Adult Height after Growth Hormone Treatment at Pubertal Onset in Short Adolescents Born Small for Gestational Age: Results from a Belgian Registry-Based Study.

OBJECTIVES: Information on the efficacy of GH treatment in short SGA children starting their treatment in adolescence is limited. Therefore, adult height (AH), total height gain, and pubertal height gain were evaluated in short SGA children who started GH treatment at pubertal onset. PATIENT AND METHODS: Growth data of 47 short SGA adolescents (22 boys) who started GH treatment at pubertal onset (PUB group) were compared with results from 27 short SGA patients (11 boys) who started GH therapy at least 1 year before pubertal onset (PrePUB group). RESULTS: The PUB group achieved a mean (±SD) total height gain of 0.8 ± 0.7 SDS and an AH of -2.5 ± 0.7 SDS after 4.1 ± 1.1 years of GH treatment with a dosage of 41.8 ± 8.4 µg/kg/day. These results were comparable with those in the PrePUB group, which was treated for a longer duration (5.8 ± 2.1 years), resulting in a total height gain of 1.1 ± 0.7 SDS and an AH of -2.1 ± 1.0 SDS. Multiple regression analysis showed a significantly lower height gain in pubertal patients, females, and patients weighing less at start of GH treatment. An AH above -2 SDS and above the parent-specific lower limit of height was, respectively, reached in 28% and 70% of PUB and 44% and 67% of PrePUB patients (NS). AH SDS was positively correlated with the height SDS at start of GH. CONCLUSIONS: Short SGA adolescents starting GH therapy at an early pubertal stage have a modest and variable height gain. A normal AH can be expected in one third of the patients, especially in those with a smaller height deficit at onset of GH treatment.

Clinical presentation and outcome of children with central diabetes insipidus associated with a self-limited or transient pituitary stalk thickening, diagnosed as infundibuloneurohypophysitis.

OBJECTIVE: Despite lymphocytic or autoimmune infundibuloneurohypophysitis (INH) is an increasingly recognized aetiology in children with central diabetes insipidus (CDI); clinical data on epidemiology (clinical evolution, predisposing factors, complications), diagnosis and management of this entity are limited and mostly based on published case reports. The aim of this study was to gain a broader insight in the natural history of this disease by analysing the clinical presentation, radiological pituitary stalk changes, associated autoimmunity and hormonal deficiencies in children with CDI and a self-limiting or transient stalk thickening (ST), diagnosed as autoimmune infundibuloneurohypophysitis, during the last 15 years in four Belgian university hospitals. DESIGN AND PATIENTS: The medical files of nine CDI patients with a ST at initial presentation and no signs of Langerhans cell histiocytosis or germinoma at presentation and/or during follow-up of more than 1.5 years were reviewed. RESULTS: Age at presentation ranged from 3 to 14 years. Two patients had a positive family history of autoimmunity. Three children presented with associated growth failure, two with nausea and one with long-standing headache. Median maximal diameter of the stalk was 4.6 mm (2.7-10 mm). Four patients had extra-pituitary brain anomalies, such as cysts. One patient had central hypothyroidism, and another had a partial growth hormone deficiency at diagnosis. Within a mean follow-up of 5.4 (1.5-15) years, stalk thickening remained unchanged in two patients, regressed in one and normalized in six children. CDI remained in all, while additional pituitary hormone deficiencies developed in only one patient. CONCLUSIONS: In this series of children INH with CDI as initial presentation, CDI was permanent and infrequently associated with anterior pituitary hormone deficiencies, despite a frequent association with nonstalk cerebral lesions.

Outcomes of algorithm-based modifications of insulinotherapy during exercise in MDI vs insulin pump-treated children with type 1 diabetes: Results from the TREAD-DIAB study.

OBJECTIVES: To evaluate the evolution of subcutaneous glucose (SG) after a standardized aerobic exercise in children and adolescents treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) regimen before and after adaptation of insulin doses. RESEARCH DESIGN AND METHODS: Eleven CSII- and 13 MDI-treated patients performed 2 30-minute sessions of moderate to vigorous (70% of age-based maximal heart rate) exercise on a treadmill under continuous glucose monitoring (CGM). First sessions were scheduled without insulin modification (TT#1) while patients performed second sessions (TT#2) after preemptive algorithm-based insulin dose modifications. RESULTS: While insulin adaptations did not modify immediate postexercise drops in blood glucose during TT#2 in either group, CSII-treated patients had their glucose control improved during TT#2 (mean of 141 ± 56 mg/dL vs 144 ± 80 mg/dL in TT#1; P < .05) with up to 86% of SG levels within targets during 16 hours postexercise. Contrarily, SG levels did not normalize during TT#2 in MDI-treated patients who experienced higher rates of hyperglycemia during the afternoon snack. As compared with TT#1, CSII-treated patients had reduced rates of hypoglycemia during 4 hours post-TT#2 (from 19.5% to 2.1%; P < .01) and had shorter duration of nocturnal hypoglycemia (35.5 ± 12.8 vs 204.7 ± 165 minutes; P = .04) whereas in the MDI group no changes in percentages of hypoglycemia were observed during TT#2. CONCLUSION: In our pediatric cohort, algorithmic adaptations of insulin doses were associated with better outcomes in terms of postexercise glucose control in patients with CSII therapy but not with MDI treatment.

Persistence of a chimerical phenotype after hepatocyte differentiation of human bone marrow mesenchymal stem cells.

OBJECTIVES: Recent studies have suggested the potential of mesenchymal stem cells (MSCs) to differentiate into a hepatocyte-like lineage. Here, we evaluate the efficacy of hepatocyte differentiation of MSCs by studying acquisition of hepatocyte-like features together with alteration of the native mesenchymal phenotype. MATERIAL AND METHODS: In vitro, we have investigated protein and mRNA level expression of hepatocyte and mesenchymal markers of mesenchymal-derived hepatocyte-like cells (MDHLCs) and we have evaluated their functionality using metabolic assays. In vivo, we investigated co-expression of hepatocyte (albumin, alpha-foetoprotein, cytokeratin 18) and mesenchymal (fibronectin, vimentin) markers after transplantation of MSCs or MDHLCs into severe combined immune deficiency mice. RESULTS: We observed that while in vitro these cells acquired some phenotypic and functional features of mature hepatocytes, they partially preserved their mesenchymal phenotype. After intrasplenic transplantation, engrafted MSCs with isolated expression of fibronectin and alpha-foetoprotein were observed. When these cells were injected into the liver, they expressed all analysed markers, confirming the chimaeric co-expression observed in vitro. Conversely, liver-engrafted MDHLCs conserved their hepatocyte-lineage markers but lost their chimaeric phenotype. CONCLUSIONS: Hepatocyte differentiation of MSCs predominantly allows the acquisition of phenotypic hallmarks and provides chimaeric cells that maintain expression of initial lineage markers. However, advanced maturation to the hepatocyte-like phenotype could be obtained in vivo by conditioning MSCs prior to transplantation or by infusing cells into the liver micro-environment.

Re-fixation in a lymph node revealing solution is a powerful method for identifying lymph nodes in colorectal resection specimens.

AIM: To verify an impact of a lymph node revealing solution (LRS) on the number of lymph nodes (LN) revealed in colorectal resection specimens. MATERIAL AND METHOD: Fifty-nine cases of rectosigmoid carcinomas divided into two subgroups-stage pT2&3 (20 cases) and ypT2&3 (with pre-operative radiotherapy-39 cases)-were formalin fixed for 42-72 h, serially sectioned and re-fixed in LRS containing ethanol, diethyl ether, glacial acetic acid, and formalin for 24 h. The number of LNs was matched to a control group consisting of 34 cases of colorectal carcinoma, 14 pT2&3 and 20 ypT2&3 rectosigmoid carcinomas examined routinely. Results were statistically tested by Student's t-test. RESULTS: In the study group the total number of revealed LNs was 869, range 1-48, average 14.7 per specimen, median 15. In the control group the number of LNs was 200, range 0-13, average 5.9 per specimen, median 6. The difference between the study and the control group was statistically significant (P = 0.05). CONCLUSION: Using LRS leads to a significant increase in the number of revealed LNs in colorectal resection specimens and makes it possible to find more than 12 LNs in a majority of stage pT2 and pT3 adenocarcinomas.

Home assessment and care.

OBJECTIVE: To describe the scope of home care and to give practical advice for incorporating home visits into family practice. QUALITY OF EVIDENCE: Most of the literature is based on expert opinion, but there are some randomized trials and well done surveys. MAIN MESSAGE: Although physicians make fewer housecalls than they used to, home visiting is essential to providing good care to certain patients. An approach to evaluating patients and their home environments is presented. Management plans should be formulated in collaboration with home care teams. We offer practical advice for incorporating home visits into practice. CONCLUSION: Home visits can be a valuable and rewarding complement to family practice and are essential for the development of home care.