Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study.

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.

Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients. PATIENTS AND METHODS: ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line ≥12 weeks. RESULTS: Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC {hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36}. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade ≥3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002). CONCLUSIONS: In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted.

Evaluation of scientific output in Dentistry in Spanish Universities.

BACKGROUND: The aim of this study was to assess the scientific output of Spanish universities that offer a bachelor's degree in dentistry through the use of various bibliometric indicators. MATERIAL AND METHODS: A total of 21 universities offered a bachelor's degree in dentistry in academic year 2016-2017. The search for papers published by authors associated with these institutions was carried out using the selection of journals listed in the Journal Citation Reports (JCR) and the Web of Knowledge database for the period 1986-2017. On the basis of these data, we determined the output, the h-, g- and hg-indexes, the most productive authors, international collaborations, and the most relevant journals. RESULTS: Public universities obtained better results than private universities. The University of Valencia was ranked first, followed by the Complutense University of Madrid and the University of Granada. The most productive author was José Vicente Bagán, but the author with the highest h-index was Mariano Sanz and Manuel Toledado. The universities with the greatest output and highest citation rates had more international collaborations. The most developed fields in Spanish universities were Oral surgery, Oral medicine and Dental materials. The universities had different models of production. At universities such as Barcelona or Valencia, the production was focused on very few departments and authors. At the other extreme, the University of Granada had various sources of research and authors, which meant that its output and citation rate could increase more. CONCLUSIONS: University faculties must provide suitable academic and research training, and therefore must be assessed using objective criteria and bibliometric tools. Although the number of university schools and faculties that teach dentistry has increased, and particularly the number of private universities, there is no correlation between their quality and output and the number of places offered on their courses.

Lowering bronchoaspiration rate in an acute stroke unit by means of a 2 volume/3 texture dysphagia screening test with pulsioximetry. / Reducción de la tasa de broncoaspiración con el test 2 volúmenes/3 texturas con pulsioximetría en una unidad de ictus.

INTRODUCTION: During acute stroke, 30% of all patients present dysphagia and 50% of that subgroup will experience bronchoaspiration. Our aim was to compare mortality and bronchoaspiration rates associated with the water test compared to those associated with a 2 volume/3 texture test controlled with pulse oximetry (2v/3t-P test) in our stroke unit. PATIENTS AND METHODS: Over a 5-year period, we performed a prospective analysis of all consecutive acute ischaemic stroke patients hospitalised in the Stroke Unit. Dysphagia was evaluated using the water test between 2008 and 2010 (group 0 or G0), and the 2v/3t-P test (group 1 or G1) between 2011 and 2012. We analysed demographic data, vascular risk factors, neurological deficit on the NIHSS, aetiological subtype according to TOAST criteria, clinical subtype according to the Oxfordshire classification, prevalence of dysphagia, percentage of patients with bronchoaspiration, and mortality. RESULTS: We examined 418 patients with acute stroke (G0=275, G1=143). There were significant differences between the 2 groups regarding the percentage of patients with TACI (17% in G0 vs. 29% in G1, P=.005) and median NIHSS score (4 points in G0 vs. 7 points in G1, P=.003). Since adopting the new swallowing test, we detected a non-significant increase in the percentage of dysphagia (22% in G0 vs. 25% in G1, P=.4), lower mortality (1.7% in G0 vs. 0.7% in G1, P=.3) and a significant decrease in the bronchoaspiration rate (6.2% in G0 vs. 2.1% in G1, P=.05). CONCLUSIONS: Compared to the water test used for dysphagia screening, the new 2v/3t-P test lowered bronchoaspiration rates in acute stroke patients.

An overview of animal science research 1945-2011 through science mapping analysis.

The conceptual structure of the field of Animal Science (AS) research is examined by means of a longitudinal science mapping analysis. The whole of the AS research field is analysed, revealing its conceptual evolution. To this end, an automatic approach to detecting and visualizing hidden themes or topics and their evolution across a consecutive span of years was applied to AS publications of the JCR category 'Agriculture, Dairy & Animal Science' during the period 1945-2011. This automatic approach was based on a coword analysis and combines performance analysis and science mapping. To observe the conceptual evolution of AS, six consecutive periods were defined: 1945-1969, 1970-1979, 1980-1989, 1990-1999, 2000-2005 and 2006-2011. Research in AS was identified as having focused on ten main thematic areas: ANIMAL-FEEDING, SMALL-RUMINANTS, ANIMAL-REPRODUCTION, DAIRY-PRODUCTION, MEAT-QUALITY, SWINE-PRODUCTION, GENETICS-AND-ANIMAL-BREEDING, POULTRY, ANIMAL-WELFARE and GROWTH-FACTORS-AND-FATTY-ACIDS. The results show how genomic studies gain in weight and integrate with other thematic areas. The whole of AS research has become oriented towards an overall framework in which animal welfare, sustainable management and human health play a major role. All this would affect the future structure and management of livestock farming.

[Recommendations for radiological diagnosis and assessment of treatment response in lung cancer: a national consensus statement by the Spanish Society of Medical Radiology and the Spanish Society of Medical Oncology]. / Recomendaciones para el diagnóstico radiológico y la valoración de la respuesta terapéutica en el cáncer de pulmón. Consenso nacional de la Sociedad Española de Radiología Médica y la Sociedad Española de Oncología Médica.

The last decade has seen substantial progress in the diagnostic and therapeutic approach to lung cancer, thus meaning that its prognosis has improved. The Spanish Society of Medical Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM) have therefore produced a national consensus statement in order to make recommendations for radiological diagnosis and assessment of treatment response in patients with lung cancer. This expert group recommends multi-detector computed tomography (MDCT) as the technique of choice for investigating this disease. The radiology report should include a full assessment by the TNM staging system. Lastly, when the patient is on immunotherapy, response evaluation should employ not only Response Evaluation Criteria in Solid Tumours (RECIST 1.1) but also Immune-Related Response Criteria (irRC).

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.

BACKGROUND: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). TREATMENT: gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. RESULTS: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7). CONCLUSION: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.

Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies.

BACKGROUND: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. PATIENTS AND METHODS: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). RESULTS: Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). CONCLUSION: Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches. TRIAL REGISTRATION: NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA.

Identification of hazardous organic compounds in e-waste plastic using non-target and suspect screening approaches.

End-of-life electric and electronic devices stand as one of the fastest growing wastes in the world and, therefore, a rapidly escalating global concern. A relevant fraction of these wastes corresponds to polymeric materials containing a plethora of chemical additives. Some of those additives fall within the category of hazardous organic compounds (HOCs). Despite the significant advances in the capabilities of analytical methods, the comprehensive characterization of WEEE plastic remains as a challenge. This research strives to identify the primary additives within WEEE polymers by implementing a non-target and suspect screening approach. Gas chromatography coupled to time-of-flight mass spectrometry (GC-QTOF-MS), using electron ionization (EI), was applied for the detection and identification of more than 300 substances in this matrix. A preliminary comparison was carried out with nominal resolution EI-MS spectra contained in the NIST17 library. BPA, flame retardants, UV-filters, PAHs, and preservatives were among the compounds detected. Fifty-one out of 300 compounds were confirmed by comparison with authentic standards. The study establishes a comprehensive database containing m/z ratios and accurate mass spectra of characteristic compounds, encompassing HOCs. Semi-quantification of the predominant additives was conducted across 48 WEEE samples collected from handling and dismantling facilities in Galicia. ABS plastic demonstrated the highest median concentrations, ranging from 0.154 to 4456 µg g-1, being brominated flame retardants and UV filters, the families presenting the highest concentrations. Internet router devices revealed the highest concentrations, containing a myriad of HOCs, such as tetrabromobisphenol A (TBBPA), tribromophenol (TBrP), triphenylphosphate (TPhP), tinuvin P and bisphenol A (BPA), most of which are restricted in Europe.

Bibliometric analysis of parasite vaccine research from 1990 to 2019.

Bibliometric and bibliographic analyses are popular tools for investigating publication metrics and thematic transitions in an expanding codex of biomedical literature. Bibliometric techniques have been employed in parasitology and vaccinology, with only a few malaria-specific literature analyses being reported specifically on parasite vaccines. The pursuit of parasite prophylactics is an important, global endeavour both medically and economically. As such, a comprehensive understanding of the research topics would be a valuable tool in assessing the current status and future directions of parasite vaccine development. Consequently, this study investigated parasite vaccinology from 1990 to 2019 by analysing literature exported from the Web of Science and Dimensions databases using two, commonly used, bibliometric programs: SciMAT and VOSviewer. The results of this study show the common, emerging, and transient themes within the discipline, and where the future lies as vaccine development moves further into the age of omics and informatics.

Can cyanotoxins explain the clinical features of the thermal crisis in balneotherapy?

Microbial biofilms communities in mineral waters and hot springs have a particular composition with species belonging to different groups such as epsilonproteobacteria and gammaproteobacteria or different siderobacteria and other chymoautrophic organisms, in addition to certain bacillaryophytes, chlorophytes and especially cyanobacteria. Balneotherapy can cause adverse reactions to the usual doses of application of treatments, that consists of a non-specific clinical picture, the so-called "thermal crisis" or "balneointoxication". Despite its clinical similarity (gastric discomfort, hepatic congestive outbreaks, cutaneous reactions, etc.) with that observed in acute cyanotoxin poisonings, thermal crisis has never been associated with the abundant growth of potentially toxic cyanobacteria in the mineral water sources. The aim of this work was to verify the hypothetical involvement of cyanotoxins in this clinical picture. Samples from mostly sulphurous water sources, with thermal characteristics ranging from cold to hyperthermal waters were analysed. ELISA (both in solution and in cellular matrix samples), LC-ESI-HRMS (in cellular matrix samples), and analysis of potential toxicity by means of a standardized bioassay were carried out. The toxic effect observed in the toxicity bioassays in one third of the sources may be related to the existence of microcystins and nodularins and even with other cyanobacterial peptides detected. In addition, several responses observed in the toxicity analyses reflect a pattern, probably linked to a type of hormetic response (hormesis is an adaptive response to low levels of stress, characterized by a biphasic dose-response curve).

The EPICAL trial, a phase Ib study combining first line afatinib with anti-EGF vaccination in EGFR-mutant metastatic NSCLC.

INTRODUCTION: Combination of anti-EGFR monoclonal antibodies or immune checkpoint inhibitors with TKIs has shown minimal benefit in EGFR mutant (EGFR-mut) NSCLC patients. Consequently, new combination approaches are needed. PATIENTS AND METHODS: The EPICAL was a single arm, phase 1b study to evaluate safety, tolerability and anti-tumor activity of first line afatinib combined with anti-EGF vaccination in advanced EGFR-mut patients. EGFR status and mutations in liquid biopsies were determined by reverse transcriptase-polymerase chain reaction; serum biomarkers by ELISA and Western blotting analysis. RESULTS: The assay enrolled 23 patients, 21 completed the anti-EGF immunization phase. Treatment was well tolerated and no serious adverse events (SAEs) related to the anti-EGF vaccine were reported. Objective response and disease control rates were 78.3% (95%CI = 53.6-92.5) and 95.7% (95%CI = 78.1-99.9), respectively. After a median follow-up of 24.2 months, median progression-free survival (PFS) was 14.8 months (95% CI = 9.5-20.1) and median overall survival (OS) 26.9 months (95% CI = 23.0-30.8). Among the 21 patients completing the immunization phase, PFS was 17.5 months (95% CI = 12.0-23.0) and OS 26.9 months (95% CI = 24.6-NR). At the end of the immunization phase, all 21 patients showed high serum titers of anti-EGF antibodies, while EGF levels had decreased significantly. Finally, treatment with fully immunized patient's sera inhibited the EGFR pathway in tumor cells growing in vitro. CONCLUSIONS: Combination treatment with an anti-EGF vaccine is well tolerated; induces a sustained immunogenic effect and might enhance the clinical efficacy of EGFR TKIs.

Physiological and tissue-specific vectors for treatment of inherited diseases.

After more than 1500 gene therapy clinical trials in the past two decades, the overall conclusion is that for gene therapy (GT) to be successful, the vector systems must still be improved in terms of delivery, expression and safety. The recent development of more efficient and stable vector systems has created great expectations for the future of GT. Impressive results were obtained in three primary immunodeficiencies and other inherited diseases such as congenital blindness, adrenoleukodystrophy or junctional epidermolysis bullosa. However, the development of leukemia in five children included in the GT clinical trials for X-linked severe combined immunodeficiency and the silencing of the therapeutic gene in the chronic granulomatous disease clearly showed the importance of improving safety and efficiency. In this review, we focus on the main strategies available to achieve physiological or tissue-specific expression of therapeutic transgenes and discuss the importance of controlling transgene expression to improve safety. We propose that tissue-specific and/or physiological viral vectors offer the best balance between efficiency and safety and will be the tools of choice for future clinical trials in GT of inherited diseases.

A tissue-specific, activation-inducible, lentiviral vector regulated by human CD40L proximal promoter sequences.

The application of new protocols for gene therapy against monogenic diseases requires the development of safer therapeutic vectors, particularly in the case of diseases in which expression of the mutated gene is subject to fine regulation, as it is with CD40L (CD154). CD40L, the gene mutated in the X-linked hyper-immunoglobulin M syndrome (HIGM1), is tightly regulated to allow surface expression of its product only on T cells stimulated by antigen encounter. Previous studies in an HIGM1 animal model showed that transduction of progenitor cells corrected the syndrome but caused a thymic lymphoproliferative disease because of the unregulated expression of the transgene by constitutive vectors. To develop a tissue-specific, activation-inducible, lentiviral vector (LV) for gene therapy to counter HIGM1, we have constructed two self-inactivating LVs, pCD40L-eGFP and pCD40L-CD40L, regulated by a 1.3 kb fragment of the human CD40L proximal promoter. The expression of pCD40L-eGFP LV is restricted to cells in which mRNA transcripts of the endogenous CD40L gene can be detected. Moreover, the expression of the reporter gene in primary T lymphocytes depends on the activation state of the cells. Remarkably, primary HIGM1 lymphocytes transduced with pCD40L-CD40L LV expressed CD40L only after T-cell stimulation. Therefore, the CD40L-promoter-driven vectors are able to achieve a near-physiological expression pattern that follows very closely that of the endogenous CD40L gene.

A novel EDA gene mutation in a Spanish family with X-linked hypohidrotic ectodermal dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by abnormal development of the hair, teeth, and sweat glands. It is caused by mutations in the EDA gene, which maps to the X chromosome and encodes a protein called ectodysplasin-A, a member of the tumor necrosis factor-related ligand family. Affected males typically exhibit all the typical features of HED, but heterozygous carriers may show mild to moderate clinical manifestations. We describe the case of a Spanish family in which a novel heterozygous c.733_734insGA mutation at the EDA gene was identified. It was located in exon 5 and consisted of a frame-shift mutation at codon 245, which gave rise to an abnormal protein with a premature stop codon after 35 residues. Genetic analyses in families with XLHED are useful for checking carrier status, but they also provide information for genetic counseling and prenatal diagnosis.

On the diversity of abyssal Dondersiidae (Mollusca: Aplacophora) with the description of a new genus, six new species, and a review of the family.

So far, of the 292 known species of solenogasters (Mollusca, Aplacophora), 62 belong to the clade Pholidoskepia Salvini-Plawen, 1978. Of these, only two have an abyssal distribution (3500-6000 m depth). Among Pholidoskepia, Dondersiidae Simroth, 1893 is the most diverse family. This study contributes to the knowledge of this family with the description of one new genus and six new species from the abyssal South Atlantic Ocean: Dondersia ? foraminosa sp. n., Nematomenia divae sp. n., Nematomenia brasiliensis sp. n., Nematomenia ? guineana sp. n., Helluoherpia vieiralaneroi sp. n. and Inopinatamenia (gen. n.) calamitosa sp. n. Specimens were collected during DIVA (Latitudinal Gradients of Deep-Sea BioDIVersity in the Atlantic Ocean) expeditions in the Guinea (DIVA 2 Me 63/2, 2005) and Brazil (DIVA 3 Me 79/1, 2008) Basins. Specimens were characterized based primarily on the sclerites and internal anatomy, which was studied using histology. The importance of the radula and mantle sclerites for taxonomy is emphasized. Amended diagnoses for the family and some genera within this family are provided. This contribution increases the described diversity of Dondersiidae to ten genera and 38 species and highlights the need for more study of solenogasters in the deep sea.

First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update.

BACKGROUND: To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. PATIENTS AND METHODS: Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. RESULTS: With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. CONCLUSIONS: With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.

[Goodpasture's syndrome with neurologic involvement and negative ANCA]. / Síndrome de Goodpasture asociado con vasculitiscerebral ANCA negativa.

Goodpasture's syndrome is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis (RPGN) and alveolar hemorrhage in the presence of antiglomerular basement membrane (anti-GBM) antibodies. Central nervous system involvement is highly unusual in the absence of anti-neutrophil cytoplasmic antibodies. We report the case of a 20-year-old man with RPGN accompanied by bloody sputum, tonic-clonic seizure and high titers of anti-GBM antibody. After treatment with immunosuppressants and plasmapheresis, the patient showed reduced anti-GBM antibody titers and improved neurologic and respiratory symptoms, but renal failure persisted, requiring hemodialysis. Twenty months later, with the disease in remission, he underwent deceased-donor renal transplantation.

Expression-based, consistent biomarkers for prognosis and diagnosis in lung cancer.

OVERVIEW: Lung cancer is one of the deadliest cancers in the world. Its histological classification depends on early diagnosis and successful treatment. Therefore, having specific biomarkers for a quick sorting widens the successful output of lung cancer treatment. MATERIAL AND METHODS: High-throughput sequencing (RNA-seq) was performed of small cohorts of BioBanco samples from healthy and tumour cells from lung adenocarcinoma (LUAD) and squamous cell carcinoma of the lung (lSCC). RNA-seq samples from small cell lung cancer (SCLC) were downloaded from databases. A bioinformatic workflow has been programmed for the identification of differentially expressed genes (DEGs). RESULTS: A total of 4777 DEGs were differentially expressed in SCLC, 3676 DEGs were in lSCC, while the lowest number of DEGs, 2819, appeared in LUAD. Among them, 945 DEGs were common to the three histological types. Once validated their expression profile and their survival predictive capacity in large, public cohorts, three DEGs can be exclusively considered as diagnostic biomarkers, three as prognosis biomarkers, and other three exhibit both diagnosis and prognosis capabilities. CONCLUSIONS: This prospective study presents evidences for the diagnostic and prognostic capabilities of expression changes in CAPN8-2, TMC5 and MUC1 in LUAD, while they are non-significant in SCLC and lSCC. Their translation to clinical practice is proposed.