A multidisciplinary team reduces in-hospital clinical complications and mortality in patients with diabetic foot ulcers.

AIMS: The current study aims to evaluate the effectiveness of a multidisciplinary diabetic foot team (MDFT) in the management of in-patients affected by diabetic foot problems. MATERIALS AND METHODS: The study was a retrospective observational study. Consecutive patients with a diabetic foot problem requiring hospitalisation were included. All patients were managed by a MDFT led by diabetologists according to the guidance. The rate of in-hospital complications (IHCs), major amputation, and survival were recorded at the end of patient's hospitalisation. IHC was defined as any new infection different from wound infection, cardiovascular events, acute renal injury, severe anaemia requiring blood transfusion, and any other clinical problem not present at the assessment. RESULTS: Overall, 350 patients were included. The mean age was 67.9 ± 12.6 years, 254 (72.6%) were males, 323 (92, 3%) showed Type 2 diabetes with a mean duration of 20.2 ± 9.6 years; 224 (64%) had ischaemic diabetic foot ulcers (DFUs) and 299 (85.4%) had infected DFUs. IHCs were recorded in 30/350 (8.6%) patients. The main reasons for IHCs were anaemia requiring blood transfusion (2.8%), pneumonia (1.7%), acute kidney failure (1.1%). Patients with IHCs showed a higher rate of major amputation (13.3 vs. 3.1%, p = 0.02) and mortality (16.7 vs. 0.6%, p < 0.0001) in comparison to those without. Ischaemic heart disease (IHD) and wound duration at the assessment (>1 month) were independent predictors of IHC, whereas IHCs, heart failure, and dialysis were independent predictors of in-hospital mortality. CONCLUSIONS: The multidisciplinary management of diabetic foot problems leads to an IHC rate of 8%. The risk of IHCs is higher in patients with IHD and long wound duration.

Recent Pharmacological Options in Type 2 Diabetes and Synergic Mechanism in Cardiovascular Disease.

Diabetes Mellitus is a multifactorial disease with a critical impact worldwide. During prediabetes, the presence of various inflammatory cytokines and oxidative stress will lead to the pathogenesis of type 2 diabetes. Furthermore, insulin resistance and chronic hyperglycemia will lead to micro- and macrovascular complications (cardiovascular disease, heart failure, hypertension, chronic kidney disease, and atherosclerosis). The development through the years of pharmacological options allowed us to reduce the persistence of chronic hyperglycemia and reduce diabetic complications. This review aims to highlight the specific mechanisms with which the new treatments for type 2 diabetes reduce oxidative stress and insulin resistance and improve cardiovascular outcomes.

Treatment of HFpEF beyond the SGLT2-Is: Does the Addition of GLP-1 RA Improve Cardiometabolic Risk and Outcomes in Diabetic Patients?

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome frequently seen in elderly patients, the incidence of which is steadily increasing due to an ageing population and the increasing incidence of diseases, such as diabetes, hypertension, obesity, chronic renal failure, and so on. It is a multifactorial disease with different phenotypic aspects that share left ventricular diastolic dysfunction, and is the cause of about 50% of hospitalizations for heart failure in the Western world. Due to the complexity of the disease, no specific therapies have been identified for a long time. Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2-Is) and Glucagon-Like Peptide Receptor Agonists (GLP-1 RAs) are antidiabetic drugs that have been shown to positively affect heart and kidney diseases. For SGLT2-Is, there are precise data on their potential benefits in heart failure with reduced ejection fraction (HFrEF) as well as in HFpEF; however, insufficient evidence is available for GLP-1 RAs. This review addresses the current knowledge on the cardiac effects and potential benefits of combined therapy with SGLT2-Is and GLP-1RAs in patients with HFpEF.

The Protective Effect of a Unique Mix of Polyphenols and Micronutrients against Neurodegeneration Induced by an In Vitro Model of Parkinson's Disease.

Parkinson's disease (PD) is second-most common disabling neurological disorder worldwide, and unfortunately, there is not yet a definitive way to prevent it. Polyphenols have been widely shown protective efficacy against various PD symptoms. However, data on their effect on physio-pathological mechanisms underlying this disease are still lacking. In the present work, we evaluated the activity of a mixture of polyphenols and micronutrients, named A5+, in the murine neuroblastoma cell line N1E115 treated with 6-Hydroxydopamine (6-OHDA), an established neurotoxic stimulus used to induce an in vitro PD model. We demonstrate that a pretreatment of these cells with A5+ causes significant reduction of inflammation, resulting in a decrease in pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α, and CXCL1), a reduction in ROS production and activation of extracellular signal-regulated kinases (ERK)1/2, and a decrease in apoptotic mechanisms with the related increase in cell viability. Intriguingly, A5+ treatment promoted cellular differentiation into dopaminergic neurons, as evident by the enhancement in the expression of tyrosine hydroxylase, a well-established dopaminergic neuronal marker. Overall, these results demonstrate the synergic and innovative efficacy of A5+ mixture against PD cellular pathological processes, although further studies are needed to clarify the mechanisms underlying its beneficial effect.

Metabolic characteristics in patients with COVID-19 and no-COVID-19 interstitial pneumonia with mild-to-moderate symptoms and similar radiological severity.

BACKGROUND AND AIMS: It is known that the highest COVID-19 mortality rates are among patients who develop severe COVID-19 pneumonia. However, despite the high sensitivity of chest CT scans for diagnosing COVID-19 in a screening population, the appearance of a chest CT is thought to have low diagnostic specificity. The aim of this retrospective case-control study is based on evaluation of clinical and radiological characteristics in patients with COVID-19 (n = 41) and no-COVID-19 interstitial pneumonia (n = 48) with mild-to-moderate symptoms. METHODS AND RESULTS: To this purpose we compared radiological, clinical, biochemical, inflammatory, and metabolic characteristics, as well as clinical outcomes, between the two groups. Notably, we found similar radiological severity of pneumonia, which we quantified using a disease score based on a high-resolution computed tomography scan (COVID-19 = 18.6 ± 14.5 vs n-COVID-19 = 23.2 ± 15.2, p = 0.289), and comparable biochemical and inflammatory characteristics. However, among patients without diabetes, we observed that COVID-19 patients had significantly higher levels of HbA1c than n-COVID-19 patients (COVID-19 = 41.5 ± 2.6 vs n-COVID-19 = 38.4 ± 5.1, p = 0.012). After adjusting for age, sex, and BMI, we found that HbA1c levels were significantly associated with the risk of COVID-19 pneumonia (odds ratio = 1.234 [95%CI = 1.051-1.449], p = 0.010). CONCLUSIONS: In this retrospective case-control study, we found similar radiological and clinical characteristics in patients with COVID-19 and n-COVID-19 pneumonia with mild-to-moderate symptoms. However, among patients without diabetes HbA1c levels were higher in COVID-19 patients than in no-COVID-19 individuals. Future studies should assess whether reducing transient hyperglycemia in individuals without overt diabetes may lower the risk of SARS-CoV-2 infection.

Activation of Peripheral Blood Mononuclear Cells and Leptin Secretion: New Potential Role of Interleukin-2 and High Mobility Group Box (HMGB)1.

Activation of innate immunity and low-grade inflammation contributes to hyperglycemia and an onset of Type 2 Diabetes Mellitus (T2DM). Interleukin-2 (IL-2), leptin, High Mobility Group Box-1 (HMGB-1), and increased glucose concentrations are mediators of these processes also by modulating peripheral blood mononuclear cells (PBMCs) response. The aim of this study was to investigate if HMGB-1 and IL-2 turn on PBMCs and their leptin secretion. In isolated human PBMCs and their subpopulations from healthy individuals and naïve T2DM patients, leptin release, pro-inflammatory response and Toll-like Receptors (TLRs) activation was measured. After treatment with IL-2 and HMGB1, NK (Natural Killer) have the highest amount of leptin secretion, whilst NK-T have the maximal release in basal conditions. TLR4 (TAK242) and/or TLR2 (TLR2-IgA) inhibitors decreased leptin secretion after IL-2 and HMGB1 treatment. A further non-significant increase in leptin secretion was reported in PBMCs of naive T2DM patients in response to IL-2 and HMGB-1 stimulation. Finally, hyperglycemia or hyperinsulinemia might stimulate leptin secretion from PBMCs. The amount of leptin released from PBMCs after the different treatments was enough to stimulate the secretion of IL-1ß from monocytes. Targeting leptin sera levels and secretion from PBMCs could represent a new therapeutic strategy to counteract metabolic diseases such as T2DM.

Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings.

AIMS: The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 patients undergoing hydroxychloroquine (HCQ) therapy in different clinical settings. METHODS AND RESULTS: COVID-19 patients at seven institutions receiving HCQ therapy from whom a baseline and at least one ECG at 48+ h were available were enrolled in the study. QT/QTc prolongation, QT-associated and QT-independent arrhythmic events, arrhythmic mortality, and overall mortality during HCQ therapy were assessed. A total of 649 COVID-19 patients (61.9 ± 18.7 years, 46.1% males) were enrolled. HCQ therapy was administrated as a home therapy regimen in 126 (19.4%) patients, and as an in-hospital-treatment to 495 (76.3%) hospitalized and 28 (4.3%) intensive care unit (ICU) patients. At 36-72 and at 96+ h after the first HCQ dose, 358 and 404 ECGs were obtained, respectively. A significant QT/QTc interval prolongation was observed (P < 0.001), but the magnitude of the increase was modest [+13 (9-16) ms]. Baseline QT/QTc length and presence of fever (P = 0.001) at admission represented the most important determinants of QT/QTc prolongation. No arrhythmic-related deaths were reported. The overall major ventricular arrhythmia rate was low (1.1%), with all events found not to be related to QT or HCQ therapy at a centralized event evaluation. No differences in QT/QTc prolongation and QT-related arrhythmias were observed across different clinical settings, with non-QT-related arrhythmias being more common in the intensive care setting. CONCLUSION: HCQ administration is safe for a short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attributable arrhythmic deaths.

Whole-body Electromyostimulation plus Caloric Restriction in Metabolic Syndrome.

We investigated early effects of Whole-Body Electromyostimulation added to hypocaloric diet on metabolic syndrome features in sedentary middle-aged individuals. We randomly assigned 25 patients to Whole-Body Electromyostimulation plus caloric restriction or caloric restriction alone for 26 weeks. Anthropometrics, blood pressure, fasting glucose and insulin, HOMA-IR, glycated hemoglobin, lipids, uric acid, creatinphosphokynase, C-reactive protein were assessed. Body composition was evaluated with direct-segmental, multi-frequency Bioelectrical Impedance Analysis. Both groups lost approximately 10% of weight, with similar effects on waist circumference and fat mass. Change in free-fat mass was significantly different between groups (caloric restriction -1.5±0.2 vs. Whole-Body Electromyostimulation plus caloric restriction +1.1±0.4 kg, p=0.03). Whole-Body Electromyostimulation plus caloric restriction group experienced greater percent reductions in insulin (-45.5±4.4 vs. -28.2±3.6%, p=0.002), HOMA-IR (-51.3±3.2 vs. -25.1±1.8%, p=0.001), triglycerides (-22.5±2.9 vs. -4.1±1.6%, p=0.004) and triglycerides/HDL (p=0.028). Subjects trained with Whole-Body Electromyostimulation had also significant improvement in systolic pressure (138±4 vs. 126±7 mmHg, p=0.038). No discontinuations for adverse events occurred. In middle-aged sedentary subjects with the metabolic syndrome, Whole-Body Electromyostimulation with caloric restriction for 26 weeks can improve insulin-resistance and lipid profile compared to diet alone. Further studies are needed to ascertain long-term efficacy and feasibility of this approach in individuals with the metabolic syndrome.

Proposed Tandem Effect of Physical Activity and Sirtuin 1 and 3 Activation in Regulating Glucose Homeostasis.

Sirtuins (SIRTs) are seven nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases enzymes (SIRT1-7) that play an important role in maintaining cellular homeostasis. Among those, the most studied are SIRT1 and SIRT3, a nuclear SIRT and a mitochondrial SIRT, respectively, which significantly impact with an increase in mammals' lifespan by modulating metabolic cellular processes. Particularly, when activated, both SIRT1 and 3 enhance pancreatic ß-cells' insulin release and reduce inflammation and oxidative stress pancreatic damage, maintaining then glucose homeostasis. Therefore, SIRT1 and 3 activators have been proposed to prevent and counteract metabolic age-related diseases, such as type 2 diabetes mellitus (T2DM). Physical activity (PA) has a well-established beneficial effect on phenotypes of aging like ß-cell dysfunction and diabetes mellitus. Recent experimental and clinical evidence reports that PA increases the expression levels of both SIRT1 and 3, suggesting that PA may exert its healthy contribute even by activating SIRTs. Therefore, in the present article, we discuss the role of SIRT1, SIRT3, and PA on ß-cell function and on diabetes. We also discuss the possible interaction between PA and activation of SIRTs as a possible therapeutic strategy to maintain glucose hemostasis and to prevent T2DM and its complications, especially in the elderly population.

Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection.

Neurodegenerative diseases are among the leading causes of mortality and disability worldwide. However, current therapeutic approaches have failed to reach significant results in their prevention and cure. Protein Kinase Cs (PKCs) are kinases involved in the pathophysiology of neurodegenerative diseases, such as Alzheimer's Disease (AD) and cerebral ischemia. Specifically ε, δ, and γPKC are associated with the endogenous mechanism of protection referred to as ischemic preconditioning (IPC). Existing modulators of PKCs, in particular of εPKC, such as ψεReceptor for Activated C-Kinase (ψεRACK) and Resveratrol, have been proposed as a potential therapeutic strategy for cerebrovascular and cognitive diseases. PKCs change in expression during aging, which likely suggests their association with IPC-induced reduction against ischemia and increase of neuronal loss occurring in senescent brain. This review describes the link between PKCs and cerebrovascular and cognitive disorders, and proposes PKCs modulators as innovative candidates for their treatment. We report original data showing εPKC reduction in levels and activity in the hippocampus of old compared to young rats and a reduction in the levels of δPKC and γPKC in old hippocampus, without a change in their activity. These data, integrated with other findings discussed in this review, demonstrate that PKCs modulators may have potential to restore age-related reduction of endogenous mechanisms of protection against neurodegeneration.

The role of epsilon PKC in acute and chronic diseases: Possible pharmacological implications of its modulators.

Epsilon Protein kinase C (εPCK) is a particular kinase that, when activated, is able to protect against different stress injuries and therefore has been proposed to be a potential molecular target against acute and chronic diseases. Particular attention has been focused on εPCK for its involvement in the protective mechanism of Ischemic Preconditioning (IPC), a powerful endogenous mechanism characterized by subthreshold ischemic insults able to protect organs against ischemic injury. Therefore, in the past decades several εPCK modulators have been tested with the object to emulate εPCK mediate protection. Among these the most promising, so far, has been the ΨεRACK peptide, a homologous of RACK receptor for εPKC, that when administrated can mimic its effect in the cells. However, results from studies on εPCK indicate controversial role of this kinase in different organs and diseases, such as myocardial infarct, stroke, diabetes and cancer. Therefore, in this review we provide a discussion on the function of εPCK in acute and chronic diseases and how the different activators and inhibitors have been used to modulate its activity. A better understanding of its function is still needed to definitively target εPCK as novel therapeutic strategy.

Liver protein profiles in insulin receptor-knockout mice reveal novel molecules involved in the diabetes pathophysiology.

Liver has a principal role in glucose regulation and lipids homeostasis. It is under a complex control by substrates such as hormones, nutrients, and neuronal impulses. Insulin promotes glycogen synthesis, lipogenesis, and lipoprotein synthesis and inhibits gluconeogenesis, glycogenolysis, and VLDL secretion by modifying the expression and enzymatic activity of specific molecules. To understand the pathophysiological mechanisms leading to metabolic liver disease, we analyzed liver protein patterns expressed in a mouse model of diabetes by proteomic approaches. We used insulin receptor-knockout (IR(-/-)) and heterozygous (IR(+/-)) mice as a murine model of liver metabolic dysfunction associated with diabetic ketoacidosis and insulin resistance. We evaluated liver fatty acid levels by microscopic examination and protein expression profiles by orthogonal experimental strategies using protein 2-DE MALDI-TOF/TOF and peptic nLC-MS/MS shotgun profiling. Identified proteins were then loaded into Ingenuity Pathways Analysis to find possible molecular networks. Twenty-eight proteins identified by 2-DE analysis and 24 identified by nLC-MS/MS shotgun were differentially expressed among the three genotypes. Bioinformatic analysis revealed a central role of high-mobility group box 1/2 and huntigtin never reported before in association with metabolic and related liver disease. A different modulation of these proteins in both blood and hepatic tissue further suggests their role in these processes. These results provide new insight into pathophysiology of insulin resistance and hepatic steatosis and could be useful in identifying novel biomarkers to predict risk for diabetes and its complications.

Morning meal more efficient for fat loss in a 3-month lifestyle intervention.

OBJECTIVE: To evaluate the effects of 2 low-calorie diets but with different distributions of calories throughout the day on weight loss and other major obesity-related metabolic parameters. METHODS: We randomly assigned 42 nonsmoking homemakers (age = 46.3 ± 2.3 years, body mass index [BMI] = 35.7 ± 0.8 kg/m(2), mean ± SD) in 2 groups of 21 subjects (G1 and G2). The participants underwent a 3 month individualized Mediterranean-style diet (55% carbohydrate, 30% fat, 15% protein and fiber > 30 g), calorie (600 kcal daily deficit compared to the total energy expenditure measured by a metabolic Holter). Diets consisted of the same food and complied with cardiovascular disease prevention guidelines but differed in the distribution of calories throughout the day (G1: 70% breakfast, morning snack, lunch and 30% afternoon snack and dinner; G2: 55 breakfast, morning snack, lunch and 45% afternoon snack and dinner). Dual-energy X-ray absorptiometry was used for pre- and postintervention body composition assessment. RESULTS: Thirty-six subjects completed the study (G1 = 18, G2 = 18). Both groups had significant improvements in body composition and metabolic parameters but G1 had enhanced results for weight loss (G1: -8.2 ± 3.0 kg; G2: -6.5 ± 3.4 kg; p = 0.028), waist circumference reduction (G1: -7 ± 0.6 cm; G2: -5 ± 0.3 cm; p = 0.033), and fat mass loss (G1: -6.8 ± 2.1 kg, G2: -4.5 ± 2.9 kg, p = 0.031; mean ± SD). Improvements were detected in both groups for blood pressure and blood and lipid parameters. G1 subjects showed a greater improvement in insulin sensitivity measured by homeostasis model assessment-estimated insulin resistance (G1: -1.37 ± 0.27, G2: -0.74 ± 0.12, p = 0.017). CONCLUSIONS: These data suggest that a low-calorie Mediterranean diet with a higher amount of calories in the first part of the day could establish a greater reduction in fat mass and improved insulin sensitivity than a typical daily diet.

Early Treatment of Acute Stage 0/1 Diabetic Charcot Foot Can Avoid Major Amputations at One Year.

Background: If unrecognized, Charcot neuro-osteoarthropathy (CNO) can be a devastating complication of diabetes. Methods: The aim of this retrospective study was to evaluate the outcomes in a cohort of diabetic patients diagnosed with active CNO managed in a tertiary level diabetic foot clinic (DFC). We included consecutive patients with active CNO, stage 0-1, according to the Eichenholtz-Shibata classification, who were referred from 1 January 2019 to 27 September 2022. Diagnosis of CNO was based on clinical signs and imaging (X-rays and magnetic resonance). All patients were completely offloaded by a total-contact cast (TCC) or removable knee-high device. Each patient was closely monitored monthly until CNO remission or another outcome. At 12 months of follow-up, the following outcomes were analyzed: remission, time to remission, major amputations (any above the ankle), and surgical indication. Results: Forty-three patients were included. The mean age was 57.6 ± 10.8 years; 65% were males and 88.4% had type 2 diabetes, with a mean duration of 20.6 ± 9.9 years. At baseline, 32.6% was affected by peripheral artery disease. Complete remission was recorded in 40/43 patients (93%), with a mean time to remission of 5.6 ± 1.5 months; major amputation and surgical indication occurred, respectively in 1/43 patients (2.3%) and 3/43 patients (7%). Conclusions: Early treatment of active Stage 0/1 CNO leads to high rates of remission and limb salvage.

Glucose variability: a new risk factor for cardiovascular disease.

AIMS AND DATA SYNTHESIS: Glucose variability (GV) is increasingly considered an additional index of glycemic control. Growing evidence indicates that GV is associated with diabetic vascular complications, thus being a relevant point to address in diabetes management. GV can be measured using various parameters, but to date, a gold standard has not been identified. This underscores the need for further studies in this field also to identify the optimal treatment. CONCLUSIONS: We reviewed the definition of GV, the pathogenetic mechanisms of atherosclerosis, and its relationship with diabetic complications.

Peripheral Blood Mononuclear Cells: A New Frontier in the Management of Patients with Diabetes and No-Option Critical Limb Ischaemia.

The current study aimed to evaluate the effectiveness of peripheral blood mononuclear cell (PB-MNC) therapy as adjuvant treatment for patients with diabetic foot ulcers (DFUs) and no-option critical limb ischaemia (NO-CLI). The study is a prospective, noncontrolled, observational study including patients with neuro-ischaemic DFUs and NO-CLI who had unsuccessful revascularization below the ankle (BTA) and persistence of foot ischaemia defined by TcPO2 values less than 30 mmHg. All patients received three cycles of PB-MNC therapy administered through a "below-the-ankle approach" in the affected foot along the wound-related artery according to the angiosome theory. The primary outcome measures were healing, major amputation, and survival after 1 year of follow-up. The secondary outcome measures were the evaluation of tissue perfusion by TcPO2 and foot pain defined by the numerical rating scale (NRS). Fifty-five patients were included. They were aged >70 years old and the majority were male and affected by type 2 diabetes with a long diabetes duration (>20 years); the majority of DFUs were infected and nearly 90% were assessed as gangrene. Overall, 69.1% of patients healed and survived, 3.6% healed and deceased, 10.9% did not heal and deceased, and 16.4% had a major amputation. At baseline and after PB-MNC therapy, the TcPO2 values were 17 ± 11 and 41 ± 12 mmHg, respectively (p < 0.0001), while the pain values (NRS) were 6.8 ± 1.7 vs. 2.8 ± 1.7, respectively (p < 0.0001). Any adverse event was recorded during the PB-MNC therapy. Adjuvant PB-MNC therapy seems to promote good outcomes in patients with NO-CLI and neuro-ischaemic DFUs.

Prevalence and risk of new-onset diabetes mellitus after COVID-19: a systematic review and meta-analysis.

Aims: After the acute phase of SARS-CoV-2 infection, the onset of glycemic impairment and diabetes have been reported. Nevertheless, the exact burden of glycemic impairment and diabetes after COVID-19 has not been clearly described. Materials and methods: Electronic search was run in Pubmed (MEDLINE), Web of Science, Scopus, and ClinicalTrial.org for reports published from database inception to September 2022. We included observational studies reporting quantitative data on diabetes prevalence or its onset in subjects with a history of SARS-CoV-2 infection from at least 60 days. Risk of bias was assessed by the JBI's critical appraisal checklist. Random effect model was used to calculate pooled data. The review protocol was registered on PROSPERO (CRD42022310722). Results: Among 1,630 records screened, 20 studies were included in the analysis. The mean or median age of participants ranged from ~ 35 to 64 years, with a percentage of males ranging from 28% to 80%. Only two studies were considered at low risk of bias. The estimate of diabetes prevalence, calculated on a total of 320,948 participants pooled with 38,731 cases, was 16% (95%CI: 11-22%). The estimate of proportion of incident cases of diabetes was 1.6% (95%CI: 0.8-2.7%). Subgroup analysis showed that previous hospitalization increased the prevalence of diabetes and the proportion of incident cases. Conclusion: Diabetes is common in individuals who have experienced SARS-CoV-2 infection, especially if they required hospitalization. This data may be helpful to screen for diabetes and manage its complications in individuals who experienced COVID-19. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022310722, identifier CRD42022310722.

Hospital Readmission in Patients With Diabetic Foot Ulcers: Prevalence, Causes, and Outcomes.

The aim of the current study was to evaluate the rate of readmission in patients affected by diabetes and foot ulcers (DFUs), and causes and outcomes of patients requiring a new hospitalization. The current study is a retrospective observational study including patients who have required hospitalization since January 2019 to September 2022 due to a DFU. Once patients were discharged, they were regularly followed as outpatients. Within 6 months of follow-up, the rate of hospital readmission for a diabetic foot problem was recorded. According to the readmission or not, patients were divided into 2 groups, readmitted and not readmitted patients, respectively. Hence, all patients were followed for 6 months more and outcomes of the 2 groups were analyzed and compared. Overall, 310 patients were included. The mean age was 68 ± 12 years, the majority of patients reported type 2 diabetes (>90%), and the mean diabetes duration was approximately 20 years. Sixty-eight (21.9%) patients were readmitted. The main reason for hospital readmission was the presence of critical limb ischemia (CLI) in the contralateral limb (6.1%), the recurrence of CLI in the previous treated limb (4.5%), and the onset of new infected DFU in the contralateral foot (4.5%). Readmitted patients reported lower rate of healing (51.5% vs 89.2%, P < .0001) and higher rate of major amputation (10.3% vs 4.5%, P = .2) in comparison to not readmitted patients. Critical limb ischemia resulted in the only independent predictor of hospital readmission. Hospital readmission is a frequent issue among patients with DFUs, and readmitted patients showed a lower chance of wound healing. Critical limb ischemia resulted in the main cause of new hospitalization.

Microbiological and Clinical Characteristics of Infected Diabetic Foot Ulcers Managed in a Tertiary Level Diabetic Foot Service.

The study aimed to evaluate the clinical and microbiological characteristics of diabetic foot infections (DFIs) in patients referring to a specialized diabetic foot service (DFS). The study is a retrospective observational study conducted in a single center, including patients who were referred for a new DFI. All patients were managed through a limb salvage protocol according to international guidelines. The following items were recorded: type of bacteria, presence of single or polymicrobial infection, and the antibiotic resistance. Overall, 268 patients were included. The mean age was 68.9 ± 10.9 years, 75% were male, and 97.2% had type 2 diabetes with a mean diabetes duration of 16 ± 9 years. One hundred thirty-nine (51.9%) DFU were ischemic, 120 (44.7%) patients had osteomyelitis, 107 (39.9%) had gangrene, 37 (13.9%) had phlegmon/abscess/cellulitis and 4 (1.5%) had necrotizing fasciitis. Among 370 bacteria isolated, gram positive were found in 207 (55.9%) cases, and gram negative in 163 (44.1%) cases. The higher rates of isolates were Staphylococcus aureus (32.9%), Pseudomonas aeruginosa (10.8%), and Enterococcus faecalis (8.9%). Polymicrobial infection was reported in 33.6% of cases and antibiotic resistance was recorded in 16.5% of isolates. Among them, 10.3% were methicillin-resistant S. aureus (MRSA). Antibiotic resistance was detected in 40.9% of cases in association with gangrene and osteomyelitis. The current study shows as polymicrobial infections and antibiotic resistance is frequently reported in DFIs, and antibiotic resistance was more associated with gangrene and osteomyelitis. Among bacteria reporting antimicrobial resistance, the highest rate was found for MRSA.

Omega-3-Enriched Diet Improves Metabolic Profile in Prdx6-Deficient Mice Exposed to Microgravity.

BACKGROUND: Space travel has always been one of mankind's greatest dreams. Thanks to technological innovation, this dream is becoming more of a reality. Soon, humans (not only astronauts) will travel, live, and work in space. However, a microgravity environment can induce several pathological alterations that should be, at least in part, controlled and alleviated. Among those, glucose homeostasis impairment and insulin resistance occur, which can lead to reduced muscle mass and liver dysfunctions. Thus, it is relevant to shed light on the mechanism underlaying these pathological conditions, also considering a nutritional approach that can mitigate these effects. METHODS: To achieve this goal, we used Prdx6-/- mice exposed to Hindlimb Unloading (HU), a well-established experimental protocol to simulate microgravity, fed with a chow diet or an omega-3-enriched diet. RESULTS: Our results innovatively demonstrated that HU-induced metabolic alterations, mainly related to glucose metabolism, may be mitigated by the administration of omega-3-enriched diet. Specifically, a significant improvement in insulin resistance has been reported. CONCLUSIONS: Although preliminary, our results highlight the importance of specific nutritional approaches that can alleviate microgravity-induced harmful effects. These findings should be considered soon by those planning trips around the earth.