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An increasing number of patients are presenting to allergists with concerns about mast cell activation syndrome (MCAS), often in the context of persistent, unexplained, multisystem symptoms. This review aims provide a practical, stepwise approach to the diagnosis and management of MCAS, based on the consensus criteria established by the European Competence Network on Mastocytosis—American Initiative on Mast Cell Diseases, an international consortium of leading experts in mast cell disorders endorsed by major scientific organizations. The first step is to evaluate whether the clinical presentation is consistent with MCAS, recognizing that the prototypical presentation is idiopathic anaphylaxis. Symptoms should be severe, episodic, typical of mast cell activation, and involve at least two organ systems. The next step is to exclude secondary causes of mast cell activation, particularly cofactor-dependent food allergy and nonsteroidal anti-inflammatory drug hypersensitivity. Objective evidence of mast cell activation must then be obtained, preferably by identifying an acute increase in serum tryptase (on a sample drawn within four hours of an episode) compared to baseline. Alternatively, urinary metabolites of mast cell mediators can be assessed by comparing baseline values with those obtained 3–6 h post-event. Importantly,elevated baseline values in serum tryptase or urinary metabolites are not diagnostic of MCAS, nor do normal values exclude the diagnosis. In patients with idiopathic anaphylaxis, evaluation for a clonal mast cell disorder is recommended. This includes measuring baseline serum tryptase, testing for the KIT p.D816V mutation in peripheral blood (using high-sensitivity assays, if available), and calculating a mast cell clonality prediction score. A bone marrow biopsy should be considered for those with a high probability of mast cell clonality. Management includes instructing patients to treat acute episodes with an epinephrine auto-injector, particularly when anaphylaxis criteria are met. For patients with recurrent episodes, prophylactic therapy may be initiated, starting with H1-antihistamines and stepping-up as needed. While most patients have a favourable clinical course, some may require multiple medications to prevent or attenuate episodes. Future research should focus on validating and refining diagnostic and therapeutic strategies. In clinical practice, expanding access to key diagnostic tools—such as urinary mediator assays, sensitive KIT mutation testing, and tryptase genotyping—would facilitate and improve care of those patients.

Background Dextromethorphan (DM) is a cough suppressant that is widely available in many prescribed and over-the-counter medications. Both immediate and delayed hypersensitivity reactions have been reported following the ingestion of DM. Anaphylaxis to DM is rare, with only three reported cases in the literature. Among these, skin prick testing for DM yielded a positive result in one case, a negative result in another, and was not performed in the third. Case presentation We present a rare case of anaphylaxis linked to DM, confirmed by skin testing. The patient experienced a severe allergic reaction after taking Vicks Dayquil Complete®, a common over-the-counter cold and flu medicine that contains acetaminophen, DM, phenylephrine hydrochloride, and guaifenesin. Among these, only DM triggered a positive response on skin testing. Conclusion This case highlights an uncommon allergy to a combination cold medicine, with skin testing identifying DM as the cause.

Both obesity and DENV infections are growing public health concerns that have far-ranging socioeconomic effects, especially in developing countries. Despite the increasing prevalence of these conditions, there is a scarcity of data investigating the potential relationships between these two entities. Our study aims to examine the influence of obesity on various clinical and laboratory parameters amongst patients with DENV infections. A total of 335 hospitalized patients aged >12 years who were DENV non-structural protein 1 (NS1) antigen-positive were enrolled in this study. Clinical and laboratory variables were compared between patients with and without obesity. Multivariate analysis showed that the following admission clinical findings and laboratory results were independently associated with obesity; chills and rigors (AOR:2.653, 95% CI: 1.286-5.474), higher temperature (AOR:1.485, 95% CI: 1.080-2.042), higher systolic BP (AOR:1.057, 95% CI:1.037-1.078), raised haematocrit (AOR: 1.953, 95% CI: 1.010-3.778), elevated creatinine (AOR:3.504, 95% CI:1.351-9.008) and elevated ALT (AOR: 4.146, 95% CI:1.878-9.154). Obesity was found to be significantly associated with hospitalization >3 days (AOR: 1.990, 95% CI: 1.134-3.494) and the presence of increasing haematocrit with decreasing platelets (AOR: 2.134, 95% CI = 1.235-3.688). Serial assessment of laboratory data revealed that peak haematocrit was significantly higher and nadir platelets levels were significantly lower in obese patients. Both peak and admission levels of leukocyte counts, AST, ALT and creatinine were significantly higher in the obese group. Conversely, both admission and nadir albumin levels were lower for the obese group, although only nadir albumin levels achieved statistical significance. These findings support closer clinical monitoring of obese patients who present with DENV infections, as this patient cohort may possess an increased tendency towards developing more severe clinical manifestations of DENV infections as compared to non-obese patients.

While Inuit living in Nunavut have been advocating for decades for the return of birthing to their own communities, over two-third of births continue to occur outside of the territory. We conducted a literature review to answer the question, why has birthplace choice not been given back to Inuit yet. Based on our review we identified a number of factors impacting birthplace choice, including the organisation of the Nunavut medical system that is focused on primary health care and that cannot easily accommodate the potential clinical risks Western health care associates with birthing, often in isolation from socio-cultural risks; staffing vacancies and turn over in Nunavut, which creates challenges in continuity of care and in maintaining trust; and trends in Canada towards the medicalisation of birthing, which resulted in the displacement of traditional midwifery, and lately in the professionalisation of midwifery with training centres mostly located outside of Nunavut. We recognise that providing more options to birth in the north is complex. While birthing in the north as an option is a given objective, operationalising this objective in a consistent manner is likely going to be a challenge for years to come.

Background Perflutren lipid microsphere suspension, sold under the brand name Definity®, is a microbubble ultrasound contrast agent. The microspheres contain octafluoropropane (C 3 F 8 ) gas encapsulated by an outer lipid shell of phospholipids and a polyethylene glycol (PEG)ylated phospholipid. Anaphylaxis to perflutren lipid microsphere is very rare, with only one case report clearly attributing the reaction to the PEG excipient. We report a novel case of anaphylaxis likely caused by a non-PEGylated component of Definity®. Case presentation Our patient is a healthy 54-year-old female, who underwent an exercise stress transthoracic echocardiogram using Definity® as an enhancing agent. She experienced anaphylaxis within 15 min of injection. Symptoms resolved after she was treated with diphenhydramine and epinephrine, followed by a systemic corticosteroid and ondansetron in the Emergency Department. The patient underwent allergy testing at our clinic for Definity® and various PEG-containing substances. While all PEG products tested negative, she had positive intradermal tests to Definity®. She also had negative skin prick testing to PEG 8000 and passed an oral challenge to PEG 3350, thus ruling out PEG as the causative agent of anaphylaxis. Conclusions Our case report highlights a previously undocumented instance of anaphylaxis to Definity® not caused by PEG. We suspect the reaction to be an IgE-mediated response to a non-PEGylated component of Definity®. An alternative explanation for the reaction could be a complement activation-related pseudoallergy. This report provides critical information to physicians on the potential risks of using Definity® and contributes to growing research surrounding the profile of Definity®.

A rare subset of IL-10-producing B cells, named regulatory B cells (Bregs), suppresses adaptive immune responses and inflammation in mice. In this study, we examined the role of IL-10-producing B cells in HIV-1 infection. Compared to uninfected controls, IL-10-producing B cell frequencies were elevated in both blood and sigmoid colon during the early and chronic phase of untreated HIV-1 infection. Ex vivo IL-10-producing B cell frequency in early HIV-1 infection directly correlated with viral load. IL-10-producing B cells from HIV-1 infected individuals were enriched in CD19(+)TIM-1(+) B cells and were enriched for specificity to trimeric HIV-1 envelope protein. Anti-retroviral therapy was associated with reduced IL-10-producing B cell frequencies. Treatment of B cells from healthy donors with microbial metabolites and Toll-like receptor (TLR) agonists could induce an IL-10 producing phenotype, suggesting that the elevated bacterial translocation characteristic of HIV-1 infection may promote IL-10-producing B cell development. Similar to regulatory B cells found in mice, IL-10-producing B cells from HIV-1-infected individuals suppressed HIV-1-specific T cell responses in vitro, and this suppression is IL-10-dependent. Also, ex vivo IL-10-producing B cell frequency inversely correlated with contemporaneous ex vivo HIV-1-specific T cell responses. Our findings show that IL-10-producing B cells are induced early in HIV-1 infection, can be HIV-1 specific, and are able to inhibit effective anti-HIV-1 T cell responses. HIV-1 may dysregulate B cells toward Bregs as an immune evasion strategy.

Key Clinical Message Prompt diagnosis of tuberculous meningitis (TBM) is crucial to prevent severe complications like cranial nerve involvement and irreversible visual impairment. Early suspicion and intervention are essential, especially in tuberculosis‐endemic regions. Rapid initiation of anti‐tuberculosis therapy and vigilant monitoring for complications, such as hydrocephalus, improve patient outcomes and prevent long‐term disabilities. This case study provides a comprehensive overview of the difficulties associated with predicting and managing tuberculous meningitis (TBM). The predictive aspect is hindered by the subacute nature of TBM, featuring a prodromal phase lasting 7–10 days, followed by manifestations like severe headaches, altered mental status, stroke, hydrocephalus, and cranial neuropathies. Additionally, vision loss is a disabling complication. All components of the visual pathway, especially the optic nerve and optic chiasma, are frequently and dominantly affected. While antibiotics can promptly resolve meningitis in most cases, approximately 10% of infections progress to chronic meningitis, with tuberculosis meningitis being the most common form. Our patient initially presented with nonspecific symptoms, which later evolved into symptoms that indicate viral meningitis and was started on empirical therapy. Subsequently, due to clinical suspicion of tuberculosis meningitis and persistent symptoms despite treatment, she was placed in anti‐tuberculosis therapy (ATT) but unfortunately developed complications such as hydrocephalus and blindness. To address the hydrocephalus, a Ventriculo‐Peritoneal shunt was implanted. Despite delayed treatment and diagnosis, most of her symptoms resolved except for blindness, for which there was only partial recovery.

Antibiotics are commonly used in intensive care units (ICUs), yet differences in antibiotic use across ICUs are unknown. Herein, we studied antibiotic use across ICUs and examined factors that contributed to variation. We conducted a retrospective cohort study using data from Ontario's Critical Care Information System (CCIS), which included 201 adult ICUs and 2,013,397 patient days from January 2012 to June 2016. Antibiotic use was measured in days of therapy (DOT) per 1,000 patient days. ICU factors included ability to provide ventilator support (level 3) or not (level 2), ICU type (medical-surgical or other), and academic status. Patient factors included severity of illness using multiple-organ dysfunction score (MODS), ventilatory support, and central venous catheter (CVC) use. We analyzed the effect of these factors on variation in antibiotic use. Overall, 269,351 patients (56%) received antibiotics during their ICU stay. The mean antibiotic use was 624 (range 3-1460) DOT per 1,000 patient days. Antibiotic use was significantly higher in medical-surgical ICUs compared to other ICUs (697 vs 410 DOT per 1,000 patient days; P < .0001) and in level 3 ICUs compared to level 2 ICUs (751 vs 513 DOT per 1,000 patient days; P < .0001). Higher antibiotic use was associated with higher severity of illness and intensity of treatment. ICU and patient factors explained 47% of the variation in antibiotic use across ICUs. Antibiotic use varies widely across ICUs, which is partially associated with ICUs and patient characteristics. These differences highlight the importance of antimicrobial stewardship to ensure appropriate use of antibiotics in ICU patients.

Background The mechanism of action behind anaphylactic reactions to the mRNA COVID-19 vaccines remains unknown, but the excipient polyethylene glycol, PEG-2000, has been implicated. Initial recommendations were made for excipient testing with PEG-3350 to help risk stratify individuals and identify an etiology. Here we present a case of a patient with a history of polyethylene glycol anaphylaxis and positive skin testing to PEG-3350, who successfully received both doses of the Pfizer-BioNTech COVID-19 mRNA vaccine in a single step with only premedication. Case presentation A 56-year-old man was referred to our clinic for assessment of his eligibility in receiving the COVID-19 vaccine given a history of anaphylaxis to PEG. He had two anaphylactic episodes: one in 2018 to methylprednisolone acetate intra-articular injection and one to oral PEG-3350 in 2020. Confirmatory skin prick testing was done in our clinic to PEG-3350 that was positive at 35 mm with appropriate positive and negative controls. Despite this he wanted to receive the PEG-containing mRNA COVID-19 vaccines and was counselled on the risks and benefits. He successfully received both doses of the Pfizer-BioNTech COVID-19 mRNA vaccine in a single step with only pre-treatment with Cetirizine 20 mg daily and Montelukast 10 mg daily for 5 days. Conclusions In conclusion, our case demonstrates that a patient with a confirmed polyethylene glycol anaphylaxis could safely receive both doses of the COVID-19 mRNA vaccines in a single step with pre-treatment. We hope that our case will further support the limited role in skin testing to PEG in the assessment of COVID-19 mRNA vaccine allergy and highlight the need for further research to elucidate the mechanism of action behind these allergic reactions.

Introduction Most patients significantly benefit from cochlear implantation (CI). However, speech understanding varies widely, with a small proportion of patients demonstrating limited audiometric outcomes. While there are well‐documented determinants of poor performance, there remains a cohort of patients that do not meet expected outcomes. Preoperative prognostication is desirable to manage expectations, ensure value of the intervention, and reduce risk. The objective of the study is to evaluate variables found within a single CI center's most limited functioning cohort following implantation. Methods A retrospective review of a single CI program's cohort of (344 ears) patients implanted between 2011 and 2018 whose 1‐year postimplantation AzBio scores fall 2 SDs below the mean was performed. Exclusion criteria includes skullbase pathology, pre/peri‐lingual deafness, cochlear anatomic abnormalities, English as an additional language, and limited electrode insertion depth. Overall, 26 patients were identified. Results The study population's postimplantation net benefit AzBio score is 18% compared to the entire program's 47% (p < 0.05). This group is older (71.8 vs. 59.0 years, p < 0.05) with a longer duration of hearing loss (26.4 vs. 18.0 years, p < 0.05) and with a lower preoperative AzBio score [14% lower (p < 0.05)]. A host of medical conditions were identified in the subpopulation, with a trend towards significance in those suffering from either malignancy or cardiac condition. Escalating comorbid status was associated with worse performance (p < 0.05). Conclusion Within a cohort of limited‐performing CI users, benefit tended to decrease with escalating number of comorbid conditions. This information may serve to inform preoperative patient counseling. Level of evidence Level IV (evidence from a case control study). Many patients receive benefit from cochlear implant surgery, however a cohort of patients remain that do not perform as expected with age and duration of hearing loss the primary risk factors.