Effects of insulin therapy optimization with sensor augmented pumps on glycemic control and body composition in people with cystic fibrosis-related diabetes.

Objective: Cystic fibrosis (CF)-related diabetes (CFRD) resulting from partial-to-complete insulin deficiency occurs in 40-50% of adults with CF. In people with CFRD, poor glycemic control leads to a catabolic state that may aggravate CF-induced nutritional impairment and loss of muscle mass. Sensor augmented pump (SAP) therapy may improve glycemic control as compared to multiple daily injection (MDI) therapy. Research design and methods: This non-randomized clinical trial was aimed at evaluating the effects of insulin therapy optimization with SAP therapy, combined with a structured educational program, on glycemic control and body composition in individuals with insulin-requiring CFRD. Of 46 participants who were offered to switch from MDI to SAP therapy, 20 accepted and 26 continued the MDI therapy. Baseline demographic and clinical characteristics were balanced between groups using a propensity score-based overlap weighting procedure and weighted mixed-effects regression models were used to estimate changes in study outcomes. Results: After 24 months changes in HbA1c were: -1.1% (-12.1 mmol/mol) (95% CI: -1.5; -0.8) and -0.1% (-1 mmol/mol) (95% CI: -0.5; 0.3) in the SAP and MDI therapy group, respectively, with a between-group difference of -1.0 (-10 mmol/mol) (-1.5; -0.5). SAP therapy was also associated with a decrease in mean glucose (between group difference: -32 mg/dL; 95% CI: -44; -20) and an increase in TIR (between group difference: 19.3%; 95% CI 13.9; 24.7) and in fat-free mass (between group difference: +5.5 Kg, 95% CI: 3.2; 7.8). Conclusion: Therapy optimization with SAP led to a significant improvement in glycemic control, which was associated with an increase in fat-free mass.

Effects of bilateral lung transplantation on cardiac autonomic modulation and cardiorespiratory coupling: a prospective study.

BACKGROUND: Although cardiac autonomic modulation has been studied in several respiratory diseases, the evidence is limited on lung transplantation, particularly on its acute and chronic effects. Thus, we aimed to evaluate cardiac autonomic modulation before and after bilateral lung transplantation (BLT) through a prospective study on patients enrolled while awaiting transplant. METHODS: Twenty-two patients on the waiting list for lung transplantation (11 women, age 33 [24-51] years) were enrolled in a prospective study at Ospedale Maggiore Policlinico Hospital in Milan, Italy. To evaluate cardiac autonomic modulation, ten minutes ECG and respiration were recorded at different time points before (T0) and 15 days (T1) and 6 months (T2) after bilateral lung transplantation. As to the analysis of cardiac autonomic modulation, heart rate variability (HRV) was assessed using spectral and symbolic analysis. Entropy-derived measures were used to evaluate complexity of cardiac autonomic modulation. Comparisons of autonomic indices at different time points were performed. RESULTS: BLT reduced HRV total power, HRV complexity and vagal modulation, while it increased sympathetic modulation in the acute phase (T1) compared to baseline (T0). The HRV alterations remained stable after 6 months (T2). CONCLUSION: BLT reduced global variability and complexity of cardiac autonomic modulation in acute phases, and these alterations remain stable after 6 months from surgery. After BLT, a sympathetic predominance and a vagal withdrawal could be a characteristic autonomic pattern in this population.

Bone involvement in young adults with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure.

Patients with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure have high prevalence of reduced bone mineral density and fragility fracture. Suboptimal 25-hydroxyvitamin D levels could significantly contribute to the development of cystic fibrosis-related bone disease. INTRODUCTION: The assessment of the prevalence of cystic fibrosis-related bone disease (CFBD) and its associated risk factors in young adults with cystic fibrosis (CF) awaiting lung transplantation for end-stage respiratory failure. METHODS: Clinical characteristics, bone mineral density (BMD), the parameters of calcium metabolism, including vitamin D (25OHVitD) levels, and the presence of fragility fractures were evaluated in 42 CF patients (24 females, age 34.0 ± 8.4 years) consecutively referred as lung transplant candidates. RESULTS: Mean 25OHVitD levels (54.9 ± 26.2 nmol/L) were below the reference range and hypovitaminosis D (25OHVitD < 75 nmol/L) was found in 34 patients (81%) and daily calcium intakes (median 550 mg/day) were lower than recommended. A BMD below the expected range for age (Z-score of - 2.0 or lower) and at least one prevalent fragility fracture were found in 22 patients (52.4%) and 18 patients (45.2%), respectively. The coexistence of low BMD and the presence of fracture was observed in 13 patients (31.0%). In these patients, the prevalence of nephrolithiasis was higher than in the remaining ones (p = 0.046). The presence of kidney stones was associated with a worse bone status and with severe vitamin D deficiency. In the whole sample, femoral BMD Z-scores were directly correlated with albumin-adjusted calcium (p < 0.05) and 25OHVitD levels (p < 0.01). CONCLUSIONS: Despite the improvement of CF care, CFBD is still highly prevalent in young adults awaiting lung transplantation for end-stage CF. Suboptimal 25OHVitD levels could significantly contribute to the development of CFBD. The presence of nephrolithiasis could be an additional warning about the need for a careful evaluation of bone health in CF patients.

Surveillance Transbronchial Biopsy Program to Evaluate Acute Rejection After Lung Transplantation: A Single Institution Experience.

BACKGROUND: There is no unanimity in the literature regarding the value of transbronchial biopsies (TBBs) performed at a scheduled time after lung transplantation (surveillance TBBs [SBs]), compared to biopsies performed for suspected clinical acute rejection (clinically indicated TBBs [CIBs]). This study exposes an assessment of our experience over the last 4 years through a retrospective analysis of the data collected. METHODS: In our center, SBs are performed at 3, 6, and 12 months after a transplant. Data from 110 patients who underwent a TBB were collected from January 2013 to November 2017. Clinical and functional data along with the histologic results and complications were collected. RESULTS: Overall 251 procedures were performed: 223 for surveillance purposes and 28 for clinical indications. The SBs diagnostic rate was 84%. A grade 2 acute rejection (AR) was detected in 9 asymptomatic patients, all of whom were medically treated, with downgrading of AR documented in all cases. The rate of medical intervention in the SB group was 8%. The CIBs diagnostic rate was 96%. The rate of AR detected by CIBs was significantly higher than by SBs (36% versus 4%; P < .0001). Overall the major complication rate was 4%; no patients required transfusions and no mortality occurred in the patient cohort. CONCLUSIONS: The surveillance protocol did not eliminate the necessity of CIBs, but in 8% of patients early rejection was histologically assessed. The correlation between histologic and clinical data allows a more careful approach to transplanted patients.

Lung Transplantation as Successful Treatment of End-stage Idiopathic Pleuroparenchymal Fibroelastosis: A Case Report.

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition, characterized by predominantly upper-lobe pleural and subjacent parenchymal fibrosis, the latter being intra-alveolar with accompanying elastosis of the alveolar walls that leads a clinical progression to respiratory failure. This condition may not be as rare as it seems to be, because nowadays the increasing awareness among specialists is raising the number of new diagnoses. Limited data are available about the prognosis, both for secondary and idiopathic forms. Nevertheless, the idiopathic form seems to be rapidly progressive and no treatment can control the disease, which is why management is challenging. Since the disease was characterized, PPFE cases have been reported in the literature, but most have been secondary rather than idiopathic. Of these, few have successfully undergone lung transplantation as a treatment of end-stage respiratory failure. We here report a successful case of a 38-year-old man affected by idiopathic PPFE who underwent bilateral lung transplantation after extracorporeal membrane oxygenation bridging for an abrupt transition to critical clinical conditions. After a complex postoperative course and a first year characterized by acute rejection, the patient is alive at 5 years with a good quality of life. Our experience confirms that lung transplantation would be a valuable treatment option in case of end-stage idiopathic PPFE cases.

Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorders in Cystic Fibrosis Lung Transplant Recipients: A Case Series.

BACKGROUND: Solid organ transplantation is associated with a higher risk of Epstein-Barr virus (EBV)-related lymphoproliferative disease due to immunosuppressive regimen. Little evidence is currently available on post-transplant lymphoproliferative disorders (PTLDs) in the lung transplant (LuTx) setting, particularly in cystic fibrosis (CF) recipients. METHODS: We retrospectively analyzed all the cases of PTLDs that occurred in our LuTx center between January 2015 and December 2017. We reviewed clinical and radiologic data, donor and recipient EBV serostatus, immunosuppressive therapy, histologic data, and follow-up of these patients. RESULTS: A total of 77 LuTxs were performed at our center in the study period; 39 (50.6%) patients had CF; 4 developed EBV-related PTLDs. They were all young (17-26 years) CF patients with high serum EBV DNA load. Disease onset was within the first 3 months after LuTx. In 3 cases presentation was associated with fever and infection-like symptoms, whereas in 1 case radiologic suspicion arose unexpectedly from a CT scan performed for different clinical reasons. Diagnosis was reached through lung biopsy in all cases. All patients received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), and prednisone with variable response and complications. CONCLUSION: In our experience, the early development of EBV-related PTLD was a highly aggressive, life-threatening condition, which exclusively affected young CF patients in the early post-transplant period. The rate of this complication was relatively high in our population. Diagnosis with lung biopsy is crucial in all suspected cases and regular monitoring of EBV DNA levels is of utmost importance given the high correlation with PTLDs in patients at increased risk.

Lobar Lung Transplantation From Deceased Donor: Monocentric Experience.

INTRODUCTION: Lung transplantation is considered a therapeutic option in selected patients affected by end-stage pulmonary disease. The mortality on the waiting list is mainly attributed to the shortage of the donor pool available for transplantation. There are various strategies to overcome this shortage; one of them is lobar transplantation. METHODS: The aim of the current study was to analyze the outcome of lobar lung transplantation from deceased donors in our Lung Transplant Center. Overall survival, perioperative mortality and morbidity, problem on bronchial anastomosis, and chronic rejection were prospectively recorded in a 5-year time-frame. RESULTS: From November 2010 to October 2015, we performed 100 lung transplantations; 6 of which (6%) were lobar transplantations from deceased donors. Three recipients were on an emergency list due to preoperative extracorporeal support. The causes of lobectomy leading to lobar transplantation were: size mismatch (3), iatrogenic vascular damage (2), and chronic atelectasis (1). One patient died 5 months after surgery for sepsis; and 5 patients were alive at the study end (median follow-up: 17.5 months). Prevalence of grade 3 primary graft dysfunction at 72 hours was 50%. One patient developed bronchial stenosis. No cases of chronic rejection were recorded. CONCLUSIONS: Lobar transplantation can be considered a valid tool to overcome the donor pool shortage in selected cases; such a technique has proved particularly useful in critically ill patients who were scheduled in an emergency transplant program.

Lung Allocation Score: A Single-Center Simulation.

BACKGROUND: The lung allocation score (LAS) was introduced in the United States in May 2005 with the main goal of reducing the waiting list mortality of patients with end-stage lung diseases, but also to enhance the lung transplant benefit and improve the management of urgent candidates. Several papers have reported that LAS resulted in a reduction of the waiting list mortality but no significant survival benefit was noted. METHODS: We evaluate the usefulness of LAS as a predictor for lung transplantation outcome in 123 patients listed for lung transplantation in an Italian center. Primary endpoints were waiting list mortality and posttransplant mortality at 1 year; secondary endpoints included perioperative circulatory support, cardiopulmonary bypass, primary graft dysfunction, and long-term survival after transplantation. RESULTS: We observed the absence of correlation between LAS and waiting list mortality. The LAS did not affect the long-term survival in our population. CONCLUSIONS: High LAS was predictive of primary graft dysfunction of grade 3 in the first 72 hours after transplantation.

Boys who are born preterm show a relative lack of fat-free mass at 5 years of age compared to their peers.

AIM: Prematurity is associated with features of metabolic syndrome in young adulthood. We investigated the body composition and blood pressure of children born preterm. METHODS: A longitudinal, observational study was conducted with preterm infants who had a birth weight of <1500 g and a gestational age of <32 weeks. Growth and body composition were assessed by air displacement plethysmography at term equivalent age and at school age and were compared to those of 61 healthy, term breastfed subjects. RESULTS: A total of 63 preterm infants were enrolled. At term equivalent age, growth and fat-free mass were lower in preterm infants than in term newborns, but fat mass was higher. At 5 years of age, children born preterm were still lighter and shorter than children born at term. When the results were analysed by gender, the fat-free mass index was lower in boys born preterm than in their peers (12.1 ± 1.1 versus 13.0 ± 1.0 kg/h(2) p < 0.005), whereas no difference was detected among girls. Diastolic blood pressure was higher in children born preterm than in children born at term (61.14 ± 7.8 vs 56.69 ± 8.2 mmHg, p = 0.009). CONCLUSION: Boys born preterm showed a relative lack of fat-free mass at school age compared to their peers.

Can infants be protected by means of maternal vaccination?

The administration of vaccines is not usually recommended in pregnant women because of a fear of severe adverse events for the fetus. However, contraindication to vaccination applies only to vaccines based on live attenuated viruses for the theoretical possibility that they might infect the fetus. In contrast, the use of several inactivated vaccines is useful and recommended. As a result of the transplacental passage of antibodies, maternal immunization can reduce the risk of vaccine-preventable diseases that may occur in the first months of life before the start or completion of the suggested vaccination schedule. One of the best examples is vaccination against influenza that can protect pregnant women from a disease that can lead to hospitalization and death in a significantly higher number of cases than in the general population and can induce protective specific antibody levels as well as being effective in infants in the first months of life. Other examples are vaccinations against tetanus, pertussis, pneumococcal infections and Haemophilus influenzae type b infection. This review analyses the advantages and limitations of maternal immunization as revealed by experience and the main publications.

[Quality of post-discharge growth in small for gestational age preterm infants: an explorative study]. / Qualità della crescita post-dimissione in prematuri nati piccoli per età gestazionale: studio esplorativo.

OBJECTIVES: The Preterm newborns, especially if born small for gestational age (SGA), appear to be at risk for developing post-natal growth failure and an altered body composition. Nutrition-related growth during a critical window in infancy may affect the development of metabolic syndrome in adult life. Aim of the present study was to test the hypothesis that the post-discharge period is critical for programming the catch up growth and the later development of metabolic syndrome in small for gestational-age infants fed either standard or enriched formula. METHODS: A clinic randomized explorative study was conducted. Twenty-seven preterm SGA infants (gestational age < or = 33 weeks; birth weight < or = 1500 g) underwent assessment of growth and body composition by means of an air displacement system at 36 weeks, 15 days and 1 months adjusted age. SGA infants were randomized to receive standard formula (Kcal: 67/100 ml, proteins: 1,4 g/100 ml) or enriched formula (Kcal: 75/100 ml, proteins: 2 g/100 ml) after discharge. RESULTS: No differences in weight, fat mass, length and head circumference were found in SGA infants fed standard formula as compared to those fed enriched formula at 15 day or 1 months adjusted age. CONCLUSIONS: This explorative study suggests that in SGA infants growth, both in terms of quantity and quality, is not influenced by different nutritional management during the early post-discharge period.

[Early nutrition: the role of genetics and epigenetics]. / Nutrizione nelle prime epoche della vita: ruolo della genetica e dell' epigenetica.

Many adult diseases seem to be associated with early nutrition and the subsequent growth pattern. Epidemiological studies hypotized that babies with intrauterine and/or neonatal growth retardation may be at greater risk of metabolic syndrome later in life. According to the Barker's "thrifty phenotype hypotesis" early malnutrition, whereas inducing physiological compensation by the promotion of early survival, appears to confer greater susceptibility to adults diseases. Epigenetics, that is the interindividual variation in DNA methylation patterns and chromatin remodelling, provide a potential explanation for how environmental factors can modify the risk for development of many common diseases. Beginning from animal models, many studies concerning early nutrition, epigenetic modifications and genes expression have been carried out. Maternal undernutrition during pregnancy, especially in the peri-implantation period, not only causes a prolonged growth retardation but also modifies the programming of biochemical mechanisms related to endocrine-metabolic control. Human studies have demonstrated the role played by IGF-1 as indicator of nutritional status and fetal/postnatal growth retardation. It has been reported that alterations in IGF axis, which predispose to adults diseases, may be due to an alterated epigenetic regulation that can modify IGF expression. Despite the critical inter-relation between early nutrition, growth, development, and subsequent health, there are few data on the influence of early nutrition on the modifications of the epigenetic gear. Furthermore it is hoped for a bigger attention to the early nutrition to prevent the development of diseases later in life.

[Quality of growth in preterm infants assessed at term equivalent age: a pilot study]. / E possibile mimare nel neonato pretermine la composizione corporea fetale? Uno studio pilota.

BACKGROUND: The American Academy of Pediatrics (AAP) recommends that preterm infants' growth duplicates fetal growth rates and that body composition replicates in utero body composition. Aim ofthe study was to compare the total body fat mass between preterm infants assessed at term and full-term newborns. METHODS: A prospective observational study was conducted. Forty-five preterm infants (mean (SD) gestational age: 30,1 (2.3) weeks; birth weight: 1125 (280) g), and 40 full term (mean (SD) 38.5 (1.2) weeks, 3203 (385) g, breast fed infants underwent assessment of growth and body composition by means of an air displacement system at term adjusted-age and on day 3 of life, respectively. A T test was used to compare % fat mass between preterm and term infants. RESULTS: Weight, length and head circumference were smaller in the preterm group assessed at term adjusted-age as compared to the term group. Mean (SD) percentage of fat mass in preterm infants was significantly higher as compared to term infants [14.5 (4.3) vs 7,6 (3.6), P < 0.0001]. CONCLUSIONS: Our data demonstrate that preterm infants are at risk of developing an increased adiposity in addition to postnatal growth retardation.

[Body composition in small for gestational age newborns]. / Composizione corporea in neonati piccoli per età gestazionale.

OBJECTIVES: Aim of the present study was to test the hypothesis that the body composition of small for gestational age preterm infants, assessed at term equivalent age, was different as compared to that of small for gestational age full-term newborns. METHODS: Growth parameters and body composition, assessed by means of an air displacement pediatric plethysmography system, was measured in 120 newborns (67 preterm and 53 full-term). RESULTS: Similar weight was found in preterm and full-term newborns at term equivalent age and at birth, respectively. On the contrary, percentage of total body fat mass was significantly higher in preterm newborns as compared to full-term newborns (14.3 +/- 4.7% vs. 5.7 +/- 3.8% respectively, P < 0.05). In the preterm group gestational age was negatively associated with total fat mass at term equivalent age. CONCLUSIONS. The preterm newborns, especially if born small for gestational age, appear to be at risk for developing an altered body composition, which is a risk factor for the development of the metabolic syndrome in adult life. Preterm infants, born small for gestational age, appear to develop a quantity of fat mass higher than the adipose tissue they would have accumulated if they had completed their intrauterine gestation. The gestational age and the nutritional management in the early postnatal life could play a key role in affecting the body composition in these vulnerable infants.