The COVID-19 ibuprofen controversy: A systematic review of NSAIDs in adult acute lower respiratory tract infections.

AIMS: In light of the recent safety concerns relating to NSAID use in COVID-19, we sought to evaluate cardiovascular and respiratory complications in patients taking NSAIDs during acute lower respiratory tract infections. METHODS: We carried out a systematic review of randomised controlled trials and observational studies. Studies of adult patients with short-term NSAID use during acute lower respiratory tract infections, including bacterial and viral infections, were included. Primary outcome was all-cause mortality. Secondary outcomes were cardiovascular, renal and respiratory complications. RESULTS: In total, eight studies including two randomised controlled trials, three retrospective and three prospective observational studies enrolling 44 140 patients were included. Five of the studies were in patients with pneumonia, two in patients with influenza, and one in a patient with acute bronchitis. Meta-analysis was not possible due to significant heterogeneity. There was a trend towards a reduction in mortality and an increase in pleuro-pulmonary complications. However, all studies exhibited high risks of bias, primarily due to lack of adjustment for confounding variables. Cardiovascular outcomes were not reported by any of the included studies. CONCLUSION: In this systematic review of NSAID use during acute lower respiratory tract infections in adults, we found that the existing evidence for mortality, pleuro-pulmonary complications and rates of mechanical ventilation or organ failure is of extremely poor quality, very low certainty and should be interpreted with caution. Mechanistic and clinical studies addressing the captioned subject are urgently needed, especially in relation to COVID-19.

Is a diagnostic video-assisted thoracoscopic thymectomy an acceptable first-line approach to the suspicious anterior mediastinal mass?

INTRODUCTION: The incidental early-stage thymic mass presents a diagnostic challenge. Video-assisted thoracoscopic (VAT) thymectomy is an attractive but potentially morbid solution. The aim was to show it can be safely applied as a first-line modality in those with undiagnosed thymic enlargement with acceptable long-term results. METHODS: A total of 45 patients were identified (24 male, median age 52 interquartile range [IQR]: 41-66 years) in a 14-year experience who had CT evidence of an enlarged, possibly malignant thymic mass, but no tissue diagnosis before undertaking VAT thymectomy. The clinical outcomes of both benign and malignant diagnoses were compared. RESULTS: Myasthenic symptoms were present in 20 patients (44%), whereas 15 (33%) were asymptomatic. Benign lesions were resected in 27 patients (60%): thymic hyperplasia (56%), thymic cyst (33%), lipoma (7%) and xanthogranulomatous inflammation (4%). Of the 18 malignant patients, 82% had thymoma (three had Masaoka Stage I, 11 Stage II and one Stage III), 6% thymic carcinoma, 6% teratoma and 6% seminoma. Seven patients required radiotherapy for R1 resection. There was no difference in median hospital stay in either group: Benign group: 4 versus 5 days (P = 0.07). One patient in both groups required conversion to open. Two patients in the malignant group had significant morbidity (one myocardial infarction and one pulmonary embolism). There were no cases of tumour recurrence or mortality at a median follow-up of 6.6 years (IQR: 4.4-9.5 years). CONCLUSION: Right-sided diagnostic VAT thymectomy is a safe and effective first-line approach to suspected malignant thymic enlargement. At 5-year follow-up, there were no cases of recurrence in the malignant group.

Role of vitamin D supplementation in modifying outcomes after surgery: a systematic review of randomised controlled trials.

BACKGROUND: There is increasing evidence to suggest vitamin D plays a role in immune and vascular function; hence, it may be of biological and clinical relevance for patients undergoing major surgery. With a greater number of randomised studies being conducted evaluating the impact of vitamin D supplementation on surgical patients, it is an opportune time to conduct further analysis of the impact of vitamin D on surgical outcomes. METHODS: MEDLINE, EMBASE and the Cochrane Trials Register were interrogated up to December 2023 to identify randomised controlled trials of vitamin D supplementation in surgery. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool. A narrative synthesis was conducted for all studies. The primary outcome assessed was overall postoperative survival. RESULTS: We screened 4883 unique studies, assessed 236 full-text articles and included 14 articles in the qualitative synthesis, comprising 1982 patients. The included studies were highly heterogeneous with respect to patient conditions, ranging from open heart surgery to cancer operations to orthopaedic conditions, and also with respect to the timing and equivalent daily dose of vitamin D supplementation (range: 0.5-7500 mcg; 20-300 000 IU). No studies reported significant differences in overall survival or postoperative mortality with vitamin D supplementation. There was also no clear evidence of benefit with respect to overall or intensive care unit length of stay. DISCUSSION: Numerous studies have reported the benefits of vitamin D supplementation in different surgical settings without any consistency. However, this systematic review found no clear evidence of benefit, which warrants the supposition that a single biological effect of vitamin D supplementation does not exist. The observed improvement in outcomes in low vitamin D groups has not been convincingly proven beyond chance findings. TRIAL REGISTRATION NUMBER: CRD42021232067.

Renal Function Underpins the Cyclooxygenase-2: Asymmetric Dimethylarginine Axis in Mouse and Man.

Introduction: Through the production of prostacyclin, cyclooxygenase (COX)-2 protects the cardiorenal system. Asymmetric dimethylarginine (ADMA), is a biomarker of cardiovascular and renal disease. Here we determined the relationship between COX-2/prostacyclin, ADMA, and renal function in mouse and human models. Methods: We used plasma from COX-2 or prostacyclin synthase knockout mice and from a unique individual lacking COX-derived prostaglandins (PGs) because of a loss of function mutation in cytosolic phospholipase A2 (cPLA2), before and after receiving a cPLA2-replete transplanted donor kidney. ADMA, arginine, and citrulline were measured using ultra-high performance liquid-chromatography tandem mass spectrometry. ADMA and arginine were also measured by enzyme-linked immunosorbent assay (ELISA). Renal function was assessed by measuring cystatin C by ELISA. ADMA and prostacyclin release from organotypic kidney slices were also measured by ELISA. Results: Loss of COX-2 or prostacyclin synthase in mice increased plasma levels of ADMA, citrulline, arginine, and cystatin C. ADMA, citrulline, and arginine positively correlated with cystatin C. Plasma ADMA, citrulline, and cystatin C, but not arginine, were elevated in samples from the patient lacking COX/prostacyclin capacity compared to levels in healthy volunteers. Renal function, ADMA, and citrulline were returned toward normal range when the patient received a genetically normal kidney, capable of COX/prostacyclin activity; and cystatin C positively correlated with ADMA and citrulline. Levels of ADMA and prostacyclin in conditioned media of kidney slices were not altered in tissue from COX-2 knockout mice compared to wildtype controls. Conclusion: In human and mouse models, where renal function is compromised because of loss of COX-2/PGI2 signaling, ADMA levels are increased.

Cyclooxygenases and the cardiovascular system.

Cyclooxygenase (COX)-1 and COX-2 are centrally important enzymes within the cardiovascular system with a range of diverse, sometimes opposing, functions. Through the production of thromboxane, COX in platelets is a pro-thrombotic enzyme. By contrast, through the production of prostacyclin, COX in endothelial cells is antithrombotic and in the kidney regulates renal function and blood pressure. Drug inhibition of COX within the cardiovascular system is important for both therapeutic intervention with low dose aspirin and for the manifestation of side effects caused by nonsteroidal anti-inflammatory drugs. This review focuses on the role that COX enzymes and drugs that act on COX pathways have within the cardiovascular system and provides an in-depth resource covering COX biology and pharmacology. The review goes on to consider the role of COX in both discrete cardiovascular locations and in associated organs that contribute to cardiovascular health. We discuss the importance of, and strategies to manipulate the thromboxane: prostacyclin balance. Finally within this review the authors discuss testable COX-2-hypotheses intended to stimulate debate and facilitate future research and therapeutic opportunities within the field.

Cardiorenal Tissues Express SARS-CoV-2 Entry Genes and Basigin (BSG/CD147) Increases With Age in Endothelial Cells.

Vascular and cardiovascular inflammation and thrombosis occur in patients with severe coronavirus disease-2019 (COVID-19). Advancing age is the most significant risk factor for severe COVID-19. Using transcriptomic databases, the authors found that: 1) cardiovascular tissues and endothelial cells express putative genes for severe acute respiratory syndrome coronavirus-2 infection, including angiotensin-converting enzyme 2 (ACE2) and basigin (BSG); 2) severe acute respiratory syndrome coronavirus-2 receptor pathways ACE2/transmembrane serine protease 2 and BSG/peptidylprolyl isomerase B(A) polarize to lung/epithelium and vessel/endothelium, respectively; 3) expression of host genes is relatively stable with age; and 4) notable exceptions are ACE2, which decreases with age in some tissues, and BSG, which increases with age in endothelial cells, suggesting that BSG expression in the vasculature may explain the heightened risk for severe disease with age.

Impact of a streamlined rotational system for the management of acute aortic syndrome: sharing is caring†.

OBJECTIVES: Acute type A aortic dissection is an emergency associated with up to 30% of hospital mortality. It has been established that outcomes are improved with specialist aortic team care in high-volume centres. Most centres are limited to a small number of aortic specialists, thus making it logistically impractical to have a dedicated 24/7 single-centre service. In 2011, a rotational 24/7 service between 3 centres covering a geographical location was introduced including 24/7 access to a dissection 'Hotline'. METHODS: We analysed data since 2003 from a prospectively collected database. A total of 227 patients underwent surgery for acute aortic syndrome between 2003 and 2017. The results on outcomes were compared before and after the initiation of the dissection hotline and 24/7 dedicated service. RESULTS: We identified 128 patients from the pre-rotational group and 99 patients from the post-rotational group. Both groups were well matched in terms of demographics and comorbidities. In the post-rotational group, there was an increase in arch surgery (11.8% vs 20.2%, P: 0.07). The introduction of the rotational service reduced 30-day mortality (20% vs 8%, P: 0.010). The introduction of the service improved the overall long-term survival [P: 0.04, hazard ratio 1.86; confidence interval (1.03-3.38)] in the multivariable analysis. There was no difference between the groups in postoperative complications. There was an increase in the median length of hospital stay in the post-rotational group (13 days vs 20 days, P: 0.014). CONCLUSIONS: A streamlined aortic dissection service allows for centralized care. This provides the referring centres with 24/7 access to an experienced aortic team and may improve patient outcomes.

The Ozaki Procedure With CardioCel Patch for Children and Young Adults With Aortic Valve Disease: Preliminary Experience - a Word of Caution.

BACKGROUND: The Ozaki procedure is a surgical technique for patients with significant aortic stenosis or regurgitation or both where valve repair cannot be performed. Individual cusps are cut from glutaraldehyde-treated autologous pericardium or bovine pericardium and implanted into the aortic valve position. Encouraging results have been reported within the adult population. There are limited published data on success of this procedure in younger patients. METHODS: We present a series of five children and young adults who underwent the Ozaki procedure with neoaortic valve cusps made from CardioCel, a decellularized bovine pericardial patch treated with a monomeric glutaraldehyde. RESULTS: There were no complications in the initial postoperative period and short inpatient stay. At a mean follow-up of 29.6 months (range: 22-36 months), 4 patients had no evidence of stenosis and 3 patients had trivial or no regurgitation from the neoaortic valve. Overall, two patients had complications related to the valve and underwent reintervention during the follow-up period with a Ross procedure. One of these patients who was not taking long-term anticoagulation experienced a transient ischemic attack. CONCLUSIONS: Our experience demonstrates that the Ozaki procedure with CardioCel in pediatric and young adult patients should be approached with caution. Further research with larger groups of pediatric patients, comparison of different graft materials, and longer follow-up is required to ascertain long-term success in children.

The use of extracorporeal membrane oxygenation in neonates with severe congenital diaphragmatic hernia: a 26-year experience from a tertiary centre.

OBJECTIVES: Neonates with severe congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation (ECMO) have a high rate of mortality. There is controversy regarding optimal time of surgical intervention. We present our data over a 26-year period. METHODS: We analysed data from our Extracorporeal Life Support Organization registry forms between 1989 and 2015, in order to determine the factors affecting survival outcome for repair of congenital diaphragmatic hernia with ECMO as a bridge to surgery and/or recovery. RESULTS: Ninety-eight neonates with congenital diaphragmatic hernia requiring ECMO were identified. In-hospital mortality was 32%. The overall mortality (47.9%) in our study was seen up to 7 months, after this point there was no mortality. There was no difference in survival in patients repaired using pre-, intra- or postoperative ECMO (P = 0.65). Requiring haemofiltration at any point was significantly associated with reduced survival [hazard ratio 2.7 (95% confidence interval 1.5-4.9); P = 0.01] as was the presence of neurological complications [hazard ratio 3.7 (95% confidence interval 1.6-8.5); P = 0.003]. Age, Apgar score, mode of delivery, side, associated cardiac comorbidities, pH, partial pressure of carbon dioxide, partial pressure of oxygen, oxygen saturations, bicarbonate, high-frequency oscillatory ventilation, mode of ECMO, inhaled nitric oxide, pulmonary complications and bleeding were not associated with any survival difference. CONCLUSIONS: We believe that all neonates with severe diaphragmatic hernia should be given the option of ECMO if clinically indicated. Provided these patients survive the initial postoperative period, they go on to have a sustained survival benefit. Long-term cost analysis and morbidity need to be taken into account to determine the true effect of ECMO on congenital diaphragmatic hernia.

Starting out in minimally invasive aortic valve replacement in the UK.

OBJECTIVES: Here we aim to describe in detail the logical procedure and philosophical approach to establish a minimally access aortic valve replacement programme in the current era. METHODS: A real example of a National Health Service Trust in the United Kingdom has been described in a step-wise manner. RESULTS: The outcomes of the new procedure established in this fashion are reported and the philosophical lessons learnt from the experiences are highlighted. CONCLUSIONS: It is hoped that this paper will act as a template for newly established surgeons to embark onto a mini-AVR programme. An open-minded and enthusiastic team will undoubtedly be able to facilitate the introduction of this 'new service'. A sensible approach will provide safe and sustainable outcomes.

Five-year experience with mobile adult extracorporeal membrane oxygenation in a tertiary referral center.

INTRODUCTION: Mobile extracorporeal membrane oxygenation (ECMO) is reserved for critically unstable patients who may not otherwise survive transfer to the ECMO center. We describe our experience with mobile ECMO. METHODS: We retrospectively reviewed adult patients between 2010 and 2014 who were referred for ECMO support and were too unwell for conventional transfer. They were cannulated at their referring center by our team and subsequently transported back to our hospital on ECMO. RESULTS: A total of 102 patients were put on ECMO by our team. Of 102 patients, 95 (93%) were managed by venovenous ECMO, and 7 (7%), by venoarterial ECMO. The average distance traveled was 195 miles (SD, ±256.8; range, 3.6-980). Transportation was via road in 77 cases (77%), by air in 22 cases (22%), and in 3 cases (3%) a combination of road and air was used. A double-lumen Avalon cannula was used in 72 patients (70%). One patient had a ventricular tachycardia arrest during cannulation but was successfully resuscitated. There was no mortality or major complications during transfer. CONCLUSION: The use of mobile ECMO in adult patients is a safe modality for transfer of critically unwell patients. We have safely used double-lumen cannulas in most of these patients.