Cobimetinib plus atezolizumab in BRAFV600 wild-type melanoma: primary results from the randomized phase III IMspire170 study.

BACKGROUND: Emerging data suggest that the combination of MEK inhibitors and immunotherapeutic agents may result in improved efficacy in melanoma. We evaluated whether combining MEK inhibition and immune checkpoint inhibition was more efficacious than immune checkpoint inhibition alone in patients with previously untreated BRAFV600 wild-type advanced melanoma. PATIENTS AND METHODS: IMspire170 was an international, randomized, open-label, phase III study. Patients were randomized 1 : 1 to receive cobimetinib (60 mg, days 1-21) plus anti-programmed death-ligand 1 atezolizumab (840 mg every 2 weeks) in 28-day cycles or anti-programmed death-1 pembrolizumab (200 mg every 3 weeks) alone until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. The primary outcome was progression-free survival (PFS), assessed by an independent review committee in the intention-to-treat population. RESULTS: Between 11 December 2017, and 29 January 2019, 446 patients were randomized to receive cobimetinib plus atezolizumab (n = 222) or pembrolizumab (n = 224). Median follow-up was 7.1 months [interquartile range (IQR) 4.8-9.9] for cobimetinib plus atezolizumab and 7.2 months (IQR 4.9-10.1) for pembrolizumab. Median PFS was 5.5 months [95% confidence interval (CI) 3.8-7.2] with cobimetinib plus atezolizumab versus 5.7 months (95% CI 3.7-9.6) with pembrolizumab [stratified hazard ratio 1.15 (95% CI 0.88-1.50); P = 0.30]. Hazard ratios for PFS were consistent across prespecified subgroups. In exploratory biomarker analyses, higher tumor mutational burden was associated with improved clinical outcomes in both treatment arms. The most common grade 3-5 adverse events (AEs) were increased blood creatine phosphokinase (10.0% with cobimetinib plus atezolizumab versus 0.9% with pembrolizumab), diarrhea (7.7% versus 1.9%), rash (6.8% versus 0.9%), hypertension (6.4% versus 3.7%), and dermatitis acneiform (5.0% versus 0). Serious AEs occurred in 44.1% of patients with cobimetinib plus atezolizumab and 20.8% with pembrolizumab. CONCLUSION: Cobimetinib plus atezolizumab did not improve PFS compared with pembrolizumab monotherapy in patients with BRAFV600 wild-type advanced melanoma.

Biodegradation of organophosphate pesticide quinalphos by Ochrobactrum sp. strain HZM.

AIMS: Isolation and identification of bacteria capable of degrading organophosphate pesticide quinalphos and elucidation of its biodegradative pathway. METHODS AND RESULTS: A bacterium capable of degrading organophosphate pesticides was isolated from the pesticide-contaminated soil samples by selective enrichment on quinalphos (QP) as a sole source of carbon and energy. The bacterial strain was identified as Ochrobactrum sp. strain HZM on the basis of its morphological and biochemical characteristics and by phylogenetic analysis based on 16S rRNA gene sequences. The organism utilized various organophosphate pesticides such as quinalphos, profenofos, parathion-methyl and chlorpyrifos as growth substrates. Response surface methodology (RSM) showed optimum conditions for quinalphos degradation at pH 7 and 27°C. 2-Hydroxyquinoxaline and diethyl phosphate were identified as metabolites of quinalphos degradation by HPLC and GC-MS analysis. Cell-free extract of Ochrobactrum sp. strain HZM grown on quinalphos contained the quinalphos hydrolase activity. CONCLUSIONS: A bacterial strain capable of degrading quinalphos was isolated and identified as Ochrobactrum sp. strain HZM. The organism utilized organophosphate pesticides quinalphos, profenofos, parathion-methyl and chlorpyrifos as carbon sources. The organism degraded quinalphos by hydrolysis to yield 2-hydroxyquinoxaline and diethyl phosphate which were further utilized as carbon sources. SIGNIFICANCE AND IMPACT OF THE STUDY: The isolated bacterium Ochrobactrum sp. strain HZM was versatile in degrading various organophosphate pesticides. There was complete mineralization of quinalphos by Ochrobactrum sp. This strain could potentially be useful in the bioremediation of soil and water contaminated with toxic organophosphate pesticides.

Study of the relation between quality of inpatient care and early readmission for diabetic patients at a hospital in the Eastern province of Saudi Arabia.

Readmission of diabetic patients after discharge from hospital has potential value as a quality of care indicator. This retrospective cohort and case-control study aimed to determine the readmission rate for diabetic patients within 28 days after discharge and the association between quality of inpatient care and unplanned readmission. An audit of records was conducted in a hospital in the Eastern province of Saudi Arabia during 2000-2008. The rate of unplanned readmission of patients originally admitted with diabetes mellitus (n = 1125) was 5.2%. Comparison of data from readmitted patients (n = 62) and a sample of nonreadmitted patients (n = 62) showed that adherence by health care providers to American Diabetes Association guidelines for admission work-up (OR 0.91, 95% CI: 0.85-0.99) and readiness for discharge criteria (OR 0.89, 95% CI: 0.84-0.95) were significantly more likely to decrease the risk of readmission within 28 days.

Seed Treatment With Systemic Fungicides: Time for Review.

Pre-sowing seed treatment with systemic fungicides is a firmly entrenched practice for most agricultural crops worldwide. The treatment is intended to protect the crop against seed- and soil-borne diseases. In recent years, there is increasing evidence that fungicidal applications to manage diseases might inadvertently also affect non-target organisms, such as endophytes. Endophytes are ubiquitously present in plants and contribute to plant growth and development besides offering resistance to biotic and abiotic stresses. In seeds, endophytes may play a role in seed development, seed germination, seedling establishment and crop performance. In this paper, we review the recent literature on non-target effects of fungicidal applications on endophytic fungal community and discuss the possible consequences of indiscriminate seed treatment with systemic fungicide on seed endophytes. It is now well recognized that endophytes are ubiquitously present in all parts of the plant, including the seeds. They may be transmitted vertically from seed to seed as in many grasses and/or acquired horizontally from the soil and the environment. Though the origins and evolution of these organisms in plants are a matter of conjecture, numerous studies have shown that they symbiotically aid in plant growth and development, in nutrient acquisition as well in protecting the plants from abiotic and biotic stresses. Against this background, it is reasonable to assume that the use of systemic fungicides in seed treatment may not only affect the seed endophytes but also their attendant benefits to seedling growth and establishment. While there is evidence to indicate that fungicidal applications to manage plant diseases also affect foliar endophytes, there are only few studies that have documented the effect of seed treatment on seed-borne endophytes. Some of the convincing examples of the latter come from studies on the effect of fungicide application on rye grass seed endophyte AR37. More recently, experiments have shown that removal of seed endophytes by treatment with systemic fungicides leads to significant loss of seedling vigour and that such losses could be partially restored by enriching the seedlings with the lost endophytes. Put together, these studies reinforce the importance of seed endophytes to seedling growth and establishment and draw attention on how to trade the balance between the benefits of seed treatments and the direct and indirect costs incurred due to loss of endophytes. Among several approaches, use of reduced-risk fungicides and identifying fungicide-resistant endophytes are suggested to sustain the endophyte contribution to early seedling growth.

Prevalence of Trichomonas vaginalis infection in and around Surat.

Trichomonas culture method was used for the diagnosis of trichomoniasis along with gram staining and wet mount preparation. We selected 51 urban women and 51 rural women in this study. Samples were taken from both symptomatic and asymptomatic individuals. Out of 102 samples 35 samples were positive for Trichomonas vaginalis by culture method. 20 women were positive for Trichomonas vaginalis by wet mount and 15 by gram staining technique. So it is a fact that culture of Trichomonas vaginalis is a "gold standard" in the diagnosis of trichomoniasis. As we had the opportunity to compare both urban and rural women in our study we were able to come to the conclusion that incidence of Trichomonas vaginalis is more in urban women than in rural women.

Treatment of chronic viral hepatitis C in children and adolescents: UK experience.

AIM: To review the efficacy and tolerability of pegylated interferon-α and ribavirin for treatment of chronic hepatitis C (CHC) in children in the UK. METHODS: Retrospective review of children treated for CHC in 3 UK paediatric specialist liver centres between 2005 and 2010. Data on viral response to treatment, demographic and clinical details were collected. Treatment outcome was assessed by the absence of detectable viral RNA in blood 24 weeks after treatment-sustained viral response (SVR). RESULTS: 75 children were included; 34 genotype 1; 39 genotypes 2 and 3; 2 genotype 4. Overall SVR was achieved in 54/71 (76%); 65% genotype 1; 89% genotypes 2 and 3; 100% genotype 4. Early response at 12 weeks was achieved in 53 and sustained in 47 (89%). Data on rapid response after 4 weeks of treatment were available in 25; 17/25 (68%) responded and 16 of these (94%) achieved SVR. IL28 T/T genotype was associated with higher SVR. There were no significant changes in weight and height z scores from baseline compared with 24 weeks post-treatment follow-up. No child discontinued treatment due to side effects, although 43 required dose modification. Treatment affected quality of life (QoL) in the initial 12 weeks of treatment, which improved by the end of treatment. CONCLUSIONS: Children respond well to therapy for CHC. Treatment was tolerated with minimal impact on QoL and no significant effect on growth. Knowledge of viral and IL28 genotypes and early viral response is useful to plan treatment in children and provide appropriate counselling.

Staphylococcus aureus isolated from a horse in a sudden death condition in Kassala state, eastern Sudan.

In this study, Staphylococcus aureus was isolated from a draught horse presented to Kassala Veterinary Research Laboratory (KVRL) for investigation and diagnosis. The affected animal was previously treated with Gentamycin and Tetracycline before submitted to this laboratory, but the animal was not cure. Thereafter, the animal was attended to the laboratory; it was suffering from inguinal abscess and some clinical signs. Clinical and laboratory examinations were carried out however, the animal was suddenly fallen and died immediately. Then post-mortem, bacteriological and histopathological examinations were done. S. aureus was isolated as pure culture from the lungs and peritoneum of the necropsied animal. This isolate showed highly sensitivity to Erythromycin and Clindamycin and it was resistant to Penicillin, Cloxacillin, Cefotaxime, Co-Trimoxazole, Cephalexin and Tetracycline. It was concluded from this study, the shock resulted from S. aureus was the causative agent of the death in this case.

Circulating filarial antigen in serum and hydrocele fluid from individuals living in an endemic area for bancroftian filariasis.

This study examined circulating filarial antigen by monoclonal antibody Og4C3-enzyme-linked immunosorbent assay (ELISA) from 114 men with hydrocele, living in an endemic area. Nocturnal blood and hydrocele fluid were collected and examined for microfilaria. ELISA was performed on serum and hydrocele fluid for detection of antigen. Amongst 114 cases, 5(4.4%) showed microfilaria in blood but none in fluid. ELISA was positive in 13(11.40%) serum and 5 (4.4%) fluid samples. All five fluid antigen positive cases were positive for antibodies and showed microfilaria in blood. These findings emphasize the use of circulating filarial antigen detection and alternative usage of hydrocele fluid for diagnosis of filariasis.