Challenges in the Diagnosis and Management of Bacterial Lung Infections in Solid Organ Recipients: A Narrative Review

Respiratory infections pose a significant threat to the success of solid organ transplantation, and the diagnosis and management of these infections are challenging. The current narrative review addressed some of these challenges, based on evidence from the literature published in the last 20 years. Specifically, we focused our attention on (i) the obstacles to an etiologic diagnosis of respiratory infections among solid organ transplant recipients, (ii) the management of bacterial respiratory infections in an era characterized by increased antimicrobial resistance, and (iii) the development of antimicrobial stewardship programs dedicated to solid organ transplant recipient

Autofluorescence bronchoscopy in lung transplantation

Despite little is known about airway perfusion in the early period after lung transplantation, central bronchial stenosis is attributed to pour vascularization. Autofluorescence bronchoscopy was developed to discover preinvasive lesions, based on the fact that dysplasia shows less fluorescence than normal tissue when excited by blue light. Despite some questions about the origin of autofluorescence are left, the presence of good vascularization seems to be crucial. The aim of the present study was to evaluate the bronchial mucosa modification after lung transplantation by autofluorescence bronchoscopy

Bronchoalveolar Lavage-microRNAs Are Potential Novel Biomarkers of Outcome after Lung Transplantation

Background. Primary graft dysfunction, infections, and acute rejection (AR) worsen lung transplantation (LTx) outcome and patient survival. Despite significant efforts, reliable biomarkers of acute lung allograft dysfunction are lacking. To address this issue, we profiled the bronchoalveolar lavage (BAL) miRNome in LTx patients. Methods. BAL-microRNAs (miRNAs) from 16 patients were collected 7 days (T0), 15 days (T1), and 3 months (T2) after bilateral LTx and profiled on low-density array. Unsupervised and supervised analyses were used to identify miRNAs associated with clinical features, pneumonia, or AR. Prognostic markers were identified using the Cox model. Targeted signaling pathways were predicted in silico. A second series of 11 patients were used to validate AR-associated miRNAs. Results. Variation in BAL-miRNAs was associated with acute lung allograft dysfunction. Increased levels of miR-23b-3p at T2 were detected in patients with pneumonia, whereas let-7f-5p, miR-146b-3p, miR-22-5p, miR-29c-5p, miR-362-5p, and miR-452-5p were upregulated at T2 in patients with AR. miR-148b-5p and miR-744-3p distinguished LTx patients with AR in both cohorts. Low miR-148b-5p and high miR-744-3p expression levels were significantly associated with a shorter time to AR either within the first year after LTx or during follow-up. Combination of the 2 miRNAs identified LTx patients with higher AR risk independently of clinical variables. Conclusions. Our data provide new insights into the roles of BAL-miRNAs in regulating the pulmonary environment after transplantation and suggest that these miRNAs could serve as biomarkers of early- or mid-stage events. If validated, these findings could pave the way to a personalized clinical approach in LTx patients

Is targeted fortification of human breast milk an optimal nutrition strategy for preterm infants? An interventional study

BACKGROUND: Fortifying human milk contributes to the prevention of postnatal growth failure in preterm infants. Because of the natural variability of human milk, targeted fortification of human milk has been advocated. However, data regarding the efficacy and safety of prolonged targeted fortification are scarce. We aimed to assess the safety of targeted fortification of human milk in preterm infants compared with standard fortification, as well as the effects on infant growth. METHODS: We conducted an interventional study during hospital stay in healthy very low birth weight preterm infants who were exclusively fed human milk. Pools of human milk collected for 24 h were analysed using mid-infrared transmission spectroscopy. Targeted fortification of human milk was performed by adding macronutrients to native human milk to obtain optimal ratios of fat (4.4 g), carbohydrates (8.8 g), and protein (3 g) per 100 ml. The intervention period lasted 4-7 weeks. Weekly weight and daily growth rates were compared with those of a standardized fortification group of very low birth weight preterm infants who received standard fortified human milk (n = 10). The osmolality as well as the metabolic and gastrointestinal tolerance were monitored. Intergroup differences were evaluated using the Mann-Whitney U-test. RESULTS: A total of 10 preterm infants (birth weight 1223 \ub1 195 g; gestational age 29.1 \ub1 1.03 weeks) were enrolled and 118 samples of pooled milk were analysed. On average, 1.4 \ub1 0.1 g of protein, 2.3 \ub1 0.5 g of carbohydrate, and 0.3 \ub1 0.1 g of fat per 100 ml were added to the milk. Osmolality values after target fortification were within recommended limits (376 \ub1 66 mOsml/kg). Weekly weight gain (205.5 g; 95 % CI 177-233 vs 155 g; 95 % CI 132-178; p = 0.025) and daily growth rates (15.7 g/kg/day; 95 % CI 14.5-16.9 vs 12.3 g/kg/day; 95 % CI 10.7-13.9; p = 0.005) were higher in infants receiving target fortification than in infants receiving standardized fortification. The infants receiving targeted fortified milk consumed similar volumes as infants in the standardized fortification group (148 \ub1 4.5 vs 146 \ub1 4 ml/kg/day). No signs of either gastrointestinal or metabolic intolerance were observed. CONCLUSIONS: Target fortification appears to promote growth in very low birth weight preterm infants without any detrimental effects. Trial registration NCT02716337

Does human milk modulate body composition in late preterm infants at term-corrected age?

(1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content \u3b2 = - 47.9, 95% confidence interval (CI) = -95.7; p = 0.18; p = -0.049; = \u3b2=-89.6, 95% CI = -131.5; -47.7; p < 0.0001; - = -104.1, 95% CI = -151.4; -56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants

Determinants of breastfeeding discontinuation in an Italian cohort of mother-infant dyads in the first six months of life: A randomized controlled trial

Background: Among breastfeeding determinants, the marketing of breast milk substitutes might contribute to suboptimal breastfeeding rates. The aim of this study was to investigate the effect of receiving information on breast milk substitutes on breastfeeding rates. Methods: We conducted a randomized, single-blind, controlled trial from 2012 to 2014 in a northern Italian maternity ward. We enrolled 802 Caucasian mothers who gave birth to healthy, full-term singletons with a birth weight > 2500 g and who were exclusively breastfeeding from delivery to discharge. Mothers who gave birth to infants with congenital diseases, chromosomal abnormalities, perinatal infections and/or cardio-respiratory instability and/or mothers being affected by endocrine and/or metabolic and/or gastrointestinal and/or renal diseases were excluded. Mothers were randomized to either receive (group A, n = 405) or not (group B, n = 397) written information on a breast milk substitute at discharge. Breastfeeding was promoted and supported in all mother-infant pairs equally. The mode of feeding for up to 6 months after delivery was determined by phone interview. To detect a 10% difference between groups in the discontinuation rate of exclusive breastfeeding at three months of age at 5% significance and 80% power, a total of 356 mother-infant pairs per group were needed. Results: The exclusive breastfeeding prevalence was 91% and 92% at 7 days, 79% and 70% at 1 month, 75% and 66% at 2 months, 72% and 62% at 3 months, and 3% and 2% at 6 months in groups A and B, respectively. The relative risk (95% confidence interval) of exclusive breastfeeding (group A vs B) at 7 days and at 1, 2, 3 and 6 months was as follows: 0.99 (0.95-1.03), 1.12 (1.03-1.21), 1.13 (1.03-1.24), 1.15 (1.04-1.27), and 1.49 (0.62-3.61). Nutritional, lifestyle and lactational factors were the primary contributing determinants to early breastfeeding discontinuation. Conclusions: The present findings indicate that receiving written information on breast milk substitutes at hospital discharge, provided that breastfeeding support and education are offered, does not negatively affect breastfeeding rates. Trial registration: NCT03208114. Registered 5 July 2017

Regional analysis with quantitative computed tomography after lung transplantation

Regional analysis with quantitative computed tomography (CT) of graft could be an attractive technique to interpret lung patterns after transplantation. Aim of this study was the definition of lung regional patterns in the early post-transplantation period. We prospectively collected the CT scans at end-expiration (EXP) and full-inspiration (INSP) of patients at 3 months after lung transplantation (LT). Lungs were segmented from both scans. INSP images were registered to EXP by optical flow to obtain maps of density variation (\u394HU) with pixel-by-pixel subtraction. We evaluated a classification of the pixels from maps of \u394HU in low ventilation (LV), consolidation (C), air trapping (AT) and healthy parenchyma (H). Patients who experienced uneventful early postoperative course after bilateral LT were enrolled. The figure shows the resulted composition of the parenchyma in 20 patients: LV=59.6\ub15.4%, C=1.7\ub10.4%, AT=0.06\ub10.05%, H=38.7\ub15.6%. To note that low ventilation pattern still affected the majority of lung tissue while consolidation and air trapping were negligible. Quantitative CT regional analysis may provide a significant advance in the interpretation of ventilation abnormalities after LT

Clinical evaluation of two different protein content formulas fed to full-term healthy infants: A randomized controlled trial

Background: A high early protein intake is associated with rapid postnatal weight gain and altered body composition. We aimed to evaluate the safety of a low-protein formula in healthy full-term infants. Methods: A randomized controlled trial was conducted. A total of 118 infants were randomized to receive two different protein content formulas (formula A or formula B (protein content: 1.2 vs. 1.7g/100mL, respectively)) for the first 4 months of life. Anthropometry and body composition by air displacement plethysmography were assessed at enrolment and at two and 4 months. The reference group comprised 50 healthy, exclusively breastfed, full-term infants. Results: Weight gain (g/day) throughout the study was similar between the formula groups (32.5\ub16.1 vs. 32.8\ub16.8) and in the reference group (30.4\ub15.4). The formula groups showed similar body composition but a different fat-free mass content from breastfed infants at two and 4 months. However, the formula A group showed a fat-free mass increase more similar to that of the breastfed infants. The occurrence of gastrointestinal symptoms or adverse events was similar between the formula groups. Conclusions: Feeding a low-protein content formula appears to be safe and to promote adequate growth, although determination of the long-term effect on body composition requires further study

Growth and Fat Mass in Preterm Infants Fed A Protein-Enriched Postdischarge Formula (PDF): A Randomized Controlled Trial

Background and aims: Male infants with BW< 1250 g benefit from PDF. Fetal growth seems to influence growth recovery whereas fat restoration occurs irrespective of BW. To evaluate whether being fed a PDF determines a growth benefit in two subgroups of infants. Methods: 123 preterm infants born AGA (BW=1193.4\ub1 230 g; GA=29\ub11.9 wks) and 84 born SGA (BW=1127\ub1 262g; GA=31.3\ub11.9 wks) were randomized at term corrected age (CA) in G1: 59 AGA fed PDF (2.9 g/100 kcal), G2: 64 AGA fed term formula (TF) (2.1 g/100 kcal), G3: 41 SGA fed PDF, G4: 43 SGA fed TF. From 6 months infants were fed a follow on formula and weaned according to ESPGHAN recommendations. Growth and body composition were assessed by an air displacement plethysmography system at term, 1, 3, 5, 6, 12 months. ANOVA, regression analysis. Results: G1 and G3 protein intakes were higher than those of G2 (p< 0.005) and G4(p< 0.05), respectively, whereas weight, length and fat mass were similar at each study point. G1 mean HC (cm) was bigger than that of G2 at six months (43.5\ub1 1.9 vs 42.6\ub11.6, p=0.03) whereas at 12 months no difference was found (45.4\ub11.6 vs 46\ub11.6). In AGA infants being fed a PDF formula, being male, not having a postnatal growth retardation at term correlated with bigger HC at six months [(p< 0.001), unstandardized B coefficient (SE) 0.9 (0.36); 1.2 (0.36); 1.2 (0.37), respectively]. Conclusions: Male AGA without postnatal growth retardation at term but not SGA infants appear to benefit from being fed PDF

Trapianto di polmone e disordini linfoproliferativi post trapianto (PTLD) ebv-correlati

I disordini linfoproliferativi post trapianto sono un\u2019importate causa di morbidit\ue0 soprattuto nel primo anno dal trapianto. Tale possibilit\ue0 diagnostica andrebbe sempre tenuta in considerazione in casi di lesioni polmonari di difficile interpretazione. Essendoci una stretta correlazione con Ebstein-Barr virus si ritiene mandatorio il monitoraggio di EBV-DNA nel siero nel follow up post trapianto. Introduzione: I trapianti di organo solido, a causa dell\u2019immunosoppressione, comportano un alto rischio di sviluppo di malattie linfoproliferative. Spesso questi disordini sono correlati ad Ebstein-Barr Virus. Pochi studi sono attualmente disponibili nell\u2019ambito dell\u2019incidenza nel trapianto di polmone. Metodologia: \uc8 stata condotta una analisi retrospettiva sui pazienti sottoposti a trapianto polmonare presso il nostro centro che abbiano sviluppato un linfoma EBV-correlato. Risultati: Dal Gennaio 2009 al Gennaio 2017 sono stati eseguiti 100 trapianti polmonari. Di questi, 2 pazienti hanno sviluppato PTLD EBV correlata. Entrambi i pazienti sono stati trapiantati in regime di urgenza per Fibrosi Cistica, con necessit\ue0 di supporto respiratorio extracorporeo. La diagnosi \ue8 stata effettuata nei primi mesi post trapianto mediante biopsia di lesioni polmonari, in quadro infettivo non responsivo alla terapia antibiotica ad ampio spettro, in presenza di elevata carica di EBV-DNA su siero. La malattia ha interessato prevalentemente il parenchima e linfonodi polmonari in un caso mentre nel secondo caso si \ue8 resa evidente un\u2019estensione anche extrapolmonare (epatica e linfonodale). I pazienti sono stati sottoposti a chemioterapia secondo schema specifico. Entrambi i pazienti sono vivi a 24 e 14 mesi dal trapianto, in remissione completa (1\ub0 caso) e parziale (2\ub0 caso). Conclusioni: I disordini linfoproliferativi post trapianto sono un\u2019importate causa di morbidit\ue0 soprattuto nel primo anno dal trapianto. Tale possibilit\ue0 diagnostica andrebbe sempre tenuta in considerazione in casi di lesioni polmonari di difficile interpretazione. Essendoci una stretta correlazione con Ebstein-Barr virus si ritiene mandatorio il monitoraggio di EBV-DNA nel siero nel follow up post trapianto