Transition from gynaecomastia to lipomastia in pubertal boys.

OBJECTIVE: Gynaecomastia is frequent in pubertal boys and is regarded as a self-limiting abnormality. However, longitudinal studies proving this hypothesis are scarce. DESIGN: Longitudinal follow-up study (median 2.4, range 1.0-4.8 years). METHODS: The regression of breast diameter was analysed in 31 pubertal boys aged 11.7-16.1 (median 13.2) years with gynaecomastia. Furthermore, weight changes (as BMI-SDS) and pubertal stage, oestradiol [E2], oestriol, oestrone, androstenedione, testosterone [T], dihydrotestosterone, gonadotropins, IGF-1, and IGFBP-3 serum concentrations determined at first clinical presentation were related to breast diameter regression determined by palpation and disappearance of breast glandular tissue in ultrasound in follow-up to identify possible predictors of breast regression. RESULTS: During the observation period, the breast diameter decreased (in median -1 (interquartile range [IQR] -5 to +1) cm). At follow-up, 6% of boys had no breast enlargement any more, and 65% developed lipomastia. Gynaecomastia was still present in 29%. None of the analysed hormones was related significantly to breast diameter regression or disappearance of breast glandular tissue. In multiple linear regression analyses adjusted for observational period, as well as age and BMI-SDS at first presentation, changes in BMI-SDS (ß-coefficient 6.0 ± 2.3, p = .015) but not the E2/T ratio or any other hormone determined at baseline was related to changes in breast diameter. CONCLUSIONS: Breast diameter regression seems not to be predictable by a hormone profile in pubertal boys with gynaecomastia. In pubertal boys presenting with gynaecomastia, conversion to lipomastia of smaller volume is common. The reduction of weight status was the best predictor of breast diameter regression.

Adipose-derived stromal cell therapy combined with a short course nonmyeloablative conditioning promotes long-term graft tolerance in vascularized composite allotransplantation.

The risks of chronic immunosuppression limit the utility of vascularized composite allotransplantation (VCA) as a reconstructive option in complex tissue defects. We evaluated a novel, clinically translatable, radiation-free conditioning protocol that combines anti-lymphocyte serum (ALS), tacrolimus, and cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) with adipose-derived stromal cells (ASCs) to allow VCA survival without long-term systemic immunosuppression. Full-mismatched rat hind-limb-transplant recipients received tacrolimus (0.5 mg/kg) for 14 days and were assigned to 4 groups: controls (CTRL) received no conditioning; ASC-group received CTLA4-Ig (10 mg/kg body weight i.p. postoperative day [POD] 2, 4, 7) and donor ASCs (1 × 106 iv, POD 2, 4, 7, 15, 28); the ASC-cyclophosphamide (CYP)-group received CTLA4-Ig, ASC plus cyclophosphamide (50 mg/kg ip, POD 3); the ASC-ALS-group received CTLA4-Ig, ASCs plus ALS (500 µL ip, POD 1, 5). Banff grade III or 120 days were endpoints. ASCs suppressed alloresponse in vitro. Median rejection-free VCA survival was 28 days in CTRL (n = 7), 34 in ASC (n = 6), and 27.5 in ASC-CYP (n = 4). In contrast, ASC-ALS achieved significantly longer, rejection-free VCA survival in 6/7 animals (86%), with persistent mixed donor-cell chimerism, and elevated systemic and allograft skin Tregs , with no signs of acute cellular rejection. Taken together, a regimen comprised of short-course tacrolimus, repeated CTLA4-Ig and ASC administration, combined with ALS, promotes long-term VCA survival without chronic immunosuppression.

Lower medial thigh perforator (LMTP) propeller flap for reconstruction of soft tissue defects around the knee.

BACKGROUND: Skin and soft-tissue defects around the knee are common and their reconstruction is still challenging and argued. Thin, pliable and well-vascularized tissues are required in order to restore the aesthetic appearance of the knee and facilitate joint function. Historically local muscle flaps were employed for the upper third of the lower limb reconstruction; however, since their introduction, different perforator flaps have been proposed for this purpose. The aim of this report is to share our clinical experience with the pedicled lower medial thigh perforator (p-LMT) flap for the reconstruction of skin and soft tissue defects around the knee. PATIENTS AND METHODS: Between August 2013 and July 20, 2018, patients underwent pedicled LMT propeller flap reconstruction for defects around the knee. The subunits of the defects were the suprapatellar, the infrapatellar and patellar area and in two cases a full around the knee defect was reported. Cause of defects included trauma (13), tumor (4) and infection after knee operation (3) and defect sizes ranged from 4 × 3 cm2 to 7 × 8 cm2 . RESULTS: Flap sizes ranged from 4 × 9 cm2 to 6 × 16 cm2 . One to two perforators based on the superficial femoral artery or descending genicular artery were found between the septum of satorius and vastus medialis, or piercing the vastus medialis during dissection. All flaps were rotated 180° in propeller fashion. All the donor sites were primarily closed and no complication at the donor site was detected. In the two cases of the total knee soft tissue defect, a double pedicled flaps reconstruction was required. After a 6 months follow-up, all the patients in the series achieved a full range of motion. CONCLUSIONS: Fasciocutaneous flaps are currently the first reconstructive option for the soft tissue defects around the knee. The p-LMT flap reconstruction in this case series achieved good aesthetic and functional outcomes and this flap may be a valuable option for the reconstruction of the small to medium soft tissue defects around the knee.

A pedicled split extended vertical deep inferior epigastric (s-vDIEP) flap and an adipo-dermal thigh local flap for the reconstruction of the medial thigh compartment after sarcoma resection: A case report.

Large upper medial thigh defects in prior irradiated tissue require challenging reconstructions. Several techniques have been reported to reconstruct this region and according to the literature, pedicled perforator flaps are the first reconstructive option. The anterolateral thigh flap is considered the gold standard, while surprisingly the pedicle deep inferior epigastric (DIEP) flap in vertical fashion has not been frequently employed, if compared with its muscular counterpart, the pedicle vertical rectus abdomins flap (vRAM). We report a case of a multilayered flaps reconstruction of the left medial thigh after an excision of a sarcoma involving the whole adductors compartment. A 75-year-old male patient underwent a free margins resection of the sarcoma. After the resection, a soft tissue defect of 24 cm × 14 cm × 14 cm spreading from the groin to the medial tuberosity of the tibia, was left. We performed a reconstructive technique based on a pedicled split extended vertical deep inferior epigastric (s-vDIEP) flap and an adipo-dermal thigh local flap in order to fill and cover the thigh defect. The s-vDIEP had 2 islands: a cranial de-epithelialized island to fill the dead space and a caudal for the skin closure. The postoperative follow-up was complicated by seroma formation and it was managed by sclerotherapy and at the 6 months follow-up the patient showed good cosmetic and functional outcomes with no sign of tumor relapse. Our result suggests that the proposed multilayered reconstruction may be employed for the restoration of large and deep upper medial thigh defects.

Is there a link between progranulin, obesity, and parameters of the metabolic syndrome in children? Findings from a longitudinal intervention study.

BACKGROUND: The inflammatory cytokine progranulin has been proposed to play a role in obesity and its associated comorbidities such as insulin resistance. OBJECTIVE: In a longitudinal study, we analyzed the links between progranulin, parameters of fat mass, insulin resistance, and metabolic syndrome (MetS) in obese children. METHODS: We measured the following parameters in 88 obese children at baseline, at the end of a 1-year lifestyle intervention and 1-year later (=2 years after baseline): progranulin, bioactive leptin, body mass index-SD score (BMI-SDS), waist circumference, body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index homeostasis model assessment (HOMA), and blood pressure. As a control, we determined progranulin in 23 normal-weight children. RESULTS: The progranulin concentrations did not differ significantly (P = .795) between obese and normal-weight children. Progranulin concentrations decreased significantly during and after the lifestyle intervention in children with and without decrease of BMI-SDS. There was no relationship between progranulin concentrations and pubertal stage or gender. Progranulin was not significantly associated with insulin resistance HOMA, parameters of the MetS or transaminases both in cross-sectional and longitudinal multiple linear regression analyses adjusted to multiple confounders. Progranulin was significantly, negatively related to age (b-coefficient -1.24 ± .97, P = .012, r2 = .07). CONCLUSIONS: Our data do not support the hypothesis that progranulin is an important link between obesity, insulin resistance, and MetS in childhood.

Reconstruction of an upper posterior thigh extensive defect with a free split-anterolateral thigh (s-ALT) flap by perforator-to-perforator anastomosis: A case report.

The anterolateral thigh (ALT) flap is one of the most commonly used flap worldwide in reconstructive surgery, as both free flap and pedicled local flap. Here, we report the use of a free split anterolateral thigh (s-ALT) flap for reconstruction of a 14 cm × 16 cm soft tissue defect of the left upper posterior thigh region due to sarcoma resection in a patient. The ALT flap was harvested based on two musculocutaneous perforators from the right thigh and anastomosed to the contralateral descending branch of the lateral circumflex femoral artery (LCFA) in perforator-to-perforator manner, in order to gain more pedicle length and being able to cover the posterior thigh defect. The post-operative course was uneventful and the patient was discharged at 1 week post-operative. Eleven months after the operation, the aesthetic outcome was satisfactory with no functional deficit. Even though it requires technical skills and experience in perforator dissection, we believe that the s-ALT flap anstomosed to the contralateral LCFA in perforator to perforator fashion, may be a good solution in case of such a difficultly located extensive defect of the posterior thigh.

Link between chemerin, central obesity, and parameters of the Metabolic Syndrome: findings from a longitudinal study in obese children participating in a lifestyle intervention.

OBJECTIVE: Chemerin has been suggested as a potential link between obesity and associated comorbidities in humans. Therefore, we studied the relationships between chemerin, parameters of fat mass, and Metabolic Syndrome (MetS) in obese children before and after weight reduction. METHODS: We determined chemerin, bioactive leptin (bioLep), BMI-SDS, waist circumference (WC), body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index HOMA, and blood pressure in 88 obese children participating in a lifestyle intervention at baseline and 1 year later. Furthermore, we determined chemerin concentrations in 23 normal-weight children. RESULTS: Obese children demonstrated significantly (p < 0.001) higher chemerin concentrations compared to normal-weight children (96.2 ± 23.0 versus 63.1 ± 12.4 ng/ml). The chemerin concentrations were not related to age or gender. Prepubertal children had higher (p = 0.024) chemerin concentrations than pubertal children (71.0 ± 13.4 versus 58.0 ± 8.9 ng/ml). Weight loss was associated with a decrease of chemerin (-14.0 ± 22.0 ng/ml; p < 0.001) and an improvement of all parameters of the MetS. Chemerin was significantly related to BMI-SDS, WC, and bioLep in cross-sectional and longitudinal analyses. Chemerin and its changes were significantly related to insulin, HDL-cholesterol, triglycerides and their changes in multiple linear regression analyses adjusted to age, gender, pubertal stage, leptin and BMI. CONCLUSIONS: Since chemerin was related to parameters of central fat mass and MetS both in cross-sectional and longitudinal analyses these findings suggest an impact of chemerin on factors of the MetS in obese children.

Perforator flap based on the third perforator of the profunda femoris artery (PFA)-assisted closure of the free vertical posteromedial thigh (vPMT) flap donor site.

INTRODUCTION: The primary closure of the vertical posteromedial thigh (vPMT) free flap donor site is very important to minimize donor site morbidity and maximize cosmetic appearance. However, sometimes due to the dimension of the defect, a vPMT flap is wider than the 8-10 cm requirement. The authors report their experience with the third perforator of the profunda femoris artery (PFA) during the vPMT free flap donor-site closure. PATIENTS AND METHODS: Between January 2016 and December 2017, 5 patients underwent reconstruction of lower extremity (2 pts.) and head and neck (3 pts.) area with the free vPMT flaps. Attempts to close the vPMT free flap donor site directly failed due to the flaps' width (average: 11 cm) and pedicled perforator flaps based on the third perforator of the PFA at the distal thigh were harvested to close the defect primary without the use of a skin graft. The size of perforator flap based on 3rd perforator of PFA was on average 6 cm × 4 cm (ranged: 4-8 cm × 3-6 cm). RESULTS: In all patients, the third perforator of the PFA was identified and the perforator diameter was on average 2.0 mm (range, 1.8-2.2 mm). All perforators were musculocutaneous and single. The dimensions of the flaps were on average 6 cm × 4 cm (range: 4 to 8 cm × 3 to 6 cm). All flaps healed uneventfully without complications and the patients were satisfied with cosmetic and functional results at 6 months follow-up. CONCLUSION: The third perforator of the PFA may be an option to ensure primary closure of the PMT flap donor site, when a larger flap for reconstruction is needed with subsequent impossibility to achieve primary closure of the donor site.

Bilateral pedicle anterolateral thigh (ALT) flap combined with bilateral sartorius muscle flap for reconstruction of extensive perineoscrotal and medial thigh defect because of Fournier's gangrene.

Fournier's gangrene is an acute and potentially lethal necrotizing fasciitis that can lead to extensive defects of the perineoscrotal area and lower abdominal wall as well. Such defect poses challenging tasks for both functional and cosmetic reconstruction. Local perforator pedicle flaps and muscle flaps can be employed and combined for such a reconstruction. In this report we present a case of reconstruction of a massive perineoscrotal and upper medial thigh defect because of Fournier's gangrene using a bilateral pedicle anterolateral thigh (ALT) flap and sartorius muscle flap. A 61 year-old male who suffered from Fournier's gangrene resulted in a perineal, scrotal, and medial thigh defect of 27 × 30 cm2 with exposure of the femoral vessels. A bilateral pedicle ALT flap measuring 30 × 9 cm2 based on two perforators and a bilateral sartorius muscle flap were harvested for soft tissue defect reconstruction and inguinal vessels coverage, respectively. The flaps survived completely, with no recipient or donor site morbidity. The length of follow-up was 6 months and was uneventful. A bilateral pedicle ALT flap combined with bilateral sartorius flap may be considered as a valid and safe option for an extensive inguinal and perineoscrotal reconstruction in selected cases. © 2016 Wiley Periodicals, Inc. Microsurgery 37:669-673, 2017.

Free fillet flap application to cover forequarter or traumatic amputation of an upper extremity: A case report.

Reusing tissue of amputated or unsalvageable limbs to reconstruct soft tissue defects is one aspect of the "spare parts concept." Using a free fillet flap in such situations enables the successful formation of a proximal stump with the length needed to cover a large defect from forequarter amputation without risking additional donor-site morbidity. The use of free fillet flaps for reconstruction after forequarter and traumatic upper extremity amputations is illustrated here in a case report. A 41-year old patient required a forequarter amputation to resect a desmoid tumor, resulting in an extensive soft-tissue defect of the upper extremity. A free fillet flap of the amputated arm and an additional local epaulette flap were used to reconstruct the defect. At 9 months after the procedure, a satisfactory result with a very well healed flap was attained. Free fillet flaps can be used successfully for reconstruction of large upper extremity defects, without risking additional donor-site morbidity. © 2015 Wiley Periodicals, Inc. Microsurgery 36:700-704, 2016.

Diagnostic and prognostic value of the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) based on an 18 years' experience.

BACKGROUND: Necrotising fasciitis (NF) represents a rare but often life-threatening condition. Early diagnosis and surgical treatment are of vital importance. The LRINEC score was developed to distinguish necrotising fasciitis from other soft tissue infections (STI) at initial evaluation using six laboratory values. In this retrospective study, we attempted to determine the diagnostic and prognostic value of the LRINEC score. METHODS: A total of 125 patients, hospitalised in our clinic between 2003 and 2021 with a histologically confirmed diagnosis of necrotising fasciitis (NF group) and 319 patients with surgically treated soft tissue infections (STI group) were included in this study. Individual LRINEC scores were calculated and analysed retrospectively. RESULTS: The sensitivity of the LRINEC score at the cut-off point of ≥ 6 was 59%, whereas the specificity was 82%. The positive and negative predictive values were 57% and 84%, respectively. The mean LRINEC score was significantly higher in the NF group than in the STI group (6.0 compared to 2.4, respectively). All clinical outcome parameters such as amputation and mortality rates (15% vs 1%) were found to be significantly higher in the NF group (p<0.001). Within the NF group, there was no statistically significant association between the LRINEC score and clinical outcomes except for the necessary number of operations. CONCLUSION: In isolation, we found the LRINEC score not to be a reliable enough diagnostic tool for the differentiation between NF and other soft tissue infections, because of its low sensitivity. Although we cannot recommend it as a prognostic tool either, we do believe it can be a useful adjunct to the clinical suspicion of NF.

Time Is Fascia: Laboratory and Anamnestic Risk Indicators for Necrotizing Fasciitis.

Background: Necrotizing fasciitis is a potentially fatal soft tissue infection in which the timing of surgical intervention significantly affects clinical outcome. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score, the Site other than the lower limb, Immunosuppression, Age <60 years, Renal impairment (creatinine >141), and Inflammatory markers (CRP ≥150, WCC >25) (SIARI) score, and procalcitonin levels are intended to aid in the decision-making process to differentiate between necrotizing fasciitis and soft tissue infections. Methods: A retrospective analysis of cases of necrotizing fasciitis and soft tissue infections treated at Klinikum Nürnberg was performed. The two scores as well as procalcitonin levels were tested for their diagnostic value and a new score, the Laboratory and Anamnestic Risk Indicator for Necrotizing Fasciitis (LARINF), was created based on the results. Results: Procalcitonin, LRINEC score, and SIARI score showed insufficient discriminatory ability in our study. The newly created LARINF score combined laboratory parameters of the LRINEC score (hemoglobin and C-reactive protein) with procalcitonin and three comorbidities, resulting in a sensitivity of 84% and a specificity of 75% and the highest area under the receiver operating characteristic (ROC) curve of 0.83. Conclusions: The LARINF score is a novel decision-supporting tool. The decision, in which cases surgical exploration should be initiated, remains a clinical one. However, the score seems to provide an improved basis for identifying a rare clinical picture.

Microsurgical Reconstruction of Foot Defects: A Case Series with Long-Term Follow-Up.

(1) Background: Microsurgical reconstruction of foot defects with free flaps is rare as it is a challenging task for a surgeon. For extensive defects, advanced surgical procedures, such as free flap transfer with microsurgical anastomosis, may be the last chance to avoid major amputation. The aim of the study was to examine the opportunities and risks posed by free flap reconstruction of foot defects and to illustrate in which situations reconstruction is useful on the basis of case characteristics. (2) Methods: In this study, we retrospectively analyzed data of cases with free flap reconstruction of the foot from 2007 to 2022. Therefore, demographic data, comorbidities, information about the defect situation, data on the operational procedure, and complications were evaluated. (3) Results: A total of 27 cases with free flap coverage of foot defects could be included. In 24 of these cases (89%), defect coverage was successful. In 18 patients, some form of complication occurred in the postoperative stage. The most frequently used flap was the latissimus dorsi flap, with 13 procedures. (4) Conclusions: Foot reconstruction using free flaps is a proven procedure for the treatment of larger foot defects and can offer a predominantly good functional outcome. The lengthy process and possible complications should be thoroughly discussed in advance so as to provide criteria, suitably adjusted to the individual prerequisites of the patients, for deciding whether limb salvage using advanced surgical procedures should be attempted.

Identification of ALP+/CD73+ defining markers for enhanced osteogenic potential in human adipose-derived mesenchymal stromal cells by mass cytometry.

BACKGROUND: The impressive progress in the field of stem cell research in the past decades has provided the ground for the development of cell-based therapy. Mesenchymal stromal cells obtained from adipose tissue (AD-MSCs) represent a viable source for the development of cell-based therapies. However, the heterogeneity and variable differentiation ability of AD-MSCs depend on the cellular composition and represent a strong limitation for their use in therapeutic applications. In order to fully understand the cellular composition of MSC preparations, it would be essential to analyze AD-MSCs at single-cell level. METHOD: Recent advances in single-cell technologies have opened the way for high-dimensional, high-throughput, and high-resolution measurements of biological systems. We made use of the cytometry by time-of-flight (CyTOF) technology to explore the cellular composition of 17 human AD-MSCs, interrogating 31 markers at single-cell level. Subcellular composition of the AD-MSCs was investigated in their naïve state as well as during osteogenic commitment, via unsupervised dimensionality reduction as well as supervised representation learning approaches. RESULT: This study showed a high heterogeneity and variability in the subcellular composition of AD-MSCs upon isolation and prolonged culture. Algorithm-guided identification of emerging subpopulations during osteogenic differentiation of AD-MSCs allowed the identification of an ALP+/CD73+ subpopulation of cells with enhanced osteogenic differentiation potential. We could demonstrate in vitro that the sorted ALP+/CD73+ subpopulation exhibited enhanced osteogenic potential and is moreover fundamental for osteogenic lineage commitment. We finally showed that this subpopulation was present in freshly isolated human adipose-derived stromal vascular fractions (SVFs) and that could ultimately be used for cell therapies. CONCLUSION: The data obtained reveal, at single-cell level, the heterogeneity of AD-MSCs from several donors and highlight how cellular composition impacts the osteogenic differentiation capacity. The marker combination (ALP/CD73) can not only be used to assess the differentiation potential of undifferentiated AD-MSC preparations, but also could be employed to prospectively enrich AD-MSCs from the stromal vascular fraction of human adipose tissue for therapeutic applications.

Electrical stimulation of Broca's area enhances implicit learning of an artificial grammar.

Artificial grammar learning constitutes a well-established model for the acquisition of grammatical knowledge in a natural setting. Previous neuroimaging studies demonstrated that Broca's area (left BA 44/45) is similarly activated by natural syntactic processing and artificial grammar learning. The current study was conducted to investigate the causal relationship between Broca's area and learning of an artificial grammar by means of transcranial direct current stimulation (tDCS). Thirty-eight healthy subjects participated in a between-subject design, with either anodal tDCS (20 min, 1 mA) or sham stimulation, over Broca's area during the acquisition of an artificial grammar. Performance during the acquisition phase, presented as a working memory task, was comparable between groups. In the subsequent classification task, detecting syntactic violations, and specifically, those where no cues to superficial similarity were available, improved significantly after anodal tDCS, resulting in an overall better performance. A control experiment where 10 subjects received anodal tDCS over an area unrelated to artificial grammar learning further supported the specificity of these effects to Broca's area. We conclude that Broca's area is specifically involved in rule-based knowledge, and here, in an improved ability to detect syntactic violations. The results cannot be explained by better tDCS-induced working memory performance during the acquisition phase. This is the first study that demonstrates that tDCS may facilitate acquisition of grammatical knowledge, a finding of potential interest for rehabilitation of aphasia.

Link between omentin-1, obesity and insulin resistance in children: Findings from a longitudinal intervention study.

OBJECTIVE: The adipokine omentin-1 has been suggested to be inversely associated with obesity and insulin resistance in humans. We studied the relationships between omentin-1, parameters of fat mass, insulin resistance, lipids and blood pressure in children with obesity in a longitudinal study. METHODS: We analysed omentin-1 concentrations in 23 normal-weight children and in 82 children with obesity participating in a one-year lifestyle intervention. In the children with obesity, omentin-1, bioactive and conventional leptin, thyroid hormones (thyroid-stimulating hormone, free thyroxine 4, free triiodothyronine), body mass index, waist circumference, body fat based on skin-fold measurements and bioimpedance analyses, lipids, insulin resistance as homeostatic model assessment of insulin resistance (HOMA-IR) and blood pressure were determined at baseline and 1 year later. Furthermore, we measured omentin-1 concentrations 1 year after the end of the lifestyle intervention. RESULTS: The omentin-1 concentrations were significantly (P = .008) lower in children with obesity compared to normal-weight children (296 ± 108 ng ml-1 vs. 232 ± 99 ng ml-1 ). Omentin-1 concentrations increased significantly (P < .001) in children with obesity and substantial weight loss (35 ± 55 ng ml-1 ), while omentin-1 concentrations did not change significantly (P = .750) in children with obesity without weight loss (-5 ± 108 ng ml-1 ) during the intervention. Substantial weight loss after the end of intervention led to a significant (P < .001) increase of omentin-1 concentrations (+64 ± 14 ng ml-1 ). Omentin-1 was significantly and negatively associated with HOMA-IR both in cross-sectional (r = -.27, P = .006) and longitudinal analyses (r = -.33, P = .001). Omentin-1 concentrations were not related to pubertal stage, sex or thyroid hormones. CONCLUSIONS: Our data do support the hypothesis that omentin-1 is reversibly decreased in obesity and is a link between obesity and insulin resistance.

Thyroid Volume and Thyroid Function Parameters Are Independently Associated with Weight Status in Overweight Children.

BACKGROUND: A relation between thyroid-stimulating hormone (TSH), insulin resistance - both of which are related to obesity - and thyroid volume has been suggested. Therefore, we analyzed thyroid volume and structure in relation to thyroid function parameters, weight status, and insulin resistance. METHODS: This is a cross-sectional study in which weight status (BMI-SDS), thyroid function parameters (TSH, free tri-iodothyronine [fT3], and free thyroxine [fT4]), insulin resistance index (HOMA-IR), and thyroid volume (ultrasound) were determined in 617 overweight children (aged 10.4 ± 2.2 years, 50% male, BMI-SDS 2.5 ± 0.6) and in 27 normal-weight children of a similar age and gender. Furthermore, changes in thyroid volume and structure, and thyroid function parameters were analyzed in 83 obese children (51% male, mean age 10.3 ± 2.2) at baseline and at the end of a 1-year lifestyle intervention. RESULTS: Overweight children had a significant greater thyroid volume (4.2 ± 1.8 vs. 4.1 ± 0.5 mL) and higher TSH (3.1 ± 1.5 vs. 2.4 ± 1.1 mU/L) and fT3 (4.4 ± 0.7 vs. 4.1 ± 0.5 pg/mL) concentrations compared to normal-weight children. In multiple linear regression analyses adjusted to multiple confounders, thyroid volume was significantly related to BMI-SDS (b coefficient 0.44 ± 0.10, r2 = 0.41) but not to any thyroid function parameter or HOMA-IR. Changes in BMI-SDS were significantly associated with changes in thyroid volume (r = 0.22). The changes in thyroid volume were not correlated to changes of any thyroid function parameter or HOMA-IR. CONCLUSIONS: Thyroid volume is positively correlated to weight status in childhood obesity and the change is reversible after weight loss independently of thyroid function parameters and insulin resistance. Further studies are needed to understand why thyroid volume is increased reversibly in overweight children.

Sex Hormone Profile in Pubertal Boys With Gynecomastia and Pseudogynecomastia.

CONTENT: Gynecomastia (defined by proliferation of glandular elements) and pseudogynecomastia (defined by adipose tissue) are frequent in pubertal boys. An association with sex hormones and the growth hormone axis has been discussed. OBJECTIVE: The objective of this work is to compare sex hormones, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein 3 (IGFBP-3) between boys with gynecomastia and pseudogynecomastia (separation by ultrasound). DESIGN: An observational study was performed. SETTING: The setting of this study was an outpatient clinic. PARTICIPANTS: A total of 124 pubertal boys (mean age 14 ±â€…2 years) with breast enlargement and 84 healthy boys (mean age 14 ±â€…2 years) without breast enlargement participated in this study. INTERVENTIONS: No interventions were performed. MAIN OUTCOME MEASURES: Measurements were taken for sex hormones (progesterone, estradiol [E2], estriol, estrone, androstendione, testosterone [T], dihydrotestosterone) measured by liquid chromatography-tandem mass spectrometry, as well as gonadotropins, prolactin, IGF-1, and IGFBP-3. RESULTS: Eighty-six boys suffered from gynecomastia and 38 from pseudogynecomastia. In boys with gynecomastia, the E2/T ratio (median 22, interquartile range [IQR] 8-75) was significantly (P < .05) higher compared to boys with pseudogynecomastia (median 12, IQR 5-21) or healthy controls without breast enlargement (median 18, IQR 6-44) even after adjustment for testes volume. T concentrations were significantly (P < .05) lower in boys with gynecomastia (median 1.8, IQR 0.7-4.2 nM/L) compared to boys with pseudogynecomastia (median 4.3, IQR 1.4-6.9 nM/L) or healthy controls without breast enlargement (median 3.1, IQR 0.6-7.6 nM/L). Boys with gynecomastia did not differ from boys with pseudogynecomastia according to other sex hormones, prolactin, IGF-1, or IGFBP-3 concentrations. CONCLUSIONS: True gynecomastia is characterized by a relative T deficiency to E2 concentrations in contrast to pseudogynecomastia.

Bioactive leptin is stronger related to parameters of fat mass and distribution than conventionally measured leptin: Findings from a longitudinal study in obese children participating in a lifestyle intervention.

OBJECTIVE: This study analyzed the relationships between bioactive leptin, conventionally measured leptin, and parameters of fat mass and distribution in obese children before and after weight reduction. METHODS: We determined bioactive leptin (bioLep), conventional measured leptin (conLep), weight, height, body fat based on skinfold measurements and bioimpedance analyses, waist circumference (wc), and pubertal stage in 88 obese children participating in a lifestyle intervention at baseline and one year later. RESULTS: We identified no child with homozygous or heterozygous status for bioinactive leptin mutations. The baseline associations between bioLep and BMI (r = 0.53), BMI-SDS (r = 0.48), body fat (bioimpedance: r = 0.61, skinfold thickness: r = 0.49), wc (r = 0.42), and waist to height ratio (whr) (r = 0.39) were stronger than the associations between conLep and BMI (r = 0.50), BMI-SDS (r = 0.44), body fat (bioimpedance: r = 0.57, skinfold thickness: r = 0.41), wc (r = 0.41), and whr (r = 0.37). The changes of bioLep were stronger related to changes of BMI-SDS (r = 0.54), body fat (bioimpedance r = 0.59, skinfold thickness: r = 0.37), wc (r = 0.22), and whr (r = 0.21) than the associations between changes of conLep and changes of BMI-SDS (r = 0.48), body fat (bioimpedance: r = 0.56, skinfold thickness: r = 0.43), wc (r = 0.20), and whr (r = 0.20). The same findings were observed in multiple linear regression analyses adjusted to multiple confounders. In contrast to changes of conLep (r = 0.22), the changes of bioLep during intervention were not related to weight regain after the end of intervention. BioLep concentrations did not differ between prepubertal girls and boys, but were higher in pubertal girls compared to pubertal boys (p = 0.031). CONCLUSIONS: Bioactive leptin was stronger related to fat mass and distribution compared to conventionally measured leptin.

Incidence of risk factors for bloodstream infections in patients with major burns receiving intensive care: A retrospective single-center cohort study.

OBJECTIVES: The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens. METHODS: A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray. RESULTS: A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p<0.0001) and need for fasciotomy (p<0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p<0.0001). CONCLUSIONS: A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp.