The effect of SGLT2 inhibitors and GLP1 receptor agonists on arterial stiffness: A meta-analysis of randomized controlled trials.

BACKGROUND: Pulse wave velocity (PWV) and augmentation index (AIx) are indices used to assess arterial stiffness. We evaluated the effect of sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) on arterial stiffness indices. METHODS: We searched PubMed (up to January 2024) for RCTs assessing the effect of SGLT2i or GLP1-RA on arterial stiffness with reporting outcomes PWV and AIx. Effect sizes of the included studies were expressed as weighted mean difference (WMD) and 95 % confidence interval. Subgroup analyses were performed based on comparator (placebo vs. active comparator), design (RCT vs. crossover), population (diabetic vs. all) and blindness (yes vs. no). RESULTS: A total of 19 studies (SGLT2i, 12 studies; GLP1-RA, 5 studies; SGLT2i/GLP1-RA combination, 2 studies) assessing 1212 participants were included. We did not find any statistically significant association between GLP1-RA or SGLT2i and PWV or AIx. None of the subgroup analyses showed any statistically significant result. CONCLUSION: No evidence of a favorable change in arterial stiffness indices (PWV, AIx) was found following the administration of SGLT2i or GLP1-RA.

The effect of rosuvastatin alone or in combination with fenofibrate or omega-3 fatty acids on lipoprotein(a) levels in patients with mixed hyperlipidemia.

Introduction: Lipoprotein(a) [Lp(a)] is a strong, genetically determined, pathogenetic factor of atherosclerotic cardiovascular disease (ASCVD). The aim of this post-hoc analysis was to compare the effect of hypolipidemic treatment on Lp(a) levels of patients with mixed hyperlipidemia. Material and methods: We previously randomized patients with mixed hyperlipidemia (low-density lipoprotein [LDL-C] > 160 mg/dl and triglycerides > 200 mg/dl) to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or omega-3 fatty acids 2 g/day (RΩ group, n = 30). In the present post-hoc analysis, we included only the patients whose Lp(a) levels were assessed (16, 16 and 15 in the R, RF and RΩ groups, respectively). Lipid profile and Lp(a) were measured at baseline and after 3 months of treatment. Results: Significant reductions in total cholesterol, LDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C) and triglyceride levels were observed in all groups. A significant increase in Lp(a) levels was noted in the R (p = 0.017) and RF (p = 0.029) groups, while no significant difference was seen in the RΩ group (p = NS). Regarding Lp(a) elevations, no differences were found between groups. In the R group, a strong negative correlation between the changes in Lp(a) and LDL-C (r = -0.500, p = 0.049) was observed, while a significant negative correlation between the changes in Lp(a) and triglycerides (r = -0.531, p = 0.034) was noted in the RF group. Conclusions: Rosuvastatin and/or fenofibrate treatment increases Lp(a) levels in patients with mixed hyperlipidemia. Novel therapies should target Lp(a) level reduction to decrease the residual ASCVD risk in patients with mixed hyperlipidemia.

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.

Pathophysiological Mechanisms and Clinical Associations of Non-Alcoholic Fatty Pancreas Disease.

Non-Alcoholic Fatty Pancreas disease (NAFPD), characterized by fat accumulation in pancreatic tissue, is an emerging clinical entity. However, the clinical associations, the underlying molecular drivers, and the pathophysiological mechanisms of NAFPD have not yet been characterized in detail. The NAFPD spectrum not only includes infiltration and accumulation of fat within and between pancreatic cells but also involves several inflammatory processes, dysregulation of physiological metabolic pathways, and hormonal defects. A deeper understanding of the underlying molecular mechanisms is key to correlate NAFPD with clinical entities including non-alcoholic fatty liver disease, metabolic syndrome, diabetes mellitus, atherosclerosis, as well as pancreatic cancer and pancreatitis. The aim of this review is to examine the pathophysiological mechanisms of NAFPD and to assess the possible causative/predictive risk factors of NAFPD-related clinical syndromes.

High-density lipoprotein cholesterol and multiple myeloma: A systematic review and meta-analysis.

Background and aims: To systematically investigate all relevant evidence on the association between high-density lipoprotein cholesterol (HDL-C) and multiple myeloma (MM). Methods: We searched PubMed and Cochrane library databases (up to 20 September 2022) for studies with evidence on HDL-C in patients with MM. A qualitative synthesis of published prospective and retrospective studies for the role of HDL-C and other lipid profile parameters in MM was performed. Additionally, a meta-analysis on HDL-C mean differences (MD) between MM cases and controls was performed. Results: Fourteen studies (3 prospective, 11 retrospective) including 895 MM patients were eligible for this systematic review. Ten studies compared HDL-C levels in MM patients with healthy controls. In these 10 studies (n = 17,213), pooled analyses showed that MM patients had significantly lower HDL-C levels compared to healthy controls (MD: -13.07 mg/dl, 95% CI: -17.83, -8.32, p < 0.00001). Regarding secondary endpoints, total cholesterol (TC) (MD: -22.19 mg/dl, 95% CI: -39.08, -5.30) and apolipoprotein A-I (apoA-I) (-40.20 mg/dl, 95% CI: -55.00, -25.39) demonstrated significant decreases, while differences in low-density lipoprotein cholesterol (LDL-C) (MD: -11.33 mg/dl, 95% CI: -36.95, 14.30) and triglycerides (MD: 9.93 mg/dl, 95% CI: -3.40, 23.26) were not shown to be significant. Conclusions: HDL-C, as well as TC and apoA-I, levels are significantly decreased in MM. Hence, lipid profile parameters should be taken into account when assessing such patients.

Statins in Children with Neurofibromatosis Type 1: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Statins, apart from their plasma-cholesterol-lowering ability, exert several pleiotropic effects, making them a potential treatment for other diseases. Animal studies have showed that statins, through the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, can affect the Ras/MAPK pathway, thus providing impetus to examine the efficacy of statins in the pediatric population with neurofibromatosis type 1 (NF1). We aimed to systematically address all relevant evidence of statin treatment in children with NF1. METHODS: We searched PubMed and Cochrane Library resources up to 2 June 2023 for randomized controlled trials (RCTs) written in English and evaluating statins versus placebo in children with NF1 (PROSPERO registration number: CRD42023439424). RESULTS: Seven RCTs were suitable to be included in this qualitative synthesis, with a total participation of 336 children with NF1. The duration of the studies ranged from 12 to 52 weeks. The mean age of the pediatric population was 10.9 years old. Three studies investigated the role of simvastatin, while four studies examined lovastatin. According to our analysis, neither simvastatin nor lovastatin improved cognitive function, full-scale intelligence, school performance, attention problems, or internalizing behavioral problems when compared with placebo in children with NF1. Statins were well tolerated in all included RCTs. CONCLUSION: Although safe, current evidence demonstrates that statins exert no beneficial effect in cognitive function and behavioral problems in children with NF1.

Lipoprotein(a), Interleukin-6 inhibitors, and atherosclerotic cardiovascular disease: Is there an association?

Background and aims: Lipoprotein(a) [Lp(a)] and interleuking-6 (IL-6), an inflammation biomarker, have been established as distinct targets of the residual atherosclerotic cardiovascular disease (ASCVD) risk. We aimed to investigate the association between them, and the potential clinical implications in ASCVD prevention. Methods: A literature search was conducted in PubMed until December 31st, 2022, using relevant keywords. Results: Elevated lipoprotein(a) [Lp(a)] levels constitute the most common inherited lipid disorder associated with ASCVD. Although Lp(a) levels are mostly determined genetically by the LPA gene locus, they may be altered by acute conditions of stress and chronic inflammatory diseases. Considering its resemblance with low-density lipoproteins, Lp(a) is involved in atherosclerosis, but it also exerts oxidative, thrombotic, antifibrinolytic and inflammatory properties. The cardiovascular efficacy of therapies lowering Lp(a) by >90% is currently investigated. On the other hand, interleukin (IL)-1b/IL-6 pathway also plays a pivotal role in atherosclerosis and residual ASCVD risk. IL-6 receptor inhibitors [IL-6(R)i] lower Lp(a) by 16-41%, whereas ongoing trials are investigating their potential anti-atherosclerotic effect. The Lp(a)-lowering effect of IL-6(R)i might be attributed to the inhibition of the IL-6 response elements in the promoter region of the LPA gene. Conclusions: Although the effect of IL-6(R)i on Lp(a) levels is inferior to that of available Lp(a)-lowering therapies, the dual effect of the former on both inflammation and apolipoprotein (a) synthesis may prove of equal or even greater significance when it comes ASCVD outcomes. More trials are required to establish IL-6(R)i in ASCVD prevention and elucidate their interplay with Lp(a) as well as its clinical significance.

The Effect of Statins on the Incidence and Prognosis of Bladder Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Statins are widely used due to their ability to lower plasma cholesterol and offer protection from the effects of atherosclerosis. However, their role in urology and specifically bladder cancer remains unclear. We aimed to systematically address this issue in the literature and determine any possible effects of statin therapy on bladder cancer. METHODS: We searched MEDLINE (PubMed) and Cochrane Library databases for records up to 26 March 2023, for studies evaluating the effects of statins on urinary bladder cancer (UBC). We included all randomized controlled trials (RCTs), cohorts, and case-control studies that were conducted on the adult population. PROSPERO registration number: CRD42023407795. RESULTS: Database searches returned 2251 reports, and after thorough investigation and assessment for eligibility, 32 reports were included in the analysis. Of them, 4 were RCTs, 6 were case-control studies, and 22 were cohort studies. Our qualitative analysis demonstrated no association between statin administration and UBC local control, recurrence, survival, or mortality, or between statin administration and bacille Calmette-Guérin (BCG) immunotherapy effectiveness. A meta-analysis of 10 trials revealed a non-significant reduction of 11% in UBC risk among users compared with non-users in RCTs (RR: 0.89, 95% CI 0.68-1.16, p = 0.37) and a non-significant increase of 32% of UBC risk among statin users compared with non-users in the analysis of the cohort studies (RR: 1.32, 95% CI 0.76-2.30, p = 0.33). CONCLUSIONS: Our results provide strong evidence to support the neutral effect of statins on UBC local control, recurrence, survival, and mortality, and on BCG immunotherapy. Our meta-analysis revealed a non-significant effect on UBC risk among statin users when compared with non-users, indicating no statin effect on UBC incidence and overall prognosis.

The Effect of Statins on Ocular Disorders: A Systematic Review of Randomized Controlled Trials.

AIM: Statins have been established in the market not only due to their ability to lower plasma cholesterol levels but also due to their pleiotropic effects. In the literature, there is a controversy regarding the role of statins in ophthalmology. We aimed to systematically address the possible effect of statin therapy on ocular diseases and to identify if there is a beneficial relationship. METHODS: We searched PubMed and Cochrane Library databases up to 31 December 2022 for studies evaluating the effect of statins on ocular diseases. We included all relevant Randomized Control Trials (RCTs) that have been conducted in the adult population. PROSPERO registration number: CRD42022364328. RESULTS: Nineteen RCTs were finally considered eligible for this systematic review, with a total of 28,940 participants. Ten studies investigated the role of simvastatin, suggesting a lack of cataractogenic effect and a possible protective role in cataract formation, retinal vascular diseases, and especially diabetic retinopathy, age-related macular disease progression, and non-infectious uveitis. Four studies investigated lovastatin, showing no cataractogenic effect. Three studies examined atorvastatin, revealing conflicting results regarding diabetic retinopathy. Two studies examined rosuvastatin, indicating a possibly harmful effect on lenses and a significant protective effect on retinal microvasculature. CONCLUSIONS: Based on our findings, we believe that statins have no cataractogenic effect. There are indications that statins may have a protective role against cataract formation, AMD, diabetic retinopathy progression, and non-infectious uveitis. However, our results were insufficient for any robust conclusion. Future RCTs, with large sample sizes, on the current topic are therefore recommended to provide more solid evidence.

Endophthalmitis caused by Enterococcus casseliflavus: a systematic review of literature.

Introduction: Enterococcus casseliflavus is a rare pathogen in human infections, despite being widely distributed in natural environments. This systematic review aims to evaluate the evidence related to endophthalmitis caused by E. casseliflavus. Methods: A thorough search of PubMed, PubMed Central, and Scopus databases was conducted, covering the period up to October 2022. Results: A total of 53 records were identified, with 8 studies reporting a total of 21 cases meeting the inclusion criteria. Among these studies, 7 described isolated case reports, while 1 study described 14 cases. The overall quality of the reports was good, as all articles were determined to have low risk of bias. Vancomycin susceptibility was reported in only one case of isolated case reports, while the remaining cases were all vancomycin resistant. With regard to management, in most cases intravenous ampicillin and linezolid were administered, while only one study reported administration of vancomycin. Conclusions: Ophthalmologists should be aware of the potential for E. casseliflavus to cause endophthalmitis infections and the challenges associated with its intrinsic resistance to vancomycin.

In vitro study on the transmission of multidrug-resistant bacteria from textiles to pig skin.

BACKGROUND: The survival of microorganisms on textiles and specifically on healthcare professionals' (HCP) attire has been demonstrated in several studies. The ability of microorganisms to adhere and remain on textiles for up to hours or days raises questions as to their possible role in transmission from textile to skin via HCP to patients. AIM: To evaluate the presence, survival and transmission of different multidrug-resistant bacteria (MDRB) from HCP attire onto skin. METHODS: Three MDRB [methicillin-resistant Staphylococcus aureus (MRSA); vancomycin-resistant Enterococcus faecium (VRE); carbapenem-resistant Klebsiella pneumoniae, CRKP)] were inoculated on textiles from scrubs (60% cotton-40% polyester) and white coat (100% cotton) at concentrations of 108 colony-forming units (CFU), 105 CFU, and 103 CFU per mL. The inoculation of swatches was divided in time intervals of 1 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, and 6 h. At the end of each period, textiles were imprinted onto pig skins and each skin square was inverted onto three different selective chromogenic media. Growth from the pig skin squares was recorded for the 3 MDRB at the three above concentrations, for the whole length of the 6-h experiment. RESULTS: MRSA was recovered from pig skins at all concentrations for the whole duration of the 6-h study. VRE was recovered from the concentration of 108 CFU/mL for 6 h and from 105 CFU/mL for up to 3 h, while showing no growth at 103 CFU/mL. CRKP was recovered from 108 CFU/mL for 6 h, up to 30 min from 105 CFU/mL and for 1 min from the concentration of 103 CFU/mL. CONCLUSION: Evidence from the current study shows that MRSA can persist on textiles and transmit to skin for 6 h even at low concentrations. The fact that all MDRB can be sustained and transferred to skin even at lower concentrations, supports that textiles are implicated as vectors of bacterial spread.

The Effect of Upadacitinib on Lipid Profile and Cardiovascular Events: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Our aim was to systematically investigate the effect of upadacitinib, an oral JAK-1 selective inhibitor, on lipid profile and cardiovascular disease risk. METHODS: PubMed, PubMed Central and ClinicalTrials.gov databases were searched for relevant randomized controlled trials (RCTs) up to 31 July 2022. We performed a qualitative synthesis of published RCTs to investigate the associations of upadacitinib with lipoprotein changes, along with a quantitative synthesis of MACE and mean lipoprotein changes where there were available data. RESULTS: Nineteen RCTs were eligible for the present systematic review, which included 10,656 patients with a mean age of 51 years and a follow-up period of 12-52 weeks. Increases in low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were noted upon upadacitinib administration (3-48 mg/day) in 15 studies, while the LDL-C:HDL-C ratio remained unchanged. The pooled analyses of three placebo-controlled RCTs (n = 2577) demonstrated that upadacitinib at 15 mg increased the LDL-C by 15.18 mg/dL (95% CI: 7.77-22.59) and HDL-C by 7.89 mg/dL (95% CI: 7.08-8.69). According to the pooled analysis of 15 placebo-controlled RCTs (n = 7695), upadacitinib had no effect on MACE (risk ratio, RR: 0.62; 95% CI: 0.24-1.60). A sub-analysis focusing on upadacitinib at 15 mg (12 studies, n = 5395) demonstrated similar results (RR: 0.67; 95% CI: 0.19-2.36). CONCLUSIONS: Treatment with upadacitinib increases both LDL-C and HDL-C levels. Nevertheless, upadacitinib had no significant effect on the cardiovascular disease risk during a ≤52-week follow-up.

Medical students' attitudes and perceptions of influenza and SARS-CoV-2 vaccination in Cyprus.

Introduction: Infectious diseases constitute a significant problem globally and healthcare professionals (HCP) show suboptimal vaccination rates. We aimed to evaluate the determinants affecting vaccination against influenza and SARS-CoV-2 among medical students in Cyprus. Methods: We conducted a cross-sectional study based on a self-reported, anonymous questionnaire that was sent to all medical students of two Medical Schools in the Republic of Cyprus. Results: Among 266 respondents, 50.8% had been vaccinated against influenza in the past and 20.1% in 2020-21. The majority believed that influenza and SARS-CoV-2 vaccines are safe and effective. Regarding vaccination in Cyprus, 41.3% did not know the current recommendations and a higher proportion of preclinical students replied incorrectly, compared to clinical students. Slightly over half (56.4%) considered themselves adequately informed about influenza vaccination, with more clinical students appearing confident (p=0.068). An overwhelming 71.2% were concerned about contracting SARS-CoV-2, compared to 25.4% with regards to influenza. Up to 76.8% considered themselves adequately informed about SARS-CoV-2 vaccination, with significantly more clinical students being confident (p<0.001). Although more preclinical students appeared hesitant, most students had either been vaccinated against SARS-CoV-2 (49.4%) or would be as soon as possible (32.1%). Vaccination refusal was 2.3%, a group comprised entirely of preclinical students. Conclusions: Our study provides relevant and actionable information about differences in attitudes and perceptions between clinical and preclinical medical students regarding vaccination against influenza and SARS-CoV-2 and highlights the importance of organized, systemic efforts to increase vaccination coverage.

The Use of Antenatal Dexamethasone in Late Preterm and Term Pregnancies to Improve Neonatal Morbidity and Mortality: A Systematic Review and Meta-Analysis.

There are no acceptable worldwide recommendations regarding the use of dexamethasone in late-preterm newborns delivered either vaginally or via cesarean section and term gestation that are performed via cesarean section. The present study aims to compare the effectiveness of antenatal intramuscular dexamethasone versus placebo/no-treatment in reducing neonatal respiratory complications in high-risk for imminent preterm birth in late preterm pregnancies and term pregnancies undergoing elective cesarean section. The PubMed, Scopus, and Cochrane Library databases were searched to assess the effectiveness of dexamethasone during late preterm and term gestation. The last literature search was performed on March 20th, 2022. Randomized controlled trials compared antenatal dexamethasone administration with placebo or no treatment. The outcomes of interest were: the incidence of Respiratory Distress Syndrome; Transient Tachypnea of the Newborn, Neonatal Intensive Care Unit admissions; and the need for ventilatory support or mechanical ventilation. A standardized data form and three independent investigators performed the data extraction. Ten RCTs fulfilled our inclusion criteria. No statistically significant difference was found regarding all of the outcomes in the 34th-36th gestational week group. In the >37th gestational week group, a statistically significant difference was found regarding the incidence of RDS [RR (95% CI); p-value: 0.56 (0.36, 0.87); 0.01], TTN [RR (95% CI); p-value: 0.54 (0.42, 0.71); <0.00001], need for ventilatory support [RR (95% CI); p-value: 0.71 (0.52, 0.96); 0.03] and need for mechanical ventilation [RR (95% CI); p-value: 0.56 (0.33, 0.95); 0.03]. To conclude, the antenatal administration of dexamethasone can be considered to prevent neonatal complications and reduce perinatal morbidity in term pregnancies.

Lomentospora prolificans: An Emerging Opportunistic Fungal Pathogen.

Lomentospora prolificans is an emerging opportunistic pathogen that primarily affects immunocompromised individuals leading to disseminated disease with high mortality rates while also causing infections in healthy populations. Successful recovery from infection is difficult due to high rates of intrinsic resistance to antifungals. Rapid and readily available diagnostic methods, aggressive surgical debridement wherever appropriate, and effective and timely antifungal treatment are the pillars for successful management. Future research will need to clarify the environmental niche of the fungus, further investigate the pathophysiology of infection and define species-specific therapeutic targets.

Infections Caused by Moellerella wisconsensis: A Case Report and a Systematic Review of the Literature.

BACKGROUND: Moellerella wisconsensis, a member of the family of Enterobacteriaceae, although isolated widely in nature, rarely causes infections in humans. Herein, we report a case of isolation of M. wisconsensis from pigtail end culture, urine culture and blood culture in a 76-year-old patient. OBJECTIVE: To systematically address all the relevant information regarding M. wisconsensis through literature. METHODS: We searched PubMed and Scopus databases up to January 2022 and performed a qualitative synthesis of published articles reporting infection from M. wisconsensis in humans. RESULTS: We identified 25 records on PubMed and 43 additional records on Scopus. After removing duplicates, we examined in detail 15 articles. Ten studies with a total of 17 cases were included in our systematic review. Nine studies described isolated case reports, while 1 study described 8 cases. The origin of the infection was the alimentary tract in 9 cases, gallbladder in 4 cases, peritoneal cavity in 2 cases, respiratory tract in 1 case and hemodialysis catheter insertion site in 1 case. In 3 of the aforementioned cases M. wisconsensis was also isolated in blood cultures. CONCLUSION: Physicians should be aware that M. wisconsensis can be present in multiple clinical specimens and that the antibiotic resistance profile of the isolates may pose significant challenges.