Genome-resolved metagenomics reveals diverse taxa and metabolic complexity in Antarctic lake microbial structures.

Lake Untersee, a lake in Antarctica that is perennially covered with ice, is home to unique microbial structures that are not lithified. We have evaluated the structure of the community and its metabolic potential across the pigmented upper layers and the sediment-enriched deeper layers in these pinnacle and cone-shaped microbial structures using metagenomics. These microbial structures are inhabited by distinct communities. The upper layers of the cone-shaped structures have a higher abundance of the cyanobacterial MAG Microcoleus, while the pinnacle-shaped structures have a higher abundance of Elainellacea MAG. This suggests that cyanobacteria influence the morphologies of the mats. We identified stark contrasts in the composition of the community and its metabolic potential between the upper and lower layers of the mat. The upper layers of the mat, which receive light, have an increased abundance of photosynthetic pathways. In contrast, the lower layer has an increased abundance of heterotrophic pathways. Our results also showed that Lake Untersee is the first Antarctic lake with a substantial presence of ammonia-oxidizing Nitrospiracea and amoA genes. The genomic capacity for recycling biological molecules was prevalent across metagenome-assembled genomes (MAGs) that cover 19 phyla. This highlights the importance of nutrient scavenging in ultra-oligotrophic environments. Overall, our study provides new insights into the formation of microbial structures and the potential metabolic complexity of Antarctic laminated microbial mats. These mats are important environments for biodiversity that drives biogeochemical cycling in polar deserts.

Diabetes as a risk factor for pneumococcal disease and severe related outcomes and efficacy/effectiveness of vaccination in diabetic population. Results from meta-analysis of observational studies.

AIMS: To collect all available evidence on the effect of diabetes mellitus (DM) as a risk factor for pneumococcal disease incidence and related complications, and on the efficacy/effectiveness of vaccines in patients with DM. METHODS: Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and EMBASE databases were performed, one for each meta-analysis, collecting all observational (cohort and case-control) studies and randomized clinical trials performed on humans up to June 1st, 2023. RESULTS: We retrieved 36 observational studies comparing risk for pneumococcal disease and related complications in people with or without DM, and 11 studies (1 randomized clinical trial and 10 observational studies) assessing conjugated and polysaccaridic vaccines efficacy/effectiveness on preventing such outcomes. People with DM were at higher risk for Invasive Pneumococcal Disease (unadjusted OR 2.42 [2.00; 2.92]); Case-Fatality Rate (unadjusted OR 1.61 [1.25; 2.07], Pneumococcal pneumonia (unadjusted OR 2.98 [2.76; 3.22), and Intensive care unit admission for pneumococcal disease (unadjusted OR 2.09 [1.20; 3.66]). In diabetic individuals vaccinated with conjugated vaccine, incidence of pneumonia specific for vaccine type in a clinical trial (OR 0.237 [0.008; 0.704]), and hospitalization for overall pneumonia during the year following the polysaccharide vaccination in observational studies (unadjusted OR 0.63 [0.45-0.89]) were significantly lower in comparison with unvaccinated DM subjects, with no significant differences for other outcomes. CONCLUSIONS: People with diabetes mellitus are at higher risk for less favourable course of pneumococcal disease and should be therefore targeted in vaccination campaigns; more evidence needs to be collected on vaccination outcomes in people with diabetes.

Alterations in the Menstrual Cycle as a Peculiar Sign of Type 1 Diabetes Mellitus: A Meta-analytic Approach.

BACKGROUND: Menstrual irregularities are present in >30% of women with type 1 diabetes mellitus (T1DM). These abnormalities will likely lead to reduced fertility and earlier menopause. T1DM management has changed over time, with even more emphasis on stringent levels of glycemic management. Thus, we investigated whether therapeutic T1DM changes have an influence on the proportion of menstrual disorders in women with T1DM. METHODS: A meta-analysis was performed that included clinical trials in which menstrual abnormalities in women with T1DM were studied. The literature was checked for studies in which women with T1DM were compared with healthy, age-matched controls. Case-control, cohort, and cross-sectional studies were included. The primary endpoint was rate of menstrual dysfunction. RESULTS: Menstrual dysfunction was higher in women with T1DM compared with controls (odds ratio 2.08, 95% confidence interval [CI] 1.43 to 3.03, p<0.001), even when sensitivity analysis was performed, considering only studies published after 2000. The age at menarche was higher for women with T1DM compared with controls (mean difference 0.53, 95% CI 0.32 to 0.74 years, p<0.001). The proportion of menstrual abnormalities in T1DM was inversely related to diabetes duration, but was unrelated to both body mass index and glycated hemoglobin. CONCLUSIONS: The meta-analytic approach used confirmed the correlation between T1DM and menstrual irregularities. T1DM menstrual dysfunction seemed unrelated to change in therapeutic management across years, as well as to glycemic management and body weight. The underlying pathogenetic mechanisms are not fully understood.

Microbiota Composition and Probiotics Supplementations on Sleep Quality-A Systematic Review and Meta-Analysis.

The gut microbiota (GM) plays a crucial role in human health. The bidirectional interaction between GM and the central nervous system may occur via the microbiota-gut-brain axis, possibly regulating the sleep/wake cycle. Recent reports highlight associations between intestinal dysbiosis and sleep disorders, suggesting that probiotics could ameliorate this condition. However, data are poor and inconsistent. The aim of this quantitative metanalytic study is to assess the GM composition in sleep disturbances and evaluate probiotics' effectiveness for managing sleep disorders. A systematic review was carried out until July 2022 in online databases, limiting the literature research to human studies and English language articles. No significant GM diversity between patients with sleep disturbances versus healthy controls was found, revealed by α-diversity, while ß-diversity is missing due to lack of proper reporting. However, probiotics supplementation significantly reduced the self-assessed parameter of sleep quality and disturbances Pittsburgh Sleep Quality Index (PSQI) score compared with the placebo. No difference in the Epworth Sleepiness Scale (ESS) score was found. While available data suggest that GM diversity is not related to sleep disturbances, probiotics administration strongly improves sleep quality as a subjective perception. However, heterogeneity of data reporting in the scientific literature should be considered as a limitation.

Glycemic control predicts SARS-CoV-2 prognosis in diabetic subjects.

AIM: The coronavirus disease (COVID)-19 incidence was higher in diabetes mellitus (DM), although several differences should be considered on the basis of characteristics of cohorts evaluated. This study was designed to evaluate the prevalence and potential consequences of COVID-19 in a large diabetic population in Northern Italy. DESIGN: Observational, longitudinal, retrospective, clinical study. METHODS: Subjects with both type 1 and type 2 DM living in the Province of Modena and submitted to at least one SARS-CoV-2 swab between March 2020 and March 2021 were included. Data were extracted from the Hospital data warehouse. RESULTS: 9553 diabetic subjects were enrolled (age 68.8 ± 14.1 years, diabetes duration 11.0 ± 6.9 years, glycated hemoglobin 57.2 ± 16.2 mmol/mol). COVID-19 was detected in 2302 patients (24.1%) with a death rate of 8.9%. The mean age and diabetes duration were significantly lower in infected versus non-infected patients. SARS-CoV-2 infection was more frequent in youngest people, according to quartile of age and retirement pension age of 65 years. No differences were detected considering sex. Higher HbA1c was detected in infected compared to non-infected patient. Death was predicted by diabetes duration and HbA1c. ROC analyses for death risk showed significant threshold for diabetes duration (10.9 years) and age (74.4 years). CONCLUSION: In our cohort, SARS-CoV-2 infection correlates with age, diabetes duration and disease control. Diabetic patients with COVID-19 should be carefully followed when older than 74 years and with more than 10 years of DM duration.

Ketogenic state improves testosterone serum levels-results from a systematic review and meta-analysis.

BACKGROUND: It is widely demonstrated that obesity and hypogonadism are bi-directionally correlated, since the hypogonadism prevalence is higher in obese population, while weight loss increases testosterone serum levels. Several approaches are available to contrast weight excess, from simple dietary regimens to more complex surgical procedures. Ketogenic diets (KD) fit in this context and their application is growing year after year, aiming to improve the metabolic and weight patterns in obese patients. However, KD influence on testosterone levels is still poorly investigated. OBJECTIVES: To systematically evaluate the potential effect of KD on testosterone levels. METHODS: A systematic literature search was performed until April 2022 including studies investigating testosterone levels before and after KD. Secondary endpoints were body weight, estradiol and sex-hormone binding globulin serum levels. Any kind of KD was considered eligible, and no specific criteria for study populations were provided. RESULTS: Seven studies (including eight trials) were included in the analysis for a total of 230 patients, five using normocaloric KD and three very low calories KD (VLCKD). Only three studies enrolled overweight/obese men. A significant total testosterone increase was recorded after any kind of KD considering 111 patients (2.86 [0.95, 4.77], p = 0.003). This increase was more evident considering VLCKD compared to normocaloric KD (6.75 [3.31, 10.20], p < 0.001, versus 0.98 [0.08, 1.88], p = 0.030). Meta-regression analyses highlighted significant correlations between the post-KD testosterone raise with patients' age (R-squared 36.4, p < 0.001) and weight loss (R-squared 73.6, p < 0.001). CONCLUSIONS: Comprehensively, KD improved testosterone levels depending on both patients' age and KD-induced weight loss. However, the lack of information in included studies on hormones of the hypothalamic-pituitary-gonadal axis prevents an exhaustive comprehension about mechanisms connecting ketosis and testosterone homeostasis.

Clinical scoring systems for the risk of cardiovascular autonomic neuropathy in type 1 and type 2 diabetes: A simple tool.

This study was aimed at developing a clinical risk score for cardiovascular autonomic neuropathy (CAN) for type 1 and type 2 diabetes. In a retrospective cross-sectional one-centre study in an unselected population, 115 participants with type 1 diabetes (age 41.1 ± 12.2 years) and 161 with type 2 diabetes (age 63.1 ± 8.9 years), well-characterized for clinical variables, underwent standard cardiovascular reflex tests (CARTs). Strength of associations of confirmed CAN (based on 2 abnormal CARTs) with clinical variables was used to build a CAN risk score. CAN risk score was based on resting heart rate, HbA1c, retinopathy, nephropathy, cardiovascular disease in both type 1 and type 2 diabetes, and on HDL cholesterol, systolic blood pressure, and smoking in type 1 diabetes or insulin treatment and physical activity in type 2 diabetes (range 0-10). In type 1 diabetes, CAN risk score showed an area under the ROC curve (AUC) of 0.890 ± 0.034, and at cut-off of 4 sensitivity of 88%, specificity of 74.4%, and negative predictive value (NPV) of 95.7% for confirmed CAN. In type 2 diabetes, CAN risk score showed an AUC of 0.830 ± 0.051 and at the cut-off of 4 sensitivity and specificity of 78.6% and 73.5%, respectively, and NPV of 97.3% for confirmed CAN. These newly developed CAN risk scores are accessible in clinical practice and, if confirmed in a validation study, they might identify asymptomatic individuals with diabetes at greater risk of CAN to be referred to CARTs, thus limiting the burden of a universal screening.

Diabetic Neuropathic Cachexia: A Clinical Case and Review of Literature.

A 46-year-old man was admitted to the surgical department because of abdominal pain and anemia, with the radiological finding of a perforated duodenal ulcer, and underwent laparoscopic surgical treatment. Type 2 diabetes mellitus (T2DM) had been diagnosed 5 years earlier and treated with diet. At clinical investigation, the patient was depressed and anorexic; moreover, he complained of lower extremity weakness and bilateral feet pain, burning in nature and accompanied by allodynia. This painful sensation had been preceded by an 8-month history of fatigue and anorexia with profound weight loss of 35 kg. After clinical evaluation and a nerve conduction study, diagnosis of diabetic cachectic neuropathy was made based on the rapid onset of severe neuropathic pain in the context of diabetic neuropathy, marked weight loss, and depressed mood. The therapy with pregabalin and duloxetine had scarce effect and was gradually discontinued. The patient, however, obtained progressive relief and amelioration of neuropathic lower-limb pain concomitant with weight gain. This clinical trend also confirmed the diagnosis of this rare form of diabetic neuropathy. A few cases of diabetic neuropathic cachexia have been reported in the literature and are briefly reviewed here.

Effect of the Glucagon-Like Peptide-1 Receptor Agonists on Autonomic Function in Subjects with Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: In addition to the metabolic effects in diabetes, glucagon-like peptide 1 receptor (GLP-1R) agonists lead to a small but substantial increase in heart rate (HR). However, the GLP-1R actions on the autonomic nervous system (ANS) in diabetes remain debated. Therefore, this meta-analysis evaluates the effect of GLP-1R agonist on measures of ANS function in diabetes. METHODS: According to the Cochrane Collaboration and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we conducted a meta-analysis considering clinical trials in which the autonomic function was evaluated in diabetic subjects chronically treated with GLP-1R agonists. The outcomes were the change of ANS function measured by heart rate variability (HRV) and cardiac autonomic reflex tests (CARTs). RESULTS: In the studies enrolled, HR significantly increased after treatment (P<0.001), whereas low frequency/high frequency ratio did not differ (P=0.410); no changes in other measures of HRV were detected. Considering CARTs, only the 30:15 value derived from lying-to-standing test was significantly lower after treatment (P=0.002), but only two studies reported this measurement. No differences in other CARTs outcome were observed. CONCLUSION: The meta-analysis confirms the HR increase but seems to exclude an alteration of the sympatho-vagal balance due to chronic treatment with GLP-1R agonists in diabetes, considering the available measures of ANS function.

Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Peripheral Diabetic Polyneuropathy: A Systematic Review and Meta-Analysis.

AIMS: The relationship between nonalcoholic fatty liver disease (NAFLD) and diabetic polyneuropathy (DPN) has been demonstrated in many studies, although results were conflicting. This meta-analysis aims to summarize available data and to estimate the DPN risk among NAFLD patients. MATERIALS AND METHODS: We performed a comprehensive literature review until 4 June 2021. Clinical trials analyzing the association between NAFLD and DPN were included. RESULTS: Thirteen studies (9614 participants) were included. DPN prevalence was significantly higher in patients with NALFD, compared to patients without NAFLD (OR (95%CI) 2.48 (1.42-4.34), p = 0.001; I2 96%). This finding was confirmed in type 2 diabetes (OR (95%CI) 2.51 (1.33-4.74), p = 0.005; I2 97%), but not in type 1 diabetes (OR (95%CI) 2.44 (0.85-6.99), p = 0.100; I2 77%). Also, body mass index and diabetes duration were higher in NAFLD subjects compared to those without NAFLD (p < 0.001), considering both type 2 and type 1 diabetes. CONCLUSION: Despite a high heterogeneity among studies, a significantly increased DPN prevalence among type 2 diabetes subjects with NAFLD was observed. This result was not found in type 1 diabetes, probably due to the longer duration of disease. Physicians should pay more attention to the early detection of DPN, especially in patients with NAFLD.

The "Hitchhiker's Guide to the Galaxy" of Endothelial Dysfunction Markers in Human Fertility.

Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and represents the first step in the pathogenesis of cardiovascular diseases. The evaluation of endothelial health is fundamental in clinical practice and several direct and indirect markers have been suggested so far to identify any alterations in endothelial homeostasis. Alongside the known endothelial role on vascular health, several pieces of evidence have demonstrated that proper endothelial functioning plays a key role in human fertility and reproduction. Therefore, this state-of-the-art review updates the endothelial health markers discriminating between those available for clinical practice or for research purposes and their application in human fertility. Moreover, new molecules potentially helpful to clarify the link between endothelial and reproductive health are evaluated herein.

Microbial Diversity of Pinnacle and Conical Microbial Mats in the Perennially Ice-Covered Lake Untersee, East Antarctica.

Antarctic perennially ice-covered lakes provide a stable low-disturbance environment where complex microbially mediated structures can grow. Lake Untersee, an ultra-oligotrophic lake in East Antarctica, has the lake floor covered in benthic microbial mat communities, where laminated organo-sedimentary structures form with three distinct, sympatric morphologies: small, elongated cuspate pinnacles, large complex cones and flat mats. We examined the diversity of prokaryotes and eukaryotes in pinnacles, cones and flat microbial mats using high-throughput sequencing of 16S and 18S rRNA genes and assessed how microbial composition may underpin the formation of these distinct macroscopic mat morphologies under the same environmental conditions. Our analysis identified distinct clustering of microbial communities according to mat morphology. The prokaryotic communities were dominated by Cyanobacteria, Proteobacteria, Verrucomicrobia, Planctomycetes, and Actinobacteria. While filamentous Tychonema cyanobacteria were common in all mat types, Leptolyngbya showed an increased relative abundance in the pinnacle structures only. Our study provides the first report of the eukaryotic community structure of Lake Untersee benthic mats, which was dominated by Ciliophora, Chlorophyta, Fungi, Cercozoa, and Discicristata. The eukaryote richness was lower than for prokaryote assemblages and no distinct clustering was observed between mat morphologies. These findings suggest that cyanobacterial assemblages and potentially other bacteria and eukaryotes may influence structure morphogenesis, allowing distinct structures to form across a small spatial scale.

Effect of a standard schema of self-monitoring blood glucose in patients with poorly controlled, non-insulin-treated type 2 diabetes mellitus: A controlled longitudinal study.

The effect of self-monitoring of blood glucose (SMBG) on glycemic control with regard to non-insulin-treated Type 2 diabetes mellitus (NIT-Type 2 DM) is still a controversial topic. Against this backdrop, we sought to compare the effect of a continuous short-term SMBG schema with as-usual treatment, based on changes in oral antidiabetic treatment in patients with poorly controlled Type 2 DM. We reviewed 492 NIT-Type 2 DM record charts, selecting 27 patients, with poor glycemic control, who were thought to self-monitor their blood glucose levels (SMBG group). We then compared them with 27 patients treated with modifying drugs or diets to achieve and maintain the glycemic target (Control Group). Haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) were evaluated at baseline, after 3 and 6 months. HbA1c values decreased after 3 and 6 months in the SMBG group (P < 0.001 on both occasions) and in the control group (P < 0.05 and P < 0.01, respectively), but without a significant difference between the two groups when compared at the same time. The FPG progressively decreased in both groups, reaching a significant difference in the SMBG group after 3 months and in the control group after 6 months, and without a significant difference between the two groups. The SMBG schema used in our study could be adopted for target groups before proceeding to the next therapeutic enhancement drug step, representing a useful tool that can help diabetic patients in raising awareness of and treating their disease.

Long-term effects on growth of an energy-enhanced parenteral nutrition in preterm newborn: A quasi-experimental study.

AIM: To assess the best energy intake in Parenteral Nutrition (PN) for preterm newborns, considering both possible benefits for growth and risk of complications. METHODS: Quasi-experimental study comparing two cohorts of newborns, receiving Energy-Enhanced vs. Standard PN (Cohort A, from 1st January 2015 to 31 January 2016 and Cohort B from 1st February 2016 to 31 March 2017; respectively) after implementation of a change in the PN protocol. The primary outcome measure was growth at 24 months of life. The PN associated complications were also measured. RESULTS: We enrolled 132 newborns in two Cohorts, similar for prenatal and postnatal clinical characteristics. Although, body weight and length at 24 months of life were significantly higher (p<0.05) in the Cohort A (11.1, 95% CI 10.6 to 11.6 Kg; 85.0 95% CI 83.8 to 86.2 cm) compared with Cohort B (10.4, 95% CI 9.9 to 10.9 Kg; 81.3 95% CI 79.7 to 82.8 cm), body weight and length Z-Score in the first 24 months of life were similar between the two Cohorts. The rate of PN associated complications was very high in both study Cohorts (up to 98% of enrolments). Multivariate analysis showed that length at 24 months was significantly associated with receiving standard PN (cohort A) in the first week of life and on the energy intake in the first week of life. We also found a marginally insignificant association between Cohort A assignment and body weight at 24 months of life (p = 0.060). CONCLUSIONS: Energy-enhanced PN in early life has not significant effects on long-term growth in preterm newborns. The high prevalence of PN associated complications, poses concerns about the utility of high energy intake recommended by current guidelines for PN.

Expression study of candidate miRNAs and evaluation of their potential use as biomarkers of diabetic neuropathy.

Aim: To evaluate the expression of candidate miRNAs in relation to diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). Materials & methods: The expression of six candidate miRNAs has been evaluated in 49 Type 2 diabetes patients with neurological evaluation. Results: A higher expression of miR-128a was seen in patients with DPN compared with those without DPN (p = 0.015). miR-155 and miR-499a seemed to be down-expressed in patients with DPN (p = 0.04 and p = 0.05, respectively). A lower expression of miR-155 (p = 0.05) was observed even in patients with CAN with respect to CAN-negative. A higher expression of miR-155 was associated with the rs767649 polymorphism variant allele compared with the wild-type allele (p = 0.03). Conclusion: miR-128a, miR-155 and miR-499a might be involved in diabetic neuropathies development.

Mitochondrial DNA Copy Number in Peripheral Blood Is Reduced in Type 2 Diabetes Patients with Polyneuropathy and Associated with a MIR499A Gene Polymorphism.

Our aim was to evaluate in a cohort of 125 Italian patients with type 2 diabetes (T2D), who underwent neurological evaluation, the possible differences in the number of mitochondrial DNA copies (mtDNA) comparing positive and negative patients for cardiovascular autonomic neuropathy (CAN) or diabetic peripheral neuropathy (DPN) and comparing them with healthy controls. We also investigated a possible correlation of the number of mtDNA copies with the polymorphism rs3746444 of the MIR499A. T2D patients show a decrease in the number of mtDNA copies compared to healthy controls (p = 2 × 10-10). Dividing the T2D subjects by neurological evaluation, we found a significant mtDNA decrease in patients with DPN compared with those without (p = 0.02), while no differences were observed between subjects with and without CAN. Furthermore, the homozygous variant genotype for the polymorphism rs3746444 of MIR499A correlates with a decrease in the number of mtDNA copies, particularly in T2D patients (p = 0.009). Our data show a decrease in the number of mtDNA copies in subjects with T2D and suggest that this decrease is more evident in patients who develop DPN. Furthermore, the association of the variant allele of MIR499A with the number of mtDNA copies allows us to hypothesize a possible effect of this polymorphism in oxidative stress.

Nutritional Intake Influences Zinc Levels in Preterm Newborns: An Observational Study.

(1) Background: Zinc is a key element for protein synthesis in preterm newborns. Early aggressive nutrition, promoting protein synthesis, may increase zinc consumption; (2) Methods: We performed a prospective observational study, to assess the relationship between early macronutrients intake and serum zinc levels, in preterm newborns with Gestational Age (GA) of 24-35 weeks, consecutively observed in Neonatal Intensive Care Unit (NICU). (3) Results: We enrolled 130 newborns (GA 31.5 ± 2.8). A significant negative correlation between serum zinc level at 28 days of life and energy (r -0.587, p < 0.001) and protein intake (r -0.556, p < 0.001) in the first week of life was observed. Linear regression analysis showed that zinc levels depended on energy (ß -0.650; p < 0.001) and protein (ß -0.669; p < 0.001) intake given through parenteral nutrition (PN) in the first week of life; (4) Conclusions: zinc status of preterm neonates was influenced by early protein and energy intake. An additional zinc supplementation should be considered when high protein and energy intake are received by preterm newborns in the first week of life.

The diagnostic usefulness of the combined COMPASS 31 questionnaire and electrochemical skin conductance for diabetic cardiovascular autonomic neuropathy and diabetic polyneuropathy.

The study investigated the diagnostic performance for diabetic cardiovascular autonomic neuropathy (CAN) and diabetic polyneuropathy (DPN) of the combined use of composite autonomic symptom score (COMPASS) 31, validated questionnaire for autonomic symptoms of CAN, and electrochemical skin conductance (ESC), proposed for detecting DPN and CAN. One-hundred and two participants with diabetes (age 57 ± 14 years, duration 17 ± 13 years) completed the COMPASS 31 before assessing cardiovascular reflex tests (CARTs), neuropathic symptoms, signs, vibratory perception threshold (VPT), thermal thresholds (TT), and ESC using Sudoscan. Two patterns were evaluated: (a) the combined abnormalities in both tests (COMPASS 31+ESC), and (b) the abnormality in COMPASS 31 and/or ESC (COMPASS 31 and/or ESC). CAN (≥1 abnormal CART) and confirmed CAN (≥2 abnormal CARTs) were present in 28.1% and 12.5%, DPN (two abnormalities among symptoms, signs, VPT, and TT) in 52%, abnormal COMPASS 31 (total weighted score >16.44) in 48% and abnormal ESC (hands ESC <50 µS and/or feet ESC <70 µS) in 47.4%. Both the patterns-COMPASS 31+ESC and COMPASS 31 and/or ESC-were associated with CAN and DPN (P < .01). COMPASS 31 and ESC reached a sensitivity of 75% and 83% for confirmed CAN, and a specificity of 65% and 67% for DPN. When combining the tests, the sensitivity for CAN rose by up to 100% for CAN and the specificity up to 89% for DPN. The combination of the tests can allow a stepwise screening strategy for CAN, by suggesting CAN absence with combined normality, and prompting to CARTs with combined abnormality.

Morning blood pressure surge is associated with autonomic neuropathy and peripheral vascular disease in patients with diabetes.

Although vascular and autonomic nervous system have been involved in the regulation of morning surge in blood pressure (MBPS), data on clinical correlates of MBPS in diabetic population are scarce, in particular with regard to diabetic complications. This study was aimed at investigating predictors and correlates of MBPS in diabetes. In a cross-sectional study including 167 patients with diabetes (age 58.5 ± 11.1 years, duration 15.9 ± 12.1 years), clinical variables, diabetic and neuropathic complications, and MBPS (using 24-h ambulatory blood pressure monitoring) were measured. The upper quartile of MBPS (>30.5 mmHg) was associated with higher values of waist circumference (P = 0.027), triglycerides (P = 0.021), and Michigan Diabetic Neuropathy Score (P = 0.042), with lower HDL cholesterol (P = 0.030), and with the presence of cardiovascular autonomic neuropathy (CAN) (P = 0.016) and peripheral vascular disease (PVD) (P < 0.0001). In a logistic regression analysis, PVD (odds ratio: 10.2, P = 0.001), CAN (odds ratio: 6.09, P = 0.016), and diastolic blood pressure (BP) (odds ratio: 1.06, P = 0.022) predicted MBPS upper quartile (r2 = 0.20, P = 0.0005). In a multiple regression analysis, PVD (P = 0.002) and diastolic BP (P = 0.003) were the only determinants of MBPS (r2 = 0.20). MBPS upper quartile was associated with BP dipping (systolic BP day-night reduction > 10%) (P = 0.012), and MBPS was positively related to systolic (rho = 0.41, P < 0.0001) and diastolic BP day-night reduction. In conclusion, metabolic syndrome stigmata, diastolic BP, CAN and PVD are the main predictors of MBPS in the diabetic population. Excessive MBPS and nondipping are not concurrent 24-h BP alterations. Autonomic dysfunction might exert an exacerbating effect on MBPS phenomenon.

Acute ataxia in paediatric emergency departments: a multicentre Italian study.

OBJECTIVES: To evaluate the causes and management of acute ataxia (AA) in the paediatric emergency setting and to identify clinical features predictive of an underlying clinically urgent neurological pathology (CUNP). STUDY DESIGN: This is a retrospective medical chart analysis of children (1-18 years) attending to 11 paediatric emergency departments (EDs) for AA in an 8-year period. A logistic regression model was applied to identify clinical risk factors for CUNP. RESULTS: 509 patients (mean age 5.8 years) were included (0.021% of all ED attendances). The most common cause of AA was acute postinfectious cerebellar ataxia (APCA, 33.6%). Brain tumours were the second most common cause (11.2%), followed by migraine-related disorders (9%). Nine out of the 14 variables tested showed an OR >1. Among them, meningeal and focal neurological signs, hyporeflexia and ophthalmoplegia were significantly associated with a higher risk of CUNP (OR=3-7.7, p<0.05). Similarly, the odds of an underlying CUNP were increased by 51% by each day from onset of ataxia (OR=1.5, CI 1.1 to 1.2). Conversely, a history of varicella-zoster virus infection and vertigo resulted in a significantly lower risk of CUNP (OR=0.1 and OR=0.5, respectively; p<0.05). CONCLUSIONS: The most frequent cause of AA is APCA, but CUNPs account for over a third of cases. Focal and meningeal signs, hyporeflexia and ophthalmoplegia, as well as longer duration of symptoms, are the most consistent 'red flags' of a severe underlying pathology. Other features with less robust association with CUNP, such as seizures or consciousness impairment, should be seriously taken into account during AA evaluation.