Not all vaping is the same: differential pulmonary effects of vaping cannabidiol versus nicotine.

RATIONALE: Vaping has become a popular method of inhaling various psychoactive substances. While evaluating respiratory effects of vaping have primarily focused on nicotine-containing products, cannabidiol (CBD)-vaping is increasingly becoming popular. It currently remains unknown whether the health effects of vaping nicotine and cannabinoids are similar. OBJECTIVES: This study compares side by side the pulmonary effects of acute inhalation of vaporised CBD versus nicotine. METHODS: In vivo inhalation study in mice and in vitro cytotoxicity experiments with human cells were performed to assess the pulmonary damage-inducing effects of CBD or nicotine aerosols emitted from vaping devices. MEASUREMENTS AND MAIN RESULTS: Pulmonary inflammation in mice was scored by histology, flow cytometry, and quantifying levels of proinflammatory cytokines and chemokines. Lung damage was assessed by histology, measurement of myeloperoxidase activity and neutrophil elastase levels in the bronchoalveolar lavage fluid and lung tissue. Lung epithelial/endothelial integrity was assessed by quantifying BAL protein levels, albumin leak and pulmonary FITC-dextran leak. Oxidative stress was determined by measuring the antioxidant potential in the BAL and lungs. The cytotoxic effects of CBD and nicotine aerosols on human neutrophils and human small airway epithelial cells were evaluated using in vitro air-liquid interface system. Inhalation of CBD aerosol resulted in greater inflammatory changes, more severe lung damage and higher oxidative stress compared with nicotine. CBD aerosol also showed higher toxicity to human cells compared with nicotine. CONCLUSIONS: Vaping of CBD induces a potent inflammatory response and leads to more pathological changes associated with lung injury than vaping of nicotine.

Do alternative tobacco products induce less adverse respiratory risk than cigarettes?

RATIONALE: Due to the relatively short existence of alternative tobacco products, gaps exist in our current understanding of their long-term respiratory health effects. We therefore undertook the first-ever side-by-side comparison of the impact of chronic inhalation of aerosols emitted from electronic cigarettes (EC) and heated tobacco products (HTP), and combustible cigarettes (CC) smoke. OBJECTIVES: To evaluate the potential differential effects of alternative tobacco products on lung inflammatory responses and efficacy of vaccination in comparison to CC. METHODS: Mice were exposed to emissions from EC, HTP, CC, or air for 8 weeks. BAL and lung tissue were analyzed for markers of inflammation, lung damage, and oxidative stress. Another group was exposed for 12 weeks and vaccinated and challenged with a bacterial respiratory infection. Antibody titers in BAL and sera and pulmonary bacterial clearance were assessed. MAIN RESULTS: EC- and HTP-aerosols significantly augmented lung immune cell infiltrates equivalent to that achieved following CC-exposure. HTP and CC significantly increased neutrophil numbers compared to EC. All products augmented numbers of B cells, T cells, and pro-inflammatory IL17A+ T cells in the lungs. Decreased lung antioxidant activity and lung epithelial and endothelial damage was induced by all products. EC and HTP differentially augmented inflammatory cytokines/chemokines in the BAL. Generation of immunity following vaccination was impaired by EC and HTP but to a lesser extent than CC, with a CC > HTP > EC hierarchy of suppression of pulmonary bacterial clearance. CONCLUSIONS: HTP and EC-aerosols induced a proinflammatory pulmonary microenvironment, lung damage, and suppressed efficacy of vaccination.

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma.

BACKGROUND: The immunostimulatory monoclonal antibody elotuzumab plus lenalidomide and dexamethasone has been shown to be effective in patients with relapsed or refractory multiple myeloma. The immunomodulatory agent pomalidomide plus dexamethasone has been shown to be effective in patients with multiple myeloma that is refractory to lenalidomide and a proteasome inhibitor. METHODS: Patients with multiple myeloma that was refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor were randomly assigned to receive elotuzumab plus pomalidomide and dexamethasone (elotuzumab group) or pomalidomide and dexamethasone alone (control group). The primary end point was investigator-assessed progression-free survival. RESULTS: A total of 117 patients were randomly assigned to the elotuzumab group (60 patients) or the control group (57 patients). After a minimum follow-up period of 9.1 months, the median progression-free survival was 10.3 months in the elotuzumab group and 4.7 months in the control group. The hazard ratio for disease progression or death in the elotuzumab group as compared with the control group was 0.54 (95% confidence interval [CI], 0.34 to 0.86; P=0.008). The overall response rate was 53% in the elotuzumab group as compared with 26% in the control group (odds ratio, 3.25; 95% CI, 1.49 to 7.11). The most common grade 3 or 4 adverse events were neutropenia (13% in the elotuzumab group vs. 27% in the control group), anemia (10% vs. 20%), and hyperglycemia (8% vs. 7%). A total of 65% of the patients in each group had infections. Infusion reactions occurred in 3 patients (5%) in the elotuzumab group. CONCLUSIONS: Among patients with multiple myeloma in whom treatment with lenalidomide and a proteasome inhibitor had failed, the risk of progression or death was significantly lower among those who received elotuzumab plus pomalidomide and dexamethasone than among those who received pomalidomide plus dexamethasone alone. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-3 ClinicalTrials.gov number, NCT02654132 .).

Acute Effects of Heated Tobacco Product (IQOS) Aerosol Inhalation on Lung Tissue Damage and Inflammatory Changes in the Lungs.

INTRODUCTION: Emerging heated tobacco products (HTPs) were designed to reduce exposure to toxicants from cigarette smoke (CS) by avoiding burning tobacco and instead heating tobacco. We studied the effects of short-term inhalation of aerosols emitted from HTP called IQOS, on lung damage and immune-cell recruitment to the lungs in mice. METHODS: Numerous markers of lung damage and inflammation including albumin and lung immune-cell infiltrates, proinflammatory cytokines, and chemokines were quantified in lungs and bronchoalveolar (BAL) fluid from IQOS, CS, or air-exposed (negative control) mice. RESULTS: Importantly, as a surrogate marker of lung epithelial-cell damage, we detected significantly increased levels of albumin in the BAL fluid of both HTP- and CS-exposed mice compared with negative controls. Total numbers of leukocytes infiltrating the lungs were equivalent following both IQOS aerosols and CS inhalation and significantly increased compared with air-exposed controls. We also observed significantly increased numbers of CD4+IL-17A+ T cells, a marker of a T-cell immune response, in both groups compared with air controls; however, numbers were the highest following CS exposure. Finally, the numbers of CD4+RORγt+ T cells, an inflammatory T-cell subtype expressing the transcription factor that is essential for promoting differentiation into proinflammatory Th17 cells, were significantly augmented in both groups compared with air-exposed controls. Levels of several cytokines in BAL were significantly elevated, reflecting a proinflammatory milieu. CONCLUSIONS: Our study demonstrates that short-term inhalation of aerosols from IQOS generates damage and proinflammatory changes in the lung that are substantially similar to that elicited by CS exposure. IMPLICATIONS: Exposure of mice to IQOS, one of the candidate modified-risk tobacco products, induces inflammatory immune-cell accumulation in the lungs and augments the levels of proinflammatory cytokines and chemokines in the BAL fluid. Such an exacerbated pulmonary proinflammatory microenvironment is associated with lung epithelial-cell damage in IQOS-exposed mice, suggesting a potential association with the impairment of lung function.

Malignant hyperthermia during pediatric kidney transplantation-A medical and ethical quandary.

Malignant hyperthermia (MH) is a rare life-threatening anesthetic complication with high mortality rates. MH during adult kidney transplant has been reported previously. However, the occurrence of MH after multiple previous uneventful anesthetic exposures in a pediatric kidney transplant recipient is rare. To our knowledge, this is the first reported case of MH in a child undergoing a live donor kidney transplant. The approaches for addressing perioperative challenges and ethical dilemmas to ensure successful outcomes are described. The recipient, a 5-year-old male child, weighing 20 kg, with a history of multiple previous uneventful anesthetic exposures, underwent live donor kidney transplant for end-stage renal disease (ESRD). Post-reperfusion he developed fulminant MH with rapidly progressing hyperthermia, hypercarbia, tachycardia, and muscle rigidity, which in addition to complicating the medical management raised several ethical issues as well. MH was successfully managed with dantrolene and other supportive measures. Judicious use of inotropes and fluids helped maintain stable hemodynamics and graft perfusion. Management of MH is complicated in a pediatric patient with ESRD undergoing live donor kidney transplant. Preference for non-depolarizing muscle relaxants instead of succinylcholine during endotracheal intubation can result in delayed onset of clinical manifestations. However, the metabolic complications may be more severe due to preexisting electrolyte and acid-base disturbances. Maintaining optimal graft perfusion while simultaneously combating MH can be very challenging in a child. Since the allograft is a precious commodity, critical decisions regarding the harvesting of the donor kidney need to be well thought out. Early diagnosis and prompt treatment with dantrolene are critical to preserving graft function and the recipient's life.

An exploration of the oral health beliefs and behaviors of people living with HIV in Mangalore, India: a qualitative study.

INTRODUCTION: People living with HIV (PLWHIV) have increased oral healthcare needs due to an increase in the prevalence of oral and dental diseases. Their oral health is influenced by psychosocial, behavioral and biologic factors. The aim of this study was to explore and obtain a deeper understanding of the oral health beliefs and behaviors of PLWHIV that could potentially affect their oral health. METHODS: We have used the Health Belief Model (HBM) and qualitative methods using in-depth interviews with 16 PLWHIV. Content analysis of the transcribed data was done. The data was grouped under the constructs of the HBM. FINDINGS: The perceived susceptibility to oral diseases and awareness on the importance of good oral health was low. Regular tooth brushing and traditional methods for oral hygiene maintenance were considered beneficial. Regular dental visits were not considered important. Psychosocial issues, time and financial constraints were the barriers. Participants believed that information on oral health should be provided by the health providers in hospitals and dental clinics.  CONCLUSION: The findings on the oral health beliefs and behaviors support the need for education on oral health and preventive healthcare practices among PLWHIV. Oral health promotion should include behavioral change as one of its components.

Genetic Variant Associated With Survival of Patients With Stage II-III Colon Cancer.

BACKGROUND & AIMS: Many genetic variants have been associated with colorectal cancer risk, although few have been associated with survival times of patients. Identification of genetic variants associated with survival times might improve our understanding of disease progression and aid in outcome prediction. We performed a genome-wide association study to identify variants associated with colon cancer survival time. METHODS: We performed a post hoc analysis of data from NCCTG N0147 (Alliance), a randomized phase 3 trial of patients with resected stage III colon cancer, and from NSABP C-08 (NRG), a phase 3 trial that compared therapy regimens for patients with resected stage II or III colon cancer. Genotype analyses were performed on DNA from blood samples from 4974 patients. We used Cox proportional hazards regression to evaluate the association of each single nucleotide polymorphism with times of overall survival and disease-free survival, adjusting for age at diagnosis, sex, treatment group, and principal components of genetic ancestry. We performed the analysis for studies N0147 and C-08 separately, and results were combined in a fixed-effects meta-analysis. RESULTS: A locus on chromosome 7p15.2 was significantly associated with overall survival time (P ≤ 5x10-08). The most significant variant at this locus, rs76766811 (P = 1.6x10-08), is common among African Americans (minor allele frequency, approximately 18%) but rare in European Americans (minor allele frequency <0.1%). Within strata of self-reported ancestry, this variant was associated with times of overall survival and disease-free survival in only African Americans (hazard ratio for overall survival, 2.82; 95% CI, 1.88-4.23; P = 5.0x10-07 and hazard ratio for disease-free survival, 2.27; 95% CI, 1.62-3.18; P = 1.8x10-06). CONCLUSIONS: In an analysis of data from 2 trials of patients with stage II or III colon cancer, we identified rs76766811 as a potential prognostic variant in African American patients. This finding should be confirmed in additional study populations. ClinicalTrials.gov Identifiers: NCT00096278 (NSABP C-08) and NCT00079274 (NCCTG N0147).

Dramatic Response to Concurrent Anti-PD-1 Therapy and Radiation in Resistant Tumors with Sarcomatoid Differentiation.

A substantial fraction of patients demonstrate resistance to immune checkpoint inhibitors, which limits their use. Use of radiation concurrently with checkpoint inhibitors has been shown to boost immune responsiveness, resulting in significant tumor regression in patients with metastatic melanoma. However, it is unknown whether radiation could play a role in reversing the inherent resistance to checkpoint inhibition in certain tumor types. Most trials testing this concurrent approach exclude such modestly responsive tumors and pursue checkpoint inhibition using anti-cytotoxic T-lymphocyte-associated protein 4 antibody (anti-CTLA-4, ipilimumab). The efficacy of anti-programmed-death-1 (anti-PD-1) therapy when used concurrently with radiation is less known but remains an attractive option due to less autoimmune toxicity compared with CTLA-4 inhibition. In this first reported experience, we have safely and effectively combined anti-PD-1 therapy (nivolumab) concurrently with radiation to treat two patients with relapsed sarcomatoid renal carcinoma and heavily pretreated pleomorphic sarcoma. Both patients experienced a dramatic response that was durable.

Infrared Thermal Imaging for Diabetes Detection and Measurement.

The diabetes mellititus (type 1) condition occur when the beta cell destroy partially due to autoimmune process. The beta cells produce insulin with respect to blood glucose level. The insulin hormone regulates blood glucose in body. The blood glucose increases in body when insulin secretion is low from pancreas, termed as Diabetes mellititus. The Diabetes mellititus causes infection, pain in mouth. The regions in mouth affected by diabetes mellititius include gums, teeth, jaw and tongue. The glucose level increases in saliva which grows harmful bacteria. The bacteria in combination with plaque cause bad breath, gum disease and coating on tongue. The coating and sugar level in tongue alters the temperature of tongue. In this paper we propose to analyze tongue thermal image to diagnose diabetes at early stage.

Chryseobacterium salipaludis sp. nov., isolated at a wild ass sanctuary.

A Gram-stain-negative, rod-shaped, non-motile, aerobic bacterium was isolated from a sediment sample obtained from a wild ass sanctuary in Gujarat, India. The strain designated JC490T was oxidase- and catalase-positive. The 16S rRNA gene sequence analysis and sequence comparison data indicated that strain JC490T was a member of the genus Chryseobacterium and was closely related to Chryseobacterium jeonii AT1047T (96.4 %) and with other members of the genus Chryseobacterium (<96.3 %). The DNA G+C content of strain JC490T was 34 mol%. Strain JC490T had phosphatidylethanolamine, two unidentified aminolipids, two unidentified phospholipids and five unidentified polar lipids. Menaquinone-6 was the only respiratory quinone found. Iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0 3-OH were the major fatty acids of strain JC490T. On the basis of physiological, genotypic, phylogenetic and chemotaxonomic analyses, it is concluded that strain JC490T constitutes a novel species of the genus Chryseobacterium, for which the name Chryseobacterium salipaludis sp. nov. is proposed. The type strain is JC490T (=KCTC 52835T=LMG 30048T).

Description of Rhodobacter azollae sp. nov. and Rhodobacter lacus sp. nov.

Three strains (JA826T, JA912T and JA913), which were yellowish brown colour, rod to oval shaped, Gram-stain-negative, motile, phototrophic bacteria with a vesicular architecture of intracytoplasmic membranes, were isolated from different pond samples. The DNA G+C content of the three strains was between 64.6 and 65.5 mol%. The highest 16S rRNA gene sequence similarity of all three strains was with the type strains of the genus Rhodobacter sensu stricto in the family Rhodobacteraceae. Strain JA826T had highest sequence similarity with Rhodobacter maris JA276T (98.5 %), Rhodobacter viridis JA737T (97.5 %) and other members of the genus Rhodobacter (<97 %). Strain JA912T had highest sequence similarity with Rhodobacter viridis JA737T (99.6 %), Rhodobacter sediminis N1T (99.3 %), Rhodobacter capsulatus ATCC 11166T (98.8 %) and less than 97 % similarity with other members of the genus Rhodobacter. The 16S rRNA gene sequence similarity between strains JA826T and JA912T was 96.9 %. DNA-DNA hybridization showed that strains JA826T and JA912T (values among themselves and between the type strains of nearest members <44 %) did not belong to any of the nearest species of the genus Rhodobacter. However, strains JA912T and JA913 were closely related (DNA-DNA hybridization value >90 %). The genomic distinction was also supported by differences in phenotypic and chemotaxonomic characteristics in order to propose strains JA826T (=KCTC 15478T=LMG 28758T) and JA912T (=KCTC 15475T=LMG 28748T) as new species in the genus Rhodobacter sensu stricto with the names Rhodobacter lacus and Rhodobacter azollae, respectively.

Molecular characterization of ß-lactamase genes in clinical isolates of carbapenem-resistant Acinetobacter baumannii.

BACKGROUND: Acinetobacter baumannii is a nosocomial pathogen which is establishing as a major cause of morbidity and mortality within the healthcare community. The success of this pathogen is largely due to its ability to rapidly gain resistance to antimicrobial therapies and its capability to persist in an abiotic environment through the production of a biofilm. Our tertiary-care hospital has showed high incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. METHODS: In this study we explore both genotypic and phenotypic properties of 26 CRAB isolates: 16 isolates were collected from January 2010 to March 2011, and 10 were collected between February and May 2015. RESULTS: We determined that all 26 CRAB isolates possessed multiple ß-lactamase genes, including genes from Groups A, C, and D. Specifically, 42% of the isolates possesses the potentially plasmid-borne genes of OXA-23-like or OXA-40-like ß-lactamase. The presence of mobile gene element integron cassettes and/or integrases in 88% of the isolates suggests a possible mechanism of dissemination of antibiotic resistance genes. Additionally, the location of insertion sequence (IS) ISAba1 in promotor region of of the OXA-51-like, ADC-7, and ampC genes was confirmed. Multilocus sequence typing (MLST) demonstrated that all 26 CRAB isolates were either sequence type (ST)-229 or ST-2. Interestingly, ST-2 went from being the minority CRAB strain in the 2010-2011 isolates to the predominant strain in the 2015 isolates (from 32 to 90%). We show that the ST-2 strains have an enhanced ability to produce biofilms in comparison to the ST-229 strains, and this fact has potentially led to more successful colonization of the clinical environment over time. CONCLUSIONS: This study provides a longitudinal genetic and phenotypic survey of two CRAB sequence types, and suggests how their differing phenotypes may interact with the selective pressures of a hospital setting effecting strain dominance over a 5-year period.

Native valve endocarditis caused by Kocuria rosea complicated by peripheral mycotic aneurysm in an elderly host.

Infective endocarditis still remains a dreaded illness among treating physicians because of the disease course, its need for meticulous antibiotic management, complications, and overall morbidity. Peripheral mycotic aneurysms are a rarely reported complication of infective endocarditis. Mycotic aneurysms occur in about 5%-10% of cases of infective endocarditis, and most of them involve the intracranial vessels. Here, we report a case of native valve endocarditis in a 74-year-old man caused by Kocuria rosea. He presented with septic shock and acute kidney injury. His illness was complicated by a right popliteal artery mycotic aneurysm. He was treated with intravenous ceftriaxone and vancomycin. The mycotic aneurysm needed aneurysmectomy and anastomosis with a graft.

Association between DPYD c.1129-5923 C>G/hapB3 and severe toxicity to 5-fluorouracil-based chemotherapy in stage III colon cancer patients: NCCTG N0147 (Alliance).

Severe (grade≥3) adverse events (AEs) to 5-fluorouracil (5-FU)-based chemotherapy regimens can result in treatment delays or cessation, and, in extreme cases, life-threatening complications. Current genetic biomarkers for 5-FU toxicity prediction, however, account for only a small proportion of toxic cases. In the current study, we assessed DPYD variants suggested to correlate with 5-FU toxicity, a deep intronic variant (c.1129-5923 C>G), and four variants within a haplotype (hapB3) in 1953 stage III colon cancer patients who received adjuvant FOLFOX±cetuximab. Logistic regression was used to assess multivariable associations between DPYD variant status and AEs common to 5-FU (5FU-AEs). In our study cohort, 1228 patients (62.9%) reported any grade≥3 AE (overall AE), with 638 patients (32.7%) reporting any grade≥3 5FU-AE. Only 32 of 78 (41.0%) patients carrying DPYD c.1129-5923 C>G and the completely linked hapB3 variants c.1236 C>G and c.959-51 T>C showed at least one grade≥3 5FU-AE, resulting in no statistically significant association (adjusted odds ratio=1.47, 95% confidence interval=0.90-2.43, P=0.1267). No significant associations were identified between c.1129-5923 C>G/hapB3 and overall grade≥3 AE rate. Our results suggest that c.1129-5923 C>G/hapB3 have limited predictive value for severe toxicity to 5-FU-based combination chemotherapy.

Relationship Between Metformin Use and Recurrence and Survival in Patients With Resected Stage III Colon Cancer Receiving Adjuvant Chemotherapy: Results From North Central Cancer Treatment Group N0147 (Alliance).

BACKGROUND: Preclinical and epidemiological data suggest that metformin might have antineoplastic properties against colon cancer (CC). However, the effect of metformin use on patient survival in stage III CC after curative resection is unknown. The survival outcomes were comparable regardless of the duration of metformin use. PATIENTS AND METHODS: Before randomization to FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with stage III CC enrolled in the N0147 study completed a questionnaire with information on diabetes mellitus (DM) and metformin use. Cox models were used to assess the association between metformin use and disease-free survival (DFS), overall survival (OS), and the time to recurrence (TTR), adjusting for clinical and/or pathological factors. RESULTS: Of the 1,958 patients, 1,691 (86%) reported no history of DM, 115 reported DM with metformin use (6%), and 152 reported DM without metformin use (8%). The adjuvant treatment arms were pooled, because metformin use showed homogeneous effects on outcomes across the two arms. Among the patients with DM (n = 267), DFS (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.59-1.35; p = .60), OS (aHR, 0.99; 95% CI, 0.65-1.49; p = .95), and TTR (aHR, 0.87; 95% CI, 0.56-1.35; p = .53) were not different for the metformin users compared with the nonusers after adjusting for tumor and patient factors. The survival outcomes were comparable regardless of the duration of metformin use (<1, 1-5, 6-10, ≥11 years) before randomization (ptrend = .64 for DFS, ptrend = .84 for OS, and ptrend = .87 for TTR). No interaction effects were observed between metformin use and KRAS, BRAF mutation status, tumor site, T/N stage, gender, or age. CONCLUSIONS: Patients with stage III CC undergoing adjuvant chemotherapy who used metformin before the diagnosis of CC experienced DFS, OS, and TTR similar to those for non-DM patients and DM patients without metformin use. IMPLICATIONS FOR PRACTICE: The present study did not find any relationship between metformin use or its duration and disease-free survival, time to recurrence, and overall survival in a large cohort of patients with resected stage III colon cancer receiving adjuvant FOLFOX (folinic acid, fluorouracil, oxaliplatin)-based chemotherapy. This relationship was not modified by KRAS or BRAF mutation or DNA mismatch repair status. Metformin use did not increase or decrease the likelihood of chemotherapy-related grade 3 or higher adverse events.

Salinicoccus amylolyticus sp. nov., isolated from a saltern.

A Gram-stain-positive coccus, strain JC304T, was isolated from a saltern of Nari along the Bhavnagar Coast, Gujarat, India. The 16S rRNA gene sequence analysis and sequence comparison data indicated that JC304T represented a member of the genus Salinicoccus and was most closely related to Salinicoccus roseus 9T (99.6 %), Salinicoccus luteus YIM 70202T (97.0 %), Salinicoccus hispanicus J-82T (97.0 %) and the remaining species of the genus Salinicoccus (<97 %). Genome relatedness based on DNA-DNA hybridization of JC304T with the type strains of the most closely related species was less than 46 % and the ΔTmwas >5 °C indicating that the strain represents a novel species of the genus Salinicoccus. Independent and concatenated phylogenetic analysis of recA/fusA gene translated product showed a clear distinction of JC304T from its phylogenetic neighbors. Diphosphotidylglycerol, phosphatidylglycerol, an unidentified glycolipid and three unidentified lipids (L1, L2 and L3) were the polar lipids of JC304T. Iso-C15 : 0 and anteiso-C15 : 0 were the major (>10 %) fatty acids in strain JC304T. The cell-wall amino acids were l-lysine and d-glycine. Hopanoids were not detected. The major isoprenoid quinone was menaquinone (MK-6). The DNA G+C content of JC304T was 48 mol%. On the basis of physiological, genotypic, phylogenetic and chemotaxonomic analyses, strain JC304T is considered to represent a novel species of the genus Salinicoccus, for which the name Salinicoccusamylolyticus sp. nov. is proposed. The type strain is JC304T (=KCTC 33661T=LMG 28757T).

Rare associations of tetralogy of Fallot with anomalous left coronary artery from pulmonary artery and totally anomalous pulmonary venous connection.

We describe the cases of two patients with tetralogy of Fallot, aged 4 years and 8 months, who were incidentally detected to have concomitant anomalous left coronary artery from pulmonary artery and total anomalous pulmonary venous connection, respectively, on preoperative imaging. They underwent surgical correction with good mid-term outcomes. In this study, we discuss the embryological basis, physiological effects, and review the literature of these two unusual associations. Awareness of these rare associations will avoid missed diagnoses and consequent surgical surprises.

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.

BACKGROUND: Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. METHODS: We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. FINDINGS: Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7-22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2-4·8), and median duration of response was not reached (95% CI 8·31-not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7-10·9). 20 (17%) of 117 patients reported grade 3-4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. INTERPRETATION: Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. FUNDING: Bristol-Myers Squibb.

A new biomarker quantifies differences in clot microstructure in patients with venous thromboembolism.

This study compared patients with venous thromboembolism (VTE) to non-VTE patients using a biomarker of clot microstructure (df ) and clot formation time (TGP ). df was the only marker that identified a significant difference (P < 0·001) between the VTE (n = 60) and non-VTE cohorts (n = 69). The 'abnormal' clot microstructures in the VTE patients suggests either inadequate response to anticoagulant therapy or the presence of a procoagulant state not detected by other markers of coagulation (i.e., International Normalized Ratio). Furthermore, elevated values of df in first time VTE patients who later develop a secondary event indicates that df may identify those at risk of recurrence.