Subcision with and without suction for acne scars: a split-faced, rater-blinded randomized control trial.

Therapeutic options for acne scars include subcision and suction with microdermabrasion, but these treatment modalities have not been studied in conjunction. To compare effectiveness of subcision alone versus subcision with suction for the treatment of facial acne scars. Randomized, split-faced, evaluator-blinded control trial. Participants underwent one subcision treatment on both sides of the face followed by 10 sessions of suction to one side. Photographs at baseline, 1-month, and 4-months were assessed. Primary outcome measures were the validated Acne Scar Severity Scale (ASSS) (0 = no acne scarring, 4 = severe), Acne Scar Improvement Grading Scale (ASIGS) (-100 to 100%), and modified Quantitative Global Scarring Grades (QGSG) (point-based questionnaire instrument), as well as subject preference. Twenty-eight treatment areas and 154 treatments were analyzed. Dermatologist raters found no differences between subcision alone and subcision-suction at 1-month or 4-months. Mean subject-assessed percent improvement for subcision-suction was higher than that for subcision alone at 1-month (37% versus 24%, p = 0.04) but not at 4-months (p = 0.37). Subjects preferred combination therapy to monotherapy at 1-month (50% vs. 21%) and 4-months (43% vs. 21%). While blinded raters did not detect significant differences, subjects perceived combination treatment as working more quickly than monotherapy, and preferred combination treatment at all time points.Clinical trial registration NCT01696513 on Clinicaltrials.gov.

Electrolyte-Enabled High-Voltage Operation of a Low-Nickel, Low-Cobalt Layered Oxide Cathode for High Energy Density Lithium-Ion Batteries.

The lithium-ion battery industry acknowledges the need to reduce expensive metals, such as cobalt and nickel, due to supply chain challenges. However, doing so can drastically reduce the overall battery energy density, attenuating the driving range for electric vehicles. Cycling to higher voltages can increase the capacity and energy density but will consequently exacerbate cell degradation due to the instability at high voltages. Herein, an advanced localized high-concentration electrolyte (LHCE) is utilized to enable long-term cycling of a low-Ni, low-Co layered oxide cathode LiNi0.60Mn0.31Co0.07Al0.02O2 (NMCA) in full cells with graphite or graphite-silicon anodes at 4.5 V (≈4.6 vs Li+/Li). NMCA cells with the LHCE deliver a high initial capacity of 194 mA h g-1 at C/10 rate along with 73% capacity retention after 400 cycles compared to 49% retention in a baseline carbonate electrolyte. This is facilitated by reduced impedance growth, active material loss, and gas evolution with the NMCA cathode. These improvements are attributed to the formation of robust, inorganic-rich interphase layers on both the cathode and anode throughout cycling, which are induced by a favorable salt decomposition in the LHCE. This study demonstrates the efficacy of electrolytes toward facilitating the operation of high-energy-density, long-life, and cost-effective cathodes.

Protocol of a scoping review of outcome domains in dermatology.

INTRODUCTION: Core outcome sets (COSs) are agreed outcomes (domains (subdomains) and instruments) that should be measured as a minimum in clinical trials or practice in certain diseases or clinical fields. Worldwide, the number of COSs is increasing and there might be conceptual overlaps of domains (subdomains) and instruments within disciplines. The aim of this scoping review is to map and to classify all outcomes identified with COS projects relating to skin diseases. METHODS AND ANALYSIS: We will conduct a scoping review of outcomes of skin disease-related COS initiatives to identify all concepts and their definitions. We will search PubMed, Embase and Cochrane library. The search dates will be 1 January 2010 (the point at which Core Outcome Measures in Effectiveness Trials (COMET) was established) to 1 January 2024. We will also review the COMET database and C3 website to identify parts of COSs (domains and/or instruments) that are being developed and published. This review will be supplemented by querying relevant stakeholders from COS organisations, dermatology organisations and patient organisations for additional COSs that were developed. The resulting long lists of outcomes will then be mapped into conceptually similar concepts. ETHICS AND DISSEMINATION: This study was supported by departmental research funds from the Department of Dermatology at Northwestern University. An ethics committee review was waived since this protocol was done by staff researchers with no involvement of patient care. Conflicts of interests, if any, will be addressed by replacing participants with relevant conflicts or reassigning them. The results will be disseminated through publication in peer-reviewed journals, social media posts and promotion by COS organisations.

Acquired ichthyosis: a clinical review.

Acquired ichthyosis (AI) is a rare, nonhereditary cutaneous disorder that has been associated with numerous neoplastic, infectious, drugs, endocrine, metabolic, autoimmune, and malabsorptive diseases. Review all demographical, clinical, histological, and therapeutic features of AI and focus on all reported associated diseases. We performed a systematic literature review in Pubmed/Medline, Embase, and Cochrane collaboration databases, searching for all articles on AI, with no limits on publication date, participant age, sex or nationality. Eighty-four articles were included. Total number of included patients was 167 patients with a mean age at presentation of 39 years [range 0.5-85] and a sex ratio M:F of 5:2. The most common malignancy associated with AI is Hodgkin's lymphoma. AI occurred before, simultaneously or after the onset of malignancy or systemic disease. The severity of AI depends on the severity of the underlying disorder and regresses once the disease goes into remission and may also be a marker of disease recurrence or relapse. 8% have been reported to be drug related and all occurred weeks to months after drug intake and resolved after stopping or decreasing the dose of the drug. Data were derived from case reports and observational studies. Limitations include the accuracy of published data, potential patient selection, and reporting bias. AI can be associated with numerous systemic diseases and drugs. Physicians should be particularly alert to these associations to provide adequate screening and management of patients with AI.

Development of an international glossary for clinical guidelines collaboration.

OBJECTIVES: Clinical practice guidelines (CPGs) are often created through collaboration among organizations. The use of inconsistent terminology may cause poor communication and delays. This study aimed to develop a glossary of terms related to collaboration in guideline development. STUDY DESIGN AND SETTING: A literature review of collaborative guidelines was performed to develop an initial list of terms related to guideline collaboration. The list of terms was presented to the members of the Guideline International Network Guidelines Collaboration Working Group, who provided presumptive definitions for each term and proposed additional terms to be included. The revised list was subsequently reviewed by an international, multidisciplinary panel of expert stakeholders. Recommendations received during this pre-Delphi review were implemented to augment an initial draft glossary. The glossary was then critically evaluated and refined through two rounds of Delphi surveys and a virtual consensus meeting with all panel members as Delphi participants. RESULTS: Forty-nine experts participated in the pre-Delphi survey, and 44 participated in the two-round Delphi process. Consensus was reached for 37 terms and definitions. CONCLUSION: Uptake and utilization of this guideline collaboration glossary by key organizations and stakeholder groups may facilitate collaboration among guideline-producing organizations by improving communication, minimizing conflicts, and increasing guideline development efficiency.

Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy.

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells1-14. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies15-17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.

Treatment of actinic keratosis: a systematic review.

Treatment of actinic keratoses (AKs) can help lower the risk of eventual skin cancer and address field pre-cancerization. This review compares the different therapeutic options for actinic keratosis. Databases used include Medline, EMBASE, Web of Science and the Cochrane Library from inception to December 2019. Randomized control trials that were related to any approved or recognized treatment for actinic keratosis were included. 1186 studies were found, of which 80 with 6748 patients were included in the analysis. A network meta-analysis was not possible due to interstudy heterogeneity. The greatest degree of improvement was seen with photodynamic therapy (PDT) used adjunctively with other modalities, but this was not significantly different compared to other treatments. PDT, cryotherapy, imiquimod, ingenol mebutate (IMB), 5-fluorouracil (5-FU), trichloroacetic acid (TCA), and ablative fractional laser (AFXL), were all non-inferior to one another in terms of percent clearance of AKs, but the lowest rates of clearance were seen with diclofenac sodium. When results were substratified by body site, 5-FU, combination PDT and combination 5-FU with calcipotriol were the most beneficial for AKs on the head and neck, although they often caused the highest proportion of initial side effects. Absence of randomized control trials for surgical treatments and non-ablative laser limits comparison of these treatments to other modalities. Limitations include the lack of standardized outcome reporting limited the comparability of results across trials. The results of this analysis do not account for individual patient risk or cumulative risk for development of skin cancer. At present, PDT, cryotherapy, imiquimod, IMB, 5-FU, TCA, AFXL, and combination treatments are similarly efficacious in reducing AKs in immunocompetent patients.Registration: N/A.

Non-viral precision T cell receptor replacement for personalized cell therapy.

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRß). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial ( NCT03970382 ). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

The Effects of Loaded Plyometric Exercise during Warm-Up on Subsequent Sprint Performance in Collegiate Track Athletes: A Randomized Trial.

Prior evidence demonstrates the efficacy by which plyometric activities during warm-up conditions augment the subsequent performance in power-centric exercise. We investigated the acute effects of loaded jump squats incorporated into a standard sprinters' warm-up protocol on subsequent sprint performance in collegiate track athletes. Sprint times of 22 male and female collegiate track athletes were measured in 10-m intervals during a 30-m sprint trial following a standard sprinters' warm-up routine with or without plyometric exercise. Subjects were tested on two separate occasions, once with loaded jump squats as the experimental treatment (two sets of eight jumps, load = 13% bodyweight) (PLYO) and once with time-equated rest as the control treatment (CON). Treatments were implemented following a standard sprinters' warm-up routine familiar to the subjects. A dependent T-test was used for comparison of sprint interval times between conditions with a significant effect indicated by a p-value < 0.05. Sprint time did not differ between CON vs. PLYO at the 10 m (PLYO = 1.90 ± 0.12 s vs. CON = 1.90 ± 0.11 s, p = 0.66), 20 m (PLYO = 3.16 ± 0.21 s vs. CON = 3.15 ± 0.19 s, p = 0.53), and 30 m (PLYO = 4.32 ± 0.32 s vs. CON = 4.31 ± 0.28 s, p = 0.61) intervals. There was no interaction between treatment and sex, sex-specific ranking (above vs. below sex-specific mean), or sprint event (short vs. short-long vs. long) for 10 m, 20 m, or 30-m interval sprint times. At least within the limits of the current investigation, no evidence was provided to suggest that jump squats loaded at 13% bodyweight are an effective means to acutely potentiate sprint performance in collegiate track athletes. However, a further examination of responders indicates that the present loaded jump squat protocol may preferentially potentiate sprint performance in faster male athletes.