Diabetic angiopathy including micro- and macroangiopathy is concerned with high rate of morbidity and mortality in patients with long-standing diabetes. Receptor for advanced glycation end products (RAGE) and its ligands have been considered as important pathogenic triggers for the progression of the vascular injuries in diabetes. The deleterious link between RAGE and diabetic angiopathy has been demonstrated in animal studies. Preventive and therapeutic strategies focusing on RAGE and its ligand axis may be of great importance in relieving diabetic vascular complications and reducing the burden of disease.

Background Persistent hypoglycaemia is common in the newborn and is associated with poor neurodevelopmental outcome. Adequate monitoring is critical in prevention, but is dependent on frequent, often hourly blood sampling. Continuous glucose monitoring (CGM) is increasingly being used in children with type 1 diabetes mellitus, but use in neonatology remains limited. We aimed to introduce real-time CGM to provide insights into patterns of dysglycaemia and to support the management of persistent neonatal hypoglycaemia. Methods This is a single centre retrospective study of real-time CGM use over a 4-year period in babies with persistent hypoglycaemia. Results CGMs were inserted in 14 babies: 8 term and 6 preterm infants, 9 with evidence of congenital hyperinsulinism (CHI). A total of 224 days of data were collected demonstrating marked fluctuations in glucose levels in babies with CHI, with a higher sensor glucose SD (1.52±0.79 mmol/l vs 0.77±0.22mmol/l) in infants with CHI compared to preterm infants. A total of 1254 paired glucose values (CGM and blood) were compared and gave a mean absolute relative difference (MARD) of 11%. Conclusion CGM highlighted the challenges of preventing hypoglycaemia in these babies when using intermittent blood glucose levels alone, and the potential application of CGM as an adjunct to clinical care.

Glucolipotoxicity, which is exerted by free fatty acids (FFA) and prolonged hyperglycemia, is implicated in pancreatic b-cell failure in diabetes. Pattern recognition receptors such as receptor for advanced glycation end products (RAGE) and toll-like receptors 2 and 4 could mediate danger signals in b-cells. We examined whether RAGE contributes to b-cell failure in a type 2 diabetes mouse model. Pancreatic islets were isolated from ob/ob, db/db, diet-induced obesity (DIO), RAGE-null (RAGE À/À ), and RAGE +/+ wild-type (WT) control mice and dispersed into single cells for flow cytometry. RAGE expression was detected in insulin-positive b-cells of ob/ob and db/db mice, but not of WT, DIO, or RAGE À/À mice: thus, inadequate leptin receptor signaling and RAGE expression may be linked. Compared with RAGE +/+ db/db mice, RAGE À/À db/db mice showed higher b-cell number and mass with less apoptosis as well as glucose tolerance with higher insulin secretion without any differences in serum levels of FFA and adiponectin. Palmitate or oleate pretreatment combined with a leptin antagonist induced RAGE expression, AGE-elicited apoptosis, and impaired glucose-stimulated insulin secretion by advanced glycation end products (AGE) in MIN6 cells. FFA elevation with concomitant AGE formation during prolonged hyperglycemia could cause b-cell damage through insufficient leptin action and subsequent RAGE induction in type 2 diabetes.

No abstract

Pilonidal sinus is an acquired condition caused by irritation to the hair follicles at the natal cleft, presenting with an abscess or chronic infection. It is prevalent in young adults affecting their productive lifestyle with morbidities. There are varieties of treatment options; however, there is no consensus yet for the ideal procedure. Less invasive procedures have evolved to replace the traditional surgical techniques, which cannot significantly reduce the risks of recurrence and wound complications despite extensive surgeries. We aimed to assess the effect of fibrin glue as a primary treatment after cleaning the sinus in pilonidal sinus disease. We searched for articles from PubMed®, Ovid MEDLINE®, Ovid EMBASE®, and Cochrane CENTRAL. Six studies that included 336 patients in total were analyzed. Fibrin glue treatment in these studies reported a quicker return to normal activities postoperatively, a low rate of infection, and an acceptable rate of recurrence. Thus, fibrin glue seems beneficial in the management of pilonidal disease. However, further high-quality studies are essential to support and confirm this evidence. Future research should also evaluate its cost and implications in the ambulatory service.

Surgical site infections (SSIs) represent one of the most important complications occurring postoperatively following surgical procedures. The SSI incidence is higher following gastrointestinal (GI) surgeries compared to any other surgery. It contributes to the majority of morbidity and mortality in patients undergoing GI surgeries. The accepted practice worldwide for the prevention and control of SSIs is providing antimicrobial prophylaxis. The appropriate antimicrobial and dose are chosen depending on the microbial flora, complications, and patient risk factors. The objective of this review was to determine the sufficient number of prophylactic antimicrobial doses that would be efficacious and safe in controlling the SSIs following GI oncological surgeries. Single-dose antimicrobial prophylaxis has shown the same efficacy as the multipledose antimicrobial regimen in controlling SSIs in esophageal, gastric, and colorectal surgeries. The advantages of a single-dose regimen include less chance of emergence of resistance, less chance for allergies or toxicity, and less cost. The addition of metronidazole with single-dose antimicrobial prophylaxis in colorectal surgery should be considered due to its beneficial effect in further reducing infections. Further randomized controlled trials are needed for the literature to determine the efficacy and safety of single-dose antimicrobial prophylaxis in patients undergoing esophageal and colorectal surgeries. In addition, studies are required to determine the individual effectiveness of metronidazole in controlling SSIs in colorectal surgeries.

Traumatic brain injury (TBI), also known as the "Silent Epidemic," is a growing devastating global health problem estimated to affect millions of individuals yearly worldwide with little public recognition, leading to many individuals living with a TBI-related disability. TBI has been associated with up to five times increase in the risk of dementia among multiple neurologic complications compared with the general population. Several therapies, including statins, have been tried and showed promising benefits for TBI patients. In this systematic review, we evaluated the recent literature that tested the role of statins on neurological and cognitive outcomes such as Alzheimer’s Disease and non-Alzheimer’s dementia in survivors of TBI with various severities. We conducted a systematic search on PubMed, PubMed Central, MEDLINE, and Google Scholar. MeSH terms and keywords were used to search for full-text randomized clinical trials (RCTs), cross-sectional, case-control, cohort studies, systematic reviews, and animal studies published in English. Inclusion and exclusion criteria were applied, and the articles were subjected to quality appraisal by two reviewers. Our data search retrieved 4948 nonduplicate records. A total of 18 studies were included - nine human studies, and nine animal laboratory trials - after meeting inclusion, eligibility, and quality assessment criteria. Simvastatin was the most tested statin, and the oral route of administration was the most used. Eight human studies showed a significant neuroprotective effect and improvement in the cognitive outcomes, including dementia. Four randomized clinical trials with 296 patients showed that statins play a neuroprotective role and improve cognitive outcomes through different mechanisms, especially their anti-inflammatory effect; they were shown to lower tumor necrosis factor (TNF)-α and C-reactive protein (CRP) levels. Also, they decreased axonal injury and cortical thickness changes. In addition, four cohort studies compared a total of 867.953 patients. One study showed a decrease in mortality in statin-treated patients (p=0.05). Another study showed a reduction in the incidence of Alzheimer's disease and related dementias (RR, 0.77; 95% CI, 0.73-0.81), while one study showed a decreased risk of dementia after concussions by 6.13% (p=0.001). On the other hand, one cohort study showed no significant difference with the use of statins. In eight animal trials, statins showed a significant neuroprotective effect, improved cognitive outcomes, and neurological functions. Different molecular and cellular mechanisms were suggested, including anti-inflammatory effects, promoting angiogenesis, neurogenesis, increasing cerebral blood flow, neurite outgrowth, promoting the proliferation and differentiation of neural stem cells, and reducing axonal injury. On the contrary, one study showed no benefit and actual adverse effect on the cognitive outcome. Most of the studies showed promising neuroprotective effects of sta...

Long QT syndrome (LQTS) is one of the most common inherited cardiac channelopathies with a prevalence of 1:2000. The condition can be congenital or acquired with 15 recognized genotypes; the most common subtypes are LQTS 1, 2, and 3 making up to 85%-90% of the cases. LQTS is characterized by delayed ventricular cardiomyocyte repolarization manifesting on the surface electrocardiogram (EKG) by a prolonged corrected QT (QTc) interval. The mainstay of treatment for this condition involves in part or combination medical therapy via β-blockers as first-line (or other anti-arrhythmic), left cardiac sympathectomy, or implantable cardiac defibrillator placement. Given the high rate of adverse cardiac events (ACE) or sudden cardiac death (SCD) in this population of patients with this disease, this review seeks to highlight the genotype-specific treatment consensus in β-blocker therapy of the most common subtypes.A database search of PubMed, PMC, and Medline was conducted to ascertain the most recent data in the last five years on the management of LQTS types 1-3 and the role of β-blockers in reducing ACE in these types. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to in the study selection, and selected studies focused on humans, written in the English Language, and within the last five years of LQTS subtypes 1, 2, and 3.Eleven relevant studies were selected after considering inclusion criteria, exclusion criteria, and quality appraisal within the last five years, focusing on β-blocker selection directed based on the subtypes of LQTS. Two meta-analyses, one cohort study, and eight reviews provided significant data that non-selective βblockers unequivocally are of benefit in these LQTS types. Summary of findings suggested nadolol followed by propranolol yields the best results in LQTS 1, while nadolol would yield the best effect in LQTS 2 and 3.