ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors).

BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate risk of infection and no specific prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-α agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection. IMPLICATIONS: Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors).

BACKGROUND: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biologic therapies. AIMS: To review, from an infectious diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations. SOURCES: Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: Although BCR-ABL tyrosine kinase inhibitors modestly increase the overall risk of infection, dasatinib has been associated with cytomegalovirus and hepatitis B virus reactivation. BRAF/MEK kinase inhibitors do not significantly affect infection susceptibility. The effect of Bruton tyrosine kinase inhibitors (ibrutinib) among patients with B-cell malignancies is difficult to distinguish from that of previous immunosuppression. However, cases of Pneumocystis jirovecii pneumonia (PCP), invasive fungal infection and progressive multifocal leukoencephalopathy have been occasionally reported. Because phosphatidylinositol-3-kinase inhibitors (idelalisib) may predispose to opportunistic infections, anti-Pneumocystis prophylaxis and prevention strategies for cytomegalovirus are recommended. No increased rates of infection have been observed with venetoclax (antiapoptotic protein Bcl-2 inhibitor). Therapy with Janus kinase inhibitors markedly increases the incidence of infection. Pretreatment screening for chronic hepatitis B virus and latent tuberculosis infection must be performed, and anti-Pneumocystis prophylaxis should be considered for patients with additional risk factors. Cancer patients receiving mTOR inhibitors face an increased incidence of overall infection, especially those with additional risk factors (prior therapies or delayed wound healing). IMPLICATIONS: Specific preventive approaches are warranted in view of the increased risk of infection associated with some of the reviewed agents.

Essential oils for dairy calves: effects on performance, scours, rumen fermentation and intestinal fauna.

UNLABELLED: The first cause of death of dairy calves is often diarrhea which is mainly caused by pathogenic bacteria, which can result in excessive use of antibiotics. However, facing the increase concern by the industry and consumers, the use of antibiotics not only to control pathogens, but also to manipulate growth, has become a challenge. Alternative additives, such essential oils, have the potential to decrease antibiotic use, without reducing performance or increasing mortality of dairy calves. The objective of this study was to evaluate the use of a commercial blend of essential oils, incorporated into the calf starter and/or milk replacer to monitor the effect on overall calf performance, fecal scores and rumen fermentation parameters. A total of 30 Holstein calves received 6 l/day of a liquid diet, consisting of a commercial milk replacer containing 20% CP : 15% fat (EE). Calves had free choice access to water and calf starter. Weaning occurred at week 8, and calves were followed until the 10th week of age. Calves were assigned to one of the three treatment groups in a randomized block design. TREATMENTS: (1) control without essential oils supplementation (C); (2) essential oils blend in the milk replacer at 400 mg/kg (MR) and (3) essential oils blend in the milk replacer (200 mg/kg) and starter feed (200 mg/kg) (MRS). From the 2nd week, calves were weighed and body measurements were taken, while concentrate intake and fecal scores were monitored daily. Blood samples were drawn weekly for determination of glucose and ß-hydroxybutyrate. Fecal samples were collected weekly and analyzed for lactic acid bacteria and Enterobacteria; and ruminal fluid for determination of pH, short chain fatty acids, ammonia-N and counts of amylolytic and cellulolytic bacteria, and protozoa. Performance, fecal scores and intestines microorganisms were not affected by the essential oils supplementation. Ruminal and blood parameters were also not affected, with the exception the rumen ammonia-N concentration, with higher values when essential oils were supplemented in a combination of milk replacer and starter feed. Most of the evaluated parameters were affected by age of calves, mainly as a response to the increase in concentrate intake as animals' aged. Essential oils are promising substitutes for antibiotics. However, the dose and routes of administration deserve further studies, allowing a better animal performance and health to be achieved.

Wernicke's encephalopathy induced by total parental nutrition.

Wernicke's encephalopathy is an acute neurological syndrome due to thiamine deficiency, which is characterized by a typical triad of mental status changes, oculomotor dysfunction and ataxia. Despite the fact that Wernicke's encephalopathy, in developed countries, is frequently associated with chronic alcoholism, there have been a number of published cases associating this encephalopathy with parenteral feeding without vitamin supplementation. Diagnosis is primarily a clinical one, and can be supported by laboratory tests and imaging studies; treatment should start as soon as possible, for the morbidity and mortality (almost 20%) associated with this syndrome is high. Thiamine supplementation, along with other vitamins, is recommended for patients in risk of developing this syndrome.