Sacituzumab govitecan in metastatic triple-negative breast cancer

BACKGROUND: Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker. METHODS In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary end point was progression-free survival (as determined by blinded independent central review) among patients without brain metastases. RESULTS A total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients). The median age was 54 years; all the patients had previous use of taxanes. The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with sacituzumab govitecan and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P<0.001). The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy (hazard ratio for death, 0.48; 95% CI, 0.38 to 0.59; P<0.001). The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy. The incidences of key treatment-related adverse events of grade 3 or higher were neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered to be related to sacituzumab govitecan treatment. CONCLUSIONS Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan

A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group

Background Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.Objective Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.Methods Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation.Results A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.Conclusion The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc

Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination

Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings

Point-of-Care Testing for Clostridium Difficile Infection: A Real-World Feasibility Study of a Rapid Molecular Test in Two Hospital Settings

INTRODUCTION: In the developed world, Clostridium difficile infection (CDI) is the most important cause of nosocomial infectious diarrhea. In addition to providing epidemiological data and helping to indicate that a local outbreak may be occurring, laboratory tests are used to augment clinical decisions on individual patients. Very rarely do diagnostic tests provide results at the point of decision making; in the intervening period between requesting investigations on a patient with suspected CDI and return of the laboratory result, decisions must be made regarding patient isolation and treatment. METHODS: A 22-month, real-world feasibility study was conducted in patients with clinically significant diarrhea, in a London Hospital between March 2011 and January 2013, in three older persons’ wards and two intensive care units (ICUs) to determine acceptability, ease of use, change in turnaround time and clinical utility of a rapid, polymerase chain reaction (PCR)-based point-of-care test (POCT) (Cepheid GeneXpert(®), Sunnyvale, California, USA) for diagnosis of Clostridium difficile. Nurses in the older persons’ ward and laboratory technicians in the ICU were trained to perform the test. Residual samples were sent to the centralized laboratory for parallel testing using a two-step algorithm. RESULTS: A total of 335 samples were tested using the POCT with a median turnaround time of 1.85 h compared with 18 h for the centralized laboratory test. Overall agreement with centralized laboratory testing was 98.1%. Discrepant samples were more frequent on elderly wards than ICU. Overall 20/335 (6%) processing errors were encountered and were highest in the first few months of the study. Significantly more processing errors occurred on the older persons’ wards 13/102 (12.7%) than on ICU 7/271 (2.6%). Older persons’ patients who had POCT were significantly less likely to have a test requested for bacterial stool culture (3.1% vs. 10.9% p = 0.044). This difference was not observed in the ICU patients. No other differences in ancillary test requesting, mortality or length of stay were observed. CONCLUSIONS: The majority of users reported that the POCT was easy to perform and was an acceptable part of their job. POCT using this system is feasible and acceptable to nursing staff and technicians working within these two hospital-based settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40121-014-0038-6) contains supplementary material, which is available to authorized users

Positive species interactions strengthen in a high-CO(2) ocean

Negative interactions among species are a major force shaping natural communities and are predicted to strengthen as climate change intensifies. Similarly, positive interactions are anticipated to intensify and could buffer the consequences of climate-driven disturbances. We used in situ experiments at volcanic CO2 vents within a temperate rocky reef to show that ocean acidification can drive community reorganization through indirect and direct positive pathways. A keystone species, the algal-farming damselfish Parma alboscapularis, enhanced primary productivity through its weeding of algae whose productivity was also boosted by elevated CO2. The accelerated primary productivity was associated with increased densities of primary consumers (herbivorous invertebrates), which indirectly supported increased secondary consumers densities (predatory fish) (i.e. strengthening of bottom-up fuelling). However, this keystone species also reduced predatory fish densities through behavioural interference, releasing invertebrate prey from predation pressure and enabling a further boost in prey densities (i.e. weakening of top-down control). We uncover a novel mechanism where a keystone herbivore mediates bottom-up and top-down processes simultaneously to boost populations of a coexisting herbivore, resulting in altered food web interactions and predator populations under future ocean acidification.Camilo M. Ferreira, Sean D. Connell, Silvan U. Goldenberg and Ivan Nagelkerke

CO(2) emissions boost the benefits of crop production by farming damselfish

Published online: 9 July 2018Farming is a technique employed by both humans and animals to enhance crop yields, allowing their populations to increase beyond the natural carrying capacity of the environment. Using volcanic CO₂ vents, we investigate how a species of herbivorous fish (the black scalyfin Parma alboscapularis) may use increasing anthropogenic CO₂ emissions to enhance its crop yields. We found that these farming fish can take advantage of this resource enrichment, to grow crops within smaller territories and increase the capacity of the environment to support more densely packed fish populations.Camilo M. Ferreira, Ivan Nagelkerken, Silvan U. Goldenberg and Sean D. Connel

Reduction in Clostridium difficile environmental contamination by hospitalized patients treated with fidaxomicin.

Fidaxomicin is sporicidal and may be associated with a reduced time to resolution of diarrhoea when used to treat patients with Clostridium difficile infection (CDI). This study investigated whether fidaxomicin for treatment of all patients with CDI reduced C. difficile environmental contamination. Surfaces in the rooms of 66 hospitalized patients treated with metronidazole and/or vancomycin and 68 hospitalized patients treated with fidaxomicin were sampled. Patients treated with fidaxomicin were less likely to contaminate their environment (25/68, 36.8%) than patients treated with metronidazole and/or vancomycin (38/66 57.6%) (P = 0.02). Treatment with fidaxomicin was associated with reduced environmental contamination with C. difficile

Trophic pyramids reorganize when food web architecture fails to adjust to ocean change

As human activities intensify, the structures of ecosystems and their food webs often reorganize. Through the study of mesocosms harboring a diverse benthic coastal community, we reveal that food web architecture can be inflexible under ocean warming and acidification and unable to compensate for the decline or proliferation of taxa. Key stabilizing processes, including functional redundancy, trophic compensation, and species substitution, were largely absent under future climate conditions. A trophic pyramid emerged in which biomass expanded at the base and top but contracted in the center. This structure may characterize a transitionary state before collapse into shortened, bottom-heavy food webs that characterize ecosystems subject to persistent abiotic stress. We show that where food web architecture lacks adjustability, the adaptive capacity of ecosystems to global change is weak and ecosystem degradation likely.Ivan Nagelkerken, Silvan U. Goldenberg, Camilo M. Ferreira, Hadayet Ullah, Sean D. Connel

Surface-attached cells, biofilms and biocide susceptibility: implications for hospital cleaning and disinfection

Microbes tend to attach to available surfaces and form biofilms readily, which is problematic in healthcare settings. Biofilms are traditionally associated with wet or damp surfaces such as indwelling medical devices and tubing on medical equipment. However, microbes can survive for extended periods in a desiccated state on dry hospital surfaces, and biofilms have recently been discovered on dry hospital surfaces. Microbes attached to surfaces and in biofilms are less susceptible to biocides, antibiotics and physical stress. Thus, surface attachment and/or biofilm formation may explain how vegetative bacteria can survive on surfaces for weeks to months (or more), interfere with attempts to recover microbes through environmental sampling, and provide a mixed bacterial population for the horizontal transfer of resistance genes. The capacity of existing detergent formulations and disinfectants to disrupt biofilms may have an important and previously unrecognized role in determining their effectiveness in the field, which should be reflected in testing standards. There is a need for further research to elucidate the nature and physiology of microbes on dry hospital surfaces, specifically the prevalence and composition of biofilms. This will inform new approaches to hospital cleaning and disinfection, including novel surfaces that reduce microbial attachment and improve microbial detachment, and methods to augment the activity of biocides against surface-attached microbes such as bacteriophages and antimicrobial peptides. Future strategies to address environmental contamination on hospital surfaces should consider the presence of microbes attached to surfaces, including biofilm