Association of dietary patterns with sarcopenia in adults aged 50 years and older.

PURPOSE: Although numerous studies have investigated the impact of dietary factors on the prevention of decreased muscle mass and function, limited research has examined the relationship between dietary patterns and sarcopenia. This study aimed to assess the associations between dietary patterns, and sarcopenia, muscle strength, and mass in adults following a Mediterranean diet residing in southern Italian cities. METHODS: This cross-sectional study utilized data from an existing database, comprising 528 individuals aged 50 years or older who underwent health-screening tests at the Clinical Nutrition Unit of the "R.Dulbecco" University Hospital. Strength was assessed through handgrip strength, and appendicular skeletal muscle mass was estimated using bioelectrical impedance analysis. Dietary intake information was collected through a food frequency questionnaire linked to the MetaDieta 3.0.1 nutrient composition database. Principal Component Analysis, a statistical technique identifying underlying relationships among different nutrients, was employed to determine dietary patterns. Multinomial logistic regression analysis was conducted to estimate the odds ratio for sarcopenia or low handgrip strength in relation to the lowest tertile of dietary pattern adherence compared to the highest adherence. RESULTS: The participants had a mean age of 61 ± 8 years. Four dietary patterns were identified, with only the Western and Mediterranean patterns showing correlations with handgrip strength and appendicular skeletal muscle mass. However, only the Mediterranean pattern exhibited a correlation with sarcopenia (r = - 0.17, p = 0.02). The highest tertile of adherence to the Mediterranean dietary pattern demonstrated significantly higher handgrip strength compared to the lowest tertile (III Tertile: 28.3 ± 0.5 kg vs I Tertile: 26.3 ± 0.5 kg; p = 0.01). Furthermore, even after adjustment, the highest tertile of adherence to the Mediterranean pattern showed a significantly lower prevalence of sarcopenia than the lowest adherence tertile (4% vs 16%, p = 0.04). The lowest adherence to the Mediterranean dietary pattern was associated with increased odds of having low muscle strength (OR = 2.38; p = 0.03; 95%CI = 1.05-5.37) and sarcopenia (OR = 9.69; p = 0.0295; %CI = 1.41-66.29). CONCLUSION: A high adherence to the Mediterranean dietary pattern, characterized by increased consumption of legumes, cereals, fruits, vegetables, and limited amounts of meat, fish, and eggs, is positively associated with handgrip strength and appendicular skeletal muscle mass. The highest adherence to this dietary model is associated with the lowest odds of low muscle strength and sarcopenia. Despite the changes brought about by urbanization in southern Italy compared to the past, our findings continue to affirm the superior benefits of the Mediterranean diet in postponing the onset of frailty among older adults when compared to other dietary patterns that are rich in animal foods.

Dapagliflozin acutely improves kidney function in type 2 diabetes mellitus. The PRECARE study.

Dapagliflozin has been demonstrated to improve glycemic control, blood pressure, and body weight in type 2 diabetes mellitus (T2D); indeed, it can also reduce the risk of progression to renal failure, of hospitalization for heart failure and of cardiovascular death. We aim to investigate the acute effect of Dapagliflozin on kidney function in the common clinical practice in T2D. This is a study including 1402 patients with T2D recruited from 11 centers in Lombardia, Italy, who were evaluated at baseline and after 6 months of treatment with Dapagliflozin 10 mg per day. The primary outcome of the study was the change in HbA1c, while the secondary outcomes were modification of weight, BMI, systolic and diastolic pressure, creatinine, eGFR and albuminuria status. After 24 weeks of treatment with Dapagliflozin, a reduction in Hb1Ac was observed (-0.6 ± 1.8%) as well as in BMI (-1.5 ± 5.2 kg/m2). Statistically significant changes were also found for systolic and diastolic blood pressure, cholesterol and triglycerides. Interestingly, a statistically significant acute improvement of kidney function was evident. Our analyses confirm the beneficial effects of dapagliflozin after 6 months of therapy, with improvements of glycemic and lipid profiles, blood pressure, BMI. Finally, an acute positive effect on albuminuria and KIDGO classes was observed during a 6 months treatment with dapagliflozin in patients with T2D.

Bending Resistance at Hip and Fractures Risk in Postmenopausal Women Independent of Bone Mineral Density.

Several studies suggest that aging loss of bone mass is not necessarily associated with reduced mechanical proprieties as bending resistance. Since postmenopausal women with fracture and without osteoporosis might have an impairment in the bending mechanisms at hip, our aim was to assess if women with and without fractures differ in the femoral parameters of resistance to bending, independent of the bone loss. In this cross-sectional study we enrolled 192 postmenopausal women who underwent X-ray absorptiometry scan to measure bone mineral density as well as cross-sectional geometry parameters at the hip (Hip structure analysis). Among women with osteoporosis, a higher odds ratio for fracture was found in the first tertile of NN-Dmax, a parameter linked to the resistance to bending forces in a cross-section (tertile I, OR = 6.7, p = 0.03; CI 1.19-38.01; reference tertile III). We also found a significantly higher risk for major fracture in the first tertile of NN-Dmax (tertile I, OR = 6.0, p = 0.02; CI 1.26-28.4; reference tertile III). Among women without osteoporosis, a significantly higher odds ratio for fracture was found in the first tertile of IT-CSA, a parameter of resistance to axial load (tertile I, OR = 7.2, p = 0.002; CI 2.04-25.9; reference tertile III). We also found a significantly higher risk for major fracture in the first tertile of IT-CSA (OR = 18.4, p = 0.001; CI 1.52-221.8; tertile III reference). We demonstrate that some hip structural parameters are independently associated to the fracture risk in postmenopausal women.

Lupus anticoagulant and mortality in patients hospitalized for COVID-19.

Coronavirus disease 2019 (COVID-19) is characterized by a procoagulant state that can lead to fatal thromboembolic events. Several studies have documented a high prevalence of lupus anticoagulant that may at least partially explain the procoagulant profile of COVID-19. However, the association between lupus anticoagulant and thrombotic complications in COVID-19 is controversial and no study has specifically evaluated the impact of lupus anticoagulant on mortality. The aim of our study was to investigate the association between lupus anticoagulant and mortality in a large group of 192 consecutive patients hospitalized for COVID-19. Lupus anticoagulant was found in 95 patients (49.5%). No difference in the percentage of patients with lupus anticoagulant was observed between 130 survivors and 62 non-survivors (47.7 versus 53,2%; p = 0.4745). When the combined outcome of death or need for mechanical ventilation in survivors was taken into account, the difference in the prevalence of patients with lupus anticoagulant between the patients with the combined outcome (n = 76) and survivors who did not require mechanical ventilation (n = 116) was not significant (52.6% versus 47.4%; p = 0.4806). In multivariate analysis predictors of mortality or need for mechanical ventilation in survivors were obesity, low oxygen saturation and elevated troponin levels measured on admission. In conclusion, our study did not show any association of lupus anticoagulant with mortality and with need for mechanical ventilation in survivors. The role of obesity, low SaO2 and elevated troponin levels as predictors of a worse prognosis in patients hospitalized for COVID-19 was confirmed.

Effects of C-Peptide Replacement Therapy on Bone Microarchitecture Parameters in Streptozotocin-Diabetic Rats.

C-peptide therapy protects against diabetic micro- and macrovascular damages and neuropatic complications. However, to date, the role of C-peptide in preventing diabetes-related bone loss has not been investigated. Our aim was to evaluate if C-peptide infusion improves bone quality in diabetic rats. Twenty-three male Wistar rats were randomly divided into three groups: normal control group; sham diabetic control group; diabetic plus C-peptide group. Diabetes was induced by streptozotocin injection and C-peptide was delivered subcutaneously for 6 weeks. We performed micro-CT and histological testing to assess several trabecular microarchitectural parameters. At the end, diabetic plus C-peptide rats had a higher serum C-peptide (p = 0.02) and calcium (p = 0.04) levels and tibia weight (p = 0.02) than the diabetic control group. The diabetic plus C-peptide group showed a higher trabecular thickness and cross-sectional thickness than the diabetic control group (p = 0.01 and p = 0.03). Both the normal control and diabetic plus C-peptide groups had more Runx-2 and PLIN1 positive cells in comparison with the diabetic control group (p = 0.045 and p = 0.034). Diabetic rats receiving C-peptide had higher quality of trabecular bone than diabetic rats not receiving this treatment. If confirmed, C-peptide could have a role in improving bone quality in diabetes.

Association between antithrombin and mortality in patients with COVID-19. A possible link with obesity.

BACKGROUND AND AIMS: Despite anticoagulation, usually with heparin, mortality for thromboembolic events in COVID-19 remains high. Clinical efficacy of heparin is due to its interaction with antithrombin (AT) that may be decreased in COVID-19. Therefore, we correlated AT levels with outcomes of COVID-19. METHODS AND RESULTS: We recruited 49 consecutive patients hospitalized for COVID-19. AT levels were significantly lower in 16 non-survivors than in 33 survivors (72.2 ± 23.4 versus 94.6 ± 19.5%; p = 0.0010). A multivariate Cox regression analysis showed that low AT (levels below 80%) was a predictor of mortality (HR:3.97; 95%CI:1.38 to 11.43; p = 0.0103). BMI was the only variable that showed a significant difference between patients with low and those with normal AT levels (32.9 ± 7.9 versus 27.5 ± 5.9%; p = 0.0104). AT levels were significantly lower in obese patients than in subjects with normal weight or overweight (77.9 ± 26.9 versus 91.4 ± 26.9 versus 91.4 ± 17.1%; p = 0.025). An inverse correlation between AT levels and BMI was documented (r:-0.33; p = 0.0179). CONCLUSIONS: Our data first suggest that AT is strongly associated with mortality in COVID-19. In addition, AT may be the link between obesity and a poorer prognosis in patients with COVID-19. Other studies should confirm whether AT may become a prognostic marker and a therapeutic target in COVID-19.

Evaluation of circulating sRAGE in osteoporosis according to BMI, adipokines and fracture risk: a pilot observational study.

BACKGROUND: Osteoporosis is a systemic metabolic disease based on age-dependent imbalance between the rates of bone formation and bone resorption. Recent studies on the pathogenesis of this disease identified that bone remodelling impairment, at the base of osteoporotic bone fragility, could be related to protein glycation, in association to oxidative stress. The glycation reactions lead to the generation of glycation end products (AGEs) which, in turn, accumulates into bone, where they binds to the receptor for AGE (RAGE). The aim of this study is to investigate the potential role of circulating sRAGE in osteoporosis, in particular evaluating the correlation of sRAGE with the fracture risk, in association with bone mineral density, the fracture risk marker FGF23, and lipid metabolism. RESULTS: Circulating level of soluble RAGE correlate with osteopenia and osteoporosis level. Serum sRAGE resulted clearly associated on the one hand to bone fragility and, on the other hand, with BMI and leptin. sRAGE is particularly informative because serum sRAGE is able to provide, as a single marker, information about both the aspects of osteoporotic disease, represented by bone fragility and lipid metabolism. CONCLUSIONS: The measure serum level of sRAGE could have a potential diagnostic role in the monitoring of osteoporosis progression, in particular in the evaluation of fracture risk, starting from the prevention and screening stage, to the osteopenic level to osteoporosis.

The link between nutritional parameters and bone mineral density in women: results of a screening programme for osteoporosis.

BACKGROUND: A positive association between handgrip strength and bone mineral density was demonstrated, but not all the investigations confirmed these results. We conducted a screening programme for osteoporosis in a large cohort of postmenopausal women to investigate the relationship between handgrip strength, other nutritional parameters and bone density. METHODS: This investigation involved 1,300 white volunteers. All participants underwent a bone mineral density evaluation at the heel and a handgrip strength measurement. RESULTS: The mean T-score value was -1.15 ± 1; a total of 181 participants reported at least one osteoporotic fracture. In the univariate analysis, both handgrip strength and body mass index were associated with the T-score value. Adjustment for confounding factors confirmed this relationship showing, in the multivariate analysis, that the body mass index was positively correlated to the T-score (B = 0.034; p = 0.001) and, in the logistic regression analysis, that handgrip strength was associated with the presence of osteoporosis (P = 0.005). CONCLUSION: Both body mass index and handgrip strength were strongly correlated to bone mineral density, assessed with ultrasound, suggesting a possible key role as bone disease predictors.

A nutraceutical with Citrus bergamia and Cynara cardunculus improves endothelial function in adults with non-alcoholic fatty liver disease.

OBJECTIVE: Polyphenol intake may prevent hepatic steatosis and cardiovascular disease by potentially improving endothelial function. The purposes of this study are to investigate the association between fatty liver disease and endothelial dysfunction and to test the effects of a nutraceutical containing extracts made from Citrus bergamia and Cynara cardunculus on peripheral vascular endothelial function in adults with liver steatosis. METHODS: We analyzed data from 32 individuals with hepatic steatosis and endothelial dysfunction (reactive hyperemia index ≤ 1.67). Sixteen subjects took 1 capsule/d (300 mg/d) containing Cynara cardunculus extract and bergamot polyphenol fraction, while the other 16 subjects matched for age, sex, and body mass index took 1 capsule/d of placebo (maltodextrin) for 12 wk. All anthropometric parameters were assessed at baseline and after 12 wk as were lipids, glucose, and reactive hyperemia index using an EndoPAT 2000. RESULTS: The mean age was 52 ± 9 y. The mean reactive hyperemia index was 1.15 ± 0.4. After 12 wk, we found a greater increase in reactive hyperemia index in the participants taking the nutraceutical rather than placebo (0.58 ± 0.5 versus 0.13 ± 0.5; P = 0.02, respectively). The stepwise multivariable analysis confirmed a positive association between reactive hyperemia index change and the nutraceutical treatment (B = 0.38; P = 0.025) and negative association with reactive hyperemia index values at baseline (B = -0.81; P < 0.001). No association was found between the reduction in the amount of intrahepatic fat and the improvement of endothelial function (B = 0.002; P = 0.56). CONCLUSIONS: A nutraceutical containing bergamot and artichoke extracts improves peripheral vascular endothelial function in adults with hepatic steatosis and early phase of atherosclerosis.

Therapeutic patient education and treatment intensification of diabetes and hypertension in subjects with newly diagnosed type 2 diabetes mellitus: a longitudinal study.

PURPOSE: The aim of this study is to prospectively evaluate whether individual and group Therapeutic Patient Education (TPE) can reduce the need to intensify treatment of diabetes and hypertension in newly diagnosed type 2 diabetic patients. METHODS: A total of 937 patients were recruited and followed-up for 42.7 ± 21.5 months. TPE was a structured comprehensive education delivered by trained nurses: 322 patients received individual TPE (ITPE), 291 underwent group TPE (GTPE), and 324 were in Usual Care (UC). The primary endpoints were intensification of diabetes treatment and intensification of hypertension treatment. RESULTS: The rate of diabetes treatment intensification was 40.1% in patients receiving ITPE, 47.8% in patients undergoing GTPE, and 64.2% in patients in UC (p < 0.001). The rate of hypertension treatment intensification was 24.2% in patients following ITPE, 31.3% in patients receiving GTPE, and 41.0% in patients in UC (p < 0.001). Multivariate analysis showed that both ITPE and GTPE were associated with reduced intensification of diabetes (ITPE: HR:0.51; 95% IC:0.40-0.64; p < 0.001 - GTPE: HR:0.46; 95% IC:0.44-0.70; p < 0.001) and hypertension medication (ITPE: HR:0.45; 95% IC:0.34-0.61; p < 0.001 - GTPE: HR:0.49; 95% IC:0.38-0.65; p < 0.001). The association was independent of age, sex, BMI, HbA1c, and presence of hypertension at baseline. CONCLUSIONS: TPE, delivered as both individual and group sessions, represents an effective tool to reduce the need to intensify treatment of both diabetes and hypertension. Therefore, it can ensure better control of diabetes and hypertension with fewer medications. This could reduce adverse effects and costs and improve quality of life and medication taking in patients with type 2 diabetes.

Type 2 diabetes mellitus is associated with faster degeneration of bioprosthetic valve: results from a propensity score-matched Italian multicenter study.

BACKGROUND: The present study was aimed at determining the impact of type 2 diabetes mellitus (DM) on postoperative bioprosthetic structural valve degeneration. METHODS AND RESULTS: Twelve Italian centers participated in the study. Patient data refer to bioprosthetic implantations performed from November 1988 to December 2009, which resulted in 6184 patients (mean age 71.3±5.4 years, 60.1% male) being enrolled. Of these patients, 1731 (27.9%) had type 2 DM. The propensity score-matching algorithm successfully matched 1113 patients with type 2 DM with the same number of no-DM patients. The postmatching standard differences were less than 0.1 for each of the covariates, and 64.2% of DM patients were matched. The early (30 days) mortality rate was 7.8% (n=87) versus 2.9% (n=33) in patients with or without type 2 DM (P<0.001), respectively. Seven-year freedom from valve deterioration was significantly lower in patients with DM (73.2% [95% confidence interval, 61.6-85.5] versus 95.4% [95% confidence interval, 83.9-100], P<0.001). In Cox regression models with robust SEs that accounted for the clustering of matched pairs, DM was the strongest predictor of structural valve degeneration (hazard ratio 2.39 [95% confidence interval 2.28-3.52]). When we allowed for interaction between type 2 DM and other key risk factors, DM remained a significant predictor beyond any potentially associated variable. CONCLUSIONS: Patients with type 2 DM undergoing bioprosthetic valve implantation are at high risk of early and long-term mortality, as well as of structural valve degeneration.

Fat utilization and arterial hypertension in overweight/obese subjects.

BACKGROUND: The Respiratory Quotient is a parameter reflecting the utilization of the nutrients by a subject. It is associated with an high rate of subsequent weight gain and with the atherosclerosis. Subjects tending to burn less fat have an increased Respiratory Quotient. Aim of this study was to investigate on the relationship between the Respiratory Quotient and the cardiovascular risk factors. METHODS: In this cross-sectional study we enrolled 223 individuals of both sexes aged 45-75 ys that were weight stable, receiving a balanced diet, and not affected by debilitating disease or cardiovascular disease. The Respiratory Quotient was measured by Indirect Calorimetry. The measurement of the Blood Pressure was obtained by a mercury sphygmomanometer. RESULTS: We enrolled 133 female and 90 male. Systolic blood pressure only was positively correlated to the Respiratory Quotient in univariate and multivariate regression analysis (p=0,017). The prevalence of hypertension was significatively different between the quartiles of the Respiratory Quotient, with the highest prevalence in the IV quartile (p=0,024). CONCLUSION: High value of the Respiratory Quotient, an index of nutrients utilization, is associated to an high prevalence of Hypertension. It is possible that in the subjects with high Respiratory Quotient and high body mass index, the activation of the renin angiotensin system, in concert to the reduction of the utilization of the endogenous fat stores, could increase the risk of hypertension.

Primary headache and silent myocardial ischemia in patients with coronary artery disease.

OBJECTIVE: The mechanisms by which migraine is linked to ischemic vascular disease remain uncertain and are likely to be complex. The aim of this study was to investigate the correlation between silent myocardial ischemia (SMI) and a history of documented primary headache in a large population of patients with exercise-induced myocardial ischemia. METHODS: The study involved 1,427 consecutive patients (918 symptomatic and 509 asymptomatic patients) with exercise-induced myocardial ischemia and documented coronary artery disease (CAD). RESULTS: Patients with anginal symptoms during exercise-induced myocardial ischemia had a significantly higher prevalence of primary headache than those without (41 vs. 30%, p < 0.001). Patients with angina pectoris in daily life also had greater prevalence of primary headache than those without anginal symptoms (37 vs. 20%; p < 0.0001). Symptomatic patients during percutaneous transluminal coronary angiography or myocardial infarction had a greater prevalence of primary headache than asymptomatic patients (p < 0.001 and p = 0.005, respectively). CONCLUSIONS: Our data suggest that a history of headache in CAD population is correlated to a high probability of anginal symptoms and a decreased probability of SMI. The anamnestic absence of headache requires a close monitoring for patients with risk factors for CAD, because this population seems to have a lower susceptibility to pain and the risk of developing SMI might be increased.

Percutaneous transluminal angioplasty for critical limb ischemia in very elderly diabetic patients.

In diabetic subjects, new less invasive therapies for critical limb ischemia (CLI) are available to obtain limb salvage. One of these is the percutaneous transluminal angioplasty (PTA), a minor surgical intervention which allows obtaining an effective revascularization, avoiding the traditional major surgery and its post-operative complications. Our case report regards a 94-year-old woman with CLI due to critical obstruction (stage IV according to Leriche's classification) of superficial femoral and popliteal arteries and infrapopliteal arteries that should have been treated by the left limb amputation considering her age, severe co-morbidities, and poor compliance. Instead of this quite common approach, our team treated the patient with PTA. This led to very good outcomes, above all in terms of pain control. PTA is able to avoid major surgery, lower intra and post-operative risks, reduce length of hospital stay, and preserve functional autonomy. Therefore, this procedure should be taken into account also for frail very elderly diabetic patients with peripheral artery disease (PAD).

Soluble RAGE plasma levels in patients with coronary artery disease and peripheral artery disease.

The objective of the present study was define in a relatively large patient population with coronary artery disease (CAD) whether the concomitant presence of peripheral artery disease (PAD), which is known to convey additional cardiovascular risk, was associated with different circulating levels of sRAGE with respect to CAD alone and control subjects. Clinical and laboratory parameters including the ankle brachial index (ABI) and sRAGE (enzyme-linked immunosorbent assay kit) were investigated in 544 patients with angiographically documented CAD and 328 control subjects. 213/554 CAD patients (39%) showed an ABI <0.9 associated with typical symptoms (group CAD + PAD), whereas 331 patients were free from PAD. The concentration of plasma sRAGE was significantly lower (P < 0.0001) in CAD population, with and without PAD, than in control subjects. Among CAD patients, those with PAD showed lower levels of sRAGE. The distribution of the three groups (CAD, CAD + PAD, and controls) according to sRAGE tertiles showed that lower levels were more frequent in patients with CAD and CAD + PAD, whereas higher levels were more frequently found in controls. CAD patients presenting with PAD have lower sRAGE levels than CAD patients without peripheral atherosclerosis showing that stable atherosclerotic lesions in different vascular districts are inversely related to soluble decoy receptor sRAGE.

Association of erectile dysfunction with diabetic foot and its outcomes in type 2 diabetic men.

PURPOSE: Erectile dysfunction (ED) and diabetic foot (DF) are common complications in patients with diabetes. However, the relationship between ED and DF has been little studied. In particular, no study has evaluated whether ED is associated with the outcomes of DF. The aim of this retrospective cohort study was to investigate whether ED is a predictor of the outcomes of DF in a large population of men with DF. METHODS: Three hundred and twenty-six consecutive men with type 2 diabetes and a recent and single DF ulcer were recruited and followed up for 41.7 ± 22.7 months. RESULTS: Among men with DF, 56.1% had ED (ED group) and 43.9% did not (NO ED group). Wound healing rate was significantly higher in the NO ED than in the ED group (90.2 versus 73.3%; p = 0.0001). Minor amputation rate (13.7 versus 4.8%; p = 0.007) and mortality (25.7 versus 0.7%; p < 0.001) were significantly greater in the ED than in the NO ED group. Among 263 patients with healed ulcers, recurrence rate was significantly higher in the ED than in the NO ED group (51.5 versus 26.3%; p < 0.001). Multivariate analysis showed that the absence of ED was associated with wound healing (OR: 0.459; 95% CI: 0.213-0.993; p = 0.048), while the presence of ED predicted mortality (OR: 22.644; 95% CI: 2.976-34.271; p = 0.002) and DF recurrence (OR: 3.498; 95% CI: 1.882-6.499; p < 0.001). CONCLUSIONS: Our data show that among men with DF the prevalence of ED is very high. Moreover, ED may be a strong predictor of wound healing, mortality, and ulcer recurrence.

A Comprehensive Therapeutic Patient Education May Improve Wound Healing and Reduce Ulcer Recurrence and Mortality in Persons With Type 2 Diabetes.

OBJECTIVES: The impact of a comprehensive therapeutic patient education (TPE) on the prognosis of diabetic foot ulcer (DFU) has not yet been evaluated in the literature. The purpose of this study was to determine whether TPE is a predictor of outcome in type 2 diabetes patients with DFU. METHODS: We evaluated 583 consecutive individuals with a recent and single DFU. They were treated and followed for 42.8±23.3 months. Patients were divided into 2 groups. The TPE group included subjects who had been receiving regular sessions of a comprehensive TPE, including a specific foot care education (FCE), for at least 12 months before DFU occurred (n=129). The non-TPE group comprised the remaining subjects (n=454). All 583 patients received intensive FCE during the treatment period. RESULTS: We identified a significantly higher percentage of healed DFUs (96.0% vs 74.9%; p<0.0001) and a lower percentage of major amputations (0.8% vs 4.4%; p=0.0511), minor amputations (1.6% vs 12.3%; p=0.0003), DFU persistence (1.6% vs 8.4%; p=0.0069) and deaths (1.6% vs 21.4%; p<0.0001) in the TPE group than in the non-TPE group. Among 464 patients with healed ulcers, the proportion of subjects with re-ulceration was greater in the non-TPE group than in the TPE group (48.8% vs 6.5%; p<0.0001). Multivariate analysis showed that TPE can predict healing (odds ratio [OR], 4.202; 95% confidence interval [CI], 1.604 to 11.004; p=0.0035) and may significantly reduce DFU recurrence (OR, 0.093; 95% CI, 0.043 to 0.201; p<0.0001) and mortality (OR, 0.096; 95% CI, 0.022 to 0.410; p=0.0016). CONCLUSION: A comprehensive TPE may have a positive impact on wound healing, ulcer recurrence and mortality in people with DFU.

Impact of microvascular complications on the outcomes of diabetic foot in type 2 diabetic patients with documented peripheral artery disease.

PURPOSE: Microvascular disease (MVD) is associated with amputation linked to peripheral artery disease (PAD) in the general population. No study evaluated the impact of diabetic microvascular complications on the outcomes of vascular diabetic foot ulcers (DFU). The aim of the study was to investigate whether retinopathy, nephropathy, and polyneuropathy can predict the outcomes of DFU in type 2 diabetic patients with PAD. METHODS: Three hundred and thirty-one consecutive patients with vascular DFU were enrolled and followed up for 44.1 ± 23.9 months. RESULTS: The prevalence of retinopathy was significantly higher in subjects with ulcer persistence (45.2%; p < 0.01), minor amputation (48.9%; p < 0.001), and major amputation (57.9%; p < 0.001) than in healed patients (23.3%), and in non-survivors than in survivors (64.9 versus 20.5%; p < 0.001). The prevalence of nephropathy was significantly greater in subjects with ulcer persistence (83.9%; p < 0.01), minor amputation (86.7%; p < 0.001), and major amputation (94.7%; p < 0.001) than in those with healed DFU (64.4%), and in non-survivors than in survivors (88.3 versus 65.7%; p < 0.001). The prevalence of polyneuropathy was significantly higher in non-survivors than in survivors (76.6 versus 61.0%; p = 0.012). Multivariate analysis showed that absence of retinopathy (OR: 0.451; 95% CI: 0.250-0.815; p < 0.001) and nephropathy (OR: 0.450; 95% CI: 0.212-0.951; p = 0.036) were independently associated with healing. Moreover, retinopathy was a predictor both of minor amputation (OR: 2.291; 95% CI: 1.061-4.949; p = 0.034) and mortality (OR: 5.274; 95% CI: 2.524-11.020; p < 0.001). Polyneuropathy never entered the regression model. CONCLUSIONS: Diabetic microvascular complications, in particular retinopathy, may predict the outcomes of vascular DFU. Longitudinal studies should confirm this finding.

Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation.

Introduction: Long-COVID is a broadly defined condition and there are no effective therapies. Cardiovascular manifestations of long-COVID include high heart rate, postural tachycardia, and palpitations. Previous studies have suggested that mast cell activation (MCA) may play a role in the pathophysiology of long-COVID, including in the mechanisms of its cardiovascular manifestations. The present study aimed to evaluate the effectiveness of a treatment with blockers of histamine receptors in patients with long-COVID who did not respond to other therapies. Methods: In all, 14 patients (F/M = 9/5; 49.5 ± 11.5 years) and 13 controls (F/M = 8/5; 47.3 ± 8.0 years) with long-COVID symptoms attributed to MCA were evaluated. Patients were treated with fexofenadine (180 mg/day) and famotidine (40 mg/day). Fatigue, brain fog, abdominal disorders, and increased heart rate were evaluated in treated and untreated patients at baseline and 20 days later. Results: Long-COVID symptoms disappeared completely in 29% of treated patients. There was a significant improvement in each of the considered symptoms (improved or disappeared) in all treated patients, and the improvement grade was significantly greater in treated patients compared to controls. No significant differences in the outcomes were observed in the controls. Conclusions: Our data confirm that histamine receptors blockade may be an effective target to successfully treat long-COVID. Our finding supports the underlying role of MCA in the pathophysiology of long-COVID.

Predictors of healing, ulcer recurrence and persistence, amputation and mortality in type 2 diabetic patients with diabetic foot: a 10-year retrospective cohort study.

PURPOSE: Predictors of outcome of diabetic foot ulcer (DFU) are important to improve the management of patients. Aim of the study was to find these predictors in type 2 diabetic patients with DFU. METHODS: We recruited 583 patients. They were followed-up by a multidisciplinary team. A holistic and conservative approach was used and all risk factors and co-morbidities were aggressively treated. RESULTS: During the follow-up period, 79.6% of patients healed in a mean time of 7.6 ± 3.8 months, 6.9% showed DFU persistence, 9.9% had minor amputations, and 3.6% experienced major amputation. Seventeen percent of the patients died. Among patients who healed, 37.1% of them showed DFU recurrence. Impairment of renal function was associated to DFU persistence, amputation, and mortality. Previous cardiovascular disease predicted DFU persistence, DFU recurrence, and mortality. Lower BMI predicted DFU persistence and mortality. Osteomyelitis was a predictor of amputation and death. Markers of peripheral artery disease (PAD) predicted minor amputation and DFU recurrence. Our study shows a relatively low incidence of complications of DFU. CONCLUSIONS: Some predictors of outcome of DFU were confirmed and new predictors, like BMI and markers of PAD, were found. Our new findings suggest future strategies for nutrition support and revascularization. In addition, a holistic and conservative approach may improve the prognosis.