Consistent evidence associates IGF-1 deficiency and metabolic syndrome. In this review, we will focus on the metabolic effects of IGF-1, the concept of metabolic syndrome and its clinical manifestations (impaired lipid profile, insulin resistance, increased glucose levels, obesity, and cardiovascular disease), discussing whether IGF-1 replacement therapy could be a beneficial strategy for these patients. The search plan was made in Medline for Pubmed with the following mesh terms: IGF-1 and “metabolism, carbohydrate, lipids, proteins, amino acids, metabolic syndrome, cardiovascular disease, diabetes” between the years 1963–2015. The search includes animal and human protocols. In this review we discuss the relevant actions of IGF-1 on metabolism and the implication of IGF-1 deficiency in the establishment of metabolic syndrome. Multiple studies (in vitro and in vivo) demonstrate the association between IGF-1 deficit and deregulated lipid metabolism, cardiovascular disease, diabetes, and an altered metabolic profile of diabetic patients. Based on the available data we propose IGF-1 as a key hormone in the pathophysiology of metabolic syndrome; due to its implications in the metabolism of carbohydrates and lipids. Previous data demonstrates how IGF-1 can be an effective option in the treatment of this worldwide increasing condition. It has to distinguished that the replacement therapy should be only undertaken to restore the physiological levels, never to exceed physiological ranges.

Recipients of liver transplantation (LT) may develop immunological tolerance. Factors predictive of tolerance are not clearly understood. Transplant recipients with normal liver function tests and without active viral hepatitis or autoimmune disease who presented with side effects of immunosuppression or a high risk of de novo malignancies were selected to participate in this prospective study. Twenty-four patients fulfilled the inclusion criteria and, therefore, underwent a gradual reduction of immunosuppression. Tolerance was defined as normal liver function tests after immunosuppression withdrawal. Basal clinical and immunological characteristics, including lymphocyte counts and subpopulations (T, B, natural killer, CD4 1 , CD8 1 , and regulatory T cells) and the phytohemagglutinin stimulation index (SI), were compared for tolerant and nontolerant patients. Fifteen of the 24 patients (62.5%) were tolerant at a median of 14 months (interquartile range 5 8.5-22.5 months) after complete immunosuppression withdrawal. Tolerant patients had a longer median interval between transplantation and inclusion in the study (156 for tolerant patients versus 71 months for nontolerant patients, P 5 0.003) and a lower median SI (7.49 for tolerant patients versus 41.73 for nontolerant patients, P 5 0.01). We identified 3 groups of patients with different probabilities of tolerance: in the first group (n 5 7 for an interval > 10 years and an SI < 20), 100% reached tolerance; in the second group (n 5 10 for an interval > 10 years and an SI > 20 or an interval < 10 years and an SI < 20), 60% reached tolerance; and in the third group (n 5 7 for an interval < 10 years and an SI > 20), 29% reached tolerance. In conclusion, a high proportion of select LT recipients can reach tolerance over the long term. Two simple basal variables-the time from transplantation and the SI-may help to identify these patients. Liver Transpl 19:937-944, 2013. V C 2013 AASLD. Received February 25, 2013 accepted May 19, 2013. Although the survival of liver transplantation (LT) patients has improved since the early 1980s with refinements in immunosuppression therapy and surgical techniques, the morbidity and mortality rates of these patients are still greater than those of the general population. 1,2 The quality of life and survival are still diminished in comparison with those of ageand sex-matched controls. 3,4 As long-term survival after transplantation has improved, side effects See Editorial on Page 933

Insulin-like growth factor 1 (IGF-1) is an anabolic hormone with several biological activities, such as proliferation, mitochondrial protection, cell survival, tissue growth and development, anti-inflammatory, antioxidant, antifibrogenic and antiaging. This hormone plays an important role in embryological and postnatal states, being essential for normal foetal and placental growth and differentiation. During gestation, the placenta is one of the major sources of IGF-1, among other hormones. This intrauterine organ expresses IGF-1 receptors and IGF-1 binding proteins (IGFBPs), which control IGF-1 activities. Intrauterine growth restriction (IUGR) is the second most frequent cause of perinatal morbidity and mortality, defined as the inability to achieve the expected weight for gestational age. Different studies have revealed that IUGR infants have placental dysfunction and low circulating levels of insulin, IGF-1, IGF-2 and IGFBPs. Such data suggest that IGF-1 deficiency in gestational state may be one of the major causes of foetal growth retardation. The aim of this review is to study the epidemiology, physiopathology and possible causes of IUGR. Also, it intends to study the possible role of the placenta as an IGF-1 target organ. The purpose is to establish if IUGR could be considered as a novel condition of IGF-1 deficiency and if its treatment with low doses of IGF-1 could be a suitable therapeutic strategy.

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Cirrhosis represents the final stage of chronic liver damage, which can be due to different factors such as alcohol, metabolic syndrome with liver steatosis, autoimmune diseases, drugs, toxins, and viral infection, among others. Nowadays, cirrhosis is an important health problem and it is an increasing cause of morbidity and mortality, being the 14th most common cause of death worldwide. The physiopathological pathways that lead to fibrosis and finally cirrhosis partly depend on the etiology. Nevertheless, some common features are shared in this complex mechanism. Recently, it has been demonstrated that cirrhosis is a dynamic process that can be altered in order to delay or revert fibrosis. In addition, when cirrhosis has been established, insulin-like growth factor-1 (IGF-1) deficiency or reduced availability is a common condition, independently of the etiology of chronic liver damage that leads to cirrhosis. IGF-1 deprivation seriously contributes to the progressive malnutrition of cirrhotic patient, increasing the vulnerability of the liver to establish an inflammatory and oxidative microenvironment with mitochondrial dysfunction. In this context, IGF-1 deficiency in cirrhotic patients can justify some of the common characteristics of these individuals. Several studies in animals and humans have been done in order to test the replacement of IGF-1 as a possible therapeutic option, with promising results.

Listeriosis can be a cause of arthritis. Here, we present a case of Listeria monocytogenes septic arthritis of the right hip in a 66-year-old male treated with mycophenolate mofetil for polyarteritis nodosa. So far, septic arthritis due to this microorganism has not been reported in patients treated with mycophenolate mofetil. We review the literature of L. monocytogenes septic arthritis and discuss the role of mycophenolate mofetil treatment in precipitating listeriosis.

Cartilage-hair hypoplasia syndrome (CHH) is a rare autosomal recessive condition characterized by metaphyseal chondrodysplasia and characteristic hair, together with a myriad of other symptoms, being most common immunodeficiency and gastrointestinal complications. A 15-year-old Mexican male initially diagnosed with Hirschsprung disease and posterior immunodeficiency, presents to our department for genetic and complementary evaluation for suspected CHH. Physical, biochemical, and genetic studies confirmed CHH together with IGF-1 deficiency. For this reason, we propose IGF-1 replacement therapy for its well-known actions on hematopoiesis, immune function and maturation, and metabolism. Ó 2016 Wiley Periodicals, Inc.Key words: cartilage-hair hypoplasia; IGF-1; RMRP gene; GHR INTRODUCTIONCartilage-hair hypoplasia syndrome (CHH) is a rare autosomal recessive condition that was originally described by McKusik in 1964 in Amish children. In this population, it accounts for one in 1,300 newborns [McKusick et al., 1965], while in the Finnish population it accounts for one in 23,000 newborns [M€ akitie and Kaitila, 1993]. Outside those populations it is extremely rare, with no incidence data available [M€ akitie and Kaitila, 1993]. The genetic locus for this disease falls within the RNA Component Of Mitochondrial RNA Processing Endoribonuclease (RMRP) gene, localized in chromosome 9p12, which codes for the RMRP, believed to be required for cell cycle, mtDNA replication and rRNA processing [Ridanp€ a€ a et al., 2001;Hermanns et al., 2005;Thiel et al., 2005;Martin and Li, 2007]. The RMRP RNA product associates with at least seven proteins whose interactions and roles remain to be discovered [Welting et al., 2004].The hallmark of this condition is a metaphyseal chondrodysplasia and characteristic hair (fine, sparse with scalp, blond eyelashes-93%), with other several signs and symptoms including short stature and skeletal dysplasia (100%) with varum deformation of lower extremities, hypoplastic anemia during childhood (79%), immunodeficiency (during childhood they may present different recurrent infections secondary to an immunodeficiency that may be humoral, B-cell or T-cell, or combined-56%) [Pierce and Polmar, 1982;M€ akitie et al., 1998, 2000bBaradaran-Heravi et al., 2008] with higher risk of malignancies, skin and nails abnormalities, gastrointestinal diseases (such as Hirschsprung disease [HD], malabsorption, anal stenosis and esophageal atresia-18%) [M€ akitie et al., 2002, 2000a], and failure to thrive [M€ akitie et al., 1992;Glass and Tifft, 1999;Riley et al., 2015]. The growth failure is progressive, owing, partly, to a weak or absent pubertal growth spurt; pubertal maturation is normal; testicular size is abnormal in some patients with normal serum concentrations of testosterone, inhibin B and gonadotropins [M€ akitie et al., 2001].These patients are symptomatic since birth, showing short-limb dwarfism and short puffy hands, with normal head circumference [Giedion, 1998]. The final adult heights range from 100.7 t...