Maintaining Safety with SARS-CoV-2 Vaccines Castells, Mariana C; Phillips, Elizabeth J
New England journal of medicine/The New England journal of medicine,
02/2021, Volume:
384, Issue:
7
Journal Article
Peer reviewed
Open access
The vast majority of people who have received the Covid-19 vaccine to date have had self-limited local or low-grade systemic reactions that resolve within 2 or 3 days. A very small number of people ...have had serious anaphylactic reactions requiring catecholamine infusion and respiratory support. It is important to survey patients in advance of vaccination for allergic responses and to be aware of the early signs of an immediate hypersensitivity reaction.
Penicillin Allergy Castells, Mariana; Khan, David A; Phillips, Elizabeth J
The New England journal of medicine,
12/2019, Volume:
381, Issue:
24
Journal Article
Peer reviewed
Many more patients are labeled as penicillin-allergic than actually are allergic. The label should be analyzed with skin testing and test exposure. Patients with true penicillin allergy can be ...desensitized with a slow-escalation protocol under physician observation.
The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 presents with a spectrum of clinical manifestations from asymptomatic or mild, self-limited ...constitutional symptoms to a hyperinflammatory state ("cytokine storm") followed by acute respiratory distress syndrome and death. The objective of this study was to provide an evidence-based review of the associated pathways and potential treatment of the hyperinflammatory state associated with severe acute respiratory syndrome coronavirus 2 infection. Dysregulated immune responses have been reported to occur in a smaller subset of those infected with severe acute respiratory syndrome coronavirus 2, leading to clinical deterioration 7 to 10 days after initial presentation. A hyperinflammatory state referred to as cytokine storm in its severest form has been marked by elevation of IL-6, IL-10, TNF-α, and other cytokines and severe CD4
and CD8
T-cell lymphopenia and coagulopathy. Recognition of at-risk patients could permit early institution of aggressive intensive care and antiviral and immune treatment to reduce the complications related to this proinflammatory state. Several reports and ongoing clinical trials provide hope that available immunomodulatory therapies could have therapeutic potential in these severe cases. This review highlights our current state of knowledge of immune mechanisms and targeted immunomodulatory treatment options for the current coronavirus disease 2019 pandemic.
Antibiotic allergy Blumenthal, Kimberly G; Peter, Jonny G; Trubiano, Jason A ...
Lancet,
01/2019, Volume:
393, Issue:
10167
Journal Article
Peer reviewed
Open access
Antibiotics are the commonest cause of life-threatening immune-mediated drug reactions that are considered off-target, including anaphylaxis, and organ-specific and severe cutaneous adverse ...reactions. However, many antibiotic reactions documented as allergies were unknown or not remembered by the patient, cutaneous reactions unrelated to drug hypersensitivity, drug-infection interactions, or drug intolerances. Although such reactions pose negligible risk to patients, they currently represent a global threat to public health. Antibiotic allergy labels result in displacement of first-line therapies for antibiotic prophylaxis and treatment. A penicillin allergy label, in particular, is associated with increased use of broad-spectrum and non-β-lactam antibiotics, which results in increased adverse events and antibiotic resistance. Most patients labelled as allergic to penicillins are not allergic when appropriately stratified for risk, tested, and re-challenged. Given the public health importance of penicillin allergy, this Review provides a global update on antibiotic allergy epidemiology, classification, mechanisms, and management.
The evolution of human immunodeficiency virus (HIV) treatment has improved our understanding and management of complex pharmacological issues that have driven improved outcomes and quality of life of ...the HIV‐infected patient. These issues include adherence, long‐ and short‐term toxicities, pharmacoenhancement, pharmacogenomics, therapeutic drug monitoring, differential penetration of drugs into sanctuary sites, such as the central nervous system, genital tract and small bowel, and drug–drug and drug–food interactions related to cytochrome P450 drug‐metabolizing enzymes, uridine diphosphate glucuronyltransferases and drug transporters, to name a few. There is future promise, as an increased understanding of the immunopathogenesis of HIV and global public health initiatives are driving novel treatment approaches with goals to prevent, control and, ultimately, eradicate HIV.
Cortical function is regulated by a strikingly diverse array of local-circuit inhibitory neurons. We evaluated how optogenetically activating somatostatin- and parvalbumin-positive interneurons ...subtractively or divisively suppressed auditory cortical cells’ responses to tones. In both awake and anesthetized animals, we found that activating either family of interneurons produced mixtures of divisive and subtractive effects and that simultaneously recorded neurons were often suppressed in qualitatively different ways. A simple network model shows that threshold nonlinearities can interact with network activity to transform subtractive inhibition of neurons into divisive inhibition of networks, or vice versa. Varying threshold and the strength of suppression of a model neuron could determine whether the effect of inhibition appeared divisive, subtractive, or both. We conclude that the characteristics of response inhibition specific to a single interneuron type can be “masked” by the network configuration and cellular properties of the network in which they are embedded.
•Activation of Sst or Pvalb cells causes diverse mixtures of division and subtraction•Simultaneously recorded neurons can show qualitatively different suppression•Network interactions can mask subtractive inhibition as divisive, and vice versa•In active networks, optogenetic effects must be interpreted with extreme caution
Seybold et al. show that in auditory cortex, both parvalbumin- and somatostatin-positive interneurons evoke a mixture of divisive and subtractive inhibition, consistent with a model in which network-mediated indirect effects of inhibition mask direct effects of inhibition on single cells.
The overlabeling of pediatric antibiotic allergy represents a huge burden in society. Given that up to 10% of the US population is labeled as penicillin allergic, it can be estimated that at least 5 ...million children in this country are labeled with penicillin allergy. We now understand that most of the cutaneous symptoms that are interpreted as drug allergy are likely viral induced or due to a drug-virus interaction, and they usually do not represent a long-lasting, drug-specific, adaptive immune response to the antibiotic that a child received. Because most antibiotic allergy labels acquired in childhood are carried into adulthood, the overlabeling of antibiotic allergy is a liability that leads to unnecessary long-term health care risks, costs, and antibiotic resistance. Fortunately, awareness of this growing burden is increasing and leading to more emphasis on antibiotic allergy delabeling strategies in the adult population. There is growing literature that is used to support the safe and efficacious use of tools such as skin testing and drug challenge to evaluate and manage children with antibiotic allergy labels. In addition, there is an increasing understanding of antibiotic reactivity within classes and side-chain reactions. In summary, a better overall understanding of the current tools available for the diagnosis and management of adverse drug reactions is likely to change how pediatric primary care providers evaluate and treat patients with such diagnoses and prevent the unnecessary avoidance of antibiotics, particularly penicillins.
Bidirectional manipulations - activation and inactivation - are widely used to identify the functions supported by specific cortical interneuron types. Implicit in much of this work is the notion ...that tonic activation and inactivation will both produce valid, internally consistent insights into interneurons' computational roles. Here, using single-unit recordings in auditory cortex of awake mice, we show that this may not generally hold true. Optogenetically manipulating somatostatin-positive (Sst+) or parvalbumin-positive (Pvalb+) interneurons while recording tone-responses showed that Sst+ inactivation increased response gain, while Pvalb+ inactivation weakened tuning and decreased information transfer, implying that these neurons support delineable computational functions. But activating Sst+ and Pvalb+ interneurons revealed no such differences. We used a simple network model to understand this asymmetry, and showed how relatively small changes in key parameters, such as spontaneous activity or strength of the light manipulation, determined whether activation and inactivation would produce consistent or paradoxical conclusions regarding interneurons' computational functions.
Several sensory cues affect food intake including appearance, taste, odor, texture, temperature, and flavor. Although taste is an important factor regulating food intake, in most cases, the first ...sensory contact with food is through the eyes. Few studies have examined the effects of the appearance of a food portion on food acceptance and consumption. The purpose of this review is to identify the various visual factors associated with food such as proximity, visibility, color, variety, portion size, height, shape, number, volume, and the surface area and their effects on food acceptance and consumption. We suggest some ways that visual cues can be used to increase fruit and vegetable intake in children and decrease excessive food intake in adults. In addition, we discuss the need for future studies that can further establish the relationship between several unexplored visual dimensions of food (specifically shape, number, size, and surface area) and food intake.
•First sensory contact with food is mostly through the eyes.•Seeing food can change feeding behaviors and food consumption volumes.•Portion size, number, and size are some visual cues that can affect food intake.•Visual cues can be used to increase healthy food intake in both children and adults.
Fatal autoimmune myocarditis with rhabdomyolysis and refractory arrhythmias developed in two patients treated with a combination of anti–CTLA-4 and anti–PD-1 blockers. On histologic examination, a ...myocardial infiltrate suggested acute cardiac allograft rejection.
Immune checkpoint inhibitors have transformed the treatment of several cancers by releasing restrained antitumor immune responses.
1
Ipilimumab, an anti–cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) antibody, and nivolumab, an anti–programmed death-1 (PD-1) antibody, have individually improved survival in patients with melanoma, and early results suggest that their combination further enhances antitumor activity and survival.
2
–
5
Other adverse events associated with these agents include dermatitis, endocrinopathies, colitis, hepatitis, and pneumonitis, which are all thought to arise from aberrant activation of autoreactive T cells.
6
,
7
These toxic effects are more frequent and severe when ipilimumab and nivolumab are used in combination.
4
Here, we report . . .
PDF
