Microenvironmental immune cell alterations across the spectrum of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma.

Background: The clinicopathological spectrum of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), also known as nodular lymphocyte predominant B-cell lymphoma, partially overlaps with T-cell/histiocyte-rich large B-cell lymphoma (THRLCBL). NLPHL histology may vary in architecture and B-cell/T-cell composition of the tumour microenvironment. However, the immune cell phenotypes accompanying different histological patterns remain poorly characterised. Methods: We applied a multiplexed immunofluorescence workflow to identify differential expansion/depletion of multiple microenvironmental immune cell phenotypes between cases of NLPHL showing different histological patterns (as described by Fan et al, 2003) and cases of THRLBCL. Results: FOXP3-expressing T-regulatory cells were conspicuously depleted across all NLPHL cases. As histology progressed to variant Fan patterns C and E of NLPHL and to THRLBCL, there were progressive expansions of cytotoxic granzyme-B-expressing natural killer and CD8-positive T-cells, PD1-expressing CD8-positive T-cells, and CD163-positive macrophages including a PDL1-expressing subset. These occurred in parallel to depletion of NKG2A-expressing natural killer and CD8-positive T-cells. Discussion: These findings provide new insights on the immunoregulatory mechanisms involved in NLPHL and THLRBCL pathogenesis, and are supportive of an increasingly proposed biological continuum between these two lymphomas. Additionally, the findings may help establish new biomarkers of high-risk disease, which could support a novel therapeutic program of immune checkpoint interruption targeting the PD1:PDL1 and/or NKG2A:HLA-E axes in the management of high-risk NLPHL and THRLBCL.

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: clinical characteristics and treatment outcome - a report from the SFCE & CCLG groups.

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non-Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression-free survival events). The median time to progression for those who progressed was 21 months (5·9-73·8). The median time since last diagnosis is 87·3 months (8·44-179·20). Thirty-six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi-agent chemotherapy as first line treatment seems to be a reasonable therapeutic option.

Relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents - a report from the United Kingdom's Children's Cancer and Leukaemia Study Group.

There is a paucity of data on the treatment outcome in children with relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma (nLPHL). This retrospective report evaluates the treatment outcome in a national cohort of children with relapsed or poorly responsive nLPHL. A total of 37 patients, 22 with relapsed and 15 with poorly responding disease, are the subjects of this report. Of the 22 patients with relapsed nLPHL, 11 had relapsed after primary excision biopsy, 10 after chemotherapy and 1 after chemotherapy and involved field radiotherapy. The majority had localized disease at relapse. The median time to relapse was 8 months after chemotherapy and 11 months after excision biopsy. Seven of the 15 patients with poorly responding nLPHL had variant histology. Three patients with initial poor response did not receive any further treatment and have had no disease progression. Transformation to diffuse large B cell lymphoma, in addition to evolution from typical to variant nLPHL occurred in one patient each. Thirty-four patients have been successfully re-treated with second chemotherapy or radiotherapy. Multiple relapses were uncommon but treatable. Relapse or poorly responsive nLPHL is fully salvageable with either additional chemotherapy and or radiotherapy.

Childhood and Adolescent nodular lymphocyte predominant Hodgkin lymphoma - A review of clinical outcome based on the histological variants.

Nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) comprises approximately 10-12% of all childhood Hodgkin lymphoma. As the majority have low stage disease recent years have seen a de-escalation of treatment intensity to avoid treatment-related morbidity. This report evaluates treatment outcome in children with histopathological variants of nLPHL after therapy de-escalation. Biopsies from 60 patients were reviewed and histology categorized as typical (n = 47; 78%) or variant nLPHL (n = 13; 22%). Furthermore, presence of immunoglobulin D (IgD) expression by the lymphocyte predominant (LP) cells was assessed in 41 patients. Treatment outcomes were compared according to treatment received and histopathology of nLPHL. Compared to typical nLPHL, children with variant nLPHL had higher stage disease at diagnosis (stage III: 3/13; 23% vs. 3/47; 6%, P = 0·11), lower complete response rates (6/13; 46% vs. 38/47; 81%, P = 0·029) and higher relapse rates (2/13; 15% vs. 2/47; 4%, P = 0·20). Additionally, IgD expression by LP cells was associated with poorer treatment response and was more commonly seen in patients with variant nLPHL. (11/13; 85% vs. 15/28; 54%, P = 0·08). Variant histology appears to be indicative of a poorer prognosis in patients with early stage disease, and may be an important factor to take into account when moving towards reduced intensity treatment for nLPHL.

Layer number dependence of MoS2 photoconductivity using photocurrent spectral atomic force microscopic imaging.

Atomically thin MoS2 is of great interest for electronic and optoelectronic applications because of its unique two-dimensional (2D) quantum confinement; however, the scaling of optoelectronic properties of MoS2 and its junctions with metals as a function of layer number as well the spatial variation of these properties remain unaddressed. In this work, we use photocurrent spectral atomic force microscopy (PCS-AFM) to image the current (in the dark) and photocurrent (under illumination) generated between a biased PtIr tip and MoS2 nanosheets with thickness ranging between n = 1 to 20 layers. Dark current measurements in both forward and reverse bias reveal characteristic diode behavior well-described by Fowler-Nordheim tunneling with a monolayer barrier energy of 0.61 eV and an effective barrier scaling linearly with layer number. Under illumination at 600 nm, the photocurrent response shows a marked decrease for layers up to n = 4 but increasing thereafter, which we describe using a model that accounts for the linear barrier increase at low n, but increased light absorption at larger n creating a minimum at n = 4. Comparative 2D Fourier analysis of physical height and photocurrent images shows high spatial frequency spatial variations in substrate/MoS2 contact that exceed the frequencies imposed by the underlying substrates. These results should aid in the design and understanding of optoelectronic devices based on quantum confined atomically thin MoS2.

TrialDB: A web-based Clinical Study Data Management System.

Clinical Study Data Management Systems (CSDMSs) are a class of software that support centralized management of data generated during the conduct of clinical studies. Commercial CSDMSs include Oracle Clinical, ClinTrial and MetaTrial. Such systems, which are typically deployed at an institutional or organizational level, must accommodate diverse types of data from different clinical domains that is generated by different groups of clinical investigators. Large-scale CSDMSs typically employ a high-end database engine that is usually accessed over an intranet or the Internet using Web-based technologies. CSDMSs in institution-wide use for a variety of clinical domains are best served by entity-attribute-value (EAV) modeling for the clinical data: all the commercial CSDMSs that we are aware of use EAV design. However, de novo development of EAV databases for data management is a challenging task. A large body of generic metadata-driven code must be developed before a basic EAV application can be written. Clearly, the availability of pre-existing software with the requisite functionality would be very valuable. We will discuss the benefits of such software being in open-source form.

Human activities as sources of volatile organic compounds in residential environments.

The objectives of the present work were to investigate techniques for the continuous, qualitative monitoring of VOCs and to see how VOC levels were influenced by normal household activities. Three different methods were investigated to measure the VOC levels: infrared spectroscopy, photoionization detection, and gas chromatographic analysis of absorbent tube samples. Results were presented that related changes in levels of VOCs to various human activities commonly occurring in residences, and data were presented that indicated activities such as cooking, arts and crafts, cleaning floors, and painting contributed to short-term increases in VOC levels. VOC levels were diminished by turning on the air conditioner. Results on the effect of humidity on VOCs, both in homes and controlled chambers, were reported.