Visualization of oxidized guanine nucleotides accumulation in living cells with split MutT.

Cancer cells produce vast quantities of reactive oxygen species, leading to the accumulation of toxic nucleotides as 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP). The human MTH1 protein catalyzes the hydrolysis of 8-oxo-dGTP, and cancer cells are dependent on MTH1 for their survival. MTH1 inhibitors are possible candidates for a class of anticancer drugs; however, a reliable screening system using live cells has not been developed. Here we report a visualization method for 8-oxo-dGTP and its related nucleotides in living cells. Escherichia coli MutT, a functional homologue of MTH1, is divided into the N-terminal (1-95) and C-terminal (96-129) parts (Mu95 and 96tT, respectively). Mu95 and 96tT were fused to Ash (assembly helper tag) and hAG (Azami Green), respectively, to visualize the nucleotides as fluorescent foci formed upon the Ash-hAG association. The foci were highly increased when human cells expressing Ash-Mu95 and hAG-96tT were treated with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-dGTP. The foci formation by 8-oxo-dG(TP) was strikingly enhanced by the MTH1 knockdown. Moreover, known MTH1 inhibitors and oxidizing reagents also increased foci. This is the first system that visualizes damaged nucleotides in living cells, provides an excellent detection method for the oxidized nucleotides and oxidative stress, and enables high throughput screening for MTH1 inhibitors.

Action-at-a-distance mutations induced by 8-oxo-7,8-dihydroguanine are dependent on APOBEC3.

DNA oxidation is a serious threat to genome integrity and is involved in mutations and cancer initiation. The G base is most frequently damaged, and 8-oxo-7,8-dihydroguanine (GO, 8-hydroxyguanine) is one of the predominant damaged bases. In human cells, GO causes a G:C→T:A transversion mutation at the modified site, and also induces untargeted substitution mutations at the G bases of 5'-GpA-3' dinucleotides (action-at-a-distance mutations). The 5'-GpA-3' sequences are complementary to the 5'-TpC-3' sequences, the preferred substrates for apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) cytosine deaminases, and thus their contribution to mutagenesis has been considered. In this study, APOBEC3B, the most abundant APOBEC3 protein in human U2OS cells, was knocked down in human U2OS cells, and a GO-shuttle plasmid was then transfected into the cells. The action-at-a-distance mutations were reduced to ~25% by the knockdown, indicating that GO-induced action-at-a-distance mutations are highly dependent on APOBEC3B in this cell line.

Role of Helicopter Transfer and Cloud-Type Imaging for Acute Type A Aortic Dissection.

BACKGROUND: This study explored if long-distance transfer was safe for patients suffering from acute aortic dissection type A (AADA) and also analyzed the effectiveness of helicopter transfer and cloud-type imaging transfer systems for such patients in northern Hokkaido, Japan. METHODS AND RESULTS: The study included 112 consecutive patients who underwent emergency surgical treatment for AADA from April 2014 to September 2020. The patients were divided into two groups according to the location of referral source hospitals: the Asahikawa city group (group A, n = 49) and the out-of-the-city group (group O, n = 63). Use of helicopter transfer (n = 13) and cloud-type telemedicine (n = 20) in group O were reviewed as subanalyses.Transfer distance differed between groups (4.2 ± 3.5 km in group A vs 107.3 ± 69.2 km in group O; p = 0.0001), but 30-day mortality (10.2% in group A vs 7.9% in group O; p = 0.676) and hospital mortality (12.2% in group A vs 9.5% in group O; p = 0.687) did not differ. Operative outcomes did not differ with or without helicopter and cloud-type telemedicine, but diagnosis-to-operation time was shorter with helicopter (240.0 ± 70.8 vs 320.0 ± 78.5 minutes; p = 0.031) and telemedicine (242.0 ± 75.2 vs 319.0 ± 83.8 minutes; p = 0.007). CONCLUSION: We found that long-distance transfer did not impair surgical outcomes in AADA patients, and both helicopter transfer and cloud-type telemedicine system could contribute to the reduction of diagnosis-to-operation time in the large Hokkaido area. Further studies are mandatory to investigate if both the systems will improve clinical outcomes.

Hypothermic circulatory arrest at 20 ℃ does not deteriorate coagulopathy compared to 28 ℃ in a pig model.

It is believed that a lower temperature setting of hypothermic circulatory arrest (HCA) in thoracic aortic surgery causes coagulopathy, resulting in excessive bleeding. However, experimental studies that eliminate clinical factors are lacking. The objective of this study is to investigate the influence of the temperature setting of HCA on coagulation in a pig model. Ten pigs were divided into the following two groups: moderate temperature at 28 °C (group M, n = 5) or lower temperature at 20 °C (group L, n = 5). Two hours of HCA during a total of 4 h of cardiopulmonary bypass (CPB) were performed. Blood samples were obtained at the beginning (T1) and the end (T2) of the surgery, and coagulation capability was analyzed through standard laboratory tests (SLTs) and rotational thromboelastometry (ROTEM). In SLTs, hemoglobin, fibrinogen, platelet count, prothrombin time, and activated partial thromboplastin time were analyzed. In ROTEM analyses, clotting time and clot formation time of EXTEM, maximum clot firmness (MCF), and maximum clot elasticity (MCE) of EXTEM and FIBTEM were analyzed. Fibrinogen decreased significantly in both groups (group M, p = 0.008; group L, p = 0.0175) at T2, and FIBTEM MCF and MCE also decreased at T2. There were no differences regarding changes in parameters of SLTs and ROTEM between groups. CPB decreases coagulation capacity, contributed by fibrinogen. However, a lower temperature setting of HCA at 20 °C for 2 h did not significantly affect coagulopathy compared to that of HCA at 28 °C after re-warming to 37 °C.

[Early Outcomes and Indications for Surgical Intervention of Preoperative Atrial Fibrillation].

BACKGROUND: This study investigates short-term outcomes following surgical interventions for atrial fibrillation (Af), including the Cox-maze Ⅳ procedure (maze procedure) and pulmonary vein isolation (PVI), performed concurrently with other cardiac surgeries. Additionally, we aim to determine the indications for surgical intervention for Af. METHOD: We retrospectively studied a total of 1,580 patients, out of which 274 had preoperative Af, that underwent cardiac surgery between January 2015 and April 2023. Patients who underwent emergency surgery, died in the hospital postoperatively, or received pacemaker implantation were excluded. Patients were first divided into two groups:the intervention group (n=135, 53.6%) and the non-intervention group( n=117, 46.4%), further categorized by whether they were in sinus rhythm at discharge. The intervention group was then subdivided into the maze procedure group( n=54), and the PVI group (n=76). RESULTS: Within the maze procedure group, significant differences were observed between the sinus rhythm and non-sinus rhythm groups in terms of age, preoperative Af duration, and aortic valve intervention status. In the PVI group, patients with persistent Af, longer preoperative Af duration, and larger left atrium diameter( LAD) were less likely to return to sinus rhythm. Smaller LAD was also a significant factor for returning to sinus rhythm in the non-intervention group. Multivariate analysis for all patients revealed that an LAD smaller than 50 mm was the strongest predictor for returning to sinus rhythm post operation( p<0.01). CONCLUSION: For patients with persistent Af, the maze procedure is favored over PVI as a surgical intervention. When LAD exceeds 50 mm, the likelihood of returning to sinus rhythm is diminished.

Neuron-specific enolase levels immediately following cardiovascular surgery is modulated by hemolysis due to cardiopulmonary bypass, making it unsuitable as a brain damage biomarker.

Neuron-specific enolase (NSE) is one of the biomarkers used as an indicator of brain disorder, but since it is also found in blood cell components, there is a concern that a spurious increase in NSE may occur after cardiovascular surgery, where cardiopulmonary bypass (CPB) causes hemolysis. In the present study, we investigated the relationship between the degree of hemolysis and NSE after cardiovascular surgery and the usefulness of immediate postoperative NSE values in the diagnosis of brain disorder. A retrospective study of 198 patients who underwent surgery with CPB in the period from May 2019 to May 2021 was conducted. Postoperative NSE levels and Free hemoglobin (F-Hb) levels were compared in both groups. In addition, to verify the relationship between hemolysis and NSE, we examined the correlation between F-Hb levels and NSE levels. We also examined whether different surgical procedures could produce an association between hemolysis and NSE. Among 198 patients, 20 had postoperative stroke (Group S) and 178 had no postoperative stroke (Group U). There was no significant difference in postoperative NSE levels and F-Hb levels between Group S and Group U (p = 0.264, p = 0.064 respectively). F-Hb and NSE were weakly correlated (r = 0.29. p < 0.01). In conclusion, NSE level immediately after cardiac surgery with CPB is modified by hemolysis rather than brain injury, therefore it would be unreliable as a biomarker of brain disorder.

Impella Implantation as a Bridge to Surgery for Repair of Aorto-Right Ventricular Fistula Following Prosthetic Valve Endocarditis: A Case Report.

For patients with cardiogenic shock, delaying surgery with mechanical circulatory support is reported to yield better outcomes than emergency surgery. We report on an 82-year-old man diagnosed with vertebral osteomyelitis with concomitant infective endocarditis. Chest radiographs revealed a growing abscess, which resulted in an aorto-right ventricular fistula. Providing Impella support allowed for hemodynamic stabilization prior to surgery. The patient had an uneventful postoperative course and reported to be well in a follow-up 1 year later. Impella support can be used as a bridge to surgery for repairing fistulous tract formation in patients in cardiogenic shock.

Evaluating Short-Term Postoperative Outcomes in Minimally Invasive Mitral Valve Surgery for Patients with Rheumatic Disease.

Minimally invasive mitral valve surgery (MIMVS) is widespread and has become a standard procedure in cardiac surgery [Chitwood 1997; Carpentier 1996]. Therefore, MIMVS is a common procedure for patients with degenerative disease [Raanani 2010; Iribarne 2010] as well. However, the safety of MIMVS in patients with rheumatic heart disease (RHD) has not thoroughly been investigated, due to the low prevalence of RHD in developed countries, where MIMVS is standardized [Miceli 2015]. Here, we investigated the safety of MIMVS for patients with RHD at Lampang Hospital in Thailand.

Interventional Bridging Therapy for Radical Cardiac Surgery in a Patient Seemed to be Inoperable Due to Very Poor Left Ventricular Function: A Case Report.

Cases that are inoperable owing to poor preoperative conditions are sometimes encountered. However, there are some cases that are led to radical treatment by performing bridge therapy. Here, we presented a case of a patient with complex cardiac disease in an inoperable state who underwent bridging therapy that led to successful surgical treatment. A 73-year-old male who received hemodialysis treatment and had severe aortic valve stenosis and coronary artery disease planned surgical treatment. However, he was deemed inoperable owing to his low cardiac function and hemodynamic instability. Therefore, to escape from a fatal condition, we first performed balloon aortic valvuloplasty and percutaneous coronary intervention as palliative procedures. Subsequently, his cardiac function and hemodynamic stability remarkably improved; therefore, after 1 month, we performed a successful radical surgical treatment. Even in inoperable patients, bridging therapy leading to radical treatment is possible.

[Low Output Syndrome:Points to Consider for Intraoperative Myocardial Protection and Treatment Methods].

Low cardiac output syndrome (LOS) is a condition that causes low perfusion and perfusion failure of the entire body's tissues due to a decline in heart contractile strength, posing a significant challenge in cardiothoracic surgical perioperative management. Appropriate myocardial protection is crucial to prevent ischemia-reperfusion injury during open-heart surgery and prevent LOS. The integrated myocardial protection method, proposed by Buckberg et al., is one technique employed for this purpose. In the treatment of LOS, interventions are made in the parameters of stroke volume and heart rate, structural abnormalities are excluded and dealt with, and mechanical assistance is utilized when necessary. With the aging and increasing severity of surgical patients, the risk of postoperative LOS is on the rise. Therefore, the application of appropriate myocardial protection and treatment methods leads to improved prognosis. It's worth noting that ensuring optimal myocardial protection during surgery and the correct application of medication and devices for intervention can significantly improve patient outcomes. With the rise in high-risk surgical cases due to aging and an increase in severe conditions, the importance of these interventions cannot be overstated.

Investigations into the Potential of Using Open Source CFD to Analyze the Differences in Hemodynamic Parameters for Aortic Dissections (Healthy versus Stanford Type A and B).

BACKGROUND: The objective of this study was to develop a method to evaluate the effects of an aortic dissection on hemodynamic parameters by conducting a comparison with that of a healthy (nondissected) aorta. Open-source software will be implemented, no proprietary software/application will be used to ensure accessorily and repeatability, in all the data analysis and processing. Computed tomography (CT) images of aortic dissection are used for the model geometry segmentation. Boundary conditions from literature are implemented to computational fluid dynamics (CFD) to analyze the hemodynamic parameters. METHODS: A numerical simulation model was created by obtaining accurate 3-dimensional geometries of aortae from CT images. In this study, CT images of 8 cases of aortic dissection (Stanford type-A and type-B) and 3 cases of healthy aortae are used for the actual aorta model geometry segmentation. These models were exported into an open-source CFD software, OpenFOAM, where a simplified pulsating flow was simulated by controlling the flow pressure. Ten cycles of the pulsatile flow (0.50 sec/cycle) conditions, totaling 5 sec, were calculated. RESULTS: The pressure distribution, wall shear stress (WSS) and flow velocity streamlines within the aorta and the false lumen were calculated and visualized. It was found that the flow velocity and WSS had a high correlation in high WSS areas of the intermittent layer between the true and false lumen. Most of the Stanford type-A dissections in the study showed high WSS, over 38 Pa, at the systole phase. This indicates that the arterial walls in type-A dissections are more likely to be damaged with pulsatile flow. CONCLUSIONS: Using CFD to estimate localized high WSS areas may help in deciding to treat a type-A or B dissection with a stent graft to prevent a potential rupture.

Comparing Conscious Sedation With Regional Anesthesia Versus General Anesthesia in Minimally Invasive Mitral Valve Surgery With Right-Sided Minithoracotomy: A Retrospective Study.

OBJECTIVES: The aims of the present study were to evaluate and compare the safety and feasibility, including hospitalization, intensive care unit (ICU) stay, frequency of conversion to general anesthesia (GA), pH, PaCO2, and PaO2, of selected patients who underwent minimally invasive mitral valve surgery (MIMVS) via a right minithoracotomy under conscious sedation (CS) to avoid GA. The authors also aimed to evaluate the perioperative management of spontaneous breathing. DESIGN: A retrospective, observational study. SETTING: Single-center. PARTICIPANTS: This study enrolled 101 patients who underwent MIMVS under CS or GA. INTERVENTIONS: The patients who underwent MIMVS were managed under CS or GA according to indication criteria. MEASUREMENTS AND MAIN RESULTS: ICU stay (p = 0.010), postoperative time until first fluid intake (p < 0.0001), and duration of mechanical ventilation (p = 0.004) were shorter in the CS group than in the GA group. No patients converted to GA from CS. PaCO2 during cardiopulmonary bypass (CPB) in the CS group was significantly lower than that in the GA group. However, PaCO2 at the termination of CPB in the CS group was significantly higher than that in the GA group. CONCLUSIONS: In the CS group, advanced-age patients with comorbidities underwent mitral surgery without postoperative complications. The authors' findings suggested that MIMVS under CS could be a potentially less-invasive method, providing a quicker recovery than MIMVS under GA.

Hypothermic circulatory arrest does not induce coagulopathy in vitro.

Hypothermic circulatory arrest (HCA) is an essential procedure during aortic surgery to protect organs; however, hypothermia is believed to cause coagulopathy, which is a major fatal complication. This study aimed to clarify the impact of hypothermia on coagulation by eliminating clinical biases in vitro. In the hypothermic storage study, blood samples from five healthy volunteers were stored at 37 â„ƒ (group N) for 3 h or at 20 â„ƒ for 2 h, followed by 1 h of rewarming at 37 â„ƒ (group H). Thromboelastography was performed before and after 3 h of storage. In the mock circulation loop (MCL) study, blood samples were placed in the MCL and (a) maintained at 37 â„ƒ for 4 h (group N, n = 5), or (b) cooled to 20 â„ƒ to simulate HCA with a 0.1 L/min flow rate for 3 h and then rewarmed to 37 â„ƒ (group H, n = 5). The total MCL duration was 4 h, and the flow rate was maintained at 1 L/min, except during HCA. Blood samples collected 15 min after the beginning and end of MCL were subjected to standard laboratory tests and rotational thromboelastometry analyses. Hypothermia had no impact on coagulation in both the hypothermic storage and MCL studies. MCL significantly decreased the platelet counts and clot elasticity in the INTEM and EXTEM assays; however, there was no effect on fibrinogen contribution measured by FIBTEM. Hypothermia does not cause irreversible coagulopathy in vitro; however, MCL decreases coagulation due to the deterioration of platelets.

The Influence of Left Ventricular Dysfunction on The Early and Midterm Outcome in The Patients Undergoing Off Pump Coronary Artery Bypass Grafting Assessed by Propensity Matched Score Analysis.

BACKGROUND: It still remains unclear the depth of influence of left ventricular dysfunction on the recovery of patients' physical conditions in the early and midterm period following off-pump coronary artery bypass grafting (OPCAB). METHODS: From April 2011 to May 2018, 851 patients underwent OPCAB in our center. All were grouped into two groups: Those whose ejection fraction (EF) was under 35% were defined as the Low EF group (N = 158) and those who maintained EF over 35% were defined as the Faired EF group (N = 693). Preoperatively, there was significant difference in NYHA class (P < 0.001), CCS class (P = 0.038), level of creatinine (P < 0.001), and rate of establishment of IABP (P < 0.001). RESULTS: Regarding all-cause death in the early postoperative period, low EF was a not a risk factor in patients (P = 0.52) or in the matched cohort (P = 0.398); however, in the midterm, it was a significant risk factor in patients (HR 2.07, P = 0.016) and in the matched cohort (HR 2.72, P = 0.029). Overall survival at 5 years in the Low EF group was significantly inferior to that of the Faired EF group in all (67.4±4.1% and 86.1±2.9%, P = 0.001) and in the matched cohort (66.5±6.4% vs. 86.5±4.5%, P = 0.008). CONCLUSION: OPCAB seems beneficial for patients with LV dysfunction considering the early outcome, however, low EF is a significant risk factor for overall death in the midterm period.

Mesenteric Ischemia After Cardiac Surgery in Dialysis Patients: An Overlooked Risk Factor.

BACKGROUND: No study has examined the association of the calcification of abdominal artery orifices with nonocclusive mesenteric ischemia (NOMI) in dialysis patients undergoing cardiac surgery. Thus, this study aimed to determine whether calcification of abdominal blood vessel orifices in hemodialysis patients may be a risk factor for NOMI and examine the long-term survival of dialysis patients after undergoing cardiac surgery. METHODS: From April 2014 to September 2020, 100 dialysis patients underwent cardiac surgery at our hospital. The calcification of the celiac artery (CA) and superior mesenteric artery (SMA) was evaluated by computed tomography, and the degree of orifice stenosis was graded as follows: patent, 0; partial occlusion, 1; and complete occlusion, 2. RESULTS: Eight patients experienced NOMI, and all of them died. SMA calcification scores were not significantly different between the NOMI and non-NOMI groups (1.38±0.52 vs. 1.13±0.69; P = 0.247). However, the average CA orifice calcification score was significantly greater in the NOMI group than in the non-NOMI group (1.63±0.52 vs. 1.15±0.65; P = 0.039), and the SMA+CA orifice calcification scores were significantly different between the groups (3.00±0.76 vs. [non-NOMI] 2.25±1.18; P = 0.028). In all patients, the 30-day and in-hospital mortality rates were 13% and 18%, respectively. All patients were completely followed up with a mean follow-up period of 604±585 days. Kaplan-Meier survival curves showed that patients with SMA and CA calcification tended to have a shorter overall survival than patients without calcification; however, no significant difference was noted. CONCLUSIONS: The calcification of CA and/or SMA orifices was associated with postoperative NOMI and poor long-term survival among dialysis patients undergoing cardiac surgery.

Action-at-a-distance mutations at 5'-GpA-3' sites induced by oxidised guanine in WRN-knockdown cells.

G:C sites distant from 8-oxo-7,8-dihydroguanine (GO, 8-hydroxyguanine) are frequently mutated when the lesion-bearing plasmid DNA is replicated in human cells with reduced Werner syndrome (WRN) protein. To detect the untargeted mutations preferentially, the oxidised guanine base was placed downstream of the reporter supF gene and the plasmid DNA was introduced into WRN-knockdown cells. The total mutant frequency seemed higher in the WRN-knockdown cells as compared to the control cells. Mutation analyses revealed that substitution mutations occurred at the G:C pairs of 5'-GpA-3'/5'-TpC-3' sites, the preferred sequence for the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3)-family cytosine deaminases, in the supF gene in both control and knockdown cells. These mutations were observed more frequently at G sites than C sites on the DNA strand where the GO base was originally located. This tendency was promoted by the knockdown of the WRN protein. The present results imply the possible involvement of APOBEC3-family cytosine deaminases in the action-at-a-distance (untargeted) mutations at G:C (or G) sites induced by GO and in cancer initiation by oxidative stress.

Use of laboratory testing for prediction of postoperative bleeding volume in cardiovascular surgery.

BACKGROUND: Coagulopathy and following massive bleeding are complications of cardiovascular surgery, particularly occurring after procedures requiring prolonged cardiopulmonary bypass (CPB). Reliable and rapid tests for coagulopathy are desirable for guiding transfusion. Measuring multiple coagulation parameters may prove useful. The purpose of this study is to determine the laboratory parameters predicting massive bleeding. METHODS: In a prospectively collected cohort of 48 patients undergoing cardiovascular surgery, markers of coagulation and fibrinolysis were measured using automated analyzer and their correlations with bleeding volume were determined. RESULTS: Operation time was 318 (107-654) min. CPB time was 181 (58-501) min. Bleeding volume during surgery was 2269 (174-10,607) ml. Number of transfusion units during surgery were packed red blood cells 12 (0-30) units, fresh frozen plasma 12 (0-44) units, platelets 20 (0-60) units and intraoperative autologous blood collection 669 (0-4439) ml. Post-surgery activities of coagulation factors II (FII), FV, FVII, FVIII, FIX, FX, FXI and FXII were decreased. Values of fibrinogen, antithrombin, α2 plasmin inhibitor (α2PI) and FXIII were also decreased. Values of thrombin-antithrombin complex (TAT) were increased. Values of FII, FIX, FXI and α2PI before surgery were negatively correlated with bleeding volume (FII, r = - 0.506: FIX, r = - 0.504: FXI, r = - 0.580; α2PI, r = - 0.418). Level of FIX after surgery was negatively correlated with bleeding volume (r = - 0.445) and level of TAT after surgery was positively correlated with bleeding volume (r = 0.443). CONCLUSIONS: These results suggest that several clinical and routine laboratory parameters of coagulation were individually associated with bleeding volume during cardiovascular surgery. Determining the patterns of coagulopathy may potentially help guide transfusion during cardiovascular surgery.

Proximalized Total Arch Replacement Can Be Safely Performed by Trainee.

BACKGROUND: The aim of the present study was to validate safety of total arch replacement (TAR) using a novel frozen elephant trunk device, operated by trainees as surgical education. METHODS: Sixty-four patients including 19 patients (29.6%) with acute aortic dissection type A (AADA) underwent TAR in our institute between April 2014 and March 2019 were retrospectively analyzed. Twenty-nine patients were operated by trainees (group T) and 35 patients were operated by attending surgeons (group A). RESULTS: Patient characteristics did not differ between groups. Operative time (409.4 ± 87.8 vs. 468.6 ± 129.6 minutes, p = 0.034), cardiopulmonary bypass time (177.7 ± 50.4 vs. 222.9 ± 596.7 minutes, p = 0.019), and hypothermic circulatory arrest time (39.5 ± 13.4 vs. 54.5 ± 18.5 minutes, p = 0.001) were significantly shorter in group A than in group T, but aortic clamping time did not differ between groups (115.3 ± 55.7 vs. 114.2 ± 35.0 minutes, p = 0.924) because the rate of concomitant surgery was higher in group A (37.1 vs. 10.3%, p = 0.014). Thirty-day mortality was 3.1% in the entire cohort. Although operation time was longer in group T, there were no significant difference in postoperative results between the groups, and the experience levels of the main operator were not independent predictors for in-hospital mortality + major postoperative complications. There was no difference in late death and aortic events between groups. CONCLUSIONS: The present study demonstrated that TAR can be safely performed by trainees, and suggests TAR as a possible and safe educational operation.

A systematic review of the incidence, risk factors and prognosis of acute exacerbation of systemic autoimmune disease-associated interstitial lung disease.

INTRODUCTION: Acute exacerbation (AE) is a devastating phenomenon and reported to be complicated with systemic autoimmune disease-associated interstitial lung disease (ILD). The aim of this study was to investigate the incidence and prognosis of AE of systemic autoimmune disease-ILD and clarify relevant clinical information predictive of these outcomes. METHOD: This study was designed as a systematic review and meta-analysis. A primary study except for a case report, which reported the incidence and/or prognosis of AE of systemic autoimmune disease-ILD, was eligible for the review. Electronic databases such as Medline and EMBASE were searched from 2002 through 23 February 2020. Two reviewers independently selected eligible reports and extracted relevant data. Risk of bias of individual studies was assessed similarly. The incidence and prognosis of the disease were analysed qualitatively. Univariate results of risk and prognostic factors were combined if feasible. RESULTS: Out of a total of 2662 records, 24 studies were eligible. A total of 420 subjects with 45.7% of men developed AE of systemic autoimmune disease-ILD and the two major underlying systemic autoimmune diseases were rheumatoid arthritis (34.2%) and polymyositis/dermatomyositis (31.9%). The frequency ranged from 4.3 to 32.9% with the incident rate being 3.19 and 5.77 per 100 patient-years and all-cause mortality was between 30.0 and 58.3% at 90 days. Age at initial presentation was significantly associated with the development of AE of systemic autoimmune disease-ILD with an HR of 1.22 (95%CI 1.05-1.50) while a percentage of predicted diffusing capacity of the lung for carbon monoxide (%DLCO) was also significantly associated with the development of the disease with an HR of 0.95 (95%CI 0.90-1.00) and an OR of 0.97 (95%CI 0.95-0.99). Partial pressure of arterial oxygen/fraction of inspired oxygen ratio (PaO2/FiO2) at AE was significantly associated with all-cause mortality of AE of systemic autoimmune disease-ILD with an HR of 0.99 (95%CI 0.98-0.99). CONCLUSION: AE of systemic autoimmune disease-ILD was not uncommon and demonstrated dismal prognosis. Age at initial presentation and %DLCO were deemed as risk factors while PaO2/FiO2 at AE was considered as a prognostic factor of the disease. Registration CRD42019138941.

The analysis of left ventricular ejection fraction after minimally invasive surgery for primary mitral valve regurgitation.

BACKGROUND: Although minimally invasive mitral valve surgery (MIMVS) has become the first choice for primary mitral regurgitation (MR) in recent years, clinical evidence in this field is yet limited. The main focus of this study was the analysis of preoperative (Pre), postoperative (Post), and 1-year follow-up (Fu) data in our series of MIMVS to identify factors that have an impact on the left ventricular ejection fraction (LVEF) evolution after MIMVS. METHODS: We reviewed the perioperative and 1-year follow-up data from 436 patients with primary MR (338 isolated MIMVS und 98 MIMVS combined with tricuspid valve repair) to analyze patients' baseline characteristics, the change of LV size, the postoperative evolution of LVEF and its factors, and the clinical outcomes. RESULTS: The overall mean value of ejection fraction (EF) slightly decreased at 1-year follow-up (mean change of LVEF: -2.63 ± 9.00%). A significant correlation was observed for preoperative EF (PreEF) und EF evolution, the higher PreEF the more pronounced decreased EF evolution (in all 436 patients; r = -.54, p < .001, in isolated MIMVS; r = -.54, p < .001, in combined MIMVS; r = -.53, p < .001). Statistically significant differences for negative EF evolution were evident in patients with mild or greater tricuspid valve regurgitation (TR) (in all patients; p < .05, odds ratio [OR] = 1.64, in isolated MIMVS; p < .01, OR = 1.93, respectively). Overall clinical outcome in New York Heart Association classification at 1 year was remarkably improved. CONCLUSIONS: Our results suggest an excellent clinical outcome at 1 year, although mean LVEF slightly declined over time. TR could be a predictor of worsened follow-up LVEF in patients undergoing MIMVS.