Functional Plasmonic Microscope: Characterizing the Metabolic Activity of Single Cells via Sub-nm Membrane Fluctuations.

Metabolic abnormalities are at the center of many diseases, and the capability to film and quantify the metabolic activities of a single cell is important for understanding the heterogeneities in these abnormalities. In this paper, a functional plasmonic microscope (FPM) is used to image and measure metabolic activities without fluorescent labels at a single-cell level. The FPM can accurately image and quantify the subnanometer membrane fluctuations with a spatial resolution of 0.5 µm in real time. These active cell membrane fluctuations are caused by metabolic activities across the cell membrane. A three-dimensional (3D) morphology of the bottom cell membrane was imaged and reconstructed with FPM to illustrate the capability of the microscope for cell membrane characterization. Then, the subnanometer cell membrane fluctuations of single cells were imaged and quantified with the FPM using HeLa cells. Cell metabolic heterogeneity is analyzed based on membrane fluctuations of each individual cell that is exposed to similar environmental conditions. In addition, we demonstrated that the FPM could be used to evaluate the therapeutic responses of metabolic inhibitors (glycolysis pathway inhibitor STF 31) on a single-cell level. The result showed that the metabolic activities significantly decrease over time, but the nature of this response varies, depicting cell heterogeneity. A low-concentration dose showed a reduced fluctuation frequency with consistent fluctuation amplitudes, while the high-concentration dose showcased a decreasing trend in both cases. These results have demonstrated the capabilities of the functional plasmonic microscope to measure and quantify metabolic activities for drug discovery.

Multi-channel delay sampling to extend imaging depth in high-speed swept-source OCT systems.

We present a multi-channel delay sampling method to extend imaging depth in high-speed swept-source optical coherence tomography (SS-OCT). A balanced detector captures interference signals, converting them into electrical signals, which are then split into N channels, each with fixed time delays determined by the length of electrical cables. Then, they are digitized by an N-channel acquisition card. A calibration procedure is utilized to compensate for non-uniform phase shifts resulting from fixed time delays. The N-channel signals are merged in k-space and resampled to obtain a linearized spectrum, which increases the sampling rate by a factor of N, thereby extending the ranging distance by N times, all without altering k-clock triggering or sacrificing other imaging performance. The signal-to-noise ratio and sensitivity within the original depth range also have been enhanced. This advancement contributes to the improvement of the overall performance of SS-OCT systems.

Peripheral Intravenous Waveform Analysis Responsiveness to Subclinical Hemorrhage in a Rat Model.

BACKGROUND: Early detection and quantification of perioperative hemorrhage remains challenging. Peripheral intravenous waveform analysis (PIVA) is a novel method that uses a standard intravenous catheter to detect interval hemorrhage. We hypothesize that subclinical blood loss of 2% of the estimated blood volume (EBV) in a rat model of hemorrhage is associated with significant changes in PIVA. Secondarily, we will compare PIVA association with volume loss to other static, invasive, and dynamic markers. METHODS: Eleven male Sprague Dawley rats were anesthetized and mechanically ventilated. A total of 20% of the EBV was removed over ten 5 minute-intervals. The peripheral intravenous pressure waveform was continuously transduced via a 22-G angiocatheter in the saphenous vein and analyzed using MATLAB. Mean arterial pressure (MAP) and central venous pressure (CVP) were continuously monitored. Cardiac output (CO), right ventricular diameter (RVd), and left ventricular end-diastolic area (LVEDA) were evaluated via transthoracic echocardiogram using the short axis left ventricular view. Dynamic markers such as pulse pressure variation (PPV) were calculated from the arterial waveform. The primary outcome was change in the first fundamental frequency (F1) of the venous waveform, which was assessed using analysis of variance (ANOVA). Mean F1 at each blood loss interval was compared to the mean at the subsequent interval. Additionally, the strength of the association between blood loss and F1 and each other marker was quantified using the marginal R2 in a linear mixed-effects model. RESULTS: PIVA derived mean F1 decreased significantly after hemorrhage of only 2% of the EBV, from 0.17 to 0.11 mm Hg, P = .001, 95% confidence interval (CI) of difference in means 0.02 to 0.10, and decreased significantly from the prior hemorrhage interval at 4%, 6%, 8%, 10%, and 12%. Log F1 demonstrated a marginal R2 value of 0.57 (95% CI 0.40-0.73), followed by PPV 0.41 (0.28-0.56) and CO 0.39 (0.26-0.58). MAP, LVEDA, and systolic pressure variation displayed R2 values of 0.31, and the remaining predictors had R2 values ≤0.2. The difference in log F1 R2 was not significant when compared to PPV 0.16 (95% CI -0.07 to 0.38), CO 0.18 (-0.06 to 0.04), or MAP 0.25 (-0.01 to 0.49) but was significant for the remaining markers. CONCLUSIONS: The mean F1 amplitude of PIVA was significantly associated with subclinical blood loss and most strongly associated with blood volume among the markers considered. This study demonstrates feasibility of a minimally invasive, low-cost method for monitoring perioperative blood loss.

Preemptive Pharmacogenetic-Guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery: The Preemptive Pharmacogenetic-Guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery Pilot Trial.

OBJECTIVES: To test the hypothesis that implementation of a cytochrome P-450 2D6 (CYP2D6) genotype-guided perioperative metoprolol administration will reduce the risk of postoperative atrial fibrillation (AF), the authors conducted the Preemptive Pharmacogenetic-Guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery pilot study. DESIGN: Clinical pilot trial. SETTING: Single academic center. PARTICIPANTS: Seventy-three cardiac surgery patients. MEASUREMENTS AND MAIN RESULTS: Patients were classified as normal, intermediate, poor, or ultrarapid metabolizers after testing for their CYP2D6 genotype. A clinical decision support tool in the electronic health record advised providers on CYP2D6 genotype-guided metoprolol dosing. Using historical data, the Bayesian method was used to compare the incidence of postoperative AF in patients with altered metabolizer status to the reference incidence. A logistic regression analysis was performed to study the association between the metabolizer status and postoperative AF while controlling for the Multicenter Study of Perioperative Ischemia AF Risk Index. Of the 73 patients, 30% (n = 22) developed postoperative AF; 89% (n = 65) were normal metabolizers; 11% (n = 8) were poor/intermediate metabolizers; and there were no ultrarapid metabolizer patients identified. The estimated rate of postoperative AF in patients with altered metabolizer status was 30% (95% CI 8%-60%), compared with the historical reference incidence (27%). In the risk-adjusted analysis, there was insufficient evidence to conclude that modifying metoprolol dosing based on poor/intermediate metabolizer status was associated significantly with the odds of postoperative AF (odds ratio 0.82, 95% CI 0.15-4.55, p = 0.82). CONCLUSIONS: A CYP2D6 genotype-guided metoprolol management was not associated with a reduction of postoperative AF after cardiac surgery.

Screening for the high-need population using single institution versus state-wide admissions discharge transfer feed.

BACKGROUND: Access to programs for high-needs patients depending on single-institution electronic health record data (EHR) carries risks of biased sampling. We investigate a statewide admission, discharge, and transfer feed (ADT) in assessing equity in access to these programs. METHODS: This is a retrospective cross-sectional study. We included high-need patients at Vanderbilt University Medical Center (VUMC) 18 years or older, with at least three emergency visits (ED) or hospitalizations in Tennessee from January 1 to June 30, 2021, including at least one at VUMC. We used the Tennessee ADT database to identify high-need patients with at least one VUMC ED/hospitalization. Then, we compared this population with high-need patients identified using VUMC's Epic® EHR database. The primary outcome was the sensitivity of VUMC-only criteria for identifying high-need patients compared to the statewide ADT reference standard. RESULTS: We identified 2549 patients with at least one ED/hospitalization and assessed them as high-need based on the statewide ADT. Of those, 2100 had VUMC-only visits, and 449 had VUMC and non-VUMC visits. VUMC-only visit screening criteria showed high sensitivity (99.1%, 95% CI: 98.7 - 99.5%), showing that the high-needs patients admitted to VUMC infrequently access alternative systems. Results showed no meaningful difference in sensitivity when stratified by patient's race or insurance. CONCLUSIONS: ADT allows examination for potential selection bias when relying upon single-institution utilization. In VUMC's high-need patients, there's minimal selection bias when depending on same-site utilization. Further research must understand how biases vary by site and durability over time.

Automated Emails to Improve Evening Staffing for Anesthesiologists.

Scheduling flexibility and predictability to the end of a clinical workday are strategies aimed at addressing physician burnout. A voluntary relief shift was created to increase the pool of anesthesiologists providing end of the day relief. We hypothesized that an automated email reminder would improve the number of evening relief shifts filled and increase the number of anesthesiologists participating in the program. An automated email reminder was implemented, which selectively emailed anesthesiologists without a clinical assignment one day in advance when the voluntary relief shifts were not filled, and anticipated case volume past 4:00 PM was expected to exceed the capacity of the on-call team. After implementation of the automated email reminder, the median number of providers who worked the relief shift on a typical day was 2.6, compared to 1.75 prior to the intervention. After the initial increase in the number of volunteers post-intervention, the trend in the weekly average number of volunteers tended to decrease but remained higher than before the intervention. A total of 22 unique anesthesiologists chose to participate in this program after the intervention. An automated email reminder increased the number of anesthesiologists volunteering for a relief shift. Leveraging automation to match staffing needs with case volume allows for recruitment of additional personnel on the days when volunteers are most needed. Increasing the pool of anesthesiologists available to provide relief is one strategy to improve end of the day predictability and work-life balance.

De-aliased depth-range-extended optical coherence tomography based on dual under-sampling.

We demonstrate a dual under-sampling (DUS) method to achieve de-aliased and depth-range-extended optical coherence tomography (OCT) imaging. The spectral under-sampling can significantly reduce the data size but causes well-known aliasing artifacts. A change in the sampling frequency used to acquire the interference spectrum alters the aliasing period within the output window except for the true image; this feature is utilized to distinguish the true image from the aliasing artifacts. We demonstrate that with DUS, the data size is reduced to 37% at an extended depth range of 24 mm, over which the true depth can be precisely measured without ambiguity. This reduction in data size and precise measuring capability would be beneficial for reducing the acquisition time for OCT imaging in various biomedical and industrial applications.

Paeonol Suppresses Vasculogenesis Through Regulating Vascular Smooth Muscle Phenotypic Switching.

OBJECTIVE: Smooth muscle cell (SMC) phenotypic switching is associated with development of a variety of occlusive vascular diseases. Paeonol has been reported to be involved in suppressing SMC proliferation. However, it is still unknown whether paeonol can regulate SMC phenotypic switching, and which eventually result in suppressing vasculogenesis. METHODS: Murine left common carotid artery was injured by completely ligation, and paeonol was administrated by intraperitoneal injection. Hematoxylin and eosin (H&E) staining was performed to visualize vascular neointima formation. Rat aortic SMCs were used to determine whether paeonol suppresses cell proliferation and migration. And murine hind limb ischemia model was performed to confirm the function role of paeonol in suppressing vasculogenesis. RESULTS: Complete ligation of murine common carotid artery successfully induced neointima formation. Paeonol treatment dramatically reduced the size of injury-induced neointima. Using rat aortic primary SMC, we identified that paeonol strongly suppressed cell proliferation, migration, and decreased extracellular matrix deposition. And paeonol treatment dramatically suppressed vasculogenesis after hind limb ischemia injury. CONCLUSION: Paeonol could regulate SMC phenotypic switching through inhibiting proliferation and migration of SMC, which results in inhibiting ischemia-induced vasculogenesis.

Cadherins and the pathogenesis of epilepsy.

Epilepsy is a nervous system disease caused by abnormal discharge of brain neurons, which is characterized by recurrent seizures. The factors that induce epilepsy include genetic and environmental factors. Genetic factors are important pathogenic factors of epilepsy, such as epilepsy caused by protocadherin-19 (PCDH-19) mutation, which is an X-linked genetic disease. It is more common in female heterozygotes, which are caused by mutations in the PCDH-19 gene. Epilepsy caused by environmental factors is mainly caused by brain injury, which is commonly caused by brain tumors, brain surgery, or trauma to the brain. In addition, the pathogenesis of epilepsy is closely related to abnormalities in some signaling pathways. The Wnt/ß-catenin signaling pathway is considered a new target for the treatment of epilepsy. This review summarizes these factors inducing epilepsy and the research hypotheses regarding the pathogenesis of epilepsy. The focus of this review centers on cadherins and the pathogenesis of epilepsy. We analyzed the pathogenesis of epilepsy induced by N-cadherin and PCDH-19 in the cadherin family members. Finally, we expect that in the future, new breakthroughs will be made in the study of the pathogenesis and mechanism of epilepsy at the cellular and molecular levels.

Nuclear and cytoplasmic quality of oocytes derived from serum-free culture of secondary follicles in vitro.

In vitro culture of follicles is a promising technology to generate large quantities of mature oocytes and it could offer a novel option of assisted reproductive technologies. Here we described a 2-dimensional follicular serum-free culture system with 3-dimensional effect that can make secondary follicles develop into antral follicles (78.52%), generating developmentally mature oocytes in vitro (66.45%). The oocytes in this serum-free system completed the first meiosis; spindle assembly and chromosome congression in most oocytes matured from follicular culture were normal. However, these oocytes showed significantly lower activation and embryonic development rates, and their ability to produce Ca2+ oscillations was also lower in response to parthenogenetic activation, after which a 2-cell embryonic developmental block occurred. Oocytes matured from follicular culture displayed increased abnormal mitochondrial distribution and increased reactive oxygen species levels when compared to in vivo matured oocytes. These data are important for understanding the reasons for reduced developmental potential of oocytes matured from follicular culture, and for further improving the cultivation system.

Electrochemical Impedance Imaging on Conductive Surfaces.

Electrochemical impedance spectroscopy (EIS) is a powerful tool to measure and quantify the system impedance. However, EIS only provides an average result from the entire electrode surface. Here, we demonstrated a reflection impedance microscope (RIM) that allows us to image and quantify the localized impedance on conductive surfaces. The RIM is based on the sensitive dependence between the materials' optical properties, such as permittivity, and their local surface charge densities. The localized charge density variations introduced by the impedance measurements will lead to optical reflectivity changes on electrode surfaces. Our experiments demonstrated that reflectivity modulations are linearly proportional to the surface charge density on the electrode and the measurements show good agreement with the simple free electron gas model. The localized impedance distribution was successfully extracted from the reflectivity measurements together with the Randles equivalent circuit model. In addition, RIM is used to quantify the impedance on different conductive surfaces, such as indium tin oxide, gold film, and stainless steel electrodes. A polydimethylsiloxane-patterned electrode surface was used to demonstrate the impedance imaging capability of RIM. In the end, a single-cell impedance imaging was obtained by RIM.

Motoric Subtypes of Delirium and Long-Term Functional and Mental Health Outcomes in Adults After Critical Illness.

OBJECTIVES: Adult ICU survivors that experience delirium are at high risk for developing new functional disabilities and mental health disorders. We sought to determine if individual motoric subtypes of delirium are associated with worse disability, depression, and/or post-traumatic stress disorder in ICU survivors. DESIGN: Secondary analysis of a prospective multicenter cohort study. SETTING: Academic, community, and Veteran Affairs hospitals. PATIENTS: Adult ICU survivors of respiratory failure and/or shock. INTERVENTIONS: We assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation and Sedation Scale daily during hospitalization. We classified delirium as hypoactive (Richmond Agitation and Sedation Scale ≤ 0) or hyperactive (Richmond Agitation and Sedation Scale > 0). At 3- and 12-month postdischarge, we assessed for dependence in activities of daily living and instrumental activities of daily living, symptoms of depression, and symptoms of post-traumatic stress disorder. Adjusting for baseline and inhospital covariates, multivariable regression examined the association of exposure to delirium motoric subtype and long-term outcomes. MEASUREMENTS AND MAIN RESULTS: In our cohort of 556 adults with a median age of 62 years, hypoactive delirium was more common than hyperactive (68.9% vs 16.8%). Dependence on the activities of daily living was present in 37% at 3 months and 31% at 12 months, whereas dependence on instrumental activities of daily living was present in 63% at 3 months and 56% at 12 months. At both time points, depression and post-traumatic stress disorder rates were constant at 36% and 5%, respectively. Each additional day of hypoactive delirium was associated with higher instrumental activities of daily living dependence at 3 months only (0.24 points [95% CI, 0.07-0.41; p = 0.006]). There were no associations between the motoric delirium subtype and activities of daily living dependence, depression, or post-traumatic stress disorder. CONCLUSIONS: Longer duration of hypoactive delirium, but not hyperactive, was associated with a minimal increase in early instrumental activities of daily living dependence scores in adult survivors of critical illness. Motoric delirium subtype was neither associated with early or late activities of daily living functional dependence or mental health outcomes, nor late instrumental activities of daily living functional dependence.

The Attributable Mortality of Postoperative Bleeding Exceeds the Attributable Mortality of Postoperative Venous Thromboembolism.

BACKGROUND: Bleeding and venous thromboembolic disease are considered important sources of postoperative morbidity and mortality. Clinically, treatment of these 2 disorders is often competing. We sought to better understand the relative contributions of bleeding and venous thromboembolic disease to postoperative attributable mortality in a national cohort. METHODS: A retrospective analysis of the 2006-2017 American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database was performed to assess the adjusted odds ratio and attributable mortality for postoperative bleeding and venous thromboembolism, adjusted by year. RESULTS: After adjustment for confounding variables, bleeding exhibited a high postoperative attributable mortality in every year studied. Venous thromboembolism appeared to contribute minimal attributable mortality. CONCLUSIONS: Bleeding complications are a consistent source of attributable mortality in surgical patients, while the contribution of venous thromboembolic disease appears to be minimal in this analysis. Further studies are warranted to better understand the etiology of this disparity.

Abnormal neuronal damage and inflammation in the hippocampus of kainic acid-induced epilepsy mice.

In this study, we established a mouse model of epilepsy and analysed abnormal neuronal damage and inflammation in the hippocampus of mice with kainic acid (KA)-induced epilepsy to provide the basis for the pathogenesis of epilepsy. C57 mice, aged 4 weeks, were injected intraperitoneally in the KA group with 20 mg/kg of KA and in the sham experimental group with normal saline. The whole brain and hippocampus of mice in the sham experimental group and KA epilepsy model group were collected on days 7, 14, 21 and 28 after injection. The difference in the protein expression in the hippocampus was detected using fluorescence immunohistochemistry. The hippocampal tissue was also collected and frozen to detect protein expression by western blot. The results of the haematoxylin and eosin (HE) and Nissl staining showed that the mouse model of temporal lobe epilepsy could be established by intraperitoneal injection of KA, and the success rate of the model was 53.8%. The expression of DCX-, ß-catenin-, GFAP- and Iba-1-labelled glial cells in the KA-induced epilepsy model group were higher than those in the sham group. The results of western blotting showed that the expression of DCX and ß-catenin in the KA-induced epilepsy model group was higher than that in the sham experimental group, while the expression of N-cadherin and Iba-1 on days 14 and 28 was significantly (P < .05) higher than that in the sham experimental group. In KA-induced epilepsy model group, the expression of Bcl-2 was decreased, while the expression of Bad and PUMA was increased.

Characterization and Caco-2 Cell Transport Assay of Chito-Oligosaccharides Nano-Liposomes Based on Layer-by-Layer Coated.

Chito-oligosaccharides (COSs) were encapsulated by the film-ultrasonic method into three nano-liposomes, which were uncoated liposomes (COSs-Lip), chitosan-coated liposomes (CH-COSs-Lip), and sodium alginate (SA)/chitosan (CH)-coated liposomes (SA/CH-COSs-Lip). The physicochemical and structural properties, as well as the stability and digestive characteristics, of all three nano-liposomes were assessed in the current study. Thereafter, the characteristics of intestinal absorption and transport of nano-liposomes were investigated by the Caco-2 cell monolayer. All nano-liposomes showed a smaller-sized distribution with a higher encapsulation efficiency. The ζ-potential, Z-average diameter (Dz), and polydispersity index (PDI) demonstrated that the stability of the SA/CH-COSs-Lip had much better stability than COSs-Lip and CH-COSs-Lip. In addition, the transport of the nano-liposomes via the Caco-2 cell monolayer indicated a higher transmembrane transport capacity. In summary, the chitosan and sodium alginate could serve as potential delivery systems for COSs to fortify functional foods and medicines.

Mechanistic insights into the reduced developmental capacity of in vitro matured oocytes and importance of cumulus cells in oocyte quality determination.

In vitro maturation of oocytes is a promising assisted reproductive technology (ART) for infertility treatment, although it is still not a routine technique for human ART due to reduced embryonic development. The aim of the present study was to clarify the possible reasons for reduced capacity of in vitro matured oocytes. Our results showed that the oocytes matured in vitro displayed increased abnormal mitochondrial distribution, reduced mitochondrial membrane potential, and increased reactive oxygen species levels when compared to in vivo matured oocytes. These results were not different in oocytes matured in vitro with or without cumulus cells. Notably, in vitro matured oocytes displayed increased mitochondrial DNA numbers probably due to functional compensation. In vitro matured oocytes showed significantly lower activation and embryonic development rates, and their ability to produce Ca2+ oscillations was much lower in response to parthenogenetic activation, especially in oocytes matured in vitro without cumulus cells with nearly half of them failing to produce calcium waves upon strontium chloride stimulation. These data are important for understanding the reasons for reduced developmental potential of in vitro matured oocytes and the importance of cumulus cells for oocyte quality.

Observational Study of Clinician Attentional Reserves (OSCAR): Acuity-Based Rounds Help Preserve Clinicians' Attention.

OBJECTIVES: Team rounding in the ICU can tax clinicians' finite attentional resources. We hypothesized that a novel approach to rounding, where patients are seen in a decreasing order of acuity, would decrease attentional attrition. DESIGN: Prospective interventional internal-control cohort study in which stop signal task testing was used as a proxy for attentional reserves. Stop signal task is a measure of cognitive control and response inhibition in addition to performance monitoring, all reflective of executive control abilities, and our surrogate for attentional reserves. SETTING: The ICUs of Vanderbilt University Medical Center (site 1) and the University of Pennsylvania (site 2) from November 2014 to August 2017. SUBJECTS: Thirty-three clinicians at site 1, and 24 clinicians at site 2. INTERVENTIONS: Acuity-based rounding, in which clinicians round from highest to lowest acuity as determined by Sequential Organ Failure Assessment score or an equivalent acuity score. MEASUREMENTS AND MAIN RESULTS: The stop signal task results of ICU staff at two sites were compared for conventional (in room order) versus novel (in decreasing order of acuity) rounding order. At site 1, the difference in stop signal reaction time change between two rounding types was -39.0 ms (95% CI, -50.6 to -27.4 ms; p < 0.001), and at site 2, the performance stop signal reaction time was -15.6 ms (95% CI, -29.1 to -2.1 ms; p = 0.023). These sub-second changes, while small, are significant in the neuroscience domain. CONCLUSIONS: Rounding in decreasing order of patient acuity mitigated attrition in attentional reserves when compared with the traditional rounding method.

Pediatric Perioperative Mortality in Kenya: A Prospective Cohort Study from 24 Hospitals.

BACKGROUND: The global surgery access imbalance will have a dramatic impact on the growing population of the world's children. In regions of the world with pediatric surgery and anesthesia manpower deficits and pediatric surgery-specific infrastructure and supply chain gaps, this expanding population will present new challenges. Perioperative mortality rate is an established indicator of the quality and safety of surgical care. To establish a baseline pediatric perioperative mortality rate and factors associated with mortality in Kenya, the authors designed a prospective cohort study and measured 24-h, 48-h, and 7-day perioperative mortality. METHODS: The authors trained anesthesia providers to electronically collect 132 data elements for pediatric surgical cases in 24 government and nongovernment facilities at primary, secondary, and tertiary hospitals from January 2014 to December 2016. Data assistants tracked all patients to 7 days postoperative, even if they had been discharged. Adjusted analyses were performed to compare mortality among different hospital levels after adjusting for prespecified risk factors. RESULTS: Of 6,005 cases analyzed, there were 46 (0.8%) 24-h, 62 (1.1%) 48-h, and 77 (1.7%) 7-day cumulative mortalities reported. In the adjusted analysis, factors associated with a statistically significant increase in 7-day mortality were American Society of Anesthesiologists Physical Status of III or more, night or weekend surgery, and not having the Safe Surgery Checklist performed. The 7-day perioperative mortality rate is less in the secondary (1.4%) and tertiary (2.4%) hospitals when compared with the primary (3.7%) hospitals. CONCLUSIONS: The authors have established a baseline pediatric perioperative mortality rate that is greater than 100 times higher than in high-income countries. The authors have identified factors associated with an increased mortality, such as not using the Safe Surgery Checklist. This analysis may be helpful in establishing pediatric surgical care systems in low-middle income countries and develop research pathways addressing interventions that will assist in decreasing mortality rate.

Mean platelet volume and cardiac-surgery-associated acute kidney injury: a retrospective study.

PURPOSE: Increased mean platelet volume (MPV) may indicate platelet activation, platelet aggregation, and a resulting prothrombotic state. Such changes in the postoperative period have been associated with organ injury and adverse outcomes. We hypothesized that changes in MPV after cardiac surgery are associated with both a higher risk of acute kidney injury (AKI) and mortality. METHODS: In this retrospective study, we evaluated consecutive patients undergoing adult cardiac surgery patients between 12 December 2011 and 5 June 2018. The change in MPV was derived by calculating the difference between the baseline MPV before surgery and the average postoperative MPV just prior to the occurrence of AKI. We defined postoperative AKI according to Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury as either a ≥ 50% increase in serum creatinine in the first ten postoperative days, or an increase of ≥ 0.3 mg·dL-1 during any 48-hr window across the ten-day postoperative period. Multivariable logistic regression analysis was used to examine the association between MPV change and postoperative AKI and mortality. RESULTS: Of the 4,204 patients studied, 1,373 (32.7%) developed postoperative AKI, including 83 (2.0%) and 38 (0.9%) who developed stages II and III AKI, respectively. Compared with patients who had an increase in median postoperative MPV of 0.2 femtolitre (fL), those with an increase of 0.8 fL had an 80% increase in the odds of developing AKI (adjusted odds ratio [aOR], 1.80; 95% confidence interval [CI],1.36 to 2.38; P < 0.001) and were almost twice as likely to progress to a higher severity AKI (aOR, 1.66; 95% CI, 1.28 to 2.16; P < 0.001). Change in MPV was not associated with mortality (aOR,1.32; 95% CI, 0.92 to 1.89; P = 0.14). CONCLUSION: Increased MPV change in the postoperative period was associated with both increased risk and severity of AKI, but not mortality.

RéSUMé: OBJECTIF: Un volume plaquettaire moyen (VPM) augmenté peut être indicatif d'une activation plaquettaire, d'une agrégation plaquettaire, et de l'état prothrombotique qui en résulte. De tels changements en période postopératoire ont été associés à des lésions aux organes et à des devenirs défavorables. Nous avons émis l'hypothèse que des changements du VPM après une chirurgie cardiaque seraient associés à un risque plus élevé d'insuffisance rénale aiguë et de mortalité. MéTHODE: Dans cette étude rétrospective, nous avons évalué des patients adultes consécutifs subissant une chirurgie cardiaque entre le 12 décembre 2011 et le 5 juin 2018. Le changement de VPM a été dérivé en calculant la différence entre le VPM de base avant la chirurgie et le VPM postopératoire moyen juste avant la survenue de l'IRA. Nous avons défini une IRA postopératoire sur la base des Directives Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury (Les maladies rénales: Guide d'exercice clinique pour améliorer les devenirs globaux pour l'insuffisance rénale aiguë) en tant qu'une augmentation ≥ 50 % de la créatine sérique au cours des dix premiers jours postopératoires, ou une augmentation de ≥ 0,3 mg·dL−1 pendant toute fenêtre de 48 h au cours des dix premiers jours postopératoires. Une analyse multivariée de régression logistique a été utilisée pour examiner l'association entre le changement de VPM et l'IRA postopératoire et la mortalité. RéSULTATS: Parmi les 4204 patients à l'étude, 1373 (32,7 %) ont souffert d'IRA postopératoire, y compris 83 (2,0 %) et 38 (0,9 %) qui ont développé des IRA de stade II et III, respectivement. Par rapport aux patients ayant manifesté une augmentation du VPM postopératoire médian de 0,2 femtolitre (fL), ceux affichant une augmentation de 0,8 fL ont démontré une augmentation de 80 % de la probabilité d'IRA (rapport de cotes ajusté [RCA], 1,80; intervalle de confiance [IC] 95 %, 1,36 à 2,38; P < 0,001) et couraient un risque pratiquement deux fois plus élevé de voir leur IRA progresser à un stade plus grave (RCA, 1,66; IC 95 %, 1,28 à 2,16; P < 0,001). Les changements de VPM n'étaient pas associés à la mortalité (RCA, 1,32; IC 95 %, 0,92 à 1,89; P = 0,14). CONCLUSION: Une augmentation accrue du VPM en période postopératoire a été associée à un risque et une gravité accrus d'IRA, mais pas à la mortalité.

Carbon emissions in countries that failed to ratify the intended nationally determined contributions: A case study of Kyrgyzstan.

The Paris Agreement aims to increase global participation in climate change actions, yet attentions are not equally given among countries. The knowledge gap remains in understanding the structure and drivers of the emission in small developing countries. Eighteen countries have failed to ratify their Intended National Determined Contributions (INDCs) as an officially recognized emission target. Among these countries, we chose Kyrgyzstan as a case to construct its emission inventories from both production-based and consumption-based perspectives and to identify the drivers of emission changes using structural decomposition analysis (SDA). The empirical results revealed that CO2 emissions in Kyrgyzstan depicted a wavelike rise from 2007 to 2015, whilst the production structure contributed to 14% of the production-based CO2 emission growth from 2012 to 2015. As a net emission importer, Kyrgyzstan transferred large quantities of CO2 emissions to China and Russia through imports. However, if all manufacturing imports were produced within Kyrgyzstan, the emission would be over five times compared to the current level. It is helpful to reduce global emissions for Kyrgyzstan to import goods from other countries whose carbon intensities are lower. Overall, this study highlights the need to focus on these countries' failure to ratify INDCs while calling the Paris Agreement to provide a better understanding and mitigation mechanism for these small developing countries.