Sclerosing injections to treat midportion Achilles tendinosis: a randomised controlled study evaluating two different concentrations of Polidocanol

Two to three ultrasound (US) and colour Doppler (CD)-guided injections of the sclerosing substance Polidocanol (5 mg/ml) have been demonstrated to give good clinical results in patients with chronic midportion Achilles tendinopathy. This study aimed to investigate if a higher concentration of Polidocanol (10 mg/ml) would lead to a less number of treatments, and lower volumes, needed for good clinical results. Fifty-two consecutive Achilles tendons (48 patients, mean age 49.6 years) with chronic painful midportion Achilles tendinopathy, were randomised to treatment with Polidocanol 5 mg/ml (group A) or 10 mg/ml (group B). The patients and treating physician were blinded to the concentration of Polidocanol injected. All patients had structural tendon changes and neovascularisation in the Achilles midportion. Treatment was US + CD-guided injections targeting the region with neovascularisation (outside ventral tendon). A maximum of three treatments (6-8 weeks in between) were given before evaluation. Patients not satisfied after three treatments were given additional treatment with Polidocanol 10 mg/ml, up to five treatments. For evaluation, the patients recorded the severity of Achilles tendon pain during activity on a visual analogue scale (VAS), before and after treatment. Patient satisfaction with treatment was also assessed. At follow-up (mean 14 months) after three treatments, 18/26 patients in group A and 19/26 patients in group B were satisfied with the treatment and had a significantly reduced level of tendon pain (P < 0.05). After completion of the study, additional treatments with Polidocanol 10 mg/ml in the not satisfied patients resulted in 26/26 satisfied patients in both groups A and B. In summary, we found no significant differences in the number of satisfied patients, number of injections or volumes given, between patients treated with 5 or 10 mg/ml Polidocanol.     

Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First-Phase Glucose-Stimulated Insulin Secretion During Hyperglycemic Clamps

OBJECTIVE

At least 20 type 2 diabetes loci have now been identified, and several of these are associated with altered β-cell function. In this study, we have investigated the combined effects of eight known β-cell loci on insulin secretion stimulated by three different secretagogues during hyperglycemic clamps.

RESEARCH DESIGN AND METHODS

A total of 447 subjects originating from four independent studies in the Netherlands and Germany (256 with normal glucose tolerance [NGT]/191 with impaired glucose tolerance [IGT]) underwent a hyperglycemic clamp. A subset had an extended clamp with additional glucagon-like peptide (GLP)-1 and arginine (n = 224). We next genotyped single nucleotide polymorphisms in TCF7L2, KCNJ11, CDKAL1, IGF2BP2, HHEX/IDE, CDKN2A/B, SLC30A8, and MTNR1B and calculated a risk allele score by risk allele counting.

RESULTS

The risk allele score was associated with lower first-phase glucose-stimulated insulin secretion (GSIS) (P = 7.1 × 10⁻⁶). The effect size was equal in subjects with NGT and IGT. We also noted an inverse correlation with the disposition index (P = 1.6 × 10⁻³). When we stratified the study population according to the number of risk alleles into three groups, those with a medium- or high-risk allele score had 9 and 23% lower first-phase GSIS. Second-phase GSIS, insulin sensitivity index and GLP-1, or arginine-stimulated insulin release were not significantly different.

CONCLUSIONS

A combined risk allele score for eight known β-cell genes is associated with the rapid first-phase GSIS and the disposition index. The slower second-phase GSIS, GLP-1, and arginine-stimulated insulin secretion are not associated, suggesting that especially processes involved in rapid granule recruitment and exocytosis are affected in the majority of risk loci.Type 2 diabetes is a polygenic disease in which the contribution of a number of detrimental gene variants in combination with environmental factors is thought to be necessary for the development of disease. In the past 2 years, results of several genome-wide association studies (GWASs) have been published (1–5), leading to a rapidly increasing number of detrimental type 2 diabetes susceptibility loci. More recently, it has indeed been shown that combining information from these diabetes loci into a risk allele score for all loci enhances diabetes risk (6–9). However, the predictive power of this combined risk allele score is yet insufficient to substitute or largely improve predictive power of known clinical risk factors (8,9). At present, little is known about how these gene variants in combination affect insulin secretion or insulin resistance. Based on recent data, mainly obtained from oral glucose tolerance tests (OGTTs), it was shown that a combined risk allele score from gene variants associated with type 2 diabetes is associated with insulin secretion and not with insulin sensitivity (10–13). However, the OGTT is unable to distinguish between first- and second-phase insulin secretion. Furthermore, other secretagogues, like glucagon-like peptide (GLP)-1 and arginine, were not included in these studies.It is thought that the rapid recruitment and release of insulin granules from the readily releasable pool (RRP) is responsible for the first phase of insulin secretion, whereas the slower prolonged second phase involves recruitment to the membrane of more distant granules and de novo insulin synthesis. Although the exact pathways regulating both phases of glucose-stimulated insulin secretion (GSIS) are not completely resolved, it seems logical that they are at least in part different. This is further corroborated by our recent observation that the heritability for both phases of GSIS in twins is derived from partly nonoverlapping sets of genes (13a).Also, other nonglucose, stimuli-like incretins and amino acids can evoke an insulin response. Detailed phenotypic investigations of the response to these different stimuli may help to elucidate which processes are primarily affected by these loci. Previously, we have already shown that type 2 diabetes genes/loci can have different effects on first- and second-phase GSIS, as measured using hyperglycemic clamps. Also, based on the method of stimulation (i.e., oral versus intravenous), the outcome may differ substantially (14–17), which provides further clues about the mechanism by which they affect insulin secretion.In this study, we genotyped gene variants in TCF7L2, KCNJ11, HHEX/IDE, CDKAL1, IGF2BP2, SLC30A8, CDKN2A/CDKN2B, and MTNR1B in 447 hyperglycemic clamped subjects (256 with normal glucose tolerance [NGT] and 191 with impaired glucose tolerance [IGT]) from four independent studies in the Netherlands and Germany. These eight loci were chosen based on the fact that they were reproducibly associated with β-cell function in various studies (rev. in 18,19). A combined risk allele score of all eight gene variants was calculated for each individual and tested against the various detailed measurements of β-cell function using the hyperglycemic clamp, generally considered to be the gold standard for quantification of first- and second-phase GSIS (20). Furthermore, we also assessed the combined effect of these eight genes on two other stimuli, GLP-1 and arginine-stimulated insulin secretion during hyperglycemia, in a subset of the study sample (n = 224). The latter test provides an estimation of the maximal insulin secretion capacity of a subject and may, according to animal studies, serve as a proxy for β-cell mass (21).     

Growth impairment shows an age-dependent pattern in boys with chronic kidney disease

The impact of chronological age on longitudinal body growth from early childhood through adolescence using detailed anthropometric methods has not yet been studied in children with chronic kidney disease (CKD). We have evaluated growth failure by measuring four components of linear growth: body height (HT), sitting height (SHT), arm length (AL) and leg length (LL). Data were prospectively collected for up to 7 years on 190 boys (3–21 years old) with congenital or hereditary CKD (all had developed at least stage 2 CKD by the age of 10 years). Patients showed the most severe growth failure in early childhood, followed by an acceleration in growth in pre-puberty, a slowing-down of growth at puberty, as expected, and thereafter a late speeding-up of growth until early adulthood. This pattern was observed irrespective of the degree of CKD and different treatment modalities, such as conservative treatment, recombinant human growth hormone (rhGH) therapy or transplantation. LL showed the most dynamic growth changes of all the parameters evaluated and emerged as the best indicator of statural growth in children with CKD. A specific age-dependent pattern of physical growth was identified in pediatric male CKD patients. This growth pattern should be considered in the evaluation of individual growth and the assessment of treatment efficacy such as rhGH therapy.     

Low birth weight,but not postnatal weight gain,aggravates the course of nephrotic syndrome

Clinical and animal studies have shown a higher risk of an aggravated course of renal disease in childhood after birth for babies small for gestational age (SGA). In addition relative “supernutrition” and fast weight gain in early infancy seem to support the development of later disease. In a retrospective analysis of 62 cases of idiopathic nephrotic syndrome treated between 1994 and 2004 at a university centre for paediatric nephrology, we related the course of disease to birth weight and to the weight gain in the first 2 years of life. Six children were born SGA (birth weight <−1.5 standard deviation score), and 56 were born as appropriate for gestational age (AGA). In all SGA children renal biopsy was performed, while only 55% of the AGA children underwent renal biopsy (P = 0.07), showing no difference in renal histology. In the SGA group, four of six patients developed steroid resistance (vs 12/56 AGA, P < 0.05). Of the SGA children, 83% needed antihypertensive treatment in the course of the disease compared to 39% of the AGA children (P = 0.07). The extent of weight gain between birth and 24 months of age did not influence the course of disease. In conclusion, we were able to find evidence for an aggravated course of idiopathic nephrotic syndrome in former SGA children. Independently of birth weight, weight gain in the first 2 years of life did not influence the course of disease.     

Importance of Early Screening and Prophylactic Thyroidectomy in Asymptomatic Nonindex RET Germline Carriers

Genetic testing for RET germline mutations affords rapid identification of germline carriers, offering the prospect of cure before C-cell hyperplasia (CCH) has progressed to medullary thyroid carcinoma (MTC). Although nonindex RET mutation carriers have a better prognosis than do the index patients, it remains to be ascertained whether age represents a risk factor for MTC when screening patients. The current institutional study (October 1994 through June 1999) was set up to compare asymptomatic nonindex patients who were grouped by age: < 20 years and ≥ 20 years. Inclusion criteria were confirmed RET mutations in the germline, with no MTC being more advanced than pT1pN1M0. Adult patients (≥ 20 years) had MTC significantly more often (84% vs. 43%), significantly larger tumors (5 mm vs. 3 mm), and significantly higher basal calcitonin levels preoperatively (78.0 vs. 9.7 pg/ml) than their pediatric/adolescent counterparts (< 20 years). There was a close correlation between pT1 MTC and an elevated basal serum calcitonin level (r= 0.67; Spearman's rho). All three patients with lymph node metastases from MTC had elevated basal calcitonin levels. The two groups did not differ in terms of multifocality of MTC (pT1b), lymph node involvement (pN1) or bilateral lymph node metastasis (pN1b), or preoperative stimulated and postoperative basal and stimulated serum calcitonin. Prophylactic thyroidectomy should not be postponed beyond the age of 20, and it should be performed before basal serum calcitonin has turned positive. Pathologic conversion of stimulated serum calcitonin obviously marks the time in carriers of RET germline mutations when surgery should be scheduled at the latest to be prophylactic.     

Education in people with venous leg ulcers based on a brochure about compression therapy: A quasi‐randomised controlled trial

Brochures are a useful supplement to patient education. There is increasing evidence that they are an effective medium to support patient satisfaction, adherence, and empowerment. This study aims to produce reliable data on how much patients with venous leg ulcer (VLU) may profit from a brochure that focuses on VLU and on measures and aims of the related compression therapy. The evaluation took part from October 2018 until March 2019 and included 136 patients with VLU and related compression therapy. They were randomly sorted into a case group and a control group of 68 patients each. The case group received a brochure about venous disease and compression therapy and filled in a questionnaire after reading. The questions ranged from basic knowledge about VLU and compression therapy to aspects of self‐care. The control group answered the same questions without previous reading of the brochure. The results show that in almost every aspect, the patients in the case group were better informed about their diseases, the compression therapy, and how they may support the measures adequately. This study suggests that patients with VLU may profit from a brochure that explains their disease and the related compression therapy. Better knowledge and understanding may strengthen their empowerment and adherence.     

Reinterpretation of cross-sectional images in patients with head and neck cancer in the setting of a multidisciplinary cancer center

BACKGROUND AND PURPOSE: Patients referred to tertiary care centers frequently arrive with images obtained at outside institutions; these images require reinterpretation. We assessed the clinical value of reinterpreting cross-sectional imaging studies of patients with head and neck cancer, in the setting of a multidisciplinary cancer center. METHODS: Outside CT and MR images of 136 patients with known or presumed head and neck cancer were reinterpreted by a neuroradiologist. Clinical history and findings on physical examination were available. Reinterpretation was performed before review of outside reports, which were subsequently compared with those generated at the cancer center. Changes in interpretation were noted, and their effects on TNM staging, patient care, and prognosis were assessed. Reliability and statistical significance of rates of change in diagnosis were analyzed with 95% confidence intervals (CIs) and the sign test, respectively. Verification of change in diagnosis was confirmed by pathologic analysis (75%), characteristic radiologic findings (18%), or clinical and imaging follow-up (7%). RESULTS: Change in interpretation occurred in 56 patients (41%) (95% CI: 33-49%, P <.001). Forty-six patients (34%) had a change in T, N, and/or M staging (26-42%, P <.001). Change in T stage occurred in 27 cases (20%) (13-27%, P <.001) (upstaged in 22, downstaged in five), and a change in N stage in 26 cases (19%) (12-26%, P <.001) (upstaged in 20, downstaged in six). Two patients (1.5%) had missed systemic metastases. Three patients with an initial diagnosis of cancer were found to be cancer-free, and six patients had a diagnosis of new second primary cancers that were missed at original interpretation. One patient had a missed middle cerebral artery aneurysm. Changes in image interpretation altered treatment in 55 (98%) of 56 patients and affected prognosis in 53 patients (95%) (P <.001). CONCLUSION: Reinterpretation of cross-sectional images in the setting of a multidisciplinary cancer center has a significant effect on staging, management, and prognosis in patients with head and neck cancer.     

The fracture gap size influences the local vascularization and tissue differentiation in callus healing

Background Revascularization of a fracture depends on fracture stability and fracture gap conditions. The aim of the study was to determine quantitatively the revascularization and tissue differentiation in an animal model with different fracture gaps and controlled biomechanical conditions.Materials and method The study was performed on ten sheep with an osteotomy on the right metatarsal. The fracture was stabilized by an external fixator that allowed adjustable axial interfragmentary movement. Two groups of five sheep each were adjusted to a medium sized gap (M, 2.1 mm) and a large gap (L, 5.7 mm) under comparable interfragmentary strain (30–32%). The animals were killed after 9 weeks, and the metatarsals were prepared for undecalcified histology and analysis of tissue differentiation and vessel distribution.Results Group M showed significantly more revascularization (M=1.62, L=0.85 vessels/mm²), more bone formation (M=37.2%, L=13.9%) and less fibrocartilage tissue (M=18.1%, L=39.1%) than group L. Larger vessels (>40 m) were found mainly in the medullary channel, and smaller vessels (<20 m) mainly in the peripheral callus. Histologically, group M showed partial bony bridging of the osteotomy gap, and the group L had delayed healing.Conclusion A good reduction of a fracture with small interfragmentary gaps is important for its revascularization and healing.     

MRI visible Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> polypropylene mesh: 3D reconstruction of spatial relation to bony pelvis and neurovascular structures

Introduction and hypothesis

To demonstrate mesh magnetic resonance imaging (MRI) visibility in living women, the feasibility of reconstructing the full mesh course in 3D, and to document its spatial relationship to pelvic anatomical structures.

Methods

This is a proof of concept study of three patients from a prospective multi-center trial evaluating women with anterior vaginal mesh repair using a MRI-visible Fe₃O₄ polypropylene implant for pelvic floor reconstruction. High-resolution sagittal T2-weighted (T2w) sequences, transverse T1-weighted (T1w) FLASH 2D, and transverse T1w FLASH 3D sequences were performed to evaluate Fe₃O₄ polypropylene mesh MRI visibility and overall post-surgical pelvic anatomy 3 months after reconstructive surgery. Full mesh course in addition to important pelvic structures were reconstructed using the 3D Slicer® software program based on T1w and T2w MRI.

Results

Three women with POP-Q grade III cystoceles were successfully treated with a partially absorbable MRI-visible anterior vaginal mesh with six fixation arms and showed no recurrent cystocele at the 3-month follow-up examination. The course of mesh in the pelvis was visible on MRI in all three women. The mesh body and arms could be reconstructed allowing visualization of the full course of the mesh in relationship to important pelvic structures such as the obturator or pudendal vessel nerve bundles in 3D.

Conclusions

The use of MRI-visible Fe₃O₄ polypropylene meshes in combination with post-surgical 3D reconstruction of the mesh and adjacent structures is feasible suggesting that it might be a useful tool for evaluating mesh complications more precisely and a valuable interactive feedback tool for surgeons and mesh design engineers.