 95% and 5% hazardous concentrations (HC5 and HC95) of maize fields were 0.67 for Cd, 771.99 for As, 40.85 for Pb and 609.88 for Cr mg·kg-1, and HC95were 48.47 for Cd, 159.67 for As, 1735.68 for Pb and 1671.74 for Cr mg·kg-1, respectively. The HC5 values of rice fields were 2.42 for Cd, 8.88 for As, 41.41 for Pb and 27.84 for Cr mg·kg-1, and the HC95 values were 48.47 for Cd, 159.67 for As, 1735.68 for Pb and 1671.74 for Cr mg·kg-1, respectively. The HC5 values of Cd, As, and Cr in maize fields and Cd in rice fields were significantly higher than the soil risk screening values in the current standard, and the HC95 values of the two fields were higher than the soil risk intervened values. The results indicated that the current standard would be too strict to evaluate the actual pollution level of soil heavy metals in this area.

Reduction in hemodialysis catheter-related bloodstream infections after implementation of a novel care program.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) due to dialysis is the major factor causing morbidity and mortality factor for patients undergoing hemodialysis and is associated with additional costs for these patients. This study investigated the effect of a novel care program in terms of reducing CRBSIs for hemodialysis patients with nontunneled (temporary) catheters inserted in their femoral veins. METHODS: This study included dialysis patients (inpatients and outpatients) from July 2018 to September 2019, covering two periods, pre-intervention (baseline period) and intervention with a novel care program (novel care period). The novel care program was initiated on December 1, 2018. The CRBSI rates (/1000 catheter-days) for the baseline and novel care periods were compared, and the characteristics of the pathogens were determined. FINDINGS: Of a total of 72 patients, 33 were from the baseline period and 39 were from the novel care period. Patients in the baseline and novel care periods had the catheter inserted in their femoral veins for a median of 20 and 29 days, respectively. The CRBSI rate decreased by 82.63%, from 8.52/1000 catheter-days in the baseline period to 1.48/1000 catheter-days in the novel care period (p = 0.036). The most common organisms involved in CRBSIs were coagulase-negative staphylococcus and Burkholderia cepacia (26% for both). DISCUSSION: The novel care program reduced the incidence of CRBSIs in patients with temporary catheters inserted in their femoral veins.

Effects of Electrical Stimulation of Acupoints on Xerostomia for Patients Who Undergo Hemodialysis.

Xerostomia plays a major role in higher interdialytic weight gain (IDWG), which causes cardiovascular complications in patients who undergo hemodialysis. However, few studies have determined a method to manage xerostomia. This study determines the effect of transcutaneous electrical acupoint stimulation (TEAS) on hemodialysis patients with xerostomia and the percentage of IDWG. The study was a single-blind and quasi-experimental study. There are 75 participants: 37 in the TEAS group and 38 in the contrast group. The TEAS group used 250 µs and 50 Hz and the contrast group used 50 µs and 2 Hz three times a week for 3 weeks to stimulate ST 6 and TE17 acupoints. The salivary flow rates, dry mouth, and %IDWG were determined before, during and one week after the program. Compared with the contrast group, the TEAS group showed a significantly improved salivary flow rate (mL/min) (F (2, 123) = 15.28, p < 0.0001), and patients recovered their normal salivary flow rate. However, the results show that both groups showed significant improvement in dry mouth after treatment. The TEAS group demonstrated no effect in terms of %IDWG, as expected. The results show that a TEAS program is an effective means of symptom management for xerostomia patients who undergo hemodialysis. A TEAS program can be used to manage symptoms for xerostomia patients who undergo hemodialysis.

Plasma Anion Gap and Risk of In-Hospital Mortality in Patients with Acute Ischemic Stroke: Analysis from the MIMIC-IV Database.

We aimed to investigate the association between the plasma anion gap (AG) and in-hospital mortality among patients with acute ischemic stroke (AIS). In total, 1236 AIS patients were enrolled using the Medical Information Mart for Intensive Care Database IV. Primary outcome was in-hospital mortality. The patients were divided into four groups according to AG category. The mean age and Charlson comorbidity index increased as the AG category increased. The fourth AG category was most related to the in-hospital mortality (hazards ratio (HR), 95% confidence interval (CI): 2.77, 1.60-4.71), even after adjusting for possible confounding variables (Model 1: HR, 95% CI: 3.37, 1.81-6.09; Model 2: HR, 95% CI: 3.57, 1.91-6.69). Moreover, intensive care unit mortality (p = 0.008) was higher in the highest AG category, but the intracranial hemorrhage (p = 0.071) did not associate with the plasma AG. The plasma AG had a satisfactory predictive ability for in-hospital mortality among AIS patients (areas under the receiver operating characteristic curve: 0.631). The plasma AG is an independent risk factor that can satisfactorily predict the in-hospital mortality among AIS patients.

Atrial Fibrillation Is Not an Independent Determinant of Mortality Among Critically Ill Acute Ischemic Stroke Patients: A Propensity Score-Matched Analysis From the MIMIC-IV Database.

BACKGROUND/OBJECTIVE: This study was conducted to investigate the clinical characteristics and outcomes of patients with acute ischemic stroke and atrial fibrillation (AF) in intensive care units (ICUs). METHODS: In the Medical Information Mart for Intensive Care IV database, 1,662 patients with acute ischemic stroke were identified from 2008 to 2019. Of the 1,662 patients, 653 had AF. The clinical characteristics and outcomes of patients with and without AF were compared using propensity score matching (PSM). Furthermore, univariate and multivariate Cox regression analyzes were performed. RESULTS: Of the 1,662 patients, 39.2% had AF. The prevalence of AF in these patients increased in a stepwise manner with advanced age. Patients with AF were older and had higher Charlson Comorbidity Index, CHA2DS2-VASc Score, HAS-BLED score, and Acute Physiology Score III than those without AF. After PSM, 1,152 patients remained, comprising 576 matched pairs in both groups. In multivariate analysis, AF was not associated with higher ICU mortality [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.64-1.42] or in-hospital mortality (HR, 1.08; 95% CI, 0.79-1.47). In Kaplan-Meier analysis, no difference in ICU or in-hospital mortality was observed between patients with and without AF. CONCLUSIONS: AF could be associated with poor clinical characteristics and outcomes; however, it does not remain an independent short-term predictor of ICU and in-hospital mortality among patients with acute ischemic stroke after PSM with multivariate analysis.

[Impact of Chest Physical Therapy on Length of Stay and Medical Expenditures for Patients With Pulmonary Infection].

BACKGROUND: Sputum retention increases significantly the risk of repetitive respiratory tract infections, which may result in dyspnea and lung injury. Chest physical therapy is the most commonly used method to assist patients to expel sputum. This intervention promotes sputum clearance and prevents airway obstruction, thereby reducing the risk of lung infection. PURPOSE: The purpose of this study was to investigate the impact of chest physical therapy on the length of hospitalization and the medical expenditures of patients with pulmonary infection. METHODS: A retrospective-correlation study was used. Data were collected from 2013 to 2017 in the medical ward of a medical center located in southern Taiwan. The annual differences in the length of stay, medical expenditures, and readmission rates for patients with pulmonary infection after chest physical therapy were analyzed. RESULTS: A total of 707 patients with pulmonary infection were recruited and enrolled as participants. The mean age of the participants was 75.4 (± 13.8) years. The results showed that length of stay (F = 6.66, p < .001) and medical expenditures (F = 5.34, p < .001) were both significantly lower after chest physical therapy and that the corresponding readmission rates had decreased significantly, from 6.9% in 2013 to 1.7% in 2017 (x2 = 5.84, p = .016). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: After conducting a yearly comparison, the results of this study indicate that administering chest physical therapy may be an effective strategy for reducing the length of stay, readmission rates, and medical expenditures of patients with pulmonary infection. The findings of this study may serve as a reference for the clinical implementation of chest physical therapy in patients with pulmonary infection.

High-flow nasal cannula therapy as apneic oxygenation during endotracheal intubation in critically ill patients in the intensive care unit: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to assess the clinical efficacy of high-flow nasal cannula (HFNC) therapy as apneic oxygenation in critically ill patients who require endotracheal intubation in the intensive care unit (ICU). This systematic review and meta-analysis included six randomized controlled trials and a prospective study identified in PubMed, Embase, Cochrane Library, and the Web of Science until August 18, 2019. In this meta-analysis including 956 participants, HFNC was noninferior to standard of care during endotracheal intubation regarding incidence of severe hypoxemia, mean lowest oxygen saturation, and in-hospital mortality. HFNC significantly shortened the ICU stay by a mean of 1.8 days. In linear meta-regression interaction analysis, the risk ratio of severe hypoxemia decreased with increasing baseline partial oxygen pressure (PaO2) to fraction of inspired oxygen (FiO2) ratio. In subgroup analysis, HFNC significantly reduced the incidence of severe hypoxemia during endotracheal intubation in patients with mild hypoxemia (PaO2/FiO2> 200 mmHg; risk difference, -0.06; 95% confidence interval, -0.12 to -0.01; number needed to treat = 16.7). In conclusion, HFNC was noninferior to standard of care for oxygen delivery during endotracheal intubation and was associated with a significantly shorter ICU stay. The beneficial effect of HFNC in reducing the incidence of severe hypoxemia was observed in patients with mild hypoxemia.

Reduction of AHI1 in the serum of Taiwanese with probable Alzheimer's disease.

OBJECTIVE: The development of blood-based biomarkers for early diagnosis and treatment of Alzheimer's disease (AD) is desirable. In AD model mouse brain and neuronal cells, Abelson helper integration site-1 (AHI1) protein is reduced. AHI1 facilitates intracellular amyloid precursor protein (APP) translocation to inhibit amyloidogenic pathology of AD, and thus may be an AD biomarker. METHODS: This study was conducted among 32 AD patients and 54 healthy control (HC) subjects. AHI1-related protein levels from initially collected serum samples in each group were screened using Western blotting. The protein concentrations of AHI1 and amyloid-ß (Aß), peptide(s) derived from APP, from all serum samples were analyzed using ELISA. RESULTS: In AD serum, AHI1 and a large truncated C-terminal APP fragment were significantly reduced. The average concentrations of serum AHI1 and Aß in AD were significantly lower than those in HC. Notably, AHI1 concentration in HC serum was decreased in an age-dependent manner, while it was consistently low in AD serum and had no correlation with Aß or mini-mental state examination score. The receiver operating characteristic analysis on all subjects demonstrated an area under curve (AUC) value of 0.7 for AHI1 on AD diagnosis, while the AUC increased to 0.82 on the subjects younger than 77 years old, suggesting a good diagnostic performance of serum AHI1 for AD especially at relatively young age. CONCLUSION: An early event of AHI1 reduction in the body of AD patients was observed. Serum AHI1 may be valuable for early diagnosis of AD.