Detecting T-cell receptor clonality in patients with severe atopic dermatitis refractory to dupilumab.

BACKGROUND: Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response. OBJECTIVE: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab. METHODS: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL. RESULTS: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements. CONCLUSION: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.

Drug Eluting Stent vs. Drug Coated Balloon for Native Femoropopliteal Artery Disease: A Two Centre Experience.

OBJECTIVE: There have been limited clinical trials comparing drug eluting stents (DESs) and drug coated balloons (DCBs) in the treatment of femoropopliteal artery disease. This two centre retrospective and prospective cohort study sought to compare DES with DCB for the treatment of native femoropopliteal artery disease. METHODS: A total of 288 limbs (242 patients) with native femoropopliteal artery disease were treated with DESs (Zilver PTX; 102 limbs) or DCBs (IN.PACT Admiral; 186 limbs) in two Korean endovascular centres between 19 January 2013 and 5 May 2018 and followed for a median duration of 19.6 months. The primary endpoint was primary clinical patency. Propensity score matching (PSM, 162 limbs) and inverse probability weighted (IPW) adjustment were performed to adjust for confounding baseline characteristics. RESULTS: The DCB group had fewer lesions with Trans-Atlantic Inter-Society Consensus (TASC) II type C/D (55.9% vs. 70.6%, p = .021) or total occlusions (43.5% vs. 77.5%, p < .001) and showed shorter lesion lengths (164.2 ± 105.4 mm vs. 194.8 ± 86.8 mm, p = .009) than the DES group. After PSM, baseline clinical and lesion characteristics of the two groups were comparable except for larger reference vessel diameter in the DES group (5.4 ± 0.6 vs. 5.1 ± 0.7, p = .025). Adjunctive atherectomy was performed in 32.1% of the DCB group and in 2.5% of the DES group (p < .001). The provisional stenting was required in 14.8% of the DCB group. At two year follow up, the DCB group showed higher primary clinical patency (74.6% vs. 56.7%, hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.27-0.96, p = .032) and freedom from target lesion revascularisation (85.9% vs. 71.3%, HR 0.39, 95% CI 0.17-0.89, p = .021) than the DES group. Survival from all cause death did not differ between groups (87.6% vs. 92.1%, HR 1.85, 95% CI 0.62-5.52, p = .26). CONCLUSION: In this two centre cohort, DCBs with selective use of adjunctive atherectomy achieved more favourable outcomes than DESs for native femoropopliteal artery disease.

Identification of plaque ruptures using a novel discriminative model comprising biomarkers in patients with acute coronary syndrome.

Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), neutrophil gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-9 (MMP-9) are inflammatory biomarkers involved in plaque destabilization resulting in acute coronary syndrome (ACS). This study aimed to investigate the diagnostic value of a combination of biomarkers to discriminate plaque ruptures in the setting of ACS. Eighty-five ACS patients with optical coherence tomography (OCT) images of the culprit plaque were included and categorized into two groups: ACS with plaque rupture (Rupture group, n = 42) or without plaque rupture (Non-rupture group, n = 43) verified by OCT. A discriminative model of plaque rupture using several biomarkers was developed and validated. The Rupture group had higher white blood cell (WBC) counts and peak creatine kinase-myocardial band (CK-MB) levels (13.39 vs. 2.69 ng/mL, p = 0.0016). sLOX-1 (227.9 vs. 51.7 pg/mL, p < 0.0001) and MMP-9 (13.4 vs. 6.45 ng/mL, p = 0.0313) levels were significantly higher in the Rupture group, whereas NGAL showed a trend without statistical significance (59.03 vs. 53.80 ng/mL, p = 0.093). Receiver operating characteristic curves to differentiate Rupture group from Non-rupture group calculated the area under the curve for sLOX-1 (p < 0.001), MMP-9 (p = 0.0274), and NGAL (p = 0.0874) as 0.763, 0.645, and 0.609, respectively. A new combinatorial discriminative model including sLOX-1, MMP-9, WBC count, and the peak CK-MB level showed an area under the curve of 0.8431 (p < 0.001). With a cut-off point of 0.614, the sensitivity and specificity of plaque rupture were 62.2% and 97.6%, respectively. The new discriminative model using sLOX-1, MMP-9, WBC count, and peak CK-MB levels could better identify plaque rupture than each individual biomarker in ACS patients.

Unnecessary PCI Attempt for Presumed CTO Which Was Revealed To Be Anomalous Coronary Arteries - Role of Coronary CT Angiography.

Herein, we present a brief case of anomalous coronary arteries mistaken to be chronic total occlusion. Since we first presumed the anomalous coronary arteries to be chronic total occlusion of the distal right coronary artery, percutaneous coronary intervention was attempted for the presumed lesion, but it failed. Before the second attempt of percutaneous coronary intervention, coronary computed tomography angiography revealed the coronary artery from the left anterior descending artery corresponding with the distal part of the right coronary artery without connection to the right coronary artery. Therefore, we recognized the patient had anomalous coronary arteries with no connection of the vascular wall between the main and distal segments of the right coronary artery. This case may give insights to the importance of meticulous examination of coronary computed tomography angiography imaging before chronic total occlusion percutaneous coronary intervention to avoid the unnecessary procedure.

Savior in Desperate Situation: Successful TAVI for Critically Ill Patient with Severe Aortic Stenosis and Concomitant Constrictive Pericarditis Accompanied by Radiation Dermatitis, Complicated by Cold Abscess in Anterior Chest Wall.

BACKGROUND: Constrictive pericarditis (CP) can coexist with severe aortic stenosis (AS), especially in patients with previous mediastinal radiation. Because impaired diastolic filling by CP may aggravate hemodynamic abnormalities from severe AS, leading to very low cardiac output, concomitant AS and CP result in a critical debilitating condition and pose a challenge to therapy. CASE REPORT: A 79-year-old woman was brought to our hospital with New York Heart Association class IV dyspnea and severe frailty (clinical frailty scale 8). She had a history of chronic constrictive pericarditis, severe aortic stenosis with reduced left ventricular systolic function (ejection fraction 40%), paroxysmal atrial fibrillation, diabetes mellitus, and radiation dermatitis complicated by a cold abscess in the anterior chest wall from previous mediastinal radiation. She continually complained of dizziness, general weakness, and dyspnea despite optimal medical treatment, and her symptoms worsened recently while bedridden. Although simultaneous surgical pericardiectomy and aortic valve replacement is curative treatment, and the surgical risk was not high (Society of Thoracic Surgery score 4.745), her other comorbidities (radiation dermatitis, cold abscess, and severe frailty) eliminated the possibility of surgical treatment. Therefore, we decided on palliative treatment for CP after performing transcatheter aortic valve implantation (TAVI) for severe AS. We could not predict how she would recover from these conditions and were concerned about the high procedural risk associated with TAVI. Indeed, the patient had cardiac arrest during the TAVI procedure, and we implanted a 31-mm CoreValve while performing cardiac massage. After the patient recovered from cardiac arrest, we safely completed the TAVI procedure with a temporary pacemaker because of complete atrioventricular block. She recovered remarkably after TAVI with permanent pacemaker implantation, and is now able to walk without support. CONCLUSION: Reduced diastolic filling by chronic CP aggravates hemodynamic deterioration through severe AS, leading to a very serious debilitating condition including severe frailty and decompensated heart failure. Although surgical pericardiectomy and aortic valve replacement are recommended as optimal therapy, TAVI alone can be an alternative therapeutic option if surgery is not possible.