Management of diabesity: Current concepts.

The global prevalence of obesity is increasing rapidly with an exponential rise in incidence of type 2 diabetes mellitus in recent years. 'Diabesity', the term coined to show the strong interlink between obesity and diabetes, is the direct cons-equence of the obesity pandemic, and poses significant challenges in the management of the disease. Without addressing the clinical and mechanistic complications of obesity such as metabolic-associated fatty liver disease and obstructive sleep apnoea, a rational management algorithm for diabesity cannot be developed. Several classes of anti-diabetic medications including insulins, sulphonylureas, thiazolidinediones and meglitinides are associated with the risk of weight gain and may potentially worsen diabesity. Therefore, appropriate selection of antidiabetic drug regimen is crucial in the medical management of diabesity. The role of non-pharmacological measures such as dietary adjustments, exercise interventions and bariatric procedures should also be emphasised. Unfortunately, the importance of appropriate and optimal management of diabesity is often overlooked by medical professionals when achieving adequate glycemic control which results in inappropriate management of the disease and its complications. This review provides a narrative clinical update on the evidence behind the management of diabesity.

Recalibration of thinking about adrenocortical function assessment: how the 'random' cortisol relates to the short synacthen test results.

BACKGROUND: The short synacthen test (SST) is the most commonly performed investigation to assess adrenal function. Appropriate criteria for when an SST is performed are subject to debate. We investigated how random serum cortisol levels relate to SST response. METHODS: We examined random cortisol measurements taken between 04.40-23.55 p.m. results of SST baseline and 30-/60-min cortisol performed over 12 months (225 SSTs) at Salford Royal Hospital. Serum cortisol was measured on the Siemens Centaur Analyser.A 30-60-min cortisol concentration of ≥450 nmol/L defined a pass; 350-449 nmol/L defined borderline. RESULTS: Patients only proceeded to SST if random cortisol was <400 nmol/L. For those not on corticosteroids for at least 2 weeks, 42/43 (97.7%) cases with random cortisol concentration of ≥200 nmol/L had an SST 'pass'. The relation was less clear with corticosteroid treatment (19/35 cases; 54%).For those not taking glucocorticoid treatment (including inhaled/topical corticosteroids) in the previous 2 weeks, 91.8% of SSTs were pass/2.7% borderline/5.5% fail. For those on steroids, 51.9% of SSTs were a pass/11.4% were borderline.In relation to the postsynacthen cortisol pass cut-off of ≥450 nmol/L, in 15/207 (7.2%) of cases, the 60-min cortisol was ≥450 nmol/L (adequate adrenocortical function), but 30-min cortisol was below this. In all cases where the 30-min cortisol did indicate a pass (i.e. was ≥450 nmol/L) the 60-min cortisol was also ≥450 nmol/L. CONCLUSION: Our findings suggest that if the random cortisol level is ≥200 nmol/L, regardless of the time of day and the person was not taking corticosteroid treatment in the previous 2 weeks, SST may not be needed. Our data also suggests that 60-min cortisol retains utility.

Improved adherence and growth outcomes with jet-delivered growth hormone.

Background We previously reported improved persistence and adherence to daily recombinant growth hormone (rGH) in children using jet transjection delivery compared to using needle-based devices. This study examines the relationship between improved adherence and medium-term growth outcomes in children receiving jet-delivered rGH (JrGH) at a single centre. Methods This was a retrospective longitudinal follow-up study of children (<16 years) treated with daily JrGH (somatropin; Ferring Pharmaceuticals) in the form of Zomacton® with the Zomajet® device. Delivery schedules of home distribution services were utilised to calculate adherence, quantified as the proportion of days covered (PDC) index (PDC > 0.8 adherent, PDC ≤ 0.8 less adherent). Demography, patient history, height standard deviation scores (HTSDS) and difference from mid-parental height SDS (MPHSDS - HTSDS) were extracted from hospital records for up to 3 years of treatment. Results Of 75 patients eligible for JrGH, 52 had PDC treatment and height data for at least 1 year and 22 for 3 years. A greater proportion of patients were classified as adherent in both 1- and 3-year treated cohorts (adherent 30 [57.7%] and 14 [63.6%], less adherent 22 [42.3%] and 8 [36.4%]). After 1 year of JrGH treatment, HTSDS was not significantly different in either adherence group. After 3 years, only adherent patients demonstrated sustained year-on-year increments in HTSDS and significant improvement in target HTSDS positions (by 1.32 SDS) compared to baseline (p = 0.0008). MPHSDS - HTSDS showed a similar significant improvement at 3 years in adherent patients only (p = 0.0043). Conclusions Patients adherent to JrGH demonstrate significant growth improvement compared to baseline over 3 years.

Vineland adaptive behavior scales to identify neurodevelopmental problems in children with Congenital Hyperinsulinism (CHI).

BACKGROUND: Congenital Hyperinsulinism (CHI) is a disease of severe hypoglycaemia caused by excess insulin secretion and associated with adverse neurodevelopment in a third of children. The Vineland Adaptive Behavior Scales Second Edition (VABS-II) is a parent report measure of adaptive functioning that could be used as a developmental screening tool in patients with CHI. We have investigated the performance of VABS-II as a screening tool to identify developmental delay in a relatively large cohort of children with CHI. VABS-II questionnaires testing communication, daily living skills, social skills, motor skills and behaviour domains were completed by parents of 64 children with CHI, presenting both in the early neonatal period (Early-CHI, n = 48) and later in infancy (Late-CHI, n = 16). Individual and adaptive composite (Total) domain scores were converted to standard deviation scores (SDS). VABS-II scores were tested for correlation with objective developmental assessment reported separately by developmental paediatricians, clinical and educational psychologists. VABS-II scores were also investigated for correlation with the timing of hypoglycaemia, gender and phenotype of CHI. RESULTS: Median (range) total VABS-II SDS was low in CHI [-0.48 (-3.60, 4.00)] with scores < -2.0 SDS in 9 (12%) children. VABS-II Total scores correctly identified developmental delay diagnosed by objective assessment in the majority [odds ratio (OR) (95% confidence intervals, CI) 0.52 (0.38, 0.73), p < 0.001] with 95% specificity [area under curve (CI) 0.80 (0.68, 0.90), p < 0.001] for cut-off < -2.0 SDS, although with low sensitivity (26%). VABS-II Total scores were inversely correlated (adjusted R2 = 0.19, p = 0.001) with age at presentation (p = 0.024) and male gender (p = 0.036), males having lower scores than females in those with Late-CHI [-1.40 (-3.60, 0.87) v 0.20 (-1.07, 1.27), p = 0.014]. The presence of a genetic mutation representing severe CHI also predicted lower scores (R2 = 0.19, p = 0.039). CONCLUSIONS: The parent report VABS-II is a reliable and specific tool to identify developmental delay in CHI patients. Male gender, later age at presentation and severity of disease are independent risk factors for lower VABS-II scores.

Evolution of the 3-dimensional video system for facial motion analysis: ten years' experiences and recent developments.

Since the implementation of the computer-aided system for assessing facial palsy in 1999 by Frey et al (Plast Reconstr Surg. 1999;104:2032-2039), no similar system that can make an objective, three-dimensional, quantitative analysis of facial movements has been marketed. This system has been in routine use since its launch, and it has proven to be reliable, clinically applicable, and therapeutically accurate. With the cooperation of international partners, more than 200 patients were analyzed. Recent developments in computer vision--mostly in the area of generative face models, applying active--appearance models (and extensions), optical flow, and video-tracking-have been successfully incorporated to automate the prototype system. Further market-ready development and a business partner will be needed to enable the production of this system to enhance clinical methodology in diagnostic and prognostic accuracy as a personalized therapy concept, leading to better results and higher quality of life for patients with impaired facial function.

3D video analysis of facial movements.

This article presents a review of 3D video analysis for use in patients with facial paralysis. The difficulties inherent in quantifying the degree of facial paralysis and the effect of therapeutics that has led to the use of videos and computer-assisted 3D analysis are discussed, which can yield quantifiable results of treatment, allow the description and quantification of facial paralysis, and become a tool in the planning of operative procedures. The authors provide a step-by-step overview of video analysis, and present case studies from two specific techniques they have used in reconstruction surgery.

Correlation of functional recovery with the course of electrophysiological parameters after free muscle transfer for reconstruction of the smile in irreversible facial palsy.

INTRODUCTION: The aim of this study was to determine whether processes of denervation and reinnervation, as measured by electrodiagnostic methods, correlate with clinical function, as measured by three-dimensional (3D) video analysis and whether electrodiagnostic data can serve as a prognostic indicator. METHODS: Eighteen patients with facial palsy were investigated by 3D video analysis, needle electromyography, and electrical muscle testing at 6, 12, and 18 months after free muscle transplantation for smile reconstruction. RESULTS: Electrophysiological parameters determined 6 months postoperatively correlated significantly with the index of dynamic symmetry 12 and 18 months postoperatively. CONCLUSIONS: Processes of reinnervation can be detected earlier by electrophysiological analysis than by quantified clinical analysis. Pathological spontaneous activity alone and combined assessment with motor unit action potentials in the early postoperative stage are strong prognostic indicators.

The combination of muscle transpositions and static procedures for reconstruction in the paralyzed face of the patient with limited life expectancy or who is not a candidate for free muscle transfer.

BACKGROUND: In long-standing complete and irreversible facial palsy where reconstruction by nerve grafting alone is no longer sufficient, reconstruction by dynamic procedures such as muscle transplantation or muscle transposition is required. The authors present the results obtained by regional muscle transposition for reconstruction of eye closure and smile in patients with irreversible facial palsy. METHODS: Twenty-nine patients treated by temporalis transposition for the eye and eight patients treated by masseter transposition for the mouth are presented. Assessment of outcome was based on clinical examination and analysis of facial movements by three-dimensional video analysis. RESULTS: Preoperatively, the paretic eye fissure was on average 2.30 +/- 2.17 mm wider than the healthy one. The difference was reduced postoperatively to 0.95 +/- 1.89 mm. Paralytic lagophthalmus during closure of the eyes was 9.59 +/- 3.03 mm preoperatively and was reduced postoperatively to 4.33 +/- 2.68 mm. Ocular tearing and desiccation were reduced drastically in all patients. Static asymmetry of the mouth corner improved from 14.17 +/- 5.26 mm preoperatively to 5.38 +/- 3.23 mm postoperatively. The index of dynamic symmetry improved from -0.17 +/- 0.25 preoperatively to 0.18 +/- 0.19 postoperatively. This means that, postoperatively, the amplitude of motion on the reconstructed side reached 18 +/- 19 percent that of the amplitude on the healthy side, whereas preoperatively a shift of the paralyzed mouth corner toward the healthy side occurred. CONCLUSIONS: Muscle transposition improves static symmetry and provides dynamic activity to a certain degree. It is therefore a valuable concept for patients with limited life expectancy.

Three-dimensional video analysis of the paralyzed face reanimated by cross-face nerve grafting and free gracilis muscle transplantation: quantification of the functional outcome.

BACKGROUND: Surgeons have found it difficult to quantify facial paralysis and its improvement by reconstructive surgery. This article presents the results achieved by free functional muscle transplantation for reconstruction of the paralyzed face, registered by three-dimensional video analysis of facial movements. METHODS: Of patients treated consecutively between 1997 and 2006, two groups were constituted: group 1 comprised 22 patients with reinnervation completed after a single cross-face nerve graft and a free gracilis muscle graft for reconstruction of the smile; group 2 comprised nine patients treated with two cross-face nerve grafts followed by a territorially differentiated gracilis muscle transplant for reconstruction of the smile and eye closure. Smiling with showing teeth, maximal showing of teeth, and closing the eyes as in sleep were analyzed in detail. RESULTS: In group 1, static asymmetry was reduced from 12.19 +/- 8.73 mm preoperatively to -1.84 +/- 7.67 mm at 18 months postoperatively. Smile amplitude increased from 9 to 60 percent of that on the healthy side in 10 incomplete facial palsies of this group, and from 0 to 62 percent in eight functionally successful muscle grafts among 11 patients with complete lesions. In group 2, static asymmetry improved from 7.24 +/- 12.64 mm to -5.36 +/- 9.07 mm; the overcorrection was intentional. Movement was improved in eight cases. Smile amplitude reached 68 +/- 43 percent of that on the normal side. Lagophthalmus improved from 7.21 +/- 3.59 mm to 1.38 +/- 2.49 mm. All improvements were statistically significant (p

Functional upgrading of partially recovered facial palsy by cross-face nerve grafting with distal end-to-side neurorrhaphy.

BACKGROUND: Cross-face nerve grafting combined with functional muscle transplantation has become the standard in reconstructing an emotionally controlled smile in complete irreversible facial palsy. A special problem exists in incomplete or partially recovered facial palsies, when the little existing function should be preserved but the existing function alone is clinically insufficient. METHODS: In this situation, cross-face nerve grafting performed by means of end-to-end coaptation to a zygomatic branch of the healthy side and by end-to-side neurorrhaphy to a corresponding branch of the incompletely paralyzed side is proposed to upgrade smile function on the latter side and contribute to more static and dynamic overall symmetry. The interposition nerve graft is set in overlength to preserve the possibility of a later muscle transplantation in case of unsatisfying functional result through the additional neuronal input. The authors have used this concept in seven patients with irreversible partial facial palsy. Three cases have a sufficiently long follow-up to be presented here. Outcome was objectively quantified with three-dimensional video analysis of facial movements. RESULTS: In all three cases, functional improvement and a positive effect on the static and dynamic symmetry of the face could be measured. None of the patients was disappointed by the smile function achieved or wanted to undergo additional muscle transplantation. CONCLUSION: On the basis of these first clinical experiences, the authors recommend cross-face nerve grafting with overlength and a distal end-to-side neurorrhaphy in patients with irreversible incomplete facial palsy affecting the smile.