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Abstract The Milos, Christiana‐Santorini‐Kolumbo (CSK) and Kos‐Yali‐Nisyros (KYN) volcanic complexes of the Aegean Volcanic Arc have repeatedly produced highly explosive eruptions from at least ∼360 ka into historic times and still show recent unrest. We present the marine tephra record from an array of 50, up to 7.4 m long, sediment cores along the arc collected in 2017 during RV Poseidon cruise POS513, which complements earlier work on distal to ultra‐distal eastern Mediterranean sediment cores. A unique set of glass‐shard trace element (LA‐ICPMS) compositions complements our major element (EMP) data on 220 primary ash layers and 40 terrestrial samples to support geochemical fingerprinting for correlations with 19 known tephras from all three volcanic complexes and with the 39 ka Campanian Ignimbrite from the Campi Flegrei, Italy. The correlations include 11 eruptions from CSK (Kameni, Kolumbo 1650, Minoan, Cape Riva, Cape Tripiti, Upper Scoriae 1 and 2, Middle Pumice, Cape Thera, Lower Pumice, Cape Therma 3). We identify a previously unknown widespread tephra from a plinian eruption on Milos (Firiplaka Tephra). Near the KYN we correlate marine tephras with the Kos Plateau Tuff, the Yali 1 and Yali 2 tephras, and the Upper and Lower Pumice on Nisyros. Between these two major tephras, we found two tephras from Nisyros not yet observed on land. The four Nisyros tephras form a systematic trend toward more evolved magma compositions. In the companion paper we use the tephrostratigraphic framework established here to constrain new eruption ages and magnitudes as a contribution to volcanic hazard assessment.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Primary analysis of the phase III randomized AATT study showed that younger patients with peripheral T-cell lymphoma (PTCL) consolidated with autologous or allogeneic transplantation (alloSCT) had similar event-free survival (EFS) and overall survival (OS). Seven-year EFS of patients randomly assigned to alloSCT was 38% (95% CI, 25 to 52) compared with 34% (95% CI, 22 to 47) for patients randomly assigned to autologous transplantation of hematopoietic stem cells (autoSCT); OS was 55% (95% CI, 41 to 69) and 61% (95% CI, 47 to 74). Among patients undergoing alloSCT (n = 26) or autoSCT (n = 41) on study, the cumulative progression/relapse rate was 8% (95% CI, 0 to 19) and 55% (95% CI, 35 to 74). Nonrelapse mortality (NRM) was 31% (95% CI, 13 to 49) and 3% (95% CI, 0 to 8) after alloSCT and autoSCT, respectively. Fifteen of 30 patients with early progression and 11 of 20 patients with progression/relapse after autoSCT received alloSCT. Seven-year OS after salvage alloSCT was 61% (95% CI, 47 to 74); NRM was 23% (95% CI, 6 to 40). Long-term follow-up documents the strong graft versus lymphoma effect of alloSCT independent of the timing of transplantation. Survival of patients unable to undergo transplantation was dismal. AlloSCT is the treatment of choice for younger, transplant-eligible patients with relapsed/refractory PTCL. AlloSCT is currently not recommended as part of first-line consolidation.

Lot release testing of diphtheria, tetanus and acellular pertussis vaccines traditionally relied on in vivo protection models involving challenge of laboratory animals with toxins. Meanwhile, many labs have switched to serological testing of these vaccines, which is often performed in separate in vivo assays, even if all components were formulated into one vaccine product. Here we describe the results of simultaneous serological potency determination of diphtheria (D), tetanus (T) and acellular pertussis (aP) antigens obtained following immunization of guinea pigs with multicomponent pediatric and booster vaccines from different manufacturers. The 4th World Health Organization (WHO) International Standard (IS) for diphtheria toxoid (No. 07/216) and the 4th WHO IS for tetanus toxoid (No. 08/218) were used as reference preparations. For aP, a pediatric vaccine batch containing the antigens pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae proteins type 2/3 was established as internal control. Quantification of IgG against D, T and aP antigens in guinea pig sera was performed using a hexaplex electrochemiluminescence immunoassay. We further provide proof-of-concept using experimental vaccine samples lacking or containing reduced amounts of diphtheria toxoid in the presence of full amounts of tetanus and pertussis antigens and alum adjuvant. Importantly, the assay confirmed dose-response relationships for all antigens tested and was able to detect diphtheria out-of-specification batches. The results confirmed the suitability of the protocol for combined serology batch release testing of DTaP combination vaccines as first measure towards implementation of full in vitro testing of DTaP vaccines. This report summarizes the data and the protocol used for validation prior to implementation of this method in routine batch release testing of DTaP vaccines, which led to replacement of in vivo challenge experiments in our laboratory following the 3 R (replace, reduce, refine) principle., (© 2024. The Author(s).)

The major depressive disorder is one of the most common mental illnesses worldwide. Current treatment standards recommend a combined therapy with medication and psychotherapy. As an additive component and to further improvements in treatment, physical activity such as yoga may be integrated into conventional treatment. This study investigates the impact of a 3-month body-oriented yoga in patients with major depressive disorder (MDD). In total, n = 83 patients were included. An intervention group received a vigorous Ashtanga-Yoga three times a week. The waiting-list control group obtained a treatment as usual (TAU). As a primary outcome depression scores (Beck Depression Inventory-II (BDI-II), Montgomery Asberg Depression Rating Scale (MADRS)) were tested at three time points. Secondary outcome was the positive and negative affect [Positive and Negative Affect Scale (PANAS)] and remission rates. To analyze the data, multilevel models and effect sizes were conducted. The results showed an improvement in BDI-II scores for both groups over time [γ =  -  3.46, t(165) =  - 7.99, p < 0.001] but not between groups [γ = 0.98, t(164) = 1.12, p = 0.263]. An interaction effect (time x group) occurred for MADRS [γ = 2.10, t(164) = 2.10, p < 0.038]. Positive affects improved over time for both groups [γ = 1.65, t(165) = 4.03, p < 0.001]. Negative affects decreased for all over time [γ =  -  1.00, t(165) = - 2.51, p = 0.013]. There were no significant group differences in PANAS. Post hoc tests revealed a greater symptom reduction within the first 6 weeks for all measurements. The effect sizes for depression scores showed a positive trend. Remission rates indicated a significant improvement in the yoga group (BDI-II: 46.81%, MADRS: 17.02%) compared to the control group (BDI: 33.33%, MADRS: 8.33%). The findings suggest that there is a trendsetting additive effect of Ashtanga-Yoga after 3 months on psychopathology and mood with a greater improvement at the beginning of the intervention. Further research in this field can help to achieve more differentiated results., (© 2021. The Author(s).)

This retrospective study examined the role of 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) in stage-related therapy of follicular lymphomas (FL). Twelve patients each in stages I and II, 13 in stage III and 11 in stage IV were treated in the Department of Radiation Oncology, University Hospital of Muenster, Germany from 2004 to 2016. Radiotherapy (RT), as well as additional chemoimmunotherapy were analyzed with a median follow-up of 87.6 months. Ultrasound (US), CT and 18 F-FDG-PET/CT were used to determine progression-free survival (PFS), overall survival (OS) and lymphoma-specific survival (LSS) over 5- and 10- years. 23 of 24 patients with stage I/II (95.8%) had complete remissions (CR) and 17 of 24 patients with stages III/IV FL showed CR (70.8%). 5- and 10-year PFS in stages I/II was 90.0%/78.1% vs. 44.3%/28.5% in stages III/IV. 5- and 10-year OS rates in stages I/II was 100%/93.3% vs. 53.7%/48.4% in stages III/IV. 5- and 10-year LSS of stages I/II was 100%/93.8% vs. 69.2%/62.3% in stages III/IV. FL of stages I/II, staged by 18 F-FDG-PET/CT, revealed better survival rates and lower risk of recurrence compared to studies without PET/CT-staging. Especially, patients with PET/CT proven stage I disease showed significantly better survival and lower relapses rates after RT.

First-line therapy for younger patients with peripheral T-cell non-Hodgkin lymphoma (T-NHL) consists of 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide (CHOEP), consolidated by high-dose therapy and autologous stem cell transplantation (auto-SCT). We hypothesized that allogeneic stem cell transplantation (allo-SCT) could improve outcomes. 104 patients with peripheral T-cell non-Hodgkin lymphoma, except ALK+ anaplastic large cell lymphoma, 18 to 60 years, all stages, and all age adjusted International Prognostic Index scores, except 0 and stage I, were randomized to 4 cycles of CHOEP and 1 cycle of dexamethasone, cytosine-arabinoside, and platinum (DHAP) followed by high-dose therapy and auto-SCT or myeloablative conditioning and allo-SCT. The primary end point was event-free survival (EFS) at 3 years. After a median follow-up of 42 months, the 3-year EFS after allo-SCT was 43%, as compared with 38% after auto-SCT. Overall survival at 3 years was 57% vs 70% after allo- or auto-SCT, without significant differences between treatment arms. None of the 21 responding patients proceeding to allo-SCT relapsed, as opposed to 13 of 36 patients (36%) proceeding to auto-SCT. Eight of 26 patients (31%) and none of 41 patients died of transplant-related toxicity after allo- and auto-SCT, respectively. The strong graft-versus-lymphoma effect after allo-SCT was counterbalanced by transplant-related mortality. This trial is registered at www.clinicaltrials.gov as #NCT00984412., (© 2021 by The American Society of Hematology.)

[This corrects the article DOI: 10.1016/j.dib.2020.105113.]., (© 2020 The Author(s).)

Objective: To evaluate clinical, histopathologic, and radiation (RT) dose parameters in patients with extranodal low-grade (ENLG) non-Hodgkin lymphoma (NHL) and their possible impact on local control (LC) and survival., Materials and Methods: The medical records of 159 patients with 181 histologically confirmed ENLG-NHL lesions treated at our institution were reviewed retrospectively., Results: The predominant histological subtype (73%) was marginal zone lymphoma (MZL). Common lesion sites were the gastrointestinal tract (GIT; 33%), skin (26%), and orbit (21%). The majority of patients (88%) presented with stage I/II disease. Thirty-three (20%) lesions were treated with reduced-dose RT (≤30.6 Gy) and 148 lesions (80%) with conventional-dose RT (>30.6 Gy), with an overall median dose of 39.6 Gy (range 4-63). The median follow-up period was 72 months. The 10-year local control (LC), Progression-free survival (PFS), and overall survival (OS) rates were 96, 65, and 82%, respectively. Higher overall response rate (ORR; 98% vs. 94%, p = 0.001) and complete response rate (CRR; 95% vs. 73%, p = 0.001) were observed in patients treated with conventional-dose regimens than in those treated with reduced-dose regimens. Ten-year PFS (p = 0.90) and OS (p = 0.40) was similar between the two dose groups. RT was well tolerated in both dose groups, with no grade 4/5 toxicities. In the multivariate analysis, RT dose and timing (upfront or salvage) were related to LC, whereas age, histology, and complete response (CR) to RT were associated with PFS. Patient age and radiation field size impacted OS., Conclusion: RT is an effective and curative local treatment for early-stage FL and MZL at conventional and reduced radiation doses. Conventional-doses seems to be associated with local response improvement, without significant differences in PFS rates. Age, histology, and response to RT may influence the PFS.

In this review, we focus on new advances regarding diagnostic and therapeutic standards of aggressive B-cell lymphomas. This includes the introduction of the so-called "cell of origin" classification which differentiates diffuse large B-cell lymphomas (DLBCL) into the ABC and GCB subtypes and became part of the revised WHO classification of 2017. While 6-8 cycles of R-CHOP remain the standard of first-line treatment in DLBCL, for young patients up to 60 years of age with an international prognostic index (IPI) of 0 the treatment can be shortened to 4 cycles of R-CHOP plus 2 cycles of rituximab.With regard to the prophylaxis of CNS relapse, the so-called CNS-IPI helps to identify patients with high risk of relapse in the CNS even if data from randomized clinical trials is sparse. For those patients, 2 courses of high-dose methotrexate in addition to first-line treatment seem advisable.For patients with relapse or refractory disease, salvage treatment followed by autologous or allogeneic transplantation remains the standard. After failure of 2 lines of treatment, 2 different CAR-T-cell products are licensed offering a potentially curative treatment options even for patients not eligible for transplantation strategies. New treatment modalities as antibody-drug conjugates and bispecific antibodies show promising results in clinical studies and will presumably broaden the spectrum of treatment options for patients with DLBCL., Competing Interests: Birte Friedrichs hielt Vorträge und/oder war als Berater tätig für Roche, Takeda und BMS und erhielt Unterstützung von Dienstreisen von Celgene und Gilead.Norbert Schmitz erhielt Honorare von Riemser, Janssen, Kite/Gilead und Takeda, hielt Vorträge und/oder war als Berater tätig für Riemser, Takeda und Kite/ Gilead und erhielt Unterstützung von Dienstreisen von Riemser, Janssen, Kite/Gilead und Takeda. Nobert Schmitz besitzt Aktien von Celgene.Georg Lenz erhielt Honorare, hielt Vorträge und/oder war als Berater tätig für Abbvie, Acerta, Amgen, AstraZeneca, Bayer, BMS, Celgene, Gilead, Janssen, NanoString, Novartis, Morphosys, Roche und Takeda und erhielt Unterstützung von Dienstreisen von Janssen, Celgene und Roche. Weiterhin erhielt er finanzielle Unterstützung bei der Durchführung wissenschaftlicher Projekte von Agios, Aquinox, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Novartis, Morphosys, Roche und Verastem., (© Georg Thieme Verlag KG Stuttgart · New York.)

Thirty-eight lava and pyroclastic samples were collected from Mt. Erciyes and Mt. Hasan, the two largest stratovolcanic complexes of the Central Anatolian Volcanic Province in Turkey. More than 1000 zircon crystals were dated by Secondary Ion Mass Spectrometry (SIMS) applying U-Th disequilibrium and U-Pb methods. Model ages were calculated from zircon 230 Th- 238 U- 232 Th isotopic compositions in combination with U-Th whole rock data of digested lava samples generated by Multi-Collector Inductively Coupled Plasma Mass Spectrometry (MC-ICP-MS). Middle and Late Pleistocene ages dominate the dataset, but are complemented by both older (predominantly Early Pleistocene) and younger (Holocene) ages. U-Th disequilibrium and U-Pb zircon data provide maximum eruption ages that can be further specified by (U-Th)/He geochronology (zircon double dating). Additionally, these data are important to constrain the longevity and size of magmatic systems, and their potential for reactivation leading to potentially hazardous eruptions., (© 2020 The Author(s).)

Introduction : Aberrant phosphatidylinositide 3-kinase (PI3K) signaling drives survival and proliferation of malignant B-cells of different lymphoma entities. Thus, inhibition of PI3K isoforms represents a novel and promising therapeutic approach for the treatment of patients with B-cell lymphomas. Areas covered : Here the authors provide an overview about the PI3K signaling pathway as well as available preclinical and clinical results of different PI3K inhibitors in both indolent and aggressive lymphoma entities. Expert opinion : PI3K inhibitors have shown to be efficacious in different entities of B-cell lymphoma, at this stage particularly in relapsed/refractory settings. However, responses of PI3K inhibitors widely vary among different lymphomas. Additionally, especially infectious and immune-mediated toxicities limit their use at this stage. Thus, the decision to use PI3K inhibitors needs to be balanced between the potential efficacy and associated toxicities as well as the availability of other therapeutic options. Future research might eventually lead to the stratification of patients according to the specific oncogenic addictions of the underlying lymphoma. Additionally, PI3K inhibitors will need to be combined with other therapeutic agents for more specific and effective treatment regimens.

To further improve outcome in young high-risk patients with diffuse large B-cell lymphoma (DLBCL) the number of rituximab (R) infusions was doubled in combination with standard CHOEP (cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone) chemotherapy. Seventy-seven patients (aged 18-60 years) with an age-adjusted International Prognostic Index of 2-3 received 12 × R (375 mg/m 2 ) on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85 and 99 together with eight cycles of CHOEP-14. Results were retrospectively compared to those of patients receiving 6 × R and 8 × CHOEP-14 in the standard arm of the randomized R-MegaCHOEP trial. Two-year overall survival (OS) was 82% [95% confidence interval (CI) 73%-92%]; 2-year event-free (EFS) and progression-free survival (PFS) was 69% (95% CI 59-80%) and 76% (95% CI 66%--6%), respectively. Comparing 12 to six doses of R revealed no differences (univariate/multivariate) in EFS (at 2 years: 69% vs. 71%), PFS (76% vs. 75%) and OS (82% vs. 85%), with P = 0·766, P = 0·871 and P = 0·843, respectively. Doubling the number of R infusions concomitant to CHOEP did not improve treatment outcomes. Nonetheless, OS and PFS of young high-risk patients who received only six infusions of R combined with CHOEP remain excellent and were confirmed in an independent cohort of patients., (© 2018 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose of Review: T - and natural killer (NK) cell neoplasms are a heterogeneous group of rare diseases with often inferior outcome. Only few studies exist, clarifying the role of allogeneic transplantation in different clinical scenarios. Larger prospective randomized studies are largely missing even for the more frequent entities. Mostly retrospective analysis and anecdotal reports of patients with advanced disease are available, hampering direct conclusions on the significance of allogeneic stem cell transplantation (alloSCT)., Recent Findings: Looking at recent data for T and NK cell neoplasm, it becomes evident that advances in donor search and availability of alternative stem cell sources as haploidentical or mismatched donors in addition to substantial improvements in graft-versus-host-disease prophylaxis reduce treatment-related mortality in alloSCT. The time point of transplantation has been described in a number of studies to be critically impacting outcome results as patients with advanced, chemorefractory disease often profit much less from alloSCT., Summary: Allogeneic transplantation offers a treatment option that can induce long-term remissions even in the relapsed setting. Many patients do not reach transplantation though because of chemorefractory disease and efforts should be made to bring more patients to transplantation earlier in the course of disease.

Lithium intoxication is known to induce cognitive deficits along with motor and behavioral changes, even in association with normal serum levels. However, cases with comprehensive neuropsychological assessment of the deficits are rare. In our patient, we initially found severe cognitive deficits, including apraxia and visuo-constructive problems, and temporo-parietal FDG-PET hypometabolism. Neuropsychological and imaging findings were highly suggestive of Alzheimer's disease. However, lithium intoxication was suspected to account for these findings because of a Parkinson's syndrome, despite serum levels being in the upper therapeutic range. This was confirmed as cessation of lithium medication not only let the Parkinson's syndrome disappear, but also lead to dramatic improvements with respect to cognition.

The current Review article provides a narrative review about the neurobiological underpinnings and treatment of treatment resistant late-life depression (TRLLD). The manuscript focuses on therapeutic targets of late-life depression, which include pharmacological, psychological, biophysical and exercise treatment approaches. Therefore, we summarize available evidences on that kind of therapies for patients suffering from late-life depression. The search for evidences of therapeutic options of late-life depression were done using searching websites as "pubmed", and using the searching terms "depression", "late-life depression", "treatment", "biophysical therapy", "exercise therapy", "pharmacological therapy" and "psychological therapy". To the end, we summarize and discuss current data, providing some directions for further research. Treatment recommendations for elderly depressive patients favour a multimodal approach, containing psychological, pharmacological and secondary biophysical therapeutic options. Particularly, a combination of psychotherapy and antidepressant medication reflects the best therapeutic option. However, mostly accepted and used is the pharmacological treatment although evidence suggests that the drug therapy is not as effective as it is in younger depressive patients. Further studies employing larger samples and longer follow-up periods are necessary and may focus on comparability of study designs and involve novel approaches to establish the validity and reliability of multimodal treatment programs.

In vitro treatment of human peripheral blood neutrophils from smokers and non-smokers with an aqueous cigarette smoke (CS) extract resulted in a concentration-dependent increase in surface expression of CD11b and CD66b and a corresponding decrease of CD62L, together with a concentration-dependent release of MMP-8, MMP-9, and lactoferrin, indicating considerable activation and degranulation. However, the burst response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) was unchanged in CS-stimulated neutrophils from both smokers and non-smokers. When supernatants from CS-treated monocytic MonoMac-6 (MM6) cells were used for activation of neutrophils, concentration-dependent changes in surface marker expression, granule protein release, and the oxidative burst response to fMLP were observed, again with no major differences between smokers and non-smokers. CS-treated MM6 cells released significant amounts of IL-8 and TNF-α into the culture supernatant. However, antibody blocking experiments showed that only TNF-α mediated the increased burst response in neutrophils. These data show that, in the presence of secondary cells, CS is able to prime neutrophils for an increased burst response to fMLP which is mediated by TNF-α, released from the secondary cells in response to CS. Following stimulation with priming agents, peripheral blood neutrophils from healthy smokers show an equal burst response compared to those from non-smokers., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Haploidentical stem cell transplantation (haploSCT) offers an alternative treatment option for advanced leukemia patients lacking a HLA-compatible donor. Transfer of NK cells represents a promising therapeutic option in combination with SCT, as NK cells can promote graft versus leukemia with low risk of GVH disease. In this study, we show results from a phase I/II trial in which 24 acute myeloid leukemia patients underwent haploSCT in combination with early transfer of unmodified NK cells and observed a promising 2-year overall survival rate of 37%. By performing immunomonitoring and subsequent principal component analysis, we tracked donor NK-cell dynamics in the patients and distinguished between NK cells reconstituting from CD34(+) precursors, giving rise over time to a continuum of multiple differentiation stages, and adoptively transferred NK cells. Transferred NK cells displayed a mature phenotype and proliferated in vivo during the early days after haploSCT even in the absence of exogenous IL-2 administration. Moreover, we identified the NK-cell phenotype associated with in vivo expansion. Thus, our study indicates a promising path for adoptive transfer of unmodified NK cells in the treatment of high-risk acute myeloid leukemia., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The Moon was probably formed by a catastrophic collision of the proto-Earth with a planetesimal named Theia. Most numerical models of this collision imply a higher portion of Theia in the Moon than in Earth. Because of the isotope heterogeneity among solar system bodies, the isotopic composition of Earth and the Moon should thus be distinct. So far, however, all attempts to identify the isotopic component of Theia in lunar rocks have failed. Our triple oxygen isotope data reveal a 12 ± 3 parts per million difference in Δ(17)O between Earth and the Moon, which supports the giant impact hypothesis of Moon formation. We also show that enstatite chondrites and Earth have different Δ(17)O values, and we speculate on an enstatite chondrite-like composition of Theia. The observed small compositional difference could alternatively be explained by a carbonaceous chondrite-dominated late veneer., (Copyright © 2014, American Association for the Advancement of Science.)

Providing compassionate bereavement care for families experiencing perinatal loss is a standard of care in most healthcare organizations. In this article, we describe the development of The Alliance of Perinatal Bereavement Support Facilitators, begun over 25 years ago in Chicago by staff who identified the need to reach out to colleagues at other area institutions for advice and support in this work. This collaboration created a regional support network that has resulted in a long-lasting, active, sustainable organization of excellence focused on enhancing practice, education, and perinatal bereavement care. Alliance activities center around four main areas: education, networking/support, policy, and recognizing outstanding service to families. By continuing to draw upon the collective talent, wisdom, and expertise of its members, The Alliance still serves grieving families and provides mentoring for future interdisciplinary team members engaged in this work. The path taken to build this organization can be used by professionals in other specialties who are looking to create their own alliance infrastructure based on mutual benefit and interest.

Cigarette smoking is the primary etiology of chronic obstructive pulmonary disease (COPD) and a risk factor for both lung and cardiovascular (CV) diseases, which are rarely investigated concomitantly. Although smoking cessation shows clear CV risk benefit, lung-related disease risk remains higher in former smokers than in never smokers. We sought to determine the differential molecular responses of murine respiratory tissues to better understand the toxicity pathways involved in smoking-related disease risk and those related to the benefits of smoking cessation. ApoE(-/-) mice were exposed to mainstream cigarette smoke (CS) or a smoking cessation-mimicking protocol for up to 6 months and transcriptomics analysis of nasal epithelium and lung parenchyma performed. We supported our gene expression profiling approach with standard lung histopathology and bronchoalveolar lavage fluid (BALF) analysis. Many BALF analytes involved in functions ranging from inflammation to cell proliferation and tissue remodeling were found elevated in BALF. Gene expression levels of these molecules were also increased in lung tissue, suggesting that the inflammatory response was the result of local tissue activation and the contribution of recruited inflammatory cells. Gene set enrichment analysis (GSEA) of expression data from murine lungs and nasal epithelium showed distinct activation patterns of inflammation, complement, and xenobiotic metabolism pathways during CS exposure that were deactivated upon smoking cessation. Pathways involved in cell proliferation and tissue remodeling were activated by CS and progressively deactivated upon smoke exposure cessation. Differential CS-mediated responses of pulmonary and nasal tissues reflect common mechanisms but also the varying degrees of epithelial functional specialization and exposure along the respiratory tract., (Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Lymphomatoid granulomatosis (LG) is a very rare, Epstein-Barr virus-associated lymphoproliferative disorder of B cells. Prognosis is poor, particularly after relapse and no curative treatment exists. We report the results of high-dose therapy and autologous stem cell transplantation (ASCT) or reduced-intensity conditioning and allogeneic stem cell transplantation (alloSCT) in patients with multiply relapsed LG. A European Group for Blood and Marrow Transplantation survey identified 10 patients who had received 9 ASCT and 4 alloSCT. All patients had active disease at the time of transplantation. With a median follow-up of 5.1 (range, 1.4 to 6.3) years, 6 patients are alive and disease-free. Two ASCT patients died of septicemia early after transplantation, and 1 committed suicide after being in continuous complete remission 19 months after ASCT. Another patient allografted 4 years after ASCT remained disease-free but died of severe graft-versus-host disease 3 months after alloSCT. High-dose therapy followed by ASCT and alloSCT are effective therapeutic options and should be considered in all patients with refractory and multiply relapsed LG., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)