Removing penicillin allergy label in a hospitalized adolescent with a remote penicillin and recent cephalosporin allergy.

Background: ß-Lactam antibiotics are widely used with increased utilization in hospitalized patients. Of this population, as high as 10-20% report an allergy to ß-lactam antibiotics but <5% are at risk of developing clinically significant immunoglobulin E- or T-lymphocyte-mediated reactions. Most of the time, these reported allergies are present during an illness with no previous inquiry of their validity, which makes investigation and possible removal of this allergy label a challenge. Methods: We report a 16-year-old boy who presented with 1 week of night sweats, chills, headaches, and fatigue, followed by 1 day of fever and right knee swelling and who was diagnosed with septic bursitis. Due to concern of a penicillin allergy label, the patient was started on a cefepime infusion. Five minutes into the infusion, the patient reported puffy eyes and itchy throat, followed by a witnessed cascading flat nonpruritic erythematous rash from head to shoulders. This rash went away in 3 minutes after stopping the infusion and the patient being given 50 mg of intravenous diphenhydramine and 10 mg of oral dexamethasone. He was subsequently diagnosed with a cefepime allergy. Results: Allergy/immunology was the speciality consulted, and, by using a screening questionnaire, the patient's reported penicillin allergy was determined to be low risk. Subsequent 1-step oral challenge was the key to providing the patient with the necessary antibiotic course to resolve his infection. Conclusion: Multiple reported antibiotic allergies lead to poor antibiotic stewardship that causes impactful health and financial burden on the patient and health-care system. It is thus important to have an evidence-based systematic approach to de-label penicillin antibiotic allergy labels to reduce these potential harms.

Is Generative Artificial Intelligence the Next Step Toward a Personalized Hemodialysis?

ABSTRACT Artificial intelligence (AI) generative models driven by the integration of AI and natural language processing technologies, such as OpenAI's chatbot generative pre-trained transformer large language model (LLM), are receiving much public attention and have the potential to transform personalized medicine. Dialysis patients are highly dependent on technology and their treatment generates a challenging large volume of data that has to be analyzed for knowledge extraction. We argue that, by integrating the data acquired from hemodialysis treatments with the powerful conversational capabilities of LLMs, nephrologists could personalize treatments adapted to patients' lifestyles and preferences. We also argue that this new conversational AI integrated with a personalized patient-computer interface will enhance patients' engagement and self-care by providing them with a more personalized experience. However, generative AI models require continuous and accurate updates of data, and expert supervision and must address potential biases and limitations. Dialysis patients can also benefit from other new emerging technologies such as Digital Twins with which patients' care can also be addressed from a personalized medicine perspective. In this paper, we will revise LLMs potential strengths in terms of their contribution to personalized medicine, and, in particular, their potential impact, and limitations in nephrology. Nephrologists' collaboration with AI academia and companies, to develop algorithms and models that are more transparent, understandable, and trustworthy, will be crucial for the next generation of dialysis patients. The combination of technology, patient-specific data, and AI should contribute to create a more personalized and interactive dialysis process, improving patients' quality of life.

Is generative artificial intelligence the next step toward a personalized hemodialysis?

Artificial intelligence (AI) generative models driven by the integration of AI and natural language processing technologies, such as OpenAI's chatbot generative pre-trained transformer large language model (LLM), are receiving much public attention and have the potential to transform personalized medicine. Dialysis patients are highly dependent on technology and their treatment generates a challenging large volume of data that has to be analyzed for knowledge extraction. We argue that, by integrating the data acquired from hemodialysis treatments with the powerful conversational capabilities of LLMs, nephrologists could personalize treatments adapted to patients' lifestyles and preferences. We also argue that this new conversational AI integrated with a personalized patient-computer interface will enhance patients' engagement and self-care by providing them with a more personalized experience. However, generative AI models require continuous and accurate updates of data, and expert supervision and must address potential biases and limitations. Dialysis patients can also benefit from other new emerging technologies such as Digital Twins with which patients' care can also be addressed from a personalized medicine perspective. In this paper, we will revise LLMs potential strengths in terms of their contribution to personalized medicine, and, in particular, their potential impact, and limitations in nephrology. Nephrologists' collaboration with AI academia and companies, to develop algorithms and models that are more transparent, understandable, and trustworthy, will be crucial for the next generation of dialysis patients. The combination of technology, patient-specific data, and AI should contribute to create a more personalized and interactive dialysis process, improving patients' quality of life.

Integrating Social Assistive Robots, IoT, Virtual Communities and Smart Objects to Assist at-Home Independently Living Elders: the MoveCare Project.

The integration of Ambient Assisted Living (AAL) frameworks with Socially Assistive Robots (SARs) has proven useful for monitoring and assisting older adults in their own home. However, the difficulties associated with long-term deployments in real-world complex environments are still highly under-explored. In this work, we first present the MoveCare system, an unobtrusive platform that, through the integration of a SAR into an AAL framework, aimed to monitor, assist and provide social, cognitive, and physical stimulation in the own houses of elders living alone and at risk of falling into frailty. We then focus on the evaluation and analysis of a long-term pilot campaign of more than 300 weeks of usages. We evaluated the system's acceptability and feasibility through various questionnaires and empirically assessed the impact of the presence of an assistive robot by deploying the system with and without it. Our results provide strong empirical evidence that Socially Assistive Robots integrated with monitoring and stimulation platforms can be successfully used for long-term support to older adults. We describe how the robot's presence significantly incentivised the use of the system, but slightly lowered the system's overall acceptability. Finally, we emphasise that real-world long-term deployment of SARs introduces a significant technical, organisational, and logistical overhead that should not be neglected nor underestimated in the pursuit of long-term robust systems. We hope that the findings and lessons learned from our work can bring value towards future long-term real-world and widespread use of SARs.

Pearls and pitfalls: Cold-induced urticaria.

Background: Cold-induced urticaria can take place either due to direct cold exposure, cryoglobulinemia, or genetic component (such as cryopyrin-associated periodic syndrome), which leads to the rapid onset of urticaria and/or angioedema. It is more common in younger patients and more likely to affect females compared with males. Objective: To increase awareness of such systemic reactions of anaphylaxis and provide a focused review of the differential diagnosis, underlying mechanisms, broad workup, and management of this disease process for allergy/immunology fellows, residents, general physicians, and general practitioners. Methods: Pertinent information was included from the patient's clinical course. Also, a review of the available literature to include additional references that were obtained by using the works cited in the most up-to-date reviews was completed. Results: A case of a patient with cold-induced urticaria with common sequela was presented, followed by a discussion of the pathophysiology, diagnosis and its differential diagnosis, workup, and management. Conclusion: Cold-induced urticaria is a complex disease with several different catalysts. Providers should be aware of the different forms of cold-induced urticaria and recognize the risk for anaphylaxis in this patient population. Pearls and pitfalls of the diagnosis and management are provided.

Comprehensive user requirements engineering methodology for secure and interoperable health data exchange.

BACKGROUND: Increased digitalization of healthcare comes along with the cost of cybercrime proliferation. This results to patients' and healthcare providers' skepticism to adopt Health Information Technologies (HIT). In Europe, this shortcoming hampers efficient cross-border health data exchange, which requires a holistic, secure and interoperable framework. This study aimed to provide the foundations for designing a secure and interoperable toolkit for cross-border health data exchange within the European Union (EU), conducted in the scope of the KONFIDO project. Particularly, we present our user requirements engineering methodology and the obtained results, driving the technical design of the KONFIDO toolkit. METHODS: Our methodology relied on four pillars: (a) a gap analysis study, reviewing a range of relevant projects/initiatives, technologies as well as cybersecurity strategies for HIT interoperability and cybersecurity; (b) the definition of user scenarios with major focus on cross-border health data exchange in the three pilot countries of the project; (c) a user requirements elicitation phase containing a threat analysis of the business processes entailed in the user scenarios, and (d) surveying and discussing with key stakeholders, aiming to validate the obtained outcomes and identify barriers and facilitators for HIT adoption linked with cybersecurity and interoperability. RESULTS: According to the gap analysis outcomes, full adherence with information security standards is currently not universally met. Sustainability plans shall be defined for adapting existing/evolving frameworks to the state-of-the-art. Overall, lack of integration in a holistic security approach was clearly identified. For each user scenario, we concluded with a comprehensive workflow, highlighting challenges and open issues for their application in our pilot sites. The threat analysis resulted in a set of 30 user goals in total, documented in detail. Finally, indicative barriers of HIT acceptance include lack of awareness regarding HIT risks and legislations, lack of a security-oriented culture and management commitment, as well as usability constraints, while important facilitators concern the adoption of standards and current efforts for a common EU legislation framework. CONCLUSIONS: Our study provides important insights to address secure and interoperable health data exchange, while our methodological framework constitutes a paradigm for investigating diverse cybersecurity-related risks in the health sector.

Stress-induced microvascular reactivity in normal-weight and obese individuals.

Obesity has been shown to have profound effects on hemodynamics and neurological states in humans. Previous studies have demonstrated that obese individuals are highly susceptible to increases in tension, anxiety, and depression. However, the relationship between mental stressors and vascular fluidity in obese humans is not well understood. Thus, the purpose of this study was to investigate mental-stress-induced microvascular reactivity (excess blood flow (EBF)) in normal-weight and obese individuals. In addition, the relationships between potential vascular response modulators (heart rate (HR) and norepinephrine (NE)) and EBF were examined. Twenty-two male subjects were classified as obese (n = 12) or normal-weight (n = 10), and each subject completed a 20 min bout of acute mental stress. Our analyses demonstrate significant elevations in forearm blood flow (FBF) and EBF immediately after mental stress in both normal-weight and obese groups. HR was only correlated with EBF immediately poststress in the normal-weight group. Furthermore, stress-induced plasma NE was not associated with FBF or EBF in either group, although in the obese group, stress-induced plasma NE was associated with body mass index and percent body fat. These results suggest that microvascular reactivity after mental stress is not directly related to plasma NE in normal-weight or obese individuals. The novel results presented in this study provide a foundation for additional examination of the mechanisms involved in the effects of mental stress on microvascular reactivity.

Chitin enhances obese inflammation ex vivo.

Infection has been implicated as a co-risk factor for obesity, but the mechanism remains uncertain. Elevated levels of plasma chitinase 3-like 1 (CHI3L1) are found in obese individuals. Since CHI3L1 is produced by activated immune cells including macrophages and recognizes microbial N-acetylglucosamine polymer (chitin), we asked whether the plasma CHI3L1 protein change in obese individuals might alter their innate immune response to chitin. Thirty-six subjects (15 obese and 21 non-obese), ages 18-30 years, were recruited. Peripheral blood mononuclear cells (PBMCs) were cultured with chitin microparticles (CMP; 1-10 µm) for 24h; tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and CHI3L1 in the culture supernatants were measured. We chose CMP, since neither large chitin beads (40-100 µm), chitosan microparticles (1-10 µm), nor soluble chitin induced the cytokine/CHI3L1 production by PBMCs isolated from non-obese PBMCs ex vivo. We found that the quantity of IL-6, but not TNF-α or CHI3L1, induced by CMP was significantly correlated with plasma IL-6, BMI, waist/hip circumferences, fasting plasma insulin, and insulin resistance. These findings suggest that chitin, a substrate of CHI3L1, further promotes obese inflammation in a size- and chemical composition- dependent manner.

Brain-derived neurotrophic factor expression ex vivo in obesity.

Obesity is associated with an increased risk in neurodegenerative diseases. To counteract the neuronal damage, the human body increases brain-derived neurotrophic factor (BDNF) expression, leading to neuronal survival and plasticity. Recently, peripheral blood mononuclear cells (PBMCs) have been found to release BDNF as a potential neuroprotective role of inflammation. Therefore, the purpose of this study was to examine whether lipopolysaccharide (LPS)-induced PBMC activation would lead to differences in BDNF and inflammatory responses between obese and non-obese subjects. Thirty-one subjects (14 obese and 17 non-obese), ages 18 to 30years, were recruited. PBMCs were cultured for 24h with 10ng/mL LPS. BDNF, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured in both plasma and cell culture supernatants. Our results did not illustrate any differences in plasma BDNF levels between obese and non-obese groups. However, obese subjects elicited a greater plasma IL-6 production, which was positively associated with plasma BDNF. Furthermore, LPS-induced PBMCs expressed significantly higher BDNF and IL-6 levels in obese subjects compared to the non-obese subjects. Finally, these BDNF levels were positively correlated with IL-6 response ex vivo. These findings suggest that under a high inflammatory state, PBMCs produce greater BDNF and IL-6 expression which may play a collaborative role to protect against neuronal damage associated with obesity.

Glucocorticoid inhibition of leptin- and lipopolysaccharide-induced interleukin-6 production in obesity.

Obesity is considered a chronic inflammatory condition that enhances the risk of numerous inflammatory diseases, including diabetes and cardiovascular disease. Glucocorticoids (GCs) and synthetic therapeutic GCs are anti-inflammatory agents, but the exact functions of GCs in obesity-related inflammation are unknown. Therefore, the objective of this study was to examine the inhibitory effect of an exogenous GC (dexamethasone, DEX) on leptin- and lipopolysaccharide (LPS)-induced IL-6 production by peripheral blood mononuclear cells (PBMCs) ex vivo in obese subjects compared to normal-weight subjects. Blood samples were drawn from 14 obese (BMI>30 kg/m(2)) and 14 normal-weight (BMI<25 kg/m(2)) subjects. Plasma cortisol, TNF-α and IL-6 levels, and insulin resistance (HOMA-IR) were quantified. Subjects' PBMCs (1×10(6) cells/mL) were isolated and cultured with leptin (18.75 and 250 ng/mL) or LPS (10ng/mL) in the presence of DEX (0, 10(-8), 10(-7), and 10(-6) M), a synthetic GC, for 24 h; IL-6 levels and GC sensitivity (IC50) were assessed in the cultured supernatants. No differences in the plasma cortisol levels were found between the two groups. We found that obese subjects showed greater leptin- and LPS-induced IL-6 production compared to normal-weight subjects. The suppressive effect of DEX on leptin- and LPS-induced IL-6 production (IC50) was not different between the two groups. However, the IC50 of DEX for LPS-induced was correlated with BMI, waist circumference, and hip circumference. These findings suggest that reduced GC sensitivity may be an important mechanism in the up-regulation of selected obese inflammation.

A expertise clássica da ausculta cardíaca para o diagnóstico do prolapso da valva mitral / The expertise of the classic cardiac auscultation for the diagnosis of mitral valve prolapses

JUSTIFICATIVA E OBJETIVOS: O prolapso da valva mitral possui inúmeras etiologias, é a valvopatia mais frequentee é a causa isolada de insuficiência mitral mais comum. Possui uma clínica muito diversificada e ultimamente tem-se buscado critérios diagnósticos mais rígidos para padronizar a sua identificação.Este estudo teve como objetivo oferecer as bases da ausculta cardíaca, determinar sua importância e aprofundar nos critérios diagnósticos, na clínica e prognóstico do prolapso da valva mitral. CONTEÚDO: A invenção do estetoscópio por René Hyacinthe Laënec em 1816 mudou o cenário da medicina. Para uma boa prática médica é necessário se ter um bom conhecimento das bases da ausculta cardíaca, que se baseia na utilização correta do estetoscópio, sistematização do exame físico cardíaco e na correta caracterização dos sons auscultados. São frequentes as novas tecnologias que auxiliam no diagnóstico das valvopatias, porém os exames complementares possuem suas limitações. A ausculta cardíaca está perdendo espaço diante dos novos equipamentos,encarecendo a prática médica. CONCLUSÃO: Mesmo com as novas tecnologias, além da correta utilização dos exames complementares, é de extrema importância a realização da anamnese e exame físico para o diagnóstico do prolapso da valva mitral, se fazendo necessário o uso dos critérios diagnósticos vigentes.

BACKGROUND AND OBJECTIVES: The mitral valve prolapsed have numerous etiologies and it is the most common valvular disease and the most common isolated cause of mitral insufficiency. Besides having a very diverse clinical, more stringent diagnostic criteria have been sought in order to reduce overdiagnosis that they had prior to these criteria. This aims to give the basics of cardiac auscultation, and deepen their importance in diagnostic criteria, the clinical course and prognosis of mitral valve prolapse. CONTENTS: The invention of the stethoscope by René Laënec Hyacinthe in 1816 changed completely the medicine scenario. For a good medical practice it is necessary to have a good knowledge of the bases of cardiac auscultation, which is focused on the correct use of the stethoscope, systematic physical examination and on the correct characterization of auscultation of heart sounds. Increasingly there are technologies that help the physicianin the diagnosis of valvular heart disease, and even studies showing that all these tests have their limitations, the cardiac auscultation has been put aside in exchange for these new technologies, making the medical practice more and more expensive. CONCLUSION: Even with new technologies, besides the correct use of supplementary tests, it is extremely important the anamnesis and physical examination for the diagnosis of mitral valve prolapse, if necessary making use of current diagnostic criteria.