Front Pharmacol. 2024 May 13;15:1423979. doi: 10.3389/fphar.2024.1423979. eCollection 2024.

NO ABSTRACT

PMID:38803436 | PMC:PMC11128889 | DOI:10.3389/fphar.2024.1423979

JAC Antimicrob Resist. 2024 May 27;6(3):dlae078. doi: 10.1093/jacamr/dlae078. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: This multicentre, observational, retrospective chart review study assessed ceftaroline fosamil treatment patterns and outcomes in adults hospitalized with community-acquired pneumonia (CAP) in usual care settings.

METHODS: Anonymized patient data were extracted from hospital records of adults with CAP who received ≥4 consecutive IV ceftaroline fosamil doses at sites in Brazil, Colombia, France, Greece, Italy, Russia and Spain.

RESULTS: The dataset included 185 patients (58.9% male; mean age 62.2 years), of whom 128 (69.2%) had severe CAP defined by CURB-65, PSI/PORT score or physician judgement. Streptococcus pneumoniae (n = 44; 23.8%) and Staphylococcus aureus [MSSA (n = 15) and MRSA (n = 14)] were the most frequently identified pathogens. Clinical response occurred in 151 (81.6%) patients overall, and in 104 (81.3%) severe CAP patients. Response within ≤4 and >4 days occurred in 79 (42.7%) and 62 (33.5%) patients (unknown, n = 10), respectively. Twenty (10.8%) patients required readmission within 30 days. Thirty-day all-cause mortality rates were 9.7% (n = 18) overall and 10.2% (n = 13) in severe CAP. In sensitivity analysis using ICU admission as a more objective marker of severe CAP (n = 75), clinical response and 30 day mortality occurred in 57 (76.0%) and 10 (13.3%) patients, respectively. Overall, clinical response to ceftaroline fosamil was associated with >60% shorter length of ICU stay (3.6 versus 9.2 days), and >30% lower hospital costs ($8449 versus $12 559) versus non-responders.

CONCLUSIONS: Ceftaroline fosamil was effective in treating adults with CAP, including severe CAP, in Europe and Latin America. Clinical response to ceftaroline fosamil was associated with reductions in healthcare resource use compared with non-responders.

PMID:38803385 | PMC:PMC11128847 | DOI:10.1093/jacamr/dlae078

Zhongguo Dang Dai Er Ke Za Zhi. 2024 May 15;26(5):506-511. doi: 10.7499/j.issn.1008-8830.2310080.

ABSTRACT

OBJECTIVES: To summarize the clinical characteristics and genetic variations in children with cystic fibrosis (CF) primarily presenting with pseudo-Bartter syndrome (CF-PBS), with the aim to enhance understanding of this disorder.

METHODS: A retrospective analysis was performed on the clinical data of three children who were diagnosed with CF-PBS in Hunan Children's Hospital from January 2018 to August 2023, and a literature review was performed.

RESULTS: All three children had the onset of the disease in infancy. Tests after admission showed hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis, and genetic testing showed the presence of compound heterozygous mutation in the CFTR gene. All three children were diagnosed with CF. Literature review obtained 33 Chinese children with CF-PBS, with an age of onset of 1-36 months and an age of diagnosis of 3-144 months. Among these children, there were 29 children with recurrent respiratory infection or persistent pneumonia (88%), 26 with malnutrition (79%), 23 with developmental retardation (70%), and 18 with pancreatitis or extrapancreatic insufficiency (55%). Genetic testing showed that c.2909G>A was the most common mutation site of the CFTR gene, with a frequency of allelic variation of 23% (15/66).

CONCLUSIONS: CF may have no typical respiratory symptoms in the early stage. The possibility of CF-PBS should be considered for infants with recurrent hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis, especially those with malnutrition and developmental retardation. CFTR genetic testing should be performed as soon as possible to help with the diagnosis of CF.

PMID:38802912 | DOI:10.7499/j.issn.1008-8830.2310080

Clin Immunol. 2024 May 25:110265. doi: 10.1016/j.clim.2024.110265. Online ahead of print.

ABSTRACT

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus spp. ABPA diagnosis may be challenging due to its non-specific presentation. Standard ABPA treatment consists of systemic corticosteroids and antifungal agents. Mepolizumab, a monoclonal antibody against interleukin-5 seems to be a promising treatment for ABPA. Data about ABPA following lung transplantation (LuTx) are scarce. LuTx recipients are at higher risk for adverse effects of ABPA treatment compared to the general population. Here we present a case of a LuTx recipient who was successfully treated with mepolizumab for ABPA following LuTx. Prolonged administration of high dose prednisone was thus avoided. To our knowledge, this is the first case describing mepolizumab administration following LuTx. Mepolizumab seems particularly attractive as a corticosteroid-sparing agent or as an alternative option to antifungal treatments, because of its excellent safety profile and low risk of drug interactions.

PMID:38801928 | DOI:10.1016/j.clim.2024.110265

Cureus. 2024 Apr 25;16(4):e59018. doi: 10.7759/cureus.59018. eCollection 2024 Apr.

ABSTRACT

Introduction Previous studies have demonstrated an increased incidence of gastrointestinal (GI) pathologies, specifically celiac disease (CD) and eosinophilic esophagitis (EoE), in patients with cystic fibrosis (CF). However, there is minimal data available regarding endoscopic findings in pediatric patients with CF and GI mucosal disease. Methods A retrospective chart review was performed on patients with CF under 18 years of age who underwent esophagogastroduodenoscopy (EGD) or colonoscopy with biopsy over a 15-year period at our institution. Patient characteristics including assigned sex at birth, CF genetic mutations (if identified), and cystic fibrosis transmembrane conductance regulator (CFTR) modulator use were recorded. Data obtained at the time of biopsy included body mass index (BMI), indication for the procedure, exocrine pancreatic status, visual endoscopic findings, and histologic findings. Results A total of 72 patients with CF were included in the study. 24% (n=17) were found to have abnormal endoscopic biopsy results. EoE (13% of all patients, n=9) and CD (6% of all patients, n=4) were the most common GI diagnoses present on endoscopic biopsy. All 3 patients taking CFTR modulator medications at the time of endoscopy had normal biopsy results. Of the 17 patients found to have abnormal pathology results, 14 (82%) were taking proton-pump inhibitor (PPI) medication at the time of endoscopy. Conclusion This study highlights the probable increased frequency of GI disease in the pediatric CF population. These findings underscore the importance of maintaining a broad differential diagnosis while considering utilization of endoscopy with biopsy in pediatric patients with CF who have GI symptoms.

PMID:38800303 | PMC:PMC11127755 | DOI:10.7759/cureus.59018

Sleep Med X. 2024 Apr 18;7:100111. doi: 10.1016/j.sleepx.2024.100111. eCollection 2024 Dec.

ABSTRACT

There are significant variations in practice regarding the use of sleep studies in children with symptoms of sleep disordered breathing (SDB) prior to adenotonsillectomy. Current UK guidance recommends the selective use of sleep studies to confirm a diagnosis of obstructive sleep apnoea (OSA) when there is diagnostic uncertainty, in children with comorbidities, or to assess perioperative risk when severe OSA is suspected. We have developed a novel paediatric sleep service over the past decade based on the routine use of multi-channel sleep studies (MCSS) before adenotonsillectomy. We present the results of a prospective evaluation assessing the impact of our service on treatment outcomes. We conducted a prospective service evaluation of 49 children with SDB seen between July 2021 and August 2022. We used medical records and a sleep study database to determine treatment outcomes. Otolaryngologists completed a questionnaire before each multi-channel sleep study to help evaluate the impact of sleep study findings on surgical decision making. Questionnaire responses before MCSS showed that clinicians thought 66 % of children were 'likely', 'very likely' or 'definitely' would require surgery but only 54 % of children underwent surgery following their sleep study. We estimate that the use of MCSS was associated with a 21 % reduction in children undergoing surgery in this small sample. We conclude that our use of MCSS facilitates conservative management, allowing a significant reduction in the number of children with SDB undergoing surgery, but further validation of MCSS against polysomnography is required.

PMID:38800098 | PMC:PMC11127274 | DOI:10.1016/j.sleepx.2024.100111

Cell Stress. 2024 Apr 30;8:51-55. doi: 10.15698/cst2024.04.295. eCollection 2024.

ABSTRACT

In a recent issue in Nature Cell Biology, Sung Min Son et al. unveil a novel layer in the regulation of the mTORC1/autophagy axis by EP300 which can undergo nucleocytoplasmic shuttling in response to alterations in nutrient availability. The study highlights that, in Hutchinson-Gilford progeria syndrome, overabundant cytoplasmic EP300 results in mTORC1 hyperactivation and impaired autophagy, potentially contributing to premature and accelerated aging.

PMID:38800095 | PMC:PMC11118783 | DOI:10.15698/cst2024.04.295

bioRxiv [Preprint]. 2024 May 14:2024.05.10.593624. doi: 10.1101/2024.05.10.593624.

ABSTRACT

Dysregulated neutrophil recruitment drives many pulmonary diseases, but most preclinical screening methods are unsuited to evaluate pulmonary neutrophilia, limiting progress towards therapeutics. Namely, high throughput therapeutic screening systems typically exclude critical neutrophilic pathophysiology, including blood-to-lung recruitment, dysfunctional activation, and resulting impacts on the air-blood barrier. To meet the conflicting demands of physiological complexity and high throughput, we developed an assay of 96-well Leukocyte recruitment in an Air-Blood Barrier Array (L-ABBA-96) that enables in vivo -like neutrophil recruitment compatible with downstream phenotyping by automated flow cytometry. We modeled acute respiratory distress syndrome (ARDS) with neutrophil recruitment to 20 ng/mL epithelial-side interleukin 8 (IL-8) and found a dose dependent reduction in recruitment with physiologic doses of baricitinib, a JAK1/2 inhibitor recently FDA-approved for severe COVID-19 ARDS. Additionally, neutrophil recruitment to patient-derived cystic fibrosis sputum supernatant induced disease-mimetic recruitment and activation of healthy donor neutrophils and upregulated endothelial e-selectin. Compared to 24-well assays, the L-ABBA-96 reduces required patient sample volumes by 25 times per well and quadruples throughput per plate. Compared to microfluidic assays, the L-ABBA-96 recruits two orders of magnitude more neutrophils per well, enabling downstream flow cytometry and other standard biochemical assays. This novel pairing of high-throughput in vitro modeling of organ-level lung function with parallel high-throughput leukocyte phenotyping substantially advances opportunities for pathophysiological studies, personalized medicine, and drug testing applications.

PMID:38798413 | PMC:PMC11118313 | DOI:10.1101/2024.05.10.593624

Front Pediatr. 2024 May 10;12:1393193. doi: 10.3389/fped.2024.1393193. eCollection 2024.

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). In 1949, it's been identified as a monogenic disease and was thought to primarily affect individuals of Northern European descent. It was the most prevalent autosomal recessive disease that shortens life. With the availability of multiple testing methodologies nowadays, there is a chance to create novel and enhanced treatment options. Even in the absence of a high sweat chloride test (SCT) result, the discovery of two causal mutations is diagnostic for cystic fibrosis (CF). For a CF diagnosis, however, at least two positive E sweat chloride tests are still required. In order to achieve early and active intervention to manage cystic fibrosis (CF) and its comorbidities, treatment regimens for pediatric patients should be evaluated, improved, and closely monitored. New developments in the treatment of cystic fibrosis (CF) have led to the development of medications derived from molecules that target the pathogenetic pathway of the illness. These options are very efficient and allow pediatric patients to receive individualized care. However, in order to better direct patient care and enhance patient outcomes, it is crucial to research uncommon CF mutations, which can provide crucial information about the prognosis of the disease and the relationships between genotype and phenotype. To ensure the success of creating novel, safer, and more efficient treatment approaches, a deeper understanding of the pathogeny of the illness is required. In the age of customized medicine, genetic research will be essential to improving patient care and quality of life for those with uncommon mutations.

PMID:38798310 | PMC:PMC11116730 | DOI:10.3389/fped.2024.1393193

Pulm Pharmacol Ther. 2024 May 24:102301. doi: 10.1016/j.pupt.2024.102301. Online ahead of print.

ABSTRACT

Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90% of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance.

PMID:38797221 | DOI:10.1016/j.pupt.2024.102301

Curr Probl Pediatr Adolesc Health Care. 2024 May 25:101638. doi: 10.1016/j.cppeds.2024.101638. Online ahead of print.

NO ABSTRACT

PMID:38797571 | DOI:10.1016/j.cppeds.2024.101638

Plants (Basel). 2024 May 18;13(10):1412. doi: 10.3390/plants13101412.

ABSTRACT

Pseudomonas aeruginosa is an opportunistic pathogen that is especially dominant in people with cystic fibrosis; the drug resistance expressed by this pathogen and its capacity for adaptation poses a significant challenge to its treatment and control, thereby increasing morbidity and mortality rates globally. In this sense, the search for new treatment alternatives is imminent today, with products of plant origin being an excellent alternative for use. The objective of this research was to evaluate the antibacterial and antibiofilm potential and to explore the possible effect of ethanolic extracts from the wood and bark of Duguetia vallicola on the cell membrane. Microdilution assays showed the inhibition of bacterial growth by more than 50%, with the lowest concentration (62.5 μg/mL) of both extracts evaluated. Furthermore, we report the ability of both extracts to inhibit mature biofilms, with inhibition percentages between 48.4% and 93.7%. Intracellular material leakage experiments (260/280 nm), extracellular pH measurements, and fluorescence microscopy with acridine orange (AO) and ethidium bromide (EB) showed cell membrane damage. This indicates that the antibacterial action of ethanolic extracts of D. vallicola is associated with damage to the integrity of the cell membrane and consequent death of these pathogens. These results serve as a reference for future studies in establishing the mechanisms of action of these extracts.

PMID:38794482 | DOI:10.3390/plants13101412

Pharmaceutics. 2024 May 11;16(5):648. doi: 10.3390/pharmaceutics16050648.

ABSTRACT

Inhaled ciprofloxacin (CFX) has been investigated as a treatment for lower respiratory tract infections (LRTIs) associated with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis. The challenges in CFX effectiveness for LRTI treatment include poor aqueous solubility and therapy resistance. CFX dry powder for inhalation (DPI) formulations were well-tolerated, showing a remarkable decline in overall bacterial burden compared to a placebo in bronchiectasis patients. Recent research using an inhalable powder combining Pseudomonas phage PEV20 with CFX exhibited a substantial reduction in bacterial density in mouse lungs infected with clinical P. aeruginosa strains and reduced inflammation. Currently, studies suggest that elevated biosynthesis of fatty acids could serve as a potential biomarker for detecting CFX resistance in LRTIs. Furthermore, inhaled CFX has successfully addressed various challenges associated with traditional CFX, including the incapacity to eliminate the pathogen, the recurrence of colonization, and the development of resistance. However, further exploration is needed to address three key unresolved issues: identifying the right patient group, determining the optimal treatment duration, and accurately assessing the risk of antibiotic resistance, with additional multicenter randomized controlled trials suggested to tackle these challenges. Importantly, future investigations will focus on the effectiveness of CFX DPI in bronchiectasis and COPD, aiming to differentiate prognoses between these two conditions. This review underscores the importance of CFX inhalable formulations against LRTIs in preclinical and clinical sectors, their challenges, recent advancements, and future perspectives.

PMID:38794310 | DOI:10.3390/pharmaceutics16050648

Life (Basel). 2024 Apr 27;14(5):565. doi: 10.3390/life14050565.

ABSTRACT

Calcitonin gene-related peptide (CGRP) has long been implicated in both the physiology and pathophysiology of the respiratory tract. The objective of our study was to determine the serum concentration of alpha CGRP (αCGRP) in cystic fibrosis (CF) that arises from mutations in the gene responsible for encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Currently, there are not many data in the literature about the role of CGRP in CF. The serum level of αCGRP was estimated using the enzyme-linked immunosorbent assay among 64 patients with CF and 31 healthy controls. The αCGRP concentration in the CF group was 62.51 ± 15.45 pg/mL, while in the control group it was 47.43 ± 8.06 pg/mL (p < 0.001). We also compared the level of αCGRP in CF patients according to the type of CFTR mutation. Homozygotes for ΔF508 had higher αCGRP levels than heterozygotes (67.9 ± 10.2 vs. 54.5 ± 18.3 pg/mL, p < 0.01). The level of this neuropeptide was statistically higher in patients with severe disease than in those with mild CF (p = 0.003) when patients were divided into three groups by spirometry results. αCGRP concentration was not correlated with age, sex, clinical parameters, and pulmonary function test results in the study participants. The results of our study suggest a significant increase in the concentration of αCGRP in the serum of patients with CF compared to the control group. This observation opens interesting possibilities for understanding the role of αCGRP in the context of CF pathophysiology.

PMID:38792587 | DOI:10.3390/life14050565

J Clin Med. 2024 May 20;13(10):3013. doi: 10.3390/jcm13103013.

ABSTRACT

Background: Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV1) (+440 mL at 36 months, p < 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Conclusions: Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab's long-term safety.

PMID:38792553 | DOI:10.3390/jcm13103013

Int J Mol Sci. 2024 May 16;25(10):5416. doi: 10.3390/ijms25105416.

ABSTRACT

Previous omics research in patients with complex congenital heart disease and single-ventricle circulation (irrespective of the stage of palliative repair) revealed alterations in cardiac and systemic metabolism, inter alia abnormalities in energy metabolism, and inflammation, oxidative stress or endothelial dysfunction. We employed an affinity-proteomics approach focused on cell surface markers, cytokines, and chemokines in the serum of 20 adult Fontan patients with a good functioning systemic left ventricle, and we 20 matched controls to reveal any specific processes on a cellular level. Analysis of 349 proteins revealed 4 altered protein levels related to chronic inflammation, with elevated levels of syndecan-1 and glycophorin-A, as well as decreased levels of leukemia inhibitory factor and nerve growth factor-ß in Fontan patients compared to controls. All in all, this means that Fontan circulation carries specific physiological and metabolic instabilities, including chronic inflammation, oxidative stress imbalance, and consequently, possible damage to cell structure and alterations in translational pathways. A combination of proteomics-based biomarkers and the traditional biomarkers (uric acid, γGT, and cholesterol) performed best in classification (patient vs. control). A metabolism- and signaling-based approach may be helpful for a better understanding of Fontan (patho-)physiology. Syndecan-1, glycophorin-A, leukemia inhibitory factor, and nerve growth factor-ß, especially in combination with uric acid, γGT, and cholesterol, might be interesting candidate parameters to complement traditional diagnostic imaging tools and the determination of traditional biomarkers, yielding a better understanding of the development of comorbidities in Fontan patients, and they may play a future role in the identification of targets to mitigate inflammation and comorbidities in Fontan patients.

PMID:38791454 | DOI:10.3390/ijms25105416

Biomedicines. 2024 May 9;12(5):1047. doi: 10.3390/biomedicines12051047.

ABSTRACT

Different factors, not limited to the lung, influence the progression of ILDs. A "treatable trait" strategy was recently proposed for ILD patients as a precision model of care to improve outcomes. However, no data have been published so far on the prevalence of TTs in ILD. A prospective, observational, cohort study was conducted within the ILD Program at the IRCCS Humanitas Research Hospital (Milan, Italy) between November 2021 and November 2023. TTs were selected according to recent literature and assigned during multidisciplinary discussion (MDD) to one of the following categories: pulmonary, etiological, comorbidities, and lifestyle. Patients were further divided into four groups according to their post-MDD diagnosis: idiopathic ILD, sarcoidosis, connective tissue disease-ILD, and other ILD. The primary study outcome was the prevalence of each TT in the study population. A total of 116 patients with ILD [63.9% male; median (IQR) age: 69 (54-78) years] were included in the study. All the TTs identified in the literature were found in our cohort, except for intractable chronic cough. We also recognized differences in TTs across the ILD groups, with less TTs in patients with sarcoidosis. This analysis provides the first ancillary characterization of TTs in ILD patients in a real setting to date.

PMID:38791009 | DOI:10.3390/biomedicines12051047

Biomedicines. 2024 Apr 27;12(5):969. doi: 10.3390/biomedicines12050969.

ABSTRACT

Dysregulation of innate immunity is deeply involved in infectious and autoimmune diseases. For a better understanding of pathogenesis and improved management of these diseases, it is of vital importance to implement convenient monitoring of systemic innate immunity. Built upon our previous works on the host transcriptional response to infection in peripheral blood, we proposed a 2D gene model for the simultaneous assessment of two major components of systemic innate immunity, including VirSig as the signature of the host response to viral infection and BacSig as the signature of the host response to bacterial infection. The revelation of dysregulation in innate immunity by this 2D gene model was demonstrated with a wide variety of transcriptome datasets. In acute infection, distinctive patterns of VirSig and BacSig activation were observed in viral and bacterial infection. In comparison, both signatures were restricted to a defined range in the vast majority of healthy adults, regardless of age. In addition, BacSig showed significant elevation during pregnancy and an upward trend during development. In tuberculosis (TB), elevation of BacSig and VirSig was observed in a significant portion of active TB patients, and abnormal BacSig was also associated with a longer treatment course. In cystic fibrosis (CF), abnormal BacSig was observed in a subset of patients, and no overall change in BacSig abnormality was observed after the drug treatment. In systemic sclerosis-associated interstitial lung disease (SSc-ILD), significant elevation of VirSig and BacSig was observed in some patients, and treatment with a drug led to the further deviation of BacSig from the control level. In systemic lupus erythematosus (SLE), positivity for the anti-Ro autoantibody was associated with significant elevation of VirSig in SLE patients, and the additive effect of VirSig/BacSig activation was also observed in SLE patients during pregnancy. Overall, these data demonstrated that the 2D gene model can be used to assess systemic innate immunity in health and disease, with the potential clinical applications including patient stratification, prescription of antibiotics, understanding of pathogenesis, and longitudinal monitoring of treatment response.

PMID:38790931 | DOI:10.3390/biomedicines12050969

Children (Basel). 2024 Apr 24;11(5):507. doi: 10.3390/children11050507.

ABSTRACT

Psychosocial consequences of false-positive results following newborn bloodspot screening have been identified as a potential risk to this highly successful public health initiative. A scoping review was undertaken in October 2023 underpinned by the Arksey and O'Malley framework. Twenty-four papers were included in the review, many of which focused on cystic fibrosis. The results indicated that impact of false-positive results is variable; some studies suggest false-positive results have the potential to result in negative sequelae including increased stress and changes in parental perceptions of their child, while others suggest these impacts are transient and, in some instances, may even lead to positive outcomes. Further evidence is needed to ensure the representation of other conditions included in newborn bloodspot screening and to support strategies to overcome potential negative sequela.

PMID:38790502 | DOI:10.3390/children11050507

Children (Basel). 2024 Apr 23;11(5):505. doi: 10.3390/children11050505.

ABSTRACT

BACKGROUND: Infants presenting with unexpected pneumoperitoneum upon abdominal X-ray, indicating a gastrointestinal perforation (GIP), have a surgical emergency with potential morbidity and mortality. Preoperative determination of the location of perforation is challenging but will aid the surgeon in optimizing the surgical strategy, as colon perforations are more challenging than small bowel perforations. Therefore, the aim of this study is to provide an overview of preoperative patient characteristics, determine the differences between the small bowel and colon, and determine underlying causes in a cohort of infants with unexpected GIP.

METHODS: All infants (age ≤ 6 months) who presented at our center with unexpected pneumoperitoneum (no signs of pneumatosis before) undergoing surgery between 1996 and 2024 were retrospectively included. The differences between the location of perforation were analyzed using chi-squared and t-tests. Bonferroni correction was used to adjust for multiple tests.

RESULTS: In total, 51 infants presented with unexpected pneumoperitoneum at our center, predominantly male (N = 36/51) and premature (N = 40/51). Among them, twenty-six had small bowel, twenty-two colon, and three stomach perforations. Prematurity (p = 0.001), birthweight < 1000 g (p = 0.001), respiratory support (p = 0.001), and lower median arterial pH levels (p = 0.001) were more present in patients with small bowel perforation compared with colon perforations. Pneumatosis intestinalis was more present in patients with colon perforation (p = 0.004). All patients with Hirschsprung disease and cystic fibrosis had colon perforation. The final diagnoses were mainly focal intestinal perforations (N = 27/51) and necrotizing enterocolitis (N = 9/51).

CONCLUSIONS: Infants with unexpected GIP, birthweight < 1000 g, and prematurity have more risk for small bowel perforation. In case of colon perforation, additional screening (for Hirschsprung and cystic fibrosis) should be considered.

PMID:38790500 | DOI:10.3390/children11050505