What Is Known and Objective
Carbaglu® or N‐carbamylglutamate (NCG) is not recommended for administration in a vehicle other than water. We aim to report the use of breast milk (BM) as an alternative ...vehicle in a neonate rejecting NCG diluted in water.
Case Summary
A neonate diagnosed with methylmalonic acidemia presented symptomatology of acidemia and hyperammonemia. After the patient refused oral NCG administration, a dissolution test was conducted in BM showing correct dissolution. The NCG‐BM solution was tolerated and plasma ammonium concentrations remained within range in subsequent analytical controls.
What Is New and Conclusion
BM as a vehicle for NCG is a safe and effective option for patients who refuse suspension in water and could lead to better treatment compliance in paediatric patients.
We aim to report the use of breast milk (BM) as an alternative vehicle in a neonate with methylmalonic acidemia rejecting carglumic acid (NCG) diluted in water. The patient presented symptomatic acidemia and hyperammonemia and after refusal of oral NCG administration, the clinician consulted the Pharmacy Department for advice. Data sheet of NCG does not recommend administration in other vehicle than water. Consequently, a dissolution test was conducted in BM showing correct dissolution. The solution was well tolerated, and plasma ammonium concentrations remained within range in subsequent analytical controls.
Few genetic polymorphisms predict early response to anti-TNF drugs in inflammatory bowel disease (IBD), and even fewer have been identified in the pediatric population. However, it would be of ...considerable clinical interest to identify and validate genetic biomarkers of long-term response. Therefore, the aim of the study was to analyze the usefulness of biomarkers of response to anti-TNFs in pediatric IBD (pIBD) as long-term biomarkers and to find differences by type of IBD and type of anti-TNF drug. The study population comprised 340 children diagnosed with IBD who were treated with infliximab or adalimumab. Genotyping of 9 selected SNPs for their association with early response and/or immunogenicity to anti-TNFs was performed using real-time PCR. Variants C rs10508884 (CXCL12), A rs2241880 (ATG16L1), and T rs6100556 (PHACTR3) (p value 0.049; p value 0.03; p value 0.031) were associated with worse long-term response to anti-TNFs in pIBD. DNA variants specific to disease type and anti-TNF type were identified in the pediatric population. Genotyping of these genetic variants before initiation of anti-TNFs would enable, if validated in a prospective cohort, the identification of pediatric patients who are long-term responders to this therapy.
Display omitted
The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association ...between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab.
Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to ...identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment.
We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs.
Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10–7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3).
We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.
Display omitted
•Baseline gene expression in blood associates with the response to anti-TNF drugs.•RNA-seq identified 102 genes associated with the response to anti-TNF drugs.•PRTN3, LTF, LCN, and CEACAM8 are overexpressed in responder children.•Cancer-related genes impact the response to anti-TNF drugs.•Overexpressed genes in responder children directly link to TNF processes.
Objectives
Mastitis is mainly caused by Gram-positive bacteria and usually involves treatment with beta-lactam antibiotics and clindamycin. Oxazolidinones show good results in the treatment of skin ...and soft tissue infections (SSTIs) due to its pharmacokinetic characteristics. We aimed to describe clinical characteristics and outcomes of patients who received oxazolidinones for the treatment of SSTIs of the mammary tissue.
Methods
Retrospective single-centre study of patients with a diagnosis of breast infection who received treatment with oxazolidinones as initial or salvage therapy between September 2016 and November 2022. Patients were identified through the pharmacy database. The primary outcome was clinical cure.
Results
Twenty-nine patients received oxazolidinones: 27 received linezolid and 2 tedizolid. Median age was 41 years (IQR 31.0–56.5) and 28 patients were female. Ten patients (35%) had a history of breast cancer, while three (10%) had an immunosuppressive condition. Microbiological isolation was obtained in 24 individuals (83%). Predominant isolations were methicillin-resistant
Staphylococcus aureus
(8, 28%) and methicillin-susceptible
S. aureus
(7, 24%). Twenty-four patients (83%) received oxazolidinones as a salvage therapy, with a median duration of 14 days (IQR 10–17). Clinical cure was achieved in 24 patients (83%), while 4 relapsed after a median of 15 days (IQR 4–34). One was lost to follow-up. Three patients (10%) were taking selective serotonin reuptake inhibitors, and one of them concurrently received linezolid for 4 days with no adverse events recorded. Cytopenia during treatment was observed in 2/12 individuals. Oxazolidinones allowed hospital discharge in 11/13 hospitalized patients.
Conclusions
Oxazolidinones could be considered as an alternative for treating breast infections.
Identifying ILA patients with progressive disease or at risk of dying is of utmost clinical importance. ...we designed a study to identify and characterize patients with ILA within the Enhanced ...Recovery After Surgery (ERAS®) program. ...this study describes the real-world evidence of ILA in major abdominal surgery. ILA patients have a higher risk of mortality. ...identifying ILA patients has essential prognostic value.
OBJECTIVEThe physical compatibility of atosiban and selected drugs during simulated Y-site administration was evaluated. We also searched for any compatibility predictions regarding its ...physicochemical properties. STUDY DESIGNTest admixtures were prepared by mixing 5 mL of each study drug solution with 5 mL of atosiban solution in a 1:1 ratio to simulate Y-site infusion. Assessments were made immediately after mixing (baseline), and at 0.5, 1, and 3 h. Visual incompatibility was defined as a presence of haze or any visible particulate matter, gas formation, or colour change. Turbidity and pH variation of the admixtures were also assessed using instrumental methods. RESULTSNone of the admixtures used with atosiban exhibited visual changes and no incompatibility regarding instrumental methods were observed, because no admixture had an increase of 0.5 nephelometric turbidity units, and no pH change was above one unit when compared to baseline. However, the pH of ampicillin and omeprazole admixtures fell outside of the atosiban stability range. CONCLUSIONSOur study showed no physical incompatibility between atosiban and the test drugs in terms of visual changes or nephelometric and pH measurements. However, we recommend against atosiban and ampicillin or omeprazole coadministration until complementary compatibility studies are performed.
The PERSEIDS study aimed to estimate incidence/prevalence of interstitial lung diseases (ILDs), fibrosing interstitial lung diseases (F-ILDs), idiopathic pulmonary fibrosis (IPF), systemic ...sclerosis-associated ILD (SSc-ILD), other non-IPF F-ILDs and their progressive-fibrosing (PF) forms in six European countries, as current data are scarce. This retrospective, two-phase study used aggregate data (2014-2018). In Phase 1, incident/prevalent cases of ILDs above were identified from clinical databases through an algorithm based on codes/keywords, and incidence/prevalence was estimated. For non-IPF F-ILDs, the relative percentage of subtypes was also determined. In Phase 2, a subset of non-IPF F-ILD cases was manually reviewed to determine the percentage of PF behaviour and usual interstitial pneumonia-like (UIP-like) pattern. A weighted mean percentage of progression was calculated for each country and used to extrapolate incidence/prevalence of progressive-fibrosing ILDs (PF-ILDs). In 2018, incidence/10
person-years ranged between 9.4 and 83.6 (ILDs), 7.7 and 76.2 (F-ILDs), 0.4 and 10.3 (IPF), 6.6 and 71.7 (non-IPF F-ILDs), and 0.3 and 1.5 (SSc-ILD); and prevalence/10
persons ranged between 33.6 and 247.4 (ILDs), 26.7 and 236.8 (F-ILDs), 2.8 and 31.0 (IPF), 22.3 and 205.8 (non-IPF F-ILDs), and 1.4 and 10.1 (SSc-ILD). Among non-IPF F-ILDs, sarcoidosis was the most frequent subtype. PF behaviour and UIP-like pattern were present in a third of non-IPF F-ILD cases each and hypersensitivity pneumonitis showed the highest percentage of progressive behaviour. Incidence of PF-ILDs ranged between 2.1 and 14.5/10
person-years, and prevalence between 6.9 and 78.0/10
persons. To our knowledge, PERSEIDS is the first study assessing incidence, prevalence and rate of progression of ILDs across several European countries. Still below the threshold for orphan diseases, the estimates obtained were higher and more variable than reported in previous studies, but differences in study design/population must be considered.
Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers ...that predict early response to anti-TNF drugs in pediatric patients with IBD.
An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR.
Genes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or <-0.6 and
value < 0.05). After validation,
,
, and
were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively,
value < 0.05).
Expression of the
,
, and
genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.
PDF
