Summary
Background
Scabies is a common parasitic skin condition that causes considerable morbidity globally. Clinical and epidemiological research for scabies has been limited by a lack of ...standardization of diagnostic methods.
Objectives
To develop consensus criteria for the diagnosis of common scabies that could be implemented in a variety of settings.
Methods
Consensus diagnostic criteria were developed through a Delphi study with international experts. Detailed recommendations were collected from the expert panel to define the criteria features and guide their implementation. These comments were then combined with a comprehensive review of the available literature and the opinion of an expanded group of international experts to develop detailed, evidence‐based definitions and diagnostic methods.
Results
The 2020 International Alliance for the Control of Scabies (IACS) Consensus Criteria for the Diagnosis of Scabies include three levels of diagnostic certainty and eight subcategories. Confirmed scabies (level A) requires direct visualization of the mite or its products. Clinical scabies (level B) and suspected scabies (level C) rely on clinical assessment of signs and symptoms. Evidence‐based, consensus methods for microscopy, visualization and clinical symptoms and signs were developed, along with a media library.
Conclusions
The 2020 IACS Criteria represent a pragmatic yet robust set of diagnostic features and methods. The criteria may be implemented in a range of research, public health and clinical settings by selecting the appropriate diagnostic levels and subcategories. These criteria may provide greater consistency and standardization for scabies diagnosis. Validation studies, development of training materials and development of survey methods are now required.
What is already known about this topic?
The diagnosis of scabies is limited by the lack of accurate, objective tests. Microscopy of skin scrapings can confirm the diagnosis, but it is insensitive, invasive and often impractical.
Diagnosis usually relies on clinical assessment, although visualization using dermoscopy is becoming increasingly common.
These diagnostic methods have not been standardized, hampering the interpretation of findings from clinical research and epidemiological surveys, and the development of scabies control strategies.
What does this study add?
International consensus diagnostic criteria for common scabies were developed through a Delphi study with global experts.
The 2020 International Alliance for the Control of Scabies (IACS) Criteria categorize diagnosis at three levels of diagnostic certainty (confirmed, clinical and suspected scabies) and eight subcategories, and can be adapted to a range of research and public health settings.
Detailed definitions and figures are included to aid training and implementation. The 2020 IACS Criteria may facilitate the standardization of scabies diagnosis.
What is already known about this topic?
The diagnosis of scabies is limited by the lack of accurate, objective tests. Microscopy of skin scrapings can confirm the diagnosis, but it is insensitive, invasive and often impractical.
Diagnosis usually relies on clinical assessment, although visualization using dermoscopy is becoming increasingly common.
These diagnostic methods have not been standardized, hampering the interpretation of findings from clinical research and epidemiological surveys, and the development of scabies control strategies.
What does this study add?
International consensus diagnostic criteria for common scabies were developed through a Delphi study with global experts.
The 2020 International Alliance for the Control of Scabies (IACS) Criteria categorize diagnosis at three levels of diagnostic certainty (confirmed, clinical and suspected scabies) and eight subcategories, and can be adapted to a range of research and public health settings.
Detailed definitions and figures are included to aid training and implementation. The 2020 IACS Criteria may facilitate the standardization of scabies diagnosis.
In 101 patients with refractory large B-cell lymphoma, anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (axicabtagene ciloleucel) resulted in an overall response rate of 82%, with a 52% ...survival at 18 months, despite serious toxic effects.
The near-term progression of ocean acidification (OA) is projected to bring about sharp changes in the chemistry of coastal upwelling ecosystems. The distribution of OA exposure across these ...early-impact systems, however, is highly uncertain and limits our understanding of whether and how spatial management actions can be deployed to ameliorate future impacts. Through a novel coastal OA observing network, we have uncovered a remarkably persistent spatial mosaic in the penetration of acidified waters into ecologically-important nearshore habitats across 1,000 km of the California Current Large Marine Ecosystem. In the most severe exposure hotspots, suboptimal conditions for calcifying organisms encompassed up to 56% of the summer season, and were accompanied by some of the lowest and most variable pH environments known for the surface ocean. Persistent refuge areas were also found, highlighting new opportunities for local adaptation to address the global challenge of OA in productive coastal systems.
Tumor-infiltrating lymphocytes (TIL) are strongly associated with survival in most cancers; however, the tumor-reactive subset that drives this prognostic effect remains poorly defined. CD39, CD103, ...and PD-1 have been independently proposed as markers of tumor-reactive CD8
TIL in various cancers. We evaluated the phenotype, clonality, and prognostic significance of TIL expressing various combinations of these markers in high-grade serous ovarian cancer (HGSC), a malignancy in need of more effective immunotherapeutic approaches.
Expression of CD39, CD103, PD-1, and other immune markers was assessed by high-dimensional flow cytometry, single-cell sequencing, and multiplex immunofluorescence of primary and matched pre/post-chemotherapy HGSC specimens.
Coexpression of CD39, CD103, and PD-1 ("triple-positive" phenotype) demarcated subsets of CD8
TIL and CD4
regulatory T cells (Treg) with a highly activated/exhausted phenotype. Triple-positive CD8
TIL exhibited reduced T-cell receptor (TCR) diversity and expressed genes involved in both cytolytic and humoral immunity. Triple-positive Tregs exhibited higher TCR diversity and a tumor-resident phenotype. Triple-positive TIL showed superior prognostic impact relative to TIL expressing other combinations of these markers. TIGIT was uniquely upregulated on triple-positive CD8
effector cells relative to their CD4
Treg counterparts.
Coexpression of CD39, CD103, and PD-1 demarcates highly activated CD8
and CD4
TIL with inferred roles in cytolytic, humoral, and regulatory immune functions. Triple-positive TIL demonstrate exceptional prognostic significance and express compelling targets for combination immunotherapy, including PD-1, CD39, and TIGIT.
Most patients with advanced-stage indolent non-Hodgkin lymphoma have multiple relapses. We assessed axicabtagene ciloleucel autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in ...relapsed or refractory indolent non-Hodgkin lymphoma.
ZUMA-5 is a single-arm, multicentre, phase 2 trial being conducted at 15 medical cancer centres in the USA and two medical cancer centres in France. Patients were eligible if they were aged 18 years or older, with histologically confirmed indolent non-Hodgkin lymphoma (follicular lymphoma or marginal zone lymphoma), had relapsed or refractory disease, previously had two or more lines of therapy (including an anti-CD20 monoclonal antibody with an alkylating agent), and an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients underwent leukapheresis and received conditioning chemotherapy (cyclophosphamide at 500 mg/m2 per day and fludarabine at 30 mg/m2 per day on days −5, −4, and −3) followed by a single infusion of axicabtagene ciloleucel (2 × 106 CAR T cells per kg) on day 0. The primary endpoint was overall response rate (complete response and partial response) assessed by an independent review committee per Lugano classification. The primary activity analysis was done after at least 80 treated patients with follicular lymphoma had been followed up for at least 12 months after the first response assessment at week 4 after infusion. The primary analyses were done in the per-protocol population (ie, eligible patients with follicular lymphoma who had 12 months of follow-up after the first response assessment and eligible patients with marginal zone lymphoma who had at least 4 weeks of follow-up after infusion of axicabtagene ciloleucel). Safety analyses were done in patients who received an infusion of axicabtagene ciloleucel. This study is registered with ClinicalTrials.gov, NCT03105336, and is closed to accrual.
Between June 20, 2017, and July 16, 2020, 153 patients were enrolled and underwent leukapheresis, and axicabtagene ciloleucel was successfully manufactured for all enrolled patients. As of data cutoff (Sept 14, 2020), 148 patients had received an infusion of axicabtagene ciloleucel (124 84% who had follicular lymphoma and 24 16% who had marginal zone lymphoma). The median follow-up for the primary analysis was 17·5 months (IQR 14·1–22·6). Among patients who were eligible for the primary analysis (n=104, of whom 84 had follicular lymphoma and 20 had marginal zone lymphoma), 96 (92%; 95% CI 85–97) had an overall response and 77 (74%) had a complete response. The most common grade 3 or worse adverse events were cytopenias (104 70% of 148 patients) and infections (26 18%). Grade 3 or worse cytokine release syndrome occurred in ten (7%) patients and grade 3 or 4 neurological events occurred in 28 (19%) patients. Serious adverse events (any grade) occurred in 74 (50%) patients. Deaths due to adverse events occurred in four (3%) patients, one of which was deemed to be treatment-related (multisystem organ failure).
Axicabtagene ciloleucel showed high rates of durable responses and had a manageable safety profile in patients with relapsed or refractory indolent non-Hodgkin lymphoma.
Kite, a Gilead Company
An ecologically and economically disruptive harmful algal bloom (HAB) affected much of the northeast Pacific margin in 2015, during a prolonged oceanic warm anomaly. Caused by diatoms of the genus ...Pseudo‐nitzschia, this HAB produced the highest particulate concentrations of the biotoxin domoic acid (DA) ever recorded in Monterey Bay, California. Bloom inception followed strong upwelling during the spring transition, which introduced nutrients and eliminated the warm anomaly locally. Subsequently, moderate and intermittent upwelling created favorable conditions for growth and accumulation of HAB biomass, which was dominated by a highly toxigenic species, P. australis. High cellular DA concentrations were associated with available nitrogen for DA synthesis coincident with silicate exhaustion. This nutrient influence resulted from two factors: (1) disproportionate depletion of silicate in upwelling source waters during the warm anomaly, the most severe depletion observed in 24 years, and (2) silicate uptake by the dense diatom bloom.
Key Points
The most toxic algal bloom ever recorded in Monterey Bay, California, occurred in spring 2015, during a hiatus in a prolonged warm anomaly
The dense bloom of Pseudo‐nitzschia australis resulted from a strong spring upwelling transition followed by intermittent upwelling
Toxicity was influenced by anomalously low ratios of silicate to nitrate that predisposed the bloom to silicate exhaustion
We describe smooth non-stationary generalized additive modelling for sample extremes, in which spline smoothers are incorporated into models for exceedances over high thresholds. Fitting is by ...maximum penalized likelihood estimation, with uncertainty assessed by using differences of deviances and bootstrap simulation. The approach is illustrated by using data on extreme winter temperatures in the Swiss Alps, analysis of which shows strong influence of the north Atlantic oscillation. Benefits of the new approach are flexible and appropriate modelling of extremes, more realistic assessment of estimation uncertainty and the accommodation of complex dependence patterns.
Objectives
This study sought to investigate the differences in the quality of dried ginger samples obtained from two places in Zambia, Lusaka and Copperbelt in terms of their secondary metabolite ...differences and heavy metals content.
Methods
Ten and eight batches of dried ginger obtained, respectively, from Lusaka and Copperbelt were analysed using untargeted Q/TOF‐MS‐based metabolomics and inductively coupled plasma optical emission spectroscopy (ICP‐OES).
Key findings
The metabolomics approach yielded 11 differential metabolites that clearly discriminated between the samples from the two locations. Eight were found to be more abundant in the samples from Lusaka while three were present in greater amounts in the samples from Copperbelt. The results of the heavy metal content analysis for four selected elements, Cd, Pb, As and Cu, showed that the samples from Copperbelt recorded higher levels. However, all samples contained levels of the toxic metals, Cd and Pb above permissible limits, making them unwholesome for human consumption.
Conclusions
The outcome of the heavy metal content analysis led us to speculate that abiotic stress as a result of these metals experienced by the ginger rhizomes during cultivation could have contributed to the metabolites abundance differences. Further studies are, however, recommended to verify this hypothesis.
This phase I/II study examined the safety and efficacy of Sepantronium Bromide (S), a small-molecule selective survivin suppressant, administered in combination with carboplatin (C) and paclitaxel ...(P).
Forty-one patients were treated on study. Twenty-two patients received escalating doses of S (3.6–12 mg/m2) and 19 with untreated stage IV non-small-cell lung cancer (NSCLC) were treated with the maximum tolerated dose of 10 mg/m2 in combination with standard doses of C (AUC6) and P (200 mg/m2) for six cycles. S was administered as a continuous intravenous infusion (CIVI) over 72 h in 21-day treatment cycles. Study end points included safety and toxic effect, response rate, progression-free and overall survival (PFS and OS), as well as exploratory pharmacodynamic correlates.
Treatment with S was well tolerated, and toxic effects were mostly hematological in the phase II study. Two (11%) partial responses were observed with a median PFS of 5.7 months and median OS 16.1 months. Pharmacodynamic analysis did not demonstrate an association with response.
The combination of S (10 mg/m2/day 72-h CIVI) administered with C and P every 3 weeks exhibited a favorable safety profile but failed to demonstrate an improvement in response rate in advanced NSCLC.
NCT01100931.
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