Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria.

BACKGROUND: Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response. METHODS: CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer. RESULTS: Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10-42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/µL (OR 13.33; 95% CI 3.32-52.63; p < .001) and the absence of hypothyroidism (OR 3.65; 95% CI 0.78-16.95; p = .099) were identified as predictive factors to achieve control with 300 mg/4 weeks. Twelve patients were able to stop OMA during the study (responders in remission, RR). RR had received OMA for a median of 29 months (12-53 months). Conversely, 32 patients had been on OMA for >29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30-100 months). There were no significant differences in clinical or analytical factors between RR and AR patients. CONCLUSIONS: Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients.

Flow-based basophil activation test in immediate drug hypersensitivity. An EAACI task force position paper.

Diagnosing immediate drug hypersensitivity reactions (IDHRs) can pose a significant challenge and there is an urgent need for safe and reliable tests. Evidence has emerged that the basophil activation test (BAT), an in vitro assay that mirrors the in vivo response, can be a complementary test for many drugs. In this position paper, members of Task Force (TF) "Basophil activation test in the evaluation of Drug Hypersensitivity Reactions" from the European Academy of Allergy and Clinical Immunology (EAACI) present the data from a survey about the use and utility of BAT in IDHRs in Europe. The survey results indicate that there is a great interest for using BAT especially for diagnosing IDHRs. However, there are still main needs, mainly in the standardization of the protocols. Subsequently consensus-based recommendations were formulated for: (i) Technical aspects of BAT in IDHRs including type of sample, management of drugs, flow cytometry protocols, interpretation of the results; and (ii) Drug-specific aspects that should be taken into account when performing BAT in relation to betalactams, neuromuscular blocking agents, fluoroquinolones, chlorhexidine, opioids, radio contrast media, chemotherapeutics, biological agents, nonsteroidal anti-inflammatory drugs, COVID vaccine, and excipients. Moreover, aspects in the evaluation of pediatric population have also been considered. All this indicates that BAT offers the clinician and laboratory a complementary tool for a safe diagnostic for IDHRs, although its place in the diagnostic algorithm depends on the drug class and patient population (phenotype, geography, and age). The standardization of BAT is important for generalizing this method beyond the individual laboratory.

From MASK-air and SILAM to CATALYSE (Climate Action To Advance HeaLthY Societies in Europe).

Plant species vary under different climatic conditions and the distribution of pollen in the air. Trends in pollen distribution can be used to assess the impact of climate change on public health. In 2015, the Mobile Airways Sentinel networK for rhinitis and asthma (MASK-air®) was launched as a project of the European Innovation Partnership on Active and Healthy Ageing (EIP-on-AHA, DG Santé and DG CONNECT). This project aimed to develop a warning system to inform patients about the onset of the pollen season, namely, the System for Integrated modeLling of Atmospheric coMposition (SILAM). A global-to-meso-scale dispersion model was developed by the Finnish Meteorological Institute (FMI). It provides quantitative information on atmospheric pollution of anthropogenic and natural origins, particularly on allergenic pollens. Impact of Air Pollution on Asthma and Rhinitis (POLLAR, EIT Health) has combined MASK-air clinical data with SILAM forecasts. A new Horizon Europe grant (Climate Action to Advance HeaLthY Societies in Europe [CATALYSE]; grant agreement number 101057131), which came into force in September 2022, aims to improve our understanding of climate change and help us find ways to counteractit. One objective of this project is to develop early warning systems and predictive models to improve the effectiveness of strategies for adapting to climate change. One of the warning systems is focused on allergic rhinitis (CATALYSE Task 3.2), with a collaboration between the FMI (Finland), Porto University (Portugal), MASK-air SAS (France), ISGlobal (Spain), Hertie School (Germany), and the University of Zurich (Switzerland). It is to be implemented with the support of the European Academy of Allergy and Clinical Immunology. This paper reports the planning of CATALYSE Task 3.2.

Barriers and facilitators to implementing a multilevel, multicomponent intervention promoting colorectal cancer screening in health centers: a qualitative study of key informant perspectives.

BACKGROUND: Colorectal cancer (CRC) continues to be a major cause of death in the U.S. despite the availability of effective screening tools. U.S. Latinos have lower rates of CRC screening and higher rates of death due to colorectal disease compared to non-Hispanic whites. Federally Qualified Health Centers (FQHCs) serve medically underserved populations, including many Latino patients. Given the low CRC screening rates, identifying culturally sensitive and cost-effective methods of promoting screening is a priority for many FQHCs. METHODS: We interviewed FQHC leaders and providers using the Consolidated Framework for Implementation Research (CFIR) to identify barriers and facilitators to implementation of a multilevel, multicomponent (ML-MC) CRC screening intervention (i.e., promotor navigation and group-based education) in FQHCs. A rapid qualitative analysis approach was used to identify themes organized according to the following CFIR constructs: intervention characteristics, outer and inner settings, and characteristics of the individual. RESULTS: We completed interviews with 13 healthcare professionals in leadership positions at six FQHCs. The participating FQHCs perceived the ML-MC screening CRC program as feasible and expressed interest in implementing the program at their sites. Facilitators included financial incentives for increasing screening rates, the need for patient education programming, and involving promotores to support the work of clinical teams. Barriers included concerns about available resources to implement new programs, lack of federal reimbursement for health education, competing priorities of other health concerns, and the need for more resources for confirmatory screening and treatment following a positive screen. CONCLUSIONS: FQHCs provide essential primary care to millions of underserved patients in the U.S. and have the ability and motivation to provide screenings for colorectal cancer. Partnering with an academic institution to deliver a group-based, promotor-led CRC screening intervention for patients not up to date with screening could help increase screening rates. By identifying the specific barriers and facilitators to implementing CRC intervention, findings suggest that group-based, promotor-led interventions are a promising approach.

Organ-specific allergen challenges in airway allergy: Current utilities and future directions.

Atopy has been long used as the screening method for airway allergy. Nevertheless, aeroallergens can trigger respiratory symptoms not only in atopic patients (atopic respiratory allergy, ARA), but also in non-atopic subjects (local respiratory allergy, LRA). Moreover, ARA and LRA can coexist in the same patient, and this clinical scenario has been called dual respiratory allergy (DRA). When the clinical history cannot determine the relevance of sensitizations in ARA patients, nasal, conjunctival or bronchial allergen challenges (NAC, CAC, and BAC, respectively) should be conducted. Moreover, these tests are required to identify patients with LRA and DRA. The clarification of the allergic triggers of airway diseases has a profound impact on the management strategies the patients can be offered. Importantly, allergen immunotherapy (AIT) remains as the only disease-modifying intervention for ARA. Recent data indicate that AIT might have a similar effect on LRA patients. Nevertheless, AIT success relies largely on the correct phenotyping of allergic individuals, and NAC, CAC, and BAC are very helpful tools in this regard. In this review, we will summarize the main indications and methodology of CAC, NAC, and BAC. Importantly, the clinical implementation of these tests might translate into precision medicine approaches and better health outcomes for patients with airway allergy.

Deconstructing adverse reactions to Amoxicillin-Clavulanic Acid: the importance of time of onset.

BACKGROUND: Amoxicillin-clavulanic acid (AX-CL) is the most consumed betalactam antibiotic worldwide. We aimed to establish the different phenotypes of betalactam allergy in those referring a reaction with AX-CL and to investigate the differences between immediate and non-immediate onset. METHODS: Cross-sectional retrospective study performed at Hospital Clínico San Carlos (HCSC) and Hospital Regional Universitario de Málaga (HRUM) in Spain. Patients reporting reactions with AX-CL who completed the allergy workup between 2017 and 2019 were included. Data of reported reaction and allergy workup were collected. Reactions were classified as immediate and non-immediate with 1hour cut-off point. RESULTS: We included 372 patients (HCSC 208, HRUM 164). There were 90 (24.2%) immediate, 252 (67.7%) non-immediate reactions, and 30 (8.1%) with unknown latency. Allergy to betalactams was ruled-out in 266 (71.5%) and confirmed in 106 patients (28.5%). The final main diagnosis in the overall population were allergy to aminopenicillins (7.3%), to CL (7%), to penicillin (6.5%) and to betalactams (5.9%). Allergy was confirmed in 77.2% and 14.3% of immediate and non-immediate reactions respectively, with a relative risk of 5.06 (95%CI 3.64-7.02) of an allergy diagnosis in those reporting immediate reactions. Only 2/54 patients with late-positive intradermal test (IDT) to CL were diagnosed of CL allergy. CONCLUSION: Allergy diagnosis was confirmed in a minority of the whole study population, but 5 times more frequently in those reporting immediate reactions, making this classification useful in risk stratification. Late-positive IDT for CL has no diagnostic value and its late reading could be retrieved from the diagnosis work-up.

A case of natural infection with Dirofilaria immitis in a coati (Nasua narica) from Mexico.

This paper aims to describe the natural infection with Dirofilaria immitis in Nasua narica (white-nosed coati) from Yucatán, Mexico. Two carcasses of N. narica were collected on a highway that crosses through a dense forest with patches used for agriculture and livestock activities. We performed necropsies, and two female adult nematode parasites from the heart of one specimen were collected and preserved for their molecular identification using a conventional PCR directed at a fragment of the small subunit (18S) ribosomal RNA (18S-rRNA) gene. Bioinformatic analysis showed a similarity of 99 % with three sequences from D. immitis (two from Japan). Additionally, we performed a phylogenetic tree with the recovered sequence. All these analyses showed that D. immitis is present in N. narica from Mexico. The transmission of D. immitis toward populations of Nasua sp. may be due to indirect and accidental contact with domestic dogs or wild canids that share the same environment.

Incidence of Fatal Anaphylaxis: A Systematic Review of Observational Studies.

BACKGROUND: Fatal anaphylaxis is very rare, with an incidence ranging from 0.5 to 1 deaths per million person-years. OBJECTIVE: Based on a systematic review, we aimed to explain differences in the reported incidence of fatal anaphylaxis based on the methodological and demographic factors addressed in the various studies. METHODS: We searched PubMed/MEDLINE, EMBASE, and the Web of Science for relevant retrospective and prospective cohort studies and registry studies that had assessed the anaphylaxis mortality rate for the population of a country or for an administrative region. The research strategy was based on combining the term "anaphylaxis" with "death", "study design", and "main outcomes" (incidence). RESULTS: A total of 46 studies met the study criteria and included 16,541 deaths. The range of the anaphylaxis mortality rate for all causes of anaphylaxis was 0.002-2.51 deaths per million person-years. Fatal anaphylaxis due to food (range 0.002-0.29) was rarer than deaths due to drugs (range 0.004-0.56) or Hymenoptera venom (range 0.02-0.61). The frequency of deaths due to anaphylaxis by drugs increased during the study period (IRR per year, 1.02; 95%CI, 1.00-1.04). We detected considerable heterogeneity in almost all of the meta-analyses carried out. CONCLUSION: The incidence of fatal anaphylaxis is very low and differs according to the various subgroups analyzed. The studies were very heterogeneous. Fatal anaphylaxis due to food seems to be less common than fatal anaphylaxis due to drugs or Hymenoptera venom.

"We will do whatever it takes": Understanding Socioecological Level Influences on Hmong-American Adolescents and Parents' Perceptions of the Human Papillomavirus Vaccine.

Human papillomavirus (HPV) vaccination completion rates in Asian-American populations are substantially lower than most White Americans. Our objective was to identify the knowledge, perceptions, and decision-making processes about HPV vaccinations in the Hmong population, an Asian-American group with increased risks of HPV-related cancers. We conducted eight focus groups with Hmong adolescents (n = 12) and parents (n = 13) to learn about barriers, facilitators, and decision-making processes regarding general vaccinations and the HPV vaccine. The focus group results were analyzed using thematic analysis, informed by the socioecological model and asset lens. Findings showed that at the individual level, Hmong adolescents and parents had low HPV and HPV vaccine awareness levels (barrier) and strong desires to learn about HPV and the HPV vaccine (facilitator). Community-level barriers included salient narratives about traumatic experiences with vaccines and vaccine research, while facilitators included strong community connections. At the institutional level, barriers included structural constraints in health care settings, while facilitators included ease of obtaining vaccines at school-based clinics and provider authoritative decision-making. Additionally, a range of decision-making processes between parents, adolescents, and providers were present, with parents expressing a strong appeal to engage in more shared decision-making with providers. A linguistically and culturally specific HPV educational program for Hmong adolescents and parents could address the barriers and build on facilitators and assets to promote HPV vaccine uptake in this growing Asian-American community.

Prevalence and morphometric analysis of the retromolar canal in a Spanish population sample: a helical CT scan study.

BACKGROUND: The retromolar canal (RMC) is an anatomical variation of the mandibular canal (MC) whose identification and study should be considered given its implication in the surgical procedures of the retromolar area. The prevalence of the RMC widely varies according to previous studies and may be influenced by the followed study method. This work aimed to evaluate the prevalence of the RMC in a Spanish population sample. MATERIAL AND METHODS: For this purpose, 225 CT scan images (with a higher resolution than the cone beam CT used in other previous studies) from the Hospital Clínico Universitario de Valencia were analyzed. The Osirix MD® radiological image analysis system was applied to analyse the dimensions, location in the retromolar area and morphologic characteristics of the RMC by classifying them according to their typology. Furthermore, the relations between the RMC and gender, age and laterality were studied. RESULTS: RMC prevalence was 23.1%. No significant relation between the presence of the canal and gender, age or laterality was found. Type Ia was the commonest type with a prevalence of 40.8%. CONCLUSIONS: Based on the results of this study, the RMC should be considered a frequent anatomical variation whose complete study is very important in daily clinical practice.

Tuberculosis infection in HIV vs. non-HIV patients.

OBJECTIVES: Tuberculosis (TB) is the most common opportunistic infection and cause of mortality among people living with HIV, and it is possible that it may also influence the evolution of the HIV infection. We assessed the differences between HIV-positive and -negative people infected with TB. METHODS: The present study is a cross-sectional retrospective study by electronic record revision. We included patients admitted to a tertiary hospital with a diagnosis of TB between 2011 and 2016, comparing those with HIV coinfection with non-HIV patients, according to demographic and clinical characteristics. RESULTS: This study included 591 patients, of whom 32% were HIV-coinfected. HIV-TB patients were younger, with a predominance of male gender. Considering TB risk factors, there was a higher prevalence of homelessness and intravenous drug use in the HIV group. In the non-HIV group, direct contact with other patients with TB and immunosuppression were more prevalent. Relative to TB characteristics, the HIV-coinfected group presents with a higher prevalence of disseminated disease and a higher occurrence of previous TB infection. Cancer was the most frequent cause of immunosuppression in the HIV group and the number testing positive for TB via microbiological culture was lower. Assessment of microbiological resistance and in-hospital mortality showed similar numbers in both groups. CONCLUSIONS: There are few papers comparing clinical course of TB between HIV-infected and non-infected patients. Our study differs from others in the literature as we focused on a country with middling incidence of TB and further characterized the differences between HIV-infected and non-infected patients which can contribute to the management of these patients.

Polymorphisms in eicosanoid-related biosynthesis enzymes associated with acute urticaria/angioedema induced by nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity, with NSAID-induced acute urticaria/angioedema (NIUA) the most frequent phenotype. NSAID hypersensitivity is caused by cyclooxygenase 1 inhibition, which leads to an imbalance in prostaglandin (PG) and cysteinyl leukotriene (CysLT) synthesis. As only susceptible individuals develop NSAID hypersensitivity, genetic factors are believed to be involved; however, no study has assessed the overall genetic variability of key enzymes in PG and CysLT synthesis in NSAID hypersensitivity. OBJECTIVES: To evaluate simultaneously variants in the main genes involved in PG and CysLT biosynthesis in NIUA. METHODS: Two independent cohorts of patients were recruited in Spain, alongside NSAID-tolerant controls. The discovery cohort included only patients with NIUA; the replication cohort included patients with NSAID-exacerbated respiratory disease (NERD). A set of tagging single-nucleotide polymorphisms (tagSNPs) in PTGS1, PTGS2, ALOX5 and LTC4S was genotyped using mass spectrometry coupled with endpoint polymerase chain reaction. RESULTS: The study included 1272 individuals. Thirty-five tagSNPs were successfully genotyped in the discovery cohort, with three being significantly associated after Bonferroni correction (rs10306194 and rs1330344 in PTGS1; rs28395868 in ALOX5). These polymorphisms were genotyped in the replication cohort: rs10306194 and rs28395868 remained associated with NIUA, and rs28395868 was marginally associated with NERD. Odds ratios (ORs) in the combined analysis (discovery and replication NIUA populations) were 1·7 for rs10306194 [95% confidence interval (CI) 1·34-2·14; Pcorrected = 2·83 × 10-4 ) and 2·19 for rs28395868 (95% CI 1·43-3·36; Pcorrected = 0·002). CONCLUSIONS: Variants of PTGS1 and ALOX5 may play a role in NIUA and NERD, supporting the proposed mechanisms of NSAID-hypersensitivity and shedding light on their genetic basis.

Relation between structural patterns and magnetism in small iron oxide clusters: reentrance of the magnetic moment at high oxidation ratios.

Due to quantum confinement effects, the understanding of iron oxide nanoparticles is a challenge that opens the possibility of designing nanomaterials with new capacities. In this work, we report a theoretical density functional theory study of the structural, electronic, and magnetic properties of neutral and charged iron oxide clusters FenOm0/± (n = 1-6), with m values until oxygen saturation is achieved. We determine the putative ground state configuration and low-energy structural and spin isomers. Based on the total energy differences between the obtained global minimum structure of the parent clusters and their possible fragments, we explore the fragmentation channels for cationic oxides, comparing with experiments. Our results provide fundamental insight on how the structural pattern develops upon oxidation and its connection with the magnetic couplings and net total moment. Upon addition of oxygen, electronic charge transfer from iron to oxygen is found which weakens the iron-iron bond and consequently the direct exchange coupling in Fe. The binding energy increases as the oxygen ratio increases, rising faster at low oxidation rates. When molecular oxygen adsorption starts to take place, the binding energy increases more slowly. The oxygen environment is a crucial factor related to the stabilities and to the magnetic character of iron oxides. We identified certain iron oxide clusters of special relevance in the context of magnetism due to their high stability, expected abundance and parallel magnetic couplings that cause large total magnetic moments even at high oxidation ratios.

Bacteria cultured from the gut of Meccus pallidipennis (Hemiptera: Reduviidae), a triatomine species endemic to Mexico.

The study of intestinal microbiota in vector insects like triatomines is paramount in parasitology because many parasitic species inhabit the vector's gut. Although knowledge on the gut microbiota in various vectors of the parasitic flagellate Trypanosoma cruzi has grown, research efforts have focused on South American triatomines. This study reports the isolation of bacterial microbiota in the anterior and posterior gut of Meccus pallidipennis (a triatomine species endemic to Mexico) by culture, as well as its identification by phenotypic and biochemical tests and its quantification by counting colony-forming units. The study was performed on fifth-instar nymph and adult specimens of M. pallidipennis, either laboratory-bred or collected in the field and either infected or not with T. cruzi. Overall, 17 bacterial species were identified, with the genera Bacillus and Staphylococcus being the most prevalent regardless of the origin of the insects. No differences were observed in the number of bacterial species in the gut of laboratory-bred and field-collected insects, neither with respect to life stage or infection status. In general, the Shannon-Weaver diversity index was higher in non-infected insects than in infected ones. Further studies using non-culture methods are required to determine whether bacterial species diversity is modified by laboratory breeding.

The -514C>T polymorphism in the LIPC gene modifies type 2 diabetes risk through modulation of HDL-cholesterol levels in Mexicans.

PURPOSE: Both type 2 diabetes (T2D) and low levels of high-density lipoprotein cholesterol (HDL-C) are very prevalent conditions among Mexicans. Genetic variants in the LIPC gene have been associated with both conditions. This study aimed to evaluate the association of the -514C < T (rs1800588) LIPC gene polymorphism with different metabolic traits, particularly the effects of this polymorphism on HDL-C plasma levels and T2D risk. METHODS: Mediation analysis was used to assess the direct and indirect effects of the -514C>T LIPC gene variant on HDL-C levels, T2D risk, and body mass index (BMI), in 2105 Mexican mestizo participants. We also assessed the functional effect of the -514C>T LIPC variant on the promoter activity of a reporter gene in the HepG2 cell line. RESULTS: Direct effects show that the -514C>T LIPC polymorphism is significantly associated with increased HDL-C plasma levels (ß = 0.03; p < 0.001). The -514C>T variant resulted in an indirect protective effect on T2D risk through increasing HDL-C levels (ß = - 0.03; p < 0.001). Marginal direct association between -514C>T and T2D was found (ß = 0.08; p = 0.06). Variables directly influencing T2D status were European ethnicity (ß = - 7.20; p < 0.001), age (ß = 0.04; p < 0.001), gender (ß = - 0.15; p = 0.017) and HDL-C (ß = - 1.07; p < 0.001). In addition, we found that the -514C>T variant decreases the activity of LIPC promoter by 90% (p < 0.001). CONCLUSIONS: The -514C>T polymorphism was not directly associated with T2D risk. HDL-C acts as a mediator between -514C>T LIPC gene variant and T2D risk in the Mexican population.

ARADyAL: The Spanish Multidisciplinary Research Network for Allergic Diseases.

Thematic cooperative health research networks (RETICS) are organizational structures promoted by the Instituto de Salud Carlos III of the Spanish Ministry of Science with the objective of carrying out cooperative research projects addressing challenges of general interest for society as a whole in the field of health care. The RETICS of Asthma, Adverse Drug Reactions, and Allergy (ARADyAL) received funding in 2016 for a 5-year program (2017-2021). ARADyAL integrates basic and clinical research in the areas of allergy, immunology, genetics, nanomedicine, pharmacology, and chemistry, with special interest in research on new biomarkers and the design and evaluation of new interventions for allergic patients with severe phenotypes. The consortium comprises 28 groups across Spain, including 171 clinical and basic researchers, 17 clinical groups that cover more than 10 000 000 patients of all ages from urban and rural areas and 11 basic groups active mostly at universities and research institutes. ARADyAL has proposed a research program organized into 3 different areas focusing on precision medicine, as follows: Program 1, Mechanisms and prediction of adverse drug reactions and allergic diseases; Program 2, Toward a precise diagnosis of allergic diseases; and Program 3, Predicting interventions in allergic diseases. There is also 1 common program dedicated to training. The network has a Steering Committee and an External Advisory Scientific Committee, which advise the global network coordinator, who has recognized expertise in the field. ARADyAL is a unique meeting point for clinicians and basic scientists who are already working in allergy.

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization.

Rapid drug desensitization has enabled first-line therapies in patients with drug hypersensitivity reactions to chemotherapeutic drugs including monoclonal antibodies. Desensitization is a safe and highly effective procedure, not only for IgE-mediated reactions, but also for those mediated by non-IgE mechanisms. The likelihood of breakthrough reactions during desensitization is low, and most are mild; in fact, moderate-to-severe reactions are infrequent. In this document, 16 allergy departments belonging to the Spanish research network ARADyAL present a review of the available scientific evidence and provide general guidelines for the diagnosis and management of drug hypersensitivity reactions to chemotherapeutic drugs and monoclonal antibodies. Emphasis is placed on the desensitization procedure.

Association Between Severity of Anaphylaxis and Co-occurrence of Respiratory Diseases: A Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND AND OBJECTIVE: Asthma is very prevalent in all grades of severity of anaphylaxis. Asthma and chronic obstructive pulmonary disease (COPD) have been associated with the severity of anaphylaxis. Objective: We carried out a systematic review and meta-analysis to assess the influence of respiratory diseases on the severity of anaphylaxis. METHODS: We searched PubMed/MEDLINE, EMBASE, and the Web of Science for observational studies. The target studies were those that compared the severity of anaphylaxis between patients who had or did not have respiratory diseases. RESULTS: A total of 13 studies assessed the severity of anaphylaxis in respiratory disease. Respiratory disease increased the severity of anaphylaxis (OR, 1.87; 95%CI, 1.30-2.70), as did asthma (OR, 1.89; 95%CI, 1.26-2.83). For the meta-analysis of all studies (adjusted and nonadjusted), COPD increased the severity of anaphylaxis (OR, 2.47; 95%CI, 1.46-4.18). In the case of asthma studies, only 1 study assessed the influence of severity of asthma on severity of anaphylaxis. CONCLUSIONS: Evidence showing that respiratory disease increases the severity of anaphylaxis is low to moderate, although studies do not usually assess the importance of severity of asthma.

Loperamide exerts a direct bactericidal effect against M. tuberculosis, M. bovis, M. terrae and M. smegmatis.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis. TB is highly prevalent, characterized by the constant occurrence of drug-resistant cases, and confounded by the incidence of respiratory disease caused by non-tuberculous mycobacteria (NTB). Expanding the spectrum of drugs for the treatment of TB is indispensable. Loperamide, an antidiarrhoeal drug, enhances immune-driven antimycobacterial activity, and we aimed to evaluate its bactericidal activity against M. tuberculosis, Mycobacterium bovis BCG, Mycobacterium terrae and Mycobacterium smegmatis. Loperamide exhibited an inhibitory effect against all mycobacterial species tested, with MICs of 100 and 150 µg ml-1 . Thus, loperamide is a mycobactericidal drug with potential as adjunctive therapy for TB and NTB infections.

Not all that glitters is COVID-19: a case series demonstrating the need for histopathology when skin findings accompany SARS-CoV-2 infection.

BACKGROUND: Descriptions of cutaneous findings associated with COVID-19 have not been consistently accompanied by histopathology or confirmatory testing for SARS-CoV-2. OBJECTIVE: To describe and classify the cutaneous findings with supporting histopathology of confirmed COVID-19 inpatients. METHODS: We included consecutive inpatients with a confirmed diagnosis of COVID-19 for whom a dermatology consult was requested. A skin biopsy was performed in all cases. Skin findings were classified as being compatible with a cutaneous manifestation of COVID-19 or as representing a distinct clinical entity. RESULTS: Twenty-eight patients were studied in whom thirty-one dermatologic diagnoses were made. Twenty-two of the dermatoses were compatible with a cutaneous manifestation of COVID-19; nine entities were not associated with infection by SARS-CoV-2. The most common COVID-19-associated pattern was an exanthematous presentation. In four patients, a new pattern was observed, characterized by discrete papules with varied histopathological findings including a case of neutrophilic eccrine hidradenitis. No cases of pernio-like lesions were identified. Skin findings not associated with COVID-19 represented 29% of diagnoses and included Malassezia folliculitis, tinea, miliaria and contact dermatitis. LIMITATIONS: There is no gold-standard test to distinguish between viral exanthems and drug reactions. CONCLUSION: A histopathological study is critical before attributing skin findings to a manifestation of COVID-19.