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Αλέξανδρος Γ. Σφακιανάκης

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Monday, June 27, 2022

Molecular Imaging on ACE2‐dependent Transocular Infection of Coronavirus

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Abstract

Rationale

Transocular infection has been proved as one of the main approaches that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the body, and angiotensin converting enzyme 2 (ACE2) plays a key role in this procedure. Dynamic and quantitative details on virus distribution are lacking for virus prevention and drug design.

Methods

In this research, radio-traceable pseudovirus packed with enhanced green fluorescent protein (EGFP) gene, 125I-CoV, was prepared and inoculated in the unilateral eye of humanized ACE2 (hACE2) mice or ACE2-knock out (ACE2-KO) mice. SPECT/CT images were acquired at multiple time points to exhibit ACE2-dependent procedures from invasion to clearance. PET and western blot were performed to quantify ACE2 expression and verify the factors affecting transocular infection.

Results

For the transocular infection of coronavirus, renin-angiotensin-aldosterone system, lungs, intestines and genital glands were t he main targeted organs. Due to the specific anchor to ACE2-expressed host cells, virus concentrations of genital glands, liver, and lungs ranked the top three most and stabilized at 3.75 ± 0.55, 3.30 ± 0.25 and 2.10 ± 0.55 % inoculated dose (ID)/mL at 48 hours post treatment. Meanwhile, ACE2-KO mice have already completed the in vivo clearance. In consideration of organ volumes, lungs (14.50 ± 3.75 %ID) and liver (10.94 ± 0.71 %ID) were the main in-store reservoirs of coronavirus. However, the inoculated eye (5.52 ± 1.85 %ID for hACE2, 5.24 ± 1.45 %ID for ACE2-KO, P > 0.05) and the adjacent brain exhibited ACE2-independent virus infection at the end of 72 hours observation, and absolute amount of virus played a key role in host cell infection. These observations on coronavirus infection were further manifested by infection-driven intracellular EGFP expression. ACE2 PET revealed an infection-related systematic upregulation of ACE2 expression in the organs involved in RAAS (e.g., brain, lung, heart, liver and kidney) and the organ that was of own local RA-system (e.g., eye).

Conclusions

Transocular infection of coronavirus is ACE2-dependent and constitutes the cause of disturbed ACE2 expression in the host. The brain, genital glands and intestines were of the high unit uptake, potentially accounting for the sequelae. Lungs and liver were of the highest absolute amount, closely related with the respiratory diffusion and in vivo duplication. ACE2 expression was upregulated in the short term after infection with CoV. These visual and quantitative results are helpful to fully understand the transocular path of SARS-CoV-2 and other coronavirus.

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Surgical site infections in orthognathic surgery: prolonged versus single-dose antibiotic prophylaxis

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The oral cavity is densely populated with microorganisms. As a result, intraoral surgical sites are prone to contamination by pathogens, potentially triggering surgical site infections (SSIs). Prophylactic antibiotics have proven beneficial in reducing the rate of SSIs. However, no consensus has been reached regarding the most effective regimen. The purpose of this study was to investigate two different antibiotic regimens – single-dose and prolonged antibiotic prophylaxis – regarding the rate and severity of postoperative SSIs in patients undergoing orthognathic surgery. (Source: International Journal of Oral and Maxillofacial Surgery)
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Delayed splenic pseudoaneurysm identification with surveillance imaging

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imageBACKGROUND Recent studies have shown that nonoperative management of patients with splenic injury has up to a 90% success rate. However, delayed hemorrhage secondary to splenic artery pseudoaneurysm occurs in 5% to 10% of patients with up to 27% of patients developing a pseudoaneurysm on delayed imaging. The goal of our study was to evaluate the safety and utility of delayed computed tomography (CT) imaging for blunt splenic injury patients. METHODS A retrospective evaluation of all traumatic splenic injuries from 2018 to 2020 at a single level 1 trauma center was undertaken. Patients were subdivided into four groups based on the extent of splenic injury: grades I and II, grade III, grade IV, and grade V. Patient injury characteristics along with hospital length of stay, imaging, procedures, and presence/absence of pseudoaneurysm were documented. RESULTS A total of 588 trauma patients were initially included for evaluation, with 539 included for final analysis. Two hundred ninety-seven patients sustained grades I and II; 123 patients, grade III; 61 patients, grade IV; and 58 patients, grade V splenic injuries. One hundred twenty-nine patients (24%) underwent either emergent or delayed (>6 hours) splenectomy with an additional six patients having a splenorrhaphy on initial operation. Of the patients who were treated nonoperatively, 98% of grade III, 91% of grade IV, and 100% of grade V splenic injury patients underwent follow-up CT imaging. The mean ± SD time from admission to follow-up abdominal CT scan was 5 ± 4.4 days. Twenty-two pseudoaneurysms were identified including grade III (10 of 84), grade IV (7 of 22), and grade V (2 of 5) patients; of these patients, 33% of grade III and 30% of grade IV required subsequent splenectomy. CONCLUSION Routine follow-up CT imaging after high-grade splenic injury identifies splenic artery pseudoaneurysm in a significant proportion of patients. Standardized surveillance imaging for high-grade splenic trauma promotes prospective identification of pseudoaneurysms, allowing for interventions to minimize delayed splenic injury complications. LEVEL OF EVIDENCE Therapeutic/Care Management; level IV.
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A multicenter validation of the modified brain injury guidelines: Are they safe and effective?

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imageBACKGROUND The modified Brain Injury Guidelines (mBIG) are an algorithm for treating patients with traumatic brain injury and intracranial hemorrhage by which selected patients do not require a repeat head computed tomography, a neurosurgery consult, or even an admission. The mBIG refined the original Brain Injury Guidelines (BIG) to improve safety and reproducibility. The purpose of this study is to assess safety and resource utilization with mBIG implementation. METHODS The mBIG were implemented at three Level I trauma centers in August 2017. A multicenter retrospective review of prospectively collected data was performed on adult mBIG 1 and 2 patients. The post-mBIG implementation period (August 2017 to February 2021) was compared with a previous BIG retrospective evaluation (January 2014 to December 2016). RESULTS There were 764 patients in the two study periods. No differences were identified in demographics, Injury Severity Score, or admission Glasgow Coma Scale score. Fewer computed tomography scans (2 [1,2] vs. 2 [2,3], p
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Tranexamic acid is not inferior to placebo with respect to adverse events in suspected traumatic brain injury patients not in shock with a normal head computed tomography scan: A retrospective study of a randomized trial

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imageBACKGROUND A 2-g bolus of tranexamic acid (TXA) has been shown to reduce 28-day mortality in a randomized controlled trial. This study investigates whether out-of-hospital TXA use is associated with adverse events or unfavorable outcomes in suspected traumatic brain injury (TBI) when intracranial hemorrhage (ICH) is absent on initial computed tomography. METHODS This study used data from a 2015 to 2017, multicenter, randomized trial studying the effect of the following TXA doses on moderate to severe TBI: 2-g bolus, 1-g bolus plus 1-g infusion over 8 hours, and a placebo bolus with placebo infusion. Of the 966 participants enrolled, 395 with an initial computed tomography negative for ICH were included in this analysis. Fifteen adverse events (28-day incidence) were studied: myocardial infarction, deep vein thrombosis, seizure, pulmonary embolism, acute respiratory distress syndrome, cardiac failure, liver failure, renal failure, cerebrovascular accident, cardiac arrest, cerebral vasospasm, "any thromboembolism," hypernatremia, acute kidney injury, and infection. Other unfavorable outcomes analyzed include mortality at 28 days and 6 months, Glasgow Outcome Scale—Extended score of ≤4 at discharge and 6 months, intensive care unit–free days, ventilator-free days, hospital-free days, and combined unfavorable outcomes. In both study dr ug groups, the incidence of dichotomous outcomes and quantity of ordinal outcomes were compared with placebo. RESULTS No statistically significant increase in adverse events or unfavorable outcomes was found between either TXA dosing regimen and placebo. Demographics and injury scores were not statistically different other than two methods of injury, which were overrepresented in the 1-g TXA bolus plus 1-g TXA infusion. CONCLUSION Administration of either a 2-g TXA bolus or a 1-g TXA bolus plus 1-g TXA 8-hour infusion in suspected TBIs without ICH is not associated with increased adverse events or unfavorable outcomes. Because the out-of-hospital 2-g bolus is associated with a mortality benefit, it should be administered in suspected TBI. LEVEL OF EVIDENCE Therapeutic/Care Management; Level II.
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Not all is lost: Functional recovery in older adults following emergency general surgery

alexandrossfakianakis shared this article with you from Inoreader
imageBACKGROUND Although functional decline and death are common long-term outcomes among older adults following emergency general surgery (EGS), we hypothesized that patients' postdischarge function may wax and wane over time. Periods of fluctuation in function may represent opportunities to intervene to prevent further decline. Our objective was to describe the functional trajectories of older adults following EGS admission. METHODS This was a population-based retrospective cohort study of all independent, community-dwelling older adults (age ≥65 years) in Ontario with an EGS admission (2006–2016). A multistate model was used to examine patients' functional trajectories over the 5 years following discharge. Patients were followed as they transitioned back and forth between functional independence, use of chronic home care (in-home assistance for personal care, homemaking, or medical care for at least 90 days), nursing home admission, and death. RESULTS We identified 78,820 older adults with an EGS admission (mean age, 77 years; 53% female). In the 5 years following admission, 32% (n = 24,928) required new chronic home care, 21% (n = 5,249) of whom had two or more episodes of chronic home care separated by periods of independence. The average time spent in chronic home care was 11 months, and 50% (n = 12,679) of chronic home care episodes ended with a return to independence. For patients requiring chronic home care at any time, the probability of returning to independent living during the subsequent 5 years ranged from 36% to 43% annually. CONCLUSION Not all is lost for older adults who experience functional decline following EGS admission. Half of those who require chronic home care will recover to independence, and one-third will have a durable recovery, remaining independent after 5 years. Fluctuations in function in the years following EGS may represent a unique opportunity for interventions to promote rehabilitation and recovery among older adults. LEVEL OF EVIDENCE Prognostic and Epidemiologic; Level III.
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Ultrasound is superior to supine chest x-ray for the diagnosis of clinically relevant traumatic pneumothorax

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No abstract available
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Fluoxetine reduces organ injury and improves motor function after traumatic brain injury in mice

alexandrossfakianakis shared this article with you from Inoreader
imageBACKGROUND Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in trauma patients worldwide. Brain injury is associated with significant inflammation, both within the brain and in the peripheral organs. This inflammatory response in TBI leads to a secondary injury, worsening the effects of the original brain injury. Serotonin is also linked to inflammation in the intestine and inflammatory bowel disease, but its role in the gut-brain axis is not known. We hypothesized that using fluoxetine to block serotonin reuptake would reduce organ inflammation and improve outcomes after TBI. METHODS C57/B6 mice were given a severe TBI using a controlled cortical impact. To measure intestinal permeability, a piece of terminal ileum was resected, the lumen was filled with 4-kDa fluorescein isothiocyanate (FITC)-dextran, and the ends were tied. The intestinal segment was submerged in buffer and fluorescence in the buffer measured over time. To measure lung permeability, 70-kDa FITC-dextran is injected retro-orbitally. Thirty minutes later, the left lung was homogenized and the fluorescence was measured. To measure performance on the rota-rod, mice were placed on a spinning rod, and the time to fall off was measured. Those treated with fluoxetine received a single dose of 5 mg/kg via intraperitoneal injection immediately after injury. RESULTS Traumatic brain injury was associated with an increase in intestinal permeability to FITC-dextran, increased lung vascular permeability, and worse performance on the rota-rod. Fluoxetine significantly reduced lung and intestinal permeability after TBI and improved performance on the rota-rod after TBI. CONCLUSION Use of fluoxetine has the potential to reduce lung injury and improve motor coordination in severe TBI patients. Further study will be needed to elucidate the mechanism behind this effect.
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Do not forget the platelets: The independent impact of red blood cell to platelet ratio on mortality in massively transfused trauma patients

alexandrossfakianakis shared this article with you from Inoreader
imageBACKGROUND Balanced blood component administration during massive transfusion is standard of care. Most literature focuses on the impact of red blood cell (RBC)/fresh frozen plasma (FFP) ratio, while the value of balanced RBC:platelet (PLT) administration is less established. The aim of this study was to evaluate and quantify the independent impact of RBC:PLT on 24-hour mortality in trauma patients receiving massive transfusion. METHODS Using the 2013 to 2018 American College of Surgeons Trauma Quality Improvement Program database, adult patients who received massive transfusion (≥10 U of RBC/24 hours) and ≥1 U of RBC, FFP, and PLT within 4 hours of arrival were retrospectively included. To mitigate survival bias, only patients with consistent RBC:PLT and RBC:FFP ratios between 4 and 24 hours were analyzed. Balanced FFP or PLT transfusions were defined as having RBC:PLT and RBC:FFP of ≤2, respectively. Multivariable logistic regression was used to compare the independent relationship between RBC:FFP, RBC:PLT, balanced transfusion, and 24-hour mortality. RESULTS A total of 9,215 massive transfusion patients were included. The number of patients who received transfusion with RBC:PLT >2 (1,942 [21.1%]) was significantly higher than those with RBC:FFP >2 (1,160 [12.6%]) (p
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Dimethyl malonate slows succinate accumulation and preserves cardiac function in a swine model of hemorrhagic shock

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imageBACKGROUND Succinate (SI) is a citric acid cycle metabolite that accumulates in tissues during hemorrhagic shock (HS) due to electron transport chain uncoupling. Dimethyl malonate (DMM) is a competitive inhibitor of SI dehydrogenase, which has been shown to reduce SI accumulation and protect against reperfusion injury. Whether DMM can be therapeutic after severe HS is unknown. We hypothesized that DMM would prevent SI buildup during resuscitation (RES) in a swine model of HS, leading to better physiological recovery after RES. METHODS The carotid arteries of Yorkshire pigs were cannulated with a 5-Fr catheter. After placement of a Swan-Ganz catheter and femoral arterial line, the carotid catheters were opened and the animals were exsanguinated to a mean arterial pressure (MAP) of 45 mm. After 30 minutes in the shock state, the animals were resuscitated to a MAP of 60 mm using lactated ringers. A MAP above 60 mm was maintained throughout RES. One group received 10 mg/kg of DMM (n = 6), while the control received sham injections (n = 6). The primary end-point was SI levels. Secondary end-points included cardiac function and lactate. RESULTS Succinate levels increased from baseline to the 20-minute RES point in control, while the DMM cohort remained unchanged. The DMM group required less intravenous fluid to maintain a MAP above 60 (450.0 vs. 229.0 mL; p = 0.01). The DMM group had higher pulmonary capillary wedge pressure at the 20-minute and 40-minute RES points. The DMM group had better recovery of cardiac output and index during RES, while the control had no improvement. While lactate levels were similar, DMM may lead to increased ionized calcium levels. DISCUSSION Dimethyl malonate slows SI accumulation during HS and helps preserve cardiac filling pressures and function during RES. In addition, DMM may protect against depletion of ionized calcium. Dimethyl malonate may have therapeutic potential during HS.
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