Large Prospective Multicenter Study Research Articles

1020: THERAPEUTIC ENOXAPARIN IN MORBIDLY OBESE PATIENTS: SINGLE-CENTER EXPERIENCE

Introduction: Enoxaparin is a low molecular weight heparin commonly used in the treatment of venous thromboembolisms (VTEs); however, evidence on optimal therapeutic dosing recommendations and bleeding adverse events are lacking in patients with morbid obesity (BMI > 35). Recommendation for VTE is 1 mg/kg every 12 hours using total body weight (TBW) for all patients. Methods: We performed a retrospective chart review of patients who were admitted to the ICU between 1/2020 and 9/2021 and were treated for VTE with 1 mg/kg TBW enoxaparin (full dose, FD) to look at bleeding complication rates in patients with BMI >35 and compared with patients who received 0.5 – 0.8 mg/kg TBW (adjusted dose, AD) and BMI > 35. Bleeding complications rates were defined as: needing one or more unit RBC transfusion (RBC), intracranial hemorrhage (ICH), retroperitoneal hemorrhage (RPH), or GI bleed (GIB). The following data were also collected from electronic medical records: Gender (Male), anti-Xa checked (AX), BMI (kg/m2), acute kidney injury (AKI based on KDIGO definitions), and hospital mortality. Results: We identified a total of 55 patients (42 in FD group and 13 in AD group). Compared to AD group, the FD group had more RBC transfusions (50% vs 31%), more ICH (7% vs 0 %), more RPH (9.5% vs 0 %), and more GIB (2.4 % vs 0%) respectively. Both groups were comparable regarding gender (M: 52 vs 38%, p = 0.4), anti-Xa (64% vs 62%, p = 0.9), BMI (44 +/- 7 vs 47 +/- 15, p = 0.3), AKI (17 % vs 15 %, p = 0.7), and mortality (29 % vs 31 %, p = 0.9). Conclusions: These data suggest that enoxaparin at recommended dosing of 1 mg/kg every 12 hours using total body weight for obese patients with BMI > 35 is associated with increased bleeding complications. These findings should be investigated in large multicenter prospective studies.

Cytology Smears: An Enhanced Alternative Method for Colorectal Cancer pN Stage-A Multicentre Study.

Stage II colorectal cancer (CRC) recurrence remains a clinical problem. Some of these patients are true stage III CRC with a pN0 pathology stage. This large prospective multicentre cohort study aimed at evaluating the diagnostic ability of lymph node (LN) cytology smears to perform the pN stage and compare it with the conventional haematoxylin and eosin (H&E) pathology pN stage. Additionally, we used the One-Step Nucleic Acid Amplification (OSNA), a high-sensitive molecular method of LN staging. A total of 3936 fresh LNs from 217 CRC surgical specimens were examined by three methods, H&E, LN cytology smears, and OSNA. H&E detected 29% of patients with positive LNs, cytology smears 35%, and OSNA 33.2% (p < 0.0001). H&E and cytology concordantly classified 92.2% of tumours, and 88.5% between OSNA and H&E. Cytology had 96.8% sensitivity and 90.3% specificity to discriminate positive/negative patients compared to H&E (p = 0.004), and 87.3% sensitivity and 89% specificity when compared to OSNA (p = 0.56). Patients with positive LNs detected by any of the three methods had significantly worse disease-free and overall survival. We conclude that pN stage accuracy for detecting positive LNs is superior with LN cytological smears than with conventional H&E, which would enable a better pN stage and management of early-stage CRC patients.

Predictors of cerebrospinal fluid leakage after elective cranial surgery

BackgroundCerebrospinal fluid (CSF) leaks are well-known and frequent complications of intracranial procedures. Numerous studies have focused on the clinical aspects of incidence, risk factors, outcome, treatment, and prevention; however, large prospective multicentre studies are missing. Dural closure seems a critical step in neurosurgical procedures to avoid CSF leakage. “Watertight” dural closure is an important adage within neurosurgery, although this is subject to debate. This study aimed to prospectively analyze the rate of CSF leaks and associated factors. ObjectiveTo describe the frequency of postoperative CSF leak and associated factors after elective cranial procedures. MethodologyInstitution-based observational cohort study was conducted from September 1, 2020, to August 2021. Patients were followed for the development of CSF leaks. Data was collected using a pretested structured questionnaire. Bivariate and multivariate correlation analysis was performed to identify associated variables. A p-value < 0.05 was considered significant. ResultA total of 289 patients were included in the study. The mean age of the study population was 36.36 ± 15.47 and 54.7 % were females. The incidence of postoperative CSF leaks was 12.8 %. Hydrocephalus, non-watertight dural closure, and degree of intraoperative blood loss were strongly associated with postoperative CSF leak (p < 0.05). Preoperative hydrocephalus treatment was a negative predictor of leaks (OR = 0.06). Patients with CSF leaks have a higher risk of developing postoperative infection (OR = 25.54) and prolonged hospital stay (OR = 2.63). ConclusionThe rate of CSF leaks in our study was (12.8%). Though this is similar to the finding in most studies, it is still high and needs additional solutions to decrease this bothersome complication. We found that watertight dural closure must be achieved whenever possible either primarily or using dural patch material. Preoperative treatment of hydrocephalus significantly decreases postoperative CSF leak. CSF leak increases the risk of postoperative infection and length of hospital stay.

Incidence of falls and fall-related injuries and their predictive factors in frail older persons with cancer: a multicenter study

BackgroundFalls and fall-related injuries are a major public health problem. Data on falls in older persons with cancer is limited and robust data on falls within those with a frailty profile are missing. The aim of this study is to investigate the incidence and predictive factors for falls and fall-related injuries in frail older persons with cancer.MethodsThis study is a secondary data analysis from data previously collected in a large prospective multicenter observational cohort study in older persons with cancer in 22 Belgian hospitals (November 2012–February 2015). Patients ≥70 years with a malignant tumor and a frailty profile based on an abnormal G8 score were included upon treatment decision and evaluated with a Geriatric Assessment (GA). At follow-up, data on falls and fall-related injuries were documented.ResultsAt baseline 2141 (37.2%) of 5759 included patients reported at least one fall in the past 12 months, 1427 patients (66.7%) sustained an injury. Fall-related data of 3681 patients were available at follow-up and at least one fall was reported by 769 patients (20.9%) at follow-up, of whom 289 (37.6%) fell more than once and a fall-related injury was reported by 484 patients (62.9%). Fear of falling was reported in 47.4% of the patients at baseline and in 55.6% of the patients at follow-up. In multivariable analysis, sex and falls history in the past 12 months were predictive factors for both falls and fall-related injuries at follow-up. Other predictive factors for falls, were risk for depression, cognitive impairment, dependency in activities of daily living, fear of falling, and use of professional home care.ConclusionGiven the high number of falls and fall-related injuries and high prevalence of fear of falling, multifactorial falls risk assessment and management programs should be integrated in the care of frail older persons with cancer. Further studies with long-term follow-up, subsequent impact on cancer treatment and interventions for fall prevention, and integration of other important topics like medication and circumstances of a fall, are warranted.Trial registrationB322201215495.

Post-Thyroidectomy Hematoma: Risk Factors To Be Considered for Ambulatory Thyroidectomy.

Post-thyroidectomy hematoma is a serious, potentially life-threatening complication and it is the most frequent indication for reoperation. In this study, we aimed to identify the risk factors and prevalence of post-thyroidectomy hematoma and perform a literature review of the incidence of post-thyroidectomy hematoma at other centers in Saudi Arabia. We retrospectively enrolled 372 consecutive patients who had undergone thyroidectomy between January 2015 and December 2020. Patients with bleeding disorders were excluded from the study. Data were analyzed using SPSS software, version 20.0 (IBM Corp., Armonk, NY). Three female (0.8%) patients developed a hematoma after thyroidectomy. Two patients developed a hematoma 24 hours after surgery and were treated conservatively. The third patient developed a hematoma within two hours of surgery and required surgical intervention. None of the patients required a tracheostomy, and there was no mortality. No significant association was found between age, sex, final pathology, the extent of thyroidectomy, and risk of hematoma. A post-thyroidectomy hematoma is a rare but dangerous complication. Identifying the risk factors for hematoma formation is of great importance, particularly when considering outpatient thyroidectomy. A large prospective multicenter study is needed for further investigation.

Phase II Study of PD-1 Blockade Following Fludarabine/Melphalan-Based Autologous Transplantation for Acute Myeloid Leukemia Patients Ineligible for Allogeneic Transplant

Allogeneic transplant (allo) remains the best post-remission therapy for non-favorable risk acute myeloid leukemia (AML) patients, secondary to the potent graft-versus-leukemia (GVL) effect of donor immune cells. Unfortunately, some patients may be ineligible for allogeneic transplant due to psychosocial barriers (e.g. lack of appropriate caregiver support) or unavailability of a suitable donor. Inhibition of the programmed cell death protein-1 (PD-1) pathway is an effective immunotherapeutic anti-cancer strategy for a number of malignancies. We hypothesized that PD-1 blockade following autologous transplant might simulate an allogeneic GVL effect and represent an alternative post-remission strategy in patients with non-favorable risk AML. To this end, we initiated a phase II study whereby AML patients deemed ineligible for allogeneic transplant received a high dose preparative regimen consisting of fludarabine on day -4, -3, -2 (30mg/m2/d) and melphalan on day -1 (180mg/m2 for age ≤60, 140mg/m2 for age >60), followed by autologous stem cell transplantation and post-transplant pembrolizumab starting day +1 (200mg/dose q3weeks x 8 doses) (auto-pembro). Eligible patients were AML patients beyond CR1 or non-favorable CR1 patients, including c-kit-mutated core-binding factor and FLT3-ITD+/NPM1+ AML. Of 32 patients consented/screened for the study, 20 received protocol-directed therapy from January 2017 to July 2021. Reasons for not receiving transplant were mobilization failure [6], failure to achieve CR [2], patient refusal [2], compliance issues [1] and insurance issues [1]. Baseline patient characteristics included a median (range) age of 64 (26-75) years, KPS <80 in 30%, HCT-CI ≥3 in 85% and non-Hispanic white in 45%. Disease characteristics included ELN 2017 favorable, intermediate and adverse risk in 20%, 40% and 40%, disease-risk index low, intermediate and high in 10%, 75% and 15%, secondary/treatment-related in 20%, CR1 status in 80%, and pre-BMT measurable residual disease (MRD) in 30%. Treatment was well tolerated in only 1 non-relapse death. Infections included 5 patients with bacterial infections, 2 with CMV viremia, 1 with localized VZV and 1 patient with HHV6 reactivation. Grade 3 non-hematologic toxicities included febrile neutropenia (30%), nausea/vomiting (25%), diarrhea (25%), hypertension (20%) and stomatitis/esophagitis (15%). There were no study-related grade 4 or 5 toxicities. Possible immune-related adverse events included 4 cases of hypothyroidism, 2 cases of colitis and 1 case each of pneumonitis, erythema multiforme and seronegative arthritis. After a median follow-up of 80 months (range, 15-134), 14 patients remain alive with 10 in continuous remission. Estimated 3-yr OS, DFS, NRM and CIR was 66%, 48%, 5% and 47% respectively. Transplant outcomes in auto-pembro recipients were compared to a contemporaneous cohort of consecutive AML patients receiving allo transplant in first or later CR (n=112) by Cox proportional hazards model, adjusting for significant demographic and risk variables. Compared with allo recipients, auto-pembro recipients were less likely to be non-Hispanic white (45% vs. 69%) and male (35% vs. 59%) but were otherwise similar in regard to baseline patient and disease characteristics. In multivariable analysis, OS and DFS were significantly impacted by age, ELN risk and year of transplant. In contrast, transplant type (auto-pembro vs. allo) had no effect on OS (HR 0.58, p=0.24) or DFS (HR 1.19, p=0.65). Adjusted 3-yr OS and DFS was 76% vs. 66% and 54% vs. 62% respectively (see figure). Although relapse was significant higher following auto-pembro (HR 2.38, p=0.031), it was offset by a corresponding decrease in NRM risk. In conclusion, auto-pembro is a safe and effective consolidation therapy for non-favorable AML patients who are ineligible for allo transplant, with comparable adjusted survival outcomes. Correlative studies are planned to analyze anti-leukemic effect of post-transplant PD-1 blockade following autologous transplant in AML patients. Given these promising results in non-favorable-risk AML patients lacking an allogeneic transplant consolidation option, confirmation in a larger multicenter prospective study is warranted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Emicizumab Switch: Real-World Data of 251 Pediatric Patients from the Pednet Registry

Background: Despite the rapid uptake of emicizumab in the pediatric hemophilia A (HA) population, real-world data on emicizumab safety and efficacy outcomes are limited to the HAVEN-2 trial (N = 85) and single center cohort studies. Aim: To report on bleeding and safety in children and adolescents with HA receiving emicizumab prophylaxis in a large prospective multicenter cohort study. Methods: Data were extracted from the ongoing PedNet Registry (Clin.gov.trial-NCT02979119; date of extraction: Jan 2022). Patients were included if they had a diagnosis of congenital hemophilia A with a baseline factor FVIII up to 25% and were < 18 years old at start of emicizumab. Patients were required to have maintenance therapy of emicizumab and bleeding data available for a minimum of 4 weeks. Patients with concomitant coagulopathies were excluded (N = 2). Bleeding data were compared during emicizumab to bleeding data before emicizumab up to a maximum of two years prior to the start of emicizumab. Patient characteristics were summarized as numbers (%) and median with IQR (P25-P75). Mean annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) were estimated and compared between prophylactic regimens by negative binomial regression modelling. Results: 251 patients were included from 30 hemophilia treatment centers, see Table 1 for patient characteristics. The median age at start of emicizumab therapy was 6.1 years (IQR: 2.1 - 12.0). Median follow-up time before emicizumab was 1.51 years and during emicizumab was 1.23 years with a total of 361 patient years reported on emicizumab therapy. Most patients (94%) had severe HA and 76% of the patients were younger than 12 years at start of emicizumab therapy. Approximately one third (37%) of the patients had an inhibitor at start of emicizumab with a median peak titer of 128 BU/ml (IQR: 34 - 600). The ABR and AJBR significantly improved during emicizumab therapy in patients with and without inhibitors, see Figure 1. In patients without inhibitors the mean ABR reduced from 2.8 prior to emicizumab to 1.1 during emicizumab (p < 0.001), while the AJBR reduced from 0.8 to 0.3 (p < 0.001). Similar results were seen in patients with inhibitors. The mean ABR reduced from 5.5 to 1.1 (p<0.001), while the AJBR reduced from 2.3 to 0.3 (p<0.001). In this cohort, two serious adverse events and six adverse events were reported during emicizumab therapy in eight patients (3% of total cohort). Serious adverse events included one death unrelated to emicizumab therapy (retroperitoneal bleed in a baby treated with LMWH for CVL thrombosis) and one patient developed anti-drug antibodies without breakthrough bleeding, who continued emicizumab therapy. Non serious adverse events were all related to local injection site reaction in six patients. No TMA or thrombotic events were observed. Conclusions: This large cohort study with prospectively collected data showed improved bleeding control compared to previous therapy and a favorable safety profile during emicizumab treatment in pediatric patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Down-regulation of hepatic expression of GHR/STAT5/IGF-1 signaling pathway fosters development and aggressiveness of HCV-related hepatocellular carcinoma: Crosstalk with Snail-1 and type 2 transforming growth factor-beta receptor.

So far, few clinical trials are available concerning the role of growth hormone receptor (GHR)/signal transducer and activator of transcription 5 (STAT5)/insulin like growth factor-1 (IGF-1) axis in hepatocarcinogenesis. The aim of this study was to evaluate the hepatic expression of GHR/STAT5/IGF-1 signaling pathway in hepatocellular carcinoma (HCC) patients and to correlate the results with the clinico-pathological features and disease outcome. The interaction between this signaling pathway and some inducers of epithelial-mesenchymal transition (EMT), namely Snail-1 and type 2 transforming growth factor-beta receptor (TGFBR2) was studied too. A total of 40 patients with HCV-associated HCC were included in this study. They were compared to 40 patients with HCV-related cirrhosis without HCC, and 20 healthy controls. The hepatic expression of GHR, STAT5, IGF-1, Snail-1 and TGFBR2 proteins were assessed by immunohistochemistry. Compared with cirrhotic patients without HCC and healthy controls, cirrhotic patients with HCC had significantly lower hepatic expression of GHR, STAT5, and IGF-1proteins. They also displayed significantly lower hepatic expression of TGFBR2, but higher expression of Snail-1 versus the non-HCC cirrhotic patients and controls. Serum levels of alpha-fetoprotein (AFP) showed significant negative correlations with hepatic expression of GHR (r = -0.31; p = 0.029) and STAT5 (r = -0.29; p = 0.04). Hepatic expression of Snail-1 also showed negative correlations with GHR, STAT5, and IGF-1 expression (r = -0.55, p = 0.02; r = -0.472, p = 0.035, and r = -0.51, p = 0.009, respectively), whereas, hepatic expression of TGFBR2 was correlated positively with the expression of all these proteins (r = 0.47, p = 0.034; 0.49, p = 0.023, and r = 0.57, p&lt;0.001, respectively). Moreover, we reported that decreased expression of GHR was significantly associated with serum AFP level&gt;100 ng/ml (p = 0.048), increased tumor size (p = 0.02), vascular invasion (p = 0.002), and advanced pathological stage (p = 0.01). Similar significant associations were found between down-regulation of STAT5 expression and AFP level &gt; 100 ng/ml (p = 0.006), vascular invasion (p = 0.009), and advanced tumor stage (p = 0.007). Also, attenuated expression of IGF-1 showed a significant association with vascular invasion (p &lt; 0.001). Intriguingly, we detected that lower expression of GHR, STAT5 and IGF-1 were considered independent predictors for worse outcome in HCC. Decreased expression of GHR/STAT5/IGF-1 signaling pathway may have a role in development, aggressiveness, and worse outcome of HCV-associated HCC irrespective of the liver functional status. Snail-1 and TGFBR2 as inducers of EMT may be key players. However, large prospective multicenter studies are needed to validate these results.

Lipoprotein(a) in progressive coronary artery disease: beyond classical cardiovascular risk parameters

Abstract Introduction Classical primary preventive cardiovascular disease (CVD) risk algorithms, such as the Framingham risk score and the widely used QRISK score in the UK, predate large-scale deep-phenotyped biomedical research resources. There is therefore the opportunity to identify novel predictors. In addition, whilst CVD risk profiling is well studied in the context of primary prevention, there is a paucity of data examining risk in regard to secondary prevention. Purpose To identify independent predictors of repeat coronary artery revascularisation, following index coronary angioplasty. Methods The UK Biobank is a large prospective multicentre study which recruited over 500,000 participants in the UK aged 37–73 years at entry between 2006–2010. Data are derived from an array of physical measurements, self-reported measures and biological samples, together with longitudinal linkage to hospital inpatient records and death registries. Procedural codes were used to identify patients who had undergone first coronary angioplasty from 2006 onwards. Repeat revascularisation (RR) was defined as angioplasty or bypass grafting occurring at least 9 months after the index angioplasty, in order to preclude instances of staged revascularisation and in-stent restenosis. Data were censored at January 2021 or date of death as appropriate. Results A total of 12,853 participants underwent a first coronary angioplasty during the study period, with 1,394 (10.8%) requiring RR over a median follow-up of 6.5 years. The average age was 64 years in the RR cohort and 1117 (80%) were male. Univariate analyses confirmed a number of established associations with RR, including for example diabetes mellitus and hypertension. Median lipoprotein(a) concentrations were 27.6 vs. 30.3nmol/L in the RR group, p=0.066. Cox regression analyses (n=7,216) incorporating 21 biometric and clinical parameters demonstrated that lipoprotein(a) &amp;gt;80nmol/L was one of six independent predictors of time to RR (HR 1.24, p=0.006), independent of other lipids. The strength and significance of this association persisted when the number of covariates was reduced to include only other lipids and classical cardiovascular risk parameters. LDL, HDL, and triglyceride levels were not significant predictors in this model. Conclusions Lipoprotein(a) is identified as a major independent driver of RR. However current European Society of Cardiology guidance does not recommend measurement of Lipoprotein(a) in the context of progressive coronary artery disease. Furthermore, it is known that strategies such as lifestyle advice and statins – recommended in all patients with established coronary artery disease - do no reduce lipoprotein(a), whilst niacin and PCSK9 inhibitors do have a significant effect. Indications for lipoprotein(a) measurement must therefore be broadened, so that specific treatments to lower it can be instituted in order to reduce the burden of progressive coronary artery disease. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Herefordshire Heart Fund

Outcome prediction value of critical area perfusion score for acute basilar artery occlusion.

To investigate the performance of the Critical Area Perfusion Score (CAPS), based on computed tomography perfusion (CTP) time to maximum (Tmax) > 10s maps, to predict the outcome in acute basilar artery occlusion (BAO) in patients undergoing endovascular treatment (EVT). We perform a retrospective analysis of a prospectively collected database of acute BAO treated with EVT in a comprehensive stroke center. The favorable outcome was defined as the 90-day modified Rankin Scale (mRS) ≤ 3. We performed the logistic regression analysis to find the independent predictors of the favorable outcome. Then, we used receiver operating characteristic analyses to assess the predictive value of the imaging parameters, including CAPS, Posterior Circulation Alberta Stroke Program Early CT Score (PC-ASPECTS), pons midbrain index (PMI), posterior circulation computed tomography angiography (PC-CTA) score, Basilar Artery on Computed Tomography Angiography (BATMAN) score, and CTP parameters. Finally, the Delong test was used to compare the area under the curve (AUC) of CAPS against the other imaging parameters. Of the 65 enrolled patients, the incidence of the favorable outcome was 44.6% (29/65). Low CAPS (per 1- point increased odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.86; P = 0.017) and admission National Institutes of Health Stroke Scale (NIHSS) (per 1- point increased OR, 0.80; 95% CI, 0.70-0.91; P = 0.001) were independently associated with favorable outcome. The AUC of CAPS was 0.83 (95% CI, 0.74-0.93; P < 0.001) with ≤ 3 cut-off value, 89.66% sensitivity, 77.22% specificity, and 80.00% accuracy, which was greater than the other imaging parameters (All P for Delong test < 0.05). CAPS was the most accurate imaging-based outcome predictor in acute BAO patients. Future large prospective multicenter studies are needed to verify these results.

Functional status in older patients with cancer and a frailty risk profile: A multicenter observational study

IntroductionFunctional status (FS) and frailty are significant concerns for older adults, especially those with cancer. Data on FS (Activities of Daily Living [ADL]; Instrumental Activities of Daily Living [IADL]) and its evolution during cancer treatment in older patients and a frailty risk profile are scarce. Therefore, this study examines FS and its evolution in older patients with cancer and a frailty risk profile and investigates characteristics associated with functional decline. Material and MethodsThis secondary data-analysis, focusing on FS, uses data from a large prospective multicenter observational cohort study. Patients ≥70 years with a solid tumor and a frailty risk profile based on the G8 screening tool (score ≤ 14) were included. A geriatric assessment was performed including evaluation of FS based on ADL and IADL. At approximately three months of follow-up, FS was reassessed. Univariable and multivariable logistic regression analyses were used to identify predictive factors for functional decline in ADL and IADL. ResultsData on ADL and IADL were available at baseline and follow-up in 3388 patients. At baseline 1886 (55.7%) patients were dependent for ADL, whereas 2085 (61.5%) patients were dependent at follow-up. Functional decline was observed in 23.6% of patients. For IADL 2218 (65.5%) patients were dependent for IADL, whereas 2591 (76.5%) patients were dependent at follow-up. Functional decline in IADL was observed in 41.0% of patients. In multivariable analysis, disease stage III or IV, comorbidities, falls history in the past twelve months, and FS measured by IADL were predictive factors for functional decline in both ADL and IADL. Other predictive factors for functional decline in ADL were polypharmacy, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) score 2–4, and cognitive impairment, and for functional decline in IADL were female sex, fatigue, and risk for depression. DiscussionFunctional impairments are frequent in older persons with cancer and a frailty risk profile, and several characteristics are identified that are significantly associated with functional decline. Therefore, FS is an essential part of the geriatric assessment which should be standard of care for this patient population. Next step is to proceed with directed interventions with the aim to limit the risk of functional decline as much as possible.

Noninvasive computed tomography derived fractional flow reserve simulation based on microvascular tree model reconstruction.

To establish a novel method for noninvasive computed tomography derived fractional flow reserve (CT-FFR) simulation based on microvascular tree model reconstruction and to evaluate the feasibility and diagnostic performance of the novel method in coronary artery disease compared with invasive fractional flow reserve (FFR). Twenty patients (20 vessels) who underwent coronary computed tomography angiography (CCTA) and invasive FFR were retrospectively studied. The anatomic epicardial coronary artery model was reconstructed based on CCTA image, and the microvascular tree model was simulated based on patient-specific anatomical structures and physiological principles. Numerical simulation was subsequently performed using the CFD method with full consideration of the variation of viscosity in microvascular. Two patients with the FFR value of .80 were selected for adjusting the parameters of the model, while the remaining 18 patients were selected as a validation cohort. After simulation, CT-FFR was compared with invasive FFR with a threshold of .80. Eleven (55%) patients had an abnormal FFR that was less than or equal to .80. Compared with invasive FFR, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CT-FFR with an optimal threshold of .80 were 100%, 77.8%, 81.8%, 100%, 88.89%, respectively. There were a good correlation and consistency between CT-FFR and invasive FFR. Time per patient of CT-FFR analysis was less than 15 min. CT-FFR based on microvascular tree model reconstruction is feasible with good diagnostic performance. It requires a short processing time with excellent accuracy. Large multicenter prospective studies are required for further demonstrating the diagnostic performance of this novel model in myocardium ischemia evaluation.

Assessing the Relationship between Plasma Von Willebrand Factor Antigen Levels, ABO and Rh (D) Blood Groups and Risk of Sickle Cell Anaemia Vaso – Occlusive Crisis

In sickle cell anaemia (SCA), continuous activation of the vascular endothelium by inflammatory cytokines leads to increased elaboration and secretion of von Willebrand Factor (vWF), a potent mediator of adhesive interactions involving the endothelium and circulating blood cells. Non-O blood groups are associated with the elevation of vWF concentration. Thus, SCA and non – O blood groups are determinants of increased levels of vWF, which plays a pivotal role in the pathophysiology of vaso-occlusive crisis (VOC). To determine the influence of plasma vWF:Ag levels, ABO and Rh (D) blood groups on the risk of occurrence of sickle cell vaso-occlusive crisis. We conducted a prospective study of frequencies of VOC with respect to plasma vWF:Ag levels, ABO and Rh (D) blood groups of 50 SCA patients. In comparison with blood group O, patients with non – O blood groups had significantly higher mean vWF concentration (4.17+3.16 IU/l vs 3.46+3.69 IU/l, p&lt; 0.001), with a significantly higher mean number of VOC episodes per patient (3.2 vs 1.3, p&lt;0.001). The relative risk of VOC for patients with non- O blood groups was 1.87 (95% confidence interval 1.5 - 2.2, p&lt;0.001). However, the association of Rh (D) blood group of the patients and their plasma vWF:Ag levels on the risk of occurrence and frequency of VOC was not statistically significant (P = 0.155). SCA patients with non – O blood groups had more episodes and higher risk of VOC that were likely due to the effect of higher plasma vWF concentration. These results indicate that the non- O blood group is a risk factor for frequent VOC and an unfavourable prognostic marker in SCA. We hereby recommend that a large multicentre prospective study be carried out to definitely determine the impact of ABO, Rh and other blood groups on the overall clinical course of SCA.

Improving the Endoscopic Detection and Management of Gastric Intestinal Metaplasia Through Training: A Practical Guide

Improving the Endoscopic Detection and Management of Gastric Intestinal Metaplasia Through Training: A Practical Guide

Prevalence and risk factors of trimethoprim/sulfamethoxazole-related acute kidney injury in pediatric patients: an observational study from a public database.

BackgroundTrimethoprim/sulfamethoxazole (TMP/SMZ) is widely used in various clinical settings. Studies have revealed that it may cause acute kidney injury (AKI) in adults. However, the correlation between the use of TMP/SMZ and renal injury in pediatric patients is still unclear. This study aimed to identify the impact of TMP/SMZ on the occurrence of AKI in children.MethodsA retrospective observational study was conducted using data of patients treated with TMP/SMZ from the Paediatric Intensive Care clinical database. A newly developed criterion was used for the diagnosis of AKI, and univariate and multiple logistic regression analyses were performed to identify the risk factors of TMP/SMZ-related renal injury.ResultsA total of 113 patients were included. The prevalence of AKI was 21.2% (24/113). Univariate analysis indicated that the AKI group showed significantly higher baseline serum creatinine level (46.00 vs. 37.00 µmol/L; P=0.034) and in-hospital mortality rate [29.2% (7/24) vs. 9.0% (8/89); P=0.01] than that of the non-AKI group. Multivariate analysis revealed that the occurrence of AKI was significantly associated with increased baseline serum creatinine level [odds ratio (OR) =1.029; 95% CI: 1.006–1.053; P=0.014] and concurrent use of vancomycin (OR =5.349; 95% CI: 1.381–20.714; P=0.015). A proportion of 79.2% of patients (19/24) developed AKI within the first 10 days of TMP/SMZ use.ConclusionsElevated baseline serum creatinine level (≥40.25 µmol/L) and concurrent use of vancomycin were associated with the development of AKI in young patients. Further large multi-center prospective studies are necessary to confirm these relationships and validate their clinical significance.

Treatment of Light Chain Deposition Disease: A Systematic Review.

Light chain deposition disease (LCDD) is a rare hematologic disorder that can affect any organ but predominantly involves the kidneys. Existing literature is limited to case reports and small single-center retrospective series, explaining the lack of any treatment algorithms and management guidelines for patients with this disorder. In this systematic review of literature, we explored the role of standard and high-dose chemotherapy-autologous stem cell transplant for LCDD. A total of 11 studies were identified to evaluate the hematologic and renal responses to various treatment regimens. Autologous stem cell transplant and bortezomib-based regimens appear to have reasonable safety and efficacy for this rare hematologic disorder, albeit some statistical and analytical limitations. Large multicenter retrospective and prospective studies are needed to better elucidate the role of various chemotherapy regimens as well as autologous stem cell transplant for patients with LCDD.

Endoscopic ultrasound guided biliary drainage: literature review

Mantas Markauskas1 1Vilnius City Clinical Hospital, Vilnius, Lithuania Abstract Background. The first echoendoscope was introduced only as diagnostic tool in 1980 and it was mainly used to diagnose tumors, located in mediastinum, pancreas, liver or biliary tree. Therapeutic procedures using endoscopic ultrasound became possible only in 1991, when first linear echoendoscope and needle compatible with it were introduced. During past two decades echoendoscope and its accessories were improved, therefore complex therapeutic procedures using endoscopic ultrasound, such as gallbladder and biliary drainage, pancreatic duct and peripancreatic fluid drainage, pancreatic tumor ablation, brachytherapy, celiac plexus neurolysis, gastroenterostomy and many others, became possible. Aim. To discuss the recent literature describing endoscopic ultrasound guided biliary drainage. Procedure is discussed in terms of its indications, technique, results and adverse events. Methods. The literature search was performed in the PubMed database by entering relevant keywords in various combinations into the regular and advanced search fields, as well as using the bibliographies of the articles found. A total of 38 publications were found during the review, with 24 scientific publications based on the inclusion criteria. Conclusion. Literature indicates that endoscopic ultrasound guided biliary drainage can be safely performed on patients with biliary obstruction after failed endoscopic retrograde cholangiopancreatography. Present studies allow to conclude that endoscopic ultrasound guided biliary drainage is safe and efficient. However, in order to confirm endoscopic ultrasound guided biliary drainage as first-line treatment on patients with biliary obstruction after failed endoscopic retrograde cholangiopancreatography, further large prospective multicenter studies are needed. Keywords: endoscopic ultrasound, therapeutic procedures, biliary drainage.

Fried food consumption and the risk of pancreatic cancer: A large prospective multicenter study.

Background and aimsWhether fried food consumption is associated with the risk of pancreatic cancer remains elusive. We aimed to examine this association in a US population.MethodsA population-based cohort of 101,729 US adults was identified. Fried food consumption was assessed with a validated food frequency questionnaire. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Explanatory analyses were conducted to identify main contributor(s) to the observed association.ResultsDuring an average follow-up of 8.86 years (900871.2 person-years), 402 pancreatic cancer cases occurred. High consumption of total fried foods (deep-fried plus pan-fried foods; HRquartile4 vs. 1 0.71, 95% CI 0.51–0.99, Ptrend = 0.047) and deep-fried foods (HRquartile 4 vs. 1 0.64, 95% CI 0.47–0.88, Ptrend = 0.011), but not pan-fried foods (HRquartile 4 vs. 1 0.98, 95% CI 0.73–1.32; Ptrend = 0.815), was found to be associated with a reduced risk of pancreatic cancer in a non-linear dose–response manner, which was not modified by predefined stratification factors and persisted in sensitivity analyses. In explanatory analyses, only chip consumption was found to be inversely associated with the risk of pancreatic cancer; consistently, the initial significant associations between total fried food and deep-fried food consumption and the risk of pancreatic cancer changed to be non-significant after omitting or further adjusting for chip consumption.ConclusionConsumption of deep-fried foods, but not pan-fried foods, is inversely associated with the risk of pancreatic cancer in this US population. The role of deep-fried foods in reducing the risk of pancreatic cancer appears to be mainly attributable to chips. More studies are needed to confirm our findings in other populations and settings.

The Microbiological Etiology of Fracture-Related Infection.

PurposeFracture-related infection (FRI) is an important complication related to orthopaedic trauma. Although the scientific interest with respect to the diagnosis and treatment of FRI is increasing, data on the microbiological epidemiology remains limited. Therefore, the primary aim of this study was to evaluate the microbiological epidemiology related to FRI, including the association with clinical symptoms and antimicrobial susceptibility data. The secondary aim was to analyze whether there was a relationship between the time to onset of infection and the microbiological etiology of FRI.MethodsFRI patients treated at the University Hospitals of Leuven, Belgium, between January 1st 2015 and November 24th 2019 were evaluated retrospectively. The microbiological etiology and antimicrobial susceptibility data were analyzed. Patients were classified as having an early (<2 weeks after implantation), delayed (2-10 weeks) or late-onset (> 10 weeks) FRI.ResultsOne hundred ninety-one patients with 194 FRIs, most frequently involving the tibia (23.7%) and femur (18.6%), were included. Staphylococcus aureus was the most frequently isolated pathogen, regardless of time to onset (n=61; 31.4%), followed by S. epidermidis (n=50; 25.8%) and non-epidermidis coagulase-negative staphylococci (n=35; 18.0%). Polymicrobial infections (n=49; 25.3%), mainly involving Gram negative bacilli (GNB) (n=32; 65.3%), were less common than monomicrobial infections (n=138; 71.1%). Virulent pathogens in monomicrobial FRIs were more likely to cause pus or purulent discharge (n=45;54.9%; p=0.002) and fistulas (n=21;25.6%; p=0.030). Susceptibility to piperacillin/tazobactam for GNB was 75.9%. Vancomycin covered 100% of Gram positive cocci.ConclusionThis study revealed that in early FRIs, polymicrobial infections and infections including Enterobacterales and enterococcal species were more frequent. A time-based FRI classification is not meaningful to estimate the microbiological epidemiology and cannot be used to guide empiric antibiotic therapy. Large multicenter prospective studies are necessary to gain more insight into the added value of (broad) empirical antibiotic therapy.

P-17 Real-life use and long-term effectiveness results from CIREL – the multi-centre, observational study on irinotecan-eluting transarterial chemoembolization in CRLM

Transarterial chemoembolization (TACE) using irinotecan-eluting beads as a treatment approach for patients with unresectable colorectal cancer liver metastases (CRLM) is finding use beyond treatment guidelines but real-life data from multi-centre studies are lacking. The CIrse REgistry for LifePearl microspheres (CIREL, NCT03086096) is a prospective, Europe-wide, multi-centre, observational study on the real-life clinical outcomes of LifePearlTM microspheres TACE (LP-irinotecan TACE). The study was conducted by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). Eligible patients were adults with CRLM treated with LP-irinotecan TACE and were enrolled between February 2018 and August 2020. Baseline characteristics and treatment-related data were collected. The median follow-up inclusion according to reverse Kaplan-Meier was 19 months (95% CI: 17-23) during which data on overall survival (OS), progression-free survival (PFS), hepatic progression free survival (hPFS) and adverse events (AEs) graded according to CTCAE 4.03 were collected. 152 patients were enrolled in the study. Median age was 66 years and 39% were female. Eastern Cooperative Oncology Group was 0 in 59%; 1 in 34%; and ≥2 7%; liver involvement was 50% in 7% of patients. 84% had progressive disease at baseline. 42% received 1 line, 40% 2 or more lines and 18% no line of previous systemic therapy. 91 (60%) patients experienced 266 adverse events within 24 hours after a TACE session, of which 19 (7%) were grade 3 or higher in 12 (8%) patients. The complete treatment plan was administered in 80% of patients and no treatment-related deaths were reported. The median OS for the whole cohort was 13.0 months (95% CI 10.5-15.0), median hPFS was 6.2 months (95% CI 5.1-6.9) (hPFS rate at 9 months: 29%) and median PFS was 4.7 months (95% CI 3.8-5.3) (PFS rate at 9 months: 13%). We could observe statistically significant differences (p=0.005) in OS for different treatment strategies. When LP-irinotecan TACE was used as a first-line treatment or as consolidation after response to first-line treatment (41, 27%), the median OS was 17 months (95% CI 12.7-23.1). When it was used in combination with ablation (with curative intent) (19, 13%), the median OS was 17.1 (95% CI 10.5-NA). When chemo-refractory patients still eligible for further systemic treatment were treated with LP-irinotecan TACE (41, 27%), the median OS was 10.3 months (95% CI 7.5-14.0). Salvage treatment of chemo-refractory patients not eligible for further systemic treatment (46, 30%) resulted in the smallest median OS of 9.0 months (95% CI 6.8-13.0). For 5 (3%) patients LP-irinotecan TACE was used after response to second-line treatment. The results from this large prospective multi-centre observational study show that in a real-world context, LP-irinotecan TACE is well tolerated with low occurrences of severe adverse events and patients with CRLM receiving LP-irinotecan have a median overall survival comparable to gold-standard systemic treatment for later lines.