Development and internal validation of a multivariable model for the prediction of the probability of 1-year readmission to the emergency department for acute alcohol intoxication.

To develop and internally validate a multivariable logistic regression model (LRM) for the prediction of the probability of 1-year readmission to the emergency department (ED) in patients with acute alcohol intoxication (AAI). We developed and internally validated the LRM on a previously analyzed retrospective cohort of 3304 patients with AAI admitted to the ED of the Sant'Orsola-Malpighi Hospital (Bologna, Italy). The benchmark LRM employed readmission to the same ED for AAI within 1 year as the binary outcome, age as a continuous predictor, and sex, alcohol use disorder, substance use disorder, at least one previous admission for trauma, mental or behavioral disease, and homelessness as the binary predictors. Optimism correction was performed using the bootstrap on 1000 samples without replacement. The benchmark LRM was gradually simplified to get the most parsimonious LRM with similar optimism-corrected overall fit, discrimination and calibration. The 1-year readmission rate was 15.7% (95% CI 14.4-16.9%). A reduced LRM based on sex, age, at least one previous admission for trauma, mental or behavioral disease, and homelessness, performed nearly as well as the benchmark LRM. The reduced LRM had the following optimism-corrected metrics: scaled Brier score 17.0%, C-statistic 0.799 (95% CI 0.778 to 0.821), calibration in the large 0.000 (95% CI - 0.099 to 0.099), calibration slope 0.985 (95% CI 0.893 to 1.088), and an acceptably accurate calibration plot. An LRM based on sex, age, at least one previous admission for trauma, mental or behavioral disease, and homelessness can be used to estimate the probability of 1-year readmission to ED for AAI. To begin proving its clinical utility, this LRM should be validated in external cohorts.

Relationship between Muscle Mass, Bone Density and Vascular Calcifications in Elderly People with SARS-CoV-2 Pneumonia.

BACKGROUND: Little is known about the changes in organs and tissues that may make elder patients more vulnerable to acute stressors such as SARS-CoV-2 infection. METHODS: In 80 consecutive elderly patients with SARS-CoV-2 infection, we evaluated the association between the descending thoracic aorta calcium score, L1 bone density and T12 skeletal muscle density measured on the same scan by high-resolution computed tomography. RESULTS: At median regression, the ln-transformed DTA calcium score was inversely associated with L1 bone density (-0.02, 95%CI -0.04 to -0.01 ln-Agatston units for an increase of 1 HU) and with T12 muscle density (-0.03, -0.06 to -0.001 ln-Agatston units for an increase of 1 HU). At penalized logistic regression, an increase of 1 ln-Agatston unit of DTA calcium score was associated with an OR of death of 1.480 (1.022 to 2.145), one of 1 HU of bone density with an OR of 0.981 (0.966 to 0.996) and one of 1 HU of muscle density with an OR of 0.973 (0.948 to 0.999). These relationships disappeared after correction for age and age was the stronger predictor of body composition and death. CONCLUSIONS: Age has a big effect on the relationship between vascular calcifications, L1 bone density and T12 muscle density and on their relationship with the odds of dying.

Mortality and its association with chronic alcohol-related diseases in patients admitted to the emergency department for acute alcoholic intoxication: retrospective cohort study.

We assessed long-term mortality and its association with chronic alcohol-related diseases in patients admitted to the emergency department (ED) because of acute alcoholic intoxication (AAI). A retrospective cohort study was performed at the ED of Sant'Orsola-Malpighi Hospital, Bologna, Italy. 3304 patients, corresponding to 6415 admissions for AAI, who accessed the ED from January 1, 2005, to December 31, 2017, were studied. The ED electronic registry system was used to assess living status on 08 May 2020 and to obtain the prespecified potential predictors, i.e., age at first admission, sex, alcohol use disorder (AUD), substance use disorder (SUD), more than 1 admission to ED for trauma, mental and behavioral disorders, neurological disorders, and cardiovascular disease. The median follow-up time was 9.3 years and the time on risk was 30,053 person years (PY) with a death rate corresponding to 4.42 (95% CI 3.74-5.26) per 1000 PY (n = 133 deaths). The death rate was higher in patients with AUD (17.30) than in those without AUD (1.98) and in those with SUD (13.58) than in those without SUD (3.80). Lastly, there was a clearly higher death rate among AUD+ SUD+ (20.89) compared to AUD-SUD-patients (1.74). At multivariable Cox regression, AUD, SUD, and liver cirrhosis were strong and independent predictors of time-to-death. Using standardized mortality ratios, a clear excess of mortality was evident for all the age bands from (40-45] to (60-65] years. Mortality is higher in AAI than in the general population and chronic alcohol-related diseases are strongly associated with it.

Association of bone biomarkers with advanced atherosclerotic disease in people with overweight/obesity.

BACKGROUND: A growing body of evidence suggests a potential link between bone metabolism and cardiovascular disease. Aim of this study was to investigate the relationship between levels of circulating bone turnover biomarkers and advanced atherosclerosis. METHODS: Klotho (KL), sclerostin (SOST), osteopontin (OPN) and osteoprotegerin (OPG) were measured in patients undergoing elective coronary angiography and carotid Doppler ultrasound. The primary outcome was the difference in bone biomarkers levels between participants with and without advanced atherosclerosis, defined as the presence of a critical coronary (≥70%) and/or carotid (≥50%) stenosis. RESULTS: A total of 80 subjects (32.5% females) with a mean age of 68 ± 10 years were included. Advanced atherosclerosis was detected in 55 (68.8%) patients. Subjects with advanced atherosclerosis showed higher serum levels of OPG (p = 0.0015) and SOST (p = 0.017) and similar levels of KL (p = 0.62) and OPN (p = 0.06) compared to patients without. After adjustment for age and sex, only elevated levels of OPG remained significantly associated with advanced atherosclerosis (p = 0.011). CONCLUSIONS: Higher serum levels of OPG are independently associated with advanced atherosclerosis confirming a common bond between bone metabolism and vascular disease. Further investigations on the role of selected bone biomarkers in the pathogenesis of cardiovascular disease are needed.

Sarcopenia and Vitamin D Deficiency in Patients with Crohn's Disease: Pathological Conditions That Should Be Linked Together.

Sarcopenia is a prevalent condition in patients with Crohn's disease (CD), representing an independent predictor factor for the development of major postoperative complications. Thus, a proper assessment of the muscle strength, by using different validated tools, should be deemed an important step of the clinical management of these patients. Patients with CD are frequently malnourished, presenting a high prevalence of different macro- and micro-nutrient deficiencies, including that of vitamin D. The available published studies indicate that vitamin D is involved in the regulation of proliferation, differentiation, and regeneration of muscle cells. The relationship between vitamin D deficiency and sarcopenia has been extensively studied in other populations, with interesting evidence in regards to a potential role of vitamin D supplementation as a means to prevent and treat sarcopenia. The aim of this review was to find studies that linked together these pathological conditions.

The Mediterranean diet increases glucagon-like peptide 1 and oxyntomodulin compared with a vegetarian diet in patients with type 2 diabetes: A randomized controlled cross-over trial.

AIM: To compare a Mediterranean diet (MED) with a high-fibre vegetarian diet (HFV) in terms of hunger-satiety perception through post-prandial assessment of appetite-related hormones glucagon-like peptide 1 (GLP-1) and oxyntomodulin, as well as self-rated visual analogue scale (VAS) quantification, in overweight/obese subjects with type 2 diabetes (T2D). MATERIALS AND METHODS: Twelve T2D subjects (Male to female ratio = 7:5), mean age 63 ± 8.5 years, were enrolled in a randomized, controlled, crossover study. Participants consumed an MED meal as well as an isocaloric meal rich in complex carbohydrate as well as an isocaloric MED meal in two different visits with a 1-week washout period between the two visits. Appetite ratings, glucose/insulin, and gastrointestinal hormone concentrations were measured at fasting and every 30' until 210' following meal consumption. RESULTS: GLP-1 and oxyntomodulin levels were significantly higher following MED meal compared with HFV meals (210' area under the curve, p < 0.022 and p < 0.023, respectively). Both MED and HFV meal resulted in a biphasic pattern of GLP-1 and oxyntomodulin, although MED meal was related to a delayed, significantly higher second GLP-1 peak at 150' compared with that of HFV meal (p < 0.05). MED meal was related to lower glucose profile compared with HFV meal (p < 0.039), whereas we did not observe significant changes in terms of self-reported VAS scores and insulin trend. CONCLUSIONS: In T2D overweight/obese subjects, an MED meal is more effective than a HFV meal in terms of post-prandial plasma glucose homoeostasis and GLP-1 and oxyntomodulin release. These changes were not confirmed by VAS appetite self-assessment over a 210' period.

Risk of cardiac autonomic neuropathy in latent autoimmune diabetes in adults is similar to type 1 diabetes and lower compared to type 2 diabetes: A cross-sectional study.

AIMS: Microvascular complications' risk differs between people with latent autoimmune diabetes in adults (LADA) and people with type 2 diabetes. We aimed to investigate whether the prevalence of cardiac autonomic neuropathy, a life-threatening complication of diabetes, also varies depending on diabetes type. METHODS: In this cross-sectional study, 43 adults with LADA, 80 with type 1 diabetes and 61 with type 2 diabetes were screened for cardiac autonomic neuropathy with recommended tests. Logistic regression models were used to test differences between diabetes types adjusting for confounders. RESULTS: Cardiac autonomic neuropathy was diagnosed in 17 (40%) participants with LADA, 21 (26%) participants with type 1 diabetes and 39 (64%) participants with type 2 diabetes (p < 0.001). The odds ratio (OR) for cardiac autonomic neuropathy in type 1 diabetes and in type 2 diabetes compared to LADA were 0.54 (95% CI: 0.25-1.20, p-value: 0.13) and 2.71 (95% CI: 1.21-6.06, p-value 0.015) respectively. Smoking (adj OR 3.09, 95% CI: 1.40-6.82, p-value: 0.005), HDL cholesterol (adj OR 0.29, 95% CI: 0.09-0.93, p-value: 0.037) and hypertension (adj OR 2.11, 95% CI: 1.05-4.24, p-value: 0.037) were independent modifiable risk factors for cardiac autonomic neuropathy. Differences among diabetes types did not change after correction for confounders. CONCLUSIONS: This is the first study offering a comparative evaluation of cardiac autonomic neuropathy among LADA, type 1 and type 2 diabetes, showing a lower risk of cardiac autonomic neuropathy in LADA compared to type 2 diabetes and similar compared to type 1 diabetes. This disparity was not due to differences in age, metabolic control or cardiovascular risk factors.

Lifestyle Management of Diabetes: Implications for the Bone-Vascular Axis.

PURPOSE OF REVIEW: To describe the main pathways involved in the interplay between bone and cardiovascular disease and to highlight the possible impact of physical activity and medical nutrition therapy on the bone-vascular axis. RECENT FINDINGS: Diabetes increases the risk of both cardiovascular disease and bone fragility fractures, sharing common pathogenic pathways, including OPG/RANK/RANKL, the FGF23/Klotho axis, calciotropic hormones, and circulating osteogenic cells. This may offer new therapeutic targets for future treatment strategies. As lifestyle intervention is the cornerstone of diabetes treatment, there is potential for an impact on the bone-vascular axis. Evidence published suggests the bone-vascular axis encompasses key pathways for cardiovascular disease. This, along with studies showing physical activity plays a crucial role in the prevention of both bone fragility and cardiovascular disease, suggests that lifestyle intervention incorporating exercise and diet may be helpful in managing skeletal health decline in diabetes. Studies investigating the controversial role of high-fiber diet and dietary vitamin D/calcium on bone and cardiovascular health suggest an overall benefit, but further investigations are needed in this regard.

A novel germline mutation at exon 10 of MEN1 gene: a clinical survey and positive genotype-phenotype analysis of a MEN1 Italian family, including monozygotic twins.

CONTEXT: Clinical phenotype variability in MEN1 syndrome exists and evidence for an established genotype-phenotype is lacking. However, a higher aggressiveness of MEN1-associated gastro-entero-pancreatic (GEP) (neuro)endocrine tumours (NETs) tumours has been reported when MEN1 gene truncating mutations are detected. We found a novel germline truncating mutation of MEN1 gene at exon 10 in a subject with an aggressive clinical behavior of GEP-NETs. Successively, other two mutant-affected familial members have been identified. OBJECTIVE: The aim of this observational study was to investigate genotype-phenotype correlation in these three members, with attention to GPE-NETs behavior over the years. DESIGN: The genetic and clinical data obtained and the follow-up screening program (2012-2016) were according to the International Guidelines in a multidisciplinary academic reference center. The familial history collected strongly suggested MEN1 GEP-NETs in at least other four members from different generations. PATIENTS: Three MEN1 patients (aged 30-69 years at MEN1 diagnosis) were clinically screened for MEN1 GEP-NETs, both functioning and nonfunctioning. METHODS: Biochemical, imaging, and nuclear medicine tests and fine-needle agobiopsy were performed, depending on found/emerging clinical symptoms/biochemical abnormalities, and made when necessary. RESULTS: Our clinical survey found strong genotype-phenotype correlation with aggressive MEN1 GEP-NETs (G1, G2-NETs, and multiple ZES/gastrinomas) over the years. The familial history strongly suggested ZES/gastrinoma in progenitors from previous generations. CONCLUSIONS: This novel MEN1 truncating mutation correlates with an aggressive evolution and behavior of MEN1 GEP-NETs in studied affected subjects, confirming the need for MEN1 individuals to be evaluated by a skilled multidisciplinary team, as also stated by International Guidelines.

Treatment of reactive hypoglycemia with the macrobiotic Ma-pi 2 diet as assessed by continuous glucose monitoring: The MAHYP randomized crossover trial.

BACKGROUND AND AIMS: Nutritional therapy is recommended for management of reactive hypoglycemia (RH), a condition characterized by hypoglycemia that occurs within four hours after a meal. The macrobiotic Ma-Pi 2 diet improves glycemic control in subjects with type 2 diabetes. We explored the effect of this diet on outcomes in non-diabetic individuals with RH. MATERIALS AND METHODS: Twelve subjects with RH were randomized to the Ma-Pi 2 diet for three days and a control diet for three days in a randomized crossover design. Subjects received snacks on two days out of each three-day period only, and were monitored using continuous glucose monitoring. The 24-h period was divided into daytime (08:00-22:30h [subdivided into 'daytime without snacks' and 'daytime with snacks']) and night-time (22:31-07:59h). The effects of the two diets on the number of RH events (blood glucose <70mg/dL [3.9mmol/L]) and the percentage distribution of glucose readings within each of 16 glycemic intervals from <40mg/dL (2.2mmol/L) to >180mg/dL (4.4mmol/L) were determined. RESULTS: There were significantly fewer RH events on the Ma-Pi 2 diet than the control diet during daytime without snacks (-2.5 events; 95% CI: -7.5, 0.0; P=0.022) and daytime with snacks (-4.25 events; 95% CI: -7.5; -2.0; P=0.013) but no difference at night. The percentage of glucose readings in the interval 71-80mg/dL (3.9-4.4mmol/L) was significantly higher on the control diet during daytime with and without snacks (P=0.03 for both), while the percentage of glucose readings in the interval 91-100mg/dL (5.1-5.6mmol/L) was significantly higher on the Ma-Pi 2 diet during daytime without snacks (P=0.02). CONCLUSIONS: The macrobiotic Ma-Pi 2 diet reduced blood glucose excursions during the day, thereby facilitating glycemic control in subjects with RH. The Ma-Pi 2 diet represents an effective nutritional tool for management of RH.

A pilot study of D-chiro-inositol plus folic acid in overweight patients with type 1 diabetes.

AIMS: To improve insulin sensitivity, insulin-sensitizing drugs such as metformin are commonly used in overweight and obese T1D patients. Similarly to metformin, D-chiro-inositol (DCI), as putative mediator of intracellular insulin action, can act as insulin sensitizer. The aim of this pilot study was to evaluate the hypothesis that DCI plus folic acid may improve glucose control reducing insulin resistance in overweight or obese T1D patients. METHODS: A 24-week randomized control trial was carried out in 26 overweight or obese T1D patients, undergoing intensive insulin therapy. Patients were randomized to 1 g DCI plus 400 mcg folic acid once daily (treated group) or to 400 mcg folic acid only once daily (control group). The primary end point was to evaluate the efficacy of DCI on metabolic control as assessed by HbA1c. As secondary endpoints, BMI and insulin requirement (IR) were evaluated. Paired t test (two tailed) and analysis of variance were used to evaluate differences in HbA1c, BMI and IR at different time points. RESULTS: A significant reduction in HbA1c levels in treated group versus control group (7.5% ± 0.9 vs. 7.9% ± 1.7, respectively, p < 0.05) was observed. However, no significant reduction in BMI and IR was observed [(BMI 25.7 ± 2.8 vs. 26.7 ± 1.0, respectively, p NS); (IR 0.52 ± 0.26 vs. 0.52 ± 0.19, respectively, p NS)]. CONCLUSIONS: This trial demonstrated for the first time that DCI plus folic acid oral supplementation can improve metabolic control in overweight T1D patients. CLINICALTRIAL. GOV ID: NCT02730949.

Increased sclerostin and bone turnover after diet-induced weight loss in type 2 diabetes: a post hoc analysis of the MADIAB trial.

BACKGROUND: Sclerostin has been directly related to bone turnover increase in dietary-induced weight loss in non-diabetics. This has not been studied in type 2 diabetes, a condition characterized by increased circulating sclerostin and impaired bone turnover. PURPOSE: To study the effect of dietary weight loss and quality of the dietary intervention on changes of sclerostin and bone turnover markers in type 2 diabetes. METHODS: This was a post-hoc analysis of the MADIAB trial, a 21-day randomized controlled trial on overweight/obese type 2 diabetes patients. Patients were randomly assigned 1:1 to the Ma-Pi2 macrobiotic diet or a control diet based on dietary guidelines for type 2 diabetes. Serum sclerostin and circulating markers of bone resorption and formation (P1NP) were measured by enzyme linked immunosorbent assay in 40 subjects (1:1) at baseline and after 21 days treatment. RESULTS: Both Ma-Pi2 and the control diet groups had significant decreases in body weight (6.0 ± 0.2 vs. 3.2 ± 0.1 %, p < 0.001). Sclerostin increased significantly in the two groups (all p < 0.001) but Ma-Pi2 diet group experienced a greater increase in sclerostin (34.5 vs. 15 %; p = 0.024). Serum circulating markers of bone resorption increased in the two groups (all p < 0.001); circulating markers of bone resorption at the end of the treatment tended to be higher in Ma-Pi2 diet than the control diet group (p = 0.06). P1NP did not change significantly in the two group compared to baseline. Sclerostin changes were related to body mass index reduction (r = -0.37; p = 0.02). CONCLUSIONS: Diet-induced weight loss may induce significant and rapid changes in bone turnover and sclerostin levels. These changes may further impair bone health in subjects with type 2 diabetes.

Efficacy and safety of otelixizumab use in new-onset type 1 diabetes mellitus.

INTRODUCTION: Type 1 diabetes (T1DM) is an immune-mediated disease induced by antigen-specific T cells infiltrating pancreatic beta cells leading to the progressive loss of endogenous insulin secretion. AREAS COVERED: The identification of specific components of the autoimmune response favoured the implementation of several immunomodulatory therapies including antiCD3 monoclonal antibody (mAb) called otelixizumab. Otelixizumab is a chimeric monoclonal antibody that targets the ε-chain of the CD3T-lymphocyte surface receptor that has been developed with the aim of short therapeutic courses capable of inducing a remission of T1DM. Clinical trials have been carried out with otelixizumab to evaluate its safety and efficacy, but despite positive results of Phase I and II studies, the results of Phase III studies have been contradictory. EXPERT OPINION: High doses of otelixizumab have shown beneficial effects on beta cell function whereas a lower dose, which was tested to avoid the adverse effects associated with higher doses, was not effective on beta cells preservation. We believe that otelixizumab is a drug of potential interest for treating new onset T1DM patients and its use in combination with other immunomodulatory agents should be considered as a solution to circumvent adverse effects while maintaining efficacy.

The effect of macrobiotic Ma-Pi 2 diet on systemic inflammation in patients with type 2 diabetes: a post hoc analysis of the MADIAB trial.

INTRODUCTION: Current guidelines for the management of type 2 diabetes (T2D) emphasize diet as essential therapy. However, the effect of diet on systemic inflammation remains unclear. We investigated the effects of consuming a macrobiotic Ma-Pi 2 diet versus a standard recommended diet (control diet) on markers of inflammation in patients with T2D. METHODS: This was a post hoc analysis of the MADIAB trial, a 21-day randomized controlled trial conducted in 51 patients (25 males and 26 females) with T2D. Patients were randomized 1:1 to the Ma-Pi 2 macrobiotic diet or a control diet based on dietary guidelines for T2D. Biological antioxidant potential of plasma and circulating levels of high-sensitivity C reactive protein, interleukin-6, tumor necrosis factor-α, and insulin-like growth factor-1 were assessed. RESULTS: After 21 days on the Ma-Pi 2 or control diet, markers of inflammation were reduced in both groups. The antioxidant potential of plasma improved significantly in the Ma-Pi group. A significant reduction in insulin growth factor-1 was observed in the Ma-Pi group versus control group (p<0.001). CONCLUSIONS: Findings of this post hoc analysis demonstrated that the Ma-Pi 2 diet is a safe dietary strategy to reduce levels of the markers of insulin resistance and inflammation, compared with baseline values, in the short term. Furthermore, the Ma-Pi 2 diet was superior to the control diet in reducing insulin growth factor-1 and may be beneficial for patients with T2D. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN10467793.

The effect of the macrobiotic Ma-Pi 2 diet vs. the recommended diet in the management of type 2 diabetes: the randomized controlled MADIAB trial.

BACKGROUND: Diet is an important component of type 2 diabetes therapy. Low adherence to current therapeutic diets points out to the need for alternative dietary approaches. This study evaluated the effect of a different dietary approach, the macrobiotic Ma-Pi 2 diet, and compared it with standard diets recommended for patients with type 2 diabetes. METHODS: A randomized, controlled, open-label, 21-day trial was undertaken in patients with type 2 diabetes comparing the Ma-Pi 2 diet with standard (control) diet recommended by professional societies for treatment of type 2 diabetes. Changes in fasting blood glucose (FBG) and post-prandial blood glucose (PPBG) were primary outcomes. HbA1c, insulin resistance (IR), lipid panel and anthropometrics were secondary outcomes. RESULTS: After correcting for age, gender, BMI at baseline, and physical activity, there was a significantly greater reduction in the primary outcomes FBG (95% CI: 1.79; 13.46) and PPBG (95% CI: 5.39; 31.44) in those patients receiving the Ma-Pi 2 diet compared with those receiving the control diet. Statistically significantly greater reductions in the secondary outcomes, HbA1c (95% CI: 1.28; 5.46), insulin resistance, total cholesterol, LDL cholesterol and LDL/HDL ratio, BMI, body weight, waist and hip circumference were also found in the Ma-Pi 2 diet group compared with the control diet group. The latter group had a significantly greater reduction of triglycerides compared with the Ma-Pi 2 diet group. CONCLUSIONS: Intervention with a short-term Ma-Pi 2 diet resulted in significantly greater improvements in metabolic control in patients with type 2 diabetes compared with intervention with standard diets recommended for these patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10467793.