Risk factors for mortality in preterm infants with necrotizing enterocolitis: a retrospective multicenter analysis.

It is difficult to predict the risk of mortality in necrotizing enterocolitis (NEC). This study aimed at identifying risk factors for severe NEC (Bell stage III) and mortality in preterm children with NEC. In this multicenter retrospective study, we analyzed multiple data from 157 premature children with confirmed NEC in the period from January 2007 to October 2018. We performed univariate, multivariate, stepwise logistic regression, and receiver operator characteristics (ROC) analyses. We were able to demonstrate that low Apgar scores (notably at 1' and 5'), low hemoglobin concentration (Hgb), and high lactate level at disease onset and during disease correlated with NEC severity and mortality (P < 0.05, respectively). Severe NEC was related to congenital heart disease (CHD - OR 2.6, CI95% 1.2-5.8, P 0.015) and patent ductus arteriosus (PDA - OR 3.3, CI95% 1.6-6.9, P 0.0012), whereas death was related to the presence of PDA (OR 5.5, CI95% 2.3-14, P < 0.001).Conclusion: Low Apgar scores, low Hgb, high lactate levels, and the presence of CHD or PDA correlated with severe NEC or mortality in children with NEC. What is Known: • It remains difficult to predict which infant that suffers from necrotizing enterocolitis at risk of death. • Several clinical and laboratory parameters tools to predict fatal outcome in NEC. What is New: • The following laboratory parameters were associated with the risk of death from NEC: Hemoglobin concentration, base excess and lactate level. • The following clinical variables were associated with the risk of death from NEC: Apgar scores, as well as the presence of congenital heart disease and patent ductus arteriosus.

Incarcerated Small-Bowel Pericardial Diaphragmatic Hernia After Pericardio-Peritoneal Window Creation: Report of a Rare Case.

BACKGROUND Pericardio-peritoneal windows are surgically created to treat symptomatic pericardial effusion, usually of oncological origin, to alleviate cardiac tamponade-like symptoms. Common complications include infection, failure to drain the fluid correctly, and arrythmias. There are few published cases of intra-abdominal complications due to these interventions. This report discusses pericardial diaphragmatic incarcerated hernia, which is one such complication. CASE REPORT We report the case of an 84-year-old woman with advanced non-small cell lung carcinoma, who recently underwent surgery to create a pericardio-peritoneal window to treat a chronic malignant pericardial effusion. The patient presented in our Emergency Department because of abdominal pain with absence of flatus and stool for more than 4 days. Computed tomography scanning confirmed a proximal small-bowel obstruction due to incarcerated small bowel into the pericardial window. Reduction of the hernia was performed laparoscopically. After a bowel viability assessment by indocyanine green angiography, the pericardial window was covered by a noncovered macroporous mesh to avoid recurrence and to allow continuous pericardial fluid drainage. CONCLUSIONS In case of abdominal pain after the creation of a pericardio-peritoneal window, we suggest the prompt use of computed tomography after initial examination. Indeed, although rare, a pericardial diaphragmatic hernia is possible and requires surgical exploration if there is a risk of bowel strangulation. The operation can be done laparoscopically, and the hernia repair should involve the placement of a nonabsorbable and noncovered macroporous mesh. This should prevent hernia recurrence, while also allowing adequate drainage of the pericardial effusion.

Use of a real-time continuous glucose monitoring system in children and young adults on insulin pump therapy: patients' and caregivers' perception of benefit.

BACKGROUND: Real-time continuous glucose monitoring systems (RT-CGMS) are a recently introduced technology for type 1 diabetes and experience in children is limited. OBJECTIVE: To assess patient and caregiver's perception of benefits and disadvantages of RT-CGMS in children or young adults with type 1 diabetes mellitus (DM) on insulin pump therapy. SUBJECTS AND METHODS: Forty-three subjects (3-25 yr) on insulin pump therapy were included in the study. Thirty-four used RT-CGMS for a short-term trial (4 wk, ST group) and nine as a long-term tool (2-18 months, LT group). Forty subjects or their caregivers completed a questionnaire. RESULTS: On the basis of the questionnaire responses, hypoglycemia prevention was the most common perceived benefit (88%), followed by elimination of hypoglycemia-related anxiety (83%), ease of pattern management (85%), improvement of diabetes control (80%), improvement of quality of life (78%), and ease of diabetes care (78%). Negative effects included irritation/annoyance from the sensor alarm (48%) and insertion site bruising, pain, or irritation (43%). A small percentage of patients who were interested in purchasing the device (12%) decided against using it LT after a 4-wk trial on RT-CGMS. CONCLUSIONS: The most common perceived benefits of RT-CGMS are prevention of hypoglycemia and decrease in hypoglycemia-related anxiety. Negative effects are uncommon and seem to be unlikely to affect the decision to use RT-CGMS for a LT. A ST trial seems to be a valuable tool for the patient/caregiver in determining whether to purchase the device and in setting realistic expectations of its potential benefits.

Treatment of pituitary gigantism with the growth hormone receptor antagonist pegvisomant.

CONTEXT: Treatment of pituitary gigantism is complex and the results are usually unsatisfactory. OBJECTIVE: The objective of the study was to describe the results of therapy of three children with pituitary gigantism by a GH receptor antagonist, pegvisomant. DESIGN: This was a descriptive case series of up to 3.5 yr duration. SETTING: The study was conducted at a university hospital. PATIENTS: Patients included three children (one female, two males) with pituitary gigantism whose GH hypersecretion was incompletely controlled by surgery, somatostatin analog, and dopamine agonist. INTERVENTION: The intervention was administration of pegvisomant. MAIN OUTCOME MEASURES: Plasma IGF-I and growth velocity were measured. RESULTS: In all three children, pegvisomant rapidly decreased plasma IGF-I concentrations. Growth velocity declined to subnormal or normal values. Statural growth fell into lower growth percentiles and acromegalic features resolved. Pituitary tumor size did not change in two children but increased in one boy despite concomitant therapy with a somatostatin analog. CONCLUSIONS: Pegvisomant may be an effective modality for the therapy of pituitary gigantism in children. Titration of the dose is necessary for optimal efficacy, and regular surveillance of tumor size is mandatory.

Augmentation of growth hormone secretion after testosterone treatment in boys with constitutional delay of growth and adolescence: evidence against an increase in hypothalamic secretion of growth hormone-releasing hormone.

The increase in pituitary GH secretion that occurs during mid-late puberty in boys follows an increase in circulating testosterone (T) concentration; the direct mechanism by which this occurs is unknown. We hypothesized that T increases GH secretion during puberty by augmenting hypothalamic output of GHRH. Using constant infusions of a GHRH antagonist, we tested this hypothesis in six early pubertal boys with constitutional delay of growth and adolescence who had a mean chronological age of 14.0 +/- 0.3 yr and mean bone age of 11.4 +/- 0.2 yr. Blood samples were obtained from subjects every 15 min for 24 h during the overnight infusion of normal saline (2000-0600 h) and again during the overnight infusion of GHRH antagonist (0.33 microg/kg/h) the following night. Subjects then received transdermal T (5-mg patch) for 12 h nightly and were studied again after 4 wk of treatment. Serum samples were assayed for GH and total ghrelin; the percent suppression of GH during GHRH antagonist infusion was calculated. Morning serum T rose from 0.44 +/- 0.09 to 4.43 +/- 0.74 microg/liter (P = 0.005). T treatment was associated with a 92.6% increase in mean nocturnal GH secretion area under the curve (830 +/- 177 to 1599 +/- 340 microg/24 h.liter). Infusion of GHRH-antagonist suppressed mean nocturnal GH area under the curve by 29.1% before T treatment (830 +/- 177 to 621 +/- 168 microg/24 h.liter), and by 29.4% after T treatment (1599 +/- 340 to 1182 +/- 249 microg/24 h.liter; P = 0.99). Somatotroph sensitivity to GHRH was tested with 0.1- and 1.0-microg/kg doses of GHRH-44 iv; GH response did not change with regard to T treatment. The mean 24-h concentration of total ghrelin was unchanged with regard to T treatment. In summary, nightly transdermal T administration in six boys with constitutional delay of growth and adolescence increased GH output almost 2-fold, whereas the degree of GH suppressibility by GHRH antagonist remained unchanged. We conclude that the T-associated augmentation of GH secretion during early puberty in boys is unlikely to involve an absolute increase in hypothalamic GHRH output.

An uncommon case of abdominal pain: superior mesenteric artery syndrome.

Superior mesenteric artery (SMA) syndrome is a rare cause of abdominal pain, nausea and vomiting that may be undiagnosed in patients presenting to the emergency department (ED). We report a 54-year-old male presenting to a community ED with abdominal pain and the subsequent radiographic findings.The patient's computed tomgraphy (CT) of the abdomen and pelvis demonstrates many of the hallmark findings consistent with SMA syndrome, including; compression of the duodenum between the abdominal aorta and superior mesenteric artery resulting in intestinal obstruction, dilation of the left renal vein, and gastric distension. Patients diagnosed with SMA syndrome have a characteristically short distance between the superior mesenteric artery and the aorta (usually 2-8 mm) in contrast to healthy patients (10-34 mm). Our patient's aortomesenteric distance was measured to be approximately 4 mm. Furthermore, the measured angle between the superior mesenteric artery and the aorta is reduced in patients with SMA syndrome from a normal range of 28°-65° to a measurement between 6°-22°. Our patient's aortomesenteric angle was difficult to measure secondary to poor sagittal reconstructions, but appears to be approximately 30°. Following radiographic evidence suggesting SMA syndrome together with our patient's constellation of presenting symptoms, a diagnosis of SMA syndrome was made and the patient was admitted to the general surgery service. However, our patient decided to leave against medical advice owing to improvement of his symptoms following the emptying of two liters of gastric contents via nasogastric tube evacuation.

Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency.

CONTEXT: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases. OBJECTIVE: A locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified. DESIGN: The study design comprised single-nucleotide polymorphism genotyping and mutation detection. SETTING: The study was conducted at secondary and tertiary referral centers. PATIENTS: Eighty probands from families referred for investigation of the genetic cause of FGD participated in the study. INTERVENTIONS: There were no interventions. RESULTS: Analysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families. CONCLUSIONS: Mutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD.

Somatostatin analogs in medical treatment of acromegaly.

Although acromegaly remains a disease primarily addressed by pituitary microsurgery, most patients require secondary treatment for persistent growth hormone (GH) hypersecretion and elevated serum insulin-like growth factor-1 (IGF-1) concentrations following adenomectomy. Persistently abnormal serum GH and IGF-1 can be reduced to normal concentrations in better than half of post-surgery acromegalics using the pharmacologic treatments available at present, the dopamine agonists (DA) and somatostatin (SST) analogs. The long-acting SST analogs octreotide LAR and lanreotide SR have become the mainstay of medical treatment for acromegaly, having largely supplanted DA agents since the introduction of bromocriptine for the suppression of GH secretion in the 1970s. The DA cabergoline may be effective in up to half of patients, however, in particular those patients whose tumors cosecrete prolactin. On the horizon is the GH-receptor antagonist pegvisomant, which is expected to enable the reduction of serum IGF-1 to the normal range in the vast majority of postoperative acromegaly patients, representing a revolutionary development in the medical treatment of this disease. We here review the choices available to the endocrinologist in the pharmacologic treatment of acromegaly, focusing upon the SST analogs.

Medical management of growth hormone-secreting pituitary adenomas.

The primary treatment of acromegaly remains transsphenoidal adenomectomy, yet the tissue overgrowth of acromegaly often progresses following surgery, and responds to radiotherapy only after significant delay. Persistently elevated serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations can be normalized in about half of post-surgery acromegalics using the pharmacologic alternatives presently available, the dopamine agonists (DA) and somatostatin (SST) analogs. Cabergoline, the most efficacious DA, normalizes IGF-I in approximately 37% of patients, whereas the long-acting SST analogs, Octreotide LAR and Lanreotide SR, do so in 66%. Significant tumor shrinkage may be attained with SST analogs in particular, and when necessary, the primary medical treatment of acromegaly may be successfully addressed with this class of drugs. Greatly enhanced efficacy is expected from the GH receptor antagonist pegvisomant, which is nearing market availability and will enable the normalization of serum IGF-I in virtually all patients treated. We review here the pharmacologic treatments of excessive GH secretion.

Sex differences in FSH-regulatory peptides in pubertal age boys and girls and effects of sex steroid treatment.

BACKGROUND: FSH concentrations are higher in girls than in boys before puberty. We hypothesized that steroid-mediated changes in FSH-regulatory proteins underlie the sex differences in FSH secretion and pubertal timing. METHODS: FSH-regulatory proteins, LH, FSH and sex steroids were measured in five boys, 10 girls, and five girls with Turner syndrome before and during sex steroid treatment (girls, 0.05 mg/day estradiol; boys, 5 mg/day testosterone) for up to 4 weeks. Blood was obtained every 15 min from 20.00 to 08.00 h before and during sex steroid treatment. RESULTS: The mean FSH concentration was higher in girls than in boys (P = 0.0044). Activin-A concentrations were greater (P < 0.0001) and inhibin-B concentrations lower (P < 0.0001) in girls compared with boys. Steroid treatment (i) suppressed LH/FSH concentrations in all subjects; (ii) increased the mean activin-A concentration in all but the Turner girls (P = 0.001); and (iii) decreased inhibin-B concentrations in boys (P = 0.005) but not in girls. Total follistatin and follistatin 288 concentrations did not differ by sex. CONCLUSIONS: Sex steroids regulate circulating activin-A and inhibin-B concentrations in children. The lower inhibin-B and higher activin-A concentrations may explain the higher FSH and earlier onset of puberty in girls.

Clinical, autoimmune, and HLA characteristics of children diagnosed with type 1 diabetes before 5 years of age.

BACKGROUND: Little is known about auxologic, autoimmune, and HLA characteristics specific to children with early-onset diabetes (EOD). HLA subtypes have been shown to play an important part in the determination of islet-cell autoimmunity and in the pace and intensity of the beta-cell destructive process. OBJECTIVES: Our goals were to: 1) outline auxologic, autoimmune, and HLA class II characteristics of children diagnosed with type 1 diabetes before 5 years of age (EOD); 2) evaluate differences between EOD and later-onset or non-age-stratified type 1 diabetes; and 3) investigate the relation between type 1 diabetes-related HLA subtypes and markers of diabetic autoimmunity in EOD. METHODS: Forty children with EOD were studied. Auxologic and antibody radioimmunoassay data were obtained by retrospective analysis of records. HLA diabetes-related class II alleles were typed by polymerase chain reaction using sequence-specific primers. RESULTS: At diagnosis, the average age of the EOD study patients was 2.6 years, body mass index was 16.9 kg/m2, and weight was 106% of average weight for height. When compared with a matched subgroup of children with later-onset type 1 diabetes, preschoolers did not significantly differ in terms of birth weight or body mass index. The frequency of positive islet cell antibodies 512 and glutamic acid decarboxylase 65 antibodies was significantly less in EOD (28.6% and 31.6%, respectively). There were significant differences in the frequencies of some diabetes-related HLA alleles and haplotypes between the early-onset group and a large non-age-stratified type 1 diabetes group. None of the patients with EOD had either of the protective DRB1*1501 or DQB1*0602 alleles. There was a negative correlation between glutamic acid decarboxylase and the predisposing haplotype DR3/DQ2. CONCLUSIONS: Children diagnosed with type 1 diabetes before 5 years of age may have different diabetes-related autoimmune and genetic characteristics from those diagnosed at a later age.