An evaluation of the bariatric surgical patient

Obesity continues to be one of the most common prevalent chronic diseases worldwide with recent data stating that it has now reached global pandemic proportions making it a major public health problem. In 2008 the World Health Organisation (WHO) stated that worldwide around 1.4 billion adults were overweight (body mass index [BMI] 25.0-29.9 kg/m2) and a further 500 million were obese (BMI ?30 kg/m2). Of note, the prevalence of obesity has tripled in Europe over the last 30 years with around 50% of the population in the majority of European countries being overweight or obese.1-4 Locally, the situation is also alarming with data from the European Health Interview Survey (EHIS) in 2011 stating that Malta had the highest rate of obese males in Europe (24.7%) and when it comes to females, Maltese women were the second most obese after British women (21.1% and 23.9% respectively).5 Even more worrisome is the fact that Malta also tops the charts for the highest prevalence of overweight and obesity in school-aged children thus accentuating the fact that urgent action needs to be taken in order to tackle effectively this world-wide epidemic.6 Unfortunately obesity is strongly linked to several co-morbid conditions such as type 2 diabetes, hypertension, cardiovascular disease, dyslipidaemia, obstructive sleep apnoea, non-alcoholic steatohepatitis, osteoarthrosis, as well as some cancers (including breast, ovary, prostate, endometrium and colon) and psychiatric illnesses and thus it stands to reason that an increase in prevalence of obesity has also led to an increase in prevalence of these co-morbidities resulting in an impaired overall quality of life and decreased life expectancy in these subjects.peer-reviewe

Review of the risks and/or benefits of thyroxine treatment in ‘mild’ subclinical hypothyroidism

Subclinical hypothyroidism (SCH) is a form of mild thyroid failure and is a commonly encountered condition in clinical practice. It denotes the presence of a raised serum thyroid stimulating hormone (TSH) and normal serum free thyroid hormone concentrations (tri-iodothyronine [T3] and thyroxine [T4]). ‘Mild’ subclinical hypothyroidism is associated with a TSH level between 4.5-9mIU/L (0.4-4.2) whereas patients with a serum TSH level ?10mIU/L are classified as having the ‘severe’ form. The clinical significance of this condition has aroused a lot of interest over the last decade, especially its effects on various health outcomes (namely cardiovascular disease, lipid metabolism, fertility, pregnancy outcomes and fetal neurocognitive function). Unfortunately the unavailability of adequately powered, double-blind randomised controlled studies precludes the availability of clear cut guidelines as to how one should treat subclinical hypothyroidism. This review looks at the available evidence for and against treatment of SCH with levothyroixine. Most authors agree on the use of clinical judgement as well as individualising management based on the underlying unique patient characteristics when it comes to formulating a management plan for this condition.peer-reviewe

An update on pharmacotherapy for type 2 diabetes

Glucose lowering drugs have been available for clinical use for over the past 60 years or so with the last 2 decades seeing a significant number of new agents being developed making treatment increasingly complex and also somewhat controversial. This stems from the fact that while it is now known that patients with diabetes have an increased risk for cardiovascular disease and mortality there are mounting concerns with regards to the cardiovascular effects of certain antihyperglycemic agents leading to uncertainties when it comes to drug prescription. This has left many clinicians perplexed with respect to optimal strategies for management for management of such patients leading to many regulatory bodies to issue recommendations for antihyperglycimic therapy in adults with type 2 diabetes. These all uniformly advocate an individualised approach, keeping in mind each patients’ unique health profile (such as age and weight) and their cardiovascular risk factors vis-a-vie the specific attributes, side effects and adverse effects of each antihyperglycemic agent. This article will focus on the ten major categories of diabetic therapies looking specifically at their mode of action, safety profile as well as key trial data and where possible the long-term outcome studies for each class.peer-reviewe

IS THERE GOOD EVIDENCE THAT THE TWO QUESTIONS IN PHQ-2 ARE USEFUL QUESTIONS TO USE IN ORDER TO SCREEN FOR DEPRESSION?

The PHQ-2 has been presented as an ultra-short screening questionnaire to detect depression in several healthcare settings. This paper will outline its current uses, evaluate its accuracy as a screening method, and suggest potential uses

Metastatic malignant melanoma of unknown primary in temporalis muscle

Metastatic melanoma of unknown primary (MUP) is an uncommon melanocytic lesion found in distant sites with no evident skin involvement. This case report presents a 75-year-old woman who underwent local excision for a lump in the right temporal area, which had been present for 6 months and had been suspected to be a lipoma. Histology confirmed that the tissue excised from the temporalis muscle was composed of atypical, heavily pigmented melanocytes. Her history was negative for melanocytic lesions, and examination and extensive investigation including imaging had failed to identify a primary lesion. The patient is currently being followed up.peer-reviewe

Insulin prescription and administration and blood glucose monitoring at Mater Dei Hospital

Background: Incorrect insulin prescription and administration has been associated with substantial medication-related patient harm and mortality. We aimed to assess whether blood glucose was being monitored according to our local hospital protocol and whether insulin was being prescribed accurately by doctors and administered safely by nurses. Moreover, we evaluated whether education to nurses and doctors resulted in less insulin prescription and administration errors. Methods: Inpatients on insulin in Mater Dei hospital’s medical wards were recruited. Data was collected from patients’ files on errors in insulin prescription and on the timing of blood glucose monitoring and insulin administration in relation to meals. The first audit was carried out in 2013. A re-audit was carried out in 2017 following education to doctors and nurses and a change in the treatment chart format. The z-test was used to compare the two audits. Results: On re-auditing, a significant improvement was noted in the timing of blood glucose monitoring and insulin administration in relation to meals, in the legibility of the insulin doses, ‘Units’ were more written in full and supplementary Actrapid® was more frequently prescribed where indicated. However, inappropriate omission of fixed insulin doses occurred more often, while written instructions by doctors on when to administer fixed insulin, including supplementary Actrapid®, were still lacking. Moreover, there was no improvement in adherence to the supplementary Actrapid® algorithm by nurses. Conclusion: Further education and an improved treatment chart including hypo- and hyperglycaemia trouble-shooting guidelines are required to further reduce insulin prescription and administration errors.peer-reviewe

Reduced leukocyte mitochondrial copy number in metabolic syndrome and metabolically healthy obesity

Objective: This study aimed to investigate the associations between peripheral blood leukocyte mitochondrial copy number, metabolic syndrome, and adiposity-related body composition phenotypes in a high prevalence population. Methods: A single center cross-sectional study was conducted, consisting of 521 middle-aged subjects of Maltese-Caucasian ethnicity. Participants were stratified according to the presence of metabolic syndrome and different metabolic health definitions based on NCEP-ATP III criteria. Relative leukocyte mitochondrial DNA copy number was determined by quantitative polymerase chain reaction and corrected for leukocyte and platelet count. The associations between mitochondrial copy number and metabolic syndrome components was evaluated and adjusted for age and gender. Results: Significant negative correlations between mtDNA copy number and BMI, waist circumference, triglyceride levels, fasting plasma glucose, HbA1c, HOMA-IR and hsCRP were observed, along with a positive correlation with HDL-C levels. Mitochondrial copy number was lower in individuals with metabolic syndrome. When compared to metabolically healthy normal weight subjects, a reduction in mtDNA copy number was observed in both the metabolically healthy and unhealthy obese categories. Conclusion: Our data supports the association between reduced leukocyte mtDNA copy number, obesity, and metabolic syndrome. This investigation expands on the spectrum of associations between mtDNA copy number and metabolic phenotypes in different populations and underpins the role of mitochondrial dysfunction in the development and progression of metabolic syndrome and its components.peer-reviewe

Investigating adiposity-related metabolic health phenotypes in patients with hidradenitis suppurativa : a cross-sectional study

Background: Obesity and hidradenitis suppurativa (HS) are related through meta-inflammation and are both associated with increased cardiometabolic risk. Notwithstanding, cardiometabolic pathology is not uniform in obesity and a subset of individuals with excess adiposity exhibit a healthy metabolic profile. Whilst the incidence of cardiometabolic endpoints and transitions across different adiposity-related body composition phenotypes within several populations and across different ethnicities have been investigated, data regarding metabolic health (MetH) and body composition phenotypes in individuals with HS are lacking. The objective of this study was to evaluate the relationship between different body composition phenotypes in individuals with HS. Methods: This was a cross-sectional study of 632 individuals with and without HS from a population with a high prevalence of both obesity and HS. A total of four body composition phenotypes were generated based on BMI and metabolic status (defined using either the metabolic syndrome definition or the homeostasis model of insulin resistance (HOMA-IR)): metabolically healthy overweight/obese (MHOWOB), metabolically unhealthy overweight/obese (MUOWOB), metabolically healthy normal weight (MHNW), and metabolically unhealthy normal weight (MUNW). Results: Generally, subjects with HS exhibited a worse metabolic profile with higher levels of indices of central adiposity measures (including Visceral Adiposity Index and waist circumference), systolic blood pressure and markers of insulin resistance, as well as a higher prevalence of the metabolic syndrome. Moreover, when sub-stratified into the different body composition phenotypes, individuals with HS typically also demonstrated adverse metabolic characteristics relative to controls matched for both adiposity and metabolic health, particularly in the normal weight category and despite being classified as metabolically healthy. Being metabolically unhealthy in addition to being overweight/obese increases an individual’s risk of HS. Conclusions: Metabolic risk-assessment should be prioritized in the clinical management of individuals with HS even in those who are lean. Patients attending HS clinics provide a valuable opportunity for targeted cardiovascular risk reduction with respect to the management of both obesity and metabolic health.peer-reviewe

Prevalence rates of metabolic health and body size phenotypes by different criteria and association with insulin resistance in a Maltese Caucasian population

Introduction: Hyperinsulinemia and insulin resistance are known to be associated with increased cardiovascular morbidity and mortality. A metabolically unhealthy phenotype is frequently used as a surrogate marker for insulin resistance. The aims of the current study were to compare the prevalence of the body size phenotypes using different definitions of metabolic health and to investigate which one of them is most strongly associated with insulin resistance in men and women. Methods: We conducted a cross-sectional study in a middle-aged cohort of Maltese Caucasian non-institutionalized population. Metabolic health was defined using the various currently used definitions. Results: There were significant differences in the prevalence of body size phenotypes according to the different definitions. We also found significant sex differences in the predictive value of the various definitions of the metabolically unhealthy phenotype to predict insulin resistance. The strongest association was for the definition of having >2 NCEP-ATPIII criteria to characterize the metabolic unhealthy phenotype in women (odds ratio of 19.7). On the other hand, the Aguilar-Salinas et al. definition had the strongest association in men (odds ratio of 18.7). Conclusions: We found large differences in the prevalence of the various body size phenotypes when using different definitions, highlighting the need for having standard criteria. Our data also suggest the need for sex-specific definitions of metabolic health.peer-reviewe

Identification of C-β-d-Glucopyranosyl Azole-Type Inhibitors of Glycogen Phosphorylase That Reduce Glycogenolysis in Hepatocytes: In Silico Design, Synthesis, in Vitro Kinetics, and ex Vivo Studies

Several C-β-d-glucopyranosyl azoles have recently been uncovered as among the most potent glycogen phosphorylase (GP) catalytic site inhibitors discovered to date. Toward further exploring their translational potential, ex vivo experiments have been performed for their effectiveness in reduction of glycogenolysis in hepatocytes. New compounds for these experiments were predicted in silico where, for the first time, effective ranking of GP catalytic site inhibitor potencies using the molecular mechanics-generalized Born surface area (MM-GBSA) method has been demonstrated. For a congeneric training set of 27 ligands, excellent statistics in terms of Pearson (RP) and Spearman (RS) correlations (both 0.98), predictive index (PI = 0.99), and area under the receiver operating characteristic curve (AU-ROC = 0.99) for predicted versus experimental binding affinities were obtained, with ligand tautomeric/ionization states additionally considered using density functional theory (DFT). Seven 2-aryl-4(5)-(β-d-glucopyranosyl)-imidazoles and 2-aryl-4-(β-d-glucopyranosyl)-thiazoles were subsequently synthesized, and kinetics experiments against rabbit muscle GPb revealed new potent inhibitors with best Ki values in the low micromolar range (5c = 1.97 μM; 13b = 4.58 μM). Ten C-β-d-glucopyranosyl azoles were then tested ex vivo in mouse primary hepatocytes. Four of these (5a–c and 9d) demonstrated significant reduction of glucagon stimulated glycogenolysis (IC50 = 30–60 μM). Structural and predicted physicochemical properties associated with their effectiveness were analyzed with permeability related parameters identified as crucial factors. The most effective ligand series 5 contained an imidazole ring, and the calculated pKa (Epik: 6.2; Jaguar 5.5) for protonated imidazole suggests that cellular permeation through the neutral state is favored, while within the cell, there is predicted more favorable binding to GP in the protonated form