Lower Long-term Survival Research Articles

DETECTION OF PERINEURAL SPREAD OF PALATAL ADENOID CYSTIC CARCINOMA BY CT

<h3>Background</h3> A large fraction of adenoid cystic carcinoma (ACC) tumors progresses to perineural spread (PNS), with correspondingly low long-term survival rates, and ACC is often not diagnosed in early stages because the primary tumor site is hard to detect. <h3>Objective(s)</h3> This study aimed to improve detection of ACC by better understanding the imaging features of PNS. Specific aims included (1) determining whether ACC could be effectively diagnosed by CT alone using a CT bone window to examine osseous changes; (2) determining the accuracy of CT-based diagnosis; and (3) exploring the relationship between the presenting clinical features and perineural spread. <h3>Study Design</h3> A retrospective medical records search was performed from 2000 to 2017 to identify patients with a diagnosis of ACC, clinical history, and pretreatment imaging with CT and/or MRI. Descriptive statistics, as well as sensitivity and specificity data, were compared using likelihood ratio test. <h3>Results</h3> Forty-four patients (median age 51 years; range 20–87 years) met the inclusion and exclusion criteria. The most common symptoms, not mutually exclusive, included pain (41%), mass (41%), paresthesia or numbness (39%), and sinonasal congestion (21%). Most (46%) patients presented to their dentist for initial evaluation, and 55% were evaluated by a dentist at some point before diagnosis. The most common initial impressions were infection (50%) and/or dental disease (32%). Average time to histologic diagnosis from initial symptoms was 18 months. PNS was identified in 82% of all patients. Significantly, findings of erosion and/or enlargement of any foramina, fossae, or canals noted via bone-windowed CT were 97% sensitive and 100% specific for PNS. PNS was statistically associated with paresthesia (<i>P</i> = .003; specificity 100%; sensitivity 47%) but not with tumor size (<i>P</i> = .096). <h3>Discussion/Conclusions</h3> Palatal ACC PNS can be reliably diagnosed via bone-windowed CT. Dentists are often the first care providers and should be aware that patients presenting with numbness should be evaluated for PNS.

Short- and long-term survival after isolated coronary artery bypass grafting, the impact of gender and age

Objectives. Assess the short- and long-term survival for patients who underwent isolated coronary artery bypass grafting (CABG) and evaluate the impact of gender and age. Furthermore to assess the long-term survival in the CABG group compared to the general population. Design. This study included 4044 consecutive patients who underwent isolated CABG at Oslo University Hospital, Ullevål, in Oslo, Norway in the time period from 01 January 2003 to 31 December 2015. Patient data was collected retrospectively from the quality register at the department. Information on survival status was obtained from the Norwegian National Registry. Life expectancy data for the general population was gained from Statistics Norway. Results. Female patients were significantly older than male patients at the time of surgery (mean age 67.0 and 63.9 years, respectively, p < .001), and had significantly lower 30-day survival (mortality was 1.4% and 0.6%, respectively, p = .017). Male gender was independently associated with lower long-term survival (p = .0037) in a multivariate analysis. Male patients aged less than 60 years also showed significantly lower long-term survival (SMR = 1.84, 95% CI = 1.49–2.25) compared to the age-matched general population. Among patients older than 60 years, survival was similar to survival in the age-matched general population. Conclusions. Survival was excellent for patients undergoing surgery. Despite increased age and operative mortality, female patients had better adjusted long-time survival than male patients. There was lower long-term survival among male patients aged less than 60 compared to the general population. Our findings may help clinicians in selecting appropriate patients for surgery.

Invasive Respiratory or Vasopressor Support and/or Death as a Proposed Composite Outcome Measure for Perioperative Care Research.

There is a need for a clinically relevant and feasible outcome measure to facilitate clinical studies in perioperative care medicine. This large-scale retrospective cohort study proposed a novel composite outcome measure comprising invasive respiratory or vasopressor support (IRVS) and death. We described the prevalence of IRVS in patients undergoing major abdominal surgery and assessed the validity of combining IRVS and death to form a composite outcome measure. We retrospectively collected perioperative data for 2776 patients undergoing major abdominal surgery (liver, colorectal, gastric, pancreatic, or esophageal resection) at Kyoto University Hospital. We defined IRVS as requirement for mechanical ventilation for ≥24 hours postoperatively, postoperative reintubation, or postoperative vasopressor administration. We evaluated the prevalence of IRVS within 30 postoperative days and examined the association between IRVS and subsequent clinical outcomes. The primary outcome of interest was long-term survival. Multivariable Cox proportional regression analysis was performed to adjust for the baseline patient and operative characteristics. The secondary outcomes were length of hospital stay and hospital mortality. In total, 85 patients (3.1%) received IRVS within 30 postoperative days, 15 of whom died by day 30. Patients with IRVS had a lower long-term survival rate (1- and 3-year survival probabilities, 66.1% and 48.5% vs 95.2% and 84.0%, respectively; P < .001, log-rank test) compared to those without IRVS. IRVS was significantly associated with lower long-term survival after adjustment for the baseline patient and operative characteristics (adjusted hazard ratio, 2.72; 95% confidence interval, 1.97-3.77; P < .001). IRVS was associated with a longer hospital stay (median [interquartile range], 65 [39-326] vs 15 [12-24] days; adjusted P < .001) and a higher hospital mortality (24.7% vs 0.5%; adjusted P < .001). Moreover, IRVS was adversely associated with subsequent clinical outcomes including lower long-term survival (adjusted hazard ratio, 1.78; 95% confidence interval, 1.21-2.63; P = .004) when the analyses were restricted to 30-day survivors. Patients with IRVS can experience ongoing risk of serious morbidity and less long-term survival even if alive at postoperative day 30. Our findings support the validity of using IRVS and/or death as a composite outcome measure for clinical studies in perioperative care medicine.

Hostile Neck Anatomy Is Associated With Higher Perioperative Type IA Endoleaks and Lower Long-term Survival After Elective Endovascular Aneurysm Repair

Hostile Neck Anatomy Is Associated With Higher Perioperative Type IA Endoleaks and Lower Long-term Survival After Elective Endovascular Aneurysm Repair

Axillary-bifemoral and axillary-unifemoral artery grafts have similar perioperative outcomes and patency

ObjectiveIt has been suggested that more bypass outflow targets for bypass grafts improve patency and outcomes. Our objective was to examine this in a multicenter contemporary series of axillary to femoral artery grafts. MethodsThe Vascular Quality Initiative database was queried for all axillary-unifemoral (AxUF) and axillary-bifemoral (AxBF) bypass grafts performed between 2010 and 2017 for claudication, rest pain, and tissue loss. Patients with acute limb ischemia were excluded. Patients' demographics and comorbidities as well as operative details and outcomes were recorded. Univariable, multivariable, and Kaplan-Meier analyses were used to assess long-term outcomes. ResultsThere were 412 (32.9%) AxUF grafts and 839 (67.1%) AxBF grafts identified. Overall, the mean age of the patients was 68.3 years, 51.1% were male, and 84.7% were white. Compared with AxBF grafts, AxUF grafts were more often performed for urgent cases; in patients who were younger, male, nonambulatory, and diabetic; and in those with preoperative anticoagulation, critical limb ischemia, prior bypass, aneurysm repair, peripheral vascular intervention, and major amputation (P < .05 for all). There were no significant differences between AxUF and AxBF grafts in perioperative wound complications (4.2% vs 2.9%; P = .23), cardiac complications (7.3% vs 10.4%; P = .08), pulmonary complications (4.1% vs 6%, P = .18), early stenosis/occlusion (0.2% vs 0.8%; P = .22), perioperative mortality (2.9% vs 3.2%; P = .77), and length of stay (6.4 ± 5.6 days vs 6.7 ± 8 days; P = .29). The mean estimated blood loss (268.1 mL vs 348.6 mL; P < .001) and mean operative time (201 minutes vs 224.1 minutes; P < .001) were significantly lower for AxUF grafts. Kaplan-Meier analysis showed that AxUF and AxBF grafts had similar freedom from graft occlusion (62.6% vs 71.8%; P = .074), major adverse limb event-free survival (57.1% vs 66.6%; P = .052), and survival (86% vs 86%; P = .897) at 1 year. Major amputation-free survival was lower for AxUF grafts (63.7% vs 73%; P = .028). Multivariable analysis also showed that the type of graft configuration did not independently predict occlusion/death (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.77-1.46; P = .72), amputation/death (HR, 1.12; 95% CI, 0.83-1.51; P = .45), major adverse limb event/death (HR, 0.97; 95% CI, 0.73-1.3; P = .85), or mortality (HR, 0.91; 95% CI, 0.65-1.26; P = .55). Three-year survival after placement of AxUF and AxBF grafts was similar (75.1% vs 78.2%; P = .414). ConclusionsAxUF and AxBF grafts have similar perioperative and 1-year outcomes. Graft patency was not significantly different between an AxBF graft and an AxUF graft at 1 year. Overall, patients treated with these reconstructions have many comorbidities and low long-term survival.

Palliative bypass surgery in elderly patients with resectable periampullary carcinoma: a report of 45 cases

Background: This study aims to determine whether palliative bypass surgery (choledochojejunostomy and gastrojejunostomy), which has a lower incidence of complications and mortality, remains an option for elderly patients with resectable periampullary carcinoma. Methods: The clinical data of elderly patients with resectable periampullary carcinoma who had been admitted to Qilu Hospital and had undergone palliative bypass surgery in recent years was collected. Factors concerning these patients, including surgical duration, intraoperative haemorrhage, the incidence of complications, mortality, and survival rate, were compared to those in patients who had received radical surgery. Results: Surgical duration, intraoperative haemorrhage, the incidence of complications, pancreatic fistula, abdominal infections, pneumonia, and postoperative hospital stay were found to be more apparent in patients in the radical surgery group than in patients in the palliative bypass surgery group and the difference was statistically significant (P Conclusions: For elderly patients with periampullary carcinoma, palliative bypass surgery offers safety, low risks, a quick recovery, a shorter surgery duration, less intraoperative haemorrhage, and a lower incidence of complications compared to radical surgery. Although it has a lower long-term survival rate compared to radical surgery, palliative surgery remains an option for elderly patients who prefer not to undergo the invasive procedure of radical surgery.

Palliative bypass surgery in elderly patients with resectable periampullary carcinoma: a report of 45 cases.

BackgroundThis study aims to determine whether palliative bypass surgery (choledochojejunostomy and gastrojejunostomy), which has a lower incidence of complications and mortality, remains an option for elderly patients with resectable periampullary carcinoma.MethodsThe clinical data of elderly patients with resectable periampullary carcinoma who had been admitted to Qilu Hospital and had undergone palliative bypass surgery in recent years was collected. Factors concerning these patients, including surgical duration, intraoperative haemorrhage, the incidence of complications, mortality, and survival rate, were compared to those in patients who had received radical surgery.ResultsSurgical duration, intraoperative haemorrhage, the incidence of complications, pancreatic fistula, abdominal infections, pneumonia, and postoperative hospital stay were found to be more apparent in patients in the radical surgery group than in patients in the palliative bypass surgery group and the difference was statistically significant (P<0.05). However, regarding blood transfusions, deaths, biliary fistula, postoperative haemorrhage, wound infection, delayed gastric emptying, and heart disease, the difference was not statistically significant (P≥0.05).ConclusionsFor elderly patients with periampullary carcinoma, palliative bypass surgery offers safety, low risks, a quick recovery, a shorter surgery duration, less intraoperative haemorrhage, and a lower incidence of complications compared to radical surgery. Although it has a lower long-term survival rate compared to radical surgery, palliative surgery remains an option for elderly patients who prefer not to undergo the invasive procedure of radical surgery.

MRI-derived regional flow-volume loop parameters detect early-stage chronic lung allograft dysfunction.

Chronic lung allograft dysfunction (CLAD) is a major cause for the low long-term survival rates after lung transplantation (LTx). Early detection of CLAD may enable providing medical treatment before a nonreversible graft dysfunction has occurred. MRI is advantageous to pulmonary function testing (PFT) in the ability to assess regional function changes, and thus have the potential in detecting very early stages of CLAD before changes in global forced expiratory volume during the first second (FEV1%) occur. To examine whether early stages of CLAD (diagnosed based on PFT values) could also be detected using MRI-derived parameters of regional flow-volume dynamics. Retrospective. 62 lung transplantation recipients were included in the study, 29 of which had been diagnosed with CLAD at various stages. MRI datasets were acquired with a 1.5T Siemens scanner using a spoiled gradient echo sequence. MRI datasets were retrospectively preprocessed and analyzed by a blinded radiologist according to the phase resolved functional lung MRI (PREFUL-MRI) approach, resulting in fractional ventilation (FV) maps and regional flow-volume loops (rFVL). FV- and rFVL-based parameters of regional lung ventilation were estimated. Differences between groups were compared by Mann-Whitney U-test with a Bonferroni correction for multiple comparisons (n = 2). rFVL-CC-based parameters discriminated significantly between the presence or absence of CLAD (P < 0.003). Using the contrast media-free PREFUL-MRI technique, parameters of ventilation dynamics and its regional heterogeneity were shown to be sensitive for the detection of early CLAD stages. 3 TECHNICAL EFFICACY: Stage 3 J. Magn. Reson. Imaging 2019;50:1873-1882.

Upper extremity arterial endovascular interventions for symptomatic vascular access-induced steal syndrome

BackgroundCritical hand ischemia owing to vascular access-induced steal syndrome (VASS) continues to be a significant problem. The aim of this study was to examine the outcomes of arterial endovascular interventions in the upper extremity of patients presenting with VASS. MethodsA database of patients presenting with documented VASS between 2006 and 2016 was retrospectively queried. Patients who underwent isolated endovascular intervention in the upper extremity were analyzed. ResultsNinety-eight patients (66% female; average age 65 years) presented with VASS: 28 presented with upper arm atherosclerotic disease above the arteriovenous (AV) anastomosis (above elbow) and the remaining 70 patients with below AV anastomotic atherosclerotic disease at the elbow (below elbow). Sixty-three percent of the entire patient cohort (N = 65) presented with rest pain and the remainder (n = 33 [34%]) with minor digital ulceration. Of those with upper arm disease above the AV anastomosis, one-third of patients had subclavian occlusive disease and two-thirds had brachial artery occlusive disease. Patients with subclavian disease underwent stent placement, and patients with brachial artery disease underwent balloon angioplasty. Technical success was 100% (n = 28). Ninety-one percent of these patients (n = 25) had symptomatic success at 30 days and the remainder (n = 3) required proximalization of the access. Of those with below AV anastomosis at the elbow disease, all had disease in the forearm vessels with 42% (n = 29) having either the ulnar or radial artery occlusion. Balloon angioplasty was performed in one vessel in 55% (n = 38) and in two vessels in 45% (n = 32) of patients. Technical success was 79% (n = 81 of 102 vessels) with 51% of the patients (n = 36) having symptomatic success at 30 days; of those who remained symptomatic, 80% (n = 27) required proximalization of the access and 20% (n = 7) required ligation. The major adverse cardiovascular event rate for the entire patient cohort was 4% (n = 4). The 30-day complications for the entire patient cohort included continued steal (38%; all resolved with secondary procedures), thrombosis (3%; all forearm vessels treated for occlusion), bleeding (0%), infection (0%), and mortality (1%). Primary clinical success defined as the relief of distal ischemic symptoms and the preservation of a functional access site for dialysis showed rates of 42 ± 9% (mean ± standard error of the mean) and 0 ± 0% at 5 years (above and below elbow groups, respectively). ConclusionsUpper extremity interventions for VASS owing to above elbow disease are associated with a high rate of success, whereas interventions for below elbow disease have a poor clinical success with more patients requiring secondary procedures and low long-term survival for the access site. Male patients presenting with rest pain, larger forearm vessels (approximately 3 mm), short occlusive lesions (<100 mm), two-vessel runoff, and an intact palmer arch are good candidates for below elbow interventions.

Management of pancreatic head adenocarcinoma: From where to where?

Pancreatic head adenocarcinoma (PHAC) is one of the most aggressive malignancies, and it has low long-term survival rates. Surgery is the only option for long-term survival. The difficulties associated with PHAC include higher frequencies of regional or distant lymph node metastases and vascular involvement, and positive resection margins in pancreatic and retroperitoneal tissues. Radical resections increase margin negativity and life expectancy; however, the extend of the surgery applied is controversial. Thus, western and eastern centers may use different approaches. Multiorgan, peripancreatic nerve plexus, and vascular resections have been discussed in relation to radical surgery for pancreatic cancer as have the roles of neoadjuvant and adjuvant therapy regimens. Determining the appropriate limits for surgery, standardizing definitions and surgical techniques according to guidelines, and centralizing pancreatic surgery within high-volume institutions to reduce mortality and morbidity rates are among the most important issues to consider. In this review, we evaluate the basic concepts underlying and the roles of radical surgery for PHAC, and lymphadenectomy, nerve plexus, retroperitoneal tissue, vascular, and multivisceral resections, total pancreatectomy, and liver metastases are discussed.

Do Long Term Outcomes Justify Third Time Redo Lung Transplantation?

Purpose Graft failure remains a significant obstacle to long-term survival in lung transplantation (LT), however, the reported outcomes of reoperative LT are inferior to primary LT, and there is controversy of how best to manage a scarcity of donor allografts for candidates likely to derive maximum benefit. The outcomes of third-time LT have not been described in detail. Methods Review of UNOS database was performed. 3rd time recipients of LT were identified and compared to first-time and second-time LT recipients. Survival was estimated with Kaplan Meier method and compared using log-rank test. Influence of 2nd and 3rd LT was performed using univariate and multivariate analyses. Results 28 recipients of 3rd LT were compared to 1,252 2nd LT and 32,703 primary recipients. Patients of 3rd LT were younger (38.1 ± 16.0 years vs 44.4 ± 16.8 for 2nd LT, 52.6 ± 14.6 for primary LT), and have shorter wait list times (37.0 days [95% CI 9.0-67.5] vs 45.5 days [13.0-57.5] for 2nd LT and 112.0 [30.0- 329.0] for primary LT. Median survival was 60 months for primary LT, 32 months for 2nd LT, and 19 months for 3rd LT (log-rank p Conclusion Reoperative LT has significantly lower long-term survival compared to primary LT, and survival after 3rd LT appears to be worse than 2rd LT. Further work is needed to define which candidates are likely to benefit most from reoperative LT.

Donor and Recipient Racial Mismatch Impacts Thoracic Organ Transplant Survival

Purpose The purpose of this study is to look at impact of race on thoracic organ recipient (TOR) survival with respect to the donor, recipient, and donor/ recipient matching. Methods The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from 1/2000-3/2018 for donor hearts or lungs. After exclusions for multiorgan transplant and age (donor Results Donor age ranged from 15-77 y (mean 33.2y, median 31y). 66% were male, and 4% were diabetic. The mean donor ejection fraction (EF) was 60% (median 60%) and ischemic time ranged from 0.04-15 hours (h) for both heart and lungs (mean 4.00h, median 3.72h). There were 9914 (17%) AA, 9081 (15%) H, and 40003 (68%) W thoracic organ donors. Adjusted 30-day and 1 year survival of TORs was 96.2% and 87.7% from AA donors, 96.2% and 87.6% from H donors, and 96.5% and 89% from W donors. This equates to a 13% reduction in 1-year survival among AA and H donors when compared to W donors (both OR=0.87; p 0.068). AA exhibited lower long-term survival when compared to W (HR=1.12; p Conclusion While there is evidence of racial disparity in survival outcomes after thoracic organ transplant matched race donor/ recipient may improve thoracic transplant survival.

Recent Development and Long-Term Results of Open vs EVAR for Pararenal Abdominal Aortic Aneurysms.

In this article, I would like to discuss on the two different treatment options (Open vs EVAR) for pararenal abdominal aortic aneurysm (the term “PRAAA” is not clearly defined and classified). Recently, complex endovascular treatment [Fenestrated EVAR (F-EVAR), Chimney (Snorkel) EVAR (C-EVAR, S-EVAR), Branched EVAR (B-EVAR)] have been developed and applied in selected patients, with encouraging early results; however, the high rate for secondary reinterventions and long-term results remain uncertain. This article introduce new devices and a new concept with endovascular aneurysm sealing (EVAS) are currently available on the market for the treatment of PRAAA. Open repair of PRAAA can be performed with low mortality and long-term survival is favorable from single-center experience in the real world and others. We conclude that open repair remains the golden standard treatment in most centers for PRAAA. However, EVAR of PRAAA may represent an alternative option in high-risk patients. Because the indications and circumstances for PRAAA vary based on patient-specific comorbidities and anatomy, it is recommended that vascular surgeons should be familiar with both treatment strategies and tailor-made strategy for improved long-term results for PRAAA. (This is a translation of Jpn J Vasc Surg 2018; 27: 303–308.)

Invited commentary

Invited commentary

Lung allograft donors with excessive alcohol use have increased levels of human antimicrobial peptide LL-37.

The relatively low long-term survival rate of lung transplant recipients as compared to other organ recipients serves as an impetus to identify potential lung dysfunction as early as possible. There is an association between donor heavy alcohol use and acute lung injury in the lung allograft after transplant, known as primary graft dysfunction. Excessive alcohol use (EAU) can induce pulmonary immune dysregulation in response to an infection. Antimicrobial peptides (AMPs) are an important component of the innate immune response to pulmonary infections, but the impact of EAU on AMPs in the allograft lung has not been evaluated. Our hypothesis is that specific lung AMPs, LL-37, α-defensin-1,2,3, and β-defensin-2, are dysregulated in the lungs from organ donors who had EAU. In this prospective observational investigation, we measured AMPs via ELISA and inflammatory cytokines via multiplex bead array, in bronchoalveolar lavage (BAL) fluid of lung allograft donors, comparing results based on their alcohol consumption. LL-37 levels in lung donors with EAU were found to be increased compared to nondrinker (ND) donors [median 7.7ng/mL (IQR 4.1-37.0) vs. 2.3ng/mL (IQR 1.1-7.9), p=0.004], whereas α-defensins-1,2,3 were decreased only in the presence of an infection in donors with EAU compared to ND donors [median 2.2ng/mL (IQR 1.6-2.4) vs. 3.2ng/mL (IQR 2.3-3.8), p=0.049]. There was no difference in β-defensin-2 levels. Gene expression levels of these AMPs were not different. Elevated levels of CXCL8 were noted in bronchial washings of donors with EAU compared to ND donors, [median 4372pg/mL (IQR 3352-13180) vs. 867.3pg/mL (IQR 163.6-3675), p=0.04], suggesting a potentially heightened inflammatory response. At 1 month post-transplant, LL-37 and CXCL8 levels are decreased compared to levels at time of transplant. In lung donors with EAU, LL-37 and α-defensins-1,2,3 dysregulated levels in the presence of an infection may be a harbinger of dysfunction of the lungs through the transplant process.

RF82 TEN YEARS UNITED KINGDOM EXPERIENCE IN SURVIVAL FOR SURGICAL TAVI APPROACHES

Abstract Background and Aim: Compare morbidity and mortality (M&amp;M) of different surgical TAVI access alternative to the surgical femoral. Methods: 2,863 pts underwent surgical TAVI from Jan 2007 to Jan 2017 in the 33 UK TAVI Centers. Primary outcome is long-term survival up to Jul 2017. Secondary outcomes are procedural/in-hospital (in-H) complications, in-H, 30-day, and 1-year mortality. Statistical analysis by SPSS 20.0 and Stata 12.1. Results: 2,863 pts, Surgical Femoral (SF) = 1,150 + Trans Apical (TA) = 1,216 + Direct Aortic (DA) = 207 + Subclavian (SC) = 290. In-H mortality lowest in SF. Among no-SF, only SC not significantly different from SF, whereas TA and DA associated with higher mortality. Unadjusted Kaplan-Meier survival chart shows long-term survival significantly greater in SC than DA and TA. No difference in survival between TA and DA, both of which with significantly lower long-term survival than SF. Unadjusted survival rate of surgical SC cohort not significantly different from SF. Hemofiltration and long length hospitalization most common in AD and TA compared to SC and SF. Permanent PMK greater in SC and SF than in TA and DA. A comparison of M&amp;M in the two quarters 2007–2011 vs. 2012–2016 also carried out. Conclusions: This is the largest study of survival in surgical TAVI access routes from UK National dataset. SC is the only non-SF approach for which survival is not significantly different from SF. SC may represent the safest non-femoral access route for TAVI and it is the safest surgical route until now experienced.

Unrecognised myocardial infarction and its relationship to outcome in critically ill patients with cardiovascular disease.

To establish the incidence of myocardial infarction (MI) in ICU patients with co-existing cardiovascular disease (CVD), and explore its association with long-term survival. In a multi-centre prospective cohort study in 11 UK ICUs, we enrolled 273 critically ill patients with co-existing CVD. We measured troponin I (cTnI) with a high sensitivity assay for 10days; ECGs were carried out daily for 5days and analysed by blinded cardiologists for dynamic changes. Data were combined to diagnose myocardial 'infarction', 'injury' or 'no injury' according to the third universal definition of MI. Patients were followed-up for 6months. Regression and mediation analyses were used to explore relationships between acute physiological derangements, MI, and mortality. cTnI was detected in all patients, with a rise/fall pattern consistent with an acute hit. In 73% of patients, this peaked on days 1-3 [median 114ng/l (first, third quartiles: 27, 393)]. Serial ECGs indicated 24.2% (n = 66) of patients experienced MI, but > 95% were unrecognized by clinical teams. Type 2 MI was the most likely aetiology in all cases. A further 46.1% (n = 126) experienced injury (no ECG changes). Injury and MI were both associated with 6-month mortality (reference: no injury): OR injury 2.28 (95% CI 1.06-4.92, p = 0.035), OR MI 2.70 (95% CI 1.11-6.55, p = 0.028). Mediation analysis suggested MI partially mediated the relationship between acute physiological derangement and 6-month mortality (p = 0.002), suggesting a possible causal association. Undiagnosed MI occurs in around a quarter of critically ill patients with co-existing CVD and is associated with lower long-term survival.

Extrapleural pneumonectomy: still indicated?

The optimal treatment of malignant pleural mesothelioma (MPM) has not yet been established and is still under investigation. Surgery is one of the pillars in the multimodality approach with the purpose of removing as much as visible tumor as possible and to relieve symptoms. To date, two major surgical procedures are available for removal or debulking of MPM that is considered to be resectable: [extended (e)] pleurectomy/decortication (P/D) and extrapleural pneumonectomy (EPP). Historically, EPP was regarded as the only way to achieve a macroscopic complete resection. However, in the last years, there is a shift in literature towards (e)P/D as the preferred surgical procedure whenever possible as several retrospective studies and meta-analyses showed a similar or lower long-term survival and higher perioperative mortality and postoperative morbidity in patients who been treated with EPP. On the other hand, no randomized-controlled trials regarding surgical treatment with (e)P/D or EPP exist and therefore level A evidence favoring one surgical procedure is lacking. In this review we provide a nuanced and well-considered answer to the question whether EPP is still indicated in the surgical treatment of MPM.

Bronchiolitis obliterans syndrome–free survival after lung transplantation: An International Society for Heart and Lung Transplantation Thoracic Transplant Registry analysis

Lung transplant (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS). However, few long-term, multicenter, and precise estimates of BOS-free survival (a composite outcome of death or BOS) incidence exist. This retrospective cohort study of primary LTx recipients (1994-2011) reported to the International Society of Heart and Lung Transplantation Thoracic Transplant Registry assessed outcomes through 2012. For the composite primary outcome of BOS-free survival, we used Kaplan-Meier survival and Cox proportional hazards regression, censoring for loss to follow-up, end of study, and re-LTx. Although standard Thoracic Transplant Registry analyses censor at the last consecutive annual complete BOS status report, our analyses allowed for partially missing BOS data. Due to BOS reporting standards, 99.1% of the cohort received LTx in North America. During 79,896 person-years of follow-up, single LTx (6,599 of 15,268 [43%]) and bilateral LTx (8,699 of 15,268 [57%]) recipients had a median BOS-free survival of 3.16 years (95% confidence interval [CI], 2.99-3.30 years) and 3.58 years (95% CI, 3.53-3.72 years), respectively. Almost 90% of the single and bilateral LTx recipients developed the composite outcome within 10 years of transplantation. Standard Registry analyses "overestimated" median BOS-free survival by 0.42 years and "underestimated" the median survival after BOS by about a half-year for both single and bilateral LTx (p < 0.05). Most LTx recipients die or develop BOS within 4 years, and very few remain alive and free from BOS at 10 years post-LTx. Less inclusive Thoracic Transplant Registry analytic methods tend to overestimate BOS-free survival. The Registry would benefit from improved international reporting of BOS and other chronic lung allograft dysfunction (CLAD) events.

Theaflavin-3,3′-digallate inhibits ovarian cancer stem cells via suppressing Wnt/β-Catenin signaling pathway

Recent evidence indicates that ovarian cancer stem cells (CSCs) are responsible for ovarian cancer recurrence and drug resistance, resulting in the low long-term survival rate of patients with advanced ovarian cancer. We aimed to study the inhibitory effect of theaflavin-3,3′-digallate (TF3), a black tea polyphenol on ovarian CSCs. Here, we showed that TF3 inhibited the proliferation of A2780/CP70 and OVCAR3 tumorshpere cells by suppressing their cell viability and colony formation capacity. TF3 inhibited the tumorsphere formation capacity of A2780/CP70 and OVCAR3 CSCs in serum-free and non-adherent conditions. TF3 inhibited A2780/CP70 and OVCAR3 CSCs isolated from tumorspheres by decreasing their cell viability and upregulating the protein expression of caspase-3 and -7 in the cells. We also revealed that TF3 inhibited ovarian CSCs through Wnt/β-catenin signaling pathway. Our results suggested that TF3 could inhibit ovarian CSCs and might be a potential agent for eradicating ovarian cancer.