Peripheral Disease Research Articles

Acupoint catgut embedding for the treatment of sciatica: A protocol for a systematic review.

Background:Sciatica is a common and frequent peripheral neuropathic pain disease, which causes a great burden on peoples life. Recently, acupoint catgut embedding (ACE) has been widely applied for treating sciatica in China, however, there is no enough evidence to prove the efficiency and safety of ACE for sciatica. Our study aims to evaluate the efficiency and safety of ACE for sciatica.Methods and analysis:Searches of the Cochrane Library, PubMed, Springer Medline, EMBASE, China National Knowledge Infrastructure (CNKI), Wan-Fang Data (WANFANG), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP databases) will be performed from inception to November 2020. The main outcomes are the pain intensity and the whole efficiency assessment. The secondary outcomes will include Oswestry Disability Index (ODI), life quality, physical examination, and adverse events. Two reviewers will separately conduct the study selection, data extraction and study quality assessments. RevMan 5.3 software will be used for meta-analysisResults:This study will provide an evidence-based review of acupoint catgut embedding therapy for sciatica according to the pain intensity, the whole efficiency assessment, life quality, DOI index and adverse events.Conclusions:This systematic review will present the current evidence for acupoint catgut embedding therapy for sciatica.Ethics and dissemination:Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.Trial registration number:INPLASY2020110087.

A study of angiogenic activity of “Hibiscus rosa-sinensis Linn.” using chick chorioallantoic membrane model

Background: Nowadays, the search for new pharmacotherapy from medicinal plants to treat the peripheral vascular disease, chronic wound healing, and ischemic heart diseases was significantly increased. Aim and Objective: The current study was done to evaluate the angiogenic activity of ethanolic extract of Hibiscus rosa-sinensis Linn. (EEHR) using chick chorioallantoic membrane (CAM) model. Materials and Methods: The angiogenic activity of H. rosa-sinensis Linn. (50, 100, 200, and 300 mg/egg) in chick embryos was assessed using chick CAM assay. Pyruvic acid 300 mg/egg was used as standard drug which is used to promote the blood vessels growth. Results: The outcome of the study confirmed that H. rosa-sinensis contains active constituents (vitamins, proteins, and phytosterols), which possess angiogenic activity and these are probably related to the inhibition of myocardial infarction, peripheral diseases, and chronic wounds. It was exhibited angiogenic activity by triggered neovascularization in concentration dependent manner. Conclusion: We concluded that EEHR flower possesses significant angiogenic activity and these new blood vessels are participated in circulation of blood cells in chick egg.

Prevalence and distribution of peripheral musculoskeletal manifestations in spondyloarthritis including psoriatic arthritis: results of the worldwide, cross-sectional ASAS-PerSpA study

ObjectivesTo characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world.MethodsCross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA),...

Variation in four limb blood pressure and central aortic pressure: An observational study on North Indian semi-urban males

Background: Measurement of ankle pressure along with measurement of both arm blood pressure (BP) can be helpful to for calculation of ankle-brachial index (ABI) and detection of early peripheral diseases among the patients. Non-invasive measurement of central aortic pressures is possible as considered as better marker for central hemodynamic situation. Studies on normal subjects are scant. Aim and Objectives: The present study was conducted to evaluate the difference of BP in four limbs obtained from simultaneous recording and evaluate the association with central aortic BP components and peripheral BP components in normal Indian healthy male subjects. Materials and Methods: The study was conducted in the Department of Physiology of Mayo Institute of Medical Sciences, Barabanki, with 25 healthy clinically normal subjects. Four limb BP was recorded and ABI and central aortic pressures were estimated using periscope arterial health and cardiovascular analysis system. Results: Ankle systolic BP (SBP) was significantly high for both sides. Inter-ankle mean arterial pressure difference found to be significantly associated with ABI. Central aortic systolic pressure was found to be lower than the peripheral SBP. Conclusion: Ankle BP measurement to be considered for early detection of peripheral arterial disease and should be performed routinely in hypertension clinics. Central aortic pressure gives a better picture for identifying the hypertensive state of the body.

Can Type of Dizziness Influence the Vestibular Caloric Test Result?

Background:The broad range of vestibular tests used to diagnose labyrinth diseases allows for a functional assessment of the vestibular system. Among the many tests performed, the caloric test is considered the gold standard by providing an objective measurement of the vestibular function for each labyrinth.Objective:to correlate the different types of dizziness with the caloric test result.Methods:a descriptive study was performed based on the previous records of vestibular tests performed on patients with body balance disorders evaluated at Audiology Service between 2000 and 2020. The variables evaluated were sex, age, hearing loss, tinnitus, and caloric test result.Results:the sample was composed of 892 patients, 654 (73.4%) women, and 238 (26.6%) men. Normal results were obtained for 57.4% (N = 514) of the individuals, while peripheral disease 40.1% (N = 357), and central disease 2.5% (N = 21) accounted for the remaining. Complaint of vertigo was not common in central disorders (P = .02; OR = 0.17) and instability was associated with bilateral vestibular weakness (P = 0.02; OR = 5.92). Vertigo associated with tinnitus and/or hearing loss was more frequent in the caloric test with peripheral abnormality (P = 0.008).Conclusion:complaints of vertigo associated with tinnitus and/or hearing loss must be directed for clinical observation of unilateral peripheral lesion and instability to central disease or bilateral peripheral lesion.

Differential effects of minocycline on microvascular complications in murine models of type 1 and type 2 diabetes.

Diabetes is a global healthcare problem associated with enormous healthcare and personal costs. Despite glucose lowering agents that control glycaemia, both type 1 (T1D) and type (T2D) diabetes patients often develop microvascular complications that increase morbidity and mortality. Current interventions rely on careful glycemic control and healthy lifestyle choices, but these are ineffective at reversing or completely preventing the major microvascular complications, diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). Minocycline, a tetracycline antibiotic with anti-inflammatory and anti-apoptotic properties, has been proposed as a protective agent in diabetes. However, there are no reported studies evaluating the therapeutic efficacy of minocycline in T1D and T2D models for all microvascular complications (DPN, DR, and DKD). Therefore, we performed metabolic profiling in streptozotocin-induced T1D and db/db T2D models and compared the efficacy of minocycline in preventing complications to that of insulin and pioglitazone in both models. Minocycline partially ameliorated DR and DKD in T1D and T2D animals, but was less effective than insulin or pioglitazone, and failed to improve DPN in either model. These results suggest that minocycline is unlikely to improve outcomes beyond that achieved with current available therapies in patients with T1D or T2D associated microvascular complications.

Retracted] Quantitative Parameters of Contrast‐Enhanced Ultrasound Combined with Lung Biopsy Were Used to Evaluate the Benign and Malignant Lesions around the Lungs

In recent years, due to the influence of living habits and smoking, the number of lung cancer patients worldwide has increased year by year, and it has gradually developed into one of the common diseases endangering human life. CEUS can observe the lesion and realize the rapid identification of the location of the active area of the lesion. CEUS is the abbreviation of contrast‐enhanced ultrasound technology. Contrast‐enhanced ultrasound technology is to inject ultrasound contrast agent through a peripheral vein to perform ultrasound exploration to observe the enhancement of the internal nodules. Compared with color ultrasound, it can diagnose more accurately and improve the inspection effect. At present, this technology is used for the diagnosis of many types of space‐occupying lesions, but it is rarely used for the diagnosis of lung lesions. The purpose of this study is to explore the role of CEUS quantitative parameters combined with lung biopsy in the assessment of benign and malignant peripheral lung diseases. Based on the relevant theoretical basis of CEUS and lung biopsy, 158 patients with peripheral lung disease were selected as experimental subjects, and they were divided into experimental group and control group for comparative experiments. Experiments proved the effectiveness of CEUS quantitative parameters combined with lung biopsy methods. The experimental results showed that, compared with the benign group, the time‐intensity curve, the rise time, and the peak time of the malignant lesions were significantly prolonged. In addition, CEUS combined with the quantitative parameters of lung biopsy can effectively distinguish the activity of lung lesions and the site of necrosis and promote the effective increase of the positive rate of lung biopsy.

Characteristics of neural growth and cryopreservation of the dorsal root ganglion using three-dimensional collagen hydrogel culture versus conventional culture.

In vertebrates, most somatosensory pathways begin with the activation of dorsal root ganglion (DRG) neurons. The development of an appropriate DRG culture method is a prerequisite for establishing in vitro peripheral nerve disease models and for screening therapeutic drugs. In this study, we compared the changes in morphology, molecular biology, and transcriptomics of chicken embryo DRG cultured on tissue culture plates (T-DRG) versus three-dimensional collagen hydrogels (C-DRG). Our results showed that after 7 days of culture, the transcriptomics of T-DRG and C-DRG were quite different. The upregulated genes in C-DRG were mainly related to neurogenesis, axon guidance, and synaptic plasticity, whereas the downregulated genes in C-DRG were mainly related to cell proliferation and cell division. In addition, the genes related to cycles/pathways such as the synaptic vesicle cycle, cyclic adenosine monophosphate signaling pathway, and calcium signaling pathway were activated, while those related to cell-cycle pathways were downregulated. Furthermore, neurogenesis- and myelination-related genes were highly expressed in C-DRG, while epithelial-mesenchymal transition-, apoptosis-, and cell division-related genes were suppressed. Morphological results indicated that the numbers of branches, junctions, and end-point voxels per C-DRG were significantly greater than those per T-DRG. Furthermore, cells were scattered in T-DRG and more concentrated in C-DRG, with a higher ratio of 5-ethynyl-2'-deoxyuridine (EdU)-positive cells in T-DRG compared with C-DRG. C-DRG also had higher S100 calcium-binding protein B (S100B) and lower α-smooth muscle actin (α-SMA) expression than T-DRG, and contained fewer terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells after 48 hours of serum starvation. After cryopreservation, C-DRG maintained more intact morphological characteristics, and had higher viability and less TUNEL-positive cells than T-DRG. Furthermore, newly formed nerve bundles were able to grow along the existing Schwann cells in C-DRG. These results suggest that C-DRG may be a promising in vitro culture model, with better nerve growth and anti-apoptotic ability, quiescent Schwann cells, and higher viability. Results from this study provide a reference for the construction, storage, and transportation of tissue-engineered nerves. The study was approved by the Ethics Committee of Aier School of Ophthalmology, Central South University, China (approval No. 2020-IRB16), on March 15, 2020.

Association Between Peripheral Eosinophilia and Clinical Characteristics of Adult-onset Still's Disease with Persistent Eruption: A Retrospective Study.

Persistent eruption occurs in a subset of patients with adult-onset Still’s disease. In our experience, a considerable proportion of these patients present with peripheral eosinophilia. The aims of this study were to summarize the clinical and histological features of patients with adult-onset Still’s disease with persistent eruption in the current study cohort, and to assess the association between peripheral eosinophil levels and disease characteristics. A total of 21 patients with adult-onset Still’s disease with persistent eruption were included in this retrospective study. Koebner signs, an important diagnostic clue, were found in 85.7% of patients. The proportion of patients presenting with eosinophilia within the disease course was 57.1%. Skin histology revealed infiltration of eosinophils in 90.5% of patients. Peripheral eosinophil levels were positively associated with involved body surface area. Patients with normal peripheral eosinophil counts were more likely to achieve complete remission than those with abnormal peripheral eosinophil counts. Eosinophils may be involved in the pathogenesis of skin eruption. Abnormal peripheral eosinophil counts in these patients may indicate a more refractory disease course.

Eye diseases associated with psoriatic arthritis in the Amazon.

Ocular disorders are among the most frequent manifestations of psoriatic arthritis. The incidence, type, and severity of these disorders may be influenced by genetics, local environmental factors, and access to ophthalmic treatment. Here we describe the ocular manifestations of psoriatic arthritis among denizens of the Amazon region of Para, Brazil, treated by the rheumatology service of Universidade do Estado do Pará. This cross-sectional study examined 23 psoriatic arthritis patients (median age 47.78 years, no sex predominance) diagnosed according to Caspar's criteria. Disease activity was evaluated according to the Clinical Disease Activity Index for Psoriatic Arthritis. Ophthalmological examinations performed included visual acuity with distance correction, biomicroscopy, applanation tonometry, fundoscopy, Schirmer test I, tear breakup time, fluorescein staining, and lissamine green staining. Patients also completed The Ocular Surface Disease Index questionnaire. The most common ophthalmic disorders were dry eye (60.9%), cataracts (56.5%), blepharitis (47.8%), keratitis (43.5%), meibomitis (30.4%), pterygium (26, 1%), and pinguecula (13%). More than half of all patients demonstrated recent onset (>5 years), the peripheral disease type, and severe symptoms according to Clinical Disease Activity Index for Psoriatic Arthritis. The ocular manifestations of psoriatic arthritis are varied and mainly affect the ocular surface. Regular ophthalmological follow-up is recommended for patients in the early stage with high disease activity.

Erectile dysfunction in common neurological conditions: A narrative review.

Neurogenic erectile dysfunction (NED) can be defined as the inability to achieve or maintain an erection due to central or peripheral neurologic disease. Neurologic diseases can also affect the physical ability and psychological status of the patient. All these factors may lead to a primary or secondary NED. Medication history plays an important role since there are many drugs commonly used in neurologic patients that can lead to ED. The assessment of NED in these patients is generally evolving with the application of evoked potentials technology in the test of somatic and autonomic nerves, and functional magnetic resonance imaging. With the electrophysiological examinations, neurogenic causes can be determined. These tools allow to categorize neurologic lesion and assess the patient prognosis. The first-line treatment for NED is phosphodiesterase inhibitors. Second-line treatments include intracavernous and intraurethral vasoactive injections. Third-line treatments are penile prostheses. The efficacy and safety of each treatment modality depend on the specific neurologic condition. This review discusses the physiology, pathophysiology, diagnosis, and treatment of ED in multiple peripheral and central neurologic conditions, as well as for future research.

Ficus carica L. Attenuates Denervated Skeletal Muscle Atrophy via PPARα/NF-κB Pathway.

Treatment options for denervated skeletal muscle atrophy are limited, in part because the underlying molecular mechanisms are not well understood. Unlike previous transcriptomics studies conducted in rodent models of peripheral nerve injury, in the present study, we performed high-throughput sequencing with denervated atrophic biceps muscle and normal (non-denervated) sternocleidomastoid muscle samples obtained from four brachial plexus injury (BPI) patients. We also investigated whether Ficus carica L. (FCL.) extract can suppress denervated muscle atrophy in a mouse model, along with the mechanism of action. We identified 1471 genes that were differentially expressed between clinical specimens of atrophic and normal muscle, including 771 that were downregulated and 700 that were upregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the differentially expressed genes were mainly enriched in the GO terms “structural constituent of muscle,” “Z disc,” “M band,” and “striated muscle contraction,” as well as “Cell adhesion molecules,” “Glycolysis/Gluconeogenesis,” “Peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway,” and “P53 signaling pathway.” In experiments using mice, the reduction in wet weight and myofiber diameter in denervated muscle was improved by FCL. extract compared to saline administration, which was accompanied by downregulation of the proinflammatory cytokines interleukin (IL)-1β and IL-6. Moreover, although both denervated groups showed increased nuclear factor (NF)-κB activation and PPARα expression, the degree of NF-κB activation was lower while PPARα and inhibitor of NF-κB IκBα expression was higher in FCL. extract-treated mice. Thus, FCL. extract suppresses denervation-induced inflammation and attenuates muscle atrophy by enhancing PPARα expression and inhibiting NF-κB activation. These findings suggest that FCL. extract has therapeutic potential for preventing denervation-induced muscle atrophy caused by peripheral nerve injury or disease.

Comparison of fundus fluorescein angiography, optical coherence tomography and optical coherence tomography angiography features of macular changes in Eales disease: a case series

PurposeTo study the macular features in Eales disease patients observed with fundus fluorescein angiography (FA), optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA).MethodsA cross-sectional study was done on treatment naïve 31 eyes (23 patients) with Eales disease. Baseline parameters such as Best-corrected visual acuity (BCVA), slit-lamp bio microscopy (SLB), indirect ophthalmoscopy, FA, spectral-domain OCT {quantitative (central macular thickness [CMT]) and qualitative analysis on SD-OCT} and OCTA were performed. Any media opacity precluding the above investigations was excluded.ResultsMacular findings comprised of- epiretinal membrane, macular exudation, full thickness macular hole, sub internal limiting membrane bleed, cystoid macular oedema, neurosensory detachment and retinal thickening. Sixteen (51.6%) of our patients had macular changes as seen on all modalities together. SLB and indirect ophthalmoscopy missed macular findings in 50% patients and FA in 18.8% patients. OCT and OCTA diagnosed all macular findings. On comparison of mean BCVA in patients with macular involvement on FA, OCT and OCTA, compared to those without macular involvement, patients with macular involvement had lower BCVA (p 0.000, 0.01 and 0.001 respectively). Thus, FA missed many patients who had significant macular involvement and hence less vision.ConclusionEales disease though described in literature as classically being peripheral retina disease process, also has macular involvement. OCT and OCTA are useful guides to evaluation of macular involvement in these patients. The latter seems to be superior to FA in detecting macular abnormalities in this ailment. OCTA is non-invasive and shows deep capillary plexus changes which are not shown by any other modality.

Hanno Millesi: Pioneer of Plastic Surgery and Nerve Surgery (1927-2017).

Recently, plastic surgery lost one of its most prominent surgeons-Dr. Hanno Millesi. His contributions to the field continue to impact the practice of medicine and surgery. As such, it is appropriate to reflect upon his career and recognize his accomplishments in peripheral nerve surgery, hand surgery, and Dupuytren disease.

Abstract 15505: Aortic Stiffening in L-NAME Treated C57bl6 Mice Precedes Peripheral Hypertension and Cardiac Hypertrophy: Early Endothelial Dysfunction Shifts to Late-term Vascular Smooth Muscle Cell Disease

Introduction: Endothelial dysfunction (ED) acts as a common player in most cardiovascular (CV) risk factors (e.g. hypertension, smoking) underlining its importance in CV ageing. Therefore, this study aims to characterize ex vivo aortic function changes in Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) treated mice. Methods: C57Bl6 mice (male, n=10) received 0.5 mg/mL L-NAME through the drinking water for 1, 2, 4, 8, and 16 weeks, followed by in-depth ex vivo thoracic aorta isometric reactivity studies and arterial stiffness (Peterson modulus, Ep) measurements in the Rodent Oscillatory Tension set-up for Arterial Compliance (ROTSAC). In addition, peripheral blood pressure (BP, Coda), aortic pulse wave velocity (aPWV, Vevo2100), and echocardiography (Vevo2100) were measured in vivo . (Data are represented as mean±SEM) Results: L-NAME treated mice display fast-onset aortic stiffening after 1-week L-NAME (Fig. A, B), followed by the development of peripheral hypertension (Fig. C) and cardiac disease (Fig. D-F) after 4-weeks L-NAME. Ex vivo aorta studies reveal different stages of disease. Early on (1-4 weeks), mice show elevated phenylephrine (PE) contractions (Fig. G) and impaired acetylcholine (ACh) relaxations (Fig. H), consistent with L-NAME related ED. After 8 weeks, endothelial function and PE contractions normalize. Relaxations to exogenous NO remain unaltered (Fig. I). In contrast to the recovery of ACh relaxations, stiffness analysis in the ROTSAC reveals constantly reduced basal NO levels (Fig. J), and a late-term shift (16 weeks) towards vascular smooth muscle cell (VSMC) disease. This involves basal cytoplasmic calcium loading (Fig. K) and a sharply increasing contribution of voltage-gated calcium channels (Fig. L). Conclusions: NOS inhibition by L-NAME treatment causes a distinct time-dependent aortic disease phenotype, underlying fast-onset arterial stiffening which precedes peripheral hypertension and cardiac disease.

Burns Impair Blood-Brain Barrier and Mesenchymal Stem Cells Can Reverse the Process in Mice.

Neurological syndromes are observed in numerous patients who suffer burns, which add to the economic burden of societies and families. Recent studies have implied that blood–brain barrier (BBB) dysfunction is the key factor that induces these central nervous system (CNS) syndromes in peripheral traumatic disease, e.g., surgery and burns. However, the effect of burns on BBB and the underlying mechanism remains, largely, to be determined. The present study aimed to investigate the effect of burns on BBB and the potential of umbilical cord-derived mesenchymal stem cells (UC-MSCs), which have strong anti-inflammatory and repairing ability, to protect the integrity of BBB. BBB permeability was evaluated using dextran tracer (immunohistochemistry imaging and spectrophotometric quantification) and western blot, interleukin (IL)-6, and IL-1β levels in blood and brain were measured by enzyme-linked immunosorbent assay. Furthermore, transmission electron microscopy (TEM) was used to detect transcellular vesicular transport (transcytosis) in BBB. We found that burns increased mouse BBB permeability to both 10-kDa and 70-kDa dextran. IL-6 and IL-1β levels increased in peripheral blood and CNS after burns. In addition, burns decreased the level of tight junction proteins (TJs), including claudin-5, occludin, and ZO-1, which indicated increased BBB permeability due to paracellular pathway. Moreover, increased vesicular density after burns suggested increased transcytosis in brain microvascular endothelial cells. Finally, administering UC-MSCs at 1 h after burns effectively reversed these adverse effects and protected the integrity of BBB. These results suggest that burns increase BBB permeability through both paracellular pathway and transcytosis, the potential mechanism of which might be through increasing IL-6 and IL-1β levels and decreasing Mfsd2a level, and appropriate treatment with UC-MSCs can reverse these effects and protect the integrity of BBB after burns.

Preliminary Results of a Response-Adapted Study of Ibrutinib and Isavuconazole with Temozolomide, Etoposide, Liposomal Doxorubicin, Dexamethasone, Rituximab (TEDDI-R) for Secondary CNS Lymphoma

Background: Secondary CNS B-cell lymphomas (SCNSL) are aggressive lymphomas with a very poor prognosis. Genetic subtypes of DLBCL with CNS tropism are enriched for chronic active B-cell receptor signaling and may respond to BTK inhibition (BTKi). CLL, MCL, and transformed lymphomas can also involve the CNS and are BTKi responsive. TEDDI-R achieves durable remissions in relapsed/refractory primary DLBCL of the CNS (PCNSL) but the profile of SCNSL tumors that are ibrutinib-responsive is unknown. We present preliminary results from a response-adapted trial of ibrutinib with TEDD-R in SCNSL. Methods: Pts with aggressive B-cell lymphomas with secondary CNS involvement are eligible if age ≥18 and adequate organ function. Pts must have relapsed after frontline therapy or can be untreated if brain parenchyma involved. Prior BTKi is allowed, but HIVinfection and EBV+ lymphomas are excluded. Baseline tests include brain MRI, FDG-PET brain and body, CSF with flow cytometry, Ommaya, and eye exam. Pts receive isavuconazole starting at 200mg BID x 3d prior to ibrutinib to prevent fungal infections associated with TEDDI-R and then 200mg daily unless ibrutinib stopped. Pts first receive ibrutinib 560mg daily x 14d in a window. If ≥20% reduction after ibrutinib, pts receive TEDDI-R for 4 cycles every 21d with IT cytarabine. Pts with <20% reduction after ibrutinib receive TEDD-R without ibrutinib for 4 cycles every 21d with IT cytarabine. No consolidation or maintenance is permitted. Surveillance for fungal infections includes chest CT after each cycle along with Beta-D glucan and aspergillus galactomannan in blood and CSF. Brain MRI and CT scans are performed after cycles 1, 2, and 4 to determine response. All remissions by MRI are confirmed with FDG-PET and CSF analysis. Surveillance brain MRI and CT scans are q3m for 1y, q4m x 1y, q6m x 1y, then annually. Results: 16 pts with a median age 67 (range 40-79) enrolled between June 2019 and July 2020. 15 (94%) pts had DLBCL comprising 9 (60%) non-GCB, 5 (33%) GCB, and 1 (7%) transformed from MZL. One pt had plasmablastic lymphoma. Eight (50%) pts had a MYC-rearrangement including 4 (25%) with both MYC and BCL2 or BCL6 rearrangements. Eight (50%) pts had isolated CNS disease and 8 (50%) had synchronous CNS and peripheral disease. All pts relapsed after a median of 2 (range 1-4) prior therapies and all (100%) pts received prior anthracycline. Seven pts (44%) had prior CNS prophylaxis and 8 pts (50%) had prior HD-MTX based salvage therapy. Toxicity was evaluated across 35 cycles. G3 and G4 neutropenia occurred in 49% and 29% of cycles, respectively, while febrile neutropenia occurred in 9% of cycles. The median (range) duration of neutropenia was 6 (1-13) days. Five (14%) cycles were complicated by ≥G3 infection, but no opportunistic infections (including Aspergillus) were observed. One pt developed a bacterial infection during cycle 1 and died. G3 and G4 thrombocytopenia occurred in 34% and 23% of cycles, respectively, and 1 pt developed G3 hematuria. G3 mucositis occurred in 9% of cycles and palmar-plantar-erythrodysesthesia led to dose reductions of liposomal doxorubicin in 5 (36%) pts. Of 15 pts who completed the 14d ibrutinib window and were evaluable, 8 (53%) were ibrutinib-responsive and 7 (47%) were ibrutinib-resistant (Figure 1). Clinical responses were concordant across anatomic compartments; of 8 pts with both CNS and peripheral disease, 5 (63%) responded to ibrutinib in both compartments while 3 (37%) did not respond in either compartment. All 8 ibrutinib responders had a non-GCB phenotype and six (75%) achieved CR. One died of treatment-related toxicity after a PR and 1 is still on therapy. Only two (29%) pts with ibrutinib-resistant tumors achieved PR and none have achieved CR. After a median follow-up of 5.1m, a landmark analysis starting after the ibrutinib window demonstrated the PFS for pts with ibrutinib-responsive compared to ibrutinib-resistant tumors was not reached vs. 0.9m (95% CI: 0.1-2m)(p=0.002)(Figure 2). Conclusions: Patients with SCNSL tumors that are ibrutinib-responsive achieve a high rate of complete response to TEDDI-R in both CNS and peripheral disease. Patients with tumors that are ibrutinib-resistant also respond poorly to TEDD-R. Toxicity is mainly hematologic, and no Aspergillus infections have occurred with the use of isavuconazole prophylaxis. Updated clinical results from this ongoing study (NCT03964090) and will be presented at the meeting. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: ibrutinib for use in secondary cns lymphoma as part of a clinical trial

Prognostic Impact of Nutritional Status at Diagnosis and Weight Changes in Acute Myeloid Leukemia Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Overweight & obesity represent prognostic factors for survival in multiple cancer entities, but the association between body mass index (BMI) & survival is not consistent across all cancer types. In acute myeloid leukemia (AML) data on the prognostic impact of diagnostic nutritional status remain inconsistent & in patients (pts) with hematologic malignancies, obesity prior to hematopoietic stem cell transplantation (HSCT) has been linked to inferior outcomes. Therefore, obesity has been included as one risk factor into the hematopoietic cell transplant comorbidity index (HCT-CI), which predicts non-relapse mortality (NRM) & overall survival (OS) in older HSCT pts. Additionally, AML pts often suffer from weight loss during therapy, which might also impair survival. Here we investigated the prognostic impact of the nutritional status at diagnosis & weight changes during therapy in AML pts receiving a HSCT. Methods: We analyzed 662 AML pts who underwent allogeneic HSCT (median age 59.4, range 16.3-74.9 years) in complete remission (CR, 68%), CR with incomplete peripheral recovery (CRi, 14%) or active disease (18%) after non-myeloablative (59%), reduced intensity (15%) or myeloablative (26%) conditioning. Donors were matched related (20%), matched unrelated (59%), mismatched (19%) or haploidentical (2%). Comorbidities were assessed by the HCT-CI. The body mass index (BMI; kg/m2) at diagnosis, prior to HSCT & the BMI difference (∆BMI = BMIHSCT - BMIDx) were evaluated. For ∆BMI a cut-point of -2 was determined applying the R package "OptimalCutpoints" & divided pts into two groups with unchanged/increased BMI (∆BMI ≤-2, 57%) & decreased BMI (∆BMI >-2, 43%). AML disease risk was assessed according to European LeukemiaNet (ELN) 2017 classification & was 25% favorable, 30% intermediate & 45% adverse. Median follow up after HSCT was 3.1 years. Results: The median BMI at AML diagnosis was significantly higher than at HSCT (median 25.8 vs 24.7 kg/m2, P<.001). According to WHO classification, at diagnosis vs HSCT 39% vs 53% of pts were under-/normal weight (BMI <25 kg/m2), 42% vs 35% were overweight (BMI 25-29.9 kg/m2)& 20% vs 12% were obese (BMI ≥30 kg/m2). Pts with ∆BMI >-2 were older (P=.002) & more likely to have de novo AML (P<.001) but did not vary regarding HCT-CI (P=.19) or pre-HSCT remission status (P=.99). Compared to non-obese pts, obese pts at diagnosis had higher NRM (P=.05) & shorter OS (P=.004, Figure 1A, B), while no significant prognostic impact was found for BMI at HSCT (NRM P=.15, OS P=.10). Weight loss (∆BMI >-2) between diagnosis & HSCT was a strong predictor for higher NRM (P=.006) & shorter OS (P<.001, Figure 1C, D). In multivariate analyses, ∆BMI >-2 remained significant for higher NRM (Hazard ratio 1.23, P=.008) after adjustment for donor type & for shorter OS (Odds ratio 0.82, P=.001) after adjustment for ELN risk, age & remission status at HSCT. Analyzing the three ELN risk groups separately, the prognostic impact of ∆BMI >-2 was particularly seen in ELN favorable (NRM P=.09, OS P=.02) & intermediate (NRM P=.02, OS P=.002) but not in ELN adverse risk pts (NRM P=.41, OS P=.20). ∆BMI >-2 was also a significant prognostic factor in pts transplanted in CR/CRi (NRM P=.01, OS P<.001) but not in the high-risk population of pts transplanted with active disease (NRM P=.15, OS P=.10). When we analyzed the prognostic impact of weight changes depending on the BMI category at diagnosis, we observed that weight loss (∆BMI >-2) had a prognostic impact in under-/normal weight (NRM P=.08, OS P=.007) & overweight (NRM P=.10, OS P=0.09), but not in obese pts (NRM P=.81, OS P=.70). Conclusion: Obesity at diagnosis & weight loss (∆BMI >-2) associated with adverse outcomes due to higher NRM in AML pts undergoing HSCT. The prognostic impact of weight loss between diagnosis & HSCT represented a strong, potentially modifiable & independent risk factor & was particularly seen in non-high-risk pts. In high-risk pts with ELN adverse risk or with active disease at HSCT, weight loss did not impact outcomes, most likely due to the aggressive phenotype of the underlying AML. The data indicates that nutritional dynamics in AML pts destined for HSCT should be monitored & supportive therapy adjusted accordingly to improve outcomes. Disclosures Vucinic: Celgene: Honoraria. Niederwieser:Novartis: Speakers Bureau; Cellectis: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Daiichi: Research Funding. Platzbecker:Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Geron: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Jentzsch:Novartis: Honoraria; JAZZ Pharmaceuticals: Honoraria. Schwind:Pfizer: Honoraria; Novartis: Honoraria, Research Funding; JAZZ Pharmaceuticals: Honoraria.

Do European patients with peripeheral arterial disease receive optimal lipid lowering therapy and achieve LDL-C goals? Results from the DA VINCI study

Abstract Background 2016 and 2019 EAS/ESC dyslipidemia guidelines recommend lipid lowering therapy (LLT) to reduce LDL-C in patients with peripheral arterial disease (PAD) with or without established cardiovascular (CV) disease, and recommend target LDL-C goals based on individual CV risk. Data regarding the implementation of these guidelines in clinical practice across Europe is currently lacking. Purpose Describe LLT and achievement of the target LDL-C goals recommended in EAS/ESC dyslipidemia guidelines in patients with PAD. Methods The cross-sectional Da Vinci study enrolled consenting adults who had received LLT in the 12 months prior to the study visit and had at least one LDL-C measurement in the 14 months prior to the study visit, seen in a primary or secondary care setting across 18 European countries. Patients with coronary, peripheral and cerebral disease were enrolled at a ratio of 1:2:2. FH patients with prior CV events were excluded. Data were collected from medical records at a single visit between Jun '17–Nov '18, including LLT and most recent LDL-C. Primary outcome was LDL-C goal attainment ≥28 days after starting most recent LLT (treatment-stabilised LLT). Results Of 5888 patients enrolled, 2794 met our definition of atherosclerotic cardiovascular disease (ASCVD). Of these ASCVD patients, 1036 (37%) had PAD. 31% (323/1036) of PAD patients were female and mean (SD) age was 69 (9.4) years. Concomitant CV risk factors included diabetes mellitus (473/1036 patients [46%]), hypertension (809/1036 [78%]) and smoking (794/1036 [77%]). 26% (271/1036) of patients with PAD also had coronary vascular disease and 12% (122/1036) also had cerebrovascular disease. At the visit date, approximately half (497/1036 [48%]) of all PAD patients were receiving moderate intensity statins and 41% (421/1036) were receiving high intensity statins. 818 (73%) of the PAD patients had a treatment-stabilised LDL-C measurement (median, 2.20 mmol/L), of whom 40% (326/818) achieved the 2016 EAS/ESC LDL-C goal of 1.8 mmol/L and only 19% (159/818) achieved the 2019 goal of 1.4mmol/L. Conclusions European patients with PAD are not treated as per EAS/ESC recommendations, with a large proportion receiving suboptimal LLT and fewer than half achieving target LDL-C levels. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

Atrial fibrillation and ischaemic heart disease: should we use acetylsalicylic acid beside anticoagulants?

Coexistence of atrial fibrillation and ischaemic heart disease is very common and patients affected by these conditions are exposed to both a high ischaemic and haemorrhagic risk. The choice of an appropriate combination of anticoagulant therapy with single or dual antiplatelet treatment is indeed one of the most relevant and contemporary challenges in clinical practice. Several studies and meta-analyses pointed out that 1 year after an acute coronary syndrome or percutaneous revascularization, the use of the sole anticoagulant therapy is not associated with increased risk of major cardiovascular events, whereas there is a substantial reduction of clinical significant bleeding events, as compared to patients treated also with antiplatelet medications. However, there are no clear-cut data regarding the possibility to implement this strategy in each patient, regardless the cardiovascular risk class. Furthermore, for patients requiring a combined anticoagulant and antiplatelet treatment, the available data seem to favour an association of direct anticoagulant and inhibitors of P2Y12, rather than regimens including aspirin. These data are derived mainly from observational studies, with all their limitations. The use of aspirin could be beneficial in patients with significant comorbidities, such as diabetes mellitus, or with severe peripheral atherosclerotic disease, involving the carotids and other large arteries.