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Zhonghua Yi Xue Za Zhi Jun 2024To investigate the impact of intraoperative hypothermia on postoperative outcome in neonatal patients undergoing non-cardiac surgery. The data of 1 008 neonates...
To investigate the impact of intraoperative hypothermia on postoperative outcome in neonatal patients undergoing non-cardiac surgery. The data of 1 008 neonates undergoing non-cardiac surgery in Children's Hospital, Zhejiang University School of Medicine from January 2020 to October 2022 were retrospectively collected,which included 558 males and 450 females, with a midian age [ (, )] of 6 (2, 14) days. Neonates were divided into 4 groups according to whether hypothermia (below 36 ℃) occurred and the lowest body temperature during the surgery: normal temperature group (=246), mild hypothermia group (the lowest temperature ranged 35.0-35.9 ℃, =434), moderate hypothermia group (the lowest temperature ranged 34.0-34.9 ℃, =232) and severe hypothermia group (the lowest temperature<34 ℃, =96). The primary outcome was the incidence of intraoperative hypothermia. The four groups' difference of postoperative hospital stay, postoperative mortality within 30 days, postoperative pulmonary complications, postoperative hemorrhage/blood transfusion and acidosis were compared. Multivariate logistic regression was used to analyze the relationship between intraoperative hypothermia and prolonged postoperative hospital stay (>14 d), 30 d-mortality and other complications. In the 1 008 neonatal patients, 762 (75.6%) cases suffered intraoperative hypothermia, among which the incidence of mild, moderate and severe hypothermia was 43.1% (434/1008), 23.0% (232/1008) and 9.5% (96/1008), respectively. The postoperative hospital stay in normal, mild, moderate and severe hypothermia groups was 9.0 (5.8, 18.0), 12.0 (7.0, 21.0), 17.0 (10.0, 34.5) and 31.5 (12.5, 55.8) days. The mortality rate with 30 days after surgery was 2.9% (7/246), 4.4% (19/434), 6.9% (16/232) and 14.7% (14/96), the incidence of postoperative pulmonary complications was 31.7%(78/246), 39.9%(173/434), 44.8%(104/232) and 67.4%(64/96), the rate of postoperative hemorrhage/blood transfusion was 19.9%(49/246), 32.3%(140/434), 49.1%(114/232) and 79.0%(75/96), and the incidence of acidosis was 26.8%(66/246), 35.7%(155/434), 44.4%(103/232) and 46.3%(44/96), respectively. All differences were statistically significant (all <0.05). According to the adjusted logistic regression analysis, compared with the normal body temperature group, severe hypothermia was associated with prolonged postoperative hospital stay (=1.962, 95%: 1.063-3.619) and postoperative pulmonary complications (=2.020, 95%: 1.149-3.553). The mild, moderate and severe hypothermia group could increase the risk of postoperative blood/transfusion rate (mild: =1.690, 95%: 1.080-2.644; Moderate: =2.382, 95%: 1.444-3.927; Severe: =8.334, 95%: 3.123-8.929). The mild and moderate hypothermia could raise the risk of acidosis (mild: =1.458, 95%: 1.009-2.107; Moderate: =1.949, 95%: 1.279-2.972). Intraoperative hypothermia can prolong the postoperative hospital stay, and increase the risk of postoperative mortality, postoperative pulmonary complications, postoperative hemorrhage/transfusion, and acidosis.
Topics: Humans; Male; Female; Retrospective Studies; Hypothermia; Infant, Newborn; Prognosis; Postoperative Complications; Intraoperative Complications; Body Temperature; Incidence
PubMed: 38871472
DOI: 10.3760/cma.j.cn112137-20231120-01139 -
Cancer Letters Jun 2024Lysosomes are single membrane bounded group of acidic organelles that can be involved in a process called lysosomal exocytosis which leads to the extracellular release... (Review)
Review
Lysosomes are single membrane bounded group of acidic organelles that can be involved in a process called lysosomal exocytosis which leads to the extracellular release of their content. Lysosomal exocytosis is required for plasma membrane repair or remodeling events such as bone resorption, antigen presentation or mitosis, and for protection against toxic agents such as heavy metals. Recently, it has been showed that to fulfill this protective role, lysosomal exocytosis needs some autophagic proteins, in an autophagy-independent manner. In addition to these crucial physiological roles, lysosomal exocytosis plays a major protumoral role in various cancers. This effect is exerted through tumor microenvironment modifications, including extracellular matrix remodeling, acidosis, oncogenic and profibrogenic signals. This review provides a comprehensive overview of the different elements released in the microenvironment during lysosomal exocytosis, i.e. proteases, exosomes, and protons, and their effects in the context of tumor development and treatment.
PubMed: 38871244
DOI: 10.1016/j.canlet.2024.217024 -
Biochemical and Biophysical Research... Jun 2024Cardiac ischemia results in anaerobic metabolism and lactic acid accumulation and with time, intracellular and extracellular acidosis. Ischemia and subsequent...
Cardiac ischemia results in anaerobic metabolism and lactic acid accumulation and with time, intracellular and extracellular acidosis. Ischemia and subsequent reperfusion injury (IRI) lead to various forms of programmed cell death. Necroptosis is a major form of programmed necrosis that worsens cardiac function directly and also promotes inflammation by the release of cellular contents. Potential effects of increasing acidosis on programmed cell death and their specific components have not been well studied. While apoptosis is caspase-dependent, in contrast, necroptosis is mediated by the receptor-interacting protein kinases 1 and 3 (RIPK1/3). In our study, we observed that at physiological pH = 7.4, caspase-8 inhibition did not prevent TNFα-induced cell death in mouse cardiac vascular endothelial cells (MVECs) but promoted necroptotic cell death. As expected, necroptosis was blocked by RIPK1 inhibition. However, at pH = 6.5, TNFα induced an apoptosis-like pattern which was inhibited by caspase-8 inhibition. Interestingly phosphorylation of necroptotic molecules RIPK1, RIPK3, and mixed lineage kinase domain-like protein (MLKL) was enhanced in an acidic pH environment. However, RIPK3 and MLKL phosphorylation was self-limited which may have limited their participation in necroptosis. In addition, an acidic pH promoted apoptosis-inducing factor (AIF) cleavage and nuclear translocation. AIF RNA silencing inhibited cell death, supporting the role of AIF in this cell death. In summary, our study demonstrated that the pH of the micro-environment during inflammation can bias cell death pathways by altering the function of necroptosis-related molecules and promoting AIF-mediated cell death. Further insights into the mechanisms by which an acidic cellular micro-environment influences these and perhaps other forms of regulated cell death, may lead to therapeutic strategies to attenuate IRI.
PubMed: 38870845
DOI: 10.1016/j.bbrc.2024.150215 -
FASEB Journal : Official Publication of... Jun 2024Mitochondrial disease is a devastating genetic disorder, with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and m.3243A>G...
Mitochondrial disease is a devastating genetic disorder, with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and m.3243A>G being the most common phenotype and genotype, respectively. The treatment for MELAS patients is still less effective. Here, we performed transcriptomic and proteomic analysis in muscle tissue of MELAS patients, and discovered that the expression of molecules involved in serine catabolism were significantly upregulated, and serine hydroxymethyltransferase 2 (SHMT2) increased significantly in both the mRNA and protein levels. The SHMT2 protein level was also increased in myoblasts with m.3243A>G mutation, which was transdifferentiated from patients derived fibroblasts, accompanying with the decreased nicotinamide adenine dinucleotide (NAD)/reduced NAD (NADH) ratio and cell viability. After treating with SHMT2 inhibitor (SHIN1), the NAD/NADH ratio and cell viability in MELAS myoblasts increased significantly. Taken together, our study indicates that enhanced serine catabolism plays an important role in the pathogenesis of MELAS and that SHIN1 can be a potential small molecule for the treatment of this disease.
Topics: Humans; MELAS Syndrome; Glycine Hydroxymethyltransferase; Serine; Myoblasts; NAD; Male; Proteomics; Female; Transcriptome; Multiomics
PubMed: 38865203
DOI: 10.1096/fj.202302286RRR -
Clinical Toxicology (Philadelphia, Pa.) Jun 2024
PubMed: 38864889
DOI: 10.1080/15563650.2024.2350597 -
Journal of the ASEAN Federation of... 2024
Topics: Humans; Diabetic Ketoacidosis; Uric Acid; Male; Female; Adult; Crystalluria
PubMed: 38863919
DOI: 10.15605/jafes.039.01.20 -
Acute and Critical Care May 2024We evaluated relationships of vital signs and laboratory-tested physiological parameters with in-hospital mortality, focusing on values that are unusual or extreme even...
BACKGROUND
We evaluated relationships of vital signs and laboratory-tested physiological parameters with in-hospital mortality, focusing on values that are unusual or extreme even in critical care settings.
METHODS
We retrospectively studied Philips Healthcare-MIT eICU data (207 U.S. hospitals, 20142015), including 166,959 adult-patient critical care admissions. Analyzing most-deranged (worst) value measured in the first admission day, we investigated vital signs (body temperature, heart rate, mean arterial pressure, and respiratory rate) as well as albumin, bilirubin, blood pH via arterial blood gas (ABG), blood urea nitrogen, creatinine, FiO2 ABG, glucose, hematocrit, PaO2 ABG, PaCO2 ABG, sodium, 24-hour urine output, and white blood cell count (WBC).
RESULTS
In-hospital mortality was ≥50% at extremes of low blood pH, low and high body temperature, low albumin, low glucose, and low heart rate. Near extremes of blood pH, temperature, glucose, heart rate, PaO2 , and WBC, relatively. Small changes in measured values correlated with several-fold mortality rate increases. However, high mortality rates and abrupt mortality increases were often hidden by the common practice of thresholding or binning physiological parameters. The best predictors of in-hospital mortality were blood pH, temperature, and FiO2 (scaled Brier scores: 0.084, 0.063, and 0.049, respectively).
CONCLUSIONS
In-hospital mortality is high and sharply increasing at extremes of blood pH, body temperature, and other parameters. Common-practice thresholding obscures these associations. In practice, vital signs are sometimes treated more casually than laboratory-tested parameters. Yet, vitals are easier to obtain and we found they are often the best mortality predictors, supporting perspectives that vitals are undervalued.
PubMed: 38863361
DOI: 10.4266/acc.2023.01361 -
Academic Emergency Medicine : Official... Jun 2024Bupropion toxicity can lead to adverse cardiovascular events (ACVE), but delayed onset of toxicity makes risk stratification difficult. This study aimed to validate...
OBJECTIVES
Bupropion toxicity can lead to adverse cardiovascular events (ACVE), but delayed onset of toxicity makes risk stratification difficult. This study aimed to validate previously defined predictors of ACVE and identify novel predictors among patients presenting to the emergency department (ED) after bupropion overdose.
METHODS
This secondary analysis of prospective data from the Toxicology Investigators Consortium Core Registry analyzed adult acute or acute-on-chronic bupropion exposures from 2015 to 2018. The primary outcome was ACVE (any of the following: myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). Potential predictors of ACVE included previously derived predictors in the overall drug overdose population (prior cardiac disease, initial serum bicarbonate < 20 mEq/L, and initial QTc ≥ 500 ms), exposure circumstances, and initial serum lactate value. Candidate predictors were evaluated using univariate analysis and multivariable regression modeling. Receiver operator characteristic curves were used to derive optimal cutoff points for novel predictors, and prognostic test characteristics were calculated.
RESULTS
Of 355 patients analyzed, ACVE occurred in 34 (9.6%) patients. Initial serum bicarbonate < 20 mEq/L (adjusted odds ratio [aOR] 4.42, 95% confidence interval [CI] 1.94-10.0) and initial QTc ≥ 500 ms (aOR 2.52, 95% CI 1.01-6.09) independently predicted ACVE. Exposure circumstances did not predict ACVE. Initial serum lactate > 5.2 mmol/L independently predicted ACVE (aOR 12.2, 95% CI 2.50-75.2) and was 90.7% specific with 80.3% negative predictive value.
CONCLUSIONS
Metabolic acidosis and QTc prolongation were validated as predictors of ACVE in ED patients with bupropion overdose. Serum lactate elevation was strongly predictive of ACVE in this study and warrants further investigation.
PubMed: 38863233
DOI: 10.1111/acem.14960 -
Critical Care (London, England) Jun 2024Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT.
METHODS
We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité-Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO-adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment.
RESULTS
From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO-adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group (p = 0.26).
CONCLUSION
Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS.
TRIAL REGISTRATION
The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed.
Topics: Humans; Male; Female; Pilot Projects; Middle Aged; Hypercapnia; Aged; Carbon Dioxide; Respiratory Distress Syndrome; Prospective Studies; Renal Replacement Therapy; Intensive Care Units; Respiration, Artificial; Continuous Renal Replacement Therapy
PubMed: 38863072
DOI: 10.1186/s13054-024-04979-z -
Advances in Clinical and Experimental... Jun 2024Acute kidney injury (AKI) has become a common complication of acute ischemic stroke (AIS) and may have a significant impact on clinical outcomes. Anion gap (AG)/albumin...
BACKGROUND
Acute kidney injury (AKI) has become a common complication of acute ischemic stroke (AIS) and may have a significant impact on clinical outcomes. Anion gap (AG)/albumin corrected anion gap (ACAG) are used to assess acid-base balance status and help identify the severity of metabolic acidosis.
OBJECTIVES
To explore the association of AG and ACAG with the risk of AKI in AIS patients admitted to the intensive care unit (ICU).
MATERIAL AND METHODS
Data of AIS patients in this retrospective cohort study were extracted from the electronic ICU (eICU) databases (2014-2015). The outcome was the occurrence of AKI after ICU admission. The covariates included demographic data, vital signs, comorbidities, laboratory parameters, and medication use. The association of AG and ACAG levels with AKI risk in AIS patients was evaluated using univariate and multivariate logistic regression models with odds ratios (ORs) and 95% confidence intervals (95% CIs). The predictive performance of AG and ACAG for the risk of AKI in AIS patients was assessed with the area under the curve (AUC). To further explore the association of AG and ACAG levels with AKI risk, subgroup analyses were performed according to comorbidities.
RESULTS
Of the 1,260 AIS patients, 546 (43%) developed AKI. Elevated AG (OR = 1.73, 95% CI: 1.32-2.29) and ACAG (OR = 1.57, 95% CI: 1.21-2.04) were associated with the risk of AKI in AIS patients. The AUC of ACAG was superior to AG for predicting the risk of AKI (0.581 vs 0.558; p = 0.024). Elevated ACAG levels were associated with the risk of AKI in AIS patients without ischemic heart disease (OR = 1.60, 95% CI: 1.19-2.15), diabetes (OR = 1.58, 95% CI: 1.19-2.10) and hypertension (OR = 1.69, 95% CI: 1.24-2.30).
CONCLUSIONS
Albumin corrected anion gap was a better predictor than AG for AKI risk in AIS patients, which may help clinicians identify high-risk patients for AKI.
PubMed: 38860714
DOI: 10.17219/acem/186814