Quality of life assessment in diffuse large B-cell lymphoma (DLBCL) in REFLECT: a prospective, non-interventional, multicenter, German study, assessing Sandoz rituximab in combination with CHOP.

Health-related quality of life (HRQoL) data are important indicators of health status in patients with lymphoma. The objective of this analysis was to assess the impact of treatment with Sandoz rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on HRQoL in treatment-naïve adult patients with diffuse large B-cell lymphoma (DLBCL) included in the prospective, real-world REFLECT study. REFLECT is the first prospective study to assess HRQoL in patients with DLBCL treated with a rituximab biosimilar. HRQoL was assessed via the patient-reported European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire at baseline, mid-treatment (month 3), end of treatment (month 6), and follow-up (months 9 and 12). Subgroup analyses were performed to evaluate the influence of baseline characteristics on HRQoL, and associations between baseline HRQoL and treatment response. HRQoL was assessed in 169 patients. Mean global health status score remained stable from baseline (54.8) to mid-treatment (month 3; 54.7), before steadily improving through to end of treatment (month 6; 61.4), and follow-up month 9 (64.9) and month 12 (68.8). Similar trends were observed across most functional and symptom subscales. Higher cognitive, physical, or role functioning, and less appetite loss, diarrhea, fatigue, or pain at baseline, were all associated with an improved likelihood of reaching a complete versus partial response at the end of treatment. Overall, these findings confirm the HRQoL benefits of R-CHOP therapy in treatment-naïve adult patients with DLBCL, and suggest that baseline HRQoL may be predictive of treatment response.

Free Flaps in Patients with Advanced Arteriosclerosis of the Tibial Vessels: Mini Vein Graft to the Peroneal Artery.

Lower extremity reconstruction with free flaps in patients with only peroneal artery runoff remains a challenge. Here, we present a novel technique for reconstruction of medial defects in the distal leg using a medial approach to the peroneal artery and a short interposition vein graft anastomosed end to side to the peroneal artery. A retrospective, single-center study was performed including all patients who underwent lower extremity reconstruction with free flaps anastomosed to the peroneal artery using a mini vein graft from November 2020 to March 2022. The primary outcome measure was limb salvage. Secondary endpoints were flap survival and postoperative complications. Seven patients received lower extremity free flap reconstruction with a mini vein graft to the peroneal artery. Flap loss rate was 0%. Limb salvage was achieved in five patients (71%). At 6-month follow-up, all patients were ambulatory. One patient died 1 month after surgery due to heart failure. Mini vein graft to the peroneal artery allows reliable and safe free flap reconstruction of distal leg defects in patients with only peroneal artery runoff.

Final Results from RIBBIT: A Randomized Phase III Study to Evaluate Efficacy and Quality of Life in Patients with Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer Receiving Ribociclib in Combination with Endocrine Therapy or Chemotherapy with or without Bevacizumab in the First-Line Setting.

Background: We investigated the efficacy and health-related quality of life (HRQoL) in patients receiving either ribociclib plus endocrine therapy (ET) or chemotherapy with/without bevacizumab as first-line treatment of metastatic hormone receptor (HR)-positive, HER2-negative breast cancer (BC). Patients and Methods: In this randomized, phase III study (RIBBIT), 38 patients diagnosed with metastatic HR-positive, HER2-negative BC with presence of visceral metastases recruited between May 2018 and December 2020 were randomly assigned in a 1:1 ratio to either arm A (ribociclib + ET) or arm B (chemotherapy with/without bevacizumab) at 12 sites in Germany. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS), patient-reported HRQoL, and frequency and type of adverse events. During study conduction, the recruitment rate was persistently and considerably lower than originally expected. Therefore, the recruitment was ended prematurely. The study was initially designed to enroll and randomize 158 patients. Results: Median [95% CI] PFS was 27.3 months [19.1 - NA, parameter not estimable] in arm A and 15.8 months [8.2 - NA] in arm B. Complete responses were achieved only in arm A (n = 2, 10.5%). The ORR [95% CI] between arm A (57.9% [33.5-79.7]) and arm B (52.6% [28.9-75.6]) was comparable. Median OS [95% CI] was not reached in arm A, while in arm B median OS was 28.4 months [25.0 - NA]. Patients in arm A reported less burden by side-effects. No new safety signals emerged. Conclusion: Treatment of patients with visceral metastatic HR-positive, HER2-negative BC with ribociclib in combination with ET showed a tendency toward a more favorable clinical outcome. Despite small numbers of patients and sites, this head-to-head comparison with chemotherapy supports the use of ribociclib with ET in patients with visceral metastasis at risk of fast disease progression.

Low incidence of tumor lysis syndrome in elderly patients with chronic lymphocytic leukemia treated with venetoclax under real-world conditions: results from the prospective observational VeRVe study.

Venetoclax is active in both frontline and relapsed/refractory settings for the treatment of chronic lymphocytic leukemia (CLL). Although the prevalence and severity of tumor lysis syndrome (TLS) are well characterized in clinical trials, laboratory and clinical TLS remain relatively unexplored in real-world clinical practice.In this prospective, real-world observational study, we aimed to determine the incidence and outcomes of TLS in patients with CLL receiving venetoclax outside a clinical trial. The study (VeRVe) was conducted in centers in Austria, Germany, and Switzerland.Two hundred and thirty-nine patients were treated according to local label with at least one dose of venetoclax. Patient demographics, baseline characteristics, and blood chemistry at baseline were documented, and descriptive statistical analyses were conducted.Seventy eight patients (33%) were treated with venetoclax monotherapy, 101 (42%) with venetoclax in combination with rituximab and 60 (25%) with venetoclax in combination with obinutuzumab. In all cases, the TLS risk mitigation strategy adhered to the ramp-up protocol. Median age was 73 years and 66% of patients were male. The majority of patients (75%) had relapsed/refractory CLL, 63/192 (32.8%) patients tested had a del(17p) and 93/134 (69.4%) patients tested had unmutated immunoglobulin heavy chain variable region gene (IGHV). Clinical TLS occurred in 5 patients (2.1%) and laboratory TLS occurred in 15 patients (6.3%). Ten patients received specific treatment, of which 6 were hospitalized. There were no deaths due to a TLS event and venetoclax was well-tolerated. Of the 5 clinical TLS events reported, none were fatal or resulted in renal failure (NCT03342144, registered on Nov 10, 2017).

A Novel Percutaneous Technique for Aorto-Iliac Thrombectomy without the Risk of Embolization.

Classic surgical thrombectomy of the aorta and iliac arteries through an incision in the groin vessels harbors the risk of embolization to the viscero-renal as well as hypogastric arteries, while percutaneous endovascular thrombectomy techniques can lead to peripheral embolization to the lower limbs. Therefore, we describe a novel, percutaneous technique that tackles the above issues. Furthermore, we also present our initial experience using the technique. The principle of the technique is to percutaneously place large-bore sheaths in the iliac arteries that deliberately occlude the latter to protect the lower limbs from embolization. Through one of these sheaths, over wire Fogarty® catheters can be placed and inflated in the ostia of the coeliac trunk, superior mesenteric artery, renal arteries, and hypogastric arteries as needed. A large thrombectomy balloon catheter is then used to bring any aorto-iliac thrombus into the sheaths, whereafter the thrombus is removed from the sheaths by simply deflating their valves. Additional endovascular procedures of the aorto-iliac branches can be performed as needed. We report nine procedures in 8 patients (4 males and 4 females) with a median age of 63 (53-68.5). Additional endovascular procedures were performed in 6 (66.7%) procedures. All but one procedure were technically successful, and all patients had palpable foot pulses on completion of the procedures, while no patient had clinical signs of peripheral embolization. This technique is a very valid addition to the vascular surgeon's armamentarium when treating aorto-iliac thrombotic events because it is minimally invasive while still protecting against embolization and offering the flexibility to perform a wide range of additional endovascular procedures where needed.

REFLECT: prospective multicenter non-interventional study evaluating the effectiveness and safety of Sandoz rituximab (SDZ-RTX; Rixathon®) in combination with CHOP for the treatment of patients with previously untreated CD20-positive diffuse large B-cell lymphoma.

Background: REFLECT is the first prospective study of Sandoz biosimilar rituximab (SDZ-RTX) in patients with diffuse large B-cell lymphoma (DLBCL). Objective: To evaluate the 2-year effectiveness and safety of SDZ-RTX as first-line treatment for DLBCL. Design: Real-world, multicenter, open-label, single-arm, non-interventional, post-approval study of SDZ-RTX in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with treatment-naïve CD20­positive DLBCL. Methods: Treatment-naïve, CD20-positive adult patients (⩾18 years) with DLBCL eligible for therapy with R-CHOP were treated with SDZ-RTX-CHOP every 2 or 3 weeks for 6-8 cycles. The effectiveness of SDZ-RTX was measured by the complete response (CR) rate at the end of R-CHOP treatment, as assessed by the treating physician. Progression-free survival (PFS) was assessed at 24 months. Results: A total of 169 patients [52.1% female, median (range) age 70 (24-94) years] with DLBCL were included in the full analysis set. At baseline, 19.5% and 24.3% of patients had Ann Arbor disease stage III or IV, respectively, and most patients (80.5%) had Eastern Cooperative Oncology Group Performance Status of 0 or 1. A total of 100 (59.2%) patients completed the 24-month observation period. In total, 110 [65.1%; 95% confidence interval (CI): 57.4-72.3] patients achieved CR as best response and 50 (29.6%; 95% CI: 22.8-37.1) patients achieved partial response. Overall best response rate was 94.7% (95% CI: 90.1-97.5). One-year PFS was 84.9% (95% CI: 78.2-89.6), while 2-year PFS was 78.5% (95% CI: 70.9-84.4); median PFS was not reached within the observational period. A total of 143 (84.6%) patients experienced ⩾1 adverse event, 53 (31.4%) of which were suspected to be related to study drug. Conclusion: This real-world, 2-year study reconfirms that first-line treatment of CD20-positive DLBCL with R-CHOP using SDZ-RTX is effective and well tolerated. Registration: N/A.

REFLECT: A study evaluating Sandoz biosimilar rituximab (Rixathon ^® ) in combination with CHOP for the treatment of patients with previously untreated diffuse large B-cell lymphoma Why was this study done? • Biosimilars are biologic medicines that are highly similar to a reference biologic medicine that is already approved and has been used in patients for several years. • The REFLECT study was the first study of a biosimilar medicine (Sandoz biosimilar rituximab) in patients with a type of lymphatic cancer called diffuse large B-cell lymphoma (DLBCL). What did the researchers do? • Sandoz biosimilar rituximab was given as part of the standard treatment (cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP) in patients with DLBCL who had not received treatment before. • The researchers aimed to evaluate how well Sandoz biosimilar rituximab worked over a 2-year period. • The researchers also aimed to look at the safety of Sandoz biosimilar rituximab. • Patients with DLBCL had to be ⩾18 years of age, in need of treatment, and were classed as suitable for treatment with R-CHOP by their doctor. • Patients were treated with R-CHOP including Sandoz biosimilar rituximab every 2 or 3 weeks for 6­8 cycles. What did the researchers find? • A total of 169 patients with DLBCL were included in the study. • Just over half (52%) were female and the average age was 67 years. • Nearly 6 out of 10 (59%) patients completed the 2-year study. • More than 6 out of 10 (65%) patients achieved complete response and 3 out of 10 (30%) achieved partial response. • The overall response rate was 95%. • One-year progression-free survival was 85%, and 2-year progression-free survival was 79%. • Regarding safety, 85% of patients experienced at least one adverse event; just over 3 out of 10 (31%) of these were suspected to be related to the study drug. What do the findings mean? • This 2-year study shows that R-CHOP including Sandoz biosimilar rituximab is effective and well tolerated as the first treatment given to patients with DLBCL.

Long-term outcomes of perioperative myocardial infarction/injury after non-cardiac surgery.

AIMS: Perioperative myocardial infarction/injury (PMI) following non-cardiac surgery is a frequent cardiac complication. Better understanding of the underlying aetiologies and outcomes is urgently needed. METHODS AND RESULTS: Aetiologies of PMIs detected within an active surveillance and response programme were centrally adjudicated by two independent physicians based on all information obtained during clinically indicated PMI work-up including cardiac imaging among consecutive high-risk patients undergoing major non-cardiac surgery in a prospective multicentre study. PMI aetiologies were hierarchically classified into 'extra-cardiac' if caused by a primarily extra-cardiac disease such as severe sepsis or pulmonary embolism; and 'cardiac', further subtyped into type 1 myocardial infarction (T1MI), tachyarrhythmia, acute heart failure (AHF), or likely type 2 myocardial infarction (lT2MI). Major adverse cardiac events (MACEs) including acute myocardial infarction, AHF (both only from day 3 to avoid inclusion bias), life-threatening arrhythmia, and cardiovascular death as well as all-cause death were assessed during 1-year follow-up. Among 7754 patients (age 45-98 years, 45% women), PMI occurred in 1016 (13.1%). At least one MACE occurred in 684/7754 patients (8.8%) and 818/7754 patients died (10.5%) within 1 year. Outcomes differed starkly according to aetiology: in patients with extra-cardiac PMI, T1MI, tachyarrhythmia, AHF, and lT2MI 51%, 41%, 57%, 64%, and 25% had MACE, and 38%, 27%, 40%, 49%, and 17% patients died within 1 year, respectively, compared to 7% and 9% in patients without PMI. These associations persisted in multivariable analysis. CONCLUSION: At 1 year, most PMI aetiologies have unacceptably high rates of MACE and all-cause death, highlighting the urgent need for more intensive treatments. STUDY REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02573532.

Detrimental consequences after intimal disruption of subclavian artery during transcathether aortic valve implantation.

BACKGROUND: TAVI via the left subclavian artery is considered a bail-out strategy in cases where a transfemoral approach is not feasible. However, since this route is only scarcely used, major complications can arise. We describe such an adverse course and present our proceeding. CASE PRESENTATION: A 65-year-old man with severe aortic valve stenosis (AS) was referred for transcatheter aortic valve implantation (TAVI) via left subclavian artery. After uneventful deployment of the TAVI prosthesis, consequent valve assessment with transeosophageal echocardiography and angiography showed a highly mobile and tubular structure shifting within the valve. We went for a surgical extraction via sternotomy on cardiopulmonary bypass (CPB). A 6 cm longish intimal cylinder was hassle-free extracted. 4 days postoperatively the left sided radial pulse was missing. In a subsequent computed tomography angiography (CTA) scan a proximal dissection as well as an intimal flap, causing a subtotal stenosis of the left subclavian artery, was detected. Consecutively the intimal cylinder was removed using a Fogarty-balloon. Pre-discharge control revealed recurrence of peripheral radial pulse and an unimpeded function of the TAVI prosthesis. The patient presented no sequela at discharge. CONCLUSION: Though TAVI is a well-advanced technique complications are not completely avertable. It is thus advisable to have patients discussed in the heart team encompassing all potentially involved specialties.

Ultrasound-Guided Percutaneous Arteriovenous Fistula Creation Simulation Training in a Lifelike Flow Model.

Objectives: To assess the feasibility and training effect of simulation training for ultrasound-guided percutaneous arteriovenous fistula (pAVF) creation in a lifelike flow model. Methods: Twenty vascular trainees and specialists were shown an instructional video on creating a pAVF in a dedicated flow model and then randomized to a study or control group. The procedure was divided into five clearly defined steps. Two observers rated the performance on each step, and the time to perform the exercise was recorded. The study group participants underwent supervised hands-on training on the model before performing a second rated pAVF creation. All participants subsequently completed a feedback questionnaire. Results: After supervised simulation training, the study groups participants increased their mean performance rating from 2.2 ± 0.9 to 3.2 ± 0.7. A mean of 3.8 ± 0.8 procedure steps was accomplished independently (control group 2.1 ± 1.4; p < 0.05). The time taken to perform the procedure was 15.6 ± 3.8 min in the study group (control group 27.2 ± 7.3, p < 0.05). The participants with previous experience in ultrasound-guided vascular procedures (n = 5) achieved higher overall mean scores 3.0 ± 0.8 and accomplished more steps without assistance (2.0 ± 1.0) during the simulation training compared to their inexperienced peers (1.5 ± 0.3 and 0.8 ± 0.4, respectively). The feedback questionnaire revealed that the study group participants strongly agreed (n = 7) or agreed (n = 3) that training on the simulation model improved their skills regarding catheter handling. Conclusions: The study group participants increased their overall performance after training on the simulator. More experienced attendees performed better from the beginning, indicating the model to be lifelike and a potential skill assessment tool. Simulation training for pAVF creation using a lifelike model may be an intermediate step between acquiring ultrasound and theoretical pAVF skills and procedure guidance in theatre. However, this type of training is limited by its reliance on the simulator quality, demonstration devices and costs.

Therapeutic arteriogenesis by factor-decorated fibrin matrices promotes wound healing in diabetic mice.

Chronic wounds in type-2 diabetic patients present areas of severe local skin ischemia despite mostly normal blood flow in deeper large arteries. Therefore, restoration of blood perfusion requires the opening of arterial connections from the deep vessels to the superficial skin layer, that is, arteriogenesis. Arteriogenesis is regulated differently from microvascular angiogenesis and is optimally stimulated by high doses of Vascular Endothelial Growth Factor-A (VEGF) together with Platelet-Derived Growth Factor-BB (PDGF-BB). Here we found that fibrin hydrogels decorated with engineered versions of VEGF and PDGF-BB proteins, to ensure protection from degradation and controlled delivery, efficiently accelerated wound closure in diabetic and obese db/db mice, promoting robust microvascular growth and a marked increase in feeding arterioles. Notably, targeting the arteriogenic factors to the intact arterio-venous networks in the dermis around the wound was more effective than the routine treatment of the inflamed wound bed. This approach is readily translatable to a clinical setting.

Long-Term Efficacy and Safety of Luspatercept for Anemia Treatment in Patients With Lower-Risk Myelodysplastic Syndromes: The Phase II PACE-MDS Study.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Luspatercept has high clinical activity in patients with transfusion-dependent lower-risk myelodysplastic syndromes (LR-MDS) and ring sideroblasts (RS) relapsed or refractory to erythropoietin. We report long-term luspatercept safety and efficacy in 108 patients with LR-MDS in the PACE-MDS study, including 44 non-RS and 34 non-transfusion-dependent or previously untreated patients. The primary end point was safety. Secondary end points included rates of hematologic improvement (HI) erythroid (HI-E), HI neutrophil, and HI platelet. Exploratory end points included erythropoiesis biomarker quantitation and mutation data. Median duration of luspatercept exposure was 315 days (range, 21-1,934 days). No new safety signals emerged. HI-E was observed in 53.7% of patients, including 36.4% of non-RS and 70.6% of non-transfusion-dependent patients. HI neutrophil and HI platelet were observed in 33.3% and 9.5% of patients, respectively. An almost three-fold increase in bone marrow late to early progenitor cell ratio accompanied HI-E response, irrespective of RS status. Lower baseline erythropoietin levels in non-RS patients (69.6 v 623.3 IU/L; P = .0077) and higher late to early erythroid progenitor cell ratio (10.44 v 4.48; P = .0106) in RS patients were associated with HI-E. This study highlights luspatercept's effects across LR-MDS subtypes, including untreated MDS-RS, serving as a platform for future trials.

Cardiovascular imaging following perioperative myocardial infarction/injury.

Patients developing perioperative myocardial infarction/injury (PMI) have a high mortality. PMI work-up and therapy remain poorly defined. This prospective multicenter study included high-risk patients undergoing major non-cardiac surgery within a systematic PMI screening and clinical response program. The frequency of cardiovascular imaging during PMI work-up and its yield for possible type 1 myocardial infarction (T1MI) was assessed. Automated PMI detection triggered evaluation by the treating physician/cardiologist, who determined selection/timing of cardiovascular imaging. T1M1 was considered with the presence of a new wall motion abnormality within 30 days in transthoracic echocardiography (TTE), a new scar or ischemia within 90 days in myocardial perfusion imaging (MPI), and Ambrose-Type II or complex lesions within 7 days of PMI in coronary angiography (CA). In patients with PMI, 21% (268/1269) underwent at least one cardiac imaging modality. TTE was used in 13% (163/1269), MPI in 3% (37/1269), and CA in 5% (68/1269). Cardiology consultation was associated with higher use of cardiovascular imaging (27% versus 13%). Signs indicative of T1MI were found in 8% of TTE, 46% of MPI, and 63% of CA. Most patients with PMI did not undergo any cardiovascular imaging within their PMI work-up. If performed, MPI and CA showed high yield for signs indicative of T1MI.Trial registration: https://clinicaltrials.gov/ct2/show/NCT02573532 .

Open aneurysm repair in patients with concomitant abdominal aortic aneurysm and aorto-iliac occlusive disease is associated with a high mortality and surgical complication rate.

AIM OF THE STUDY: To evaluate whether the outcome after open aneurysm repair combined with aorto-femoral bypass in patients with concomitant abdominal aortic aneurysm (AAA) and aorto-iliac occlusive disease (AIOD) is inferior to open aneurysm repair for isolated AAA or aorto-femoral bypass for isolated AIOD. METHODS: We performed a retrospective analysis of 30-day mortality, 1-year mortality and surgical complications of consecutive patients undergoing elective aneurysm repair, aorto-femoral bypass or a combination of these at two vascular surgery departments from 2003 to 2013. Potential risk factors were investigated by multivariable analysis. RESULTS: Overall, 511 patients underwent open repair for isolated AAA, 104 aorto-femoral bypass for isolated AIOD and 46 open AAA repair combined with aorto-femoral bypass for concomitant AAA and AIOD. Surgical complications occurred in 17% of AAA, 23% of AIOD and 37% of combined patients (odds ratio [OR] combined vs AAA 2.76, 95% confidence interval [CI] 1.43-5.34; p = 0.003). Colon ischaemia occurred in 3.7% of AAA, 2.9% of AIOD and 13% of combined patients (incicidence rate ratio [IRR] combined vs AAA 3.27, 95% CI 1.37-7.81; p = 0.01). The 30-day mortality was 3.1% in AAA, 4.8% in AIOD, and 11% in combined patients (IRR combined vs AAA 3.17, 95% CI 1.26-7.96; p = 0.01). One-year mortality was 5.7% in AAA, 5.8% in AIOD and 15% in combined patients (IRR combined vs AAA 2.50, 95% CI 1.17-5.35; p = 0.02). CONCLUSIONS: Combined AAA repair and aorto-femoral bypass has a significantly higher 30-day mortality and postoperative complication rate than isolated AAA repair. Patients with concomitant AAA and AIOD thus represent a high-risk population, which should be considered when deciding on the indication for AAA treatment.

Robust Angiogenesis and Arteriogenesis in the Skin of Diabetic Mice by Transient Delivery of Engineered VEGF and PDGF-BB Proteins in Fibrin Hydrogels.

Non-healing ulcers are a serious complication of diabetes mellitus and a major unmet medical need. A major cause for the lack of healing is the impairment of spontaneous vascularization in the skin, despite mostly normal blood flow in deeper large vessels. Therefore, pro-angiogenic treatments are needed to increase therapeutic perfusion by recruiting new arterial connections (therapeutic arteriogenesis). Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis in physiology and disease, but exploitation of its therapeutic potential requires careful control of its dose distribution in tissue. Co-delivery of platelet derived growth factor-BB (PDGF-BB) has been shown to expand the therapeutic window of VEGF and also improve associated arteriogenesis. We used a highly controlled protein delivery system, based on a clinically applicable fibrin-based platform, to investigate the angiogenic and arteriogenic potential of engineered versions (TG-) of VEGF and PDGF-BB proteins in the skin of diabetic and obese db/db mice. Intradermal delivery of therapeutically relevant doses of TG-VEGF and TG-PDGF-BB induced robust growth of new microvascular networks with similar efficacy as in normal littermate control mice. Further, TG-PDGF-BB prevented the formation of aberrant vascular enlargements by high TG-VEGF levels. As fibrin was degraded after the first week, the induced angiogenesis mostly regressed by 4 weeks, but it promoted effective arteriogenesis in the dermal layer. Therefore, controlled co-delivery of TG-VEGF and TG-PDGF-BB recombinant proteins is effective to induce angiogenesis and arteriogenesis in diabetic mouse skin and should be further investigated to promote diabetic wound healing.

Adherence to the European Society of Cardiology/European Society of Anaesthesiology recommendations on preoperative cardiac testing and association with positive results and cardiac events: a cohort study.

BACKGROUND: European Society of Cardiology/European Society of Anaesthesiology (ESC/ESA) guidelines inform cardiac workup before noncardiac surgery based on an algorithm. Our primary hypotheses were that there would be associations between (i) the groups stratified according to the algorithms and major adverse cardiac events (MACE), and (ii) over- and underuse of cardiac testing and MACE. METHODS: This is a secondary analysis of a multicentre prospective cohort. Major adverse cardiac events were a composite of cardiac death, myocardial infarction, acute heart failure, and life-threatening arrhythmia at 30 days. For each cardiac test, pathological findings were defined a priori. We used multivariable logistic regression to measure associations. RESULTS: We registered 359 MACE at 30 days amongst 6976 patients; classification in a higher-risk group using the ESC/ESA algorithm was associated with 30-day MACE; however, discrimination of the ESC/ESA algorithms for 30-day MACE was modest; area under the curve 0.64 (95% confidence interval: 0.61-0.67). After adjustment for sex, age, and ASA physical status, discrimination was 0.72 (0.70-0.75). Overuse or underuse of cardiac tests were not consistently associated with MACE. There was no independent association between test recommendation class and pathological findings (P=0.14 for stress imaging; P=0.35 for transthoracic echocardiography; P=0.52 for coronary angiography). CONCLUSIONS: Discrimination for MACE using the ESC/ESA guidelines algorithms was limited. Overuse or underuse of cardiac tests was not consistently associated with cardiovascular events. The recommendation class of preoperative cardiac tests did not influence their yield. CLINICAL TRIAL REGISTRATION: NCT02573532.

Pooled-analysis of Lipegfilgrastim Effectiveness and Safety Among Patients With Blood Malignancies in the Real-world Setting.

BACKGROUND/AIM: The aim of this report was to summarize the real-world experience with lipegfilgrastim as a neutropenia prophylaxis in a large cohort of lymphoma patients receiving immuno-, chemo-therapy. PATIENTS AND METHODS: Observational clinical data were derived from two phase IV studies (NADIR and LEOS) with similar protocols conducted in eight European countries for 677 patients. RESULTS: Categories for risk of febrile neutropenia were predominantly high (54.5%) or intermediate (38.8%). The most frequent patient-associated risk factors were age >65 years (54.4%), female sex (43.9%), hemoglobin <12 g/dL (25.3%), and prior febrile neutropenia (14.5%). The incidence of febrile neutropenia and Grade 3/4 neutropenia was 5.9% and 14.6%, respectively over all cycles of immuno-, chemo-therapy (n=3018). Adverse drug reactions occurred in 74 patients (10.9%), with bone pain (2.2%), myalgia (1.8%), and pyrexia (1.0%) occurring in ≥1% of patients. CONCLUSION: Lipegfilgrastim prophylaxis against chemotherapy-induced neutropenia was effective and well tolerated in lymphoma patients in real-world clinical practice.

Arteriovenous Loops Enable Free Tissue Transfer With Otherwise Inadequate Local Donor and Recipient Vessels.

BACKGROUND/AIM: Free flap reconstruction with damaged or diseased vessels is a challenging problem. We describe our case series using an arteriovenous loop or bypass surgery with free flaps for complex defect reconstructions at the lower extremity and the pelvic region. PATIENTS AND METHODS: In this single-center retrospective cohort study 11 consecutive patients (mean age=73 years, range=53-88 years) were operated on, between June 2016 and August 2018. Patients were reconstructed with free gracilis flaps (n=8), free latissimus dorsi flap (n=1) and chimeric scapular flap (n=1), respectively. RESULTS: The mean loop length was 30 cm (range=12-40 cm). The loop/bypass revision rate was 27% (3/11), and the overall flap loss rate was 20% (2/10). After a mean follow-up time of 17 months (range=12-24 months), the limb salvage rate was 75% (6/8). CONCLUSION: We successfully reconstructed complex defects with poor recipient vessels using arteriovenous loops or bypass surgery and free flaps.

[Superior mesenteric vein aneurysm, a rare case]. / Anévrisme de la veine mésentérique supérieure, un cas rare.

We report the case of a 67-year-old man presenting with abdominal pain due to acute thrombosis of an aneurysm of the superior mesenteric vein. It was treated conservatively by a combination of anticoagulation and monitoring by serial imaging after multidisciplinary discussion. With more than one year of follow-up, no aneurysm growth was observed. Mesenteric vein aneurysm is a rare vascular dilatation, which was first described in 1982 and since then 17 cases have been reported. There are congenital and acquired hypotheses regarding their etiology. If asymptomatic, conservative management is recommended. Monitoring is important because of potential complications (thrombosis, portal hypertension, adjacent organs compression and rupture of aneurysm), which may mandate surgical management.

Cet article rapporte un cas rare d'anévrisme thrombosé de la veine mésentérique supérieure chez un homme de 67 ans, diag nostiqué à la suite de douleurs abdominales aspécifiques. Après discussion multidisciplinaire, une anticoagulation et une surveillance par imagerie sont effectuées. Avec plus d'une année de recul, l'anévrisme reste stable. L'anévrisme de la veine mésentérique supérieure est une pathologie exceptionnelle décrite 17 fois dans la littérature depuis 1982. Il existe des hypothèses étiologiques congénitales et acquises. En l'absence de symptôme, un traitement conservateur et une surveillance sont recommandés en raison de complications potentielles (thrombose, hypertension portale, compression d'organes adjacents et rupture d'anévrisme). Une prise en charge chirurgicale est discutée en cas de manifestations cliniques.

Incidence of major adverse cardiac events following non-cardiac surgery.

AIMS: Major adverse cardiac events (MACE) triggered by non-cardiac surgery are prognostically important perioperative complications. However, due to often asymptomatic presentation, the incidence and timing of postoperative MACE are incompletely understood. METHODS AND RESULTS: We conducted a prospective observational study implementing a perioperative screening for postoperative MACE [cardiovascular death (CVD), acute heart failure (AHF), haemodynamically relevant arrhythmias, spontaneous myocardial infarction (MI), and perioperative myocardial infarction/injury (PMI)] in patients at increased cardiovascular risk (≥65 years OR ≥45 years with history of cardiovascular disease) undergoing non-cardiac surgery at a tertiary hospital. All patients received serial measurements of cardiac troponin to detect asymptomatic MACE. Among 2265 patients (mean age 73 years, 43.4% women), the incidence of MACE was 15.2% within 30 days, and 20.6% within 365 days. CVD occurred in 1.2% [95% confidence interval (CI) 0.9-1.8] and in 3.7% (95% CI 3.0-4.5), haemodynamically relevant arrhythmias in 1.2% (95% CI 0.9-1.8) and in 2.1% (95% CI 1.6-2.8), AHF in 1.6% (95% CI 1.2-2.2) and in 4.2% (95% CI 3.4-5.1), spontaneous MI in 0.5% (95% CI 0.3-0.9) and in 1.6% (95% CI 1.2-2.2), and PMI in 13.2% (95% CI 11.9-14.7) and in 14.8% (95% CI 13.4-16.4) within 30 days and within 365 days, respectively. The MACE-incidence was increased above presumed baseline rate until Day 135 (95% CI 104-163), indicating a vulnerable period of 3-5 months. CONCLUSION: One out of five high-risk patients undergoing non-cardiac surgery will develop one or more MACE within 365 days. The risk for MACE remains increased for about 5 months after non-cardiac surgery. TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT02573532.