Sustained Clinical Improvement Research Articles

Recalcitrant pityriasis rubra pilaris in a Middle Eastern patient and arguments for early anti‐IL‐23 targeting

AbstractPityriasis rubra pilaris (PRP) is a rare, chronic cutaneous inflammatory disorder of keratinization affecting adults, children and patients with HIV. The pathogenesis of PRP is not fully understood with clinical presentations, and severity remains highly variable. Current treatment modalities for PRP result in recalcitrant disease with potentially unfavourable therapeutic side effects and low tolerability. Due to the rarity of this condition, limited data on treatment efficacies and established management guidelines are lacking. The psychological burden of PRP is detrimental to the quality of life of patients affected with PRP and remains a persistent gap of knowledge. Here, we provide a review of the literature, summarizing new developments in the treatment of PRP and a case report of a patient treated successfully with the anti‐interleukin (IL)‐23p19 antibody Risankizumab with sustained clinical improvement. Risankizumab appears to be an effective and safe treatment for PRP in Asian‐Arabic patients. Further studies are required to assess the efficacy, safety and tolerability of newer targeted therapies for severe PRP.

Long-Term Outcomes of a Japanese Prospective Multicenter Registry Using a Heparin-Bonded Expanded Polytetrafluoroethylene Graft for Above-the-Knee Femoropopliteal Bypasses.

Despite the widespread use of PROPATEN®, a bioactive heparin-bonded expanded polytetrafluoroethylene graft, in bypass surgery, there are only a few reports of long-term results. We evaluated the long-term results of PROPATEN®use for above-knee femoropopliteal bypass (AKFPB).Methods and Results: After PROPATEN®-based AKFPB, patients were prospectively registered at 20 Japanese institutions between July 2014 and October 2017 to evaluate long-term results. During the median follow-up of 76 months (interquartile range 36-88 months) for 120 limbs (in 113 patients; mean [±SD] age 72.7±8.1 years; 66.7% male; ankle-brachial index [ABI] 0.45±0.27; lesion length 26.2±5.7 cm; chronic limb-threatening ischemia in 45 limbs), there were 8 major amputations; however, clinical improvement was sustained (mean [±SD] ABI 0.87±0.23) and the Rutherford classification grade improved in 105 (87.5%) limbs at the latest follow-up. At 8 years, the primary patency, freedom from target-lesion revascularization, secondary patency, survival, and amputation-free survival, as estimated by the Kaplan-Meier method, were 66.3±4.8%, 71.5±4.4%, 86.5±3.4%, 53.1±5.0%, and 47.4±5.3%, respectively. This multicenter prospective registry-based analysis showed sustained excellent clinical improvement and secondary patency for up to 8 years following PROPATEN®-based AKFPB. PROPATEN®constitutes a durable and good revascularization option for complex superficial femoral artery lesions, especially when endovascular treatment is inappropriate or an adequate venous conduit is unavailable.

Final 3-Year Study Outcomes from the Evaluation of the Zilver Vena Venous Stent for the Treatment of Symptomatic Iliofemoral Venous Outflow Obstruction (The VIVO Clinical Study)

PurposeTo report 3-year outcomes from a prospective, multicenter, nonrandomized, single-arm study designed to assess the safety and effectiveness of the Zilver Vena Venous Stent for the treatment of symptomatic iliofemoral venous outflow obstruction. Materials and MethodsThe VIVO study included patients with symptomatic obstruction of 1 iliofemoral venous segment (ie, 1 limb), characterized by a Clinical, Etiological, Anatomic, Pathophysiology (CEAP) clinical classification of ≥3 or a Venous Clinical Severity Score (VCSS) for pain of ≥2. Patients were retrospectively grouped based on baseline clinical presentation as postthrombotic syndrome (PTS), nonthrombotic iliac vein (NIVL) obstruction, or acute deep vein thrombosis (aDVT). Clinical improvement was assessed by change in VCSS, Venous Disability Score, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) scores, and CEAP C classification. Stent performance was evaluated by rates of patency by ultrasound (US), freedom from clinically driven reintervention, and freedom from stent fracture. ResultsThe 3-year results for the 243 patients in the VIVO cohort included a 90.3% rate of patency by US and a 92.6% rate of freedom from clinically driven reintervention. The 3-year rates of patency by US for the NIVL, aDVT, and PTS groups were 100%, 84.0%, and 86.1%, respectively. Sustained clinical improvement through 3 years was demonstrated by changes in VCSS, Venous Disability Score, CIVIQ-20, and CEAP C classification. No stent fractures were observed. ConclusionsThe VIVO study demonstrated sustained high rates of patency and freedom from clinically driven reintervention and improvements in venous clinical symptoms through 3 years. Each patient group (NIVL, aDVT, and PTS) showed clinical improvement and sustained patency through 3 years; some variation existed among groups (eg, only the NIVL group had a 100% patency rate).

Impact of Glucagon-Like Peptide1 Agonist Deprescription in Type2 Diabetes in a Real-World Setting: A Propensity Score Matched Cohort Study.

Glucagon-like peptide1 receptor agonists (GLP-1) elicit substantial reductions in glycemia and body weight in people with type2 diabetes (T2D) and obesity, but existing data suggest the therapy must be continued indefinitely to maintain clinical improvements. Given the high cost and poor real-world persistence of GLP-1, an effective therapy that enables deprescription with sustained clinical improvements would be beneficial. Thus, the purpose of this real-world study was to assess the effect of GLP-1 deprescription on glycemia and body weight following co-therapy with carbohydrate restricted nutrition therapy (CRNT) supported via telemedicine in a continuous remote care model. A retrospective, propensity score matched cohort study among patients with T2D at a telemedicine clinic was conducted. Patients in whom GLP-1 were deprescribed (DeRx; n = 154) were matched 1:1 with patients in whom GLP-1 were continued (Rx). HbA1c and body weight at enrollment in clinic (pre-CRNT), at date of deprescription or index date (derx/ID), and at 6 and 12months (m) post-derx/ID were utilized in this study. No regression in weight was observed following deprescription with > 70% maintaining ≥ 5% weight loss 12m post-derx/ID. HbA1c rose 6m and 12m post-derx/ID in both DeRx and Rx cohorts, but most patients maintained HbA1c < 6.5%. HbA1c and body weight measured 6m and 12m following derx/ID did not significantly differ between cohorts and were improved at derx/ID and at follow-up intervals compared to pre-CRNT. These results demonstrate the potential for an alternate therapy, such as CRNT supported via telemedicine, to enable maintenance of weight loss and glycemia below therapeutic targets following discontinuation of GLP-1 therapy.

Rescue From Permanent Kidney Injury in Acute Thrombosis of Both Renal Veins, the Inferior Vena Cava, and Both Iliofemoral Veins by Catheter-Based Thrombectomy.

A 33-year-old man with previously diagnosed lupus membranous nephropathy presented with painful swelling in both legs. Laboratory tests revealed acute kidney injury, and imaging studies by duplex ultrasound and computed tomography scan showed acute thrombosis of both renal veins, the infrahepatic inferior vena cava, and both iliofemoral venous segments. Initially, pharmacomechanical thrombolysis led to an insufficient morphological result. The therapeutic breakthrough was achieved by catheter-based mechanical thrombectomy of the infrarenal vena cava and both renal veins, which successfully cleared all affected venous segments from thrombus, paralleled by improvement of the patient's condition. However, after 1 week, the patient experienced recurrent thrombosis of the right renal vein with hemorrhagic infarction of the right kidney. After further optimization of immunomodulatory and antithrombotic therapy, a repeated catheter-based mechanical thrombectomy resulted in sustained clinical improvement and preservation of renal venous drainage and kidney function. Extensive acute thrombosis of both renal veins, the inferior vena cava, and both iliofemoral venous segments is a rare emergency potentially threatening kidney function. Immediate effective thrombus removal is essential to preserve kidney function and can be achieved by catheter-based mechanical thrombectomy embedded in a comprehensive immunomodulatory and antithrombotic therapeutic concept. This case demonstrated the efficacy of a catheter-based therapeutic approach in patients with extensive thrombosis of the venous system. A catheter-based approach must be embedded in a comprehensive medical therapeutic concept, which is essential to achieve a sustainable result.

Super Refractory Status Epilepticus Improved After Emergency Use of Ganaxolone: Case Report

We present a case of a 34-year-old man with epilepsy who developed super refractory status epilepticus in the setting of COVID-19 pneumonia in whom aggressive therapy with multiple parenteral, enteral, and non-pharmacologic interventions were utilized without lasting improvement in clinical examination or electroencephalogram (EEG). The patient presented with multiple recurrences of electrographic status epilepticus throughout a prolonged hospital stay. Emergency use authorization was obtained for intravenous ganaxolone, a neuroactive steroid that is a potent modulator of both synaptic and extrasynaptic GABAA receptors. Following administration of intravenous ganaxolone according to a novel dosing paradigm, the patient showed sustained clinical and electrographic improvement.

The Impact Of Thymectomy In Thymomatous And Nonthymomatous Myasthenia Gravis - The Experience Of A Tertiary Center.

Thymectomy remains a mainstay of treatment in Thymomatous (T) and Nonthymomatous (nT) Myasthenia Gravis (MG), with improved clinical outcomes and reduced need for medical treatment, however, there is little research regarding long-term follow-up. We aim to assess the impact of surgery on the long-term outcome of patients with MG at our center. Retrospective analyses of MG patients submitted to thymectomy between 2007 and 2017 at the thoracic surgery department of CHUC. Clinical assessment was performed according to the MG Foundation of America (MGFA) Clinical Classification (cMGFA). The follow-up was categorized according to the MGFA Post-intervention Status (MGFA-PIS) and cMGFA. Statistical analysis was performed with SPSS, to a significance level of 5%. Thirty-seven patients underwent extended thymectomy and 67.6% were female. Median age at diagnosis was 46.68±19.2 years. Most patients (83.8%) had anti-acetylcholine receptor antibodies and 81.1% had generalized forms of MG. Many patients (67.6%) had surgery less than 12 months after the clinical diagnosis. TMG was present in 19 (51.4%) patients. Compared to nTMG, these patients were older (54.06±17.9 vs 40.17±19.4 years) and most were men (52.9% vs 16.7%). We obtained a good outcome in most patients in the first (81.1%), second (86.1%), and fifth (84.8%) year of follow-up. There was a shift towards better prognosis categories in the good outcome group: 9.1% CSR, 3.0% PR, and 66,7% MM in the fifth year. Preoperative medical treatment did not influence the long-term follow-up outcome. A shorter time to surgery (< 12 months) correlated with better outcomes at year 5 (p=0.016). Thymectomy led to a sustained clinical improvement in our cohort, allowing for a reduced need for medication. A shorter time to surgery seems to have a positive influence on long-term prognosis. We expect that an extended follow-up would improve our results.

Denosumab in a pediatric kidney transplant recipient with late, resistant hypercalcemia secondary to Pneumocystis jirovecii pneumonia.

Kidney transplant recipients (KTR) are at an increased risk of developing Pneumocystis jirovecii pneumonia (PCP), especially during the first year after transplantation. This is the first reported pediatric KTR, with chronic kidney disease (CKD) secondary to kidney dysplasia and vesicoureteral reflux, who developed refractory and symptomatic hypercalcemia 5years after transplantation. The hypercalcemia was resistant to treatment with intravenous hyperhydration, furosemide, and a low-calcium diet. A respiratory tract infection due to PCP treated with trimethoprim-sulfamethoxazole did not improve calcium levels. Due to the hypercalcemic symptom burden for the patient, a single dose of subcutaneous denosumab was used to achieve sustained clinical and biochemical improvement, without any severe adverse events. This case highlights the potential use of denosumab as a treatment option in pediatric KTR with refractory hypercalcemia related to PCP. Further study of denosumab in young people with CKD or kidney transplants is needed before routine use can be recommended.

Mycophenolate mofetil for the long-term treatment of HTLV-1 associated myelopathy: A case report

Human T-cell leukemia virus type 1 (HTLV-1) can cause HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Current treatment options for HAM/TSP are limited. We present a woman with rapidly-progressive HAM/TSP with significant, sustained clinical improvement following initiation of mycophenolate mofetil (MMA). Peripheral blood mononuclear cells from the patient, her asymptomatic carrier husband and eight healthy controls were isolated. Frequencies of T-cell populations upon exposure to low and high MMA concentrations and differences in proliferation were analyzed using flow cytometry and a CSFE-proliferation assay. Characterization of T-cell function and proliferation showed higher levels of GranzymeB in HTLV-1+ donors. The improvement and stability of symptoms in this patient with HAM/TSP following MMA initiation requires further study as a potential treatment for HAM/TSP.

Hip Arthroscopic Surgery With Chondrolabral Refixation, Osteochondroplasty, and Routine Capsular Closure for Femoroacetabular Impingement Syndrome: Clinical Outcomes at a Minimum 10-Year Follow-up

Background: Hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS) has proven to be an effective surgical intervention, with high rates of return to sport and work as well as favorable outcomes at short- and midterm follow-up. However, limited data exist on outcomes at long-term follow-up. Purpose: To evaluate patient-reported outcomes (PROs) at a minimum 10-year follow-up after primary hip arthroscopic surgery including labral repair, femoral osteochondroplasty, acetabular osteochondroplasty, and capsular closure for FAIS. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent primary hip arthroscopic surgery for FAIS between June 2012 and January 2013 were identified. PROs were collected preoperatively and at a minimum of 10 years postoperatively, including the Hip Outcome Score–Activities of Daily Living (HOS-ADL), Hip Outcome Score–Sports Subscale (HOS-SS), modified Harris Hip Score (mHHS), International Hip Outcome Tool–12 (iHOT-12), and visual analog scale (VAS) for pain and satisfaction. Unique minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) thresholds were calculated, and their rates of achievement were analyzed. An alpha level of <.05 was used to determine statistical significance. Results: A total of 94 patients (55 female; mean age, 34.3 ± 12.4 years) were analyzed with a mean follow-up of 10.1 ± 0.3 years (range, 10.0-10.7 years). Patients demonstrated significant 10-year improvement across all PRO measures (P < .001). MCID and PASS thresholds were calculated as follows: HOS-ADL (10.4 and 85.3, respectively), HOS-SS (14.6 and 60.2, respectively), mHHS (8.8 and 76.0, respectively), VAS pain (14.6 and 27.5, respectively), and iHOT-12 (PASS: 71.4). The majority of patients achieved the MCID and PASS for each PRO measure: HOS-ADL (73.4% and 70.9%, respectively), HOS-SS (78.5% and 77.2%, respectively), mHHS (81.0% and 70.9%, respectively), VAS pain (88.6% and 70.9%, respectively), and iHOT-12 (PASS: 73.4%). Overall, 9 patients (9.6%) underwent subsequent revision hip arthroscopic surgery at a mean 4.9 ± 3.7 years (range, 1.1-10.1 years) postoperatively, and 6 patients (6.4%) underwent conversion to total hip arthroplasty at a mean 4.1 ± 3.1 years (range, 0.9-9.3 years) postoperatively. Conclusion: Patients who underwent primary hip arthroscopic surgery for FAIS utilizing contemporary methods of labral repair, acetabular and/or femoral osteochondroplasty, and capsular closure commonly experienced sustained clinical improvement and reported high levels of satisfaction at a minimum 10-year follow-up with low rates of reoperation.

Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial

BackgroundIn a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence.ObjectivesTo evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19.MethodsWe conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms.ResultsThe full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported.InterpretationLHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated.Trial registrationChiCTR2200056727.

Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10

Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2.

Drug-Coated Balloon Angioplasty of Infrapopliteal Lesions in Chronic Limb-Threatening Ischemia: Six-month Outcomes of PRIME-WIFI.

To evaluate 6-month outcomes of drug-coated balloon (DCB) angioplasty of infrapopliteal lesions in patients with chronic limb-threatening ischemia (CLTI). We analyzed 6-month follow-up data from the 10-center PRIME-WIFI prospective registry on 300 consecutive patients (33.000% female) with CLTI who underwent DCB angioplasty for infrapopliteal arterial lesions. The primary outcome was freedom from major adverse event (MAE), a composite of major amputation, all-cause death, and clinically-driven target limb reintervention (CD-TLR). Secondary outcomes included amputation-free survival (AFS), freedom from each primary outcome component, primary sustained clinical improvement, and quality of life (QOL) score. Independent risk factors of MAE were determined using Cox proportional hazards regression analysis. A total of 409 infrapopliteal lesions in 312 limbs were treated with DCB, with 54.167% of the limbs being treated for isolated infrapopliteal lesions. By Kaplan-Meier analysis, at 6 months post- procedure (follow-up rate, 85.000%), freedom from MAE was 86.353%; AFS was 90.318%; and freedom from major amputation, all-cause death, and CD-TLR were 96.429%, 93.480%, and 95.079%, respectively. At 6-month follow-up, 83.590% of patients showed primary sustained clinical improvement, and QOL score (4.902±1.388) improved compared with that before procedure (2.327±1.109; p<0.001). Chronic renal insufficiency, chronic obstructive pulmonary disease, Rutherford grade, and postoperative infrapopliteal runoff score were independent risk factors for MAE within 6 months. In CLTI, DCB angioplasty of infrapopliteal lesions yields acceptable early efficacy and safety. This study evaluated the 6-month outcomes of DCB angioplasty in infrapopliteal lesions in CLTI patients by analyzing multicenter prospective data, showing that infrapopliteal DCB angioplasty can be performed with acceptable freedom from MAE rate, amputation-free survival rate, freedom from major amputation rate, survival rate, and freedom from CD-TLR rate. No patient experienced DCB-related intraoperative distal embolism. Chronic renal insufficiency, chronic obstructive pulmonary disease, Rutherford grade and postoperative infrapopliteal runoff score were independent risk factors for MAE within 6 months. Comparative real-world studies are needed.

Deep brain stimulation in multiple sclerosis-associated tremor. A large, retrospective, longitudinal open label study, with long-term follow-up.

Tremor affects up to 25%-58% in multiple sclerosis (MS) population. Deep-brain stimulation (DBS) of the ventral-intermediate nucleus (VIM) of the thalamus is considered as a potential option following medical treatments. Long term DBS efficacy is not well known in these patients with a poor outcome mostly related to disease progression. To report a large and retrospective study of thalamic DBS in MS tremor. We conducted a large and retrospective study of patients with MS disabling and pharmacologically resistant upper limb tremor, who underwent thalamic DBS procedure from January 1992 to January 2015 in University Hospital of Henri Mondor, France. Demographic data, clinical assessment and activity daily living were collected. A three-month and twelve-month post-operative assessment with clinical and functional rating scales have been achieved, as well as long term follow-up for most patients. One hundred and four patients underwent DBS procedure. There were 71 female (68%) and 33 male (32%). At three-month post-operative assessment, 64% patients were improved clinically and functionally. Among these, 93% of patients kept a good efficacy at one-year post-operative assessment. Mean duration of follow-up for these patients was 6 years. We described a long-term sustained clinical and functional improvement in this large and retrospective report of thalamic DBS. This neuromodulation approach could be a therapeutic option for all severe upper extremity refractory tremor in MS patients.

Renin-angiotensin system inhibitor discontinuation in COVID-19 did not modify systemic ACE2 in a randomized controlled trial

Despite the similar clinical outcomes after renin-angiotensin system (RAS) inhibitor (RASi) continuation or withdrawal in COVID-19, the effects on angiotensin-converting enzyme 2 (ACE2) and RAS metabolites remain unclear. In a substudy of the randomized controlled Austrian Corona Virus Adaptive Clinical Trial (ACOVACT), patients with hypertension and COVID-19 were randomized 1:1 to either RASi continuation (n= 30) or switch to a non-RASi medication (n= 29). RAS metabolites were analyzed using a mixed linear regression model (n= 30). Time to a sustained clinical improvement was equal and ACE2 did not differ between the groups but increased over time in both. Overall ACE2 was higher with severe COVID-19. ACE-S and Ang II levels increased as expected with ACE inhibitor discontinuation. These data support the safety of RASi continuation in COVID-19, although RASi were frequently discontinued in our post hoc analysis. The study was not powered to draw definite conclusions on clinical outcomes using small sample sizes.

The Vascular Quality Initiative assessment of the Bard Lifestent for the treatment of popliteal artery occlusive disease

ObjectiveThe Bard LifeStent self-expanding stent is approved for the treatment of occlusive disease involving the superficial femoral artery and proximal popliteal artery. We conducted a post-market trial of treatment of the popliteal artery above and below the knee (P1, P2, and P3 segments) within the Society for Vascular Surgery Vascular Quality Initiative (VQI) Peripheral Vascular Intervention registry. MethodsA single-arm, prospective trial was conducted at 29 VQI sites in the United States, enrolling 74 patients from November 2016 to May 2019. The primary safety outcome was freedom from major adverse events including device-/procedure-related mortality and major amputation at 1 year. The primary efficacy outcomes were freedom from target vessel revascularization and freedom from target lesion revascularization at 1 year. Secondary outcomes included lesion success; procedural success; primary, primary-assisted, and secondary patency; and sustained clinical (improvement in Rutherford class) and hemodynamic success (increase in ankle brachial index >0.10). Outcomes were assessed by Kaplan-Meier analysis. Arteriogram of patients undergoing target lesion revascularization were assessed for stent fracture by a core laboratory. ResultsThe mean age was 71 years, with 63.5% male and 55% with diabetes. The indication was claudication 28% and chronic limb-threatening ischemia in 72%. The superficial femoral artery-popliteal artery was stented in 38% and the popliteal artery alone in 62%. The majority of stents were placed in the P1 + P2 (39%) or P1 + P2 + P3 (37%) segments of the popliteal artery. The composite primary endpoint of freedom from major adverse events was 82% and 74% at 1 and 2 years, respectively. Freedom from mortality was 100% and 97%, and freedom from major amputation was 100% and 90% at 1 and 12 months, with all deaths and major amputations occurring in patients with chronic limb-threatening ischemia. freedom from target lesion revascularization was 86%, and freedom from target vessel revascularization was 84% at 12 months. At discharge, lesion treatment success was 99%, and procedural success was 82%. Primary patency was 80% and 72%, primary-assisted patency was 80% and 72%, and secondary patency was 89% and 82% at 12 and 24 months. Sustained clinical success was 98% and 95%, and sustained hemodynamic success was 100% and 79% at 12 and 24 months. ConclusionsIn this multi-center, registry-based, single-arm prospective study the Bard LifeStent self-expanding stent demonstrated favorable performance in the challenging anatomy of the P2 and P3 popliteal segment. Post-market studies for label expansion of peripheral vascular intervention devices can be successfully conducted within the Society for Vascular Surgery VQI registry.

A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2.

Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95). ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay. Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels. Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.

Long-term Results of a Heparin-bonded Expanded Polytetrafluoroethylene Grafts for Above-the-knee Femoropopliteal Bypasses: A Japanese Prospective Multicenter Registry

Propaten (WL Gore & Associates, Flagstaff, AZ) is a bioactive heparin-bonded expanded polytetrafluoroethylene graft widely used for bypass surgery; however, its long-term results are yet to be established. In this study, we evaluated the long-term results of Propaten for above-the-knee femoropopliteal bypasses (AKFPB) using a Japanese prospective multicenter registry. In this prospective single-arm multicenter registry, 120 limbs (113 patients) underwent AKFPB for superficial femoral artery (SFA) lesion in 20 Japanese institutions between July 2014 and October 2017. We evaluated the long-term results by estimating primary patency (PP), secondary patency (SP), freedom from target lesion revascularization (TLR), and freedom from death at 6 years using the Kaplan-Meier method. Factors associated with the risk for the loss of PP were investigated using the Cox proportional hazards regression model. Baseline characteristics of 120 limbs are summarized in Table. Mean lesion length was 26.2 ± 5.7 cm, chronic limb-threatening ischemia was present in 45 limbs (37.5%), and only 35 limbs (29.2%) had all three runoff vessels patent. Technical success was achieved in all cases, and 49 limbs (40.8%) had concomitant additional procedure, mainly endovascular treatment (EVT), and cuffed distal anastomosis was employed in 93 limbs (77.5%). There were eight perioperative complications (6.7%), however, mean ankle brachial index (ABI) improved from 0.45 ± 0.27 to 0.96 ± 0.14, and improvement in Rutherford classification (RC) was achieved in 98 limbs (81.7%) at 30 days. Clinical improvement was sustained at the latest follow-up as mean ABI was 0.87 ± 0.23, and improvement in RC was achieved in 105 limbs (87.5%). PP, freedom from TLR, SP, and freedom from death at 6 years were 66.1% ± 4.9%, 72.4% ± 4.5%, 85.6% ± 3.6%, and 62.9% ± 4.8%, respectively (Fig 1). As for the factors associated with the risk for the loss of PP, prior coronary disease (unadjusted hazard ratio [HR], 2.57; 95% confidence interval [CI], 1.09-4.36; P = .006), hemodialysis (unadjusted HR, 2.62; 95% CI, 1.19-5.57; P = .02), three runoff vessels patent (unadjusted HR, 0.48; 95% CI, 0.22-1.06; P = .07), and cuffed distal anastomosis (unadjusted HR, 0.51; 95% CI, 0.25-1.07; P = .08) were selected for the multivariate analysis from the result of univariate analysis; however, only prior coronary disease remained significant (adjusted HR, 2.18; 95% CI, 1.09-4.36; P = .03). Long-term sustained clinical improvement and acceptable SP was achieved for AKFPB using Propaten. When good venous conduit is unavailable, AKFPB using Propaten is a reasonable revascularization option for complex SFA lesions, especially when EVT is inappropriate.TablePatients’ demographics and characteristicsVariableN = 120 limbsAge, years72.7 ± 8.1Male sex81 (67.5%)Body mass index, kg/m222.5 ± 3.8Rutherford classification 230 (25.0%) 345 (37.5%) 413 (10.8%) 531 (25.8%) 61 (0.8%)Ankle brachial index0.45 ± 0.27Number of runoff vessels 01 (0.8) 143 (35.8) 241 (34.2) 335 (29.2)TASC II classifications A0 (0.0) B6 (5.0) C20 (16.7) D94 (78.3)Lesion length, cm26.2 ± 5.7Outflow popliteal artery diameter, mm4.9 ± 1.1Key comorbidities and medical history Smoking, current31 (25.8%) Smoking, former67 (55.8%) Prior superficial femoral artery treatment32 (26.7%) Arterial hypertension91 (75.8%) Diabetes mellitus63 (52.5%) Dyslipidemia57 (47.5%) Chronic kidney disease (eGFR <60 mL/min)69 (57.5%) Hemodialysis17 (14.2%) Prior coronary disease38 (31.7%) Prior cerebrovascular disease24 (20.8%) Serum albumin <3.0 g/dL24 (20.8%)eGFR, Estimated glomular filtration rate.Categorical variables are presented as number (%), and continuous variables are presented as mean ± standard deviation. Open table in a new tab

Treatment of Long Femoropopliteal Occlusive Lesions With Self-expanding Interwoven Nitinol Stent: 24 Month Outcomes of the STELLA-SUPERA-SIBERIA Register Trial.

The efficacy and safety of the Supera stent in superficial femoral artery (SFA) have been reported mostly in shorter lesions with relatively low proportion of occlusions. There are little data on the effectiveness of the Supera stent in long lesions. The aim of this study was to assess the clinical safety and efficiency of the Supera stent in the treatment of long femoropopliteal occlusive lesions (Trans-Atlantic Inter-Society Consensus [TASC] C/D) in patients with symptomatic peripheral artery disease. The STELLA-SUPERA-SIBERIA is a prospective, single-center, single-arm study. Patients with symptomatic (Rutherford stages 3-6) de novo and TASC C/D occlusive lesions of the femoropopliteal segment were treated with Supera stent. The primary endpoint was the 12 month rate of primary sustained clinical improvement (upward shift on the Rutherford classification to a one level without the need for repeated target lesion revascularization (TLR) in surviving patients without the need for unplanned amputation). Secondary endpoints were the 24 month of primary sustained clinical improvement, MALE, limb salvage, the primary patency, the secondary patency, 24 month MACE. Follow-up included clinical examination, duplex scan, and biplane x-ray up to 24 months. Between April 2019 and January 2020, 52 symptomatic patients with 55 long femoropopliteal occlusive lesions (52.7% TASC D lesions and 47.3% TASC C lesions) were treated. The mean target lesion length was 205±72 mm. All patients had total occlusions. The mean lesion length of the implanted Supera stents was 198±82 mm. At 12 and 24 months, the primary sustained clinical improvement rate was 80.2% and 63.6%, respectively. The Rutherford category assessment was significantly improved at 24 months compared with baseline (p=0.02). The primary patency rate at 12 and 24 months was 78.1% and 60.0%, respectively. At 12 and 24 months, freedom from TLR was 83.5% and 81.8%, respectively. There were no stent fractures at 24 months. Supera Stent implantation for TASC C/D femoropopliteal lesions revascularization appears to be a safe and efficient implant given the complexity of the treated lesions. Head-to-head studies are mandatory to establish Supera Stent as an alternative tool to open surgery for long femoropopliteal lesions. Our study indicated, that using self-expanding interwoven nitinol stent for TASC C/D femoropopliteal lesions revascularization appears to be a safe and efficient implant given the complexity of the treated lesions. Although bypass grafting is recommended for prolonged femoropopliteal lesions, open surgery is more traumatic and is associated with greater risks than endovascular procedures. Our findings suggest that the use of interwoven nitinol stents can overcome the disadvantages of traditional stents in such cases, which may help to improve patients' outcomes and reduce the risk of adverse events.

Rectal dural metastasis masquerading as chronic subdural hematoma: illustrative case.

Intracranial dural metastasis causing subdural hematoma formation is a rare clinical entity associated with significant morbidity and mortality. A 61-year-old female patient known to have rectal signet ring cell carcinoma presented with cranial computed tomography scan findings of bilateral subdural hematoma. She underwent evacuation of the hematoma with dural biopsy, which showed tumor emboli consistent with colorectal origin. There was an early recurrence of the subdural collection, and an emergency subdural-peritoneal shunt insertion was done; however, there was no sustained clinical improvement. This work reports the first case of rectal dural metastasis presenting as chronic subdural hematoma and discusses the clinical course and current literature. The cases described in these studies are consistent with the clinical course of our patient; that is, evacuation of the subdural hematoma provided temporary clinical improvement and re-accumulation occurred within 3 days. The authors recommend maintaining a high index of suspicion in this select group of patients, including prompt discussion about treatment plans with the patient's family.