Incidence and outcomes of surgical pulmonary embolectomy in the UK.

BACKGROUND: Surgical pulmonary embolectomy is rarely used for the treatment of massive acute pulmonary embolism. The aim of this study was to assess the incidence and outcomes of this operation by undertaking a retrospective analysis of a large national registry in the UK. METHODS: All acute pulmonary embolectomies performed between 1996 and 2018 were captured in the National Institute of Cardiovascular Outcomes Research central database. Trends in the number of operations performed during this interval and reported in-hospital outcomes were analysed retrospectively. Multivariable logistic regression was used to identify independent risk factors for in-hospital death. RESULTS: All 256 patients treated surgically for acute pulmonary embolism during the study interval were included in the analysis. Median age at presentation was 54 years, 55.9% of the patients were men, 48.0% had class IV heart failure symptoms, and 37.5% had preoperative cardiogenic shock. The median duration of bypass was 73 min, and median cross-clamp time was 19 min. Cardioplegic arrest was used in 53.1% of patients. The median duration of hospital stay was 11 days. The in-hospital mortality rate was 25%, postoperative stroke occurred in 5.4%, postoperative dialysis was required in 16%, and the reoperation rate for bleeding was 7.5%. Risk-adjusted multivariable analysis revealed cardiogenic shock (OR 2.54, 95% c.i. 1.05 to 6.21; P = 0.038), preoperative ventilation (OR 5.85, 2.22 to 16.35; P < 0.001), and duration of cardiopulmonary bypass exceeding 89 min (OR 7.82, 3.25 to 20.42; P < 0.001) as significant independent risk factors for in-hospital death. CONCLUSION: Surgical pulmonary embolectomy is rarely performed in the UK, and is associated with significant mortality and morbidity. Preoperative ventilation, cardiogenic shock, and increased duration of bypass were significant predictors of in-hospital death.

A blood clot in the lung can prevent the lungs from working properly and put pressure on the heart to work harder. Small clots can be treated with medications taken at home and are not a danger to life. Larger blood clots can put a lot of pressure on the heart and need immediate hospital treatment. Large blood clots can be treated with 'clot busting' medications, the delivery of a small tube into the blood vessels of the lung to suck up the clot or deliver medications directly on to its surface, and finally a form of open-heart surgery. With this surgery, a surgeon opens the chest, make a cut into the large vessels containing the clot, and physically removes the large piece of obstructing clot. The aim of this study was to describe and analyse the outcomes of this operation done in the UK over a long period. A database was used to find out how often and where this operation took place and its results. The available data were studied to try to understand how helpful this operation is to patients with lung blood clots. Between 1996 and 2018, 256 people had this operation. One in four patients did not survive the operation, 5.4% developed a clot or bleed in the brain, 16% needed to go on to a dialysis machine, and 7.5% had to be rushed back into theatre because of bleeding. Needing a ventilator machine for help with breathing, being in a sudden state of heart failure, and a long time on the heart bypass machine were all linked with patients who did not survive. This operation is rarely performed in the UK, and is often linked to a high chance of death or serious complication. In this study, the points described above were linked to a bad outcome.

The olfactory basis of orchid pollination by mosquitoes.

Mosquitoes are important vectors of disease and require sources of carbohydrates for reproduction and survival. Unlike host-related behaviors of mosquitoes, comparatively less is understood about the mechanisms involved in nectar-feeding decisions, or how this sensory information is processed in the mosquito brain. Here we show that Aedes spp. mosquitoes, including Aedes aegypti, are effective pollinators of the Platanthera obtusata orchid, and demonstrate this mutualism is mediated by the orchid's scent and the balance of excitation and inhibition in the mosquito's antennal lobe (AL). The P. obtusata orchid emits an attractive, nonanal-rich scent, whereas related Platanthera species-not visited by mosquitoes-emit scents dominated by lilac aldehyde. Calcium imaging experiments in the mosquito AL revealed that nonanal and lilac aldehyde each respectively activate the LC2 and AM2 glomerulus, and remarkably, the AM2 glomerulus is also sensitive to N,N-diethyl-meta-toluamide (DEET), a mosquito repellent. Lateral inhibition between these 2 glomeruli reflects the level of attraction to the orchid scents. Whereas the enriched nonanal scent of P. obtusata activates the LC2 and suppresses AM2, the high level of lilac aldehyde in the other orchid scents inverts this pattern of glomerular activity, and behavioral attraction is lost. These results demonstrate the ecological importance of mosquitoes beyond operating as disease vectors and open the door toward understanding the neural basis of mosquito nectar-seeking behaviors.

Propensity matched analysis of minimally invasive versus conventional isolated aortic valve replacement.

OBJECTIVE: To analyse the early and mid-term outcome of patients undergoing conventional aortic valve replacement (AVR) versus minimally invasive via hemi-sternotomy aortic valve replacement (MIAVR). METHODS: A single centre retrospective study involving 653 patients who underwent isolated aortic valve replacement (AVR) either via conventional AVR (n = 516) or MIAVR (n = 137) between August 2015 and March 2020. Using pre-operative characteristics, patients were propensity matched (PM) to produce 114 matched pairs. Assessment of peri-operative outcomes, early and mid-term survival and echocardiographic parameters was performed. RESULTS: The mean age of the PM conventional AVR group was 71.5 (±8.9) years and the number of male (n = 57) and female (n = 57) patients were equal. PM MIAVR group mean age was 71.1 (±9.5) years, and 47% of patients were female (n = 54) and 53% male (n = 60). Median follow-up for PM conventional AVR and MIAVR patients was 3.4 years (minimum 0, maximum 4.8 years) and 3.4 years (minimum 0, maximum 4.8 years), respectively. Larger sized aortic valve prostheses were inserted in the MIAVR group (median 23, IQR = 4) versus conventional AVR group (median 21, IQR = 2; p = 0.02, SMD = 0.34). Cardiopulmonary bypass (CPB) time was longer with MIAVR (94.4 ± 19.5 minutes) compared to conventional AVR (83.1 ± 33.3; p = 0.0001, SMD = 0.41). Aortic cross-clamp (AoX) time was also longer in MIAVR (71.6 ± 16.5 minutes) compared to conventional AVR (65.0 ± 52.8; p = 0.0001, SMD = 0.17). There were no differences in the early post-operative complications and mortality between the two groups. Follow-up echocardiographic data showed significant difference in mean aortic valve gradients between conventional AVR and MIAVR groups (17.3 ± 8.2 mmHg vs 13.0 ± 5.1 mmHg, respectively; p = 0.01, SMD = -0.65). There was no significant difference between conventional AVR and MIAVR in mid-term survival at 3 years (88.6% vs 92.1%; log-rank test p = 0.31). CONCLUSION: Despite the longer CPB and AoX times in the MIAVR group, there was no significant difference in early complications, mortality and mid-term survival between MIAVR and conventional AVR.

Network meta-analysis comparing blood cardioplegia, Del Nido cardioplegia and custodiol cardioplegia in minimally invasive cardiac surgery.

INTRODUCTION: Minimally invasive cardiac surgery has been evolving, with the intention of reducing surgical trauma, improve cosmesis and patient satisfaction. Single dose, crystalloid cardioplegia such as Del Nido cardioplegia and Custoidol solution have been increasingly used to reduce the interruption from repeating cardioplegia dosing to minimise the cardiopulmonary bypass and cross clamp time. However, the best cardioplegia for myocardial protection in adult minimally invasive cardiac surgery remains controversial. We aimed to conduct a meta-analysis to analyse the current evidence in the literature. METHOD: A systematic review and meta-analysis was performed following the updated 2020 PRISMA guideline. Articles published in the five major electronic databases up 1st of April 2021 were identified and reviewed. The primary outcome was in-hospital or 30-day mortality. Traditional pairwise and Bayesian network meta-analyses were conducted. RESULTS: Nine articles were included in this study. The use of Del Nido cardioplegia was associated with a lower volume of cardioplegia used (Del Nido vs Blood, 1105.62 mL+/-123.47 vs 2569.46 mL+/-1515.52, p<0.001), cardiopulmonary bypass (Del Nido vs Custoidol vs Blood: 91.67+/-14.78 vs 138.05 +/- 21.30 vs 119.38+/-26.91 minutes, p<0.001) and cross-clamp time (Del Nido vs Custoidol vs Blood: 74.99+/-18.55 vs 82.01 +/- 17.28 vs 93.66+/-8.88 minutes, p < 0.001). No differences were observed in the incidence of in-hospital/30-day mortality rate, new onset of atrial fibrillation and stroke. Ranking analysis showed the Custoidol solution has the highest probability to be the first ranked cardioplegia. CONCLUSION: No differences were found between blood and crystalloid cardioplegia in adult minimally invasive cardiac surgery in several clinical outcomes. The cardioplegia of choice in minimally invasive cardiac surgery remains the surgeons' decision and preference.

Staphylococcus lugdunensis Uses the Agr Regulatory System to Resist Killing by Host Innate Immune Effectors.

Coagulase-negative staphylococci (CoNS) are frequently commensal bacteria that rarely cause disease in mammals. Staphylococcus lugdunensis is an exceptional CoNS that causes disease in humans similar to virulent Staphylococcus aureus, but the factors that enhance the virulence of this bacterium remain ill defined. Here, we used random transposon insertion mutagenesis to identify the agr quorum sensing system as a regulator of hemolysins in S. lugdunensis. Using RNA sequencing (RNA-seq), we revealed that agr regulates dozens of genes, including hemolytic S. lugdunensis synergistic hemolysins (SLUSH) peptides and the protease lugdulysin. A murine bacteremia model was used to show that mice infected systemically with wild-type S. lugdunensis do not show overt signs of disease despite there being high numbers of bacteria in the livers and kidneys of mice. Moreover, proliferation of the agr mutant in these organs was no different from that of the wild-type strain, leaving the role of the SLUSH peptides and the metalloprotease lugdulysin in pathogenesis still unclear. Nonetheless, the tropism of S. lugdunensis for humans led us to investigate the role of virulence factors in other ways. We show that agr-regulated effectors, but not SLUSH or lugdulysin alone, are important for S. lugdunensis survival in whole human blood. Moreover, we demonstrate that Agr contributes to survival of S. lugdunensis during encounters with murine and primary human macrophages. These findings demonstrate that, in S. lugdunensis, Agr regulates expression of virulence factors and is required for resistance to host innate antimicrobial defenses. This study therefore provides insight into strategies that this Staphylococcus species uses to cause disease.

The Association of ANRIL With Coronary Artery Disease And Aortic Aneurysms, How Far Does The Gene Desert Go?

BACKGROUND: Coronary artery disease (CAD) and aortic aneurysms (AA) are 2 cardiovascular diseases that share a multifactorial aetiology. The influence of family history and genetics on the 2 diseases separately and in association is well known, but poorly elucidated. This comprehensive review aims to examine the current literature on the gene ANRIL (antisense non-coding RNA in the INK4 locus) and its associations with CAD and AA. METHODS: A database search on OVID, PubMed and Cochrane to identify articles concerning single nucleotide polymorphisms (SNPs) associated with ANRIL and their respective incidences of, and impact on, CAD and AA across populations. RESULTS: Cohort studies across various ethnicities reveal that various ANRIL SNPs are significantly associated separately with CAD (rs1333040, rs1333049 and rs2383207) and AA (rs564398, rs10757278 and rs1333049), and that these SNPs are present in significant proportions of the population. SNP rs1333049 is significantly associated with both diseases, but is positively correlated with AAA and negatively correlated with CAD. This review further outlines several pathophysiological links via endothelial and adventitial cells, vascular smooth muscle cells and sense gene interaction, which may explain these genetic associations identified. CONCLUSION: Given the associations uncovered between ANRIL polymorphisms and CAD and AA, as well as the molecular mechanisms which may explain the underlying pathophysiology, ANRIL appears to be strongly linked with both diseases. ANRIL may hence have a future application in screening normal patients and risk stratifying patients with both diseases. Its role in linking the 2 diseases is yet unclear, warranting further studies.

On- versus off-pump CABG in octogenarians: A propensity-matched analysis from the UK National Database.

INTRODUCTION: Coronary artery bypass grafting (CABG) remains a good revascularization strategy in octogenarians with excellent clinical outcomes and quality of life postoperatively. However, the benefits of off-pump over on-pump CABG in the elderly population are still controversial. We investigated this issue in the UK National Audit database. METHOD: We retrospectively analyzed all octogenarians undergoing nonemergency, isolated CABG from 1996 to 2019. Propensity score matching (PSM) was conducted to adjust for imbalance in the baseline characteristics between the off-pump and on-pump groups. Primary outcome was in-hospital mortality and postoperative cerebrovascular accidents. Secondary outcomes were bleeding requiring reoperation, deep sternal wound infection, and postoperative dialysis. RESULT: A total of 6436 patients were included for analysis. No differences were observed between off- and on-pump group in-hospital mortality (4% vs. 3.8%, p = .89), return to theater rate (5.4% vs. 6.2%, p = .16) and incidence of deep sternal wound infection (1.1% vs. 1.6%, p = .34). However, octogenarian undergoing off-pump CABG were less likely to experience postoperative transient ischemic attack (TIA)/stroke (1.4% vs. 2.3%, p = .004) but more likely to require renal dialysis (4.8% vs. 3.5%, p = .03). CONCLUSION: The data show similar in-hospital mortality in octogenarians regardless of the revascularization technique used. Off-pump when compared with on-pump CABG is associated with a lower incidence in postoperative neurological events but a higher need for renal dialysis.

Understanding aortic valve repair through Ozaki procedure: A review of literature evidence.

BACKGROUND: Aortic valve neocuspidization (AV Neo) using glutaraldehyde-treated autologous pericardium was first reported by Ozaki et al. in 2007. This technique has become an alternative to tissue and mechanical valve in selected patients as long-term anticoagulation is not required and shows promising midterm results and durability. METHOD: A comprehensive search was performed on the major database using the search terms "Ozaki technique" AND "Aortic Valve Neocuspidization" AND "AV Neocuspidization" AND "Autologous pericardium" AND "glutaraldehyde-treated autologous pericardium." Articles up to August 1st, 2021 were included in this study. RESULTS: A total of nine studies with a total of 1342 patients were included. The mean age was 67.36 and 54.23% were male. 66.32% and 23.92% of patients had aortic stenosis and aortic regurgitation, respectively. 66% of patients had a native tricuspid aortic valve (AV) and 31.37% of patients' native AV was bicuspid. Three studies reported their experience performing AV Neo via ministernotomy. CONCLUSION: AV Neo can be a suitable alternative to surgical AV replacement in selected patients. The short- and midterm outcomes are comparable without the need for long-term oral anticoagulation. Long-term follow-up data are required for this novel approach to be widely adopted.

Ambulatory blood pressure monitoring in children undergoing polysomnography.

Ambulatory blood pressure monitoring (ABPM) is recommended for the diagnosis of hypertension in children at high risk, such as children with obesity or obstructive sleep apnea (OSA). Nocturnal hypertension is highly predictive of cardiovascular outcomes. ABPM allows for early detection of nocturnal hypertension in children. Although OSA is the most common sleep disorder associated with hypertension, studies have also shown an increase in cardiovascular risk in adult patients with other sleep disorders; therefore, there is an imperative need to provide early diagnosis in children at high risk. In the present study, we evaluated the feasibility of using ABPM during polysomnography (PSG) in children referred for sleep disordered breathing to the Seattle Children's Hospital Sleep Disorders Center. A total of 41 children aged 7-18 years were included in this study. The ABPM monitor was worn for a mean (SD) of 10.2 (1.5) hr. No significant changes were seen in PSG parameters when ABPM was co-performed with PSG, including sleep efficiency and arousals. In total, 12 of the 41 patients were identified as having nocturnal hypertension. Our study is important in that it shows that concomitant use of ABPM during PSG can aid in the early identification of nocturnal hypertension in this population.

Subxiphoid incisional hernias post median sternotomy: A literature review.

BACKGROUND: Subxiphoid incisional hernias are one of the complications following a median sternotomy, a surgical procedure to provide access to the mediastinum. Incidence has been reported between 1% and 4%, although the true incidence is not well known due to its asymptomatic nature. METHOD: A comprehensive search was performed on multiple sites. Keywords included "incisional hernia OR Subxiphoid hernia" AND "Median sternotomy OR Cardiac Surgery OR Coronary artery bypass graft OR Transplant OR Valve replacement". Articles up to August 1, 2020, were included in this study. RESULTS: Eight articles were included in the study, with a total number of 132 patients identified. The incidence ranged from 0.81% to 3.44%. There was a mixture of repair methods and follow-up period reported. Recurrence post repair ranged from 10% to 43%. CONCLUSION: Subxiphoid incisional hernias remain challenging to manage. We have discussed the incidence, risk factors, preventions, and management of subxiphoid incisional hernias including both the open and laparoscopic techniques.

Top 100 Most Influential Manuscripts in Congenital Abdominal Pediatric Surgery: A Bibliometric Analysis.

Bibliometric analysis identifies the most influential manuscripts that shape our understanding of various congenital gastrointestinal pathologies. This study sets out to analyse the 100 most cited manuscripts on congenital gastrointestinal surgery. The Thomson Reuters Web of Science database was searched for all manuscripts relevant to paediatric congenital gastrointestinal surgery. The number of citations, authorship, publication date, journal of publication, institution and country were recorded for each paper. Eigenfactor and impact factor rankings were obtained for each journal of publication. 971 eligible manuscripts were returned by the search. Within the top 100 manuscripts, the most cited paper (by Metkus et al.) investigated fetal diaphragmatic hernia and was cited 413 times. University of Indianapolis had the most publications (n=5) and Journal of Pediatric Surgery had the most citations (n=3231). The country with the most publications in top 100 were the USA (n=39). The most commonly published topics were diaphragmatic hernia (n=23), abdominal wall defect (n=20) and atresia (n=6). The most cited manuscripts include various topics with a primary focus on the aetiology, diagnosis, management and outcome of diaphragmatic hernia and abdominal wall defects. Additionally, by collecting the most influential works, this study serves to reference what makes a manuscript 'citable'.

Top 100 cited manuscripts in aortic valve replacement: A bibliometric analysis.

This bibliometric analysis aims to identify publications and highlight the key areas that have shaped modern clinical practices for aortic valve replacement (AVR). In this paper, the top 100 most cited manuscripts for AVR are analyzed. The Thomson Reuters Web of Science database was searched using the terms "aortic valve replacement," "AVR," "sAVR," "tAVR," or "TAVI." The results were ranked by citation number and the top 100 articles were further analyzed by evaluating the subject, author, journal, year of publication, institution, and country of origin. Thirty-thousand and eight hundred eligible papers were examined, with an accumulation of 81 851 citations in total and a mean citation of 819 per manuscript (ranged: 344-4180). The New England Journal of Medicine had the most manuscripts whereas Circulation had the most citations. The number of citations has also significantly increased for articles published after 2000.The most cited manuscript highlighting the management of valvular heart disease, was written by Baumgartner et al By providing the most influential references, this work serves as a comprehensive guide to topics of interest in the field of AVR.

Fourteen years of litigation claims in cardiothoracic surgery in the United Kingdom National Health Service.

Approximately 36 400 cardiac and 23 100 thoracic operations are carried out in the United Kingdom between 2006 and 2015. National Health Service (NHS) resolution, as known as the NHS litigation authority, is one of the essential bodies of the Department of Health. Its purpose is to provide NHS expertise to resolve concerns fair and square share learning for improvement. We aim to evaluate and increase awareness of medicolegal cases in cardiothoracic surgery. Total numbers and details of claims coded by NHS resolution in cardiothoracic surgery from 2004 to 2017 were requested under the Freedom of Information Act 2000. The data provided in successful claims is further breakdown into damages paid to the claimant, defence cost, claimant cost paid and the sum of the three. In contrast, unsuccessful claims only include the defence cost. Moreover, data provided also includes further analysis of primary causes and primary injuries for Claims Closed/Settled with damages paid. There were 753 claims recorded from 2004 to 2017, of which 415 (55.11%) were successful. The number of claims has been steadily increasing since 2004, with two significant raises from 2009/10 to 2010/11 (37-55, 48.64% raise) and 2012/13 to 2013/14 (49-69, 40.82% raise). The mean successful claim ratio was 69.58% (range, 47.56%- 83.33%) There is also a steady increase in the successful ratio from 2004 to 2017. In summary, this is the first study published in relation to litigation claims on cardiothoracic surgery in the United Kingdom. The results have provided insight on claims made against cardiothoracic surgery.

Is there a national variation in cardiothoracic trainees' satisfaction? Evaluation of the United Kingdom General Medical Council national training surveys.

BACKGROUND: The national training surveys was first started in 2006, with an aim to determine the quality of the national training standard. All trainees working in a General Medical Council approved training post are required to complete the survey. We aimed to evaluate cardiothoracic trainees' satisfaction and determine whether there is variation in the United Kingdom. METHOD: The national training survey report in cardiothoracic surgery from 2012 to 2019 was obtained from the General Medical Council website. The cardiothoracic centers were divided based on their geographic locations. Comparisons in all 18 indicators in the national training surveys report were made between the four counties (national) and four local education training boards (LETBs) in England (Regional). Centers with less than 4 years of data were excluded from this study. RESULTS: Thirty-three cardiothoracic centers are included in this study The top three areas that trainees are most satisfied are clinical supervision (out of hours) (91.65), clinical supervision (90.65), and educational supervision (88.27). On the other hand, trainees are less satisfying with the handover (62.63), rota design (61.91), and workload (45.07). It is worth noting that workload is the only area of less than 60%. In addition, there is no national variation in all 18 indicators CONCLUSION: Our data suggested that there is no difference in overall trainee satisfaction in the United Kingdom. However, there are differences in various indicators between England and the three other nations. Individual hospital should reflect on trainees' evaluation on the national training surveys report and improve on specific areas if deemed unsatisfactory.

The 100 most cited manuscripts in coronary artery bypass grafting.

INTRODUCTION: To gain a better understanding of the progression of coronary artery bypass grafting (CABG) and its impact on clinical practice, bibliometric citation analysis can be performed. Bibliometric citation analysis is a method of determining the most influential papers on a topic based on several citations and impact factor. METHOD: A search of the Thomson Reuters Web of Science citation indexing database and research platform was completed using the terms "CABG," "Coronary artery bypass graft," "Coronary artery," "bypass," and/or "bypass grafting." The returned dataset was sorted by the number of citations. RESULTS: The search yielded a total of 11 560 papers which were ranked in order of citations. New England Journal of Medicine published the most papers in the top 100 and generated the most significant number of citations with 20 papers in total followed by Journal of the American College of Cardiology. It also has the highest impact factor and 5-year impact fact in 2007 of 79.26 and 67.513, respectively. CONCLUSION: The most cited manuscripts by Serruys et al described a randomised trial comparing percutaneous coronary intervention and CABG for treating severe coronary artery disease. This work provides the most influential references related to CABG and serves as a guide as to the area of focus in CABG.

Uncemented Metal-Backed Tantalum Patellar Components in Total Knee Arthroplasty Have a High Fracture Rate at Midterm Follow-Up.

BACKGROUND: There is interest in uncemented total knee arthroplasty due to the hope for long-term biologic fixation, but limited data are available regarding uncemented tantalum patellar components. The purpose of this study was to evaluate the radiographic outcomes of uncemented tantalum patellar implants at midterm follow-up. METHODS: We retrospectively reviewed a consecutive series of 30 knees in 29 patients who underwent cementless total knee arthroplasty with an uncemented metal-backed tantalum patella between September 2006 and April 2009. Patients were required to have a minimum radiographic follow-up of 2 years. Anteroposterior and lateral radiographs of the knee were evaluated for signs of implant fracture or gross loosening. Clinical follow-up was obtained by reviewing each patient's most recent orthopedic record. RESULTS: Thirty knees in 29 patients met inclusion criteria. The mean age of the cohort was 59.1 years with a mean body mass index of 31.9 kg/m2. Mean postoperative radiographic follow-up time was 5.5 years. Six fractures of the patellar component were noted. This represented a fracture rate of 20% among the entire cohort and 35% among the 17 knees with visible patellae on anteroposterior radiograph. All fractures had a transverse pattern. No gross patellar component loosening was noted. Among patients with component fractures, 2 required revisions for instability and 1 revision was for infection. CONCLUSION: Our results suggest a minimum 20% rate of component fracture at midterm follow-up. Although many of these patellar component fractures were asymptomatic, they have the potential to impact revision rates in the longer term.

Angiopoietin-like 4 stimulates STAT3-mediated iNOS expression and enhances angiogenesis to accelerate wound healing in diabetic mice.

Impaired wound healing is a major source of morbidity in diabetic patients. Poor outcome has, in part, been related to increased inflammation, poor angiogenesis, and deficiencies in extracellular matrix components. Despite the enormous impact of these chronic wounds, effective therapies are lacking. Here, we showed that the topical application of recombinant matricellular protein angiopoietin-like 4 (ANGPTL4) accelerated wound reepithelialization in diabetic mice, in part, by improving angiogenesis. ANGPTL4 expression is markedly elevated upon normal wound injury. In contrast, ANGPTL4 expression remains low throughout the healing period in diabetic wounds. Exogenous ANGPTL4 modulated several regulatory networks involved in cell migration, angiogenesis, and inflammation, as evidenced by an altered gene expression signature. ANGPTL4 influenced the expression profile of endothelial-specific CD31 in diabetic wounds, returning its profile to that observed in wild-type wounds. We showed ANGPTL4-induced nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of inducible nitric oxide synthase (iNOS) expression in wound epithelia, thus revealing a hitherto unknown mechanism by which ANGPTL4 regulated angiogenesis via keratinocyte-to-endothelial-cell communication. These data show that the replacement of ANGPTL4 may be an effective adjunctive or new therapeutic avenue for treating poor healing wounds. The present finding also confirms that therapeutic angiogenesis remains an attractive treatment modality for diabetic wound healing.

A case of acute tarsal tunnel syndrome following lateralizing calcaneal osteotomy.

Surgical correction of hindfoot varus is frequently performed with a lateral displacement calcaneal osteotomy. It has rarely been associated with iatrogenic tarsal tunnel syndrome in patients with pre-existing neurological disease. We report the first case of acute postoperative tarsal tunnel syndrome in a neurologically intact patient with post-traumatic hindfoot varus. Early diagnosis and emergent operative release afforded an excellent clinical outcome. Imaging studies can help outrule a compressive hematoma and assess for possible nerve transection; however it is paramount that a high index of suspicion is utilized with judicious operative intervention to minimize long-term sequelae.

Trend in mitral valve prostheses of choice and early outcomes in the United Kingdom.

OBJECTIVE: Despite the superiority of mitral valve repair, surgical mitral valve replacement (SMVR) remains an important intervention for patients with valve stenosis, infective endocarditis and complex mitral valve degeneration. There has been an increasing popularity in the worldwide use of biological valves due to the avoidance of long-term anti-coagulation and recent advancements in transcatheter techniques. We aim to evaluate the trend, early clinical outcomes and the choice of prostheses use in isolated SMVR over a 23 years period in the United Kingdom. METHODS: All patients (n = 13,147) who underwent elective or urgent isolated SMVR from March 1996 to April 2019 were identified from the National Adult Cardiac Surgery Audit database. Trends in clinical outcomes, predicted/observed mortality of patients and the utilization of biological prostheses across 5 different age groups: <50, 50-59, 60-69, 70-79 and ≥80 years old were investigated. Early clinical outcomes associated with the use of mechanical and biological mitral valve prostheses in patients between the age of 60-70 years old were analysed. RESULTS: The number of isolated SMVR performed has remained stable with approximately 600 cases annually since 2010. The in-hospital/30-day mortality rate has decreased from 7.41% (1996) to 3.92% (2018), despite the EuroScore II increasing from 1.42% in 1996 to 2.43% in 2018. Biological prostheses usage increased across all age group, and particularly in the 60-69 and 70-79 group, from 17.86% and 53.85% in 1996 to 48.85% and 82.38% in 2018, respectively. The use of mechanical prostheses was reduced in patients between the age of 50-59 from 100% in 1996 to 80.65% in 2018. There were no differences in short term outcomes among patients aged 60-70 years who received either a biological or mechanical prostheses. CONCLUSION: There has been a significant reduction in surgical mitral valve replacement early in-hospital mortality, despite an observed increase in the risk profile of patients over 23 years. A shifting trend in valve replacement choices was observed with a rise in the use of biological prostheses, particularly within the 60-69 and 70-79 age group. Early in hospital outcomes for patients aged 60-70 were not determined by the implanted valve type.

Empiric treatment with aspirin and ticagrelor is the most cost-effective strategy in patients with minor stroke or transient ischemic attack.

BACKGROUND: Patients with minor ischemic stroke or transient ischemic attacks (TIAs) are often treated with dual antiplatelet therapy regimens as part of secondary stroke prevention. Clopidogrel, an antiplatelet used in these regimens, is metabolized into its active form by the CYP2C19 enzyme. Patients with loss of function (LOF) mutations in CYP2C19 are at risk for poorer secondary outcomes when prescribed clopidogrel. AIMS: We aimed to determine the cost-effectiveness of three different treatment antiplatelet regimens in ischemic stroke populations with minor strokes or TIAs and how these treatment regimens are influenced by the LOF prevalence in the population. METHODS: Markov models were developed to look at the cost-effectiveness of empiric treatment with aspirin and clopidogrel versus empiric treatment with aspirin and ticagrelor, versus genotype-guided therapy for either 21 or 30 days. Effect ratios were obtained from the literature, and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. The primary endpoints were the incremental cost-effectiveness ratios (ICERs). RESULTS: Empiric treatment with aspirin and ticagrelor was the most cost-effective treatment. Genotype-guided therapy was more cost-effective than empiric aspirin and clopidogrel if the LOF was above 48%. Empiric ticagrelor and aspirin was cost saving when compared to genotype-guided therapy. Results in models of dual antiplatelet therapy for 30 days were similar. CONCLUSION: This study suggests that in patients with minor stroke and TIA planned for dual antiplatelet regimens, empiric ticagrelor and aspirin is the most cost-effective treatment regimen. If ticagrelor is not available, genotype-guided therapy is the most cost-effective treatment regimen if the LOF prevalence in the population is more than 48%.