SEOM clinical guidelines for cancer anorexia-cachexia syndrome (2023).

Cancer-related anorexia-cachexia syndrome (CACS) is a debilitating condition afflicting up to 80% of advanced-stage cancer patients. Characterized by progressive weight loss, muscle wasting, and metabolic abnormalities, CACS significantly compromises patients' quality of life and treatment outcomes. This comprehensive review navigates through its intricate physiopathology, elucidating its stages and diagnostic methodologies. CACS manifests in three distinct stages: pre-cachexia, established cachexia, and refractory cachexia. Early detection is pivotal for effective intervention and is facilitated by screening tools, complemented by nutritional assessments and professional evaluations. The diagnostic process unravels the complex interplay of metabolic dysregulation and tumor-induced factors contributing to CACS. Management strategies, tailored to individual patient profiles, encompass a spectrum of nutritional interventions. These include dietary counseling, oral nutritional supplements, and, when necessary, enteral nutrition and a judicious use of parenteral nutrition. Specific recommendations for caloric intake, protein requirements, and essential nutrients address the unique challenges posed by CACS. While pharmacological agents like megestrol acetate may be considered, their use requires careful evaluation of potential risks. At its core, this review underscores the imperative for a holistic and personalized approach to managing CACS, integrating nutritional interventions and pharmacological strategies based on a nuanced understanding of patient's condition.

Central carbon metabolism exhibits unique characteristics during the handling of fungal patterns by monocyte-derived dendritic cells.

Monocyte-derived dendritic cells (MDDCs) are key players in the defense against fungal infection because of their outstanding capacity for non-opsonic phagocytosis and phenotypic plasticity. Accordingly, MDDCs rewire metabolism to meet the energetic demands for microbial killing and biomass synthesis required to restore homeostasis. It has been commonplace considering the metabolic reprogramming a mimicry of the Warburg effect observed in tumor cells. However, this may be an oversimplification since the offshoots of glycolysis and the tricarboxylic acid (TCA) cycle are connected in central carbon metabolism. Zymosan, the external wall of Saccharomyces cerevisiae, contains ß-glucan and α-mannan chains that engage the C-type lectin receptors dectin-1/2 and Toll-like receptors. This makes it an optimal fungal surrogate for experimental research. Using real-time bioenergetic assays and [U-13C]glucose labeling, central hubs connected to cytokine expression were identified. The pentose phosphate pathway (PPP) exhibited a more relevant capacity to yield ribose-5-phosphate than reducing equivalents of NADPH, as judged from the high levels of isotopologues showing 13C-labeling in the ribose moiety and the limited contribution of the oxidative arm of the PPP to the production of ROS by NADPH oxidases (NOX). The finding of 13C-label in the purine ring and in glutathione unveiled the contribution of serine-derived glycine to purine ring and glutathione synthesis. Serine synthesis also supported the TCA cycle. Zymosan exhausted NAD+ and ATP, consistent with intracellular consumption and/or extracellular export. Poly-ADP-ribosylated proteins detected in the nuclear fractions of MDDCs did not show major changes upon zymosan stimulation, which suggests its dependence on constitutive Fe(II)/2-oxoglutarate-dependent demethylation of 5-methylcytosine by TET translocases and/or demethylation of histone H3 lysine 27 by JMJD demethylases rather than on NOX activities. These results disclose a unique pattern of central carbon metabolism following fungal challenge, characterized by the leverage of glycolysis offshoots and an extensive recycling of NAD+ and poly(ADP-ribose).

Indicators to evaluate quality of care in head and neck cancer in Spain.

PURPOSE: This study aimed to develop a set of criteria and indicators to evaluate the quality of care of patients with head and neck cancer (HNC). METHODS: A systematic literature review was conducted to identify valuable criteria/indicators for the assessment of the quality of care in HNC. With the aid of a technical group, a scientific committee of oncologists specialised in HNC used selected criteria to propose indicators that were evaluated with a two-round Delphi method. Indicators on which consensus was achieved were then prioritised by the scientific committee to develop a final set of indicators. RESULTS: We proposed a list of 50 indicators used in the literature or developed by us to be evaluated with a Delphi method. There was consensus on the appropriateness of 47 indicators in the first round; the remaining 3 achieved consensus in the second round. The 50 indicators were scored to prioritise them, leading to a final selection of 29 indicators related to structure (3), process (22), or outcome (4) and covering diagnosis, treatment, follow-up, and health outcomes in patients with HNC. Easy-to-use index cards were developed for each indicator, with their criterion, definition, formula for use in real-world clinical practice, rationale, and acceptable level of attainment. CONCLUSIONS: We have developed a set of 29 evidence-based and expert-supported indicators for evaluating the quality of care in HNC, covering diagnosis, treatment, follow-up, and health outcomes.

Cryotherapy versus topical nitric-zinc complex solution for the treatment of plantar warts: A randomized controlled trial.

Cryotherapy is commonly regarded as the primary treatment method for plantar warts. A new medical device called nitric-zinc complex solution (NZCS) has also emerged as a potential alternative for wart treatment. The main aim of this study was to analyze and compare the effectiveness of cryotherapy using liquid nitrogen and NZCS in treating plantar warts. We conducted a randomized and controlled clinical trial involving patients with plantar warts. A total of 62 patients were enrolled in the study and monitored for 12 weeks or until their warts were completely resolved. The patients received either cryotherapy or NZCS, with a maximum of six treatment applications. The cure rate was 65.5% in the group treated with cryotherapy and 56.6% in the group treated with NZCS. The average number of treatment applications required for curing warts was significantly lower in the cured group (3.28 ± 1.63) than in the group with unresolved warts (5.5 ± 1.27) (p < 0.01). Moreover, the average number of applications was lower in the cryotherapy group (3.6 ± 1.8) than in the NZCS group (4.8 ± 1.8) (p < 0.01). Based on the findings, NZCS could be considered a favorable first-line treatment option for plantar warts.

Comparative Analysis of Bone Resection Versus Bone Curettage in Diabetic Foot Osteomyelitis.

This study aims to describe the healing times of patients who underwent bone resection compared to bone curettage for managing diabetic foot osteomyelitis and to compare short- and long-term complications. This analytical retrospective observational cohort study collected clinical records of patients from a specialized diabetic foot clinic who underwent resection or bone curettage between January 2017 and January 2022. After surgery, a 1-year follow-up was conducted to record healing times and short- and long-term complications. The study included thirty-one patients, with 19 (61.29%) undergoing resections and 11 (38.71%) undergoing bone curettages. The resection cohort had a mean healing time of 5.70 ± 6.05 weeks, whereas the curettage cohort had a mean healing time of 14.45 ± 11.78 weeks, showing a statistically significant difference (P = 0.011). No significant differences were observed in terms of short- and long-term complications. In the resection cohort, 12 (63.20%) experienced short-term complications, compared to eight (66.70%) in the curettage cohort (P = 0.842, χ2 = 0.40, OR = 1.16). In the resection cohort, n = 6 (31.60%) had long-term complications, while n = 3 (25.00%) in the curettage cohort experienced long-term complications (P = 0.694, χ2 = 0.155, OR = 0.72). Although there were no significant differences in short- and long-term complications between resection and curettage, the resection group showed shorter healing times.

Analysis of the Influence of Diabetic Nephropathy in Patients with Diabetic Foot Osteomyelitis.

This study analyzed the influence of diabetic nephropathy on the healing prognosis after conservative surgery in diabetic foot osteomyelitis (DFO). A retrospective observational study was carried out between January 2021 and December 2022 and involved 278 outpatients with a diagnosis of DFO at a specialized diabetic foot unit, including 74 (26.62%) patients with DN (group 2) and 204 (73.38%) patients without DN (group 1). There were 266 (95.70%) ulcers on the forefoot, 8 (2.90%) on the midfoot, and 4 (1.45%) on the hindfoot (p = 0.992). The healing rates were 85.1% (n = 63) for group 2 and 81.3% (n = 165) for group 1 (p = 0.457). When exploring the influence of DN on the risk of delayed ulcer healing, the results did not show a significant effect [12 (6; 28) weeks among patients with DN vs. 12 (6; 21) weeks among patients without DN; p = 0.576]. No significant differences were observed in complications, with one (2.59%) death occurring in group 1 (p = 0.296) and three minor amputations being performed in both groups [two (5.13%) amputations in group 1 vs. one amputation (9.09%) in group 2; p = 0.217]. Bone cultures were performed for a total of 190 patients (133 in group 1 and 57 in group 2). Of these, 176 positive bone cultures were isolated: 71 positive bone cultures (57.7%) were monomicrobial cultures in group 1, with 30 (56.6%) in group 2. There were 52 (42.3%) that had at least two microorganisms in group 1, and 23 (43.4%) in group 2 (p = 0.890). The most frequently prescribed oral antibiotic was amoxicillin/clavulanate (43.89%), followed by levofloxacin (28.4%), and trimethoprim/sulfamethoxazole (14.7%). This study shows that DN does not have a significant influence on the healing prognosis of patients with DFO after conservative surgery.

In Vivo Models for the Study of Hyaluronic Acid Fillers: A Review.

BACKGROUND: Hyaluronic acid (HA) filler application is one of the most frequent minimally invasive aesthetic procedures used worldwide. Its properties and characterization, performance, effects in other tissues, and response to complication treatments have been studied in several animal models. This review aims to categorize animal models considering the advantages and disadvantages regarding the purpose of the study. METHODS: Literature research was made using MEDLINE via PubMed by two reviewers using keywords "hyaluronic acid" "filler" and "animal model". Full-text articles published in English and with an in vivo animal model were included for data extraction. RESULTS: The rat model was the most common animal used to evaluate properties or characteristics and degradation of HA fillers. Rabbits were preferred for evaluating HA embolism treatments; however, anatomical names of the arteries differ in some studies. Mice and rats used as vascular occlusion model are challenging due to the size of the vessels and viscosity of the filler. CONCLUSION: There is a wide variability of options of in vivo animal models to evaluate HA fillers. The animal characteristics, laboratory resources, and HA properties should be considered in accordance with the objective of the study, when choosing the ideal model. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Culture Concordance in Different Sections of the Metatarsal Head: Interpretations of Microbiological Results.

Microbiological cultures of per-wound bone biopsies have shown a lack of correlation and a high rate of false-negative results when compared with bone biopsy cultures in diabetic foot osteomyelitis. The selection of samples from the area of active osteomyelitis, which contains a complete census of the microorganisms responsible for the infection, is essential to properly guide antimicrobial treatment. We aimed to comparatively evaluate the quantitative and qualitative cultures taken from different areas, in metatarsal heads resected for osteomyelitis. For this purpose, we consecutively selected 13 metatarsal heads from 12 outpatients with plantar ulcers admitted to our diabetic foot unit. Metatarsal heads were divided transversally into 3 portions: plantar (A), central (B), and dorsal (C), and the 39 resulting samples were cultured. Qualitative and quantitative microbiological analysis was performed, and the isolated species and bacterial load, total and species specific, were compared between the 3 metatarsal bone segments. The primary outcome of the study was the bacterial diversity detected in the different bone sections. Cultures were positive in 12 of the 13 included metatarsal heads (92%). A total of 34 organisms were isolated from all specimens. Ten of the 12 cultures (83%) were polymicrobial. Ten of the 13 metatarsal heads (77%) had identical microbiological results in each of the 3 bone sections. The largest number of microorganisms was found in the central section. The overall concordance between sections was 91%. The predominant microorganisms were coagulase-negative staphylococci (41%). Statistical differences were not found in the bioburden between sections (range 3.25-3.41 log10 colony-forming unit/g for all sections; P = .511). The results of our study suggest that microorganisms exhibit a high tendency to spread along the metatarsal bone and that the degree of progression along the bone is species dependent. The central portions of metatarsal bones tend to accumulate a higher diversity of species. Thus, we recommend this area of bone for targeted biopsy in patients with suspected osteomyelitis.

The Influence of Arterial Calcification on Clinical Outcomes in Patients with Diabetic Foot Ulcer Complicated by Osteomyelitis Treated by Surgery.

The aim of our study was to analyze the influence of radiographic arterial calcification (RAC) on clinical outcomes and wound healing in patients with diabetic foot ulcers complicated by osteomyelitis treated by surgery. We analyzed retrospectively the clinical records of 102 patients with diabetic foot osteomyelitis who underwent surgery at a specialized diabetic foot unit between January 2014 and December 2016. The clinical data of evolution until its complete epithelialization and a follow-up 1 year were reviewed, and after reviewing the radiological images, patients were classified into 2 groups: those with RAC and those without RAC. We analyzed several clinical features in both groups. The presence of RAC was associated with a greater time of healing (10.68 ± 7.24 vs 8.11 ± 4.50 weeks; P = .029) and shorter time to recurrence and reulceration (13.30 ± 9.25 vs 18.81 ± 11.63 weeks; P = .036). However, this association was not found for patients with mild and moderate peripheral artery disease (PAD), whose time of healing was 8.97 ± 4.51 weeks compared to 9.16 ± 6.39 weeks for patients without PAD; P = .864. The time of healing of diabetic foot ulcers complicated by osteomyelitis treated by surgery can be negatively affected by the presence of RAC even more than by the presence of mild and moderate ischemia. The presence of RAC may offer clinical guidance at the level of primary care though this would need thorough validation in future studies.

Systemic treatment with cigarette smoke extract affects zebrafish visual behaviour, intraocular vasculature morphology and outer segment phagocytosis.

Introduction: Cigarette smoking adversely affects multiple aspects of human health including eye disorders such as age-related macular degeneration, cataracts and dry eye disease. However, there remains a knowledge gap in how constituents of cigarette smoke affect vision and retinal biology. We used zebrafish to assess effects of short-term acute exposure to cigarette smoke extract (CSE) on visual behaviour and retinal biology. Methods: Zebrafish larvae with a developed visual system at three days post-fertilization (dpf) were exposed to CSE for 4, 24 or 48 hours. Visual behaviour, hyaloid vasculature morphology, retinal histology, oxidative stress gene expression and outer segment phagocytosis were investigated using visual behavioural optokinetic and visual motor response assays (OKR and VMR), microscopy (light, fluorescence and transmission electron microscopy), and real-time PCR. Results: In zebrafish larvae, 48 hours of CSE treatment resulted in significantly reduced visual behaviour. Larvae treated with 10, 15 or 20 µg/mL CSE showed an average of 13.7, 10.7 or 9.4 saccades per minute, respectively, significantly lower compared with 0.05% DMSO controls (p=0.0093, p=0.0004 and p<0.0001, respectively) that exhibited 19.7 saccades per minute. The diameter of intraocular vessels increased from 4.833 µm in 0.05% DMSO controls to 5.885 µm in the 20 µg/mL CSE-treated larvae (p=0.0333). Biometry analysis highlighted a significant axial length elongation in 20 µg/mL CSE-treated larvae (216.9 µm, p<0.0001) compared to 0.05% dimethyl sulfoxide (DMSO) controls (205.1 µm). Larvae exposed to 20 µg/mL CSE had significantly (p=0.0002) higher numbers of RPE phagosomes compared to vehicle controls (0.1425 and 0.093 phagosomes/µm RPE, respectively). Conclusions: Zebrafish larvae with a developed visual system display apparent defects in visual behaviour and retinal biology after acute exposure to CSE, establishing a valuable in vivo model to investigate ocular disorders related to cigarette smoke.

This study investigates the effects of cigarette smoke on the visual system of zebrafish larvae. We exposed the larvae to cigarette smoke extract for 4, 24, or 48 hours and assessed their eye movements, retina morphology and oxidative stress gene expression. Exposure to cigarette smoke extract for 48 hours reduced eye movements behaviour in the zebrafish larvae and led to changes in the morphology of their hyaloid vasculature present in the lens and the number of phagosomes in their retinal pigment epithelium. When exposure was shortened to 4 or 24 hours, eye movements were still reduced and oxidative stress was affected. These results suggest that zebrafish larvae can be used as a valuable model to investigate ocular disorders related to cigarette smoke.

Safety and Efficacy of Several Versus Isolated Prophylactic Flexor Tenotomies in Diabetes Patients: A 1-Year Prospective Study.

Background: To assess long-term clinical outcomes of patients who underwent isolated versus several percutaneous flexor tenotomies for the treatment of toe deformities and previous diabetic foot ulcers; Methods: Twenty-three patients (mean age 66.26 ± 11.20, years) who underwent prophylactic percutaneous flexor tenotomies secondary to tip-toe ulcers participated in this 1-year prospective study. The study was stratified into two groups for analyses: (1) isolated tenotomies patients, and (2) several tenotomies patients (two or more tenotomies). Outcome measures were toe reulceration and recurrence, minor lesions, digital deformities, and peak plantar pressure (PPP­N/cm2) and pressure/time Integral (PTI­N/cm2/s) in the hallux and minor toes after a 1-year follow-up period; Results: Patients with isolated tenotomies (n = 11, 35.48%) showed a higher rate of reulceration (n = 8, 72.7%, p < 0.001) in the adjacent toes, additionally, we found more prevalence of hyperkeratosis (n = 11, 100%), minor lesions (n = 9, 81%), and claw toes (n = 11, 100%) (p < 0.001). In several tenotomies patients (n = 20, 64.52%), we found a higher rate of floating toes (n = 16, 80%) in comparison with isolated tenotomies patients (p < 0.001). PPP and PTI in the non-tenotomy toes were higher in the group of patients who underwent isolated tenotomies (p < 0.001); Conclusions: Patients who underwent several tenotomies had better clinical outcomes after a 1-year follow-up period compared to isolated tenotomies.

Clinical and Histological Outcomes of Negatively Charged Polystyrene Microspheres Applied Daily Versus Three Times per Week in Hard-to-Heal Diabetic Foot Ulcers: A Randomized Blinded Controlled Trial.

Negatively charged polystyrene microspheres (NCMs) have been demonstrated as a novel and effective therapy for managing hard-to-heal diabetic foot ulcers (DFUs). However, one limitation of this therapy is that the protocol is based on daily application, which sometimes does not fit local protocols of wound care. Thus, we aimed to analyze the safety and efficacy of a new dose regimen. We conducted a randomized blinded controlled trial in a specialized diabetic foot unit between May 2019 and February 2021 with a total of 30 patients who had neuropathic or neuroischemic DFUs that had not responded after four weeks of standard treatment. Patients were randomized consecutively into a group that received daily application (control) or one that received applications three times per week (experimental). The clinical outcomes were evaluated using the Wollina score and wound-area reduction (WAR) weekly during a treatment period of 28 days. The histological outcomes were assessed using a soft-tissue punch biopsy (3 mm) at 0, 14, and 28 days to evaluate cellular proliferation. The Wollina scores were higher at the end of treatment by week 4 in both groups, but the differences were not significant between groups. The averages were 6 (5, 7) points in Experimental group (EG) and 6 (6,7) points in Control group (CG) (p = 0.848). Wound area reduction at day 28 was 53.57 [37.43, 79.16] % in the CG and 79.37 [42.74, 93.57] % in the EG, without differences among groups (p = 0.305). Cellular proliferation was similar in both groups at day 28. Application three times per week showed similar clinical and histological outcomes to those of daily application, both dose regimens demonstrated significant improvement of granulation tissue formation and WAR during the treatment.

Discovery and Development of the Quininib Series of Ocular Drugs.

The quininib series is a novel collection of small-molecule drugs with antiangiogenic, antivascular permeability, anti-inflammatory, and antiproliferative activity. Quininib was initially identified as a drug hit during a random chemical library screen for determinants of developmental ocular angiogenesis in zebrafish. To enhance drug efficacy, novel quininib analogs were designed by applying medicinal chemistry approaches. The resulting quininib drug series has efficacy in in vitro and ex vivo models of angiogenesis utilizing human cell lines and tissues. In vivo, quininib drugs reduce pathological angiogenesis and retinal vascular permeability in rodent models. Quininib acts as a cysteinyl leukotriene (CysLT) receptor antagonist, revealing new roles of these G-protein-coupled receptors in developmental angiogenesis of the eye and unexpectedly in uveal melanoma (UM). The quininib series highlighted the potential of CysLT receptors as therapeutic targets for retinal vasculopathies (e.g., neovascular age-related macular degeneration, diabetic retinopathy, and diabetic macular edema) and ocular cancers (e.g., UM).

A comparison of hyperspectral imaging with routine vascular noninvasive techniques to assess the healing prognosis in patients with diabetic foot ulcers.

OBJECTIVE: To compare the potential healing prognosis of the different routine noninvasive techniques implemented in the International Working Group Diabetic Foot Guidelines with the novel use of hyperspectral imaging (HSI) in patients with diabetic foot ulcers (DFUs). METHODS: Twenty-one patients with active DFUs participated in this 1-year prospective study in a specialized diabetic foot unit between December 2018 and January 2020. HSI was performed at baseline to quantify tissue oxygenation and should be presented on an anatomical map by analyzing the following parameters: (1) oxygen saturation of the hemoglobin, (2) tissue hemoglobin index, (3) the near-infrared perfusion index, and (4) tissue water index. In addition, transcutaneous oxygen pressure (TcpO2), systolic toe and ankle pressures, ankle-brachial index, and toe-brachial index values were calculated for the ulcerated limb. The primary outcome measure was wound healing, defined as complete epithelization without any drainage confirmed for at least 10 days after closure was first documented at 24 weeks. RESULTS: During the follow-up period 14 patients (66.66 %) healed and 7 patients did not heal (33.3%) by 24 weeks. The TcpO2 optimal cut-off point as determined by a balance of sensitivity and specificity of 28.5 mm Hg that yielded a sensitivity of 91% and a specificity of 100%, and area under the curve of 0.989 (P = .005; 95% confidence interval [CI], 0.945-1.000). Followed by the oxygen saturation of the hemoglobin optimal cut-off point as determined by a balance of sensitivity and specificity of 48.5 mm Hg that yielded a sensitivity of 93% and a specificity of 0.71%, and area under the curve of 0.932 (P = .013; 95% CI, 0.787-1.000). The logistic regression analyses showed that TcpO2 was the only variable associated with wound healing at 24 weeks (P < .001; 95% CI, 0.046-0.642). CONCLUSIONS: The HSI was shown to be effective in the prognosis of DFU healing compared with other noninvasive test; only TcpO2 values resulted in better diagnosis potential in wound healing.

Inactivation of Fgf3 and Fgf4 within the Fgf3/Fgf4/Fgf15 gene cluster reveals their redundant requirement for mouse inner ear induction and embryonic survival.

BACKGROUND: Fibroblast growth factors (Fgfs) are required for survival and organ formation during embryogenesis. Fgfs often execute their functions redundantly. Previous analysis of Fgf3 mutants revealed effects on inner ear formation and embryonic survival with incomplete penetrance. RESULTS: Here, we show that presence of a neomycin resistance gene (neo) replacing the Fgf3 coding region leads to reduced survival during embryogenesis and an increased penetrance of inner ear defects. Fgf3neo/neo mutants showed reduced expression of Fgf4, which is positioned in close proximity to the Fgf3 locus in the mouse genome. Conditional inactivation of Fgf4 during inner ear development on a Fgf3 null background using Fgf3/4 cis mice revealed a redundant requirement between these Fgfs during otic placode induction. In contrast, inactivation of Fgf3 and Fgf4 in the pharyngeal region where both Fgfs are also co-expressed using a Foxg1-Cre driver did not affect development of the pharyngeal arches. However, these mutants showed reduced perinatal survival. CONCLUSIONS: These results highlight the importance of Fgf signaling during development. In particular, different members of the Fgf family act redundantly to guarantee inner ear formation and embryonic survival.

Hyaluronic Acid Embolism Treated with Subcutaneous High and Low Hyaluronidase Doses: Efficacy and Surrounding Tissue Effect.

BACKGROUND: The use of hyaluronidase in hyaluronic acid vascular occlusion has been evaluated; however, the models used do not accurately assimilate the facial morphologic characteristics or study the effects on adjacent tissues. The purpose of this study was to determine an effective concentration of subcutaneous hyaluronidase to dissolve a hyaluronic acid embolism and its effect on surrounding tissue. METHODS: Fifteen rabbits were divided into six groups. An inguinal incision was performed on the femoral artery to create a hyaluronic acid embolism in the control and treatment groups (low-, medium-, and high-hyaluronidase groups). Hyaluronidase was injected subcutaneously. Photographic follow-up, histologic analysis, and quantification of hyaluronic acid were performed. Kruskal-Wallis test and post hoc with Bonferroni correction (p < 0.05) was used to compare the presence of hyaluronic acid in the arterial lumen between groups. RESULTS: Despite the persistence of intravascular hyaluronic acid, macroscopic and microscopic differences were found between the embolism control group and embolism hyaluronidase high-dose group. Histologic analysis demonstrated thrombosis throughout groups. Skeletal muscle was least affected in the embolism hyaluronidase 500 IU group with less lysis and inflammatory infiltrate. CONCLUSIONS: A 500 IU hyaluronidase dose partially prevents the damage caused by the embolism, and does not affect the surrounding tissue. The use of thrombolytic therapy combined with higher doses of hyaluronidase subcutaneously in this model is proposed.

Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes.

Adipogenesis regulation is crucial for mature adipocyte function. In obesity, a major driver of type 2 diabetes (T2D), this process is disrupted and remains poorly characterized. Here we identified altered DNA methylation profiles in diabetic obese patients, during three adipocytes differentiation stages. We isolated mesenchymal cells from visceral adipose tissue of obese patients with and without T2D to analyse DNA methylation profiles at 0, 3, and 18 days of ex vivo differentiation and documented their impact on gene expression. Methylation and gene expression were analysed with EPIC and Clarion S arrays, respectively. Patients with T2D had epigenetic alterations in all the analysed stages, and these were mainly observed in genes important in adipogenesis, insulin resistance, cell death programming, and immune effector processes. Importantly, at 3 days, we found six-fold more methylated CpG alterations than in the other stages. This is the first study to document epigenetic markers that persist through all three adipogenesis stages and their impact on gene expression, which could be a cellular metabolic memory involved in T2D. Our data provided evidence that, throughout the adipogenesis process, alterations occur in methylation that might impact mature adipocyte function, cause tissue malfunction, and potentially, lead to the development of T2D.

Analysis of Plantar Pressure Pattern after Metatarsal Head Resection. Can Plantar Pressure Predict Diabetic Foot Reulceration?

To evaluate the metatarsal head that was associated with the highest plantar pressure after metatarsal head resection (MHR) and the relations with reulceration at one year, a prospective was conducted with a total of sixty-five patients with diabetes who suffered from the first MHR and with an inactive ulcer at the moment of inclusion. Peak plantar pressure and pressure time integral were recorded at five specific locations in the forefoot: first, second, third, fourth, and fifth metatarsal heads. The highest value of the four remaining metatarsals was selected. After resection of the first metatarsal head, there is a displacement of the pressure beneath the second metatarsal head (p < 0.001). Following the resection of the minor metatarsal bones, there was a medial displacement of the plantar pressure. In this way, plantar pressure was displaced under the first metatarsal head following resection of the second or third head (p = 0.001) and under the central heads after resection of the fourth or fifth metatarsal head (p < 0.009 and p < 0.001 respectively). During the one-year follow-up, patients who underwent a metatarsal head resection in the first and second metatarsal heads suffered transfer lesion in the location with the highest pressure. Patients who underwent a minor metatarsal head resection (second-fifth metatarsal heads) showed a medial transference of pressure. Additionally, following the resection of the first metatarsal head there was a transference of pressure beneath the second metatarsal head. Increase of pressure was found to be a predictor of reulceration in cases of resection of the first and second metatarsal heads.

Conservative surgery for chronic diabetic foot osteomyelitis: Procedures and recommendations.

Osteomyelitis (OM) is the most frequent infection associated with diabetic foot ulcers (DFU) that typically involve the forefoot, the most common location of DFU. Conservative surgical procedures could be attractive alternative that reduces minor and major amputations and avoid future recurrence thus preserving the functionally of the foot. This review aimed to analyze and describe the current evidence on conservative diabetic foot osteomyelitis (DFO) surgical procedures depending on DFU location and indications. A narrative revision of the evidence was carried out by searching Medline through PubMed databases from inception to late July 2020 to identify retrospective, prospective, and randomized controlled trials pertaining to conservative DFO procedures on the forefoot. Seven types of conservative surgical procedures for DFO treatment in the forefoot are described in this review: (1) partial or total distal phalangectomy, (2) arthroplasty of the proximal or distal interphalangeal joint, (3) distal Syme amputation, (4) percutaneous flexor tenotomy, (5) sesamoidectomy, (6) arthroplasty of the metatarsophalangeal joint, and (7) metatarsal head resection. When indicated, conservative surgery for DFUs in patients with chronic forefoot OM is a safe and effective option that increases the chances of healing and reduces the possibility of limb loss and death compared with radical amputation procedures. Since a lack of sufficient evidence supporting this procedure exists, future investigations should be focused on the random clinical trial (RCT) design. The results of prospective trials could help surgeons select the appropriate procedure in each case in order to minimize complications.

Diagnostic Accuracy of Bone Culture Versus Biopsy in Diabetic Foot Osteomyelitis.

OBJECTIVE: To compare the diagnostic accuracy of bone culture (microbiology) and biopsy (histology) in patients with acute or chronic diabetic foot osteomyelitis (DFO). METHODS: This cross-sectional study involved patients for whom providers had a clinical suspicion of DFO. Two bone samples were taken: one for microbiologic testing and another for histologic testing. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were calculated for bone culture results in relation to the probability of DFO diagnosis. RESULTS: Fifty-two patients were included; 69% had positive bone culture results, and 90.4% had positive histology results (P = .013), and of those 90.4%, 25.5% had acute and 74.5% had chronic DFO. The sensitivity of the microbiologic bone culture result was 0.70, the specificity was 0.40, the positive predictive value was 0.92, and the negative predictive value was 0.13. CONCLUSIONS: Histology provides more accurate diagnosis of DFO than microbiology, especially for patients with chronic DFO. These patients could be underdiagnosed because of false-negative results provided by bone culture. Providers should perform both tests to confirm the presence of DFO.