The effects of dexmedetomidine on intraoperative neurophysiologic monitoring modalities during corrective scoliosis surgery in pediatric patients: A systematic review.

BACKGROUND: During scoliosis surgery, motor evoked potentials (MEP), and somatosensory evoked potentials (SSEP) have been reported to be affected by the use of higher doses of anesthetic agents. Dexmedetomidine, a sympatholytic agent, an alpha-2 receptor agonist, has been used as an adjunctive agent to lower anesthetic dose. However, there is conflicting evidence regarding the effects of dexmedetomidine on the intraoperative neurophysiological monitoring of MEP and SSEP during surgery, particularly among pediatric patients. OBJECTIVES: This systematic review aimed to determine whether, during spinal fusion surgery in pediatric patients with scoliosis, dexmedetomidine alters MEP amplitude or SSEP latency and amplitude and, if so, whether different doses of dexmedetomidine display different effects (PROSPERO registration number CRD42022300562). METHODS: We searched PubMed, Scopus, and Cochrane Library on January 1, 2022 and included randomized controlled trials, observational cohort and case-control studies and case series investigating dexmedetomidine in the population of interest and comparing against a standardized anesthesia regimen without dexmedetomidine or comparing multiple doses of dexmedetomidine. Animal and in vitro studies and conference abstracts were excluded. RESULTS: We found substantial heterogeneity in the risk of bias (per Cochrane-preferred tools) of the included articles (n = 5); results are summarized without meta-analysis. Articles with the lowest risk of bias indicated that dexmedetomidine was associated with MEP loss and that higher doses of dexmedetomidine increased risk. In contrast, articles reporting no association between dexmedetomidine and MEP loss suffered from higher risk of bias, including suspected or confirmed problems with confounding, outcome measurement, participant selection, results reporting, and lack of statistical transparency and power. CONCLUSION: Given the limitations of the studies available in the literature, it would be advisable to conduct rigorous randomized controlled trials with larger sample sizes to assess the effects of dexmedetomidine use of in scoliosis surgery in pediatric patients.

Developing Folate-Conjugated miR-34a Therapeutic for Prostate Cancer: Challenges and Promises.

Prostate cancer (PCa) remains a common cancer with high mortality in men due to its heterogeneity and the emergence of drug resistance. A critical factor contributing to its lethality is the presence of prostate cancer stem cells (PCSCs), which can self-renew, long-term propagate tumors, and mediate treatment resistance. MicroRNA-34a (miR-34a) has shown promise as an anti-PCSC therapeutic by targeting critical molecules involved in cancer stem cell (CSC) survival and functions. Despite extensive efforts, the development of miR-34a therapeutics still faces challenges, including non-specific delivery and delivery-associated toxicity. One emerging delivery approach is ligand-mediated conjugation, aiming to achieve specific delivery of miR-34a to cancer cells, thereby enhancing efficacy while minimizing toxicity. Folate-conjugated miR-34a (folate-miR-34a) has demonstrated promising anti-tumor efficacy in breast and lung cancers by targeting folate receptor α (FOLR1). Here, we first show that miR-34a, a TP53 transcriptional target, is reduced in PCa that harbors TP53 loss or mutations and that miR-34a mimic, when transfected into PCa cells, downregulated multiple miR-34a targets and inhibited cell growth. When exploring the therapeutic potential of folate-miR-34a, we found that folate-miR-34a exhibited impressive inhibitory effects on breast, ovarian, and cervical cancer cells but showed minimal effects on and targeted delivery to PCa cells due to a lack of appreciable expression of FOLR1 in PCa cells. Folate-miR-34a also did not display any apparent effect on PCa cells expressing prostate-specific membrane antigen (PMSA) despite the reported folate's binding capability to PSMA. These results highlight challenges in the specific delivery of folate-miR-34a to PCa due to a lack of target (receptor) expression. Our study offers novel insights into the challenges and promises within the field and casts light on the development of ligand-conjugated miR-34a therapeutics for PCa.

The difference in leg lengths following total knee replacement for patients with severe osteoarthritic deformity.

PURPOSE: Increased height after total knee replacement surgery (TKR) may offer patients higher satisfaction as well as the quality of life. Therefore, in this paper, we aim to document the changes in leg length after TKR in patients with severe bilateral deformities. METHODS: The data of 61 patients were collected from the Egyptian Community Arthroplasty Register; of them, 21 patients had unilateral TKR while 40 had bilateral simultaneous TKR. The patterns of changes in height of 101 osteoarthritic knees were followed up for 1 year after having TKR. All patients had standing leg X-rays, before and after surgery, to document the length of the femur and tibia before and after TKR. Correlations were assessed using the two-sample t-test. RESULTS: The sample was mostly females (56/61, 91.8%). The distribution of the operated side was nearly equal (right knee was 47/101, 46.5%). The overall average leg length difference was 5.4 (SD = 2.3); for the unilateral group, the average was 4.6 (SD = 2.6); and for the bilateral group, the average was 5.6 (SD = 2.3), p = 0.119. We found that leg length may differ according to the varus deformity angle (p < 0.001) as well as fixed flexion deformity (p < 0.001). CONCLUSIONS: Leg length increased significantly 1 year after TKR. However, there is not enough evidence to suggest that the bilateral group had a greater height increase when compared to the unilateral group.

Total hip arthroplasty for post-firearm hip arthritis complicated by coloarticular fistula: A case report.

Hip firearm injuries are rare injuries that could lead to serious complications, such as posttraumatic hip arthritis and coloarticular fistula. We report a case of a 25-year-old male who sustained a pelvic injury caused by a single bullet which led to a bilateral acetabular fracture, concomitant with a colon injury treated on an emergency basis by a diverting colostomy; acetabular fractures were treated conservatively by traction. After the patient recovered from the abdominal injury, he was presented with bilateral hip pain and limited motion; plain radiographs showed bilateral hip arthritis with proximal migration of the femoral head and bilateral acetabular defect classified as Paprosky type ⅢA. Reconstruction of the hips was performed using the same technique: impaction bone grafting for acetabular defect reconstruction and a reversed hybrid total hip arthroplasty (THA) 6 months apart. The patient presented with loosening of the left THA acetabular cup 3 years later, which was revised; then he presented with a discharging sinus from the left THA with suspicion of coloarticular fistula, which was confirmed using CT with contrast material. A temporary colostomy and fistula excision were performed, and a cement spacer was applied to the hip. After clearing the infection, a final revision THA for the left hip was performed. Treating post-firearm hip arthritis by THA is challenging, especially in the situation of neglected cases with the presence of an acetabular defect. Concomitant intestinal injury increases the risk of infection with the possibility of coloarticular fistula formation, which could present later. Working with a multidisciplinary team is paramount.

The Use of Transesophageal Doppler and Central Venous Oxygen Saturation as Predictors of Weaning Success.

OBJECTIVES: Weaning individuals from mechanical ventilation (MV) is a challenge to physicians. Respiratory failure is the main reason for weaning failure (WF), but heart failure plays a pivotal role as well. Transesophageal Doppler (TED) is a minimally invasive method of hemodynamic tracking with fewer problems. The study authors evaluated the role of TED in predicting WF. DESIGN: An observational study. SETTING: A university teaching hospital. PARTICIPANTS: Weaning individuals. INTERVENTIONS: TED was applied before initiating the spontaneous breathing trial (SBT). Hemodynamic parameters, arterial blood gases, and TED (peak velocity [PV], cardiac output [COP]) were reported while cases were on MV before initiating the SBT, and at the successful completion of SBT. Succeeded (group S) and failed individuals (group F, who needed reintubation within 48 hours) were compared. The sensitivity, specificity, and area under the receiver operating curve were calculated. A subgroup of patients with cardiac comorbidities and impaired cardiac contractility was further analyzed. MEASUREMENTS AND MAIN RESULTS: The authors included 39 critically ill patients for weaning from MV. The reintubation rate was 54.8%. In patients with cardiac morbidity, delta change (dC) in PV and COP as predictors of WF showed 100% sensitivity and specificity, with 18% and 14% cut-offs after initiating the SBT (dC between the beginning and end of the successful SBT), respectively. Central venous oxygen saturation revealed a significant difference between patients with cardiac morbidity and noncardiac patients with lower sensitivity and specificity in the prediction of WF. CONCLUSIONS: TED could be a helpful method for the weaning of patients with cardiac morbidity from MV. The dC in PV and COP >18% and >14% were significant predictors of WF in these subjects, respectively.

Surgical training fit for the future: the need for a change.

Postgraduate training in surgical specialties is one of the longest training programmes in the medical field. Most of the surgical training programmes require 5-6 years of postgraduate training to become qualified. This is usually followed by 1-2 years of fellowship training in a subspecialised interest. This has been the case for the last 20-30 years with no significant change. The surgical practice is transforming quickly due to the advances in medical technology. This transformation is not matched in the postgraduate training, there is minimal exposure to the new technological advances in early years of postgraduate training. The current postgraduate training in surgical specialties is not fit for the future. Early exposure to robotic and artificial intelligence technologies is required. To achieve this, a significant transformation of surgical training is necessary, which requires a new vision and involves significant investment. We discuss the need for this transformation in the postgraduate surgical specialties training and analyse the threats and opportunities in relation to this transformation.

Influence of cerium oxide nanoparticles on dairy effluent nitrate and phosphate bioremediation.

This study investigated, for the first time, the role of cerium oxide nanoparticles (CeO2 NPs) on dairy effluent nitrate and phosphate bioremediation using different inoculum sources. Two inoculum sources (wastewater and sludge) were obtained from the dairy wastewater treatment plant unit. A culture was prepared to be tested in the treatment of nitrate and phosphate effluent, and the role of CeO2 NPs was checked to be completely efficient after 5 days of incubation. The reduction efficiency of nitrate using sludge as inoculum source was improved up to 89.01% and 68.12% for phosphate compared to control. In the case of using wastewater as an inoculum source, the nitrate reduction was improved up to 83.30% and 87.75% for phosphate compared to control. The bacterial richness showed a significant variance (higher richness) between control and other samples. The optimal concentration of CeO2 NPs for inoculum richness and nitrate and phosphate reduction was (sludge: 1 × 10-10 ppm) and (wastewater: 1 × 10-12 ppm). The results revealed that CeO2 NPs could enhance the microbial growth of different inoculum sources that have a key role in dairy effluent nitrate and phosphate bioremediation.

Safety, effectiveness, and quality of life following pulmonary vein isolation with a multi-electrode radiofrequency balloon catheter in paroxysmal atrial fibrillation: 1-year outcomes from SHINE.

AIMS: To evaluate the safety and effectiveness of a compliant multi-electrode radiofrequency balloon catheter (RFB) used with a multi-electrode diagnostic catheter for pulmonary vein isolation (PVI). METHODS AND RESULTS: This prospective, multicentre, single-arm study was conducted at six European sites and enrolled patients with symptomatic paroxysmal atrial fibrillation. The primary effectiveness endpoint was entrance block in treated pulmonary veins (PVs) after adenosine/isoproterenol challenge. The primary safety endpoint was the occurrence of primary adverse events (PAEs) within 7 days. Cerebral magnetic resonance imaging and neurological assessments were performed pre- and post-ablation in a subset of patients. Atrial arrhythmia recurrence was assessed over 12 months via transtelephonic and Holter monitoring. Quality of life was assessed by the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire. Of 85 patients undergoing ablation per study protocol, PV entrance block was achieved in all (one PV required touch-up with a focal catheter). Acute reconnection of ≥1 PVs after adenosine/isoproterenol challenge was observed in 9.3% (30/324) of PVs ablated. Post-ablation, silent cerebral lesions were detected in 9.7% (3/31) of patients assessed, all of which was resolved at 1-month follow-up. One patient experienced a PAE (retroperitoneal bleed). Freedom from documented symptomatic and all arrhythmia was 72.2% and 65.8% at 12 months. Four patients (4.7%) underwent repeat ablation. Significant improvements in all AFEQT subscale scores were seen at 6 and 12 months. CONCLUSION: PVI with the novel RFB demonstrated favourable safety and effectiveness, with low repeat ablation rate and clinically meaningful improvement in quality of life. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT03437733.

The Diagnostic Accuracy of Noninvasive Methods to Measure the Intracranial Pressure: A Systematic Review and Meta-analysis.

BACKGROUND: Although invasive monitoring is the standard method for intracranial pressure (ICP) measurement, it is not without potential for serious complications. Noninvasive methods have been proposed as alternatives to invasive ICP monitoring. The study aimed to investigate the diagnostic accuracy of the currently available noninvasive methods for intracranial hypertension (ICH) monitoring. METHODS: We searched 5 databases for articles evaluating the diagnostic accuracy of noninvasive methods in diagnosing ICH in PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase. The quantitative analysis was conducted if there were at least 2 studies evaluating a specific method. The accuracy measures included the sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. RESULTS: We included 134 articles. Ultrasonographic optic nerve sheath diameter (US ONSD) had high diagnostic accuracy (estimated sensitivity of 90%; 95% confidence interval [CI], 87-92, estimated specificity of 88%; 95% CI, 84-91) while the magnetic resonance imaging (MRI) ONSD had estimated sensitivity of 77%; 95% CI, 64-87 and estimated specificity of 89%; 95% CI, 84-93, and computed tomography (CT) ONSD had estimated sensitivity of 93%; 95% CI, 90-96 and estimated specificity of 79%; 95% CI, 56-92. All MRI signs had a very high estimated specificity ranging from 90% to 99% but a low estimated sensitivity except for sinus stenosis which had high estimated sensitivity as well as specificity (90%; 95% CI, 75-96 and 96%; 95% CI, 91-99, respectively). Among the physical examination signs, pupillary dilation had a high estimated specificity (86%; 95% CI, 76-93). Other diagnostic tests to be considered included pulsatility index, papilledema, transcranial Doppler, compression or absence of basal cisterns, and ≥10 mm midline shift. Setting the cutoff value of ICH to ≥20 mm Hg instead of values <20 mm Hg was associated with higher sensitivity. Moreover, if the delay between invasive and noninvasive methods was within 1 hour, the MRI ONSD and papilledema had a significantly higher diagnostic accuracy compared to the >1 hour subgroup. CONCLUSIONS: Our study showed several promising tools for diagnosing ICH. Moreover, we demonstrated that using multiple, readily available, noninvasive methods is better than depending on a single sign such as physical examination or CT alone.

Deep Hypothermic Circulatory Arrest in the Pediatric Population Undergoing Cardiac Surgery With Electroencephalography Monitoring: A Systematic Review and Meta-Analysis.

OBJECTIVE: Cardiac surgery for repair of congenital heart defects poses unique hazards to the developing brain. Deep hypothermic circulatory arrest (DHCA) is a simple and effective method for facilitating a bloodless surgical field during congenital heart defect repair. There are, however, some concerns that prolonged DHCA increases the risk of nervous system injury. The electroencephalogram (EEG) is used in adult and, to a lesser extent, pediatric cardiac procedures as a neuromonitoring method. The present study was performed to assess outcomes following DHCA with EEG monitoring in the pediatric population. DESIGN: In this systematic review and meta-analysis, the PubMed, Cochrane Central Register of Controlled Trials, Scopus, Institute of Science Index, and Embase databases were searched from inception for relevant articles. A fixed- or random-effects model, as appropriate, was used. SETTING: Surgical setting. PARTICIPANTS: Pediatric population (≤18 y old). INTERVENTIONS: DHCA (18°C) with EEG monitoring. MEASUREMENTS AND MAIN RESULTS: Nineteen articles with 1,267 pediatric patients ≤18 years were included. The event rate of clinical and EEG seizures among patients who underwent DHCA was 12.9% and 14.9%, respectively. Mortality was found to have a 6.3% prevalence. A longer duration of DHCA was associated with a higher risk of EEG seizure and neurologic abnormalities. In addition, seizures were associated with increased neurologic abnormalities and neurodevelopmental delay. CONCLUSIONS: EEG and neurologic abnormalities were common after DHCA. A longer duration of DHCA was found to lead to more EEG seizure and neurologic abnormalities. Moreover, EEG seizures were more common than clinical seizures. Seizures were found to be associated with increased neurologic abnormalities and neurodevelopmental delay.

Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study.

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn-Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.

Prediction of leg length change (LLC) after correcting varus and flexion deformity in patients undergoing TKA.

PURPOSE: Patients with varus and fixed flexion deformity (FFD) undergoing TKA may have a significant leg length change (LLC) after surgery. We aimed to determine the correlation between changes in HKA or FFD and leg length in patients undergoing TKA, the combined effect of coronal and sagittal plane deformity correction on LLC, and the possibility of estimating LLC mathematically. MATERIALS AND METHODS: This was a prospective radiographic evaluation of 242 knees, which had undergone primary unilateral TKA for advanced OA with varus and FFD. Full-length standing calibrated anteroposterior radiographs were used to measure the hip-knee-ankle axis (HKA) and functional leg length after adjusting for magnification. Clinical evaluation of FFD was done using a handheld goniometer. RESULTS: 224 knees (92.6%) showed increased limb length after TKA averaging 10.7 mm (SD 9.5 mm, P = .000). There was a significant correlation between the change in HKA and FFD from preoperatively to postoperatively with the amount of LLC (ρ 0.326 and 0.346, respectively, P = .000). FFD improvement from preoperatively to postoperatively was 8.1° to 1° (P = .000), respectively. A linear relationship was established between LLC and changes in HKA and FFD, where 10° improvement in HKA would result in an LLC of nearly 4 mm, and 10° improvement in FFD would result in a LLC of nearly 8 mm. CONCLUSION: LLC may be substantial after correcting varus and FFD with unilateral TKA, it correlates with the change in HKA and FFD and can be mathematically estimated. CLINICAL TRIALS . GOV IDENTIFIER: NCT03502382.

YEARS Algorithm Versus Wells' Score: Predictive Accuracies in Pulmonary Embolism Based on the Gold Standard CT Pulmonary Angiography.

OBJECTIVES: This study retrospectively applied Wells' score and YEARS algorithm to the same sample of patients to evaluate the predictive performance of each when compared with the gold standard CT pulmonary angiography. DESIGN: Retrospective analytical study. SETTING: A tertiary University Hospital in Ireland. PATIENTS: Data from 794 patients who underwent CT pulmonary angiography to rule out pulmonary embolism. INTERVENTIONS: Patients were analyzed using retrospective application of both Wells' score and YEARS algorithm. Sensitivity, specificity, and diagnostic odds ratio were calculated and compared. MEASUREMENTS AND MAIN RESULTS: Of 794 scans, 78 (9.8%) were positive for pulmonary embolism. The YEARS algorithm was more sensitive than the Wells' score (97.44% vs 74.36%) but was less specific (13.97% vs 33.94%). Furthermore, the diagnostic odds ratio of YEARS was higher than Wells' score (6.27 vs 1.48). YEARS provides better negative predictive value (98% vs 92.4%), and both scores have poor positive predictive value (10.9%). CONCLUSIONS: Both scores successfully exclude pulmonary embolism, although YEARS has a better negative predictive value. Both exhibit poor positive predictive value.

Timing of Tracheostomy in Pediatric Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Tracheostomy is a very common clinical intervention in critically ill adult patients. The indications for tracheostomy procedures in pediatric patients with complex conditions have increased dramatically in recent years, but there are currently no guidelines on the optimal timing of tracheostomy in pediatric patients undergoing prolonged ventilation. DATA SOURCES: We performed a systematic search of the existing literature in MEDLINE via PubMed and Embase databases and the Cochrane Library to identify clinical trials, observational studies, and cohort studies that compare early and late tracheostomy in children. The date of the last search was August 27, 2018. Included articles were subjected to manual searching. STUDY SELECTION: Studies in mechanically ventilated children that compared early with late tracheostomy were included. DATA EXTRACTION: Data were extracted into a spreadsheet and copied into Review Manager 5.3 (The Cochrane Collaboration, Copenhagen, Denmark). DATA SYNTHESIS: Data were meta-analyzed using an inverse variance, random effects model. Continuous outcomes were calculated as mean differences with 95% CIs, and dichotomous outcomes were calculated as Mantel-Haenszel risk ratios with 95% CIs. We included eight studies (10 study arms). These studies were all retrospective cohort studies. Early tracheostomy was associated with significant reductions in mortality, days on mechanical ventilation, and length of intensive care and total hospital stay, although the lack of randomized, controlled trials limits the validity of these findings. Although variance was imputed for some studies, these conclusions did not change after removing these studies from the analysis. CONCLUSIONS: In children on mechanical ventilation, early tracheostomy may improve important medical outcomes. However, our data demonstrate the urgent need for high-quality, randomized controlled trials in the pediatric population.

Antistasis Retrograde Flow Vascular Catheter: A Novel Solution to Thrombogenicity: A Computational Fluid Dynamics Study.

BACKGROUND: Catheter-related thrombosis (CRT) is a serious complication of vascular catheters. Retrograde catheter insertion has been shown to decrease pericatheter hemostasis and thrombosis, but it is technically challenging. The current in silico trial is an analytical approach to evaluating different approaches to designing retrograde flow into a vascular catheter. METHODS: The novel catheter design aims to provide antistasis retrograde flow (ASRF) of fluid through multiple backward-directed side openings, with a self-closing terminal opening to facilitate standard insertion. Four different models of the catheter were evaluated by computational fluid dynamic studies, with retrograde-angled openings of 15°, 30°, 45°, and 60° to the long axis of the catheter. RESULTS: ASRF successfully reduced the areas of fluid stagnation in models with 15° and 30° openings. Models with 45° and 60° did not significantly reduce stagnation. ASRF is reversed by the main bloodstream after a few millimeters. The novel catheter design achieved a slightly higher saline flow rate compared with the standard catheter (89.75, 91.72, 94.13, and 94.26 mL/min for 15°, 30°, 45°, and 60° designs, respectively, versus 86.93 mL/min for the standard catheter). CONCLUSIONS: The novel ASRF vascular catheter reduces pericatheter fluid stasis and has the potential to reduce CRT. Further in vitro and in vivo trials are warranted to validate these findings and evaluate clinical efficacy.

Streptokinase Versus Unfractionated Heparin Nebulization in Patients With Severe Acute Respiratory Distress Syndrome (ARDS): A Randomized Controlled Trial With Observational Controls.

OBJECTIVE: To examine and compare nebulizing heparin versus streptokinase for reversing alveolar collapse nonresponsive to recruitment. DESIGN: A clinical trial at a tertiary intensive care unit (ICU). Sixty patients with severe acute respiratory distress syndrome (ARDS) (PaO2/FIO2 <100) nonresponsive to recruitment maneuver (RM), prone position, and neuromuscular block (NMB) were randomized into intervention arms or the standard-of-care arm. SETTING: The ICU at Beni-Suef University Hospital. PARTICIPANTS: Sixty patients with severe ARDS (PaO2/FIO2 <100) nonresponsive to RM, PP, and NMB. INTERVENTIONS: Nebulized heparin (10,000 IU/4 h), nebulized streptokinase (250,000 IU/4 h), and conservative management. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in PaO2/FIO2; the secondary outcomes included the change in compliance, plateau pressure, coagulation, and ICU mortality. The PaO2/FIO2 was significantly higher in the streptokinase group from day 1 to day 8 compared to the heparin and standard-of-care groups. Streptokinase produced PaO2/FIO2>100 at day 1, >200 at day 5, and >300 at day 7. The heparin group achieved a PaO2/FIO2 >100 at day 5 but remained <200 until day 8. The standard-of-care group did not achieve a PaO2/FIO2>100 after 8 days. Streptokinase significantly reduced plateau pressure and improved compliance at day 8. Only streptokinase decreased PaCO2 (p < 0.0001). Moreover, ICU mortality was significantly lower in streptokinase patients compared to other groups. Additionally, no heparin-induced thrombocytopenia was observed in all groups. CONCLUSION: Inhaled streptokinase serves as rescue therapy in patients with severe ARDS with improving oxygenation and lung mechanics more quickly than heparin or conventional management.

Procedure-based assessments: the past, the present and the future.

One of the most significant changes to the structure of surgical training in the UK was the introduction of workplace-based assessments (WBAs). Since its integration into the Intercollegiate Surgical Curriculum Programme, we as surgical trainees became the children of WBAs. Procedure-based assessment (PBA) is one of the pillars of WBAs and no surgical trainee portfolio is complete without a significant number of PBAs completed. As a senior trauma and orthopaedics trainee myself, I have encountered PBA on a regular basis, both as a trainee and as an assessor to my junior colleagues. My journey in understanding and implementing PBAs has not been a smooth one. This is also a reflection of almost all surgical trainees across all specialties. In this review, I aim to shed some light on my perspective on PBA, its values, limitations and concerns that have risen as a result of its introduction. I also aim to use my experiences to highlight possible ways of improvement in PBA.

Too noisy to sleep safely?-An observational study of noise levels and distractions during critical phases of pediatric anesthesia.

BACKGROUND: Noise and distraction are recognized as contributing factors in critical incidents associated with surgery and anesthesia. In addition, excessive noise exposure can have negative effects on patients and staff members in these environments. AIMS: We aimed to quantify noise exposure of the anesthesiology team and patients in pediatric operating theaters, comparing them to adult studies, internationally recognized standards, and identifying factors contributing to noise and/or distraction. METHODS: We measured noise levels during three phases of anesthesia (pre-induction, induction, and postinduction/maintenance) and recorded additional environmental sources of distraction and noise. RESULTS: We included 49 theater cases. The median and interquartile range (IQR) of mean noise levels during pre-induction, induction, and maintenance were 61 (59.7-63.5), 61.9 (60.6-63.3), and 61.6 (60.4-63.7) dB, respectively, while the median (IQR) of maximal noise levels was 81.4 (77.3-86.8), 83.7 (78.5-87.4), and 86.3 (84.6-90.4), respectively. There was an average of 8.3 people present in the room during induction. In 23 cases, there were additional unnecessary conversations occurring within the room at induction. We noted the maintenance phase was the noisiest phase of anesthesia. We recorded frequent potential sources of distraction during pre-induction and induction, though no significant correlations between these distractions and recorded noise levels. CONCLUSIONS: We documented noise levels well above recommended levels during all phases of pediatric anesthesia. We highlighted factors with potential to contribute to noise and distraction but found no statistically significant correlation with noise levels.

Arginase-1 is neither constitutively expressed in nor required for myeloid-derived suppressor cell-mediated inhibition of T-cell proliferation.

Although previous reports suggest that tumor-induced myeloid-derived suppressor cells (MDSC) inhibit T cells by L-arginine depletion through arginase-1 activity, we herein show that arginase-1 is neither inherently expressed in MDSC nor required for MDSC-mediated inhibition. Employing Percoll density gradients, large expansions of MDSC in the bone marrow of tumor-bearing mice were isolated and demonstrated potent inhibition in T-cell proliferation activated by TCR-ligation, Concanavalin A, PMA plus ionomycin, or IL-2. Despite demonstrating characteristic immunosuppressive capacity, these MDSC exhibit no arginase-1 expression and/or exert their inhibitory effects independent of arginase-1 activity. However, arginase-1 expression in MDSC can be induced by exposure to TCR-activated T cells or their culture medium, but not T cells activated by other means or growing tumor cells. Further investigation reveals multiple cytokines secreted by TCR-activated T cells as orchestrating two signaling-relay axes, IL-6-to-IL-4 and GM-CSF/IL-4-to-IL-10, leading to arginase-1 expression in MDSC. Specifically, IL-6 signaling increases IL-4R, enabling IL-4 to induce arginase-1 expression; similarly, GM-CSF in concert with IL-4 induces IL-10R, allowing IL-10-mediated induction. Surprisingly, our study indicates that induction of arginase-1 expression is not conducive to the critical MDSC-mediated inhibition toward T cells, which is rather dependent on direct cell contacts undiminished by PD-L1 blockade or SIRPα deficiency.

Tumor conditions induce bone marrow expansion of granulocytic, but not monocytic, immunosuppressive leukocytes with increased CXCR2 expression in mice.

Myeloid-derived suppressor cells (MDSCs) promote tumor growth through, in part, inhibiting T-cell immunity. However, mechanisms underlying MDSC expansion and guidance of MDSCs toward the tumor microenvironment remain unclear. Employing Percoll density gradients, we separate bone marrow (BM) leukocytes from tumor-bearing mice into four density-increasing bands with myeloid leukocytes enriched in bands III and IV. Band III comprises monocytes and low-density granulocytes, both confirmed to be M-MDSCs and G-MDSCs, respectively, by displaying potent inhibition of T-cell proliferation. However, monocytes act as M-MDSCs not only under tumor conditions but also the healthy condition. In contrast, band IV contains non-inhibitory, mature granulocytes. Only band III G-MDSCs display significant expansion in mice bearing B16 melanoma, Lewis lung carcinoma, or MC38 colon carcinoma. The expanded G-MDSCs also show increased CXCR2 expression, which guides egress out of BM, and produce arginase-1 and ROS upon encountering antigen-activated T cells. Adoptive transfer assays demonstrate that both G-MDSCs and mature granulocytes infiltrate tumors, but only the former displays sustention and accumulation. Intratumoral administrations of granulocytes further demonstrate that G-MDSCs promote tumor growth, whereas mature granulocytes exert minimal effects, or execute powerful anti-tumor effects providing the presence of PMN activation mechanisms in the tumor microenvironment.