Assessment of Pulmonary Circulation of Critically Ill Patients Based on Critical Care Ultrasound.

Pulmonary circulation is crucial in the human circulatory system, facilitating the oxygenation of blood as it moves from the right heart to the lungs and then to the left heart. However, during critical illness, pulmonary microcirculation can be vulnerable to both intrapulmonary and extrapulmonary injuries. To assess these potential injuries in critically ill patients, critical point-of-care ultrasound can be used to quantitatively and qualitatively evaluate the right atrium, right ventricle, pulmonary artery, lung, pulmonary vein, and left atrium along the direction of blood flow. This assessment is particularly valuable for common ICU diseases such as acute respiratory distress syndrome (ARDS), sepsis, pulmonary hypertension, and cardiogenic pulmonary edema. It has significant potential for diagnosing and treating these conditions in critical care medicine.

Focused liquid ultrasonography in dropsy protocol for quantitative assessment of subcutaneous edema.

BACKGROUND: Although subcutaneous edema is a common symptom of critically ill patients, it is still underreported due to the lack of a systematic method for evaluating it. The present study aims to describe the occurrence and distribution of subcutaneous edema, as well as the risk factors associated with it, in critically ill patients using the focused liquid ultrasonography in dropsy (FLUID) protocol, and to assess their impact on ICU mortality. METHODS: The FLUID protocol and the pitting test were performed on general ICU patients in China. Cohen's Kappa coefficient and Bland-Altman plots were used to evaluate the agreement between the two methods at each measurement site and between the whole-body subcutaneous edema scores, respectively, while a repeated measures ANOVA was performed to compare the differences between the two methods in whole-body and body-part measurements. A generalized linear model was used to evaluate the risk factors for subcutaneous edema development and the relationship between subcutaneous edema severity and ICU mortality. RESULTS: A total of 145 critically ill patients were evaluated using both approaches, of whom 40 (27.6%) experienced subcutaneous edema. Over 1440 measurements, it was found that ultrasound discovered more subcutaneous edema than the pitting test (ultrasound: 522[36.3%], pitting test: 444[30.8%], χ2 = 9.477, p = 0.002). The FLUID protocol scored edema severity significantly higher than the pitting test in the whole body and specific body parts, including the abdominal wall, thighs, chest wall, and hands. Subcutaneous edema exhibited gravity-dependent distribution patterns, particularly in the abdominal wall. The APACHE II, NT-proBNP, serum creatinine, and sepsis were independent risk factors for subcutaneous edema development. The score of ultrasonic subcutaneous edema was related to ICU mortality. CONCLUSIONS: The FLUID protocol provides a comprehensive strategy for the semi-quantitative assessment of subcutaneous edema in critically ill patients. In detecting the onset and severity of edema, ultrasound was found to outperform the pitting test. Subcutaneous edema showed a gravity-dependent distribution pattern, and its severity was associated with mortality.

Shock Resuscitation - the Necessity and Priority of Renal Blood Perfusion Assessment.

Improving organ perfusion is the aim of shock resuscitation; therefore, improving organ blood perfusion is a direct indicator for shock resuscitation. During shock, different organs have different capacities for blood flow autoregulation. The kidney is an important organ with excellent ability to autoregulate the blood flow and with vulnerability to poor organ perfusion, which places kidney perfusion in a position of necessity and priority relative to that of other organs in shock. Critical-care ultrasonography provides the best evaluation of renal perfusion.

Risk assessment of insect pest expansion in alpine ecosystems under climate change.

BACKGROUND: Growth in insect pest populations poses a significant threat to ecosystem functions and services, societal development, and food security in alpine regions under climate change. Risk assessments are important prioritization tools for pest management, which must be used to study insect pest expansion in alpine ecosystems under global warming. We used species distribution modeling to simulate the current and future distribution probabilities of 58 insect pest species in the Qinghai Province, China, based on a comprehensive field investigation. Subsequently, general linear modeling was used to explore the relationship between the distribution probability of these species and the damage caused by them. Finally, we assessed the ecological risk of insect pest expansion across different alpine ecosystems under climate change. RESULTS: Climate change could increase the distribution probabilities of insect pest species across different alpine ecosystems. However, the presence of insect pest species may not correspond to the damage occurrence in alpine ecosystems based on percent leaf loss, amount of stunting, and seedling death of their host species. Significant positive relationships between distribution probability and damage occurrence were found for several of the examined insect pest species. Insect pest expansion is likely to increase extensively in alpine ecosystems under increasing carbon dioxide (CO2 ) emission scenarios. CONCLUSION: The relationships between distribution probability and damage occurrence should be considered in species distribution modeling for risk assessment of insect pest expansion under climate change. Our study could improve the effectiveness of risk assessment of insect pest expansion under changing climate conditions. © 2021 Society of Chemical Industry.

Short-term effect of stock volatility and cardiovascular mortality: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease (CVD) and stroke are leading causes of death. It has several risk factors, including stress and pressure. Stock volatility can cause acute stress for stockholders so that it can cause CVD events. Recently, the spread of new coronaviruses worldwide has affected economic development greatly, leading to more severe stock market fluctuations, so we systematically quantify the short-term effect of stock volatility and CVD events. METHODS: Time-series analysis on the effect of stock volatility and cardiovascular events were concluded. We conducted a systematic literature search for studies published in PubMed, Embase, and Cochrane Data up to the date February 9, 2020. We assessed publication bias using Egger's test. Overall analysis and sensitivity analysis were conducted separately. RESULTS: Four studies were finally included. Every 100-point increase in the stock market will bring about 1.01% increases in cardiovascular mortality [95% confidence intervals (CI), -0.18% to 2.21%]. The meta-analysis showed no statistical significance for cardiovascular mortality. Every 100-point increase in the stock market brought 1.01% increases in the cardiovascular mortality [95% CI, -0.18% to 2.21%]. In terms of stroke events, the estimated effect was 2.999% (95% CI, 0.325% to 5.673%). Different lag patterns also have effects on cardiovascular mortality. Every 100-point increase brought about 4.026% (95% CI, 1.516% to 6.536%) and 4.424% (95% CI, 1.145% to 7.703%) for lag 01 and 04 separately. CONCLUSIONS: Though our study has a number of limitations due to the limited studies included, it suggested that stock volatility had a lagging effect on CVD mortality, which may last for several days. Also, it might increase the incidence of stroke.

Nonclinical Safety Assessment of AMG 553, an Investigational Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Acute Myeloid Leukemia.

Feline McDonough Sarcoma-like tyrosine kinase 3 (FLT3), a tyrosine-protein kinase involved in hematopoiesis, is detectable on the cell surface of approximately 80% of leukemia isolates from adult patients with acute myeloid leukemia (AML). AMG 553 is an investigational chimeric antigen receptor (CAR) T-cell immunotherapy for the treatment of AML. FLT3 expression analysis and in vitro and in vivo studies were leveraged to evaluate the nonclinical safety of AMG 553. Cynomolgus monkeys administered autologous anti-FLT3 CAR T cells demonstrated no evidence of CAR T-cell-mediated toxicity, expansion, or persistence, likely due to restricted cell surface FLT3 protein expression in healthy animals. This highlights the limited value of such in vivo studies for safety assessment of the CAR T-cell modality when directed against a target with restricted expression. To complement these studies and directly evaluate the potential toxicities of eliciting T-cell-mediated cytotoxicity against cells with surface expression of FLT3 protein in vivo, data from cynomolgus monkey toxicology studies with 2 bispecific T-cell engager molecules targeting FLT3 were leveraged; findings were consistent with the targeted killing of bone marrow cells expressing cell surface FLT3. Potential AMG 553-induced cytotoxicity was assessed against a wide range of normal human primary cells and cell lines; cytotoxicity was observed against FLT3-positive AML cell lines and a percentage of primary bone marrow CD34+ cells. In conclusion, the nonclinical safety data suggest that AMG 553 can target FLT3 protein on AML cells, whereas only affecting a percentage of normal hematopoietic stem and progenitor cells, supporting clinical development.

Economic evaluation of guideline implementation in primary care: a systematic review.

PURPOSE: To review the economic evaluation of the guideline implementation in primary care. DATA SOURCES: Medline and Embase. STUDY SELECTION: Electronic search was conducted on April 1, 2019, focusing on studies published in the previous ten years in developed countries about guidelines of non-communicable diseases of adult (≥18 years) population, the interventions targeting the primary care provider. Data extraction was performed by two independent researchers using a Microsoft Access based form. RESULTS OF DATA SYNTHESIS: Among the 1338 studies assessed by title or abstract, 212 qualified for full text reading. From the final 39 clinically eligible studies, 14 reported economic evaluation. Cost consequences analysis, presented in four studies, provided limited information. Cost-benefit analysis was reported in five studies. Patient mediated intervention, and outreach visit applied in two studies showed no saving. Audit resulted significant savings in lipid lowering medication. Audit plus financial intervention was estimated to reduce referrals into secondary care. Analysis of incremental cost-effectiveness ratios was applied in four studies. Educational meeting evaluated in a simulated practice was cost-effective. Educational meeting extended with motivational interview showed no improvement; likewise two studies of multifaceted intervention. Cost-utility analysis of educational meeting supported with other educational materials showed unfavourable outcome. CONCLUSION: Only a minor proportion of studies reporting clinical effectiveness of guideline implementation interventions included any type of economic evaluation. Rigorous and standardized cost-effectiveness analysis would be required, supporting decision-making between simple and multifaceted interventions through comparability.

Economic burden of vertigo: a systematic review.

BACKGROUND: Vertigo, a highly prevalent disease, imposes a rising burden on the health care system, exacerbated by the ageing of the population; and further, contributes to a wide span of indirect burden due to reduced capacity to work or need of assistance in activities of daily living. The aim of this review was to summarise the evidence on the economic burden of vertigo. METHODS: All original studies published between 2008 and 2018 about the economic evaluation of peripheral or central vestibular vertigo in developed countries were considered eligible, unrestricted to setting, health care provider, or study type. RESULTS: The electronic search in three databases identified 154 studies from which 16 qualified for inclusion. All studies presented partial economic evaluation referring to a variety of vestibular vertigo including unspecified vertigo. Nine studies presented monetised cost results and seven studies reported health care utilization. Direct costs derived mainly from repeated and not well-targeted consultations at all levels of health care, excessive use of diagnostic imaging, and/or of emergency care. Considerable societal burden was caused by decreased productivity, mainly due to work absenteeism. CONCLUSION: To the best of our knowledge, this is the first systematic review of the existing evidence of the economic burden of vertigo. The lack of conclusive evidence revealed apparent targets of future research. First, studies of diagnostics and therapies for vestibular disease should include cost-effectiveness considerations. Population-based studies of health services utilization should include simple vestibular assessments to get more reliable estimates of the burden of disease and associated costs on the level of the general population. Further, clinical and population-based registries that include patients with vestibular disease, should consider collecting long-term data of societal burden. Primary data collection should increasingly include assessment of health care utilization e.g. by linking their diagnoses and outcomes to routine data from health insurances.

Nonclinical safety assessment of a human interleukin-22FC IG fusion protein demonstrates in vitro to in vivo and cross-species translatability.

Although Interleukin-22 (IL-22) is produced by various leukocytes, it preferentially targets cells with epithelial origins. IL-22 exerts essential roles in modulating various tissue epithelial functions, such as innate host defense against extracellular pathogens, barrier integrity, regeneration, and wound healing. Therefore, IL-22 is thought to have therapeutic potential in treating diseases associated with infection, tissue injury or chronic tissue damage. A number of in vitro and in vivo nonclinical studies were conducted to characterize the pharmacological activity and safety parameters of UTTR1147A, an IL-22 recombinant fusion protein that links the human cytokine IL-22 with the Fc portion of a human immunoglobulin. To assess the pharmacological activity of UTTR1147A, STAT3 activation was evaluated in primary hepatocytes isolated from human, cynomolgus monkey, minipig, rat, and mouse after incubation with UTTR1147A. UTTR1147A activated STAT3 in all species evaluated, demonstrating that all were appropriate nonclinical species for toxicology studies. The nonclinical safety profile of UTTR1147A was evaluated in rats, minipigs, and cynomolgus monkeys to establish a safe clinical starting dose for humans in Phase I trials and to support clinical intravenous, subcutaneous and/or topical administration treatment regimen. Results demonstrate the cross-species translatability of the biological response in activating the IL-22 pathway as well as the translatability of findings from in vitro to in vivo systems. UTTR1147A was well tolerated in all species tested and induced the expected pharmacologic effects of epidermal hyperplasia and a transient increase in on-target acute phase proteins. These effects were all considered to be clinically predictable, manageable, monitorable, and reversible.

Immunophenotyping: Application to Safety Assessment.

A continuing education course entitled "What You Always Wanted to Know About Immunotoxicology in Pharmaceutical Development…But Were Afraid to Ask" was offered at the Society of Toxicologic Pathology (STP) 36th annual symposium in Montreal. This article summarizes some key points made during the presentation dedicated to immunophenotyping. It describes how clusters of differentiation (CDs) are well-defined antigens used to characterize cell subsets, and how lymphocyte subsets in humans and different rodent and nonrodent species can be defined by detection of various combinations of CDs. It provides an overview of immunophenotyping study design considerations and applications to safety assessment.

[Risk assessment of different grades of hypertension during the treatment of patients with acute pulpitis].

OBJECTIVE: To evaluate the vital signs changes, influence factors in different grades of hypertension patients during the treatment of acute pulpitis, in order to obtain the risk prevention measures. METHODS: In this study, 90 different grades of hypertension patients with acute pulpitis were recruited from February 2014 to February 2015 in the Department of Oral Emergency, Peking University School and Hospital of Stomatology. The information about the patients'general health, oral treatment, life signs of change information was collected. Patients were divided into high risk group, middle risk group, and low risk group (30 patients for each group). RESULTS: (1) Compared with the preoperative, systolic blood pressure (90%), diastolic blood pressure (80%), heart rate increase (100%) were increased in the high risk group. The increase rates of the middle risk group and the low risk group were significantly lower than those of the high risk group (P<0.01). At the same time, the systolic blood pressure of 1/4 (26.7%) patients in high risk group increased more than 20 mmHg (1 mmHg=0.133 kPa), and the diastolic blood pressure of 2/5 patients in high risk group increased more than 10 mmHg, the difference was statistically significant compared with the other two groups (P<0.05). (2) Compared with the preoperative, the average increase of the maximum peak were increased [systolic blood pressure (18.0 ± 1.5) mmHg, diastolic blood pressure (8.0 ± 1.7) mmHg], the mean of heart rate changes [(7.0 ± 0.3) beats per minute] was also increased in the high risk group, while these two indicators were decreased in the low risk group and the middle risk group. The electrocardiogram (ECG) was changed in 6 cases during the treatment in the high risk group. No significantly changed were observed in the low risk group and the middle risk group. (3) Compared the risk assessment in preoperative with that in postoperative, in the middle risk group, 23 cases were evaluated as medium risk in final evaluation, 6 as low risk, and 1 as high risk (risk assessment increased); in the high risk group, 20 cases were evaluated as high risk, 7 as very high risk, and 3 as medium risk (risk assessment decreased). CONCLUSION: Oral treatment is very safe for patients with hypertension, but the risk factor, target organ damage, and complications will also increase the risk of cardiovascular events in elderly patients during the acute pulpitis treatment. Dentist should take some measures to avoid the risks.

[The role of end-tidal carbon dioxide partial pressure in fluid responsiveness assessment in septic shock patient].

OBJECTIVE: To assess whether end-tidal carbon dioxide partial pressure (PETCO2) can predict the fluid responsiveness in septic shock patients. METHODS: Septic shock patients under mechanical ventilation without spontaneous breathing and with the need of a fluid challenge test were included in this study.Heart rate, central venous pressure, pulse pressure, PETCO2, and CI before and after the fluid challenge test were conducted in all the patients. RESULTS: Of the 48 septic shock patients included, 34 had preload responsiveness, 14 had no responsiveness. ΔCI and ΔPETCO2 after the fluid challenge test in "volume responders" were (0.85 ± 0.47) L×min(-1)×m(-2) and (3.5 ± 2.5) mmHg respectively, which were higher than those in "no volume responders"(P < 0.05). The fluid-induced changes in PETCO2 and CI were correlated (r = 0.072, P < 0.05). The AUCROC of fluid challenge-induced ΔPETCO2 as the predictor for volume responsiveness was 0.943, and its sensitivity was 87.9% and specificity was 93.4% with a critical value of 5%. The AUCROC of ΔPP as the predictor for volume responsiveness was 0.801, and its sensitivity was 68.1% and specificity was 73.2% with a critical value of 10%. CONCLUSION: The changes of PETCO2 induced by a fluid challenge test can predict fluid responsiveness with reliability, and have a better sensitivity and specificity than the changes of PP.

Integrated cardiopulmonary sonography: a useful tool for assessment of acute pulmonary edema in the intensive care unit.

OBJECTIVES: Bedside sonography has become a popular method of assessment of critically ill patients with shock and dyspnea. This study evaluated the usefulness of integrated cardiopulmonary sonography for assessment of acute pulmonary edema. METHODS: A total of 128 intensive care unit (ICU) patients with acute pulmonary edema were randomly divided into 2 groups: a sonography group, which received standard treatment as well as cardiopulmonary sonography, and a control group, which received standard treatment only. All patients were treated according to the same therapeutic strategies and underwent chest radiography and central venous catheter placement. Serum myocardial injury marker levels and central venous/arterial blood gas parameters were measured 0, 24, and 72 hours after enrollment. The cumulative fluid infusion volume at 6, 12, 24, and 72 hours, the time to diagnosis of the pulmonary edema etiology by the attending physician, the lengths of ICU and hospital stays, and ICU mortality were recorded. RESULTS: The sonography group had a shorter time to diagnosis and received a smaller fluid infusion volume than the control group. There were no significant differences in ICU mortality and lengths of ICU and hospital stays between the sonography and control groups. In patients with cardiogenic pulmonary edema, the sonography group had a significantly shorter ICU stay and a faster return to normal myocardial injury marker levels and perfusion parameters than the control group (P < .05). CONCLUSIONS: Integrated cardiopulmonary sonography resulted in faster and better-informed clinical decision making, shortened the time to diagnosis of the pulmonary edema etiology, and decreased fluid use. However, the impact of this examination on prognoses requires further study. We propose that integrated cardiopulmonary sonography may be a useful bedside tool for treatment of ICU patients with acute pulmonary edema.

[Value of peripheral perfusion index in the assessment of reactive hyperemia in septic patients].

OBJECTIVE: To explore the changes of peripheral perfusion index (PI) during forearm vascular occlusion test (VOT) and examine its evaluative value of reactive hyperemia in septic patients. METHODS: Twenty-one patients with septic shock, 21 postoperative ones without infection and 18 health volunteers were prospectively recruited to undergo vascular occlusion test. An arrest of forearm blood flow was applied for 3 min with a sphygmomanometer inflated to a pressure approximately 30 mm Hg greater than systolic pressure around forearm. PI was measured and recorded continuously by conventional pulse oximetry during VOT. RESULTS: (1)In all subjects, the PI values decreased to zero during ischemic period. There were no changes in heart rate or blood pressure between baseline and reperfusion. The maximum PI (PI-max) after a release of pneumatic cuff was significantly higher than baseline PI; (2)The change rates of PI-max and PI were significantly lower and the time to PI-max was longer in septic group after reperfusion; (3) A negative relationship existed between PI change rate and sequential organ failure assessment (SOFA) score in septic group. CONCLUSIONS: PI may be used to assess vascular reactive hyperemia in critically ill patients. And the capacity of peripheral vascular reactive hyperemia decreases in septic patients.

[The value of bedside lung ultrasound in emergency-plus protocol for the assessment of lung consolidation and atelectasis in critical patients].

OBJECTIVE: To investigate the effect of the bedside lung ultrasound in emergency(BLUE)-plus lung ultrasound protocol on lung consolidation and atelectasis of critical patients. METHODS: All patients who need to receive mechanical ventilation for more than 48 hours in ICU from June 2010 to December 2011 in Peking Union Medical College Hospital were included in the study. BLUE-plus and BLUE lung ultrasound, bedside X-ray, lung CT examination were performed on all patients at the same time. The condition of lung consolidation and atelectasis discovered by BLUE-plus lung ultrasound protocol was recorded and compared with bedside X-ray or lung CT. The difference in assessment of lung consolidation and atelectasis between BLUE-plus lung ultrasound protocol and BLUE protocol was compared. RESULTS: A total of 78 patients were finally enrolled in the study. The lung CT found 70 cases (89.74%) had different degrees of lung consolidation and atelectasis. The sensitivity, specificity and diagnostic accuracy of lung consolidation and atelectasis by the bedside chest X-ray were 31.29%, 75.00% and 38.46%, respectively. BLUE-plus lung ultrasound protocol found 68 cases with lung consolidation and atelectasis, and its sensitivity, specificity, and diagnostic accuracy were 95.71%, 87.50% and 94.87%, respectively, which were significantly higher than those of lung CT. BLUE protocol found 48 cases of lung consolidation and atelectasis, and its sensitivity, specificity, and diagnostic accuracy were 65.71%, 75.00% and 66.67%, respectively. The position of lung consolidation and atelectasis which hadn't been found by BLUE protocol was mainly proved to be located in the basement of lung by lung CT. CONCLUSIONS: The incidence of lung consolidation and atelectasis in critical patients who received mechanical ventilation is high. The BLUE-plus lung ultrasound protocol has a relatively higher sensitivity, specificity and diagnostic accuracy for consolidation and atelectasis, which can find majority of consolidation and atelectasis. As BLUE-plus lung ultrasound is a bedside noninvasive method allowing immediate assessment of most lung consolidation and atelectasis, it will be likely the alternative of the CT and play a key role in assessment of lung consolidation and atelectasis.