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Chronic inflammatory skin disorders, such as atopic dermatitis, have significant disease burden worldwide. Although efficacious, the adverse effect profile of topical corticosteroids limits long-term use. As an alternative, cannabinoids have been shown to have anti-inflammatory therapeutic effects.The aim of this study was to assess the effects of a topical cannabinoid product using dermatitis mouse model.Thirty-five mice were randomized into treatment groups. 12- O -tetradecanoylphorbol-13-acetate was used as an irritant on 1 ear with the contralateral ear serving as a control. Ear edema was calipered. The test product containing 0.9% cannabidiol and palmitoylethanolamide was compared with a potent topical corticosteroid.Treatment with topical cannabinoid formulation reduced ear edema by 51.27% at 24 hours' and 65.69% at 48 hours' postapplication. Alternatively, mometasone reduced ear edema by 89.82% at 24 hours and 98.25% at 48 hours. Natural reduction (control) in ear edema was 26.32% at 24 hours and 44.21% at 48 hours. Both test groups resulted in significantly decreased edema when compared with baseline ( P0.05), as well as compared with the negative control group ( P0.05).Significant reduction in ear edema, a marker for localized cutaneous inflammation, could be attributed to anti-inflammatory properties of cannabinoids. Although effects were less robust than topical corticosteroid use, cannabinoid formulations have therapeutic promise for dermatitis.

BACKGROUND Isolated tricuspid valve (TV) surgery is a rare procedure generally considered at high risk for perioperative mortality and poor long-term outcomes. Surgical treatment can be performed with either an arrested heart (AH) or beating heart (BH) technique. The aim of this study was to compare the outcomes of isolated tricuspid surgery with 2 different approaches.METHODS The Surgical-Tricuspid Study is a multicenter international retrospective study enrolling adult patients who un- derwent isolated TV procedures (n = 406; age 56 +/- 16 years; 56% female) at 13 international sites. The AH and BH strategies were performed in 253 and 153 patients, respectively. Propensity score-matched analysis was used to compare groups.RESULTS After matching, 129 pairs were obtained and analyzed. The 30-day mortality rate was 6.2% versus 5.0% in the AH and BH groups, respectively (P = .9). The rates of acute renal failure requiring replacement therapy (10% versus 3%; P = .02) and stroke (1.6% versus 0%; P = .08) were numerically higher in the AH group. The 6-year survival rate was 67% +/- 6% versus 78% +/- 5% in the AH and BH groups, respectively (P = .18), whereas freedom from cardiac death was 75% +/- 5% versus 84% +/- 4% (P = .21). The 6-year composite cardiac end point of cardiac death and reoperation rate was 60% +/- 9% versus 86% +/- 5% (P - .024) comparing AH-TV replacement and BH-TV repair groups.CONCLUSIONS Isolated TV surgery performed with a BH strategy is a safe option and resulted in a trend of increased long-term survival and freedom from reoperation compared with the standard AH technique. Patients undergoing BH valve repair had the best long-term outcome. (C) 2022 by The Society of Thoracic Surgeons

For the newborns needing respiratory support at 36 weeks postmenstrual age, regardless of the type of ventilation used, it is critical to take into account the mechanics properties of both airways and lungs affected by severe bronchopulmonary dysplasia (sBPD). Ventilator strategies, settings, and weaning must change dramatically after sBPD is established, but to date there is almost no high-quality evidence base supporting a specific approach to guide the optimal ventilator management and weaning in patients with sBPD. Weaning from invasive mechanical ventilation, management of the immediately postextubation period, and weaning from noninvasive ventilation in patients with sBPD are the topics covered in this chapter.

In patients with coronavirus disease 2019 (COVID-19), the prevalence of pre-existing cardiovascular diseases is elevated. Moreover, various features, also including pro-thrombotic status, further predispose these patients to increased risk of ischemic cardiovascular events. Thus, the identification of optimal antithrombotic strategies in terms of the risk–benefit ratio and outcome improvement in this setting is crucial. However, debated issues on antithrombotic therapies in patients with COVID-19 are multiple and relevant. In this article, we provide ten questions and answers on risk stratification and antiplatelet/anticoagulant treatments in patients at risk of/with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on the scientific evidence gathered during the pandemic.

Amyloidosis is a systemic disease due to buildup of protein material in the extracellular space, which can affect the heart, mainly in its light chain and transtyretin forms. Historically this condition has been considered very uncommon, and it was certainly under-diagnosed. Today is well known that in certain group of patients its prevalence is, indeed, very high (25% in patients over the age of 80 years; 32% in patients over 75 years with heart failure and preserved systolic function, and 5% in post-mortem series of hypertrophic cardiomyopathy). Some genetically determined form of transthyretin amyloidosis are quite common in certain populations, such as Caribbean origin African-Americans. The wide spectrum of signs, symptoms, and first-level tests often overlapping among various other conditions, represent a diagnostic challenge for the clinical cardiologist. The opportunity to reach the diagnosis with non-invasive testing (first and foremost scintiscan with bone markers), as well as encouraging results of newer classes of drugs, raised the interest in this condition, so far burdened by an ominous prognosis. Early diagnosis of amyloidosis should always be guided by clinical suspicion but should also be supported by a multidisciplinary approach, aimed at optimizing the prognosis of the condition. Despite the newer drugs now available, a late diagnosis affect negatively the prognosis, and the opportunity to implement disease-modifying therapies (e.g. liver transplant in ATTR, or bone marrow transplant in AL) able to cure or at least delay the progression of the disease.

Acute pulmonary embolism (PE) is associated with significant morbidity and mortality. The management paradigm for acute PE has evolved in recent years with wider availability of advanced treatment modalities ranging from catheter-directed reperfusion therapies to mechanical circulatory support. This evolution has coincided with the development and implementation of institutional pulmonary embolism response teams (PERT) nationwide and internationally. Because most institutions are not equipped or staffed for advanced PE care, patients often require transfer to centers with more comprehensive resources, including PERT expertise. One of the unmet needs in current PE care is an organized approach to the process of interhospital transfer (IHT) of critically ill PE patients. In this review, we discuss medical optimization and support of patients before and during transfer, transfer checklists, defined roles of emergency medical services, and the roles and responsibilities of referring and receiving centers involved in the IHT of acute PE patients.

Diet has long been understood to have an intricate association with atopic dermatitis, although much remains unelucidated. Skin barrier dysfunction with dysbiosis and consequent impairment of immune tolerance likely underly the pathogenesis of coincident atopic dermatitis and food allergy. There is a wide range of possible skin reactions to food, complicating the diagnosis and understanding of food allergies. Many patients, parents, and providers incorrectly suspect diet as causative of atopic dermatitis symptoms and many have tried elimination diets. This frequently leads to inaccurate labeling of food allergies, contributing to a dangerous spiral of inappropriate testing, referrals, and dietary changes, while neglecting established atopic dermatitis treatment essentials. Alternatively, certain dietary supplements or the introduction of certain foods may be beneficial for atopic dermatitis management or prevention. Greater consensus on the role of diet among providers of patients with atopic dermatitis is strongly encouraged to improve the management of atopic dermatitis.

In patients with left ventricular thrombus (LVT) after acute myocardial infarction (MI), both anticoagulant and antiplatelet therapies are needed. It is unknown whether dual antithrombotic therapy (DAT) is able to reduce the incidence of bleeding complications without significantly increasing the number of thromboembolic events, compared to triple antithrombotic therapy (TAT). We retrospectively evaluated all post-MI patients with LVT discharged on TAT or DAT from our tertiary hospital in the last decade. The primary outcome was the occurrence of all-cause mortality, thromboembolic events, hospitalizations for re-MI or heart failure and any bleeding at 1 year. A propensity-score matching was performed in order to compare the primary outcome between TAT and DAT. Out of 2564 acute MI patients, 83 (3.2%) had an LVT at echocardiography: 51 (61.4%) discharged on TAT and 32 (38.6%) on DAT. At clinical follow-up, completed in 93% of cases, the incidence of the primary outcome was 18.2% (25.5% in TAT and 6.7% in DAT group; p = 0.04). More than 2/3 of the events included in the primary outcome were related to bleeding complications and occurred during the first month from hospital discharge. In the matched cohort of 42 patients with follow-up data available, the primary outcome occurred in 9 (42.9%) patients in the TAT and 2 (9.5%) in the DAT group (p = 0.03). In post-MI patients with LVT, DAT seems more effective than TAT in reducing clinical outcome, especially early bleeding complications. A randomized study is warranted to confirm this hypothesis.

Atopic dermatitis (AD) is a heterogeneous disorder with varying phenotypes. Although AD has long been associated with barrier dysfunction, the pathogenesis of this disease is more complex, involving many molecular markers in different functional domains. Biomarkers can be helpful in different ways, including predicting prognosis, measuring treatment response, and gauging disease severity. With the advent of targeted immunomodulators, biomarkers have the potential to take on new significance in terms of selecting appropriate therapies for patients. In this review, we have summarized the key findings related to biomarkers and AD, including the specific subtype differences. Clinicians will use this information to better understand the potential of biomarkers in AD and have a guide because more specific treatments are developed that are tailored toward individual molecular profiles.

Background Although anticoagulation with unfractionated heparin (UFH) is commonly used during intra-aortic balloon pump (IABP) counterpulsation to prevent thromboembolic events, no data or guidelines exist to support this strategy, especially in the setting of acute myocardial infarction (AMI). This study sought to compare the short-term outcome of UFH vs fondaparinux in AMI patients who underwent successful percutaneous coronary intervention (PCI) and IABP insertion. Methods The anticoagulation therapy of revascularised AMI patients who received IABP counterpulsation and admitted to a tertiary hospital in the last decade was retrospectively evaluated. The primary outcome was the occurrence of all-cause mortality, stroke or transient ischaemic attack, reinfarction, unplanned revascularisation, major or minor limb ischaemia, and any bleeding at 1 month. Propensity score matching was performed to compare the primary outcome between UFH and fondaparinux. Results Of 1,355 AMI survivors at 2 days after hospital admission and who underwent successful PCI, an IABP was inserted in 197 (14.5%): 72 (36.5%) were treated with UFH and 125 (63.5%) with fondaparinux (2.5 mg o.d.). At clinical follow-up, completed in 98.5% of cases, the incidence of the primary outcome was 22.5% in UFH and 5.7% in fondaparinux groups (p=0.0009). More than two-thirds of the events included in the primary outcome were related to early bleeding complications. In the matched cohort of 62 patients, the primary outcome occurred in 14 (45.2%) patients in the UFH and two (6.5%) in the fondaparinux group (p=0.01). Conclusions This study suggested that fondaparinux is safer, by reducing early bleeding complications at one month, than UFH in the management of IABP.

Background: Crisaborole is a nonsteroidal anti-inflammatory phosphodiesterase 4 inhibitor that is approved for the treatment of patients with mild-to-moderate atopic dermatitis (AD); however, the efficacy and safety of crisaborole in patients with AD and other atopic comorbidities have not been investigated. Objective: This post hoc pooled analysis of the pivotal phase III studies (CrisADe CORE 1 and CORE 2) assessed the efficacy and safety of crisaborole versus vehicle in patients aged ≥ 2 years with mild-to-moderate AD and other atopic comorbidities. Methods: Patients with mild-to-moderate AD and a medical history of asthma, allergic rhinitis, or food allergies were identified. Efficacy assessments included the proportion of patients who achieved Investigator's Static Global Assessment (ISGA) success at day 29, ISGA clear or almost clear at day 29, and improvement in the Severity of Pruritus Scale score at week 4. Safety was assessed via treatment-emergent adverse events (TEAEs). Results: This analysis included 1522 patients (crisaborole, 1016; vehicle, 506); 26.2, 15.9, and 16.5% had a medical history of asthma, allergic rhinitis, and food allergies, respectively. The mean age was 12.2 years. A significantly greater proportion of patients treated with crisaborole achieved ISGA success at day 29 compared with patients treated with vehicle for most subgroups analyzed. Furthermore, a significantly greater proportion of patients treated with crisaborole achieved ISGA clear or almost clear at day 29 across all subgroups and demonstrated improvement in the Severity of Pruritus Scale score at week 4 versus patients treated with vehicle in most of the subgroups. Overall, most TEAEs were mild or moderate in severity; the most common treatment-related TEAE in patients with atopic comorbidities was application-site pain (crisaborole, 5.1%; vehicle, 1.7%). Conclusion: Crisaborole was efficacious and well tolerated in patients with mild-to-moderate AD and other atopic comorbidities, which suggested that crisaborole should be considered for the management of AD in this population. Clinical Trials NCT02118766 (CrisADe CORE 1) and NCT02118792 (CrisADe CORE 2), www.clinicaltrials.gov

We report the case of a woman with a mass in the anterior and middle mediastinum (a non-small-cell lung carcinoma), determining significant compression of both superior vena cava and right pulmonary artery. The patient developed acute respiratory distress syndrome , necessitating intubation and admission to the Intensive Care Unit . Radiotherapy sessions to reduce the mass effect were attempted, without significant clinical improvement. Due to the persistence of severe hypoxemia, stenting of the superior vena cava and the right pulmonary artery was performed, the latter resulting in a significant improvement of the arterial blood gas parameters, allowing extubation of the patient. In our opinion, stenting of the superior vena cava and the pulmonary artery (or its branches) is an effective and safe treatment; it should be considered in similar cases, especially if other - less invasive - treatments fail.

Background Baricitinib previously demonstrated improvements in itch and sleep disturbance versus placebo in adults with moderate-to-severe atopic dermatitis (AD). Objectives Examine if itch and sleep improvements are associated with better quality of life (QoL) and productivity in patients with AD. Methods Data were drawn from BREEZE-AD5 (NCT03435081). Itch and sleep improvement at Week 16 were defined using ≥4-point improvements in the Itch Numeric Rating Scale and ≥1.5 decreases in the number of nighttime awakenings since baseline, respectively. Patients with and without improvements were compared on Dermatology Life Quality Index (DLQI) and Work Productivity and Activity Impairment-AD scores. Changes from baseline were analyzed using ANCOVA with last observation carried forward. Proportions were analyzed using logistic regression with non-responder imputation. Results Greater proportions of patients with versus without itch improvement indicated no impact of AD on QoL (37.7 vs. 1.8%). Patients with itch improvement had greater decreases in work time impaired (-29.3 vs. -5.6%). More patients with versus without sleep improvement reported no effect of AD on QoL (25.5 vs. 1.1%); patients with better sleep experienced larger reductions in work time spent impaired (-33.3 vs. -6.1%). Conclusions Patients with AD who experienced itch and sleep improvement had significantly better QoL and productivity.

BACKGROUND Atopic dermatitis (AD) is a growing burden in all ages. The aim of this study was to compare trial characteristics between pediatric and adult AD trials. METHODS Data were collected from ClinicalTrials.gov on AD therapeutic trials completed between 2003 and 2019. The trials were classified as pediatrics (mean or median age

Background: IgE-mediated reactions constitute 70% of cow's milk-induced allergic reactions (AR). There is no established treatment. Recent evidence suggests that immunomodulation with probiotics represents a safe novel strategy, influencing immunity and inducing tolerance to milk protein antigens by action on human gut microbiota. Current evidence focuses most on the infant population. Objective: We will study the impact of Lactobacillus rhamnosus GG (LGG), compared to placebo, as an effective agent to improve ARs upon exposure to cow's milk in children from 5 to 10 years of age. Methods: This will be a phase II, single-center, randomized, double-blinded, placebo-controlled study, where a total of 200 participants will be treated for 12 months, with either; LGG or placebo, randomly allocated at 1:1. A double-blinded placebo-controlled food challenge (DBPCFC) with cow's milk will be used before and after the intervention. Results will be graded using the PRACTALL scoring system. The primary outcome will be binary – 'passing' by the absence of any AR, or a decrease from the baseline results or 'not passing' the DBPCFC after treatment. Secondary outcomes will include covariate adjustment and subgroup analysis by affected body systems and severity of ARs. Secondary analyses will include a comparison of the proportions of the taxonomic composition of gut microbiota, and quality of life, with baseline measurements. Conclusion: This trial will contribute to filling knowledge gaps about cow's milk allergy management using LGG in this specific population as an affordable and accessible non-pharmacological agent with few recorded side effects. If proven to be efficacious, it has the potential to decrease the worldwide prevalence of CMA and the resulting systemic, familial, and personal burdens.

Cell therapies for the treatment of skin disorders could benefit from simple, safe and efficient technology for the transdermal delivery of therapeutic cells. Conventional cell delivery by hypodermic-needle injection is associated with poor patient compliance, requires trained personnel, generates waste and has non-negligible risks of injury and infection. Here, we report the design and proof-of-concept application of cryogenic microneedle patches for the transdermal delivery of living cells. The microneedles are fabricated by stepwise cryogenic micromoulding of cryogenic medium with pre-suspended cells, and can be easily inserted into porcine skin and dissolve after deployment of the cells. In mice, cells delivered by the cryomicroneedles retained their viability and proliferative capability. In mice with subcutaneous melanoma tumours, the delivery of ovalbumin-pulsed dendritic cells via the cryomicroneedles elicited higher antigen-specific immune responses and led to slower tumour growth than intravenous and subcutaneous injections of the cells. Biocompatible cryomicroneedles may facilitate minimally invasive cell delivery for a range of cell therapies. Cryogenic microneedle patches can deliver mammalian cells before dissolving into the skin, as shown with the transdermal delivery of ovalbumin-pulsed dendritic cells in mice with subcutaneous tumours.

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy.

Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March–April 2019 vs March–April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 2020

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores.Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs.Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Introduction An image-guided form of superficial ionizing radiation therapy (IGSRT) is becoming a commonly used alternative to surgery for non-melanoma skin cancer (NMSC). However, there is little literature evidence evaluating the efficacy and safety of this approach. This study evaluates the efficacy and safety of IGSRT in treating a large number of patients with NMSC. Methods The medical records of 1632 stage 0–II patients with 2917 invasive and in situ NMSC lesions treated from years 2017 to 2020 were reviewed. No patients had clinical evidence of regional lymph node or distant disease at presentation. Results Treatment, guided by pre-treatment ultrasound imaging to adjust radiation energy and dose, combined with a fractionation treatment schedule of 20 or more treatment fractions, was safe and well tolerated. Of 2917 NMSC lesions treated, local tumor control was achieved in 2897 lesions, representing a 99.3% rate of control. Conclusion IGSRT should be considered as a first-line option for treating NMSC tumors in suitable early stage patients. Cure rates observed in this initial period of follow-up are similar, and potentially superior with further follow-up, to traditional superficial radiation therapy (SRT) and surgical options. Supplementary Information The online version contains supplementary material available at 10.1007/s40487-021-00138-4.

Dupilumab has recently been approved by the Food and Drug Administration for use for treatment of moderate to severe atopic dermatitis in children aged 6 to 11 years. It presents a novel treatment option with a favorable safety profile for patients who are currently reliant on immunosuppressants, including cyclosporine A, methotrexate, and mycophenolate mofetil. Particularly during the current COVID-19 pandemic, immunosuppression should be avoided to retain intrinsic antiviral immunity. Transitioning to dupilumab should be executed strategically-tapering immunosuppressants and minimizing risk of flare by overlapping with the biologic. Herein, we use results of outcome measurements from LIBERTY AD ADOL and LIBERTY AD PEDS trials of dupilumab in adolescents aged 12 to 18 years and children aged 6 to 11 years, respectively, to propose a schematic for an 8-week transition between medications.

Cannabinoids (CBDs) represent a diverse class of chemicals that may be beneficial in the treatment of various skin diseases due to antipruritic, anti-inflammatory, and antinociceptive properties. Although the legal history of these compounds has previously restricted their use and study, it seems likely that CBDs will gain popularity as they become increasingly available. We examined the mechanisms in which CBDs may have potential in the field of dermatology and reviewed the existing literature. We suggest that dermatologists review the existing evidence for CBD use and be ready to discuss it with their patients. The current literature indicates that CBDs may be beneficial in skin disease, particularly in the treatment of acne, chronic pruritus, and atopic dermatitis. Although there is preliminary evidence to suggest that CBDs are beneficial in these conditions, existing studies tend to be small and lacking rigorous design. There is a clear need for high-quality randomized controlled trials to fully evaluate the efficacy and safety of these compounds before their use can be promoted in the treatment of dermatological diseases.

Atopic dermatitis (AD) is a chronic skin disorder characterized by pruritus, erythema and excoriation. While AD has a multifactorial etiology, neuro-signaling pathways are now recognized to play an essential role in the pathogenesis of AD, particularly pruritus. Neuromodulators, such as topical naltrexone, are being utilized in AD treatment. Another class of neuromodulator, Palmitoylethanolamide (PEA), has demonstrated effectiveness in the treatment of itch, excoriation and erythema in AD patients. Phytocannabinoids including cannabidiol (CBD) are becoming increasingly accessible to the public and continue to be advertised for their efficacy to treat inflammatory skin disorders such as eczema. However, no human studies have been conducted to support the claim. Therefore, this study aimed to explore the effects of CBD in individuals with self-reported eczema. Twenty individuals consented to participate and 16 completed a 28-item online questionnaire assessing subjectsrsquo; disease severity using Patient Oriented Eczema Measure (POEM) and psychosocial burden of their disease through the emotional domain of Quality of Life Hand Eczema Questionnaire (QOLHEQ). Findings demonstrated a significant reduction in the mean score of POEM from baseline (meanplusmn;SE: 16plusmn;1.35) and at a two weeks interval (8.25plusmn;1.80), Plt;0.0007. Similar reduction was seen in emotional domain of QOLHEQ from a mean score of 20.9plusmn;2.06 to 8.375plusmn;1.609 at 2 week-interval, Plt;0.004. 67% of subjects reported a decrease in itch and 50% perceived an improvement in their eczema by more than 60%. This observational study shed light on the potential clinical utility of topical CBD in the treatment of atopic dermatitis. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5464.

Supplemental Digital Content is available in the text., Background: To assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients of predominantly Chinese ancestry. Methods: We sequenced HCM disease genes in Singaporean patients (n=224) and Singaporean controls (n=3634), compared findings with additional populations and White HCM cohorts (n=6179), and performed in vitro functional studies. Results: Singaporean HCM patients had significantly fewer confidently interpreted HCM disease variants (pathogenic/likely pathogenic: 18%, P

Background Atopic dermatitis (AD) has a negative impact on patientsr quality of life (QoL). Objective To report the impact of specific AD lesion locations on QoL in adult patients with AD using real-world data. Methods The Adelphi US Disease Specific Programme was conducted between JanuarynApril 2018. Physicians documented patient demographics/characteristics, AD lesion locations, and body surface area; patients completed questionnaires reporting the impact of lesion locations on QoL. Results AD severity was moderate in 51.6% of patients and severe in 6.0%. Lesions were commonly identified in more than one location. All AD lesion locations impacted QoL. Visible areas were most bothersome, including head/neck (68%), hands/fingers (58%), front (30%), upper extremities (22%), and lower extremities (16%), with statistically significant associations for a number of Dermatology Life Quality Index (DLQI) items. Itch, soreness, pain, and stinging are also associated with a number of body areas but in particular with those that are most visible/accessible. Lesions on the head/neck and hands/fingers (58%) demonstrated an increased impact on the anxiety and depression dimension of the EuroQol 5-Dimension tool. Conclusions In patients with AD, quality of life was most affected in patients with lesions in visible areas, including head/neck, hands/fingers, and upper extremities, with statistically significant associations for a number of DLQI domains. Physicians should be aware of the burden of AD lesions on QoL and consider having conversations with patients to better understand the impact of these lesions. Prior presentation: 28th Annual European Academy of Dermatology and Venereology Congress; 9n13 October 2019, Madrid, Spain. Poster number P0233.J Drugs Dermatol. 2020;19(10): 943-948. doi:10.36849/JDD.2020.5422.

Background The central mound technique offers a relatively less common approach for breast reduction. This study evaluated the expected safety and efficacy outcomes using this technique in a large patient series. Methods A retrospective review of all patients undergoing central mound breast reduction at the authors' institution between June of 1999 and November of 2018 was performed. Both bilateral macromastia and unilateral symmetrizing reduction patients were included but evaluated separately for some outcomes. Patient demographics and comorbidities, operative details, postoperative adverse events, and BREAST-Q scores were recorded. Associations between preoperative variables and outcomes were assessed with chi-square tests, Wilcoxon tests, and Kendall tau-b correlations. Results A total of 325 patients were identified for inclusion (227 bilateral and 98 unilateral; 552 breasts). The average patient age was 46 years, and the average body mass index was 27.4 kg/m. Among the bilateral macromastia patients, the average operative time was 3 hours 34 minutes, and average breast tissue removed was 533 g (right breast) and 560 g (left breast). Among all patients, average follow-up was 169 days. On a per-breast basis for all patients, the following complication rates were observed: seroma, 0.2 percent; hematoma, 1.1 percent; dehiscence, 2.9 percent; infection, 1.5 percent; hypertrophic scar, 4.6 percent; nipple necrosis, 0.4 percent; fat necrosis, 0.9 percent; and skin flap necrosis, 1.7 percent. Using the BREAST-Q Reduction/Mastopexy questions on a Likert scale ranging from 1 to 5, restricted to the bilateral macromastia patient population, all scores improved with statistical significance. Conclusion The central mound pedicle is a safe and effective approach for reduction mammaplasty for both bilateral macromastia patients and unilateral symmetrizing operations. Clinical question/level of evidence Therapeutic, IV.

BACKGROUND AND AIM OF THE STUDY The aim of this meta-analysis was to compare short- and long-term outcomes of patients undergoing mitral annuloplasty (MA) with or without papillary muscle surgery (PMS) for the treatment of ischemic mitral regurgitation (IMR). METHODS A systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were performed. RESULTS Nine studies met the inclusion criteria. This meta-analysis identified 478 patients: 228 patients underwent MA alone and 250 patients underwent concomitant PMS. Early mortality was similar between two groups (odds ratio [OR] 1.14, 95% confidence interval [CI], 0.51-2.53; P = .75). PMS was associated at follow-up with a higher freedom from cardiac-related events (P = .050); moreover, although both surgical techniques had a positive impact on ventricular remodeling, the PMS group showed a significant higher reduction of left ventricle end-diastolic diameter (OR, 4.89, 95% CI, 2.77-7.01; P

Multiple pathways contribute to the pathogenesis of atopic dermatitis (AD), and various targeted topical, biologic, and oral systemic agents have subsequently been developed. This review examines the mechanism of action and study designs of agents that have failed trials for AD to identify lessons that may shed light on reasons for their failure. Clinicaltrials.gov was searched for completed, placebo-controlled phase II and III studies assessing agents for AD that did not meet the primary endpoint, specifically reduction of AD severity. PubMed was then searched for further data on the agents identified with known mechanism of actions. Only phase II trials met inclusion criteria. Analyses of the mechanisms of action, study design, and patient demographics of the failed clinical trials for the following agents are presented: apremilast and roflumilast (PDE-4 inhibitors), fevipiprant and temapiprant (CRTH2 inhibitors), and tezepelumab and ustekinumab (monoclonal antibodies). Agents that did not meet their trial endpoints for AD may still hold therapeutic value in certain subpopulation groups or other diseases. Validating phase II trials based off subgroup analyses from previous trials may be warranted as our understanding of the pathophysiology of AD continues to grow.

Endoleak it is the most common complication after endovascular abdominal aortic aneurysm repair and it represents the failure of endovascular treatment. In particular type 2 endoleak is associated with retrograde flow in the aneurysm sac from one or more arterial branches.We describe a reperfusion of the aortic aneurysm sac with slow-flow type II endoleak from the right internal iliac artery aneurysm through the posterior door previously closed with coils, and treatment with direct puncture of the internal iliac artery aneurysm with infixion of human thrombin under ultrasound guidance, not previously described in the literature.In this case the direct puncture of the aneurysm sac was the faster and safer way to treat this patient just because the back door was closed by coils and the entry by the iliac graft.Thrombin reduces significantly the presence of artifacts and give to us the exact extension of thrombosis into the aneurysm sac and the echo-guided offers the advantage of being able to monitor the progression of the thrombotic process induced by thrombin injection in real time. Keywords: Endoleak, Embolization, Internal iliac artery aneurysm, Thrombin injection

Background: Previous studies have demonstrated that polymorphisms involved in immune genes can affect the risk, pathogenesis, and outcome of thoracic ascending aortic aneurysms (TAAA). Here, we explored the potential associations of five functional promoter polymorphisms in interleukin-6 (IL-6), IL-1B, IL-1A, IL-18, and Tumor necrosis factor (TNF)A genes with TAAA. Methods: 144 TAAA patients and 150 age/gender matched controls were typed using KASPar assays. Effects on telomere length and levels of TAAA related histopathological and serological markers were analyzed. Results: Significant associations with TAAA risk were obtained for IL-6 rs1800795G&gt, C and IL-1B rs16944C&gt, T SNPs. In addition, the combined rs1800795C/rs16944T genotype showed a synergic effect on TAAA pathogenesis and outcome. The combined rs1800795C/rs16944T genotype was significantly associated with: (a) higher serum levels of both cytokines and MMP-9 and -2, (b) a significant CD3+CD4+CD8+ CD68+CD20+ cell infiltration in aorta aneurysm tissues, (c) a significant shorter telomere length and alterations in telomerase activity. Finally, it significantly correlated with TAAA aorta tissue alterations, including elastic fragmentation, medial cell apoptosis, cystic medial changes, and MMP-9 levels. Conclusions: the combined rs1800795C/rs16944T genotype appears to modulate TAAA risk, pathogenesis, and outcome, and consequently can represent a potential predictive and prognostic TAAA biomarker for individual management, implementation of innovative treatments, and selection of the more proper surgical timing and approaches.

Although atopic dermatitis (AD) classically presents as eczematous, pruritic plaques in the flexural regions of children, AD can present with several morphologies and distributions that may vary wi...

Objectives: interleukin 11 (IL11) is highly upregulated in skin and lung fibroblasts from patients with systemic sclerosis (SSc). Here we tested whether IL11 is mechanistically linked with activation of human dermal fibroblasts (HDFs) from patients with SSc or controls. Methods: we measured serum IL11 levels in volunteers and patients with early diffuse SSc and manipulated IL11 signalling in HDFs using gain- and loss-of-function approaches that we combined with molecular and cellular phenotyping. Results: in patients with SSc, serum IL11 levels are elevated as compared to healthy controls. All transforming growth factor beta (TGFβ) isoforms induced IL11 secretion from HDFs, which highly express IL11RA and the gp130 co-receptor, suggestive of an autocrine loop of IL11 activity in HDFs. IL11 stimulated ERK activation in HDFs and resulted in HDF-to-myofibroblast transformation and extracellular matrix secretion. The pro-fibrotic action of IL11 in HDFs appeared unrelated to STAT3 activity, independent of TGFβ upregulation and was not associated with phosphorylation of SMAD2/3. Inhibition of IL11 signaling using either a neutralizing antibody against IL11 or siRNA against IL11RA reduced TGFβ-induced HDF proliferation, matrix production and cell migration, which was phenocopied by pharmacologic inhibition of ERK. Conclusions: these data reveal that autocrine IL11-dependent ERK activity alone, or downstream of TGFβ stimulation, promotes fibrosis phenotypes in dermal fibroblasts and suggest IL11 as a potential therapeutic target in SSc., Singapore STaR Awards; National Medical Research Council (NMRC) Centre Grants; BMRC; Goh Foundation;Tanoto Foundation; Duke-NUS; SingHealth Core Funding

Background: Congenital heart defects (CHDs) are present in about 40&ndash, 60% of newborns with Down syndrome (DS). Patients with DS can also develop acquired cardiac disorders. Mouse models suggest that a critical 3.7 Mb region located on human chromosome 21 (HSA21) could explain the association with CHDs. This region includes a cluster of genes (IFNAR1, IFNAR2, IFNGR2, IL10RB) encoding for interferon receptors (IFN-Rs). Other genes located on different chromosomes, such as the vascular endothelial growth factor A (VEGFA), have been shown to be involved in cardiac defects. So, we investigated the association between single nucleotide polymorphisms (SNPs) in IFNAR2, IFNGR2, IL10RB and VEGFA genes, and the presence of CHDs or acquired cardiac defects in patients with DS. Methods: Individuals (n = 102) with DS, and age- and gender-matched controls (n = 96), were genotyped for four SNPs (rs2229207, rs2834213, rs2834167 and rs3025039) using KASPar assays. Results: We found that the IFNGR2 rs2834213 G homozygous genotype and IL10RB rs2834167G-positive genotypes were more common in patients with DSand significantly associated with heart disorders, while VEGFA rs3025039T-positive genotypes (T/*) were less prevalent in patients with CHDs. Conclusions: We identified some candidate risk SNPs for CHDs and acquired heart defects in DS. Our data suggest that a complex architecture of risk alleles with interplay effects may contribute to the high variability of DS phenotypes.

Brazil experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continuous struggle with effective control and public health preparedness. Using Oxford Nanopore sequencing, we led field and classroom initiatives for the monitoring of DENV in Brazil, generating 227 novel genome sequences of DENV1-2 from 85 municipalities (2015–2019). This equated to an over 50% increase in the number of DENV genomes from Brazil available in public databases. Using both phylogenetic and epidemiological models we retrospectively reconstructed the recent transmission history of DENV1-2. Phylogenetic analysis revealed complex patterns of transmission, with both lineage co-circulation and replacement. We identified two lineages within the DENV2 BR-4 clade, for which we estimated the effective reproduction number and pattern of seasonality. Overall, the surveillance outputs and training initiative described here serve as a proof-of-concept for the utility of real-time portable sequencing for research and local capacity building in the genomic surveillance of emerging viruses., Here, the authors present results of the ZiBRA-2 project (https://www.zibra2project.org) which is an arbovirus surveillance project, across the Midwest of Brazil using a mobile genomics laboratory, combined with a genomic surveillance training program that targeted post-graduate students, laboratory technicians, and health practitioners in universities and laboratories.

Background Unhealthy diet during pregnancy poses serious risks for both mothers and children, representing an important Public Health issue. Although Epigenetics offers a plausible explanation of the transgenerational pathway from mother to child, it is still necessary to understand if maternal epigenetic aging increases the risk for adverse outcomes in newborns. In this scenario, the “MAternal Diet, Risks and Epigenetic age during pregnancy: a Real-world Ecological momentary Assessment” (MADRE-REA) study aims to evaluate the relationship between maternal diet, epigenetic age and risk for adverse pregnancy outcomes in a mother-child cohort. Methods We will develop a smartphone-based ecological momentary assessment (EMA) of dietary, behavioral, physical, and sociopsychological information of 400 pregnant women recruited by the “Mamma & Bambino” cohort (Catania, Italy). Women will be asked to complete 6 waves of EMA during the 2nd and 3rd trimesters of pregnancy, and 3, 6, 9 and 12 months after delivery. Each wave consists of a 7-day assessment based on a signal-contingent approach, which prompts participants to record dietary consumption and other information. We will also examine maternal epigenetic age at recruitment and at delivery, using the DNAm PhenoAge. Results The novelty of the MADRE-REA study lies in the opportunity to apply a smartphone-based EMA to capture the complexity of dietary intake during and after pregnancy. Moreover, expected findings will help to understand if maternal behaviors and other exposures might affect epigenetic age, and hence if the eventual accelerated biological aging might be associated with health and disease in newborns. Conclusions This study could disentangle the relationship between maternal diet, epigenetic aging, and adverse outcomes, laying the foundation for future strategies to reduce the burden of disease in newborns throughout their life. The study is funded by the Italian Ministry of Health (Bando Ricerca Finalizzata 2019). Key messages The application of a smartphone-based tool could overcome limitations of traditional methods to assess dietary behaviors in the periconceptional period. Uncovering the relationship between maternal diet and epigenetic aging could provide the molecular basis for future strategies against adverse pregnancy outcomes.

Hutchinson-Gilford progeria syndrome is an autosomal dominant, rare, fatal pediatric segmental premature aging disease. Cardiovascular and cerebrovascular diseases constitute the major cause of morbidity and mortality. Patients with the syndrome and severe aortic valve stenosis have been described in the literature, and for all of them a strategy of conservative management has been followed. We describe the first successful treatment of a 23-year-old Hutchinson-Gilford progeria syndrome patient with severe aortic stenosis who underwent transapical transcatheter aortic valve replacement.

Left ventricular aneurysms (LVA) are a complication of myocardial infarction, that rarely involve the posterior wall; surgical repair of posterior LVA poses a technical challenge when associated with concomitant mitral regurgitation. We describe a minimally invasive treatment of ischemic MR and concomitant patch exclusion of posterior LVA through a right minithoracotomy. Using a transatrial approach, the aneurysm is closed with a "U" shaped dacron patch, whose base is anchored to the mitral annulus. Two patients were operated by this method with excellent results.

Background In Italy, 4991 cases of measles were reported in 2017 and 322 involved healthcare workers (HCWs). These professionals are at high risk of infection and transmission of virus both to other hospital staff and importantly, to patients, some of whom may be at risk of severe illness and complications. According to the Italian National Immunization and Prevention Plan, all HCWs should have demonstrable evidence of immunity to measles and specific hospital surveillance is recommended. Given a recent measles outbreak recorded in Italy, which also involved HCWs, the aim of this study has been to assess the measles immunization status of the Perugia General Hospital's HCWs. Methods A survey on all hospital staff was carried out, using a questionnaire to obtain information on demographic characteristics, personal history of measles and self-reported vaccination status, and offering the serological testing to HCWs who did not know their immune status. Results Among the 1714 HCWs included in the study, 1207 (70%) were protected against measles (due to vaccination or natural infection), and 507 (30%) did not know their immune status. Of these, 461 subjects accepted a serological control, while 46 refused. Protective measles-specific IgG antibody titres were documented in 410/461 (89%) HCWs, and the percentage of immune subjects decreased with the age. Conclusions Our study shows that in Perugia General Hospital, 26% of HCWs under the age of 30 were not protected against measles. In Italy, campaigns promoting vaccination of HCWs are needed to prevent transmission of this infection in hospital setting.

Aren (Arengapinnata) is a type of coconut palm which is one of the plants that can produce a type of traditional alcoholic beverage and has 4% alcohol content. Consumption of too much alcohol can cause anemia by affecting the process of blood formation (hematopoiesis) through metabolic and nutritional effects and also directly inhibits the proliferation of all cellular elements in the bone marrow. The purpose of this study was to determine the relationship of the duration of kameko consumption to hematological levels in Labaha Village, WatoputeSubdistrict, Muna Regency in 2018. This study is an observational analytical study with a cross sectional study design. The results showed that of the 25 respondents, the cross tabulation test showed, for the duration of consumption with hematological levels ≤ 5 years with a total of 17 respondents obtained abnormal examination scores for Hemoglobin levels (58.8%), Erythrocytes (41.2%), and Leukocytes (41.2%). While consumption of kameko> 5 years with a total of 8 respondents, abnormal hematological levels were obtained. While the spearman correlation test between the duration of consumption and the three parameters of Hemoglobin test, Erythrocyte and Leukocyte obtained sig. p

Background and aim of the study Today there is little experience with minimally invasive treatment of multiple valve disease and no standard techniques have been provided yet. We report our early experience with combined aortic and mitral valve surgery with or without tricuspid surgery through a right lateral minithoracotomy (RmT), describing the technical aspects of our approach. Methods From April 2017 to April 2019 thirty patients with mitro-aortic valve disease or with triple valve pathology underwent surgery through a 3 to 4 cm lateral RmT into the third intercostal space. Cardiopulmonary bypass was established through femoral vessels cannulation. Surgery on the mitral valve (MV) was performed first and sutures put into the mitral annulus. Aortic valve replacement (AVR) was performed next. Then, the selected ring or prosthetic valve was implanted in a mitral position throughout previously placed sutures. Finally, if required, tricuspid valve surgery was performed. Results In combined with AVR, MV replacement was performed in 20 patients (66%), and MV repair in 10 patients (34%). Concomitant tricuspid annuloplasty was performed in five patients (17%). There was no conversion to full sternotomy. Postoperatively, one patient died. Postoperative echocardiography showed no perivalvular leakage in aortic or in the mitral position. No residual mitral regurgitation was observed in patients who underwent MV repair. Conclusions Minimally invasive surgery of double and triple valve disease is feasible. Our approach through a lateral RmT allows optimal visualization of the aortic, mitral, and tricuspid valves, simplifies the surgical procedure and allows excellent results also in complex MV repair procedures.

Dupilumab, a monoclonal antibody that inhibits both interleukin (IL)-4 and IL-13 signaling, is an effective treatment option in moderate-to-severe atopic dermatitis (AD). Patients with AD are already at increased risk of developing conjunctivitis, and clinical trials and case reports have shown a greater incidence of conjunctivitis in individuals with AD treated with dupilumab. As this is one of the more commonly reported side effects of this biologic agent, it is important that clinicians are aware of this association and advise patients receiving dupilumab to report signs of conjunctivitis. This review summarizes the risk factors, clinical features, and management options for patients with AD presenting with conjunctivitis after receiving dupilumab therapy.

Purpose: Tofacitinib citrate is an oral Janus kinase 1/3 inhibitor approved for rheumatoid arthritis, ulcerative colitis, and active psoriatic arthritis. Tofacitinib is being increasingly used off-label for dermatological conditions, with varying efficacy across recent studies. A review of these studies will be a helpful resource for dermatologists considering the use of tofacitinib for conditions refractory to first-line therapies. Materials and methods: MEDLINE, Embase, CINAHL Plus, Cochrane Library, Scopus, Web of Science, Clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform were all searched for articles and trials mentioning the term 'tofacitinib', then manually reviewed to identify published data on off-label uses of tofacitinib. The article was structured according to the quality of the evidence available. Results: Tofacitinib appears to show strong efficacy for numerous dermatologic conditions. Randomized controlled trial data is available for atopic dermatitis, alopecia areata, and plaque psoriasis. Case report and case series data is available for numerous other dermatologic conditions. Conclusion: While tofacitinib has a wide array of immunoregulatory properties, making it a possible candidate for treating many dermatologic conditions refractory to other treatments, further testing is needed to better characterize its efficacy and utility moving forward, as well as its safety and adverse effect profile.

This review summarizes the mechanisms, applications, and adverse effects of colorful dyes, such as Castellani’s paint, gentian violet, and potassium permanganate, as well as two other vibrant topical creams—vitamin B12 and indigo naturalis. Certain dyes such as Castellani’s paint, gentian violet, and potassium permanganate were once commonplace topical therapies for cutaneous infections; these dyes are brightly colored on application and have been suggested to be efficacious and well tolerated through case studies as well as controlled studies. Moreover, topical vitamin B12 and topical indigo naturalis creams for atopic dermatitis and psoriasis have been extensively studied through multiple controlled trials and may also be effective, with minimal adverse effects. Understanding the composition and mechanism of action has helped guide the development of these therapies.

Despite that different registries already exist in various countries in Europe and North America, no ongoing nationwide registry exists in Latin America (LATAM), a region where the disease behaves differently than in other regions. The objective of this document is to describe the methodology behind RelevarEM, the first nationwide MS registry in Argentina and LATAM. METHODS: In this article, we described the creation, implementation and data management of the nationwide MS registry in Argentina. The registry contains information on the structure, ethical aspects, implementation and variables of the registry (Clinical Trials registry number NCT NCT03375177). CONCLUSION: RelevarEM is the first MS nationwide registry in Argentina, as well as in LATAM, with the objective of providing reliable real-world data of MS in the country.

International audience; OBJECTIVES:HIV controllers (HICs) are rare HIV-infected individuals able to maintain undetectable viremia in the absence of antiretroviral treatment. Although HIV-specific cytotoxic T cells have been well deciphered in HIC, γδ T lymphocytes remain largely uncharacterized. The aim of this study was to analyse phenotypic and functional characteristics of γδ T cells and their relationship with immune activation, which remains abnormally elevated and associated with comorbidities in HICs.METHODS:Peripheral blood mononuclear cells (PBMCs) were isolated from 16 HICs, 16 patients with untreated chronic HIV infection (UT-CHI) and 20 healthy donors. Surface marker expression and cytokine production by γδ T cells were analysed by flow cytometry.RESULTS:Despite normal frequencies of total γδ T cells, the Vδ2/Vδ2 ratio was significantly reduced in HIC, albeit to a lesser extent than UT-CHI patients. Of note, nine HICs showed elevated Vδ2 γδ T cells, as patients with UT-CHI, which was associated with higher CD8 T-cell activation. Interleukin (IL)-17-production by γδ T cells (Tγδ17) was better preserved in HIC than in UT-CHI patients. Proportion of total γδ T cells positively correlated with CD8 T-cell activation and HIV-DNA, IP-10 and sCD14 levels. Conversely, Tγδ17 cells negatively correlated with CD8 T-cell activation and plasma sCD14 levels. Moreover, transforming growth factor (TGF)-β producing Vδ2 T cells were as dramatically depleted in HIC as in UT-CHI patients.CONCLUSION:The relative preservation of IL-17-producing γδ T cells in HIC and their negative association with immune activation raise the hypothesis that Tγδ17 cells - potentially through prevention of microbial translocation - may participate in the control of chronic systemic immune activation.

Cardiac implantable electronic device (CIED) implantation has greatly increased, with an associated exponential increase in CIED infections (CDIs). Cardiac device related infective endocarditis (CDRIE) has high morbidity and mortality: approximately 10-21%. Therefore, a prompt diagnosis and radical treatment of CDRIE are needed; transvenous lead extraction (TLE) is the mainstay for the complete healing, even if associated with wide logistic problems, high therapeutic costs and high mortality risk for patients. Some criticisms about the value of Duke criteria and their limitations for the diagnosis of CDRIE are known. The significance of classic laboratory data, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE), considered in the Duke score, are reviewed and critically discussed in this article, with regard to the specific field of the diagnosis of CDI. The need for new techniques for achieving the diagnostic reliability has been well perceived by physicians, and additional techniques have been introduced in the new European Society of Cardiology (ESC) and British Heart Rhythm Society (BHRS) guidelines on infective endocarditis. These suggested techniques, such as 18-Fluorodeoxyglucose PET/computed tomography (FDG-PET/CT), white blood cell PET (WBC PET) and lung multislice CT (MSCT), are also discussed in the study. This short review is intended as an extensive summary of the diagnostic workflow in cases of CDI and will be useful for readers who want to know more about this issue.

As the first targeted systemic agent for the treatment of moderate to severe atopic dermatitis (AD), dupilumab represents a novel therapeutic opportunity for both patients and providers. However, a subset of patients receiving dupilumab are either partial responders who exhibit some improvement in Investigator's Global Assessment score but not sufficient to meet the primary endpoint, or are non-durable responders who achieve therapeutic endpoint with subsequent partial loss of efficacy. We propose a therapeutic algorithm for the management of dupilumab partial responders and non-durable responders that involves maximizing topical therapy, seeking alternative diagnoses, and using dupilumab in conjunction with traditional systemic immunosuppressive agents. With a number of targeted agents for AD in the drug development pipeline, we encourage patients who do not have an adequate response to dupilumab to remain patient and optimistic as the arsenal of AD treatment modalities continues to expand.

IMPORTANCE: Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of skin clearance and itch improvement. OBJECTIVE: To assess the safety and efficacy of upadacitinib vs dupilumab in adults with moderate-to-severe AD. DESIGN, SETTING, AND PARTICIPANTS: Heads Up was a 24-week, head-to-head, phase 3b, multicenter, randomized, double-blinded, double-dummy, active-controlled clinical trial comparing the safety and efficacy of upadacitinib with dupilumab among 692 adults with moderate-to-severe AD who were candidates for systemic therapy. The study was conducted from February 21, 2019, to December 9, 2020, at 129 centers located in 22 countries across Europe, North and South America, Oceania, and the Asia-Pacific region. Efficacy analyses were conducted in the intent-to-treat population. INTERVENTIONS: Patients were randomized 1:1 and treated with oral upadacitinib, 30 mg once daily, or subcutaneous dupilumab, 300 mg every other week. MAIN OUTCOMES AND MEASURES: The primary end point was achievement of 75% improvement in the Eczema Area and Severity Index (EASI75) at week 16. Secondary end points were percentage change from baseline in the Worst Pruritus Numerical Rating Scale (NRS) (weekly average), proportion of patients achieving EASI100 and EASI90 at week 16, percentage change from baseline in Worst Pruritus NRS at week 4, proportion of patients achieving EASI75 at week 2, percentage change from baseline in Worst Pruritus NRS (weekly average) at week 1, and Worst Pruritus NRS (weekly average) improvement of 4 points or more at week 16. End points at week 24 included EASI75, EASI90, EASI100, and improvement of 4 points or more in Worst Pruritus NRS from baseline (weekly average). Safety was assessed as treatment-emergent adverse events in all patients receiving 1 or more dose of either drug. RESULTS: Of 924 patients screened, 348 (183 men [52.6%]; mean [SD] age, 36.6 [14.6] years) were randomized to receive upadacitinib and 344 were randomized to receive dupilumab (194 men [56.4%]; mean [SD] age, 36.9 [14.1] years); demographic and disease characteristics were balanced among treatment groups. At week 16, 247 patients receiving upadacitinib (71.0%) and 210 patients receiving dupilumab (61.1%) achieved EASI75 (P = .006). All ranked secondary end points also demonstrated the superiority of upadacitinib vs dupilumab, including improvement in Worst Pruritus NRS as early as week 1 (mean [SE], 31.4% [1.7%] vs 8.8% [1.8%]; P