Search

The effectiveness of postoperative radiotherapy (PORT) in improving outcomes remains debatable for oral squamous cell carcinoma (OSCC) patients with pathological intermediate-risk factors (IRFs) after surgery. A retrospective analysis was conducted on 432 intermediate-risk OSCC patients defined by histological reporting of close margin (

In differentiated thyroid cancer, radioiodine therapy (RIT) is usually carried out after thyroidectomy. Although the potent beneficial effects of radioiodine are undisputed in high-risk patients, much controversy remains surrounding many aspects of RIT in low- and intermediate-risk patients. Other than the indication for postoperative RIT, controversies also include, among others, the intent of RIT and the choice of activity for RIT or the mode of thyroid stimulating hormone stimulation. Furthermore, there is even controversy on the definition of what constitutes low- or intermediate-risk patients. Here the various issues will be discussed and an overview of the different points of view in a number of more prominent national and international guidelines and current literature is presented.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and curative treatment for acute myeloid leukemia (AML). We explored the outcome of haploidentical donor (HID) transplantation for intermediate-risk AML and compared to that of matched sibling donor (MSD) transplants. One hundred twenty-seven consecutive patients with intermediate-risk AML in the first complete remission (CR1) who underwent allo-HSCT between January 1, 2015, and August 1, 2016, were enrolled. Thirty-seven patients received MSD grafts, and 90 received HID grafts. The 2-year leukemia-free survival (LFS) of the HID group was comparable to that of the MSD group: 82.0% ± 4.1% versus 82.7% ± 6.4%, P = 0.457. The 2-year cumulative incidences of relapse and transplantation-related mortality (TRM) were comparable between the HID and MSD groups (relapse, 4.5% ± 0.1%, versus 11.5% ± 0.3%, P = 0.550; TRM, 13.4% ± 0.1% vs. 5.8% ± 0.2%, P = 0.154). The HID recipients had a trend of a lower 2-year cumulative incidence of positive posttransplant flow cytometry (FCM+) and relapse than the MSD recipients (5.6% ± 0.1% vs. 19.9% ± 0.5%, P = 0.092). These results suggest that the outcomes of allo-HSCT with HIDs are comparable to those with MSDs in terms of LFS, TRM, and relapse for intermediate-risk AML in CR1. HIDs could be an alternative to MSDs for intermediate-risk AML.

Optimal treatment of intermediate risk prostate cancer remains unclear. National Comprehensive Cancer Network® guidelines recommend active surveillance, prostatectomy or radiotherapy. Recent trials demonstrated no difference in prostate cancer specific mortality for men undergoing active surveillance for low risk prostate cancer compared to prostatectomy or radiotherapy. The use of active surveillance for intermediate risk prostate cancer is less clear. In this study we characterize U.S. national trends for demographic, clinical and socioeconomic factors associated with active surveillance for men with intermediate risk prostate cancer.This retrospective cohort study examined 176,122 men diagnosed with intermediate risk prostate cancer from 2010 to 2016 in the National Cancer Database. Temporal trends in demographic, clinical and socioeconomic factors among men with intermediate risk prostate cancer and association with the use of active surveillance were characterized. The analysis was performed in April 2020.In total, 176,122 men were identified with intermediate risk prostate cancer from 2010 to 2016. Of these men 57.3% underwent prostatectomy, 36.4% underwent radiotherapy and 3.2% underwent active surveillance. Active surveillance nearly tripled from 1.6% in 2010 to 4.6% in 2016 (p0.001). On multivariate analysis use of active surveillance was associated with older age, diagnosis in recent years, lower Gleason score and tumor stage, type of insurance, treatment at an academic center and proximity to facility, and attaining higher education (p0.05). Race and comorbidities were not associated with active surveillance.Our findings highlight increasing active surveillance use for men with intermediate risk prostate cancer demonstrating clinical and socioeconomic disparities. Prospective data and improved risk stratification are needed to guide optimal treatment for men with intermediate risk prostate cancer.

The aim of this study was to assess the potential impact of the kinetics of serum levels of seven cytokines during induction in acute myeloid leukemia (AML) patients. Indeed, the role of cytokines, in the pathophysiology and response to therapy of AML patients, remains under investigation. Here, we report on the impact of peripheral levels of two cytokines, the Fms‐like tyrosine kinase 3 ligand (FL) and interleukin‐6 (IL‐6), evaluated during first‐line intensive induction. A new risk stratification can be proposed, which supersedes the ELN 2017 classification to predict survivals in AML patients by examining the kinetic profile of these cytokines during the induction phase. It segregates three groups of, respectively, high‐risk, characterized by a stagnation of low FL levels, intermediate risk, with dynamic increasing FL levels and high IL‐6 at day 22, and favorable risk with increasing FL levels but low IL‐6 at day 22., Here we report on the impact of the peripheral levels of two cytokines, the Fms‐like tyrosine kinase 3 ligand (FL), and interleukin‐6 (IL‐6), evaluated during first‐line intensive induction. Indeed, a new risk stratification can be proposed, which supersedes the ELN 2017 classification to predict survivals in AML patients by examining their profile during the induction phase.

We aimed to investigate the efficacy and tolerability of ultra-hypofractionated radiotherapy (UHRT) in the treatment of low and intermediate-risk prostate cancer patients.This retrospective study was conducted using data derived from 44 patients who underwent UHRT, and toxicity assessment and clinical response were investigated. Treatment consisted of 35-36.25 Gy in 5 fractions using stereotactic ablative radiotherapy (SABR) with the Linac-based delivery system.The median duration of follow-up was 52 months (8-68 months) and the median age was 71.5 years (54-85 years). Twenty-seven patients were assigned as intermediate-risk, whereas 17 patients had low-risk. The 5-year overall survival rate was 87.8%, while the 5-year biochemical recurrence-free survival (bRFS) rate was 97.4%. Acute grade 3 genitourinary (GU) side effect was not observed in any patient, whereas acute gastrointestinal (GI) system grade 3 side effect was seen in 6.8% of the patients. Late grade 3 GU and GI side effects were seen in 4.6% and 6.8% of the patients, respectively. In patients with planning target volume (PTV) ≥85 ml, acute grade ≥2 GU side effects were more common (Our data demonstrated that UHRT administered with volumetric arc therapy (VMAT) can be recommended for selected patients with low-intermediate risk prostate cancer. Further prospective, multicentric, controlled trials on larger series are warranted to reach more accurate conclusions.

BACKGROUND Intra-Operative Cholangiogram (IOC) is a procedure carried out during cholecystectomy with the primary objective of clearly delineating the biliary anatomy. Over decades, routine IOC became selective IOC and now it is being overtaken by less invasive investigations like MRCP and EUS. Role of IOC remains only to intraoperatively confirm or rule out bile duct injury in difficult cases. Laparoscopic IOC is a skilful procedure which requires training and extra added time during laparoscopic cholecystectomy. Once mastered it can be used in many situations for either anatomical reasons or to detect CBD pathology. METHODS All patients getting admitted for laparoscopic cholecystectomy with intermediate risk for choledocholithiasis were enrolled in the study from 2016 to 2019. Procedure was carried out with all necessary consents and precautions. All cases were performed by an experienced GI surgeon and followed up with proper protocol. RESULTS Fifty patients with known intermediate risk for choledocholithiasis underwent laparoscopic cholecystectomy with laparoscopic IOC. Procedure was successfully done in all patients except two, where cystic duct was very thin and cannulation was not possible. Forty-one (82%) patients had deranged liver function test and 9 patients (18%) had history of acute pancreatitis in the past as indications for the procedure. Two patients had dilated CBD (>6 mm) on ultrasound along with deranged liver function tests. An average of 12 minutes was taken to perform the procedure (range: 8 - 15 min). In cases where IOC took longer time was mainly due to technical issues (operability of C-arm). No IOC related complications occurred in any of the patients. Hospital stay was not prolonged in any of the patients due to IOC. None of the patients had any filling defect in CBD. All cases followed till date are asymptomatic. CONCLUSIONS It is a technically feasible procedure that can be performed with limited addition to OT time, minimal failure rate, and complications. All patients with limited criteria for intermediate risk of choledocholithiasis had a normal IOC with no evidence of biliary obstruction in follow up. KEYWORDS Laparoscopic Intraoperative Cholangiogram, Intermediate Risk, CBD Stones

The role of androgen deprivation therapy (ADT) in combination with radiotherapy (RT) in intermediate-risk prostate cancer (IRPC) remains controversial, particularly in patients receiving dose-escalated RT (DERT). We compared outcomes between patients with IRPC treated with ADT and two different doses of RT vs. RT alone.From December 2000 to September 2010, 600 patients with IRPC were randomised to a three-arm trial consisting of 6 months of ADT plus RT 70 Gy (ADT + RT70) vs. ADT plus a DERT of 76 Gy (ADT + DERT76) vs. DERT of 76 Gy alone (DERT76). Primary end-point was biochemical failure (BF), and secondary end-points were overall survival (OS) and toxicity. RT toxicity was assessed by Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria.With a median follow-up of 11.3 years (interquartile range: 10.9-11.7), patients receiving DERT76 alone, compared with patients receiving ADT + RT70 and ADT + DERT76, had higher rates of BF (32%, 18% and 14%, respectively, p 0.001), higher rates of prostate cancer progression (12%, 4.5% and 3.3%, respectively, p = 0.001) and more deaths due to prostate cancer (6.5%, 3.0% and 1.5%, respectively, p = 0.03) with no significant difference seen between ADT + RT70 and ADT + DERT76. There was no significant difference in OS between the 3 arms. A higher dose of RT (76 Gy) increased late gastrointestinal (GI) toxicity grade ≥ II compared with lower dose (70 Gy) (16% vs 5.3%, p 0.001) with no statistical difference for late genitourinary toxicity.In IRPC, the addition of 6 months of ADT to RT70 or DERT76 significantly improves BF and appears to decrease the risk of death from prostate cancer compared with DERT76 alone with no difference in OS. In the setting of IRPC, ADT plus RT 70 Gy yields effective disease control with a better GI toxicity profile. Clinicaltrials.gov#NCT00223145.

BACKGROUND AND OBJECTIVES: The selection of escalation of care strategies for the treatment of intermediate-risk pulmonary embolism (PE) is a matter of debate. Here, we aimed to assess the features of our population treated either with anticoagulation (AC) alone or catheter-directed thrombolysis (CDT). We also sought to identify a relationship between high residual systolic pulmonary artery pressure (sPAP) and demographic and clinical variables. PATIENTS AND METHODS: The retrospective data of 30 intermediate-high-risk PE patients were analyzed. CDT was used in 14 (46.7%) cases. Enoxaparin (b. i. d) injections were administered in the AC group. In the CDT group, patients received 5 mg bolus dose of alteplase followed by 1 mg/h infusion for 24 h. Estimated sPAP at presentation and discharge was recorded. A value equal to or greater than 40 mmHg in the latter was accepted as a significant rise. RESULTS: The patients in the CDT group had a lower HAS-BLED score (2 [0-3] vs. 1 [0-3], P = 0.03). Although initial sPAP values were comparable among treatment arms, sPAP at discharge was significantly lower in the CDT group (mmHg, 42 +/- 11.2 vs. 33.6 +/- 9.7, P = 0.04). The reduction in sPAP at discharge was also significantly higher in this group. The degree of reduction in sPAP was considerably correlated with baseline sPAP (r: 63.2, P < 0.001). Finally, the baseline sPAP measurement and HAS-BLED score of the patients with high residual sPAP were significantly higher (56.6 +/- 13.1 vs. 67.3 +/- 11.3, P = 0.02, and 1 [0-3] vs. 2 [0-3], P = 0.02, respectively). CONCLUSION: CDT was preferred over AC when lower bleeding risk was anticipated for intermediate-high-risk PE patients in our sample population. Eventually, CDT provided lower discharge sPAP levels and a greater reduction in sPAP. However, the factors associated with high sPAP at discharge were only high baseline sPAP measurement and HAS-BLED score.

Objective There is an increasing amount of evidence supporting use of transcatheter aortic valve replacement (TAVR) for treatment of aortic stenosis in patients at low or intermediate risk for surgical aortic valve replacement (SAVR). TAVR is now approved for use in all patient cohorts. Despite this, there remains debate about the relative efficacy of TAVR compared with SAVR in lower-risk cohorts and various subgroups of patients. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and propensity-matched trials to guide a consensus among expert cardiologists and surgeons. Methods Studies comparing TAVR and SAVR in low- and intermediate-risk patients were identified by a thorough search of the major databases. Mortality, stroke, and other perioperative outcomes were assessed at 30 days and 1 year. Results Early mortality was lower in TAVR compared to SAVR in RCTs, but not propensity-matched studies in low-risk cohorts (0.66% vs 1.5%; odds ratio [OR] = 0.44, 95% confidence interval [CI] 0.20 to 0.98, I2 = 0%). No difference in mortality between TAVR and SAVR was identified in intermediate-risk patients at early or later time points. Incidence of perioperative stroke in 3 low-risk RCTs was significantly lower in TAVR (0.4%) than SAVR (1.4%; OR = 0.33, 95% CI 0.13 to 0.81, I2 = 0%). There was no difference in stroke for intermediate-risk patients between TAVR and SAVR. The expert panel of cardiologists and cardiac surgeons provided recommendations for TAVR and SAVR in various clinical scenarios. Conclusions In RCTs comparing TAVR and SAVR in low-risk patients, early mortality and stroke were lower in TAVR, but did not differ at 1 year. There was no difference in mortality and stroke in intermediate-risk patients. The Multidisciplinary Heart Team must consider individual patient characteristics and preferences when recommending TAVR or SAVR. The decision must consider the long-term management of each patient’s aortic valve disease.

Introduction: Surgical treatment of thyroid cancer has become less aggressive but for many patients, the threshold for performing total thyroidectomy (TT), as opposed to thyroid lobectomy (TL), has remained unclear. Current American Thyroid Association (ATA) guidelines encourage more individualization of treatment options, which necessitates explicit review of the pros and cons of the different options with patients.Areas covered: This review focuses on the extent of surgery for treatment of intermediate-risk differentiated thyroid cancer, restricted to relevant literature available after publication of the 2015 ATA guidelines.Expert opinion: Dynamic risk-stratification facilitates a tailored approach when deciding on the extent of surgery for thyroid cancer. Treatment with TT allows for a lower recurrence risk, a simpler follow-up regimen, and treatment with adjuvant post-operative radioactive iodine. Treatment with TL has a lower associated risk of complications and avoidance of lifelong thyroid hormone replacement but has a significant risk of requiring a completion thyroid lobectomy (CT). Overall, treatment with TL and TT have comparable survival outcomes, but TL is the more cost-effective option. Larger cancer size is correlated with worse clinical outcomes, and numerous subgroup analyses have shown poorer outcomes for cancers with a diameter that is 2-4 cm compared to 1-2 cm.

Majority of patients with clear-cell renal cell carcinoma (ccRCC) at first line (1L) treatment are classified in the intermediate-risk (IR) subgroup according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score. As these patients have different prognosis, the aim of this study is to better characterize IR patients in order to better tailor the treatment. Retrospective analysis was performed from IGReCC (Institut Gustave Roussy Renal Cell Carcinoma) database. Overall survival (OS) was defined from start of 1L therapy to death or last follow-up. A multivariable Cox model with backward selection procedure (α = 0.01) and a Classification and Regression Tree (CART) analysis were performed to identify which prognostic factors were associated to OS in IR patients. From 2005 to 2017, 777 patients with ccRCC were treated with an anti-VEGF 1L therapy. Among 571 evaluable patients for IMDC score, 290 (51%) were classified as IR. With median follow-up 5.8 years (min: 0, max: 12.4) 212 deaths (73%) were observed and median OS was 25 months. Only platelet count was significantly associated to OS (hazard ratio 1.88 [95% CI 1.27–2.88] p = 0.0017). Median OS for patients with PLT > UNL was 18 months [95% CI 12–23] versus 29 months [95% CI 21.4–35.7] for patients with normal PLT count. The selection of PLT count was confirmed on bootstrap samples and was also selected for the first split of the CART-tree analysis. Patients in the IR group have a heterogeneous prognosis. Elevated PLT count seems identifies a subgroup of patients with poor outcome in the IMDC intermediate-risk population with ccRCC.

Summary Purpose The intermediate-risk (IR) prostate cancer (PCa) group is heterogeneous in terms of prognosis. For unfavorable or favorable IR PCa treated by radiotherapy, the optimal strategy remains to be defined. In routine practice, the physician's decision to propose hormonal therapy (HT) is controversial. The PROACT survey aimed to evaluate pattern and preferences of daily practice in France in this IR population. Materials and methods A web questionnaire was distributed to French radiotherapy members of 91 centers of the Groupe d’Etude des Tumeurs Uro-Genitales (GETUG). The questionnaire included four sections concerning: (i) the specialists who prescribe treatments and multidisciplinary decisions (MTD) validation; (ii) the definition of IR subsets of patients; (iii) radiotherapy parameters; (iv) the pattern of practice regarding cardiovascular (CV) and (iv) metabolic evaluation. A descriptive presentation of the results was used. Results Among the 82 responses (90% of the centers), HT schedules and irradiation techniques were validated by specific board meetings in 54% and 45% of the centers, respectively. Three-fourths (76%) of the centers identified a subset of IR patients for a dedicated strategy. The majority of centers consider PSA > 15 (77%) and/or Gleason 7 (4 + 3) (87%) for an unfavorable IR definition. Overall, 41% of the centers performed systematically a CV evaluation before HT prescription while 61% consider only CV history/status in defining the type of HT. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR patients. Finally, weight (80%), metabolic profile (70%) and CV status (77%) of patients are considered for follow-up under HT. Conclusion To the best of our knowledge, this is the first survey on HT practice in IR PCa. The PROACT survey indicates that three-quarters of the respondents identify subsets of IR-patients in tailoring therapy. The CV status of the patient is considered in guiding the HT decision, its duration and type of drug.

Introduction The accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential to ensure adequate treatment and prevent complications. First step diagnosis test are immunoassays including enzyme-linked immunosorbent assays (ELISAs) and rapid immunoassays. Methods Using a Bayesian approach, we prospectively evaluated the performance of the IgG PF4/polyvinylsulfonate ELISA and a chemiluminescent immunoassay (CLIA), which are specific for IgG and use the same antigenic target to detect HIT antibodies. Results One hundred and eighty-four 184 consecutive patients with an intermediate (n = 159) or high (n = 25) clinical pretest probability of HIT based on the 4Ts score or platelet pattern were included. Both immunoassays (IAs) were performed on all 184 samples, and definite HIT was confirmed with a positive serotonin release assay in 29 patients (12.7%). The sensitivity (Ss) and negative predictive value (NPV) of ELISA were excellent (100%) allowing HIT to be excluded with good confidence when the test was negative. In addition, the Ss and NPV of the CLIA equalled 93.1% and 98.6%, respectively, as it was negative in two definite HIT. When the CLIA was negative, the post-test probability of HIT was 0.7% in case of intermediate risk. Although there was excellent agreement between CLIA and ELISA results, the quantitative values provided by the two IAs were not correlated. Conclusion AcuStar HIT® detects more than 90% of HIT, as do all rapid IAs, and appears to be a good tool for excluding HIT when the pretest probability is intermediate. A chemiluminescent signal higher than 10 IU/mL is highly predictive of definite HIT with a PPV of 100%.

Objectives To evaluate the impact of implementing a modified Pediatric Emergency Care Applied Research Network (PECARN) rule including the S100B protein assay for managing mild traumatic brain injury (mTBI) in children. Methods A before-and-after study was conducted in a paediatric emergency department of a French University Hospital from 2013 to 2015. We retrospectively included all consecutive children aged 4 months to 15 years who presented mTBI and were at intermediate risk for clinically important traumatic brain injury (ciTBI). We compared the proportions of CT scans performed and of in-hospital observations before (2013–2014) and after (2014–2015) implementation of a modified PECARN rule including the S100B protein assay. Results We included 1,062 children with mTBI (median age 4.5 years, sex ratio [F/M] 0.73) who were at intermediate risk for ciTBI: 494 (46.5%) during 2013–2014 and 568 (53.5%) during 2014–2015. During 2014–2015, S100B protein was measured in 451 (79.4%) children within 6 h after mTBI. The proportion of CT scans and in-hospital observations significantly decreased between the two periods, from 14.4 to 9.5% (p=0.02) and 73.9–40.5% (p Conclusions The implementation of a modified PECARN rule including the S100B protein assay significantly decreased the proportion of CT scans and in-hospital observations for children with mTBI who were at intermediate risk for ciTBI.

Background: Misclassification rates defined as upgrading, upstaging, and upgrading and/or upstaging have not been tested in contemporary Black patients relative to White patients who fulfilled criteria for very-low-risk, low-risk, or favorable intermediate-risk prostate cancer. This study aimed to address this void. Methods: Within the SEER database (2010–2015), we focused on patients with very low, low, and favorable intermediate risk for prostate cancer who underwent radical prostatectomy and had available stage and grade information. Descriptive analyses, temporal trend analyses, and multivariate logistic regression analyses were used. Results: Overall, 4,704 patients with very low risk (701 Black vs 4,003 White), 17,785 with low risk (2,696 Black vs 15,089 White), and 11,040 with favorable intermediate risk (1,693 Black vs 9,347 White) were identified. Rates of upgrading and/or upstaging in Black versus White patients were respectively 42.1% versus 37.7% (absolute Δ = +4.4%; PPP=.05) in those with favorable intermediate risk. Conclusions: Rates of misclassification were particularly elevated in patients with very low risk and low risk, regardless of race, and ranged from 33.8% to 48.6%. Recalibration of very-low-, low-, and, to a lesser extent, favorable intermediate-risk active surveillance criteria may be required. Finally, our data indicate that Black patients may be given the same consideration as White patients when active surveillance is an option. However, further validations should ideally follow.

The presence of minimal residual disease (MRD) is a risk factor for relapse among children with acute myeloid leukemia (AML), and eliminating MRD can usually improve survival rates. To investigate the effect of expanded activated autologous lymphocytes (EAALs) combined with chemotherapy on eliminating MRD and improving survival rates of children with AML, we retrospectively analyzed the results of 115 children with low- or intermediate-risk AML with MRD treated at the Pediatric Hematological Center, Peking University People's Hospital, between January 2010 and January 2016. The patients were assigned to the chemotherapy plus EAAL (combined therapy) group (n = 61) and chemotherapy group (n = 54). The MRD-negativity rates were 95.1% (58/61) in the combined therapy group and 63.0% (34/54) in the chemotherapy group (P 0.0001) during consolidation treatment. The 5-year event-free survival rate was higher in the combined therapy group than in the chemotherapy group (86.3 ± 4.6% vs. 72.1 ± 6.1%, P = 0.025). No severe adverse event was observed after EAAL infusion. The present study showed that EAAL combined with chemotherapy could improve the MRD-negativity rate and event-free survival rate among children with AML with low level MRD-positive status.

Background So far there has been little evidence on the antithrombotic treatment of patients presenting with atrial fibrillation (AF) and a CHA2DS2-VASc score of 1 in men (2 in women). However, a recently published position paper suggests a personalized approach in weighing individual risk factors and considering additional patient characteristics and biomarkers for the decision for or against antithrombotic treatment in this intermediate-risk AF population. Case summary A 63-year-old male patient with a CHA2DS2-VASc score of 1 due to hypertension presents with a first episode of paroxysmal AF. The European Society of Cardiology (ESC) guidelines on the management of AF do not recommend a general antithrombotic therapy in those patients. Therefore, the decision for or against the initiation of oral anticoagulation (OAC) in the presented case is based on recent treatment recommendations of the ESC, that aim to guide clinicals through the question whether to anticoagulate or not. Discussion Oral anticoagulation in patients presenting with a CHA2DS2-VASc of 1 remains a challenging approach in clinical practice and physicians need to carefully balance the individual benefit of reducing thromboembolic risk with OAC against the potential harm due to an increase in bleeding risk in this patient population. The ESC provided an easily applicable approach for decision-making in patients with AF and a CHA2DS2-VASc score of 1 via consideration of additional risk factors, scoring tools, and established biomarkers. Of note, if an antithrombotic therapy is offered, non-vitamin K antagonist oral anticoagulants should be preferred over vitamin K antagonists based on the beneficial net clinical benefit.

The SURTAVI trial demonstrated the noninferiority of transcatheter aortic valve implantation (TAVI) to surgical aortic valve replacement (SAVR) in patients with severe, symptomatic aortic stenosis at intermediate surgical risk. Most TAVI patients received an early generation device which is no longer commercially available. This analysis compares TAVI outcomes in patients that received the Evolut R valve to those of similar patients randomized to SAVR in the SURTAVI trial. The continued access study of SURTAVI (CAS) enrolled 290 patients. Of them, 252 were implanted with the 23, 26, or 29 mm Evolut R device. Propensity-score matching between this group and SURTAVI SAVR patients with annular diameter of 26 mm or less was based on 22 clinical characteristics, resulting in 197 matched pairs for analysis. The primary end point for comparison was the rate of all-cause mortality or disabling stroke at 1-year. The mean age for TAVI and SAVR patients in the propensity-score matched population was 79.1 years and STS-PROM was 4.0 ± 1.5% for TAVI and 3.9% ± 1.3% for SAVR. The rate of all-cause mortality or disabling stroke at 30-days significantly favored TAVI (0.5% vs 5.1%; p = 0.006). At 1-year TAVI was numerically favored (4.1% vs 8.2%; p = 0.082). In conclusion, compared with SAVR, TAVI using Evolut R had a favorable 30-day safety profile, significantly better hemodynamic performance, and a comparable 1-year rate of all-cause mortality or disabling stroke, suggesting this may be a preferred treatment for patients with severe, symptomatic aortic stenosis at intermediate surgical risk.

Next-generation sequencing (NGS) increasingly influences diagnosis, prognosis and management of myelodysplastic syndrome (MDS). In addition to marrow morphology and flow cytometry, our institution performs cytogenetics (CG) and NGS-based testing routinely in patients with suspected MDS. We evaluated the relative value of NGS in the assessment of patients with suspected MDS. We initially compared the diagnostic and prognostic information derived from CG and NGS in 134 patients. NGS enhanced the diagnostic yield compared to CG for clonal myeloid disorders (sensitivity 77% vs. 42·2%; specificity 90·2% vs. 78%; positive predictive value 92·8% vs. 76%; and negative predictive value 70·8% vs. 45·5%). The identification of poor prognosis mutations by NGS altered risk category in 27/39 (69·2%) patients with MDS with good/intermediate risk CG. Subsequently, we prospectively evaluated 70 patients with suspected MDS using an 'NGS-first approach' with CG restricted to samples with morphological abnormalities. We rarely identified mutations or CG abnormalities in patients without dysplastic features. NGS has a superior diagnostic performance compared to CG in patients with suspected MDS. We estimate that by using an 'NGS-first approach' we could reduce karyotyping by approximately 30%.

Acute pulmonary thromboembolism remains a significant cause of morbidity and mortality worldwide. Its diagnosis, risk stratification and early treatment are essential. The mainstay of treatment is anticoagulation. In patients with low cardiovascular risk, the prognosis is excellent and the treatment consists only of the administration of anticoagulants. Due to the poor prognosis of patients with high risk (hemodynamic decompensation), the approach is more aggressive using systemic thrombolytics, which reduce mortality but increase the risk of major hemorrhagic complications. In the intermediate-risk patients (evidence of right ventricular failure, without hemodynamic decompensation), the risk-benefit relationship of thrombolytic treatment is more balanced, so the choice is controversial. Mechanical fragmentation with catheter-directed thrombolysis is an alternative with potential benefits. We present two cases of intermediate-risk acute pulmonary thromboembolism to whom mechanical fragmentation and catheter-directed thrombolysis was applied.

espanolIntroduccion: El implante valvular aortico transcateter (TAVI) ha mostrado ser beneficioso en los pacientes con riesgo intermedio;sin embargo,no existe ningun analisis del conjunto de los resultados del TAVI en nuestro pais.Objetivos: Realizar un metaanalisis de estudios locales de grupo unico sobre los resultados hospitalarios del TAVI en pacientesde riesgo intermedio en Argentina.Metodos: Se realizo una revision sistematica utilizando estudios observacionales de TAVI identificados en MEDLINE, Embase,SCOPUS y Cochrane hasta agosto de 2019.Resultados: De los 59 estudios identificados a traves de la citada busqueda, solamente 4 estudios observacionales locales comunicabanla mortalidad a 30 dias y las complicaciones posteriores al TAVI en pacientes de riesgo moderado, segun el puntaje dela STS (Society of Thoracic Surgeons) –entre 4 y 7%–. En 494 pacientes, la mortalidad a 30 dias fue del 4,8%. Las estimacionesponderadas del conjunto de estudios arrojaron estos valores: accidente vascular cerebral, 2,7%; infarto de miocardio,1,0%;necesidad de marcapasos definitivo, 24,8%; fuga paravalvular moderada o grave, 16,7%; y sangrado mayor, 5,5%.Conclusiones: La eficacia demostrada del TAVI esta generando una expansion de su indicacion a pacientes con riesgo intermedioy bajo; sin embargo, este avance deberia estar apoyado por evidencia local de su beneficio por sobre la cirugia valvulartradicional. Este metaanalisis de estudios de grupo unico realizados en el pais presenta la mortalidad a 30 dias y las complicacionesposteriores al TAVI en pacientes de riesgo intermedio. La informacion actualizada de los resultados locales del TAVIservira como un estandar en nuestro medio EnglishBackground: Transcatheter aortic valve implantation (TAVI) has been shown to be beneficial in patients with intermediaterisk; however, there is no overall analysis reporting TAVI results in our country.Objectives: To conduct a single-arm meta-analysis of local studies reporting 30-day outcomes after TAVI in intermediate riskpatients in Argentina.Methods: A systematic review on TAVI was performed using controlled trials and observational studies identified in MEDLINE,Embase, SCOPUS and Cochrane to August 2019.Results: Among 59 articles identified through the database search, only 4 local observational studies reported 30-day mortalityand complications after TAVI in moderate-risk patients according to the STS (Society of Thoracic Surgeons) score rangingbetween 4 and 7%. In 494 patients, 30-day mortality was 4.8%. Weighted pooled estimates of the studies were: stroke 2.7%,myocardial infarction 1.0%, need for a definitive pacemaker 24.8%, moderate or severe periprosthetic leakage 16.7%, andmajor bleeding 5.5%.Conclusions: The proven efficacy of TAVI is generating an expansion of its indication to patients with intermediate and lowrisk, However, this shift should be supported by local evidence of its benefit over traditional valve surgery. This single-armmeta-analysis of Argentine studies presents 30-day mortality and complications after TAVI in intermediate risk patients. Theupdated information of the local TAVI outcomes will serve as a standard in our settings.

Recent trials evaluated the impact of aspirin for primary prevention of cardiovascular events in patients at intermediate risk, patients with diabetes, and the elderly, and the results have been incorporated into the most recent professional guidelines. For the most part, the role of aspirin in primary prevention remains limited, albeit not adequately tested in those at higher risk.

Introduction Treatment decision-making for intermediate-risk prostate cancer (CaP) is mainly based on grade and tumor involvement on systematic biopsy. We aimed to assess the added value of multi-parametric magnetic resonance imaging (mpMRI) and targeted biopsy (TB) features for predicting final pathology and for improving the well-established favourable/unfavourable systematic biopsy-based sub-classification. Materials and Methods From a prospective database of 377 intermediate risk CaP cases, we evaluated the performance of the standard intermediate risk classification (IRC), and the predictive factors for unfavourable disease on final pathology aiming to build a new model. Overall unfavourable disease (OUD) was defined by any pT3-4 and/or pN1 and/or grade group (GG) ≥ 3. Results The standard IRC was found to be predictive for unfavourable disease in this population. However, in multivariable analysis regression, ECE on mpMRI and GG ≥3 on TB remained the 2 independent predictive factors for OUD disease (HR = 2.7, P = 0.032, and HR = 2.41, P = 0.01, respectively). By using the new IRC in which unfavorable risk was defined by ECE on mpMRI and/or GG ≥3 on TB, the proportion of unfavorable cases decreased from 62.3% to 34.1% while better predicting unfavorable disease in RP speciments. The new model displayed a better accuracy than the standard IRC for predicting OUD (AUC: 0.66 vs. 0.55). Conclusions The integration of imaging and TB features drastically improves the intermediate risk sub-classification performance and better discriminates the unfavourable risk group that could benefit from more aggressive therapy such as neo-adjuvant and/or adjuvant treatment, and the favourable group that could avoid over-treatment. External validation in other datasets is needed.

Transcatheter aortic valve replacement (TAVR) has emerged as the treatment of choice for patients with severe aortic stenosis deemed at high or intermediate risk for cardiac surgery. In light of the latest literature advances, TAVR will undoubtedly concern a growing number of patients because of the progressive extension of its indications. Whereas significant efforts have been made to reduce the burden of periprocedural complications, TAVR still exposes patients to a sizeable number of adverse outcomes, including thrombotic and bleeding events. Although contradictory, these two phenomena are closely related to pathophysiological processes inherent to flow disturbances induced by aortic stenosis itself, but also to a complex interaction between bioprosthetic valves and native tissues in frail patients clustering various co-morbidities. Reinforcing this paradigm, multiple TAVR studies have emphasized the view that both thrombosis and bleeding events have a deleterious effect on patient outcomes. Therefore, we sought to perform a comprehensive translational review of the current literature addressing the pathophysiological mechanisms leading to thrombosis and bleeding after TAVR, and underline innovative strategies aimed at reducing these complications.

Background The present study aimed to evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for localized prostate cancer. Patients and methods We investigated 25 patients treated with SBRT of 35 Gy per five fractions from May 2014 to March 2015. Results The median age of patients was 70 years, four (16%) patients were low risk and 21 (84%) were intermediate risk. Seven (28%) patients received neoadjuvant androgen-deprivation therapy. The median follow-up time was 53 months. Grade 2 acute and late genitourinary toxicities were observed in five (20%) and two (8%) patients and there were no Grade 2 gastrointestinal toxicities. There were no Grade 3 or higher acute or late toxicities at 2 years follow-up. The biochemical relapse-free survival rate at 2 years was 100%. Conclusion SBRT of 35 Gy per five fractions is a promising treatment method in the short term for prostate cancer.

Purpose Active surveillance (AS) strategies for patients with low- and early intermediate-risk prostate cancer are still not consistently defined. Within a controlled randomized trial, active surveillance was compared to other treatment options for patients with prostate cancer. Aim of this analysis was to report on termination rates of patients treated with AS including different grade groups. Methods A randomized trial comparing radical prostatectomy, active surveillance, external beam radiotherapy and brachytherapy was performed from 2013 to 2016 and included 345 patients with low- and early intermediate-risk prostate cancer (ISUP grade groups 1 and 2). The trial was prematurely stopped due to slow accrual. A total of 130 patients were treated with active surveillance. Among them, 42 patients were diagnosed with intermediate-risk PCA. Reference pathology and AS quality control were performed throughout. Results After a median follow-up time of 18.8 months, 73 out of the 130 patients (56%) terminated active surveillance. Of these, 56 (77%) patients were histologically reclassified at the time of rebiopsy, including 35% and 60% of the grade group 1 and 2 patients, respectively. No patients who underwent radical prostatectomy at the time of reclassification had radical prostatectomy specimens ≥ grade group 3. Conclusion In this prospectively analyzed subcohort of patients with AS and conventional staging within a randomized trial, the 2-year histological reclassification rates were higher than those previously reported. Active surveillance may not be based on conventional staging alone, and patients with grade group 2 cancers may be recommended for active surveillance in carefully controlled trials only.

Introduction: The revised Dutch colorectal cancer guideline (2014), led to an overall decrease in preoperative radiotherapy (RT) use. This study evaluates hospital variation in RT use for resectable rectal cancer and the influence of guideline revision, including the nationwide impact of changing RT application on short term outcomes.Methods: Data of surgically resected rectal cancer patients registered in the Dutch ColoRectal Audit were extracted between 2011 and 2017. Patients were divided into groups based on time of guideline revision (= 2014). Primary outcome was guideline adherence at hospital level regarding RT application, stratified for three stage groups. Secondary outcomes included positive circumferential resection (CRM+) and 30-day complicated postoperative course.Results: The groups consisted of 7364 and 12,057 patients, respectively. In total, 6772 patients did not receive RT (17.6% (= 2014), p < 0.001). The largest increase of surgery alone was observed for cT1-2N0 stage rectal cancer (35.1% vs. 91.8%, p < 0.001), with a substantial decrease in hospital variation (IQR 22.2-50.0% vs. IQR 87.6-98.0%). For cT1-3N1MRF-stage rectal cancer, a substantial amount of hospital variation in short course RT remained after guideline revision (IQR 26.8-54.1% vs. IQR 26.2-50.0%). A significant decrease in CRMthorn (5.8% vs. 4.2%, p < 0.001) and complicated course (22.5% vs. 18.5%, p < 0.001) was observed.Conclusions: Radiotherapy for early-stage rectal cancer was uniformly abandoned after guideline revision, while substantial hospital variation remained for intermediate risk resectable rectal cancer in the Netherlands. The substantial nationwide decrease in the use of RT for rectal cancer treatment did not negatively impact CRM involvement. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

A 61-year-old woman diagnosed with chronic myeloid leukemia (CML) (Sokal intermediate risk) was treated with the tyrosine kinase inhibitor (TKI) nilotinib 600 mg/day. The patient was a nonsmoker and had no cardiovascular history, diabetes, or other relevant diseases. Blood tests revealed

Objective was to assess if coronary calcium score (CCS) zero (1.0AU) reliably rules out coronary artery disease (CAD) by coronary CTA; and if a difference between CCS zero and ultralow CCS (0.1-0.9AU) exists.6439 low-to-intermediate ASCVD-risk patients (57.9 ± 11.1 years; 44.4% females) who underwent CTA and CCS were enrolled. Coronary CTAs were evaluated for: (1) stenosis severity (CADRADS:25%, 25-49%, 50-69%, 70-99%, and 100%), (2) mixed-plaque burden, and (3) high-risk-plaque-(HRP)-criteria. Primary endpoints were all-cause and cardiovascular (CV) mortality, secondary endpoint MACE.Overall 1451 (22.5%) had CCS1.0 AU. Among them, 1289 had CCS zero and 162 ultralow CCS (0.1-0.9AU). In CCS zero patients, 25.9% had CAD, 5.1% 50% and 20.8% less than 50% stenosis, 6.8% had HRP with min 2 criteria, respectively. LAP30HU, LAP60HU, Napkin-Ring-Sign, Spotty calcification and PR were found in 1.3%, 3.7%, 2.8%, 2.3% and 8.2%. CAD prevalence was with 87.7% markedly higher in the ultralow CCS (p 0.001) group,50% stenosis (16.6%), total plaque burden (p 0.001) and HRP-criteria rates were higher (up to 19.1%) (p 0.001, respectively).All-cause mortality was similar (2.7% and 1.9%) in CCS 0 and ultralow patients (mean follow-up 6.6 ± 4.2 years). Composite MACE (n = 7, 0.48%) was higher than CV-mortality (n = 1, 0.06%, p = 0.038, OR 1.08-1.6). More HRP were found on 128-slice-dual-source-CTA compared to 64-slice (p 0.001). There were no differences in CTA findings between patients with and without chest pain, but more females were symptomatic.Early signs of CAD on CTA are frequent in CCS zero and even present in the majority of ultralow CCS (0.1-0.9AU) patients, who should not be downgraded to CCS zero patients. High-risk plaque and50% stenosis rate is low but not negligible; and MACE rate very low.

Background: Guidelines recommend that breast radiation (RT) can be omitted for patients with a low risk of local recurrence (LR) after breast-conserving surgery (BCS) for DCIS. The inability to identify women at low risk of LR ( Methods: Prospective cohort study of women with low/moderate risk pure DCIS treated with BCS. Cases with age 2.5cm, multifocality, or prior breast cancer were excluded. Baseline CPFs, the DS and risk of LR were collected. Pre-assay, the radiation oncologist provided an estimate of 10-year LR risk without RT and a preliminary recommendation for RT. Post-assay, final recommendations were recorded. The primary outcome was change in treatment recommendation by the radiation oncologist. Target sample size was 220 to provide data on 200 evaluable patients with adequate precision. Results: 217 patients were evaluable: mean age, 63 years and mean tumor size, 1.1 cm. Nuclear grade was low in 26 (12%), intermediate in 116 (53%), and high in 75 (35%) of patients. Mean DS = 32; 140 (64%) low (15% in 128 (59%) cases. Post-assay, estimated 10-yr LR risk after BCS was 15% in 49 (22%) (RT recommended in 98%). Conclusion: The use of the DCIS Score combined with CPFs identifies more women with an estimated low ( Table 1.Post-assay 10-yr LR risk15%(N=101)(N= 67)(N=49)Pre-assay estimated 10-yr LR risk• 15% (N=128)424739RT recommended• Yes17 (17%)44 (66%)48 (98%)• No83 (83%)23 (34%)1 (2%) Citation Format: Eileen Rakovitch, Anne Koch, Laval Grimard, Hany Soliman, Christiaan Stevens, Francisco Perera, Iwa Kong, Senti Senthelal, Margaret Anthes, Ericka Wiebe, Jeffrey Cao, Mira Goldberg, Sally Smith, Luciana Spadafora, Sameer Parpia, Timothy Whelan. Refined local recurrence risk estimates based on a multigene expression assay combined with clinicopathological features significantly impacts radiotherapy recommendation in patients with low/intermediate risk DCIS treated with breast-conserving surgery [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-16-01.

IntroductionA novel handheld dual-electrode stick is a portable atrial fibrillation (AF) screening device (AFSD). We evaluated AFSD performance in primary care patients referred for echocardiogram (echo).MethodsThe AFSD has a light indication of irregular rhythm and single-lead ECG recording. Patients were instructed to hold the device for 1 min, and AF indication was recorded. A 12-lead ECG was performed for all AFSD-positive patients and 250 patients with negative AFSD screen. Echos were performed based on a clinical risk score: all high-risk patients and a sampling of low-risk patients underwent complete echo. Intermediate risk patients first had a screening echocardiogram, with a follow-up complete study if abnormality was suspected.ResultsIn 5 days, 1518 patients underwent clinical evaluation and cardiovascular risk stratification: mean age 58±16 years, 66% women. The AFSD was positive in 6.4%: 12.6% high risk, 6.1% intermediate risk and 2.2% low risk. Older age was a risk factor (9.3% vs 4.8% in those more than and less than 65 years, p=0.001). AFSD positive was independently associated with heart disease in echo (OR=3.9, 95% CI 2.1 to 7.2, pConclusionAFSD demonstrated high sensitivity for AF detection in primary care patients referred for echo. AF prevalence was substantial and independently associated with structural or functional heart disease, suggesting that AFSD screening could be a useful primary care tool to stratify risk and prioritise echo.