Early testing and grade of the reaction are affecting factors of skin test positivity in ß-Lactam allergies.

Background: ß-Lactams are the most widely used antibiotic family in the world. Nevertheless, they also stand out as the primary culprits for inducing drug hypersensitivity reactions (HSR). Methods: Between May 2018 and March 2023, patients with suspected HSRs to ß-lactams, who underwent skin tests (ST), were retrospectively screened. The determinants of allergenic penicillin (DAP) tests, which include penicillin minor and major determinants, clavulanic acid, and amoxicillin, along with ampicillin, sulbactam, the identified culprit drugs, and alternative cephalosporins, which include cefuroxime, ceftriaxone prick and/or intradermal tests, were administered. The analysis focused on identifying positive ST results and determining the true HSRs rates in this patient cohort. Results: Of the 147 patients, 78.9% (n = 116) were women and the median (minimum-maximum) age was 41 years (18-71 years). Mild HSRs (grades 1-2) were observed in 72.78% (n = 107), whereas 24.4% (n = 36) had severe reactions (grades 3-4) and 2.7% (n = 4) had an unknown grade. Of the patients, 64% (n = 94) experienced HSRs within the first hour after the last dose of the identified culprit drug. The overall positivity rate for all STs was 26.5% (n = 39). ST positivity rates were notably higher in individuals who had experienced HSRs within the past 6 months (p = 0.02) and those with severe anaphylaxis (p < 0.001). Conclusion: ß-Lactam ST positivity is higher, especially in those with grades 3-4 reactions and consulted a physician within the first 6 months after their HSRs.

Hypersensitivity Reactions to Taxanes: A Multicenter Study for Outcomes and Safety of Rapid Drug Desensitization.

PURPOSE: Taxanes can cause hypersensitivity reactions (HSRs), which pose a significant challenge in the treatment of malignancies. Patients who are eligible for rapid drug desensitization (RDD) can continue treatment; however, some patients experience breakthrough reactions (BTRs). Data about risk factors for BTRs during RDDs in patients with HSRs to taxanes are limited. METHODS: This was a multicenter, retrospective study of patients with immediate-HSRs to taxanes. Initial HSRs were classified as grade 1, 2, or 3 based on severity. Prick/intradermal skin tests were performed with implicated taxanes. A 12-step protocol was used during RDD. RESULTS: The study comprised 75 patients (F/M: 63/12, mean age 49.92 ± 11.72 years, 43 HSRs to paclitaxel, 32 HSRs to docetaxel). The majority of reactions (86.7%) occurred during the first or second exposure. The prevalence of drug allergy history was higher in patients with paclitaxel HSR than in those with docetaxel HSR, although it was not statistically significant (23.3% vs. 6.3%). The initial HSRs were mostly grade 2 (n = 50, 66.7%) or grade 3 (n = 22, 29.3%). Skin tests with implicated taxanes were done on 48 patients, and the rate of positive response in patients with grade 1, 2, and 3 initial HSRs were 50%, 17.6%, and 16.7%, respectively. . A total of 255 RDDs were completely performed, although BTRs occurred in 27 (grade 1, 55.6%; grade 2, 40.7%; grade 3, 3.7%). There were no statistically significant correlations between the risk of BTR and age, drug cycle, gender, positivity of skin test or atopy. The step reduction was successfully done on 9 eligible patients with mild or moderate HSRs during the 12-step RDDs. CONCLUSIONS: Our experience demonstrates a 100% success rate in completing the 255 RDDs for taxanes, affirming the safety and efficacy of the RDD within the study population.

The Effectiveness of Biological Agents on Chronic Rhinosinusitis with Nasal Polyposis in Patients with Comorbid Asthma: A Multicenter Real-Life Study from Türkiye.

Background and Objectives: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. Materials and Methods: We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. Results: The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] (p < 0.001), but not with mepolizumab [95% CI: -0.5-2] (p = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] (p < 0.001) and [95% CI: 2-5] (p < 0.001); and mepolizumab [95% CI: 0-2] (p = 0.002) and [95% CI: 2-8.5] (p < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Conclusions: Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.

Chanarin-Dorfman Syndrome diagnosed at the stage of liver transplantation: A rare lipid storage disease.

Chanarin-Dorfman Syndrome (CDS) is a rare lipid storage disease with ichthyosis, hepatomegaly, myopathy, neuropathy, deafness, and ocular findings. Here, we aim to present an elderly CDS case and highlight the new endocrinological findings. A 66-year-old male patient with cirrhosis was hospitalized for liver transplantation. We suspected Chanarin-Dorfman Syndrome with ichthyosis, fatty liver, and syndromic facial features with bilateral ectropion, deafness, and malocclusion. We showed the lipid droplets in neutrophils called patognomonic Jordans' anomaly. Homozygous c.47+1 G>A mutation in the ABHD5 (NM_016006.6) gene were detected by clinical exome sequencing. Out of <160 CDS cases in the literature, this is the second eldest CDS patient and first with adrenal insufficiency, parathyroid lipoadenoma and atrophic pancreas. Clinicians should be aware of CDS as a rare cause of fatty liver. We recommend a blood smear and genetic analyses in patients with severe ichtiosis, ectropion, deafness and multiple endocrinolgic disorders.

Evaluation of rheumatoid arthritis and connective tissue disease-related interstitial lung disease with pulmonary physiologic test, HRCT, and patient-based measures of dyspnea and functional disability.

OBJECTIVES: We aim to investigate the relationship between pulmonary function and imaging parameters with symptom-related patient-reported outcome measures (PROs). METHOD: We included 65 patients of rheumatoid arthritis (RA) and connective tissue disease (CTD) with and without interstitial lung disease (ILD) into this cross-sectional study. We evaluated the relationship between FVC, DLco, and PROs and compared to HRCT findings. PROs included visual analogue scale for breathing, modified Borg scale, medical research council dyspnea scale, St. George's respiratory questionnaire (SGRQ), Leicester cough questionnaire, and Short Form 36 quality of life (SF-36 QoL). RESULTS: The mean age was 57.4 ± 9.7 and 61.9% (39/65) of patients had an established ILD. In RA-ILD group, SGRQ score was higher (p < 0.001) and SF-36 physical functioning score was lower (p = 0.02) than CTD-ILD group. In RA group, there was a significant correlation between FVC and SF-36 role functioning/physical score (r = 0.724, p = 0.012). In CTD group, SF-36 general health score was correlated with both FVC (r = 0.441, p = 0.045) and DLco (r = 0.485, p = 0.035), and also SF-36 physical functioning score was correlated with FVC (r = 0.441, p = 0.040). PROs were found to be similar between ILD and non-ILD patients. SF-36 QoL total and SGRQ outcomes were worse in non-ILD group. CONCLUSIONS: We concluded that PROs could be used to evaluate health-related quality of life (HRQoL) in RA- or CTD-related ILD. The physical health determinants of HRQoL are measurably worse in RA-ILD patients than in CTD patients. But, PROs may not be very helpful in differentiating patients with cough and/or shortness of breath due to ILD or non-ILD causes in RA/CTD. KEY POINTS: • HRQoL may be affected differently among specific subtypes of ILD. • PROs can be used to evaluate dyspnea and function of patients with RA- or CTD-related ILD but are not distinguished from patients with cough and/or shortness of breath due to non-ILD causes in RA/CTD.

Screening for hepatic fibrosis and steatosis in Turkish patients with type 2 diabetes mellitus: A transient elastography study.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease is highly prevalent in patients with type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the potential usefulness of transient elastography (TE), which is a technique that allows measuring both fibrosis and liver fat content simultaneously, as a screening tool for hepatic involvement in Turkish patients with T2DM. MATERIALS AND METHODS: We obtained liver stiffness measurements (LSMs, as a measure of fibrosis) and controlled attenuation parameter (CAP, as a marker of steatosis) in 124 (46 males and 78 females; mean body mass index (BMI): 33.2±6.6 kg/m2) Turkish patients with T2DM. The prevalence rates of overweight, obesity, and metabolic syndrome in our sample were 28.2%, 64.5%, and 77.4%, respectively. Probe-specific LSM cut-off values were used to define advanced fibrosis (>F3) and cirrhosis (F4) (M probe: F3=9.6-11.4 kPa, F4 >11.5 kPa and XL probe: F3=9.3-10.9 kPa, F4 >11.0 kPa). Mild, moderate, and severe steatosis were defined as CAP 222-232 dB/m, CAP 233-289 dB/m, and CAP >290 dB/m, respectively. RESULTS: Advanced fibrosis and cirrhosis were identified in 21 (16.9%) and 10 (8.0%) patients, respectively. TE-defined hepatic steatosis (CAP>222 dB/m) was detected in 117 (94.3%) patients. Mild, moderate, and severe steatosis were identified in 0, 29, and 88 patients, respectively. CONCLUSION: TE is a useful non-invasive imaging modality to screen for liver involvement in Turkish patients with T2DM. High rates of TE-defined fibrosis and steatosis in our sample reflect the presence of an elevated mean BMI.

Neurotoxic effects of AZT on developing and adult neurogenesis.

Azidothymidine (AZT) is a synthetic, chain-terminating nucleoside analog used to treat HIV-1 infection. While AZT is not actively transported across the blood brain barrier, it does accumulate at high levels in cerebrospinal fluid, and subsequently diffuses into the overlying parenchyma. Due to the close anatomical proximity of the neurogenic niches to the ventricular system, we hypothesize that diffusion from CSF exposes neural stem/progenitor cells and their progeny to biologically relevant levels of AZT sufficient to perturb normal cell functions. We employed in vitro and in vivo models of mouse neurogenesis in order to assess the effects of AZT on developing and adult neurogenesis. Using in vitro assays we show that AZT reduces the population expansion potential of neural stem/progenitor cells by inducing senescence. Additionally, in a model of in vitro neurogenesis AZT severely attenuates neuroblast production. These effects are mirrored in vivo by clinically-relevant animal models. We show that in utero AZT exposure perturbs both population expansion and neurogenesis among neural stem/progenitor cells. Additionally, a short-term AZT regimen in adult mice suppresses subependymal zone neurogenesis. These data reveal novel negative effects of AZT on neural stem cell biology. Given that the sequelae of HIV infection often include neurologic deficits-subsumed under AIDS Dementia Complex (Brew, 1999)-it is important to determine to what extent AZT negatively affects neurological function in ways that contribute to, or exacerbate, ADC in order to avoid attributing iatrogenic drug effects to the underlying disease process, and thereby skewing the risk/benefit analysis of AZT therapy.

Subventricular zone microglia possess a unique capacity for massive in vitro expansion.

Microglia, the resident immune cells of the brain, have recently been hypothesized to play a role both in neuronal diseases and age-related neurogenic decline, and are theorized to be modulators of adult neurogenesis. Current methods for the isolation of microglia from cultured primary brain tissue result in relatively poor yield, requiring a large tissue sample or multiple specimens to obtain a sufficient number of microglia for cell and molecular analysis. We report here a method for the repetitive isolation of microglia from established glial monolayer cultures from which it is possible to expand the initial population of microglia roughly 10,000-fold. The expanded population expresses appropriate microglial morphology and phenotype markers, and demonstrates functionally normal phagocytosis, thus providing a high-yield assay for the investigation and analysis of microglia from a single initial dissection of primary tissue. Furthermore, this massive expansion is limited to microglia derived from the subventricular zone as the fold expansion of isolatable microglia was found to be up to 20 times greater than cultures from other brain regions, indicating unique properties for this persistently neurogenic region.