Abnormal LDIflare but Normal Quantitative Sensory Testing and Dermal Nerve Fiber Density in Patients with Painful Diabetic Neuropathy

OBJECTIVE—Abnormal small nerve fiber function may be an early feature of diabetic neuropathy and may also underlie painful symptoms. Methods for assessing small-fiber damage include quantitative sensory testing (QST) and determining intraepidermal nerve fiber density. We recently described a reproducible physiological technique, the LDIflare, which assesses small-fiber function and thus may reflect early dysfunction before structural damage. The value of this technique in painful neuropathy was assessed by comparing it with QST and dermal nerve fiber density (NFD).RESEARCH DESIGN AND METHODS—Fifteen healthy control subjects, 10 subjects with type 2 diabetes and painful neuropathy (PFN), and 12 subjects with type 2 diabetes and painless neuropathy (PLN) were studied. LDIflare and QST were performed on the dorsum of the foot, and dermal NFD was determined.RESULTS—Results of both large- and small-fiber quantitative sensory tests were abnormal in patients with PLN but not those with PFN compared with control subjects. Dermal NFD was also significantly reduced in the PLN group compared with control subjects (205.8 ± 165.3 vs. 424.9 ± 176.3 [mean ± SD]; P = 0.003) but not in the PFN group (307.6 ± 164.5). In contrast, the LDIflare (square centimeters) was reduced in both PFN (1.59 ± 0.41) and PLN (1.51 ± 0.56) groups compared with control subjects (4.38 ± 1.4) (P < 0.001 for both). NFD correlated significantly with the LDIflare (r = 0.57, P < 0.0001).CONCLUSIONS—The LDIflare demonstrated impaired small-fiber function in patients with PFN when other assessments revealed no abnormality. We believe that this method has potential diagnostic value, particularly because it is noninvasive, has excellent reproducibility, and correlates with NFD. Furthermore, it may have an important role in assessing preventative therapies in early neuropathy.Peripheral neuropathy affects between 40 and 60% of individuals with diabetes and is commonly diagnosed by assessing large-fiber sensory modalities. However, detection of small-fiber neuropathy may be of equal or more importance for several reasons. Structural and functional changes in small fibers precede large-fiber pathological changes and have been implicated in foot ulceration and delayed wound healing (1–3). Furthermore, C-fiber dysfunction may be involved in the genesis of neuropathic pain (4).Until recently, few objective methods have been available to quantify small-fiber function. Quantitative sensory tests to define thermal and pain thresholds using the Computer Aided Sensory Evaluator–IV (CASE IV; WR Medical Electronics, Stillwater, MN) or the TSA-II NeuroSensory Analyzer (Medoc Advanced Medical Systems, Ramat Ysihai, Israel) have been used primarily in clinical research (5,6). However, they are dependent on subjective responses and therefore have a high interobserver variability and poor reproducibility (7,8). We recently described a novel and reproducible (coefficient of variation <15%) technique to assess small-fiber dysfunction, the “LDIflare,” which measures axon reflex–mediated vasodilatation in response to skin heating (9). We have also demonstrated that LDIflare detects early C-fiber dysfunction in type 2 diabetes before small-fiber neuropathy can be detected by other currently available noninvasive methods (10). However, the structural basis for an abnormal LDIflare response has not been established.Although intraepidermal nerve fiber density (IENFD), with good intraobserver reproducibility, has been increasingly used to diagnose small-fiber neuropathies, it is an invasive procedure (11,12). In the present study we assessed small-fiber function using quantitative sensory testing (QST) and the LDIflare and compared these results with the results of dermal NFD in foot skin biopsy specimens from the same area. Dermal NFD as opposed to IENFD was quantified to define the underlying structural basis of the LDIflare, as this depends on an abnormality in dermal blood flow. In addition, as there is no current consensus as to whether an abnormality in small-fiber dysfunction and damage underlie painful diabetic neuropathy, we compared diabetic patients with painful neuropathy (PFN) and painless neuropathy (PLN).     

Clinical Evaluation of a Novel On-Strip Calibration Method for Blood Glucose Measurement

Background:This study evaluated a novel technology for improving accuracy of self-monitoring of blood glucose (SMBG). The technology calibrates each and every test by measuring the response from a predetermined amount of glucose present in the sample chamber of each test strip.Method:SMBG test strips were modified to include a lid coated with a fast dissolving formulation containing glucose. These test strips were characterized for hematocrit (Hct) and temperature induced error response to develop a calibration algorithm. The modified test strips were used in a clinical evaluation involving fingerstick blood samples from 160 subjects.Results:Experiments involving Hct and temperature induced errors show that the technology generates a signal characteristic of the error conditions in any particular test, but independent of glucose concentration, allowing a correction algorithm to be derived. The approach substantially reduced Hct and temperature derived errors. Clinical evaluation using fingerstick blood directly applied to prototype strips showed the error (measured as MARD) was reduced from 11.1 to 5.9% by the on-strip correction approach and the number of outliers reduced by approximately 90%.Conclusion:This technology could improve the accuracy and precision of glucose monitoring systems and so reduce decision errors particularly in clinical situations where hematocrit and temperature may be significant confounders.     

Audit of acute Charcot’s disease in the UK: the CDUK study

Aims/hypothesis  

We studied factors associated with the development and resolution of acute Charcot foot using a web-based observational study.     

Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes (IWGDF 2019 update)

The International Working Group on the Diabetic Foot (IWGDF) has published evidence‐based guidelines on the prevention and management of diabetic foot disease since 1999. In conjunction with advice from internal and external reviewers and expert consultants in the field, this update is based on a systematic review of the literature centred on the following: the Population (P), Intervention (I), Comparator (C) and Outcomes (O) framework; the use of the SIGN guideline/Cochrane review system; and the 21 point scoring system advocated by IWGDF/EWMA. This has resulted in 13 recommendations. The recommendation on sharp debridement and the selection of dressings remain unchanged from the last recommendations published in 2016. The recommendation to consider negative pressure wound therapy in post‐surgical wounds and the judicious use of hyperbaric oxygen therapy in certain non‐healing ischaemic ulcers also remains unchanged. Recommendations against the use of growth factors, autologous platelet gels, bioengineered skin products, ozone, topical carbon dioxide, nitric oxide or interventions reporting improvement of ulcer healing through an alteration of the physical environment or through other systemic medical or nutritional means also remain. New recommendations include consideration of the use of sucrose‐octasulfate impregnated dressings in difficult to heal neuro‐ischaemic ulcers and consideration of the use of autologous combined leucocyte, platelet and fibrin patch in ulcers that are difficult to heal, in both cases when used in addition to best standard of care. A further new recommendation is the consideration of topical placental derived products when used in addition to best standard of care.     

The first phase insulin response to intravenous glucose is highly reproducible

Summary To determine the reproducibility of the first phase insulin response to intravenous glucose, ten normal subjects underwent two intravenous glucose tolerance tests separated by at least two weeks. Intravenous dextrose (0.3 g/kg) was administered over 2 min by continuous infusion and arterialised-venous samples were taken from a retrogradely cannulated hand vein in the opposite arm. Within subjects, median coefficient of variation for the 3 min insulin was 4.0% (range 1.2–24.3%) and median coefficient of variation for the 0–10 min area was 6.7% (range 1.7–18.8%). These coefficients of variation are close to those of the assay itself (< 10%). Despite this, between subject responses varied by greater than sixfold. In conclusion, contrary to previous reports the intravenous glucose tolerance test is highly reproducible. This makes it a very valuable tool for further studies of the pathogenesis of diabetes.     

Computer-enhanced telemanipulation in mitral valve repair: preliminary experience in Canada with the da Vinci robotic system.

BACKGROUND: Investigation into the surgical application of robot technology continues to expand. We report on the first case series of robotic-assisted mitral valve (RAMV) repair in Canada with use of the da Vinci telemanipulation system (Intuitive Surgical, Sunnyvale, Calif.). METHODS: Between February 2004 and August 2004, 10 patients with normal left ventricular function and severe mitral valve regurgitation underwent RAMV repair with use of the da Vinci system. Peripheral cardiopulmonary bypass, transthoracic aortic cross-clamping and antegrade cardioplegia were used in all cases. A minithoracotomy in the fourth intercostal space and 2 ports in the third and fifth intercostal spaces allowed surgical access. All mitral valve valvuloplasties and band annuloplasties were done endoscopically with robotic assistance. RESULTS: Nine of 10 patients had successful valve repair, and 1 had conversion to mitral valve replacement due to persistent regurgitation. There were no deaths, strokes or need for sternotomy. One patient required re-exploration for bleeding. CONCLUSION: Minimally invasive RAMV repair is feasible and safe with promising early postoperative results when performed by experienced surgical personnel accomplished in both mitral valve procedures and robotic techniques.