The dense molecular gas in the z∼6\rm z\sim6 QSO SDSS J231038.88+185519.7 resolved by ALMA

We present ALMA observations of the CO(6-5) and [CII] emission lines and the sub-millimeter continuum of the $z\sim6$ quasi-stellar object (QSO) SDSS J231038.88+185519.7. Compared to previous studies, we have analyzed a synthetic beam that is ten times smaller in angular size, we have achieved ten times better sensitivity in the CO(6-5) line, and two and half times better sensitivity in the [CII] line, enabling us to resolve the molecular gas emission. We obtain a size of the dense molecular gas of $2.9\pm0.5$ kpc, and of $1.4\pm0.2$ kpc for the 91.5 GHz dust continuum. By assuming that CO(6-5) is thermalized, and by adopting a CO--to--$H_2$ conversion factor $\rm \alpha_{CO} = 0.8~ M_{\odot}~K^{-1}~ (km/s)^{-1} ~pc^{2}$, we infer a molecular gas mass of $\rm M(H_2)=(3.2 \pm0.2) \times 10^{10}\rm M_{\odot}$. Assuming that the observed CO velocity gradient is due to an inclined rotating disk, we derive a dynamical mass of $\rm M_{dyn}~sin^2(i) = (2.4\pm0.5) \times 10^{10}~ M_{\odot}$, which is a factor of approximately two smaller than the previously reported estimate based on [CII]. Regarding the central black hole, we provide a new estimate of the black hole mass based on the C~IV emission line detected in the X-SHOOTER/VLT spectrum: $\rm M_{BH}=(1.8\pm 0.5) \times 10^{9}~ M_{\odot}$. We find a molecular gas fraction of $\rm \mu=M(H_2)/M^*\sim4.4$, where $\rm M^*\approx M_{dyn} - M(H_2)-M(BH)$. We derive a ratio $v_{rot}/\sigma \approx 1-2$ suggesting high gas turbulence, outflows/inflows and/or complex kinematics due to a merger event. We estimate a global Toomre parameter $Q\sim 0.2-0.5$, indicating likely cloud fragmentation. We compare, at the same angular resolution, the CO(6-5) and [CII] distributions, finding that dense molecular gas is more centrally concentrated with respect to [CII]. We find that the current BH growth rate is similar to that of its host galaxy.Comment: A&A in pres

Fertility in female survivors of hodgkin's lymphoma.

Currently, Hodgkin's lymphoma is one of the most curable types of cancer. Patients are often young and so the long-term morbidities of treatment have become of increasing concern. Among these, infertility is one of the most challenging consequences for patients in reproductive age. Premature ovarian failure in premenopausal women is a serious long-term sequel of the toxicity of chemotherapy. The main consequence of this syndrome is infertility, but women also present other symptoms related to estrogen deprivation. Different rates of impaired gonadal function are reported, depending on the patient's age, stage of disease, dose and intensity of chemotherapy and the use of radiation therapy. The most established strategy in female infertility is cryopreservation of embryos after in vitro fertilization. Additionally, the use of oral contraceptives or gonadotropin-releasing hormone analogs (GnRH-a) during treatment is under study. This review will provide a general overview of the main studies conducted to evaluate the infertility rate among female Hodgkin's lymphoma survivors and risk factors associated to treatment, different end-pointg definitions for evaluating fertility and also a brief description of the available strategies for fertility preservation

Management of patients with lymphoma and COVID-19: Narrative review and evidence-based practical recommendations

Patients with hematologic malignancies can be immunocompromized because of their disease, anti-cancer therapy, and concomitant immunosuppressive treatment. Furthermore, these patients are usually older than 60 years and have comorbidities. For all these reasons they are highly vulnerable to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and have an increased risk of developing severe/critical Coronavirus disease 2019 (COVID-19) compared to the general population. Although COVID-19 vaccination has proven effective in reducing the incidence of severe/critical disease, vaccinated patients with lymphoma may not be protected as they often fail to develop a sufficient antiviral immune response. There is therefore an urgent need to address the management of patients with lymphoma and COVID-19 in the setting of the ongoing pandemic. Passive immunization with monoclonal antibodies against SARS-CoV-2 is a currently available complementary drug strategy to active vaccination for lymphoma patients, while monoclonal antibodies and antiviral drugs (remdesivir, ritonavir-boosted nirmatrelvir, and molnupiravir) have proven effective in preventing the progression to severe/critical COVID-19. In this narrative review we present the most recent data documenting the characteristics and outcomes of patients with concomitant lymphoma and COVID-19. Our ultimate goal is to provide practice-oriented guidance in the management of these vulnerable patients from diagnosis to treatment and follow-up of lymphoma. To this purpose, we will first provide an overview of the main data concerning prognostic factors and fatality rate of lymphoma patients who develop COVID-19; the outcomes of COVID-19 vaccination will also be addressed. We will then discuss current COVID-19 prophylaxis and treatment options for lymphoma patients. Finally, based on the literature and our multidisciplinary experience, we will summarize a set of indications on how to manage patients with lymphoma according to COVID-19 exposure, level of disease severity and former history of infection, as typically encountered in clinical practice

A diachronic-comparative analysis for the identification of the most powerful prognostic index for localized diffuse large B-cell lymphoma

BACKGROUND: In the rituximab era, the conventional International Prognostic index (IPI) lost at least in part its predictive power, while the National Comprehensive Cancer Network-IPI (NCCN-IPI) seems to be a new and valid prognosticator. However, it has not yet been evaluated in patients with localized disease and it has not been compared with the modified IPI (mIPI) of the pre-rituximab era. In order to evaluate the different prognosticators and to assess the importance of rituximab and radiotherapy (RT), we carried out the so far largest retrospective analysis of patients with localized diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: We retrospectively assessed clinical and therapeutical data of 1405 patients treated in from 1987 to 2012 in 10 cancer centers in Italy and 1 in Austria. RESULTS: All patients underwent an anthracycline containing polychemotherapy and 254 additional rituximab. The median follow-up was 5.7 years (range 0.1-23 years). The 5-year overall survival (OS) was 75%, being significantly superior in those who underwent additional rituximab, while RT consolidation did not improve the outcome of those who received immunochemotherapy. Patients with extranodal disease benefited from the addition of rituximab, while RT did not improve OS of the immunochemotherapy subgroup. In the pre-rituximab era, the mIPI showed a better performance than the others. In rituximab-treated patients, the NCCN-IPI had the highest discriminant value and the 5-years OS varied significantly (P < 0.001) between the three risk groups and was 98% in low-risk patients, 82% in those with a low-intermediate risk and 57% among high-intermediate and high-risk cases. CONCLUSIONS: The NCCN-IPI is so far the best prognosticator for patients with localized DLBCL who underwent R-CHOP(-like). The addition of rituximab is indispensable regardless of the risk category and site of involvement, while the addition of RT should be reserved to those cases who are ineligible to rituximab

The dense molecular gas in the z ∼ 6 QSO SDSS J231038.88+185519.7 resolved by ALMA

We present ALMA observations of the CO(6-5) and [CII] emission lines and the sub-millimeter continuum of the $z\sim6$ quasi-stellar object (QSO) SDSS J231038.88+185519.7. Compared to previous studies, we have analyzed a synthetic beam that is ten times smaller in angular size, we have achieved ten times better sensitivity in the CO(6-5) line, and two and half times better sensitivity in the [CII] line, enabling us to resolve the molecular gas emission. We obtain a size of the dense molecular gas of $2.9\pm0.5$ kpc, and of $1.4\pm0.2$ kpc for the 91.5 GHz dust continuum. By assuming that CO(6-5) is thermalized, and by adopting a CO--to--$H_2$ conversion factor $\rm \alpha_{CO} = 0.8~ M_{\odot}~K^{-1}~ (km/s)^{-1} ~pc^{2}$, we infer a molecular gas mass of $\rm M(H_2)=(3.2 \pm0.2) \times 10^{10}\rm M_{\odot}$. Assuming that the observed CO velocity gradient is due to an inclined rotating disk, we derive a dynamical mass of $\rm M_{dyn}~sin^2(i) = (2.4\pm0.5) \times 10^{10}~ M_{\odot}$, which is a factor of approximately two smaller than the previously reported estimate based on [CII]. Regarding the central black hole, we provide a new estimate of the black hole mass based on the C~IV emission line detected in the X-SHOOTER/VLT spectrum: $\rm M_{BH}=(1.8\pm 0.5) \times 10^{9}~ M_{\odot}$. We find a molecular gas fraction of $\rm \mu=M(H_2)/M^*\sim4.4$, where $\rm M^*\approx M_{dyn} - M(H_2)-M(BH)$. We derive a ratio $v_{rot}/\sigma \approx 1-2$ suggesting high gas turbulence, outflows/inflows and/or complex kinematics due to a merger event. We estimate a global Toomre parameter $Q\sim 0.2-0.5$, indicating likely cloud fragmentation. We compare, at the same angular resolution, the CO(6-5) and [CII] distributions, finding that dense molecular gas is more centrally concentrated with respect to [CII]. We find that the current BH growth rate is similar to that of its host galaxy

A multicenter retrospective clinical study of CD5/CD10-negative chronic B cell leukemias.

CD5-negative chronic B cell lymphoproliferative disorders in leukemic phase (B-CLPD) are heterogeneous and relatively uncommon pathologies that often lack a histopathological definition because of the absence of accessible pathological tissue. We describe the clinical features and evolution-related variables of 156 patients with CD5/CD10-negative B-CLPD (median age 66 years, range 25-86). The median follow-up was 51 months (range 6-216), and overall 3- and 5-year survival was respectively 87 and 76%; 50 patients needed therapy at diagnosis, 56 during follow-up, and 50 remained untreated until the last control. A combined clinical, histological, cytomorphological, immunophenotypical, and cytogenetic diagnostic approach allowed the complete classification of only a minority of patients as being affected by splenic marginal zone or lymphoplasmacytic lymphoma; the majority of cases remained unclassifiable. Multivariate analysis showed that the clinicohematological variables adversely related to overall survival were serum LDH levels and age, whereas high serum LDH levels, hemoglobin levels of <11 g/dl, and splenomegaly related to treatment-free time (in "wait and see" cases); only splenomegaly related to time to progression (in treated patients). In conclusion, our retrospective study describes the clinical features and variables related to evolution in a large group of patients with CD5/CD10-negative chronic B-cell lymphoid leukemias and underlines the fact that a probable lymphoplasmacytic or marginal zone normal cell origin can be supposed in such leukemic forms, but never surely demonstrated

Prevalence and distribution of vascular calcifications at CT scan in patients with and without large vessel vasculitis: A matched cross-sectional study

Objectives The aim of this study was to compare the prevalence, entity and local distribution of arterial wall calcifications evaluated on CT scans in patients with large vessel vasculitis (LVV) and patients with lymphoma as reference for the population without LVV. Methods All consecutive patients diagnosed with LVVs with available baseline positron emission tomography-CT (PET-CT) scan performed between 2007 and 2019 were included; non-LVV patients were lymphoma patients matched by age (±5 years), sex and year of baseline PET-CT (≤2013; &gt;2013). CT images derived from baseline PET-CT scans of both patient groups were retrospectively reviewed by a single radiologist who, after setting a threshold of minimum 130 Hounsfield units, semiautomatically computed vascular calcifications in three separate locations (coronaries, thoracic and abdominal arteries), quantified as Agatston and volume scores. Results A total of 266 patients were included. Abdominal artery calcifications were equally distributed (mean volume 3220 in LVVs and 2712 in lymphomas). Being in the LVVs group was associated with the presence of thoracic calcifications after adjusting by age and year of diagnosis (OR 4.13, 95% CI 1.35 to 12.66; p=0.013). Similarly, LVVs group was significantly associated with the volume score in the thoracic arteries (p=0.048). In patients &gt;50 years old, calcifications in the coronaries were more extended in non-LVV patients (p=0.027 for volume). Conclusion When compared with patients without LVVs, LVVs patients have higher calcifications in the thoracic arteries, but not in coronary and abdominal arteries

T-cell lymphoma in South America and Europe.

Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cell, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneos. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year oversall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies

Immune-related pan-cancer gene expression signatures of patient survival revealed by NanoString-based analyses

The immune system plays a central role in the onset and progression of cancer. A better understanding of transcriptional changes in immune cell-related genes associated with cancer progression, and their significance in disease prognosis, is therefore needed. NanoString-based targeted gene expression profiling has advantages for deployment in a clinical setting over RNA-seq technologies. We analysed NanoString PanCancer Immune Profiling panel gene expression data encompassing 770 genes, and overall survival data, from multiple previous studies covering 10 different cancer types, including solid and blood malignancies, across 515 patients. This analysis revealed an immune gene signature comprising 39 genes that were upregulated in those patients with shorter overall survival; of these 39 genes, three (MAGEC2, SSX1 and ULBP2) were common to both solid and blood malignancies. Most of the genes identified have previously been reported as relevant in one or more cancer types. Using Cibersort, we investigated immune cell levels within individual cancer types and across groups of cancers, as well as in shorter and longer overall survival groups. Patients with shorter survival had a higher proportion of M2 macrophages and γδ T cells. Patients with longer overall survival had a higher proportion of CD8+ T cells, CD4+ T memory cells, NK cells and, unexpectedly, T regulatory cells. Using a transcriptomics platform with certain advantages for deployment in a clinical setting, our multi-cancer meta-analysis of immune gene expression and overall survival data has identified a specific transcriptional profile associated with poor overall survival

Search for Branons at LEP

We search, in the context of extra-dimension scenarios, for the possible existence of brane fluctuations, called branons. Events with a single photon or a single Z-boson and missing energy and momentum collected with the L3 detector in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are analysed. No excess over the Standard Model expectations is found and a lower limit at 95% confidence level of 103 GeV is derived for the mass of branons, for a scenario with small brane tensions. Alternatively, under the assumption of a light branon, brane tensions below 180 GeV are excluded