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Objective: The optimal anticoagulation strategy for patients with bioprosthetic valves and atrial fibrillation remain uncertain. Thus, we conducted a meta-analysis using updated evidence comparing direct anticoagulants (DOAC) and vitamin K antagonist (VKA) in patients with bioprosthetic valves and atrial fibrillation. Methods: MEDLINE and EMBASE were searched through March, 2021 to identify randomized control trials (RCT) and observational studies that investigated the outcomes of DOAC and VKA in patients with bioprosthetic valves and atrial fibrillation. The outcomes of interest were all-cause death, major bleeding, and stroke or systemic embolism. Results: Our analysis included 4 RCTs and 6 observational studies which enrolled a total of 6,405 patients with bioprosthetic valves and atrial fibrillation assigned to the DOAC group (n =2,142) and VKA (n =4,263). Pooled analysis demonstrated the similar rates of all-cause death (HR [95% confidence interval [CI]] =0.90 [0.77-1.05]; P =0.18; I 2 =0%)between the DOAC and VKA groups. However, the rates of major bleeding were significantly lower in the DOAC group compared to the VKA group (HR [95% CI] =0.66 [0.48-0.89]; P =0.006; I 2 =0%) (Figure), while the rates of stroke or systemic embolism were similar (HR [95% CI] =0.72 [0.44-1.17]; P =0.18; I 2 =39%). Conclusion: DOAC was associated with lower rates of major bleeding without increasing the risk of stroke or systemic embolism or all-cause death compared to VKA in patients with bioprosthetic valves and atrial fibrillation.

AIMS Catheter ablation (CA) is established therapy for patients with atrial fibrillation (AF); however, there is a limited understanding of CA in elderly patients. We studied the long-term efficacy and periprocedural safety of radiofrequency and cryoballoon CA for elderly patients with AF. METHODS PubMed and Embase were searched through April 2021 to investigate the comparative outcomes between elderly and non-elderly patients who underwent CA for AF. The primary efficacy and safety endpoints were AF recurrence and procedure-related complications, respectively. Subgroup analyses were performed by procedure type of CA. RESULTS The search identified 20 observational studies with 110,606 patients, including 8,009 elderly patients (7.2%). The risk of AF recurrence was not significantly different between elderly and non-elderly patients (hazard ratio, 1.37; 95% confidence interval [CI], 0.94-2.00; P = 0.10, I2 = 70%). However, relative to the non-elderly, elderly patients had significantly higher major complications (risk ratio [RR], 1.32; 95% CI, 1.14-1.54], P

Objective Minimally invasive cardiac surgery (MICS) through right mini-thoracotomy as well as robotic surgery has emerged for the last decade for mitral valve surgery. However, their risks and benefits are not fully understood yet. Thus, we conducted a network meta-analysis comparing the early- and long-term outcomes of mitral valve surgery via the conventional sternotomy, MICS, and robotic approaches. Evidence acquisition MEDLINE and EMBASE were searched through November, 2020 to identify randomized controlled trials (RCTs) and propensity-score matched (PSM) trials that investigated early- and long-term outcomes after mitral surgery via the conventional sternotomy, MICS, and robotic approaches. A subalalysis focusing on only subjects who initially underwent mitral valve repair was also conducted. Evidence synthesis Our systematic literature search identified 2 RCTs and 19 PSM studies. MICS was related to significant risk reductions of permanent pacemaker implantation, surgical site infection, and transfusion compared to the sternotomy approach. The robotic approach was associated with a significant increase in re-exploration for bleeding compared to sternotomy. The subanalysis showed that MICS was associated with a significant increase requiring mitral valve reoperation compared to the sternotomy approach (hazard ratio [95% confidence interval] =7.33 [1.54-34.97], p=0.012), while no significant difference was observed between the sternotomy and the robotic approach. Conclusions Our network meta-analysis demonstrated that MICS was associated with better short-term outcomes compared to the sternotomy approach. Mitral valve reoperation was more frequent with MICS compared with the sternotomy approach after mitral valve repair, while no difference was observed between the sternotomy and robotic approaches.

Nutritional problems after gastrectomy affect continuation of postoperative chemotherapy. There have been no studies limited to total gastrectomy, which is particularly prone to nutritional problems. In this study, we aimed to investigate the factors that predict the continuation of postoperative chemotherapy.We included 101 patients who underwent curative total gastrectomy and postoperative chemotherapy at Hiroshima Memorial Hospital. The effects of 37 factors, including perioperative inflammatory, nutritional, and tumor status, on the persistence of postoperative chemotherapy were analyzed.In univariate analysis of preoperative factors, age, carbohydrate antigen 19-9, platelet-to-neutrophil ratio, Onodera's prognostic nutritional index (PNI), controlling nutritional status score, and nutritional risk screening (NRS-2002) score were significantly associated with the duration of postoperative chemotherapy. In multivariate analysis of preoperative factors, age (≥74 years) was an independent factor for a shorter duration of postoperative chemotherapy (hazard ratio [HR], 5.24; 95% confidence interval [CI], 2.19-12.96; P0.01). In univariate analysis of factors before postoperative chemotherapy, intraoperative blood loss, perioperative weight loss rate, postoperative performance status, PNI, albumin-to-bilirubin index, and NRS-2002 score were significantly associated with the duration of postoperative chemotherapy. In multivariate analysis of factors before postoperative therapy, age (≥74 years) (HR, 5.75; 95% CI, 1.90-19.49; P0.01) and PNI (39) (HR, 3.29; 95% CI, 1.26-8.56; P=0.02) were independent factors for a shorter duration of postoperative chemotherapy.Age and PNI are useful predictors of postoperative chemotherapy intolerance after total gastrectomy and may determine the treatment strategy and timing of chemotherapy initiation.

The evidence regarding the impact of cerebral embolic protection devices (EPDs) on outcomes following transcatheter aortic valve replacement (TAVR) is limited. The objective of this study was to evaluate in-hospital outcomes with the use of cerebral EPDs in TAVR. We performed a comprehensive EMBASE and PUBMED search to investigate randomized control studies or propensity score-matched retrospective studies which assessed patients undergoing TAVR with or without EPD up to April 2021. Endpoints of interest were in-hospital mortality, stroke, acute kidney injury, pacemaker implantation, major bleeding, vascular complication, length of stay. Ten studies involving 173,002 patients with EPD (n = 16,898, 9.8%) and those without (n = 156,104, 90.2%) fulfilled the inclusion criteria. The use of EPD was associated with significantly lower risk of in-hospital stroke (odds ratio [95% confidential interval]: 0.64 [0.46; 0.89]), but similar rate of in-hospital mortality (odds ratio [95% confidential interval]: 0.75 [0.54; 1.05]). No differences were observed in acute kidney injury, pacemaker implantation, major bleeding, vascular complication, length of stay. EPD during TAVR was associated with lower in-hospital stroke but did not affect procedural complications and length of stay.

Introduction To determine whether renin-angiotensin system inhibitor (RASI) prescription is associated with better survival after transcatheter aortic valve implantation (TAVI), we performed the first meta-analysis of currently available studies. Evidence acquisition To identify all studies reporting impact of RASI prescription on survival after TAVI, we searched PubMed, Web of Science, and Google Scholar through October 2019 We extracted adjusted (if unavailable, unadjusted) hazard ratios (HRs) with their confidence interval (CIs) of midterm (up to ≥6-month) allcause for RASI prescription from each study and combined study-specific estimates using inverse variance-weighted averages of logarithmic HRs in the random-effects model. Evidence synthesis We identified 13 eligible studies with a total of 26,132 TAVI patients and included them in the present meta-analysis. None was a randomized controlled trial, 5 were observational studies comparing patients with versus without RASI prescription (including 3 propensity score matched studies), and 8 were observational studies investigating RASI prescription as one of covariates. The primary meta-analysis of all studies demonstrated that RASI prescription was associated with significantly lower midterm mortality (HR, 0.83; 95% CI, 0.76 to 0.92; P = 0.0002). Although we identified significant funnel plot asymmetry (P = 0.036 by the rank correlation test) suggesting publication bias, correcting for it using the trim-and-fill method did not substantially alter the result favoring RASI prescription (corrected HR, 0.85; 95% CI, 0.76 to 0.95; P = 0.004). Conclusions RASI prescription may be associated with better midterm survival after TAVI.

OBJECTIVE The optimal treatment strategy in patients with coronary artery disease (CAD) and low left ventricular ejection fraction (LVEF) remains controversial. Herein, we conducted a network meta-analysis comparing coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), and optimal medical therapy (OMT) in patients with CAD and low LVEF. METHODS MEDLINE and EMBASE were searched through March, 2021 to identify randomized controlled trials (RCTs) and propensity-score matched (PSM) studies comparing CABG, PCI, and OMT. We extracted hazard ratios (HRs) of the outcomes. RESULTS A total of three RCTs and 10 PSM trials were identified, yielding a total of 18,855 patients with CAD with low EF who were treated with CABG (n = 9241), PCI (n = 8771), or OMT (n = 1003). All-cause mortality was significantly lower in patients with CABG compared with those with PCI or OMT (HR [95% confidence interval (CI)] = 0.72 [0.62-0.82], p

Background Although current guidelines recommend dual antiplatelet therapy (DAPT) for 3 to 6 months following transcatheter aortic valve replacement (TAVR), there are no studies directly comparing outcomes of different durations of DAPT following TAVR. Methods and Results PubMed, EMBASE, and Cochrane Database were searched through November 2020 to identify clinical studies that investigated single antiplatelet therapy versus DAPT use following TAVR. Studies using oral anticoagulants and antiplatelet therapy concomitantly were excluded. The DAPT group was subdivided by the duration of DAPT. We extracted the risk ratios (RRs) of major or life‐threatening bleeding, stroke, and all‐cause mortality. Four randomized controlled trials, 2 propensity‐score matched studies, and 1 observational study were identified, yielding a total of 2498 patients who underwent TAVR assigned to the single antiplatelet therapy group (n=1249), 3‐month DAPT group (n=485), or 6‐month DAPT group (n=764). Pooled analyses demonstrated that when compared with the single antiplatelet therapy group, the rates of major or life‐threatening bleeding were significantly higher in the 3‐ and 6‐month DAPT groups (RR [95% CI]=2.13 [1.33–3.40], P =0.016; RR [95% CI]=2.54 [1.49–4.33], P =0.007, respectively) with no difference between the 3‐month DAPT versus 6‐month DAPT groups. The rates of stroke and all‐cause mortality were similar among the 3 groups. Conclusions In this network meta‐analysis of antiplatelet therapy following TAVR, single antiplatelet therapy with aspirin had lower bleeding without increasing stroke or death when compared with either 3‐ or 6‐month DAPT.

BACKGROUND Robotic coronary artery bypass graft (CABG) has developed in recent decades, however, prior studies showed conflicting result of robotic CABG compared to nonrobotic CABG in terms of mortality, morbidity, and cost. Herein, we sought to analyze the in-hospital outcomes and health care utilization after robotic CABG compared to nonrobotic CABG, based on data from a nationally representative sample. METHODS Patients who underwent CABG were identified using the national inpatient sample. Endpoints were in-hospital outcomes, length of stay, and total cost. Procedure-related complications were identified via international classification of diseases (ICD)-9 and ICD-10 coding and propensity score matching analysis was performed. RESULTS A total of 1,204,125 weighted adults underwent nonrobotic CABG and 7355 underwent robotic CABG in the United States between 2012 and 2017. The comparison of 7330 pairs after propensity score matching showed that in-hospital mortality was higher for those who underwent nonrobotic CABG compared to those who underwent robotic CABG (2.1% vs. 1.1%, p = .029). Similarly, the rates of acute kidney injury, transfusion, postoperative hemorrhage, length of stay, and total cost were higher for nonrobotic CABG compared to robotic CABG (all p

Background Cerebral infarction (CI) remains one of the most common and fatal complications of infective endocarditis (IE), and the timing of surgery for IE with neurologic complications is controversial. As outcomes beyond the perioperative period have not been assessed with a meta-analysis previously, we conducted a meta-analysis comparing mid- to long-term outcomes of early and late surgery in patients with IE and neurologic complications. Methods All studies that investigated early and late surgery in patients with IE and neurologic complications were identified. The primary and secondary endpoints were all-cause mortality and recurrence, respectively. Hazard ratios (HRs) for all-cause mortality and recurrence were extracted from each study. Results Our search identified five eligible studies, which were all observational studies consisting of a total of 624 patients with IE and neurologic complications. Pooled analyses demonstrated that all-cause mortality was similar between the early and late surgery groups (HR [95% confidence interval [CI]] = 0.90 [0.49–1.64]; P = 0.10; I2 = 49%). Similarly, the recurrence rates were similar between both groups (HR [95% CI] = 1.86 [0.76–4.52]; P = 0.43; I2 = 0%). Conclusions Our meta-analysis showed similar mortality and recurrent rates between the early and late surgery groups. The optimal timing of surgery should be individualized on a case-to-case basis.

A 79-year-old woman visited our hospital complaining of bloating. An abdominal enhanced CT scan revealed pancreatic body cancer with cancerous ascites and multiple liver metastases. We started gemcitabine(GEM)plus nab-paclitaxel chemotherapy. Chemotherapy was not continued because she was unable to take oral medication owing to increased cancerous ascites. We conducted modified KM-cell-free and concentrated ascites reinfusion therapy(KM-CART). Her symptoms improved, and she began having oral intake after KM-CART. Chemotherapy was then re-initiated. Seven months have now passed since we started chemotherapy, and we can continue chemotherapy while conducting KM-CART repeatedly. KM- CART is useful for treating unresectable pancreatic cancer with massive cancerous ascites in terms of continuing chemotherapy.

Although a number of studies compared mortality after transcatheter aortic valve implantation (TAVI) with that after surgical aortic replacement (SAVR) in patients with chronic obstructive pulmonary disease (COPD), no meta-analysis of them has been conducted to date. To determine whether TAVI or SAVR is associated with better postprocedural survival in patients with COPD, a meta-analysis of all studies currently available was performed.

Background: Although moderate-severe tricuspid valve regurgitation (TR) is an independent risk factor for progressive heart failure and increased mortality, the best method for tricuspid repair remains controversial. As such, we conducted a network meta-analysis to compare early and late outcomes for suture, flexible band, and rigid ring as tricuspid annuloplasty (TAP) in patients with TR. Methods: MEDLINE and EMBASE were searched through February 15th, 2020 to identify randomized controlled trials (RCTs) and observational trials that investigated early and late outcomes after TAP for TR. The outcomes of interest were perioperative mortality, long-term survival and TR recurrence. TR recurrence was defined as at least moderate (TR grade 2) on serial echocardiogram. Results: Our systematic literature search identified 2 RCTs and 16 observational trials, including 6,788 patients who underwent TAP. Median follow-up period was 1-7.4 year. There were no significant differences of perioperative and long-term all-cause mortality among three TAP methods. Suture TAP was associated with a significant increase in TR recurrence compared to rigid ring TAP (Hazard ratio, 2.31; 95% Confidence Interval, 1.40-3.80; p =0.001) (Figure). There were no significant differences were observed in other comparisons in TR recurrence. Conclusion: Our network meta-analysis demonstrated significant reduction in TR recurrence for rigid ring TAP compared to Suture TAP. However, there was no significant mortality difference among suture, flexible band, and rigid ring TAP.

Introduction: Some have hypothesized that the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) may modify susceptibility to coronavirus disease 2019 (COVID-19) in humans. Thus, we conducted two meta-analyses to compare mortality and susceptibility of COVID-19 between those who were treated with ACEI and/or ARB and those who were not treated with ACEI or ARB. Methods: MEDLINE and EMBASE were searched through June 2020 to identify clinical trials that investigated the mortality and testing positive rates for COVID-19 for those who were treated with ACEI or/and ARB and for those who were not treated with ACEI or ARB. The first analysis investigated the testing positive rate of COVID-19. The second analysis investigated the in-hospital mortality rate for patients with COVID-19. Result: 3 eligible studies for the first analysis and 14 eligible studies for the second analysis were identified. The first analysis demonstrated that the testing positive rates were similar for those who were treated with ACEI and for those who were not treated with ACEI (odds ratio [OR] [confidence interval [CI]] =0.96 [0.88-1.04], p =0.69) and for those who were treated with ARB and for those who were not treated with ARB (OR [CI] =0.99 [0.91-1.08], p =0.35) (Figure 1A,B). The second analysis showed that in-hospital mortality for patients with positive COVID-19 was similar between for those who were on ACEI and/or ARB and for those who were not on ACEI or ARB (hazard ratio [HR] [95% [CI]] =0.88 [0.64-1.20], p =0.42) (Figure 2). The subanalysis by restricting studies only investigating patients with hypertension showed ACEI and/or ARB use was associated with a significant reduction of in-hospital mortality compared with no ACEI or ARB use (HR [CI] =0.65 [0.48-0.87]). Conclusion: Our analysis demonstrated that ACEI and/or ARB use was not associated with positive rates of COVID-19, and not associated with mortality of COVID-19 patients.

Background: It has been well documented that the use of the left internal thoracic artery (LITA) to graft the left anterior descending (LAD) artery has a significant benefit in coronary artery bypass graft (CABG) surgery. However, what graft is the best as a second conduit to complement LITA-LAD anastomosis remains uncertain. We thus conducted a network meta-analysis of RCTs to compare graft patency of the radial artery (RA), the right internal thoracic artery (RITA), the right gastroepiploic artery (RGEA), and saphenous vein (SVG) as a second conduit in CABG. Methods: MEDLINE and EMBASE were searched through February 8th, 2020 to identify randomized controlled trials (RCTs) that investigated graft patency of a second conduit in CABG. From each study, we extracted the incidence rate ratios (IRR) of the outcome. Results: A total of 11 RCTs were identified, including 3,434 patients and 2,171 angiographic results. There was no significant difference of IRR in graft failure among the 4 groups (vs. SVG: RA, IRR [95%CI] =0.66 [0.41-1.07]; RGEA, IRR [95% CI] =2.12 [0.54-8.38]; RITA, IRR [95% CI] =0.71 [0.32-1.60]). (Figure) Sensitivity analyses restricting trials with ≥3 years angiographic follow-up time or ≥5 years angiographic follow-up time showed no significant differences of IRR in graft failure among the four groups in both analyses. Conclusion: In a network meta-analysis of the updated outcomes from RCTs, no significant differences were observed in graft patency with the use of RA, RITA, RGEA or SVG as a second conduit in CABG.

Introduction: Left ventricular assist devices (LVAD) improve morbidity and mortality in end-stage heart failure patients but high rates of readmissions remain a problem after implantation. We aimed to assess the incidence, trends, outcomes and predictors of 30-day readmissions after LVAD implantation. Methods: The National Readmission Database was used to identify patients who underwent LVAD implantation between 2012 and 2017 and those with 30-day readmissions. Results: The analysis included a total of 11,947 adults who survived the index hospitalization for LVAD implantation. Among those, 28.2% were readmitted at 30 days. The baseline characteristics were balanced between those with and without 30-day readmission except for the length of stay of index admission, which was significantly higher among those readmitted (39.0 days vs. 34.3 days, p Conclusions: Over one fourth of LVAD recipients have 30-day readmissions with gastrointestinal bleeding as the most frequent cause.

Introduction: Previous studies of patients undergoing various cardiac surgeries demonstrated worse outcomes among African American (AA) patients. It remains unclear if race is a predictor of outcomes among Left Ventricular Assist Device (LVAD) recipients. Methods: Patients who underwent LVAD implantation between 2010 and 2017 were identified using the national inpatient sample (NIS). Race was classified as Caucasians vs. AA vs. Hispanics, and endpoints were in-hospital outcomes, length of stay and cost. Procedure-related complications were identified via ICD-9 and ICD-10 coding and analysis was performed via mixed effect models. Results: A total of 27,132 adults (5,114 unweighted) underwent LVAD implantation in the U.S. between 2010 and 2017, including Caucasians (63.8%), AA (23.8%) and Hispanics (6%). The number of LVAD implantations increased in both Caucasians and AA during the study period. AA LVAD recipients were younger, with higher rates of females and most of the comorbidities, but lower rates of coronary artery disease and coronary artery bypass grafting compared to Caucasians and Hispanics. Medicaid and median income at the lowest quartile were more frequent among AA LVAD recipients. We did not identify differences in in-hospital mortality, stroke, bleeding complications, infectious complications, and acute kidney injury requiring hemodialysis among racial groups (Table). AA LVAD recipients had lower rates of routine discharge than Caucasians and Hispanics, longer length of stay than Caucasians but similar cost of hospitalization. After adjustment with age gender and clinical comorbidities, race was not a predictor of in-hospital mortality. Conclusions: We identified differences in clinical characteristics but not in in-hospital complications among LVAD recipients of different race.

Background: Although current guidelines generally recommend watchful waiting strategy for patients with asymptomatic severe aortic stenosis (AS) until symptoms develop, the optimal timing of surgical intervention remains controversial. Objective: This study aimed to compare the outcomes of early surgery vs. conservative strategy for patients with asymptomatic severe AS. Methods: MEDLINE and EMBASE were searched through February, 2020 to identify clinical trials that investigatedearly surgery and conservative strategy for patients with asymptomatic severe AS. From each study, we extracted the hazard ratio (HR) of all-cause mortality and cardiovascular mortality. Subgroup analyses were conducted by dividing into severe AS (peak aortic jet velocity [Vmax] ≥4.0 m/s, mean aortic pressure gradient [PG] ≥40 mmHg, or aortic valve area [AVA] ≤1.0 cm 2 ) and very severe AS (Vmax ≥4.5 m/s, mean PG ≥50 mmHg, or AVA ≤0.75 cm 2 ) groups. Results: 1 randomized controlled, 7 observational trials were identified. Pooled analyses demonstrated that all-cause mortality and cardiovascular mortality for early surgery were significantly lower compared to conservative strategy (HR [95% Confidence Interval [CI]] =0.49 [0.36-0.68]; P P =0.01, respectively). Subgroup analyses showed significant reduction for early surgery in all-cause mortality (severe AS: HR [95% CI] =0.52 [0.35-0.78]; P =0.001, very severe AS: HR [95% CI] =0.38 [0.17-0.85]; P =0.02). Conclusions: We demonstrated that early surgery was associated with significant reduction in all-cause and cardiovascular mortality in patients with severe AS. Further randomized trials are warranted to confirm our findings.

Background: Benefits and risks of minimally invasive cardiac surgery (MICS) through right mini-thoracotomy and robotic surgery for mitral valve are not fully understood. We conducted a network meta-analysis comparing the perioperative and long-term outcomes of mitral valve surgery via conventional sternotomy, MICS and robot. Methods: MEDLINE and EMBASE were searched through March 15th, 2020 to identify randomized controlled trials (RCTs) and propensity-score matched (PSM) trials that investigated perioperative and long-term outcomes after mitral surgery via conventional sternotomy, MICS and robot. Subanalyses were conducted by restricting trials, in which mitral valve repair was tried first for all patients. Results: Our systematic literature search identified 2 RCTs and 21 PSM trials. MICS was related to significant decrease in PM ([RR] [95% confidence interval [CI] =0.56 [0.40-0.78]] and SSI (RR [95%CI] =0.53 [0.33-0.85) compared to conventional sternatomy. Re-exploration for bleeding was significantly higher in robot compared to sternotomy (RR [95% CI] =1.56 [1.03-2.37]), and transfusion was higher in sternotomy compared to MICS (RR [95%CI] =1.63 [1.27-2.08]). No significant differences were observed in perioperative mortality, MI, stroke, and LCOS among there procedures. Similarly, there were no significant differences in long-term survival and mitral valve reoperation. Suanalyses by restricting trials in which mitral valve repair tried first for all patients showed MICS was related to significant increase in mitral valve reoperation compared to conventional sternotomy (hazard ratio [95%CI] =7.33 [1.54-34.97]) (Figure). Conclusion: Our network meta-analysis demonstrated similar long-term survival and mitral valve reoperation. However, MICS was related to significant increase in mitral valve reoperation after mitral valve repair compared to conventional sternotomy.

Background: Valvular heart disease is common among Left Ventricular Assist Device (LVAD) recipients. However, its management at the time of LVAD implantation remains controversial. We sought to investigate and compare in-hospital outcomes of concomitant valvular surgery at the time of LVAD implantation. Methods: Patients who underwent LVAD implantation and concomitant aortic (AVR), mitral (MVR) or tricuspid valve (TVR) repair or replacement between 2010 and 2017 were identified using the national inpatient sample (NIS) in the US. Endpoints were in-hospital outcomes, length of stay and cost. Procedure-related complications were identified via ICD-9 and ICD-10 coding and analysis was performed via mixed effect models. Results: A total of 25,171 weighted adults underwent LVAD implantation without valvular surgery, 1,329 had isolated TVR, 1,021 AVR, 377 MVR and 615 had combined valvular surgery (411 had TVR+AVR, 115 TVR+MVR, 62 AVR+MVR, 25 AVR+MVR+TVR). During the study period, rates of AVR decreased and combined valvular surgeries increased. Patients who underwent TVR had overall higher burden of comorbidities than LVAD recipients with or without other valvular procedures. Post-operative bleeding was more frequent among those who underwent AVR whereas acute kidney injury requiring dialysis was higher among those who underwent TVR or combined valvular surgery. In-hospital mortality was higher among those who underwent AVR, MVR or combined surgery without differences in the rates of stroke among groups (Table 1). Length of stay did not differ significantly among groups but cost of hospitalization and non-routine discharge rates were higher for cases of TVR and combined surgery. Conclusion: Approximately one in nine LVAD recipients underwent concomitant valvular surgery and TVR was the most frequently performed procedure. In-hospital mortality and cost were lower among those who did not undergo valvular surgery.

Background: Although current guidelines recommend dual antiplatelet therapy (DAPT) for 3 to 6 months following transcatheter aortic valve replacement (TAVR), there are no studies directly comparing outcomes of different durations of DAPT following TAVR. Methods: Pubmed and EMBASE were searched through May, 2020 to identify clinical studies that investigated single antiplatelet therapy (SAPT) versus DAPT use following TAVR. Studies using oral anticoagulants and antiplatelet therapy concomitantly were excluded. The DAPT group was subdivided by the duration of DAPT. We extracted the risk ratios (RRs) of major or life-threatening bleeding, stroke, and all-cause mortality. Results: Three randomized controlled trials, two propensity-score matched studies, and one observational study were identified, yielding a total of 1,833 patients who underwent TAVR assigned to the SAPT group (n=918), 3-month DAPT group (n=151), or 6-month DAPT group (N=764). Pooled analyses demonstrated that the rates of major or life-threatening bleeding were significantly higher in the 6-month DAPT group compared with the SAPT group (RR [95% CI] =2.54 [1.49-4.33], P =0.007) while no such difference was observed between the SAPT vs. 3-month DAPT groups or the 3-month DAPT vs. 6-month DAPT groups (Figure). P-scores were 98.1% (SAPT), 32.3% (3-month DAPT), and 19.6% (6-month DAPT). The rates of stroke and all-cause mortality were similar among the groups. Conclusions: In our network meta-analysis, we observed that DAPT for 6 months following TAVR was associated with increased risk of bleeding without decreasing the risk of stroke compared with SAPT, while there was no difference between DAPT for 3 months and 6 months.

Findings on mutations, associated with lung cancer, have led to advancements in mutation-based precision medicine. This study aimed to comprehensively and synthetically analyze mutations in lung cancer, based on the next generation sequencing data of surgically removed lung tumors, and identify the mutation-related factors that can affect clinical outcomes. Targeted sequencing was performed on formalin-fixed paraffin-embedded surgical specimens obtained from 172 patients with lung cancer who underwent surgery in our hospital. The clinical and genomic databases of the hospital were combined to determine correlations between clinical factors and mutation profiles in lung cancer. Multivariate analyses of mutation-related factors that may affect the prognosis were also performed. Based on histology, TP53 was the driver gene in 70.0% of the cases of squamous cell carcinoma. In adenocarcinoma cases, driver mutations were detected in TP53 (26.0%), KRAS (25.0%), and epidermal growth factor receptor (EGFR) (23.1%). According to multivariate analysis, the number of pathogenic mutations (&ge, 3), presence of a TP53 mutation, and TP53 allele fraction &gt, 60 were poor prognostic mutational factors. The TP53 allele fraction tended to be high in caudally and dorsally located tumors. Moreover, TP53-mutated lung cancers located in segments 9 and 10 were associated with significantly poorer prognosis than those located in segments 1&ndash, 8. This study has identified mutation-related factors that affect the postoperative prognosis of lung cancer. To our knowledge, this is the first study to demonstrate that the TP53 mutation profile varies with the site of lung tumor, and that postoperative prognosis varies accordingly.

Introduction Some have hypothesized that the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) may modify susceptibility to coronavirus disease 2019 (COVID-19) in humans. Thus, we conducted two meta-analyses to investigate the effect of ACEI and ARB on mortality and susceptibility to COVID-19. Methods Pubmed and EMBASE were searched through June 2020 to identify clinical trials that investigated the testing positive and in-hospital mortality rates for COVID-19 for those who were treated with ACEI and/or ARB and for those who were not treated with ACEI or ARB. The first analysis investigated the testing positive rate of COVID-19. The second analysis investigated the in-hospital mortality rate for patients with COVID-19. Result Three eligible studies for the first analysis and 14 eligible studies for the second analysis were identified. The first analysis demonstrated that the use of ACEI or ARB did not affect the testing positive rates (odds ratio [OR] [confidence interval [CI]] =0.96 [0.88-1.04]; p =0.69, OR [CI] =0.99 [0.91-1.08]; p =0.35, respectively). The second analysis showed that the use of ACEI and/or ARB did not affect in-hospital mortality (risk ratio [RR] [95% [CI]] =0.88 [0.64-1.20], p =0.42). The subgroup analysis by limiting studies of patients with hypertension showed ACEI and/or ARB use was associated with a significant reduction of in-hospital mortality compared with no ACEI or ARB use (RR [CI] =0.66 [0.49-0.89], p =0.004). Conclusion Our analysis demonstrated that ACEI and/or ARB use was associated neither with testing positive rates of COVID-19, nor with mortality of COVID-19 patients. This article is protected by copyright. All rights reserved.

Highlights • We did network meta-analyses comparing clinical improvement of COVID-19 patients. • We compared 5-day course vs. 10-day course of remdesivir vs standard care. • Clinical improvement was higher in 5-day and 10-day course than standard care. • Clinical improvement was higher in 5-day than 10-day remdesivir., Several randomized controlled trials (RCTs) were conducted to investigate the effect of remdesivir for patients with COVID-19, but their results were conflicting. Thus, we conducted a network meta-analysis comparing the rate of clinical improvement among patients with COVID-19 who received 5-day course of remdesivir versus 10-day course of remdesivir versus standard care. Our network meta-analysis of 4 randomized controlled trials demonstrated that the rate of clinical improvement was significantly higher in the 5-day remdesivir group and 10-day remdesivir group compared to standard care group (OR [95% confidence interval [CI]] =1.89 [1.40-2.56], P

There is no meta-analysis comparing clinical outcomes between valve-in-valve transcatheter aortic valve implantation for failed surgical bioprosthetic valves (ViV-TAVI) and native valve TAVI for aortic stenosis (NV-TAVI). We aimed to investigate clinical outcomes between ViV-TAVI and NV-TAVI using a meta-analysis. EMBASE and MEDLINE were searched through April 2020 to investigate the comparative outcomes between ViV-TAVI and NV-TAVI. The main outcomes were short-term (30-day/in-hospital) mortality, pacemaker implantation (PMI), life threatening and/or major bleeding, stroke, and coronary obstruction, and long-term (1-year) mortality and stroke. Our search identified 5 observational studies enrolling a total of 8428 patients (1442 patients with ViV-TAVI and 6986 with NV-TAVI). ViV-TAVI was associated with significantly lower rates of short-term mortality, PMI, and life threatening and/or major bleeding, compared with NV-TAVI (relative risk [RR] [95% CI] 0.54 [0.34–0.84], P = 0.007; 0.25 [0.19–0.35], P

Nivolumab is one of the immune checkpoint inhibitors available for chemotherapy-resistant gastric cancer. There have been few reports of confirmed prominent shrinkage of the primary tumor and some reports of prolonged antitumor effect after discontinuance of the drug, but it is not universal. A 67-year-old male was admitted to our hospital and diagnosed with metastatic gastric cancer that had spread to the bilateral lobe of the liver, distant lymph nodes, and peritoneum. He received five courses of S-1 plus oxaliplatin, followed by three courses of ramucirumab plus paclitaxel leading to disease progression. Then, the patient was administered nivolumab as third-line therapy. Tumor size was markedly reduced after three courses, esophagogastroduodenoscopy (EGD) revealed scar formation on the lower gastric corpus after seven courses, and biopsy specimen showed no malignancy. When a slight lower limb muscle weakness manifested, possibly an immune-related adverse event (irAE) after 15 courses, we stopped administration of nivolumab. The patient has survived for 26 months since his first visit, and elimination of the primary tumor and ascites with noted shrinkage of liver and lymph node metastases have followed for more than 10 months since discontinuance of nivolumab.

Thymomas are rare mediastinal tumors that are difficult to treat and pose a major public health concern. Identifying mutations in target genes is vital for the development of novel therapeutic strategies. Type A thymomas possess a missense mutation in GTF2I (chromosome 7 c.74146970T&gt, A) with high frequency. However, the molecular pathways underlying the tumorigenesis of other thymomas remain to be elucidated. We aimed to detect this missense mutation in GTF2I in other thymoma subtypes (types B). This study involved 22 patients who underwent surgery for thymomas between January 2014 and August 2019. We isolated tumor cells from formalin-fixed paraffin-embedded tissues from the primary lesions using laser-capture microdissection. Subsequently, we performed targeted sequencing to detect mutant GTF2I coupled with molecular barcoding. We used PyClone analysis to determine the fraction of tumor cells harboring mutant GTF2I. We detected the missense mutation (chromosome 7 c.74146970T&gt, A) in GTF2I in 14 thymomas among the 22 samples (64%). This mutation was harbored in many type B thymomas as well as type A and AB thymomas. The allele fraction for the tumors containing the mutations was variable, primarily owing to the coexistence of normal lymphocytes in the tumors, especially in type B thymomas. PyClone analysis revealed a high cellular prevalence of mutant GTF2I in tumor cells. Mutant GTF2I was not detected in other carcinomas (lung, gastric, colorectal, or hepatocellular carcinoma) or lymphomas. In conclusion, the majority of thymomas harbor mutations in GTF2I that can be potentially used as a novel therapeutic target in patients with thymomas.

To investigate the association of real-time/observed ozone/PM2.5 levels with COVID-19 prevalence/fatality, meta-regression of data from the Northeast megalopolis was conducted. Daily Air Quality Index (AQI) values based on available ozone/PM2.5 data in these counties/cities (3/15/2020–5/31/2020) were extracted from US Environmental Protection Agency and World Air Quality Project. In each county/city, total confirmed COVID-19 cases/deaths (5/31/2020) were available from Johns Hopkins Coronavirus Resource Center, and total population was extracted from US Census Bureau. Random-effects meta-regression was performed using OpenMetaAnalyst. A meta-regression graph depicted COVID-19 prevalence and fatality (plotted as logarithm-transformed prevalence/fatality on the y-axis) as a function of mean ozone/PM2.5 AQI (plotted on the x-axis). Coefficients were not statistically significant for ozone (P = 0.212/0.814 for prevalence/fatality) and PM2.5 (P = 0.986/0.499). Although multivariable analysis had been planned, it was not performed because of non-significant covariates of interest in the univariable model. In conclusion, ozone/PM2.5 may be unassociated with COVID-19 prevalence/fatality.

Although it has been reported that coexistent chronic diseases are strongly associated with COVID-19 severity, investigations of predictors for SARS-CoV-2 infection itself have been seldom performed. To screen potential risk and protective factors for SARS-CoV-2 infection, meta-regression of data from worldwide nations were herein conducted. We extracted total confirmed COVID-19 cases in worldwide 180 nations (May 31, 2020), nation total population, population ages 0-14/≥65, GDP/GNI per capita, PPP, life expectancy at birth, medical-doctor and nursing/midwifery-personnel density, hypertension/obesity/diabetes prevalence, annual PM2.5 concentrations, daily ultraviolet radiation, population using safely-managed drinking-water/sanitation services and hand-washing facility with soap/water, inbound tourism, and bachelor’s or equivalent (ISCED 6). Restricted maximum-likelihood meta-regression in the random-effects model was performed using Comprehensive Meta-Analysis version 3. To adjust for other covariates, we conducted the hierarchical multivariate models. A slope (coefficient) of the meta-regression line for the COVID-19 prevalence was significantly negative for population ages 0-14 (–0.0636; P = .0021) and positive for obesity prevalence (0.0411; P = .0099) and annual PM2.5 concentrations in urban areas (0.0158; P = .0454), which would indicate that the COVID-19 prevalence decreases significantly as children increase and that the COVID-19 prevalence increases significantly as the obese and PM2.5 increase. In conclusion, children (negatively) and obesity/PM2.5 (positively) may be independently associated with SARS-CoV-2 infection.

Ethnics and economics may affect prevalence and case fatality of Coronavirus disease 2019 (COVID-19). To determine whether COVID-19 prevalence and fatality are modulated by ethnics and economics, meta-regression of data from the countries in the New York metropolitan area were herein conducted. We selected 31 countries in the New York metropolitan area. 1) Prevalence and case-fatality rates of confirmed COVID-19 cases on May 20, 2020 and 2) income and poverty estimates were obtained in each country. We performed random-effects meta-regression using OpenMetaAnalys. The covariates included 1) black (%), 2) Hispanic or Latino (%), 3) poverty rates (%), and 4) median household income ($). Statistically significant (P < .05) covariates in the univariable model were together entered into the multivariable model. A slope (coefficient) of the univariable meta-regression line for COVID-19 prevalence was not significant for household income (P = .639), whereas the coefficient was significantly positive for black (coefficient, 0.021; P = .015), Hispanic/Latino (0.033; P < .001), and poverty (0.039; P = .02), which indicated that COVID-19 prevalence increased significantly as black, Hispanic/Latino, and poverty increased. The multivariable model revealed that the slope was significantly positive for only Hispanic/Latino (P < .001). The coefficient in the univariable model for COVID-19 fatality, however, was not significant for all the covariate. In conclusion, black, Hispanic/Latino, and poverty (not household income), especially Hispanic/Latino independently, may be associated with COVID-19 prevalence. There may be no association of black, Hispanic/Latino, poverty, and household income with COVID-19 fatality.

To determine whether prevalence of Coronavirus disease 2019 (Covid-19) is modulated by meteorological conditions, we herein conducted meta-regression of data in large U.S. cities. We selected 33 large U.S. cities with a population of >500,000. The integrated numbers of confirmed Covid-19 cases in the country to which the city belongs on 14 May 2020, the estimated population in 2019 in the country, and monthly meteorological conditions at the city for 4 months (from January to April 2020) were obtained. Meteorological conditions consisted of mean temperature (F), total precipitation (inch), mean wind speed (MPH), mean sky cover, and mean relative humidity (%). Monthly data for 4 months were averaged or integrated. The Covid-19 prevalence was defined as the integrated number of Covid-19 cases divided by the population. Random-effects meta-regression was performed by means of OpenMetaAnalyst. In a meta-regression graph, Covid-19 prevalence (plotted as the logarithm transformed prevalence on the y-axis) was depicted as a function of a given factor (plotted as a meteorological datum on the x-axis). A slope of the meta-regression line was significantly negative (coefficient, -0.069; P < 0.001) for the mean temperature and significantly positive for the mean wind speed (coefficient, 0.174; P = 0.027) and the sky cover (coefficient, 2.220; P = 0.023). In conclusion, lower temperature and higher wind speed/sky cover may be associated with higher Covid-19 prevalence, which should be confirmed by further epidemiological researches adjusting for various risk and protective factors (in addition to meteorological conditions) of Covid-19.

A recent study from China suggests that high temperature and ultraviolet (UV) radiation cannot decrease the epidemics of Coronavirus disease 2019 (COVID-19). To determine whether COVID-19 prevalence is modulated by meteorological conditions, meta-regression of Japanese prefectural data was herein conducted. We extracted integrated number of patients testing positive for COVID-19 in each Japanese prefecture on 18 May 2020, population per 1-km2 inhabitable area in the prefecture in 2020, and monthly meteorological conditions at each prefectural capital city for 4 months (from January to April 2020). We averaged or cumulated the monthly data for the 4 months. To adjust for prefectural population density, we defined the COVID-19 prevalence as the integrated number of patients testing positive divided by the population per 100-km2 inhabitable area. Random-effects meta-regression was performed. A slope of the meta-regression line was significantly negative for mean air temperature (coefficient, −0.134; P = 0.019), mean sea level air pressure (−0.351; P = 0.001), and mean daily maximum UV index (−0.908; P = 0.012), which indicated that COVID-19 prevalence decreased significantly as air temperature, air pressure, and UV index increased. In conclusion, higher temperature, pressure, and UV may be associated with less COVID-19 prevalence, which should be confirmed by further epidemiological investigations taking other risk and protective factors of COVID-19 into account.

Background Although moderate to severe tricuspid valve regurgitation (TR) is an independent risk factor for progressive heart failure and increased mortality, the best method for tricuspid valve repair remains controversial. Therefore, this study conducted a network meta-analysis to compare early and late outcomes for suture, flexible band, and rigid ring as tricuspid annuloplasty (TAP) in patients with TR. Methods Medline and EMBASE were searched through February 15, 2020 to identify randomized controlled trials and observational trials that investigated early and late outcomes after TAP for TR. The outcomes of interest were perioperative mortality, all-cause mortality, and TR recurrence with more than 1-year follow-up. TR recurrence was defined as at least moderate (TR grade 2) on serial echocardiograms. Results Two randomized controlled trials and 15 observational trials were identified, including 6138 patients who underwent TAP. The median follow-up period was 1 to 7.4 years. There were no significant differences of perioperative and all-cause mortality among 3 TAP methods. Rigid ring TAP was associated with a significant reduction in TR recurrence compared with suture TAP (hazard ratio, 0.42; 95% confidence interval, 0.23 to 0.78; P = .005). There were no significant differences in TR recurrence were observed between flexible band and suture TAP or flexible band and rigid ring TAP. Conclusions This network meta-analysis demonstrated significant reduction in TR recurrence for rigid ring TAP compared with suture TAP, although no significant differences were observed between suture and flexible band TAP or between flexible band and rigid ring TAP. There were no significant mortality differences among suture, flexible band, and rigid ring TAP procedures.

Although current guidelines generally recommend watchful waiting strategy for patients with asymptomatic severe aortic stenosis until symptoms develop, early surgery for asymptomatic aortic stenosis remains controversial. This study aimed to compare the outcomes of early surgery versus conservative strategy for patients with asymptomatic severe aortic stenosis.MEDLINE and EMBASE were searched through February 2020 to identify clinical trials that investigated early surgery and conservative strategy for patients with asymptomatic severe aortic stenosis. From each study, we extracted the hazard ratio of all-cause mortality and cardiovascular mortality. Subgroup analyses were conducted by dividing into severe aortic stenosis (peak aortic jet velocity ≥4.0 m/s, mean aortic pressure gradient ≥40 mm Hg, or aortic valve area ≤1.0 cmOne randomized controlled trial and 7 observational studies were identified. Pooled analyses demonstrated that all-cause mortality and cardiovascular mortality for early surgery were significantly lower compared with conservative strategy (hazard ratio, 0.49; 95% confidence interval, 0.36-0.68; P .0001, hazard ratio, 0.42; 95% confidence interval, 0.22-0.82; P = .01, respectively). Subgroup analyses showed significant reduction for early surgery in all-cause mortality (severe aortic stenosis: hazard ratio, 0.52; 95% confidence interval, 0.35-0.78; P = .001, very severe aortic stenosis: hazard ratio, 0.38; 95% confidence interval, 0.17-0.85; P = .02).We demonstrated that early surgery was associated with significant reduction in all-cause and cardiovascular mortality in patients with severe aortic stenosis. Further randomized trials are warranted to confirm our findings.

Although endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) significantly decreases perioperative mortality compared with open surgical repair (OSR), we have not concluded superiority between EVAR and OSR beyond the perioperative period. The aim of this study was to compare phase-specific survival after EVAR vs OSR.The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Embase and MEDLINE were searched up to November 2019 to identify randomized controlled trials and propensity score-matched studies that investigated ≥2-year all-cause mortality (primary outcome) after EVAR vs OSR for intact infrarenal AAA. For each study, the hazard ratio (HR) with 95% confidence interval (CI) of mortality for EVAR vs OSR was calculated using survival curves for the following specific phases: early term (0-2 years after repair), midterm (2-6 years after repair), long term (6-10 years after repair), and very long term (≥10 years after repair). The risk ratio (RR) in the perioperative (in-hospital or 30-day) period was also extracted. Phase-specific HRs or RRs were separately pooled using the random effects model. Sensitivity analyses were performed by removing one study at a time to confirm that our findings were not derived from any single study. Funnel plot asymmetry was also examined using the linear regression test.Our search identified four randomized controlled trials and seven propensity score-matched studies enrolling a total of 106,243 AAA patients assigned to EVAR (n = 53,123) or OSR (n = 53,120). The mortality after EVAR compared with OSR was significantly lower in the perioperative period (RR, 0.39; 95% CI, 0.29-0.51; P .00001) and similar in the early-term period (HR, 0.93; 95% CI, 0.84-1.03; P = .16). Notably, significantly higher mortality was observed in the EVAR group compared with the OSR group in the midterm period (HR, 1.15; 95% CI, 1.03-1.29; P = .01). However, similar mortality was observed between the EVAR group and the OSR group in the long-term (HR, 1.06; 95% CI, 0.96-1.17; P = .27) and very-long-term (HR, 1.17; 95% CI, 0.93-1.47; P = .19) periods. In sensitivity analyses, the significant benefit of EVAR in the perioperative period and that of OSR in the midterm period were not changed. No funnel plot asymmetry was identified in all analyses.Compared with OSR, EVAR was associated with lower perioperative mortality and higher mortality in the midterm period for intact infrarenal AAA. The superiority of EVAR was absent in the early-term period, and the inferiority of EVAR in the midterm period disappeared in the long-term and very-long-term periods.

Gastrocolic fistula (GSF) is a rare entity that arises mainly from splenic or gastric lymphoma. Gastric and splenic lymphomas can also fistulate with other organs, including the pleura and the colon, but there has been no reported case to best of our knowledge of a fistula involving three different organs. We hereby present the case of a female patient with gastrosplenocolic fistula secondary to non-Hodgkin B-cell lymphoma. We performed an en bloc partial gastrectomy with splenectomy and partial left colon resection with colostomy. GSF can be treated with chemotherapy. However, when the definite diagnosis is unclear or GSF is causing serious complications such as bleeding or active infection, we believe surgical excision is the treatment of choice.

Objective Controversy has continued regarding the use of endovascular aneurysm repair (EVAR) vs open aneurysm repair (OAR) for infected abdominal aortic aneurysms (AAAs). In the present study, we investigated the comparative outcomes of EVAR and OAR for the treatment of infected AAAs. Methods We conducted a systematic review and meta-analysis using the MEDLINE and EMBASE databases through May 2021. We included studies that had described both EVAR and OAR for the treatment of infected AAAs. The primary endpoints were the rates of recurrent infection and related rupture and/or death. Perioperative and 1-year mortality and readmissions and reinterventions were also analyzed. Results Fourteen observational studies describing a total of 1203 patients (EVAR, 359 [29.8%]; OAR, 844 [70.2%]) were eligible for qualitative analysis. The baseline characteristics included diabetes mellitus (33.2%), fever at presentation (71.6%), rupture at diagnosis (26.1%), and positive blood cultures (52.5%). The mean follow-up period ranged from 12 to 40 months. The use of EVAR became more prevalent in recent years (2016-2020, 32.4%) compared with the former period (2010-2015, 13.8%; P Conclusions EVAR has become more prevalent as the initial treatment of infected AAAs. Although operative and 1-year survival were similar between OAR and EVAR groups, recurrent infection was more frequent after EVAR. This limitation should be weighed in selecting patients for EVAR in infected AAAs. Postoperative graft and infection surveillance are critical, especially after EVAR.

OBJECTIVES To determine whether preprocedural left ventricular (LV) diastolic dysfunction impairs midterm mortality after transcatheter aortic valve implantation (TAVI) for patients with severe aortic stenosis (AS), we performed a meta-analysis of currently available evidence. METHODS We identified all studies investigating impact of preprocedural severity of LV diastolic dysfunction on midterm (≥1-year) all-cause mortality after TAVI for patients with AS through a search of databases (MEDLINE and EMBASE) until September 2019. From each study, we extracted an adjusted (if unavailable, unadjusted) hazard ratio (HR) of midterm mortality. We pooled study-specific estimates in the random-effects model. RESULTS Ten eligible studies with a total of 2380 patients with AS undergoing TAVI were identified. In accordance with pooled analyses, higher-grade preprocedural LV diastolic dysfunction was associated with significantly worse midterm all-cause mortality after TAVI compared to lower-grade dysfunction (HR for grade II vs I, 1.15; P = .002; HR for grade III vs I, 1.35; P = .001; HR for grade III vs II; 1.16, P = .002; HR for grade II-III vs I, II-III vs 0-I, or III vs I-II, 1.34; P

Herein, we describe a rare case of neoplastic meningitis in a 54-year-old male with a history of colorectal cancer. He first noticed a loss of sensation in his left thigh along with back pain. Magnetic resonance imaging showed a tumor lesion in the cauda equina. The tumor was surgically resected and pathologically diagnosed as a metastatic tumor of the descending colon cancer for which he had undergone resection a year earlier. The patient was treated with chemotherapy using capecitabine, oxaliplatin, and cetuximab. During chemotherapy, his tumor markers decreased and magnetic resonance imaging showed tumor shrinkage, but he became aware of neurological symptoms such as hearing loss, tinnitus, and headache. The patient’s condition suddenly worsened during the 5th course of chemotherapy and he died 5 months after the diagnosis. Neoplastic meningitis occurs in 4–15% of patients with solid tumors, but it is rarely seen in colorectal cancer. It should be considered when a patient with a history of cancer has back pain or neurological symptoms. The progression of neoplastic meningitis is fast and it has a poor prognosis. Diagnosis in the early stages is important to prevent progression of neurological symptoms and to provide the most effective treatment.

Intrapericardial rupture of an aortic arch aneurysm is a rare and catastrophic event that requires emergency treatment. Recent development of thoracic endovascular repair has contributed to improved outcomes for the treatment of ruptured aneurysm of the thoracic aorta. However, when there is an aneurysm that involves the arch vessels, the treatment strategy, including conventional open surgery and endovascular stenting, is still controversial. We performed life-saving emergency total arch replacement using a modified elephant-trunk procedure for two cases of intrapericardial rupture of an aortic arch aneurysm. Prompt institution of cardiopulmonary bypass is effective for reducing the risk of re-rupture. Hybrid operation caries the risk of re-rupture during the procedure because it is performed under heparinization without blood pressure control. Open surgery is still a good option for such cases.

// Takahiro Nakagomi 1, 4 , Taichiro Goto 1, 4 , Yosuke Hirotsu 2 , Daichi Shikata 1 , Yujiro Yokoyama 1 , Rumi Higuchi 1 , Kenji Amemiya 2 , Kenichiro Okimoto 2 , Toshio Oyama 3 , Hitoshi Mochizuki 2 and Masao Omata 2, 5 1 Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, Yamanashi, Japan 2 Genome Analysis Center, Yamanashi Central Hospital, Yamanashi, Japan 3 Department of Pathology, Yamanashi Central Hospital, Yamanashi, Japan 4 Keio University, Tokyo, Japan 5 University of Tokyo, Tokyo, Japan Correspondence to: Taichiro Goto, email: taichiro@1997.jukuin.keio.ac.jp Keywords: sarcomatoid cancer; lung cancer; mutation; next-generation sequencing; programmed death ligand-1 Received: July 06, 2017 Accepted: January 21, 2018 Published: January 31, 2018 ABSTRACT Objectives: Pulmonary sarcomatoid carcinomas are rare and generally aggressive tumors composed of carcinomatous and sarcomatous components; however, the evolution of sarcomatoid cancer has not been elucidated. Here, we aimed to evaluate the mutational profiles and phylogeny of sarcomatoid carcinomas using next generation sequencing and in-silico analysis to facilitate the development of novel therapies. Methods: Four patients who underwent surgery for sarcomatoid cancer were enrolled. Cancer cells were collected from carcinomatous and sarcomatous components in each tumor by laser capture microdissection. Next-generation sequencing was performed in each component, and the mutation profiles were compared. For further inference of phylogenies, phylogenetic and PyClone analyses were performed. Mismatch repair disturbance and programmed death ligand-1 (PD-L1) expression were also evaluated. Results: Comparative genetic analysis of different histological areas revealed that the separate components shared several common mutations, which showed relatively high cellular prevalence in the PyClone statistical inference. Phylogenetic analysis showed that the sarcomatous component had ramified from the carcinomatous component in the early phase of the evolution process and accumulated a number of mutations that were different from those of the carcinomatous component. Moreover, microsatellite instability was detected in a case of sarcomatoid cancer and PD-L1 was strongly positive (≥ 50%) in all sarcomatoid cancers. Conclusions: Our data suggest that sarcomatoid carcinoma evolves from a common ancestral clone, and its phylogenetic features may reflect high-grade malignancy in pulmonary sarcomatoid carcinoma. High tumor mutation burden and strong PD-L1 staining may provide a rationale for the use of targeted immunotherapies in pulmonary sarcomatoid carcinomas.