Use of Advanced Hybrid Closed-Loop System during Pregnancy: Strengths and Limitations of Achieving a Tight Glycemic Control.

Background: Pregnant women with type 1 diabetes mellitus (T1DM) face an elevated risk of complications for both themselves and their newborns. Experts recommend strict glycemic control. The advanced hybrid closed-loop (AHCL) system, though not officially approved for pregnant T1DM patients, is promising for optimal glycemic control. Methods: We collected CGM metrics, HbA1c levels, insulin pump settings, and doses from a 33-year-old pregnant woman with 23-year history of T1DM from the 6th week of gestation to birth. She was initially on continuous insulin pump therapy with CGM and switched to the AHCL system (MiniMedTM 780G, Medtronic, Northridge, CA, USA) between weeks 13 and 14. Results: The AHCL system improved glycemic control from weeks 14 to 26, achieving international guidelines with TIR = 72%, TAR = 24%, TBR = 4%. At week 30, TIR was 66%, TAR 31%. By altering diet and adding 'fake carbohydrates', she maintained TIR ≥ 70%, TBR ≤ 4%, TAR ≤ 26% from week 34 to birth. A healthy 4 kg, 53 cm baby boy was born at week 38. Conclusions: The use of the AHCL system holds significant promise for improving glycemic control in pregnancy. Optimal glycemic control with MiniMedTM 780G in pregnancy requires accurate carbohydrate counting, specific timing of insulin doses in relation to meal consumption and dietary choices that reduce the glycemic load of meals continue to be crucial factors in achieving optimal glycemic control during pregnancy using the MiniMedTM 780G system. Further research and clinical studies are needed to explore the full potential of these advanced systems in managing T1DM during pregnancy and optimizing maternal and neonatal outcomes.

Which Is the Best Way to Treat Massive Hemoptysis? A Systematic Review and Meta-Analysis of Observational Studies.

INTRODUCTION: Hemoptysis is one of the most common symptoms of respiratory system diseases. Common causes include bronchiectasis, tumors, tuberculosis, aspergilloma, and cystic fibrosis. The severity of hemoptysis varies from mild to moderate to massive hemoptysis and can easily lead to hemodynamic instability and death from suffocation or shock. Nevertheless, the most threatening hemoptysis that is presented to the emergency department and requires hospitalization is the massive one. In these cases, today, the most common way to manage hemoptysis is bronchial artery embolization (BAE). METHODS: A systematic literature search was conducted in PubMed and Scopus from January 2017 (with the aim of selecting the newest possible reports in the literature) until May 2023 for studies reporting massive hemoptysis. All studies that included technical and clinical success rates of hemoptysis management, as well as rebleeding and mortality rates, were included. A proportional meta-analysis was conducted using a random-effects model. RESULTS: Of the 30 studies included in this systematic review, 26 used bronchial artery embolization as a means of treating hemoptysis, with very high levels of both technical and clinical success (greater than 73.7% and 84.2%, respectively). However, in cases where it was not possible to use bronchial artery embolization, alternative methods were used, such as dual-vessel intervention (80% technical success rate and 66.7% clinical success rate), customized endobronchial silicone blockers (92.3% technical success rate and 92.3% clinical success rate), antifibrinolytic agents (50% clinical success rate), and percutaneous transthoracic embolization (93.1% technical success rate and 88.9% clinical success rate), which all had high success rates apart from antifibrinolytic agents. Of the 2467 patients included in these studies, 341 experienced rebleeding during the follow-up period, while 354 other complications occurred, including chest discomfort, fever, dysphagia, and paresis. A total of 89 patients died after an episode of massive hemoptysis or during the follow-up period. The results of the meta-analysis showed a pooled technical success of bronchial artery embolization equal to 97.22% and a pooled clinical success equal to 92.46%. The pooled recurrence was calculated to be 21.46%, while the mortality was 3.5%. These results confirm the ability of bronchial artery embolization in the treatment of massive hemoptysis but also emphasize the high rate of recurrence following the intervention, as well as the risk of death. CONCLUSION: In conclusion, massive hemoptysis can be treated with great clinical and technical success using bronchial artery embolization, reducing mortality. Mortality has now been reduced to a small percentage of cases.

The Effectiveness of a Low Glycemic Index/Load Diet on Cardiometabolic, Glucometabolic, and Anthropometric Indices in Children with Overweight or Obesity: A Systematic Review and Meta-Analysis.

(1) Background: This systematic review and meta-analysis aims to evaluate the impact of a low glycemic index (LGI) and low glycemic load (LGL) diet on children with overweight and obesity, analyzing any changes in anthropometric, cardiometabolic, and glucometabolic parameters. (2) Methods: Three electronic databases (PubMed, Scopus, CENTRAL), as well as clinical trial registries and reference lists of the included studies, were searched for eligible randomized control trials (RCTs). Two independent reviewers performed the screening of the studies, data extraction, and risk of bias assessment. Mean difference (MD) and 95% confidence intervals (CI) using a random effects model were calculated for each outcome. (3) Results: Eleven RCTs (n = 634) examining the effect of LGI diet versus control were identified. The synthesized data provided from the RCTs indicate no difference between intervention and control groups regarding primary outcomes (body weight (MD: -0.14; 95% CI -1.93 to 1.64, 5 trials), body mass index (BMI) (MD: -0.31; 95% CI -0.85 to 0.23, 6 trials), BMI z-score (MD: -0.03; 95% CI -0.09 to 0.02, 5 trials), and waist circumference (MD: -0.52; 95% CI -2.35 to 1.31, 5 trials)) and other measures of cardiometabolic and glucometabolic parameters. The majority of trials were classified as "some concerns". (4) Conclusions: LGI and LGL diets do not seem to be associated with changes in adiposity, cardiometabolic or glucometabolic markers in children with overweight or obesity. Further research comparing the LGI diet to a high glycemic index diet, with proper methodological standards, is required to clarify the benefits of a LGI diet in this population.

The Prevalence of Gastrointestinal Bleeding in COVID-19 Patients: A Systematic Review and Meta-Analysis.

Introduction: Severe acute respiratory syndrome coronavirus 2 caused the coronavirus disease of 2019 (COVID-19), which rapidly became a pandemic, claiming millions of lives. Apart from the main manifestations of this infection concerning the respiratory tract, such as pneumonia, there are also many manifestations from the gastrointestinal tract. Of these, bleeding from the gastrointestinal tract is a significant complication quite dangerous for life. This bleeding is divided into upper and lower, and the primary pathophysiological mechanism is the entering of the virus into the host cells through the Angiotensin-converting enzyme 2 receptors. Also, other comorbidities and the medication of corticosteroids and anticoagulants are considered to favor the occurrence of gastrointestinal bleeding (GIB). Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the studies were searched in two different databases (Scopus and PubMed) from November 2019 until February 2023. All studies that reported GIB events among COVID-19 patients were included. Results: 33 studies were selected and reviewed to estimate the prevalence of GIB. A total of 134,905 patients with COVID-19 were included in these studies, and there were 1458 episodes of GIB. The prevalence of GIB, in these 33 studies, ranges from 0.47% to 19%. This range of prevalence is justified by the characteristics of the COVID-19 patients. These characteristics are the severity of COVID-19, anticoagulant and other drug treatments, the selection of only patients with gastrointestinal manifestations, etc. The pooled prevalence of gastrointestinal bleeding was estimated to be 3.05%, rising to 6.2% when only anticoagulant patients were included. Conclusions: GIB in COVID-19 patients is not a rare finding, and its appropriate and immediate treatment is necessary as it can be life-threatening. The most common clinical findings are melena and hematemesis, which characterize upper GIB. Treatment can be conservative; however, endoscopic management of bleeding with embolization is deemed necessary in some cases.

High Versus Low Adherence to the Mediterranean Diet for Prevention of Diabetes Mellitus Type 2: A Systematic Review and Meta-Analysis.

Diabetes mellitus type 2 (DMT-2) presents with a growing incidence, and its complications contribute mainly to cardiovascular disease and overall mortality. DMT-2 prevention and early stage management include lifestyle modification by adopting healthy eating patterns and increasing physical activity levels. The Mediterranean diet (MD) is associated with beneficial effects on human health and has been found effective for preventing and managing DMT-2. The purpose of this meta-analysis is to investigate whether the level of MD adherence plays a role in DMT-2 prevention and to what extent. A systematic literature search in PubMed, EMBASE, Web of Science Core Collection, Scopus, and Google Scholar databases was conducted until November 2022, and related observational studies fulfilling the eligibility criteria were included. The literature search concluded with 24 studies in the qualitative analysis and 23 studies in the quantitative analysis. Of those, 18 cohort studies were eligible for meta-analysis with hazard ratio as effect size and five studies providing odds ratio as effect size. The cohort studies included 248,140 participants with a mean follow-up of 10.8 years (3 to 22 years). Individuals with high adherence to MD presented an 11% and 18% decrease in risk and odds, respectively, of developing DMT-2 compared to those with low MD adherence (HR 0.89, 95%CI 0.83 to 0.95) and (OR 0.82, 95%CI 0.72 to 0.93). In studies where the follow-up was longer than 10 years, the 12% decrease in the risk of developing DMT-2 remained (HR 0.88 95%CI 0.84 to 0.92), whereas in studies where follow-up was less than 10 years, no difference between groups with different levels of adherence was found. Long-term high MD adherence is associated with a reduced risk of developing DMT-2, but further studies are needed to confirm these results.

Effects of dietary interventions on cardiovascular outcomes: a network meta-analysis.

CONTEXT: Next to a large body of epidemiological observational studies showing that the Mediterranean diet (MD) is an important lifestyle determinant of cardiovascular risk, there is less relevant evidence from well-conducted randomized controlled trials (RCTs) with hard cardiovascular outcomes. OBJECTIVE: The objective of the study was to identify the most effective dietary intervention for reducing cardiovascular morbidity and mortality. DATA SOURCES: A systematic approach following PRISMA network meta-analyses reporting guidelines was applied to a search of electronic databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Embase) without language restrictions, supplemented by scanning through bibliographies of studies and meetings' abstract material. Inclusion criteria were RCTs conducted in an adult population, investigating the effects of different type of diets or dietary patterns on all-cause mortality and cardiovascular outcomes of interest. DATA EXTRACTION: Data extraction for each study was conducted by 2 independent reviewers. DATA ANALYSIS: A frequentist network meta-analysis using a random-effects model was conducted. Death from any cardiovascular cause was defined as the primary outcome. A total of 17 trials incorporating 83 280 participants were included in the systematic review. Twelve articles (n = 80 550 participants) contributed to the network meta-analysis for the primary outcome. When compared with the control diet, only the MD showed a reduction in cardiovascular deaths (risk ratio = 0.59; 95% confidence interval, 0.42-0.82). Additionally, MD was the sole dietary strategy that decreased the risk of major cardiovascular events, myocardial infarction, angina, and all-cause mortality. CONCLUSIONS: MD may play a protective role against cardiovascular disease and death for primary and also secondary prevention. SYSTEMATIC REVIEW REGISTRATION: Center for Open Science, https://doi.org/10.17605/OSF.IO/5KX83.

Clinical Pathobiochemistry of Vitamin B12 Deficiency: Improving Our Understanding by Exploring Novel Mechanisms with a Focus on Diabetic Neuropathy.

Vitamin B12 (B12) is an essential cofactor of two important biochemical pathways, the degradation of methylmalonic acid and the synthesis of methionine from homocysteine. Methionine is an important donor of methyl groups for numerous biochemical reactions, including DNA synthesis and gene regulation. Besides hematological abnormalities (megaloblastic anemia or even pancytopenia), a deficiency in B12 may cause neurological symptoms, including symptoms resembling diabetic neuropathy. Although extensively studied, the underlining molecular mechanism for the development of diabetic peripheral neuropathy (DPN) is still unclear. Most studies have found a contribution of oxidative stress in the development of DPN. Detailed immunohistochemical investigations in sural nerve biopsies obtained from diabetic patients with DPN point to an activation of inflammatory pathways induced via elevated advanced glycation end products (AGE), ultimately resulting in increased oxidative stress. Similar results have been found in patients with B12 deficiency, indicating that the observed neural changes in patients with DPN might be caused by cellular B12 deficiency. Since novel results show that B12 exerts intrinsic antioxidative activity in vitro and in vivo, B12 may act as an intracellular, particularly as an intramitochondrial, antioxidant, independent from its classical, well-known cofactor function. These novel findings may provide a rationale for the use of B12 for the treatment of DPN, even in subclinical early states.

The Diagnostic Accuracy of SARS-CoV-2 Nasal Rapid Antigen Self-Test: A Systematic Review and Meta-Analysis.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), a disease that quickly spread into a pandemic. As such, management of the COVID-19 pandemic is deemed necessary, and it can be achieved by using reliable diagnostic tests for SARS-CoV-2. The gold standard for the diagnosis of SARS-CoV-2 is a molecular detection test using the reverse transcription polymerase chain reaction technique (rt-PCR), which is characterized by various disadvantages in contrast with the self-taken nasal rapid antigen tests that produce results faster, have lower costs and do not require specialized personnel. Therefore, the usefulness of self-taken rapid antigen tests is indisputable in disease management, facilitating both the health system and the examinees. Our systematic review aims to access the diagnostic accuracy of the self-taken nasal rapid antigen tests. METHODS: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess the risk of bias in the included studies. All the studies included in this systematic review were found after searching the two databases, Scopus and PubΜed. All but original articles were excluded from this systematic review, while all the studies concerning self-taken rapid antigen tests with a nasal sample and using rt-PCR as a reference test were included. Meta-analysis results and plots were obtained using RevMan software and the MetaDTA website. RESULTS: All 22 studies included in this meta-analysis demonstrated a specificity of self-taken rapid antigen tests greater than 98%, which exceeds the minimum required yield for the diagnosis of SARS-CoV-2, according to the WHO. Notwithstanding, the sensitivity varies (from 40% to 98.7%), which makes them in some cases unsuitable for the diagnosis of positive cases. In the majority of the studies, the minimum required performance set by the WHO was achieved, which is 80% compared with rt-PCR tests. The pooled sensitivity of self-taken nasal rapid antigen tests was calculated as 91.1% and the pooled specificity was 99.5%. CONCLUSIONS: In conclusion, self-taken nasal rapid antigen tests have many advantages over rt-PCR tests, such as those related to the rapid reading of the results and their low cost. They also have considerable specificity and some self-taken rapid antigen test kits also have remarkable sensitivity. Consequently, self-taken rapid antigen tests have a wide range of utility but are not able to completely replace rt-PCR tests.

Emergency General Surgery and COVID-19 Pandemic: Are There Any Changes? A Scoping Review.

Background and Objectives: The pandemic of SARS-CoV-19 has affected the overall spectrum of General Surgery, either in the case management part, or in the type of cases. The purpose of this review is to gather all the parameters affected and to compare these changes between the pandemic period and the corresponding time frame of the previous year. Materials and Methods: A review of literature in two electronic databases (PubMed and Scopus) was performed examining studies during the pre-pandemic (March to May 2019) and pandemic (March to May 2020) period about emergency surgeries. The differences in case presentation in emergency rooms, patient characteristics, length of hospitalization, type of surgery, complications and mortality rate were compared. Results: The comparison of the studies revealed significant results highlighting the differences between the two time periods for each parameter. There has been observed an overall decrease in the number of cases presented for emergency and urgent surgery. In terms of age, sex, and BMI, there were no significant variations amongst the patients. About the length of hospitalization, the patients hospitalized longer during the pandemic period. In terms of pathologies, the most common types of surgery were appendectomy, gastrointestinal, and colorectal resection. Mortality did not differ between the two study periods. Conclusions: COVID-19 affected a large part of Emergency General Surgery mainly concerns the type of operations performed. The hospitalization of patients, the complications that may have arisen and the recognition of emergencies were the most important issues faced by health care officials in hospitals during the period of COVID-19; however, there were parameters like mortality and patients' characteristics that did not appear to differ with pre-pandemic era.

Does COVID-19 Clinical Status Associate with Outcome Severity? An Unsupervised Machine Learning Approach for Knowledge Extraction.

Since the beginning of the COVID-19 pandemic, 195 million people have been infected and 4.2 million have died from the disease or its side effects. Physicians, healthcare scientists and medical staff continuously try to deal with overloaded hospital admissions, while in parallel, they try to identify meaningful correlations between the severity of infected patients with their symptoms, comorbidities and biomarkers. Artificial intelligence (AI) and machine learning (ML) have been used recently in many areas related to COVID-19 healthcare. The main goal is to manage effectively the wide variety of issues related to COVID-19 and its consequences. The existing applications of ML to COVID-19 healthcare are based on supervised classifications which require a labeled training dataset, serving as reference point for learning, as well as predefined classes. However, the existing knowledge about COVID-19 and its consequences is still not solid and the points of common agreement among different scientific communities are still unclear. Therefore, this study aimed to follow an unsupervised clustering approach, where prior knowledge is not required (tabula rasa). More specifically, 268 hospitalized patients at the First Propaedeutic Department of Internal Medicine of AHEPA University Hospital of Thessaloniki were assessed in terms of 40 clinical variables (numerical and categorical), leading to a high-dimensionality dataset. Dimensionality reduction was performed by applying a principal component analysis (PCA) on the numerical part of the dataset and a multiple correspondence analysis (MCA) on the categorical part of the dataset. Then, the Bayesian information criterion (BIC) was applied to Gaussian mixture models (GMM) in order to identify the optimal number of clusters under which the best grouping of patients occurs. The proposed methodology identified four clusters of patients with similar clinical characteristics. The analysis revealed a cluster of asymptomatic patients that resulted in death at a rate of 23.8%. This striking result forces us to reconsider the relationship between the severity of COVID-19 clinical symptoms and the patient's mortality.

Impact of the level of adherence to the Mediterranean Diet on blood pressure: A systematic review and meta-analysis of observational studies.

BACKGROUND: High blood pressure (BP) constitutes a common and serious medical condition which is rising globally, and is among preventable factors for cardiovascular, renal, brain and other diseases. Modifiable risk factors of high BP include unhealthy dietary patterns, presence of obesity, excess alcohol consumption and lack of physical activity. Data in regard to the different types of diets show that Mediterranean diet (MD) is associated with healthy levels of BP. In this study we aimed to investigate the impact of the level of adherence to MD in BP. AIMS-METHODS: A systematic literature search (up to 08.2021) in PubMed, Scopus, Embase, Web of Science, Cochrane and Google Scholar databases was conducted, and 54 observational studies were included. RESULTS: Systolic blood pressure (SBP) was found to be lower in the high adherence to MD group SMD: -0.08, (95%CI: -0.15, -0.02) whereas no differences regarding diastolic blood pressure (DBP) were observed between the high and low adherence to MD groups [SMD: -0.07, (95%CI: -0.13, 0.00)]. Mean DBP of all included studies for both high and low adherence groups were in healthy levels (<90 mmHg). CONCLUSIONS: Higher adherence to MD could positively influence SBP, but further research is needed in this field due to the heterogeneous definitions of low/high adherence and the type of studies used (observational).

The Diabetes Eating Problem Survey-Revised (DEPS-R) in a Greek Adult Population with Type 1 Diabetes Mellitus: Model Comparison Supporting a Single Factor Structure.

Type 1 diabetes mellitus (T1DM) patients occasionally develop disordered eating behaviors, leading to insulin manipulation without medical consultation, targeting to achieve weight control. In clinical practice, the Diabetes Eating Problem Survey-Revised Version (DEPS-R) questionnaire has been used to evaluate eating disorders in T1DM patients. This study was conducted to validate the factor structure of the Greek version of DEPS-R using Confirmatory Factor Analysis (CFA), to investigate its reliability and convergent validity in Greek T1DM adults and to compare a single factor DEPS-R model with multiple factor models. Participants were 103 T1DM adults receiving insulin, who responded to DEPS-R. Their anthropometric, biochemical and clinical history data were evaluated. The sample presented good glycemic control and 30.1% scored above the established DEPS-R cut-off score for disturbed eating behavior. CFA results revealed that the data fit well to the factor models. The DEPS-R scale had good reliability and was positively linked to BMI, HbA1c, total daily dose and time in range. Model comparison supported the superiority of the 1-factor model, implying that Greek clinicians and practitioners might not have to consider individualized treatment based on various scores across different subscales but they can adopt a single DEPS-R score for an easy and efficient screening for disordered eating.

Comparison of Premixed Human Insulin 30/70 to Biphasic Aspart 30 in Well-Controlled Patients with Type 2 Diabetes Using Continuous Glucose Monitoring.

AIM: To compare in terms of glycemic variability two premixed insulins, Premixed Human Insulin 30/70 (PHI) and Biphasic Aspart 30 (BiAsp30), using Continuous Glucose Monitoring (CGM) and to estimate the correlation of Glycated Albumin (GA) and Fructosamine (FA) with CGM data. Patients-Data: A total of 36 well-controlled patients with type 2 Diabetes Mellitus (T2DM) underwent 7-day CGM with PHI and subsequently with BiAsp30. GA and FA were measured at the first and last day of each week of CGM. RESULTS: BiAsp30 was associated with lower Average Blood Glucose (ABG) during the 23:00-03:00 period (PHI: 135.08 ± 28.94 mg/dL, BiAsp30: 117.75 ± 21.24 mg/dL, p < 0.001) and the 00:00-06:00 period (PHI: 120.42 ± 23.13 mg/dL, BiAsp30: 111.17 ± 14.74 mg/dL, p = 0.008), as well as with more time below range (<70 mg/dL) (TBR) during the 23:00-03:00 period in the week (PHI: 3.65 ± 5.93%, BiAsp30: 11.12 ± 16.07%, p = 0.005). PHI was associated with lower ABG before breakfast (PHI: 111.75 ± 23.9 mg/dL, BiAsp30: 128.25 ± 35.9 mg/dL, p = 0.013). There were no differences between the two groups in ABG, Time In Range and Time Below Range during the entire 24-h period for 7 days, p = 0.502, p = 0.534, and p = 0.258 respectively, and in TBR for the 00:00-06:00 period p = 0.253. Total daily insulin requirements were higher for BiAsp30 (PHI: 47.92 ± 12.18 IU, BiAsp30: 49.58 ± 14.12 IU, p = 0.001). GA and FA correlated significantly with ABG (GA: r = 0.512, p = 0.011, FA: r = 0.555, p = 0.005). CONCLUSIONS: In well-controlled patients with T2DM, BiAsp30 is an equally effective alternative to PHI.

Impact of the Level of Adherence to Mediterranean Diet on the Parameters of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Observational Studies.

High adherence to the Mediterranean diet (MD) has been associated with a lower prevalence of Metabolic Syndrome (MetS). The present study aimed to investigate the impact of MD adherence on parameters of MetS. A systematic literature search was performed in PubMed, Cochrane Central Registry of Clinical Trials (CENTRAL), Scopus, EMBASE, Web of Science and Google Scholar databases. Observational studies that recorded adherence to MD and components/measures of the MetS, such as waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG), high-density lipoprotein (HDL) cholesterol and triglycerides (TG), were included in this study. A total of 58 studies were included in our study. WC and TG were significantly lower in the high adherence MD group (SMD: -0.20, (95%CI: -0.40, -0.01), SMD: -0.27 (95%CI: -0.27, -0.11), respectively), while HDL cholesterol was significantly higher in the same group (SMD: -0.28 (95%CI: 0.07, 0.50). There was no difference in FBG and SBP among the two groups (SMD: -0.21 (95%CI: -0.54, 0.12) & SMD: -0.15 (95%CI: -0.38, 0.07), respectively). MD may have a positive impact on all parameters of MetS. However, further research is needed in this field.

Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial.

AIM: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 µg/day for one year in patients with diabetic neuropathy (DN). PATIENTS AND METHODS: In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score). RESULTS: B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, p < 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p < 0.001, p = 0.002, p < 0.0001, p < 0.000, p < 0.0001, p < 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p < 0.0001, and p < 0.0001, respectively). CONCLUSIONS: The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.

Efficacy and Safety of the Combination of Superoxide Dismutase, Alpha Lipoic Acid, Vitamin B12, and Carnitine for 12 Months in Patients with Diabetic Neuropathy.

AIM: To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN). PATIENTS-METHODS: In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group, n = 43), or placebo (n = 42) for 12 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured the vibration perception threshold (BIO), and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Pain (PS) and quality of life (QL) questionnaires were administered. RESULTS: At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group (p <0.001, p <0.001, p <0.001, p <0.001, p = 0.027, p = 0.031, and p <0.001 respectively), whereas the inplacebo group MCR (mean circular resultant) and PAIN deteriorated (p <0.001, p <0.001). The changes in MNSIQ, QL, SNCV, BIO, and PAIN differed significantly between groups (p <0.001, p <0.001, p = 0.031, p <0.001, and p <0.001 respectively). CONCLUSIONS: The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.

Impact of Crocus Sativus L. on Metabolic Profile in Patients with Diabetes Mellitus or Metabolic Syndrome: A Systematic Review.

BACKGROUND: Experimental studies demonstrated a positive effect of administration of Crocus sativus L. (saffron) and its bioactive ingredients on metabolic profile through their antioxidant capacity. PURPOSE: To determine if the use of saffron in humans is beneficial to patients with diabetes mellitus (DM) or metabolic syndrome (MS). METHODS: This systematic review includes 14randomized control trials that investigated the impact of saffron administration and its bioactive ingredient crocin on the metabolic profile of patients with DM, MS, prediabetes, and coronary artery disease. We documented the following clinical outcomes: fasting blood glucose (FBG), glycated haemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, systolic, and diastolic blood pressure. RESULTS: Eight studies examined the efficacy of saffron in patients with DM, four with the metabolic syndrome, one with prediabetes and one with coronary artery disease. A favorable effect on FBG was observed. The results regarding blood lipids and blood pressure were inconclusive in the current review. CONCLUSIONS: According to the available limited evidence, saffron may have a favorable effect on FBG. Many of the studies in the reviewed literature are of poor quality, and more research is needed in this direction to confirm and establish the above findings.

Mediterranean Diet Adherence is Associated with Lower Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents.

Dietary patterns may have a role in the prevention of functional gastrointestinal disorders (FGIDs). The current study aimed at examining the association between FGIDs and adherence to the Mediterranean diet (MD) among elementary school children (ESC), as well as high school students (HSS). In a prospective cohort study, data from 1116 subjects (387 ESC and 448 HSS) aged 6-18 years were collected. FGID identification was based on the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III (QPGS-RIII). Adherence to the MD was assessed using the KIDMED Index. Full data were available on 835/1116 questionnaires. Based on Rome III criteria, 184/835 participants (22%) were identified with FGID (122 (66%) with functional constipation (FC)). The prevalence of FGIDs (p = 0.001) was significantly higher in HSS (13-18 years). The KIDMED score in the cohort was 5.7 ± 2.5. Subjects with FGIDs demonstrated a lower KIDMED score compared to the non-FGID group, both in the cohort, as well as in the ESC and HSS subgroups (FGID vs. non-FGID: p = 0.001, p = 0.007, and p = 0.032, respectively). Multivariate analysis highlighted the KIDMED score as a significant predictor of FGIDs and FC after controlling for the age subgroups. We conclude that good adherence to the MD is associated to lower prevalence of FGIDs, while adolescents display a significantly higher prevalence of FGIDs compared to children.