Beau's Lines and COVID-19; A Systematic Review on Their Association.

BACKGROUND: Beau's lines are transverse grooves in the nail plate that result from transient interruption of the growth of the proximal nail matrix after severe disease. The aim of this study is to systematically report all evidence on the association of Beau's lines with COVID-19 infection or vaccination against COVID-19. METHODS: PubMed and Scopus databases were searched up to January 2024 for articles reporting Beau's lines associated with COVID-19 infection or vaccination for COVID-19. PROSPERO ID: CRD42024496830. RESULTS: PubMed search identified 299 records while Scopus search identified 18 records. After screening the bibliography, nine studies including 35 cases were included in our systematic review. The studies were reported from different areas around the world. Included studies documented Beau's lines following COVID-19 vaccination (two studies) or after COVID-19 infection (seven studies). High variability was recorded in onset and resolution times among included cases, averaging 3 months and 6 months after COVID-19 infection, respectively. In the two studies reporting Beau's lines after vaccination, onset was at 7 days and 6 weeks and resolution occurred after 8 and 17 weeks, respectively. CONCLUSIONS: To the best of our knowledge, this is the first systematic review reporting the association of Beau's lines with COVID-19 infection and vaccination. Severe immune response can result in the formation of these nail disorders. Of importance, Beau's lines represent a potential indicator of prior severe COVID-19 infection or vaccination for COVID-19, as well as a sign of long COVID-19 syndrome.

Unravelling Beau's Lines as a Potential Indicator of Severe Immune Response in Covid-19 and Reinfection.

Background: Beau's lines are transverse grooves in the nail plate that result from transient interruption of the growth of the proximal nail matrix. These rare nail disorders can be triggered mostly by infections or systemic diseases. Case Description: We describe a 65-year-old man who presented with nail changes on all fingernails. The patient, a non-smoker with no medication history, had severe immune responses during two hospitalisations, 9 and 4 months ago, for COVID-19. Both hospitalisations were accompanied by markedly elevated interleukin-6 levels, and treatment with tocilizumab on top of dexamethasone was required. The present examination revealed Beau's lines which were associated with both prior COVID-19 infections. Conclusions: Although nail changes look harmless, seeking Beau's lines during the physical examination might indicate past severe COVID-19 infection and a higher probability for reinfection and rehospitalisation. LEARNING POINTS: Beau's lines are grooves that traverse the nail plate horizontally.The appearance of Beau's lines may indicate past severe COVID-19 infection.Beau's lines can potentially indicate a higher probability of COVID-19 reinfection and rehospitalisation.

The effect of SGLT2 inhibitors, GLP1 agonists, and their sequential combination on cardiometabolic parameters: A randomized, prospective, intervention study.

BACKGROUND: Pulse wave velocity (PWV) and augmentation index (AIx) are indices used to assess arterial stiffness. We aim to compare the effect of empagliflozin, liraglutide and their sequential combination on arterial stiffness indices in patients with type 2 diabetes (T2D). METHODS: This was a randomized single blind study evaluating the effect of empagliflozin vs liraglutide in adult patients with T2D. Patients were randomized to liraglutide titrated gradually to 1.8 mg or empagliflozin 25 mg in 1:1 ratio. Three months later empagliflozin was added to the liraglutide group, and liraglutide was added to the empagliflozin group. Patients were assessed with non-invasive tests for arterial stiffness (i.e., carotid-femoral PWV and AIx of aortic pressure) at baseline, 3-month and 9-month visits (final visit was extended for 3 months from the initial design due to Covid 19 pandemic). The primary outcome was the between-group difference of PWV change (ΔPWV) and ΔAIx at 3 months. Secondary outcomes included the between-group difference of ΔPWV and ΔAIx at 9 months, as well as the ΔPWV and ΔAIx between baseline and 9-month visit when total study population was assessed. RESULTS: A total of 62 patients with T2D (30 started liraglutide; 32 empagliflozin, mean age 63 years, 25 % with established cardiovascular disease) participated in the study. We failed to show any significant between-group differences of ΔPWV and ΔΑΙx at 3 and 9 months, as well as between-group difference of ΔPWV and ΔAIx for the total study population between baseline and 9-month visit. In contrast, systemic vascular resistance and lipoprotein(a) levels improved, showing better results with liraglutide than empagliflozin. Favorable effects were also observed on body weight, body mass index, body and visceral fat, blood pressure, HbA1c, and uric acid levels. CONCLUSION: No evidence of a favorable change in arterial stiffness indices was seen with empagliflozin or liraglutide or their combination in this study. Well-designed powerful studies are needed to address any potential effects on arterial stiffness in selected populations.

Outdoor air quality and human health: An overview of reviews of observational studies.

The epidemiological evidence supporting putative associations between air pollution and health-related outcomes continues to grow at an accelerated pace with a considerable heterogeneity and with varying consistency based on the outcomes assessed, the examined surveillance system, and the geographic region. We aimed to evaluate the strength of this evidence base, to identify robust associations as well as to evaluate effect variation. An overview of reviews (umbrella review) methodology was implemented. PubMed and Scopus were systematically screened (inception-3/2020) for systematic reviews and meta-analyses examining the association between air pollutants, including CO, NOX, NO2, O3, PM10, PM2.5, and SO2 and human health outcomes. The quality of systematic reviews was evaluated using AMSTAR. The strength of evidence was categorized as: strong, highly suggestive, suggestive, or weak. The criteria included statistical significance of the random-effects meta-analytical estimate and of the effect estimate of the largest study in a meta-analysis, heterogeneity between studies, 95% prediction intervals, and bias related to small study effects. Seventy-five systematic reviews of low to moderate methodological quality reported 548 meta-analyses on the associations between outdoor air quality and human health. Of these, 57% (N = 313) were not statistically significant. Strong evidence supported 13 associations (2%) between elevated PM2.5, PM10, NO2, and SO2 concentrations and increased risk of cardiorespiratory or pregnancy/birth-related outcomes. Twenty-three (4%) highly suggestive associations were identified on elevated PM2.5, PM10, O3, NO2, and SO2 concentrations and increased risk of cardiorespiratory, kidney, autoimmune, neurodegenerative, cancer or pregnancy/birth-related outcomes. Sixty-seven (12%), and 132 (24%) meta-analyses were graded as suggestive, and weak, respectively. Despite the abundance of research on the association between outdoor air quality and human health, the meta-analyses of epidemiological studies in the field provide evidence to support robust associations only for cardiorespiratory or pregnancy/birth-related outcomes.

Dose-related meta-analysis for Omega-3 fatty acids supplementation on major adverse cardiovascular events.

BACKGROUND & AIMS: Omega-3 supplements are widely used for cardiovascular (CV) protection. We performed an updated meta-analysis for omega-3 and CV outcomes. METHODS: Random-effects meta-analysis including double-blind RCTs with duration ≥1 year, evaluating omega-3 supplements in 4 a priori defined categories (<1, 1, 2, ≥3 of 1g capsules/day) on all-cause mortality, cardiac death, myocardial infarction and stroke, reporting the relative risk (RR) as the measure of interest. Complementary approaches were Trial Sequential Analysis (TSA) and sensitivity analyses for triglycerides, prevention setting, intention-to-treat analysis, eicosapentaenoic acid (EPA), sample size, statin use and study duration. RESULTS: Nineteen randomized controlled trials (RCTs) with 97,709 participants were included. Omega-3 supplements were not statistically significantly associated with reduced all-cause mortality, cardiac death, MI, or stroke, with the exception of reduced cardiac mortality only for the equivalent dose of 2 capsules/day (RR 0.55, 95%CI 0.33, 0.90, p = 0.0169, I2 = 0%). TSA reached the required information size only for the lower doses regarding all-cause and cardiac mortality, where they show no significant association. Meta-regression on EPA dose, as well as the majority of sensitivity analyses did not show any statistically significant association. CONCLUSION: Compared to the robust evidence for low doses, higher doses and particularly for the unique type of omega-3 icosapent ethyl ester should be further addressed.

Difference on Glucose Profile From Continuous Glucose Monitoring in People With Prediabetes vs. Normoglycemic Individuals: A Matched-Pair Analysis.

INTRODUCTION: Comprehensive characteristics of the glycemic profile for prediabetes derived by continuous glucose monitoring (CGM) are unknown. We evaluate the difference of CGM profiles between individuals with prediabetes and normoglycemic individuals, including the response to oral glucose tolerance test (OGTT). METHODS: Individuals with prediabetes matched for age, sex, and BMI with normoglycemic individuals were instructed to use professional CGM for 1 week. OGTT was performed on the second day. The primary outcomes were percentages of glucose readings time below range (TBR): <54 or <70 mg/dL, time in range (TIR): 70 to 180 mg/dL, and time above range (TAR): >180 or >250 mg/dL. Area under the curve (AUC) was calculated following the OGTT. Glucose variability was depicted by coefficient of variation (CV), SD, and mean amplitude of glucose excursion (MAGE). Wilcoxon sign-ranked test, McNemar mid P-test and linear regression models were employed. RESULTS: In all, 36 participants (median age 51 years; median body mass index [BMI] = 26.4 kg/m2) formed 18 matched pairs. Statistically significant differences were observed for 24-hour time in range (TIR; median 98.5% vs. 99.9%, P = .013), time above range (TAR) >180 mg/dl (0.4% vs. 0%, P = .0062), and 24-hour mean interstitial glucose (113.8 vs. 108.8 mg/dL, P = .0038) between people with prediabetes compared to normoglycemic participants. Statistically significant differences favoring the normoglycemic group were found for glycemic variability indexes (median CV 15.2% vs. 11.9%, P = .0156; median MAGE 44.3 vs. 33.3 mg/dL, P = 0.0043). Following OGTT, the AUC was significantly lower in normoglycemic compared to the prediabetes group (median 18615.3 vs. 16370.0, P = .0347 for total and 4666.5 vs. 2792.7, P = .0429 for incremental 2-hour post OGTT). CONCLUSION: Individuals with prediabetes have different glucose profiles compared to normoglycemic individuals. CGM might be helpful in individuals with borderline glucose values for a more accurate reclassification.

High-density lipoprotein cholesterol: A marker of COVID-19 infection severity?

BACKGROUND AND AIMS: To systematically address all the relevant evidence of the association between high-density lipoprotein cholesterol (HDL-C) and COVID-19 infection. METHODS: We searched PubMed, PubMed Central and medRxiv databases (up to May 2021) for studies related to HDL-C and COVID-19 infection. A qualitative synthesis of published prospective and retrospective studies for the role of low HDL-C levels on COVID-19 infection severity was performed. RESULTS: Thirty-three studies (6 prospective, 27 retrospective) including 11,918 COVID-19 patients were eligible for the systematic review. Twelve studies compared HDL-C levels on admission in COVID-19 patients with healthy controls. In these 12 studies, COVID-19 patients had significantly lower HDL-C levels on admission compared with that of healthy controls. Twenty-eight studies observed the HDL-C levels among COVID-19 diagnosed patients, to establish the role of low HDL-C values in the prognosis of the infection. Twenty-four studies showed a correlation between low HDL-C levels with disease severity, while only 4 studies showed no association. CONCLUSIONS: Low HDL-C levels should be added in the list of the others well-known risk factors for COVID-19 severity.

Adherence to Mediterranean Diet and Cognitive Abilities in the Greek Cohort of Epirus Health Study.

The Mediterranean diet is commonly proposed as a major modifiable protective factor that may delay cognitive impairment in the elderly. The aim of the study was to investigate the cross-sectional association of adherence to the Mediterranean diet with cognitive abilities in a younger Greek population. A total of 1201 healthy adults aged 21-77 years (mean: 47.8) from the Epirus Health Study cohort were included in the analysis. Adherence to the Mediterranean diet was measured using the 14-point Mediterranean Diet Adherence Screener (MEDAS) and cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. Statistical analysis was performed using multiple linear regression models adjusted for age, sex, education, body mass index, smoking status, alcohol consumption and physical activity. Overall, no association was found between the MEDAS score and cognitive tests, which could be explained by the young mean age and high level of education of the participants. Future studies should target young and middle-aged individuals to gain further understanding of the association between Mediterranean diet and cognition in this age group.

Prevalence and Determinants of Sex-Specific Dietary Supplement Use in a Greek Cohort.

We describe the profile of dietary supplement use and its correlates in the Epirus Health Study cohort, which consists of 1237 adults (60.5% women) residing in urban north-west Greece. The association between dietary supplement use and demographic characteristics, lifestyle behaviors, personal medical history and clinical measurements was assessed using logistic regression models, separately for women and men. The overall prevalence of dietary supplement use was 31.4%, and it was higher in women (37.3%) compared to men (22.4%; p-value = 4.2-08). Based on multivariable logistic regression models, dietary supplement use in women was associated with age (positively until middle-age and slightly negatively afterwards), the presence of a chronic health condition (OR = 1.71; 95% CI, 1.18-2.46), lost/removed teeth (OR = 0.52; 95% CI, 0.35-0.78) and diastolic blood pressure (OR per 5 mmHg increase =0.84; 95% CI, 0.73-0.96); body mass index and worse general health status were borderline inversely associated. In men, dietary supplement use was positively associated with being employed (OR = 2.53; 95% CI, 1.21-5.29). A considerable proportion of our sample used dietary supplements, and the associated factors differed between women and men.

Awareness, knowledge and trust in the Greek authorities towards COVID-19 pandemic: results from the Epirus Health Study cohort.

BACKGROUND: To assess the level of knowledge and trust in the policy decisions taken regarding the coronavirus disease (COVID-19) pandemic among Epirus Health Study (EHS) participants. METHODS: The EHS is an ongoing and deeply-phenotyped prospective cohort study that has recruited 667 participants in northwest Greece until August 31st, 2020. Level of knowledge on coronavirus (SARS-CoV-2) transmission and COVID-19 severity was labeled as poor, moderate or good. Variables assessing knowledge and beliefs towards the pandemic were summarized overall and by sex, age group (25-39, 40-49, 50-59, ≥60 years) and period of report (before the lifting of lockdown measures in Greece: March 30th to May 3rd, and two post-lockdown time periods: May 4th to June 31st, July 1st to August 31st). A hypothesis generating exposure-wide association analysis was conducted to evaluate the associations between 153 agnostically-selected explanatory variables and participants' knowledge. Correction for multiple comparisons was applied using a false discovery rate (FDR) threshold of 5%. RESULTS: A total of 563 participants (49 years mean age; 60% women) had available information on the standard EHS questionnaire, the clinical and biochemical measurements, and the COVID-19-related questionnaire. Percentages of poor, moderate and good knowledge status regarding COVID-19 were 4.5, 10.0 and 85.6%, respectively. The majority of participants showed absolute or moderate trust in the Greek health authorities for the management of the epidemic (90.1%), as well as in the Greek Government (84.7%) and the official national sources of information (87.4%). Trust in the authorities was weaker in younger participants and those who joined the study after the lifting of lockdown measures (p-value≤0.001). None of the factors examined was associated with participants' level of knowledge after correction for multiple testing. CONCLUSIONS: High level of knowledge about the COVID-19 pandemic and trust in the Greek authorities was observed, possibly due to the plethora of good quality publicly available information and the timely management of the pandemic at its early stages in Greece. Information campaigns for the COVID-19 pandemic should be encouraged even after the lifting of lockdown measures to increase public awareness.

Type 2 Diabetes and Cancer: An Umbrella Review of Observational and Mendelian Randomization Studies.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of developing several common cancers, but it is unclear whether this association is causal. We aimed to summarize the evidence on T2DM and cancer and evaluate the validity of associations from both observational and Mendelian randomization (MR) studies. METHODS: We performed an umbrella review of the evidence across meta-analyses of observational studies that examined associations of T2DM with risk of developing or dying from site-specific cancers, and MR studies that explored the potential causal association of T2DM and associated biomarkers with cancer risk. RESULTS: We identified eligible observational meta-analyses that assessed associations between T2DM and cancer incidence for 18 cancer sites, cancer mortality for seven sites, and cancer incidence or mortality for four sites. Positive associations between T2DM and six cancers reached strong or highly suggestive evidence. We found eight MR studies assessing the association of genetically predicted T2DM and seven and eight studies assessing the association of genetically predicted fasting insulin or fasting glucose concentrations, respectively, upon site-specific cancers. Positive associations were found between genetically predicted T2DM and fasting insulin and risk of six cancers. There was no association between genetically predicted fasting plasma glucose and cancer except for squamous cell lung carcinoma. CONCLUSIONS: We found robust observational evidence for the association between T2DM and colorectal, hepatocellular, gallbladder, breast, endometrial, and pancreatic cancers. IMPACT: Potential causal associations were identified for genetically predicted T2DM and fasting insulin concentrations and risk of endometrial, pancreas, kidney, breast, lung, and cervical cancers.

Omega-3 supplementation and cardiovascular disease: formulation-based systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Omega-3 supplements are popular for cardiovascular disease (CVD) prevention. We aimed to assess the association between dose-specific omega-3 supplementation and CVD outcomes. DESIGN: We included double-blind randomised clinical trials with duration ≥1 year assessing omega-3 supplementation and estimated the relative risk (RR) for all-cause mortality, cardiac death, sudden death, myocardial infarction and stroke. Primary analysis was a stratified random-effects meta-analysis by omega-3 dose in 4 a priori defined categories (<1, 1, 2, ≥3 of 1 g capsules/day). Complementary approaches were trial sequential analysis and sensitivity analyses for triglycerides, prevention setting, intention-to-treat analysis, eicosapentaenoic acid, sample size, statin use, study duration. RESULTS: Seventeen studies (n=83 617) were included. Omega-3 supplementation as ≤1 capsule/day was not associated with any outcome under study; futility boundaries were crossed for all-cause mortality and cardiac death. For two capsules/day, we observed a statistically significant reduction of cardiac death (n=3, RR 0.55, 95% CI 0.33 to 0.90, I2=0%); for ≥3 capsules/day we observed a statistically significant reduction of cardiac death (n=3, RR 0.82, 95% CI 0.68 to 0.99, I2=0%), sudden death (n=1, RR 0.70, 95% CI 0.51 to 0.97) and stroke (n=2, RR 0.74, 95% CI 0.57 to 0.95, I2=0%). CONCLUSION: Omega-3 supplementation at <2 1 g capsules/day showed no association with CVD outcomes; this seems unlikely to change from future research. Compared with the robust scientific evidence available for low doses, the evidence for higher doses (2-4 1 g capsules/day) is weak. The emerging postulated benefit from high-dose supplementation needs replication and further evaluation as to the precise formulation and indication.

Is brucellosis a great mimic of tuberculosis? A case report.

Tuberculosis (TB) can manifest prolonged fever or fever of unknown origin, especially when it is located extrapulmonary. We report a case of disseminated TB complicated by iliac bone osteolysis and a gluteal abscess in a 75-year-old female patient with fever and bone marrow dysplasia. Diagnosis of TB was made despite transient false-positive high-titer agglutination tests and ELISA antibodies to Brucella. The case presented shows that in a highly suggestive case of TB, positive agglutination tests or ELISA antibodies to Brucella should be interpreted with caution, and repeated testing should be performed to assess their persistence and fluctuation over time.

Reduced Serum Vitamin D Levels Are Associated with Insulin Resistance in Patients with Obstructive Sleep Apnea Syndrome.

Background and objectives: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular and metabolic risk factors, such as insulin resistance. Furthermore, OSAS has been associated with decreased levels of vitamin D (Vit D). The aim of the study was to assess the association between Vit D levels (expressed as 25(OH)D serum levels) and insulin resistance in patients with OSAS. Materials and Methods: Serum 25(OH)D levels were measured in consecutive subjects who had undergone polysomnography and pulmonary function testing. OSAS patients were divided into those with (homeostatic model assessment [HOMA-IR] ≥ 2) and without insulin resistance (HOMA-IR < 2). Results: Overall, 92 patients (81 males) were included in the study. OSAS patients with insulin resistance significantly differed from those without insulin resistance in terms of the body-mass index (BMI) (36.3 ± 5.8 compared to 32 ± 5.6 kg/m2, respectively, p = 0.001), apnoea-hypopnoea index (AHI) (57.4 ± 28.9 compared to 40.9 ± 27.9 events/h, respectively, p = 0.009) and indices of hypoxia during sleep. Patients with OSAS and insulin resistance had lower levels of serum 25 (OH) D compared with OSAS but without insulin resistance (19.3 ± 11.5 vs 26.7 ± 12.2 ng/mL, respectively, p = 0.005). Regression analysis demonstrated a negative association of 25(OH)D levels (ß = -0.048, odds ratio [OR]: 0.953, 95% confidence interval [CI]: 0.913-0.995, p = 0.030) and a positive association of BMI (ß = 0.110, OR: 1.116, 95% CI: 1.007-1.237, p = 0.036) with insulin resistance. Conclusions: Vit D insufficiency was significantly more frequent among OSAS patients with insulin resistance. Both low 25(OH)D levels and high BMI were associated with the risk of insulin resistance in this population.

Atherogenic dyslipidemia increases the risk of incident diabetes in statin-treated patients with impaired fasting glucose or obesity.

AIM: To investigate which metabolic factors increase the risk of incident diabetes (T2D) in statin-treated patients. METHODS: A retrospective study conducted in Greece including 1241 consecutive individuals with dyslipidemia attending a lipid clinic for ≥3 years. After defining associations with incident T2D, we assessed the risk of new-onset T2D based on the presence of impaired fasting glucose (IFG), atherogenic dyslipidemia, and overweight/obesity. RESULTS: After excluding 166 patients with baseline T2D and 193 subjects taking lipid-lowering therapy at the baseline visit, 882 participants were included in the study. Eleven percent (n=94) developed T2D during their follow-up (median 6 years; IQR: 4-10). Baseline patients' age (OR: 1.05; 95% CI: 1.02-1.08, p<0.01), family history of diabetes (OR: 3.58; 95% CI: 1.86-6.91, p<0.01), IFG (OR: 6.56; 95% CI: 3.53-12.12, p<0.01), overweight/obesity (OR: 2.65; 95% CI: 1.39-5.05, p<0.01), atherogenic dyslipidemia (OR: 3.27; 95% CI: 1.50-7.15, p<0.01), and treatment with high-intensity statins (OR: 3.51; 95% CI: 1.89-6.51, p<0.01) were independently associated with increased risk of T2D in statin-treated patients. Among the IFG subjects, atherogenic dyslipidemia (OR: 3.44; 95% CI: 1.31-9.04, p=0.01) and overweight/obesity (OR: 2.54; 95% CI: 1.14-5.66, p<0.05) independently increased the risk of T2D. Among the overweight/obese ones, atherogenic dyslipidemia independently increased the risk of T2D (adjusted OR: 5.60; 95% CI: 2.19-14.30, p<0.01). CONCLUSION: Atherogenic dyslipidemia appears to be an independent risk factor for new-onset T2D in statin-treated patients, while IFG, overweight/obesity and family history of diabetes remain risk factors for new-onset T2D in this group.

IS MESENTERIC PANNICULITIS A SIGN FOR AUTOIMMUNE DIABETES IN ADULTS?

OBJECTIVE: Mesenteric panniculitis (MP) and sclerosing mesenteritis is an umbrella term used to describe a rare, chronic, and frequently benign fibrosing inflammatory disease that affects the adipose tissue of the mesentery. The diagnosis is usually based on imaging (computed tomography [CT] or magnetic resonance imaging) findings and is confirmed by biopsy. We report the unusual case of a patient with MP with typical CT findings and diabetes mellitus (DM). METHODS: A 48-year-old male presented for symptomatic new onset DM. An abdominal CT scan revealed a well-defined mesenteric mass compatible with MP. The combination of insulin degludec and sitagliptin/metformin resulted in a decrease of HbA1c; however, this was followed by a subsequent gradual increase in HbA1c and positive glutamic acid decarboxylase auto-antibodies. RESULTS: The patient developed auto-immune DM that was confirmed by the presence of auto-antibodies. CONCLUSION: Panniculitis has been infrequently reported in patients with type 2 DM. This is the first report of a patient with MP correlated with auto-immune DM. The possible pathophysiologic mechanisms are discussed.