Multicenter analysis of sputum microbiota in tuberculosis patients.

The impact of tuberculosis and of anti-tuberculosis therapy on composition and modification of human lung microbiota has been the object of several investigations. However, no clear outcome has been presented so far and the relationship between M. tuberculosis pulmonary infection and the resident lung microbiota remains vague. In this work we describe the results obtained from a multicenter study of the microbiota of sputum samples from patients with tuberculosis or unrelated lung diseases and healthy donors recruited in Switzerland, Italy and Bangladesh, with the ultimate goal of discovering a microbiota-based biomarker associated with tuberculosis. Bacterial 16S rDNA amplification, high-throughput sequencing and extensive bioinformatic analyses revealed patient-specific flora and high variability in taxon abundance. No common signature could be identified among the individuals enrolled except for minor differences which were not consistent among the different geographical settings. Moreover, anti-tuberculosis therapy did not cause any important variation in microbiota diversity, thus precluding its exploitation as a biomarker for the follow up of tuberculosis patients undergoing treatment

Melflufen and dexamethasone in heavily pretreated relapsed and refractory multiple myeloma

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade $ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease

Evidence for transit-timing variations of the 11 Myr exoplanet TOI-1227 b

TOI-1227 b is an 11 Myr old validated transiting planet in the middle of its contraction phase, with a current radius of 0.85 RJ. It orbits a low-mass pre-main sequence star (0.170 M⊙, 0.56 R⊙) every 27.4 days. The magnetic activity of its young host star induces radial velocity jitter and prevents good measurements of the planetary mass. We gathered additional transit observations of TOI-1227 b with space- and ground-based telescopes, and we detected highly significant transit-timing variations (TTVs). Their amplitude is about 40 minutes and their dominant timescale is longer than 3.7 years. Their most probable origin is dynamical interactions with additional planets in the system. We modeled the TTVs with inner and outer perturbers near first and second order resonances; several orbital configurations provide an acceptable fit. More data are needed to determine the actual orbital configuration and eventually measure the planetary masses. These TTVs and an updated transit chromaticity analysis reinforce the evidence that TOI-1227 b is a planet

Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesSolitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on high-dose radiation, but studies exploring the potential benefit of systemic therapies for high-risk patients are urgently needed. In this review, a panel of expert European hematologists updates the recommendations on the diagnosis and management of patients with solitary plasmacytoma.Belgian Foundation against Cancer Fonds National de la Recherche Scientifique Deutsche Krebshilfe Asociacion Espanola Contra el Cance

Candida albicans Infection of Caenorhabditis elegans Induces Antifungal Immune Defenses

Candida albicans yeast cells are found in the intestine of most humans, yet this opportunist can invade host tissues and cause life-threatening infections in susceptible individuals. To better understand the host factors that underlie susceptibility to candidiasis, we developed a new model to study antifungal innate immunity. We demonstrate that the yeast form of C. albicans establishes an intestinal infection in Caenorhabditis elegans, whereas heat-killed yeast are avirulent. Genome-wide, transcription-profiling analysis of C. elegans infected with C. albicans yeast showed that exposure to C. albicans stimulated a rapid host response involving 313 genes (124 upregulated and 189 downregulated, ∼1.6% of the genome) many of which encode antimicrobial, secreted or detoxification proteins. Interestingly, the host genes affected by C. albicans exposure overlapped only to a small extent with the distinct transcriptional responses to the pathogenic bacteria Pseudomonas aeruginosa or Staphylococcus aureus, indicating that there is a high degree of immune specificity toward different bacterial species and C. albicans. Furthermore, genes induced by P. aeruginosa and S. aureus were strongly over-represented among the genes downregulated during C. albicans infection, suggesting that in response to fungal pathogens, nematodes selectively repress the transcription of antibacterial immune effectors. A similar phenomenon is well known in the plant immune response, but has not been described previously in metazoans. Finally, 56% of the genes induced by live C. albicans were also upregulated by heat-killed yeast. These data suggest that a large part of the transcriptional response to C. albicans is mediated through “pattern recognition,” an ancient immune surveillance mechanism able to detect conserved microbial molecules (so-called pathogen-associated molecular patterns or PAMPs). This study provides new information on the evolution and regulation of the innate immune response to divergent pathogens and demonstrates that nematodes selectively mount specific antifungal defenses at the expense of antibacterial responses

Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group

This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes

Refining the properties of the TOI-178 system with CHEOPS and TESS

The TOI-178 system consists of a nearby late K-dwarf transited by six planets in the super-Earth to mini-Neptune regime, with orbital periods between 1.9 and 20.7 days. All planets but the innermost one form a chain of Laplace resonances. Mass estimates derived from a preliminary radial velocity (RV) dataset suggest that the planetary densities do not decrease in a monotonic way with the orbital distance to the star, contrary to what one would expect based on simple formation and evolution models. To improve the characterisation of this key system and prepare for future studies (in particular with JWST), we perform a detailed photometric study based on 40 new CHEOPS visits, one new TESS sector, as well as previously published CHEOPS, TESS, and NGTS data. First we perform a global analysis of the 100 transits contained in our data to refine the transit parameters of the six planets and study their transit timing variations (TTVs). We then use our extensive dataset to place constraints on the radii and orbital periods of potential additional transiting planets in the system. Our analysis significantly refines the transit parameters of the six planets, most notably their radii, for which we now obtain relative precisions $\lesssim$3%, with the exception of the smallest planet $b$ for which the precision is 5.1%. Combined with the RV mass estimates, the measured TTVs allow us to constrain the eccentricities of planets $c$ to $g$, which are found to be all below 0.02, as expected from stability requirements. Taken alone, the TTVs also suggest a higher mass for planet $d$ than the one estimated from the RVs, which had been found to yield a surprisingly low density for this planet. However, the masses derived from the current TTV dataset are very prior-dependent and further observations, over a longer temporal baseline, are needed to deepen our understanding of this iconic planetary system.Comment: 20 pages, 5 figures, 9 tables. Accepted for publication in A&

Special cases : moons, rings, comets, trojans

Non-planetary bodies provide valuable insight into our current under- standing of planetary formation and evolution. Although these objects are challeng- ing to detect and characterize, the potential information to be drawn from them has motivated various searches through a number of techniques. Here, we briefly review the current status in the search of moons, rings, comets, and trojans in exoplanet systems and suggest what future discoveries may occur in the near future.Comment: Invited review (status August 2017

Future Exoplanet Research: Science Questions and How to Address Them

Started approximately in the late 1980s, exoplanetology has up to now unveiled the main gross bulk characteristics of planets and planetary systems. In the future it will benefit from more and more large telescopes and advanced space missions. These instruments will dramatically improve their performance in terms of photometric precision, detection speed, multipixel imaging, high-resolution spectroscopy, allowing to go much deeper in the knowledge of planets. Here we outline some science questions which should go beyond these standard improvements and how to address them. Our prejudice is that one is never too speculative: experience shows that the speculative predictions initially not accepted by the community have been confirmed several years later (like spectrophotometry of transits or circumbinary planets).Comment: Invited review, accepte