The use of fetal bovine acellular dermal matrix in severe diabetic foot ulceration and threatened limbs with tissue loss the use of FBADM as an adjunct for complex wounds.

OBJECTIVES: Foot ulceration associated with diabetic foot disease (DFD) and chronic limb-threatening ischaemia (CLTI) presents a complex clinical challenge and failure to heal the wound imposes a significant risk of major limb amputation (MLA). In attempt to accelerate wound healing rates and decrease MLA, tissue engineering research into bio-engineered scaffolds and skin substitutes has become a growing area of interest. Advanced wound therapies such as fetal bovine acellular dermal matrix (FBADM) may have success in the treatment of difficult to heal chronic foot ulcers. The FBADM traps and binds the patients' own epithelial cells to rebuild the dermis layer of the skin. Previous studies have suggested that wounds treated with FBADM had a faster healing rate than wounds managed with conventional dressings. However, these studies excluded foot wounds with chronic exposed bone or tendon, active infection, gangrene, or osteomyelitis and patients with uncontrolled blood glucose levels were excluded. The aim of this study was to assess the efficacy of FBADM for patients admitted to hospital acutely with severe foot ulceration secondary to DFD and CLTI. METHODS: Between February 2020 and December 2021, inpatients admitted acutely at a single tertiary centre with a severe non-healing foot ulcer and had a wound suitable for application of a FBADM after primary debridement were included in the study. A severe non-healing foot wound was defined as a Society for Vascular Surgery Wound, Ischaemia, and foot Infection (WIfI) stage of 3 or 4. Participants were prospectively followed up at regular intervals at a multidisciplinary high-risk diabetic foot clinic until June 2022. The primary endpoint was time to wound closure. The secondary endpoints were number of applications of FBADM, readmission rate and amputation-free survival. RESULTS: There were 22 patients included in the study with a median age of 71 (50-87) years and 15 were male. Five patients had a WIfI stage of 3 and 17 had a WIfI score of 4. Overall, 14 patients required revascularisation procedures (6 open surgery,8 endovascular intervention). A total of 18 patients achieved complete wound healing with a median time to wound healing of 178 (28-397) days. Two patients underwent a MLA and two patients died prior to complete wound healing. The median length of stay was 16.5 (5-115) days, and 4 patients were readmitted to hospital within 12 months. CONCLUSION: FBADM may be a useful adjunct in the acute setting of complex DFD and CLTI ulceration to assist with wound healing. Future comparative prospective studies are required to further validate these preliminary findings.

Creativity in energy balance, obesity and feeding behavior research, some thoughts.

This review provides an overview of examples of especially creative work related to the fields of ingestive behavior, energetics (defined as the study of the acquisition, storage, and use of metabolizable energy by biological organisms and the causes and consequences of such acquisition, storage, and use), and nutrition, focusing on both individual works and discoveries, as well as bodies of works and in some cases the working styles of particular scientists. The paper then discusses some principles extracted from our observations as well as from the literature on creativity pointing out some factors that seem to make for more creative science and that can be done by individuals to promote creativity in their own work. Finally, we end with a short set of tips for the field in general to promote creativity among our ranks broadly.

Causal models and causal modelling in obesity: foundations, methods and evidence.

Discussing causes in science, if we are to do so in a way that is sensible, begins at the root. All too often, we jump to discussing specific postulated causes but do not first consider what we mean by, for example, causes of obesity or how we discern whether something is a cause. In this paper, we address what we mean by a cause, discuss what might and might not constitute a reasonable causal model in the abstract, speculate about what the causal structure of obesity might be like overall and the types of things we should be looking for, and finally, delve into methods for evaluating postulated causes and estimating causal effects. We offer the view that different meanings of the concept of causal factors in obesity research are regularly being conflated, leading to confusion, unclear thinking and sometimes nonsense. We emphasize the idea of different kinds of studies for evaluating various aspects of causal effects and discuss experimental methods, assumptions and evaluations. We use analogies from other areas of research to express the plausibility that only inelegant solutions will be truly informative. Finally, we offer comments on some specific postulated causal factors. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.

A quantitative assessment of dual energy computed tomography-based material decomposition for imaging bone marrow edema associated with acute knee injury.

PURPOSE: This study developed methods to quantify and improve the accuracy of dual-energy CT (DECT)-based bone marrow edema imaging using a clinical CT system. Objectives were: (a) to quantitatively compare DECT with gold-standard, fluid-sensitive MRI for imaging of edema-like marrow signal intensity (EMSI) and (b) to identify image analysis parameters that improve delineation of EMSI associated with acute knee injury on DECT images. METHODS: DECT images from ten participants with acute knee injury were decomposed into estimated fractions of bone, healthy marrow, and edema based on energy-dependent differences in tissue attenuation. Fluid-sensitive MR images were registered to DECT for quantitative, voxel-by-voxel comparison between the two modalities. An optimization scheme was developed to find attenuation coefficients for healthy marrow and edema that improved EMSI delineation, compared to MRI. DECT method accuracy was evaluated by measuring dice coefficients, mutual information, and normalized cross correlation between the DECT result and registered MRI. RESULTS: When applying the optimized three-material decomposition method, dice coefficients for EMSI identified through DECT vs MRI were 0.32 at the tibia and 0.13 at the femur. Optimization of attenuation coefficients improved dice coefficient, mutual information, and cross-correlation between DECT and gold-standard MRI by 48%-107% compared to three-material decomposition using non-optimized parameters, and improved mutual information and cross-correlation by 39%-58% compared to the manufacturer-provided two-material decomposition. CONCLUSIONS: This study quantitatively evaluated the performance of DECT in imaging knee injury-associated EMSI and identified a method to optimize DECT-based visualization of complex tissues (marrow and edema) whose attenuation parameters cannot be easily characterized. Further studies are needed to improve DECT-based EMSI imaging at the femur.

A rare case of Haemophilus parainfluenzae septic knee following prolotherapy injections.

Prolotherapy injections are becoming increasingly popular as a non-surgical treatment option for many chronic musculoskeletal conditions. Proposed benefits include reduced pain, reduced joint laxity and increased tendon strength. While a number of studies report that prolotherapy reduces pain and increases function for many conditions, the academic evidence remains extremely weak. Here, we discuss a case of a complex intra-articular knee infection in a young, previously healthy, female following prolotherapy injections for management of a partial-thickness anterior cruciate ligament (ACL) tear. To the best of our knowledge, this is the first report of its kind describing a potential complication of intra-articular prolotherapy injections.

Decreased total psoas muscle area after neoadjuvant therapy is a predictor of increased mortality in patients undergoing oesophageal cancer resection.

BACKGROUND: Oesophagectomy for locally advanced cancer carries high rates of morbidity and mortality. Patients require a thorough risk assessment alongside preoperative counselling. Total psoas area (TPA) measurements have been used as a surrogate marker of sarcopenia to predict post-operative complications in oesophageal cancer patients. No studies to date have determined whether there is an association between the proportion of TPA lost during neoadjuvant therapy and post-operative outcomes. METHODS: Clinical data and imaging of patients who underwent neoadjuvant therapy followed by open two-stage oesophagectomy between January 2008 and April 2018 were analysed retrospectively. Patients who did not undergo restaging computed tomography scan prior to surgery were excluded from the study. The TPA was measured on two cross-sectional slices at L4 on computed tomography scans pre- and post-neoadjuvant therapy. RESULTS: A total of 53 patients who met inclusion criteria were identified. The mean loss of TPA was 7.3%. Patients who had a decrease of TPA of more than 4% had significantly increased 30-day mortality compared to those who lost 4% or less (24% versus 0%, P = 0.02). Patients aged over 65 years who also had a loss of TPA >4% had significantly increased 30-day mortality (37% versus 2.9%, odds ratio 19, P = 0.008). CONCLUSION: A decrease in TPA of >4% is associated with a significantly higher risk of post-operative mortality in patients undergoing neoadjuvant therapy followed by oesophagectomy. Measuring the loss of TPA during neoadjuvant treatment could be a novel aid to preoperative risk assessment.

Test-meal palatability alters the effects of intragastric fat but not carbohydrate preloads on intake and rated appetite in healthy volunteers.

Manipulations of test meal palatability and nutritional need-state to examine feeding behaviour have, to date, been studied in isolation. Recent investigations have attempted to examine these influences in combination. In the present study, healthy young males received intragastric infusions of soup (265 or 1514 kJ) on four different occasions. The infusion was shortly followed by a meal varying in its palatability (PALATABLE or BLAND). The effect of macronutrient type (CHO or Fat) in the high-energy preloads was also examined in a between-subject manner. High CHO preloads significantly decreased test meal intake and this decrease was unaffected by meal palatability. High fat preloads did not significantly reduce test meal intake. Additionally, more food was consumed following high fat preloads when the test meal was PALATABLE. Within-meal ratings of appetite revealed that hunger was diminished to a greater extent by CHO than by Fat preloads. Appetite was stimulated by the PALATABLE meal to a greater extent in the group receiving Fat than in those receiving the CHO preload. Comparison with a similar oral preloading study revealed differences that suggest possible interactions between cognitive, oro-sensory and gastric controls of feeding when palatable foods are consumed.

Dissociation of the effects of preload volume and energy content on subjective appetite and food intake.

Previous research suggests that enhancing the volume of a food preload without altering energy content can result in reduced appetite, although the limited evidence means that the conditions under which this effect will occur are not yet clear. In the present study, we used a Universal Eating Monitor (UEM) to record test meal intake constantly, in parallel with appetite ratings, following soup-based preloads that varied both in volume (150 vs. 450 ml) and energy density (1.4 vs. 4.2 kJ/ml). Healthy young men (n=20) received four different preload conditions (repeated measures) followed by unlimited hot pasta test meals (interval 30 min). They completed appetite ratings during and after each laboratory session, and food diaries for the afternoon and evening following each session. Subjective appetite after the preloads was reduced by the high-volume preloads relative to low-volume preloads, with no difference between the two at each volume level. This indicates an effect of volume, but no effect of energy. Test meal intake in the high-volume, high-energy-density condition was reduced relative to the other conditions, which did not differ from one another. This indicates an effect of total energy, but no effect of volume. The dissociation between these different measures of appetite might be explained in terms of largely cognitive influences on subjective appetite between preload and test meal, contrasted with stronger physiological influences on actual intake during the test meal. With regard to previous studies, it is argued that food volume is more influential under circumstances where gastric volume is closer to its normal limits.

Snacks containing whey protein and polydextrose induce a sustained reduction in daily energy intake over 2 wk under free-living conditions.

BACKGROUND: The manipulation of the composition of foods consumed as between-meal snacks may aid daily energy restriction. OBJECTIVES: We compared the effects of the consumption of 2 energy-matched snack bars on appetite, energy intake (EI), and metabolic and endocrine responses. In addition, we investigated whether the acute effects of the consumption of snacks were maintained under free-living conditions and whether the habitual daily consumption of the snack over 14 d influenced these effects. DESIGN: Ten lean men [mean ± SD age: 30.7 ± 9.7 y; body mass index (in kg/m(2)): 23.2 ± 2.8] consumed a whey protein and polydextrose (PPX) snack bar or an isoenergetic control snack bar as a midmorning, between-meal snack for 14 consecutive days in a double-blind, randomized, crossover design. The two 14-d intervention phases were separated by a 14-d washout period. On the first (day 1) and last (day 15) days of each intervention phase, appetite, food intake, and blood metabolite and endocrine responses were assessed under laboratory conditions. Free-living EI was recorded on days 4, 8, and 12 of interventions. RESULTS: Total daily EI was significantly lower when the PPX snack was consumed during experimental days (10,149 ± 831 compared with 11,931 ± 896 kJ; P < 0.01), and daily EI remained lower when the PPX snack was consumed during the free-living part of the intervention (7904 ± 610 compared with 9041 ± 928 kJ; P < 0.05). The PPX snack was associated with lower glucose and ghrelin and higher glucagon-like peptide 1 and peptide tyrosine-tyrosine responses. CONCLUSION: The manipulation of the composition of foods consumed as snacks is an effective way to limit subsequent EI. This trial was registered at clinicaltrials.gov as NCT01927926.

Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort.

Cocoa flavanols (CF) positively influence physiological processes in ways that suggest their consumption may improve aspects of cognitive function. This study investigated the acute cognitive and subjective effects of CF consumption during sustained mental demand. In this randomized, controlled, double-blinded, balanced, three period crossover trial 30 healthy adults consumed drinks containing 520 mg, 994 mg CF and a matched control, with a three-day washout between drinks. Assessments included the state anxiety inventory and repeated 10-min cycles of a Cognitive Demand Battery comprising of two serial subtraction tasks (Serial Threes and Serial Sevens), a Rapid Visual Information Processing (RVIP) task and a 'mental fatigue' scale, over the course of 1 h. Consumption of both 520 mg and 994 mg CF significantly improved Serial Threes performance. The 994 mg CF beverage significantly speeded RVIP responses but also resulted in more errors during Serial Sevens. Increases in self-reported 'mental fatigue' were significantly attenuated by the consumption of the 520 mg CF beverage only. This is the first report of acute cognitive improvements following CF consumption in healthy adults. While the mechanisms underlying the effects are unknown they may be related to known effects of CF on endothelial function and blood flow.

Effects of dietary fat and carbohydrate on appetite vary depending upon site and structure.

The present review summarises the effects of different carbohydrate and fat structures on food intake and appetite and the differences in response at various levels of processing of macronutrients. Several physico-chemical properties of carbohydrate and fat molecules appear to influence the short-term satiating properties. However, long-term substantiation of these findings expressed in terms of food intake or body weight is not currently available. Such studies will be required to make clear recommendations regarding dietary composition to aid satiety.

Recent advances in the physiology of eating.

Since the discovery of the protein product of the ob/ob gene, leptin, knowledge of the neurochemical pathways involved in the regulation of feeding has increased enormously. Our understanding of the mechanisms regulating food intake in man has also progressed greatly over a similar time span. Previous research into the regulation of food intake has largely proceeded through a reductionist approach, defining ever-smaller components of these mechanisms. This research strategy has been very productive and instructive, and has yielded a great deal of information on the specific putative components linking energy status and food intake. However, to fully understand the regulation of feeding it is important that these components are systematically reconstructed to investigate relevant interactions. In the present review recent data relating to interactions between systems proposed to be involved in feeding regulation will be highlighted. The review will be directed predominantly (but not exclusively) towards the regulation of human feeding.

Fats and food intake.

PURPOSE OF REVIEW: Given the global rates of obesity and the potential link to dietary fat intake, understanding the role of fat in the regulation of food intake is critical. Some short-term, laboratory-based studies demonstrate poor compensation for manipulation of fat content, leading to passive overconsumption, while others demonstrate compensation to levels similar to other macronutrients. The observation of compensation in the short term does not concur with long-term rates of obesity increase. This review discusses factors that may explain at a physiological level these discrepancies, in particular fat structure, dietary adaptation, and palatability. RECENT FINDINGS: Medium-chain triglycerides have been demonstrated to be more satiating and promote weight loss. Recent data suggest different gastrointestinal transduction mechanisms elicit vagal afferent firing for fatty acids of different chain length. Dietary adaptation to fat can influence the sensitivity of the feedback response, which appears to be nutrient specific and relate to gastric emptying rates and hormonal feedback. Fat content has been found to influence palatability of foods. Recently it has been demonstrated that increasing palatability can partially override the satiating effects of covertly manipulated macronutrient preloads. Recent data suggest that hormonal influences may also affect the palatability response. SUMMARY: It is becoming increasingly clear that although energy density of diets is a major factor determining intake, macronutrient structure, subject, dietary and taste differences can all play an important modulatory influence on the final response on food intake. Further understanding of these factors and interactions may provide strategies to help aid weight regulation.

Increasing preload volume with water reduces rated appetite but not food intake in healthy men even with minimum delay between preload and test meal.

The role of gastric volume in the short-term control of eating in humans remains unclear, with some studies reporting that food volume alone can reduce appetite but others finding no such effect. A recent study in our laboratory, found effects of preload volume on subjective appetite (hunger, fullness) but not intake, and found effects of preload energy on intake but not appetite. That study used an interval of 30 min between serving preloads and the test meal, and the present study attempted to maximise the effects of the volume manipulation by removing the delay between the preload and test meal. We administered four soup-based preloads varying in volume (150 and 450 ml) using water, and energy density (1.4 and 4.2 kJ/ml) using maltodextrin, producing three energy levels (209, 629, 629 and 1886 kJ; repeated measures). These were followed immediately by an unlimited hot pasta lunch, during which food weight was monitored continuously by computer. Increasing soup volume at constant energy (629 kJ) reduced appetite ratings, but not intake. In contrast, increasing soup energy at constant volume (450 ml) reduced intake, without affecting appetite. The discrepancies between our results and other reported studies suggest that volume is more influential when intakes are large, or that there may be a threshold concentration for nutrients in the GI tract before volume alone is tangibly expressed in subsequent eating.

Measurement of gastric emptying in man using deuterated octanoic acid.

Gamma scintigraphy is considered the gold standard for the measurement of gastric emptying in humans. Recently, it has been proposed that a [(13)C]octanoate breath test can be used as an alternative technique for measuring gastric emptying of the solid phase, but the results from the two methods are not directly equivalent since in the breath test the label is subject to post-absorptive processing and consequently the emptying functions cannot be observed directly. This work investigates an alternative stable isotope method using deuterated octanoate where the kinetics of redistribution between and elimination from the various body pools are much more easily modelled. Gastric emptying was studied in healthy human volunteers by simultaneous measurement using both [(13)C]octanoate and [(2)H]octanoate as well as gamma scintigraphy. Comparison of the gastric emptying functions from the deuterium method and scintigraphy indicated that the two methods gave equivalent results. The new method can therefore be used in populations considered too vulnerable to ionising radiation to allow gamma scintigraphy to be performed, or as a proxy gold standard in laboratories where scintigraphic methods are unavailable, allowing further comparisons with the breath test method to be made to validate the latter in different population groups.