Long-term lung function follow-up of preterm infants less than 32 weeks of gestational age.

BACKGROUND: Preterm infants, particularly those with bronchopulmonary dysplasia (BPD), are at risk of lung development problems. Over the last decades, lung protective strategies have been used, decreasing the risk of chronic lung disease. OBJECTIVE: To evaluate the pulmonary function test (PFT) of preterm infants born after the introduction of lung protective strategies and to assess perinatal determinants of impaired lung function in this population. METHODS: A prospective, observational, single-center study was conducted in the neonatal unit of a high-complexity hospital. The study included newborns with less than 32 weeks gestational age born between 2012 and 2014, who were followed up until they reach school age. For the main outcome, two groups were stablished: no BPD or grade 1 BPD (no BPD/1) and grade 2 or 3 BPD (BPD 2/3). RESULTS: Out of 327 patients, 116 were included. BPD was diagnosed in 49.1% (47), with 50.9% (29) classified as grade 1, 35.1% (20) as grade 2, and 14.0% (8) as grade 3. Mean age at PFT was 8.59 years (SD 0.90). Mean FEV1% was 95.36% (SD 13.21) and FEV1 z-score -0.36 (SD 1.12); FVC% 97.53% (SD 12.59) and FVC z-score -0.20 (SD 1.06); FEV1/FVC ratio 85.84% (SD 8.34) and z-score -0.24 (SD 1.34). When comparing patients with no BPD/1 and BPD 2/3, we observed differences in all pulmonary function parameters, which persisted after adjusting for gestational age. No differences in PFT were observed between patients without BPD and those with grade 1 BPD. Most patients (76.7%, 89) had normal spirometry pattern, with obstructive pattern observed in 12.9% (15), restrictive pattern in 9.5% (11), and mixed pattern in 0.9% (1) of patients. CONCLUSION: Preterm infants with BPD 2/3 showed a decrease in all pulmonary function parameters compared to preterm infants with no BPD/1; an effect that was independent of gestational age. Among patients with BPD who had an altered PFT pattern, the most common pattern was obstructive, followed by restrictive and then, mixed.

Effect of Donated Premature Milk in the Prevention of Bronchopulmonary Dysplasia.

INTRODUCTION: Breastfeeding is one of the strategies that has been shown to be effective in preventing severe forms of bronchopulmonary dysplasia (BPD). When mother's own milk (MOM) is not available, pasteurized donor milk (DM) is the best alternative. However, the evidence is inconclusive on the difference in the incidence of bronchopulmonary dysplasia (BPD) between patients fed MOM and those fed with DM. As standard DM is usually mature pooled milk donated by mothers who have delivered their babies at term, the potential benefits of preterm milk may be lost. MATERIALS AND METHODS: An observational, retrospective, single-center study was conducted in the neonatology department of a high-complexity hospital. The study included newborns <32 weeks of gestational age born between January 2020 and December 2022. When supplemental milk was needed, non-pooled preterm pasteurized donor milk (PDM) matched for gestational age and moment of lactation was used in this study, classifying preterm infants in two groups: mainly MOM (>50% of the milk) or mainly PDM (>50% of the milk). Two groups were established: those who received >50% MOM and those who received >50% PDM. They were also classified according to the diagnosis of DBP: one group included no BPD or grade 1 BPD (noBPD/1), while the other included grade 2 or 3 BPD (BPD 2-3). The objectives of this study were, firstly, to evaluate the incidence of BPD 2-3 among patients who predominantly received PDM versus MOM. Secondly, to analyze differences in the type of human milk received and its nutritional components, as well as to study the growth in patients with or without BPD. RESULTS: One hundred ninety-nine patients were included in the study. A comparison of noBPD/1 versus BPD 2-3 groups between those receiving mainly MOM versus PDM showed no significant differences (19% vs. 20%, p 0.95). PDM colostrum in BPD 2-3 compared to noBPD/1 was higher in protein content (2.24 g/100 mL (SD 0.37) vs. 2.02 g/100 mL (SD 0.29) p < 0.01), although the statistical significance decreased after adjustment for gestational age and birth weight z-score (OR 3.53 (0.86-14.51)). No differences were found in the macronutrients in the mature milk of patients feeding more than 50% PDM in both study groups. Growth of BPD 2-3 showed a greater decrease in the difference in z-scores for height at birth and at discharge compared to noBPD/1 (-1.64 vs. -0.43, p 0.03). CONCLUSIONS: The use of mainly MOM or PDM demonstrates a similar incidence of noBPD/1 or BPD 2-3. Non-pooled and matched by gestational age and time of lactation preterm donor milk can probably be an alternative when mother's own milk is not available, with a similar protective effect in the prevention of severe BPD.

Genotoxicity and heating Performance of VxFe3-xO4 nanoparticles in Health applications.

The applications of magnetic nanoparticles (MNPs) as biocatalysts in different biomedical areas have been evolved very recently. One of the main challenges in this field is to design affective MNPs surfaces with catalytically active atomic centres, while producing minimal toxicological side effects on the hosting cell or tissues. MNPs of vanadium spinel ferrite (VFe2O4) are a promising material for mimicking the action of natural enzymes in degrading harmful substrates due to the presence of active V5+ centres. However, the toxicity of this material has not been yet studied in detail enough to grant biomedical safety. In this work, we have extensively measured the structural, compositional, and magnetic properties of a series of VxFe3-xO4 spinel ferrite MNPs to assess the surface composition and oxidation state of V atoms, and also performed systematic and extensive in vitro cytotoxicity and genotoxicity testing required to assess their safety in potential clinical applications. We could establish the presence of V5+ at the particle surface even in water-based colloidal samples at pH 7, as well as different amounts of V2+ and V3+ substitution at the A and B sites of the spinel structure. All samples showed large heating efficiency with Specific Loss Power values up to 400 W/g (H0 = 30 kA/m; f = 700 kHz). Samples analysed for safety in human hepatocellular carcinoma (HepG2) cell line with up to 24h of exposure showed that these MNPs did not induce major genomic abnormalities such as micronuclei, nuclear buds, or nucleoplasmic bridges (MNIs, NBUDs, and NPBs), nor did they cause DNA double-strand breaks (DSBs) or aneugenic effects-types of damage considered most harmful to cellular genetic material. The present study is an essential step towards the use of these type of nanomaterials in any biomedical or clinical application.

Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study.

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

Evaluación renal y multiorgánica en el paciente con encefalopatía hipóxico-isquémica / Renal and multiorgan evaluation in infants with post-asphyxial hypoxic-ischaemic encephalopathy

Resumen Introducción: La encefalopatía hipóxico-isquémica (EHI) moderada-grave secundaria a asfixia perinatal puede afectar a cualquier órgano, empeorando el pronóstico. Objetivo: Evaluar la afectación renal y multiorgánica de estos pacientes. Material y método: Se incluyó a recién nacidos > 35 semanas con EHI moderada-grave tratados con hipotermia activa entre 2010 y 2020. Se evaluó la creatinina en tres periodos: 48-72 horas de vida, entre el 3.o y 7.o día de vida y del 7.o al 28.o día de vida. Resultados: Se incluyeron 135 pacientes: 112 con EHI moderada y 23 con EHI grave. Al comparar ambos grupos, se obtuvieron diferencias significativas a las 48-72 horas y entre 3.o-7.o día de vida. No hubo diferencias al comparar el método de hipotermia. Los pacientes con EHI grave presentaron mayor afectación hemodinámica, respiratoria y hepática. Conclusiones: Neonatos con EHI grave presentan aumento de los niveles de creatinina sérica y mayor afectación multiorgánica respecto a aquellos con EHI moderada.

Abstract Background: Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia can affect any organ, worsening the prognosis. Objective: To describe renal and multiorgan involvement in moderate-severe HIE. Material and method: Newborns > 35 weeks diagnosed with moderate-severe HIE who required active hypothermia between 2010-2020 were included. To assess renal involvement, serum creatinine was measured in three different periods: at 48-72 hours, between the 3rd and the 7th day, and from the 7th to the 28th day. Results: A total of 135 patients were included, 112 (83%) with moderate and 23 (17%) with severe HIE. Significant differences were obtained when comparing median creatinine levels at 48-72 hours and between 3-7 days in both groups. There were no differences in creatinine according to the hypothermia method. Patients with severe HIE presented greater hemodynamic, respiratory, and hepatic involvement. Conclusions: Neonates with severe HIE present increased serum creatinine levels and greater multi-organ involvement than those with moderate HIE.

Lung recruitment in neonatal high-frequency oscillatory ventilation with volume-guarantee.

BACKGROUND AND OBJECTIVES: The optimal lung volume strategy during high-frequency oscillatory ventilation (HFOV) is reached by performing recruitment maneuvers, usually guided by the response in oxygenation. In animal models, secondary spontaneous change in oscillation pressure amplitude (ΔPhf) associated with a progressive increase in mean airway pressure during HFOV combined with volume guarantee (HFOV-VG) identifies optimal lung recruitment. The aim of this study was to describe recruitment maneuvers in HFOV-VG and analyze whether changes in ΔPhf might be an early predictor for lung recruitment in newborn infants with severe respiratory failure. DESIGN AND METHODS: The prospective observational study was done in a tertiary-level neonatology department. Changes in ΔPhf were analyzed during standardized lung recruitment after initiating early rescue HFOV-VG in preterm infants with severe respiratory failure. RESULTS: Twenty-seven patients were included, with a median gestational age of 24 weeks (interquartile range [IQR]: 23-25). Recruitment maneuvers were performed, median baseline mean airway pressure (mPaw) was 11 cm H2 O (IQR: 10-13), median critical lung opening mPaw during recruitment was 14 cm H2 O (IRQ: 12-16), and median optimal mPaw was 12 cm H2 O (IQR: 10-14, p < 0.01). Recruitment maneuvers were associated with an improvement in oxygenation (FiO2 : 65.0 vs. 45.0, p < 0.01, SpO2/FiO2 ratio: 117 vs. 217, p < 0.01). ΔPhf decreased significantly after lung recruitment (mean amplitude: 23.0 vs. 16.0, p < 0.01). CONCLUSION: In preterm infants with severe respiratory failure, the lung recruitment process can be effectively guided by ΔPhf on HFOV-VG.

Leptomeningeal carcinomatosis: prognostic value of clinical, cerebrospinal fluid, and neuroimaging features.

INTRODUCTION: Leptomeningeal carcinomatosis (LC) is a devastating complication occurring in 5% of all patients with cancer. To date there are no well-established prognostic markers in patients with LC, except for the presence of cerebrospinal fluid (CSF) blocks and the Karnofsky performance status scale (KPS). We aimed to identify clinical, neuroradiologic and CSF prognostic factors related to LC survival and to develop an easy-to-use Prognostic Scoring Scale (PSS) to identify patients who are more likely to benefit from receiving treatment. METHODS: Single-center retrospective study evaluating patients who had a diagnosis of LC during a 10-year period. Diagnosis was made by malignant cytology or imaging; suspicious cases treated as LC were also included. RESULTS: Fifty patients with LC were analyzed (58% women). Median age was 54.4 years, and KPS was 60%. The most common types of tumor were breast (35%), lung (24%), and hematologic malignancies (16%). Thirty-two percent of patients were diagnosed by imaging, 22% by cytology, and 40% by both. Median overall survival (OS) was 10 weeks (95% confidence interval 5.1-14.9). Median OS for patients who received specific treatment was 21.2 weeks vs. 6.38 weeks for patients receiving supportive care only (p<0.001). In multivariate analysis, initial KPS, initial CSF protein level (<112 mg/dL) and time from diagnosis of primary tumor to diagnosis of LC (>67 weeks) were significant and independent predictors of increased survival. CONCLUSIONS: Prognosis remains poor in LC. The predictive factors for patients with LC here identified could help to improve the selection of patients who are more likely to benefit from receiving treatment.

Fc gamma receptor polymorphisms as predictive markers of Cetuximab efficacy in epidermal growth factor receptor downstream-mutated metastatic colorectal cancer.

BACKGROUND: The immunoglobulin G1 (IgG(1)) monoclonal antibody (MoAb) Cetuximab is active in metastatic colorectal cancer (mCRC) as first or subsequent lines of therapy. Efficacy seems restricted to KRAS wild-type tumours. IgG(1) may also induce antibody dependent cell mediated citotoxicity (ADCC) by recruitment of immune effector cells. ADCC is influenced by Fc gamma receptor (FcγR) polymorphisms. We investigated the association of FcγR polymorphisms and disease control rate (DCR) in mCRC patients treated with chemotherapy plus Cetuximab. PATIENTS AND METHODS: Tumour tissues from 106 patients were screened for KRAS codon 12 and 13 mutations using a sensitive multiplex assay (DxS, Manchester, United Kingdom). NRAS (codons: 12, 13 and 61), PI3K (exon 20) and BRAF (exon 15) were analysed by direct sequencing. Fcγ RIIa and Fcγ RIIIa polymorphisms were genotyped by TaqMan assays. RESULTS: DCR was significantly higher in KRAS wild-type tumours (61% versus 39%, p = 0.049). In epidermal growth factor receptor (EGFR) downstream-mutated mCRC patients, those harbouring an FcγRIIa H/H genotype had a higher DCR than alternative genotypes (67% versus 33%, p = 0.017). By multivariate analysis, FcγRIIa-131H/H remained significantly correlated with DCR (p = 0.008). CONCLUSION: FcγR polymorphisms may play a role in the clinical efficacy of Cetuximab in EGFR downstream mutated mCRC patients. Further research into Cetuximab immune-based mechanisms in KRAS-mutated patients seems warranted.

How to provide care for patients suffering from terminal non-oncological diseases: barriers to a palliative care approach.

Despite the seemingly evident pertinence of palliative care for patients suffering from non-oncological long-term life-threatening diseases, everyday clinical practice is far from that assumption. This study aims to explore palliative care service provision for these patients in Spain. Patients, family caregivers and healthcare professionals were interviewed, individually or in a group, aiming at identifying barriers in the provision of care and strategies to overcome them. Ritchie and Spencer's framework was used for data analysis. The barriers identified were as follows: lack of clarity about prognosis, the hegemony of the curative approach, avoiding words and the desire to cheat death. Provision of palliative care services for these patients should be guided by the characteristic trajectory of each type of disease. Even if healthcare systems were capable of providing specialized palliative care services to this large group of patients, other barriers should not be overlooked. It would then seem appropriate to provide therapeutic and palliative care simultaneously, thus facilitating adaptation processes for both patients and relatives.