scMicrobe PTA: Near Complete Genomes from Single Bacterial Cells.

Microbial genomes produced by single-cell amplification are largely incomplete. Here, we show that primary template amplification (PTA), a novel single-cell amplification technique, generated nearly complete genomes from three bacterial isolate species. Furthermore, taxonomically diverse genomes recovered from aquatic and soil microbiomes using PTA had a median completeness of 81%, whereas genomes from standard amplification approaches were usually <30% complete. PTA-derived genomes also included more associated viruses and biosynthetic gene clusters.

Valoración de un nuevo apósito para úlceras por presión: a propósito de un caso / Assessment for a new dressing for pressure ulcers: regarding a case

El objetivo de este estudio fue valorar la aplicación de un nuevo apósito superabsorbente a propósito de un caso clínico de un paciente con una úlcera por presión (UPP) con alto nivel exudativo, maceración de la piel perilesional, molestias y dolor. El paciente presentaba múltiples comorbilidades, estaba institucionalizado, desorientado, y presentaba una UPP grado IV. Accedió a comenzar un tratamiento con un apósito superabsorbente de nueva implementación en la institución. Se realizó una valoración en conjunto con su enfermera de la residencia según las Necesidades de Virginia Henderson. Según los resultados de dicha valoración se enunció un plan de cuidados con Diagnósticos NANDA, Resultados NOC con sus indicadores e Intervenciones NIC con sus actividades. Se priorizaron cuatro diagnósticos enfermeros: [00032] Patrón respiratorio ineficaz, [00129] Confusión crónica, [00312] Lesión por presión en el adulto y [00132] Dolor agudo. Los resultados NOC enunciados fueron [0402] Estado respiratorio: intercambio gaseoso, [0912] Estado neurológico: consciencia, [1101] Integridad tisular: piel y membranas mucosas, [110123] Necrosis, [1103] Curación de la herida: por segunda intención, [1004] Estado nutricional y [2109] Nivel de malestar. El plan de cuidados fue eficaz en el alcance de la puntuación diana de todos los indicadores excepto el indicador [110115] Lesiones cutáneas, cuya puntuación al alta se mantuvo igual que al ingreso, en 1 “grave”. El nuevo apósito disminuyó el exudado de la úlcera, redujo el tejido necrotizado y mejoró los bordes perilesionales. Esto mejoró a su vez el malestar del paciente al disminuir la frecuencia de cura de tres veces al día a una.(AU)

The objective of this study was to assess the application of a new super absorbent dressing, regarding the clinical case of a patient with one pressure ulcer (PU) with high levels of exudate, maceration of the perilesional skin, discomfort and pain. The patient presented multiple comorbidities; he was institutionalized, disoriented, and presented a Grade IV PU. The patient agreed to initiate treatment with a super absorbent dressing newly implemented at the institution. There was joint assessment with his nurse at the elderly home, according to Virginia Henderson’s Needs. Based on the results of said assessment, a plan of care was stated with NANDA diagnoses, NOC outcomes with their indicators, and NIC interventions with their activities. Four nursing diagnoses were prioritized: [00032] Ineffective breathing pattern, [00129] Chronic confusion, [00312] Pressure lesion in adults, and [00132] Acute pain. The NOC outcomes stated were [0402] Respiratory Status: Gas Exchange, [0912] Neurological status: Consciousness; [1101] Tissue Integrity: Skin and mucous membranes, [110123] Necrosis, [1103] Wound healing: Second intention, [1004] Nutritional status, and [2109] Discomfort level. The plan of care was effective at reaching the target score in all indicators except for [110115] Skin lesions with high score that stays the same than at admission, at 1 “severe”. The new dressing reduced the ulcer exudate and the necrotic tissue, and improved the perilesional edges. At the same time, there was an improvement in discomfort for the patient by reducing the frequency of cures from three times to once a day.(AU)

Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia.

Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3 D835H or NRAS G13D/G12S mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.

Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer's disease: three key timepoints through middle-age in females.

The TgF344 rat model of Alzheimer's disease (AD) provides a comprehensive neuropathology presentation, with age-dependent development of tau tangles, amyloid-beta (A[Formula: see text]) plaques, neuronal loss, and increased gliosis. The behavioral trajectory of this model, particularly relating to spatial learning and memory, has yet to be fully characterized. The current experiment evaluated spatial working and reference memory performance, as well as several physiological markers of health, at 3 key age points in female TgF344-AD rats: 6-months, 9-months, and 12-months. At 6 months of age, indications of working and reference memory impairments were observed in transgenic (Tg) rats on the water radial-arm maze, a complex task that requires working and reference memory simultaneously; at 12 months old, Tg impairments were observed for two working memory measures on this task. Notably, no impairments were observed at the 9-month timepoint on this maze. For the Morris maze, a measure of spatial reference memory, Tg rats demonstrated significant impairment relative to wildtype (WT) controls at all 3 age-points. Frontal cortex, entorhinal cortex, and dorsal hippocampus were evaluated for A[Formula: see text]1-42 expression via western blot in Tg rats only. Analyses of A[Formula: see text]1-42 expression revealed age-dependent increases in all 3 regions critical to spatial learning and memory. Measures of physiological health, including heart, uterine, and body weights, revealed unique age-specific outcomes for female Tg rats, with the 9-month timepoint identified as critical for further research within the trajectory of AD-like behavior, physiology, and pathology.

Evaluating the Cognitive Impacts of Drospirenone, a Spironolactone-Derived Progestin, Independently and in Combination With Ethinyl Estradiol in Ovariectomized Adult Rats.

Oral contraceptives and hormone therapies require a progestogen component to prevent ovulation, curtail uterine hyperplasia, and reduce gynecological cancer risk. Diverse classes of synthetic progestogens, called progestins, are used as natural progesterone alternatives due to progesterone's low oral bioavailability. Progesterone and several synthetic analogs can negatively impact cognition and reverse some neuroprotective estrogen effects. Here, we investigate drospirenone, a spironolactone-derived progestin, which has unique pharmacological properties compared to other clinically-available progestins and natural progesterone, for its impact on spatial memory, anxiety-like behavior, and brain regions crucial to these cognitive tasks. Experiment 1 assessed three drospirenone doses in young adult, ovariectomized rats, and found that a moderate drospirenone dose benefited spatial memory. Experiment 2 investigated this moderate drospirenone dose with and without concomitant ethinyl estradiol (EE) treatment, the most common synthetic estrogen in oral contraceptives. Results demonstrate that the addition of EE to drospirenone administration reversed the beneficial working memory effects of drospirenone. The hippocampus, entorhinal cortex, and perirhinal cortex were then probed for proteins known to elicit estrogen- and progestin- mediated effects on learning and memory, including glutamate decarboxylase (GAD)65, GAD67, and insulin-like growth factor receptor protein expression, using western blot. EE increased GAD expression in the perirhinal cortex. Taken together, results underscore the necessity to consider the distinct cognitive and neural impacts of clinically-available synthetic estrogen and progesterone analogs, and why they produce unique cognitive profiles when administered together compared to those observed when each hormone is administered separately.

Tsunami of immunotherapy reaches mesothelioma.

Malignant pleural mesothelioma (MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase III clinical trials published results positioning immunotherapy as a promising option for the first- and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte-associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase III trials. In the CheckMate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naïve patients and patients with progressive disease after chemotherapy.

Simultaneous monitoring of disease and microbe dynamics through plasma DNA sequencing in pediatric patients with acute lymphoblastic leukemia.

Treatment of acute lymphoblastic leukemia (ALL) necessitates continuous risk assessment of leukemic disease burden and infections that arise in the setting of immunosuppression. This study was performed to assess the feasibility of a hybrid capture next-generation sequencing panel to longitudinally measure molecular leukemic disease clearance and microbial species abundance in 20 pediatric patients with ALL throughout induction chemotherapy. This proof of concept helps establish a technical and conceptual framework that we anticipate will be expanded and applied to additional patients with leukemia, as well as extended to additional cancer types. Molecular monitoring can help accelerate the attainment of insights into the temporal biology of host-microbe-leukemia interactions, including how those changes correlate with and alter anticancer therapy efficacy. We also anticipate that fewer invasive bone marrow examinations will be required, as these methods improve with standardization and are validated for clinical use.

Accurate genomic variant detection in single cells with primary template-directed amplification.

Improvements in whole genome amplification (WGA) would enable new types of basic and applied biomedical research, including studies of intratissue genetic diversity that require more accurate single-cell genotyping. Here, we present primary template-directed amplification (PTA), an isothermal WGA method that reproducibly captures >95% of the genomes of single cells in a more uniform and accurate manner than existing approaches, resulting in significantly improved variant calling sensitivity and precision. To illustrate the types of studies that are enabled by PTA, we developed direct measurement of environmental mutagenicity (DMEM), a tool for mapping genome-wide interactions of mutagens with single living human cells at base-pair resolution. In addition, we utilized PTA for genome-wide off-target indel and structural variant detection in cells that had undergone CRISPR-mediated genome editing, establishing the feasibility for performing single-cell evaluations of biopsies from edited tissues. The improved precision and accuracy of variant detection with PTA overcomes the current limitations of accurate WGA, which is the major obstacle to studying genetic diversity and evolution at cellular resolution.

Intranasal 17ß-Estradiol Modulates Spatial Learning and Memory in a Rat Model of Surgical Menopause.

Exogenously administered 17ß-estradiol (E2) can improve spatial learning and memory, although E2 also exerts undesired effects on peripheral organs. Clinically, E2 has been solubilized in cyclodextrin for intranasal administration, which enhances brain-specific delivery. Prior work shows that the cyclodextrin structure impacts region-specific brain distribution of intranasally administered small molecules. Here, we investigated (1) cyclodextrin type-specific modulation of intranasal E2 brain distribution, and (2) cognitive and peripheral tissue effects of intranasal E2 in middle-aged ovariectomized rats. First, brain and peripheral organ distribution of intranasally administered, tritiated E2 was measured for E2 solubilized freely or in one of four cyclodextrin formulations. The E2-cyclodextrin formulation with greatest E2 uptake in cognitive brain regions versus uterine horns was then compared to free E2 on learning, memory, and uterine measures. Free E2 improved spatial reference memory, whereas E2-cyclodextrin impaired spatial working memory compared to their respective controls. Both E2 formulations increased uterine horn weights relative to controls, with E2-cyclodextrin resulting in the greatest uterine horn weight, suggesting increased uterine stimulation. Thus, intranasal administration of freely solubilized E2 is a strategic delivery tool that can yield a cognitively beneficial impact of the hormone alongside decreased peripheral effects compared to intranasal administration of cyclodextrin solubilized E2.

Evaluation of Plasma Microbial Cell-Free DNA Sequencing to Predict Bloodstream Infection in Pediatric Patients With Relapsed or Refractory Cancer.

Importance: Bloodstream infection (BSI) is a common, life-threatening complication of treatment for cancer. Predicting BSI before onset of clinical symptoms would enable preemptive therapy, but there is no reliable screening test. Objective: To estimate sensitivity and specificity of plasma microbial cell-free DNA sequencing (mcfDNA-seq) for predicting BSI in patients at high risk of life-threatening infection. Design, Setting, and Participants: A prospective pilot cohort study of mcfDNA-seq for predicting BSI in pediatric patients (<25 years of age) with relapsed or refractory cancers at St Jude Children's Research Hospital, a specialist quaternary pediatric hematology-oncology referral center. Remnant clinical blood samples were collected during chemotherapy and hematopoietic cell transplantation. Samples collected during the 7 days before and at onset of BSI episodes, along with negative control samples from study participants, underwent blinded testing using a mcfDNA-seq test in a Clinical Laboratory Improvement Amendments/College of American Pathologists-approved laboratory. Main Outcomes and Measures: The primary outcomes were sensitivity of mcfDNA-seq for detecting a BSI pathogen during the 3 days before BSI onset and specificity of mcfDNA-seq in the absence of fever or infection in the preceding or subsequent 7 days. Results: Between August 9, 2017, and June 4, 2018, 47 participants (27 [57%] male; median age [IQR], 10 [5-14] years) were enrolled; 19 BSI episodes occurred in 12 participants, and predictive samples were available for 16 episodes, including 15 bacterial BSI episodes. In the 3 days before the onset of infection, predictive sensitivity of mcfDNA-seq was 75% for all BSIs (12 of 16; 95% CI, 51%-90%) and 80% (12 of 15; 95% CI, 55%-93%) for bacterial BSIs. The specificity of mcfDNA-seq, evaluated on 33 negative control samples from enrolled participants, was 82% (27 of 33; 95% CI, 66%-91%) for any bacterial or fungal organism and 91% (30 of 33; 95% CI, 76%-97%) for any common BSI pathogen, and the concentration of pathogen DNA was lower in control than predictive samples. Conclusions and Relevance: A clinically relevant pathogen can be identified by mcfDNA-seq days before the onset of BSI in a majority of episodes, potentially enabling preemptive treatment. Clinical application appears feasible pending further study. Trial Registration: ClinicalTrials.gov identifier: NCT03226158.

Sequencing the Genomes of Single Cells.

Single-cell genome sequencing can detect low-frequency genetic alterations present in complex tissues. However, the experimental procedures are technically challenging. This includes dissociation of the tissue, isolation of single cells, whole-genome amplification, sequencing library preparation, and an optional target enrichment. Here we describe how to perform each of these processes to obtain high-quality single-cell genome sequencing data.

Patterns of Infancy Growth and Metabolic Hormonal Profile Are Different in Very-Low-Birth-Weight Preterm Infants Born Small for Gestational Age Compared to Those Born Appropriate for Gestational Age.

BACKGROUND/AIMS: An increased preterm birth survival rate is associated with long-term neurological and metabolic risks; thus, our aim was to evaluate whether early patterns of infancy anthropometry and metabolic hormonal profile differ in preterm infants born small for gestational age (SGA) or appropriate for gestational age (AGA) from birth to 36 months of corrected age (CA). METHODS: We recruited 110 very-low-birth-weight (VLBW) preterm infants (AGA = 60 and SGA = 50) with a mean birth weight of -2.39 ± 0.77 versus 0.57 ± 0.54 standard deviation scores (SDS) (p < 0.01) and birth length of -2.1 ± 1.05 versus -0.44 ± 0.82 SDS (p < 0.01), respectively. Anthropometry and blood sampling for insulin, insulin-like growth factor (IGF)-II, IGF-I, and leptin were performed for up to 3 years. RESULTS: All neonates increased their weight, length, and head circumference SDS during the early inpatient period. Up to 90% reached a normal length within this period. The IGF-II, insulin, and glycemia concentrations changed in parallel with weight. In the first year of CA, only SGA infants gained weight and height SDS. The homoeostatic model assessment had a trend toward higher values in SGA infants at 24 and 36 months (p = 0.06 and p = 0.07). CONCLUSION: Being SGA is the strongest predictor of early recovery of height in VLBW preterm infants. Follow-up will allow us to determine whether the differences in the growth patterns of VLBW preterm infants by birth weight SDS persist.

Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours.

Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues. Here we present a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukaemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for paediatric cancers and emphasize the need for paediatric cancer-specific development of precision therapies.

Genome-wide segregation of single nucleotide and structural variants into single cancer cells.

BACKGROUND: Single-cell genome sequencing provides high-resolution details of the clonal genomic modifications that occur during cancer initiation, progression, and ongoing evolution as patients undergo treatment. One limitation of current single-cell sequencing strategies is a suboptimal capacity to detect all classes of single-nucleotide and structural variants in the same cells. RESULTS: Here we present a new approach for determining comprehensive variant profiles of single cells using a microfluidic amplicon-based strategy to detect structural variant breakpoint sequences instead of using relative read depth to infer copy number changes. This method can reconstruct the clonal architecture and mutational history of a malignancy using all classes and sizes of somatic variants, providing more complete details of the temporal changes in mutational classes and processes that led to the development of a malignant neoplasm. Using this approach, we interrogated cells from a patient with leukemia, determining that processes producing structural variation preceded single nucleotide changes in the development of that malignancy. CONCLUSIONS: All classes and sizes of genomic variants can be efficiently detected in single cancer cells using our new method, enabling the ordering of distinct classes of mutations during tumor evolution.

Serum fibroblast growth factor 21 levels are inversely associated with growth rates in infancy.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a metabolic and growth regulator. AIM: To investigate the role of FGF21 during growth in infancy. METHODS: Blood samples for FGF21, leptin, insulin and glucose were collected from cord blood obtained from 95 preterm and term newborns (cross-sectional group), and at 6 and 12 months of life in 80 preterm and term infants (longitudinal group). Length and weight were measured at birth, 6 months, and 12 months. RESULTS: From birth through 12 months of age, preterm infants' linear growth and weight gain were larger than those of term infants, irrespective of birth weight SDS. At birth and at 12 months, there was no difference in FGF21 levels between preterm and term infants; in contrast, at 6 months, serum FGF21 in term infants was significantly higher than that of preterm ones. In the 0-6-month period, in the whole longitudinal group, serum FGF21 was inversely correlated to the length change SDS, and such a significant inverse correlation persisted in the preterm-AGA group in the 6-12-month period. In addition, term infants who experienced length catch-up in the first 6 months of life exhibited lower serum FGF21 levels at 6 months, and those with length catch-up growth between 6 and 12 months had a greater decrease of serum FGF21 level in the same time period. CONCLUSIONS: Our results indicate that FGF21 in infancy is inversely correlated with linear growth rate, thus suggesting that FGF21 is a negative regulator of human growth.

[Sociodemographic/clinical characteristics and outcomes of patients admitted to the National Burn Center of Chile]. / Epidemiología del paciente gran quemado adulto en Chile: experiencia del Servicio de Quemados del Hospital de la Asistencia Pública de Santiago.

BACKGROUND: Approximately 150 subjects per year suffer severe burns in Chile. AIM: To analyze sociodemographic/clinical features and outcomes of severely burned patients. MATERIAL AND METHODS: Retrospective cohort study of 936 patients aged 47 ± 20 years (66% males), admitted to the National Burn Center of Chile between 2006 and 2010. Sociodemographic/clinical and burn variables and outcomes were studied. RESULTS: Mean total percentage of body surface area burned was 27 + 20%. A quarter of the patients had social features that could jeopardize rehabilitation. Fire was the burning agent in 73%, which along with electricity presented greater lethality (p < 0.01). Inhalation injury was diagnosed in 22% of the patients. Twenty eight percent of patients had impaired consciousness at the moment of the accident, leading to larger burns, higher incidence of inhalation injury and greater lethality. Lethality for severe, critical and exceptional survival groups was 8.4,37.7 and 70.4%, respectively. CONCLUSIONS: Severely burned patients in Chile are mainly males at working age. Fire is the main agent and 28% had impaired consciousness, which was associated with an increase in the severity of burns. Knowledge of the characteristics and outcomes of the patients is important to implement prevention and treatment strategies adjusted to the national reality.

Epidemiología del paciente gran quemado adulto en Chile: experiencia del Servicio de Quemados del Hospital de la Asistencia Pública de Santiago / Sociodemographic/clinical characteristics and outcomes of patients admitted to the National Burn Center of Chile

Background: Approximately 150 subjects per year suffer severe burns in Chile. Aim: To analyze sociodemographic/clinical features and outcomes of severely burned patients. Material and Methods: Retrospective cohort study of 936 patients aged 47 ± 20 years (66% males), admitted to the National Burn Center of Chile between 2006 and 2010. Sociodemographic/clinical and burn variables and outcomes were studied. Results: Mean total percentage of body surface area burned was 27 + 20%. A quarter of the patients had social features that could jeopardize rehabilitation. Fire was the burning agent in 73%, which along with electricity presented greater lethality (p < 0.01). Inhalation injury was diagnosed in 22% of the patients. Twenty eight percent of patients had impaired consciousness at the moment of the accident, leading to larger burns, higher incidence of inhalation injury and greater lethality. Lethality for severe, critical and exceptional survival groups was 8.4,37.7 and 70.4%, respectively. Conclusions: Severely burned patients in Chile are mainly males at working age. Fire is the main agent and 28% had impaired consciousness, which was associated with an increase in the severity of burns. Knowledge of the characteristics and outcomes of the patients is important to implement prevention and treatment strategies adjusted to the national reality.

Accelerated early pubertal progression, ovarian morphology, and ovarian function in prospectively followed low birth weight (LBW) girls.

AIM: To compare pubertal development in age-matched healthy girls born with low birth weight (LBW) or appropriate birth weight for gestational age (AGA). SUBJECTS AND METHODS: Girls with breast in Tanner stage II and normal body mass index were followed for 3 years with a complete physical exam, bone age, pelvic ultrasound, and measurement of gonadal hormones using a leuprolide test. RESULTS: Forty-one girls (AGA 25/LBW 16) were followed up for 3 years. By 3 years, they had similar bone age, adjusted height, and body composition. In LBW girls, breast Tanner stage advanced faster during the first 2 years of follow-up, which was associated with higher serum androgens. Hirsutism score, ovarian volume, and number of follicles between AGA and LBW were not different nor was age of menarche. By the third year, basal and poststimulated levels of gonadotropins and androgens anti-Müllerian hormone and inhibin B were similar in both groups and did not show differences related to birth weight or degree of catch-up growth. CONCLUSION: LBW recruits showed a slightly faster breast development but no differences in androgen excess signs, internal genitalia, and gonadal hormonal patterns.

Leptin and IGF-I/II during the first weeks of life determine body composition at 2 years in infants born with very low birth weight.

Rapid early growth is associated with adverse metabolic outcome. The aim of this study was to determine whether there are differences in body composition (BC) between very-low-birth-weight preterm (VLBWPT) infants born appropriate for gestational age (AGA) and small for gestational age (SGA) and whether these differences relate to first-year growth. Twenty-six VLBWPT (15 AGA and 11 SGA). The BC was analyzed by dual X-ray absorptiometry at 2 years, and insulin-like growth factors (IGFs) I and II and leptin were administered weekly for 8 weeks and at 1, 3, 6, and 12 months. At 24 months, the VLBW SGA infants were lighter and had less peripheral fat and lean mass than VLBW AGA infants. In all patients, the percentage of fat mass correlated inversely with the change in weight [standard deviation scores (SDS)] from newborn to 2 and 4 weeks and the 1-month leptin and lean mass (SDS) correlated inversely with the change in weight (SDS) from newborn to 2, 4, and 8 weeks and with 4-week IGF-I and 8-week IGF-II. Lean mass (SDS) inversely correlated with 6-month IGF-I and directly correlated with 1-week and 3-month IGF-I in SGA VLBW infants only. A longer follow-up period will show whether additional differences will develop later.