Clinical Recommendations for the use of Neurotropic B vitamins (B1, B6, and B12) for the Management of Peripheral Neuropathy: Consensus from a Multidisciplinary Expert Panel.

INTRODUCTION: Peripheral neuropathy (PN) is an insidious disease that is often asymptomatic during the early stages but which can have a significant impact on quality of life at later stages when nerve damage occurs. There is currently no guidance on the use of neurotropic B vitamins (B1, B6, and B12) for the management of asymptomatic and symptomatic PN. OBJECTIVE: To provide guidance to primary care physicians on an integrated approach to managing PN with neurotropic B vitamins (B1, B6, and B12). MATERIALS AND METHODS: A multidisciplinary panel of eight experts participated in an iterative quasi-anonymous Delphi survey consisting of two rounds of questions and a virtual meeting. A literature review formed the basis of the survey questions. The first round included multiple select, qualitative, and Likert Scale questions; the subsequent round consisted of 2-point scale (agree or disagree) questions that sought to develop consensus-based statements refined from the first round and recommendations derived from discussions during the virtual expert panel meeting. RESULTS: Clinical recommendations for the use of neurotropic B vitamins (B1, B6, and B12) have been developed for the prevention of PN progression or to delay onset in patients at high risk of developing PN. Recommendations have also been provided for the assessment of PN etiology and considerations for the use of loading dose (high dose) and maintenance dose (lower dose) of these neurotropic B vitamins (B1, B6, and B12). CONCLUSION: These clinical recommendations provide an initial step towards formulating comprehensive guidelines for the early and long-term management of PN with neurotropic B vitamins (B1, B6, and B12) and move beyond addressing only neuropathic pain associated with the late stages of PN.

Practical considerations for the use of SGLT-2 inhibitors in the Asia-Pacific countries-An expert consensus statement.

Recent clinical studies have demonstrated the effectiveness of SGLT-2 inhibitors in reducing the risks of cardiovascular and renal events in both patients with and without type 2 diabetes mellitus. Consequently, many international guidelines have begun advocating for the use of SGLT-2 inhibitors for the purpose of organ protection rather than as simply a glucose-lowering agent. However, despite the consistent clinical benefits and available strong guideline recommendations, the utilization of SGLT-2 inhibitors have been unexpectedly low in many countries, a trend which is much more noticeable in low resource settings. Unfamiliarity with the recent focus in their organ protective role and clinical indications; concerns with potential adverse effects of SGLT-2 inhibitors, including acute kidney injury, genitourinary infections, euglycemic ketoacidosis; and their safety profile in elderly populations have been identified as deterring factors to their more widespread use. This review serves as a practical guide to clinicians managing patients who could benefit from SGLT-2 inhibitors treatment and instill greater confidence in the initiation of these drugs, with the aim of optimizing their utilization rates in high-risk populations.

Mapping the journey of patients with painful diabetic peripheral neuropathy in the Philippines

Objectives@#Knowing the limited epidemiological studies on painful diabetic peripheral neuropathy (pDPN) in the Philippines, the present review aimed to map the prevalence of pDPN and identify the associated healthcare gaps. @*Materials and Methods@#A systematic search of MEDLINE, Embase and BIOSIS was conducted using predefine inclusion criteria, and relevant studies published in English between 2004 and 2021 were identified. An unstructured literature search was also conducted on public and government websites with no date restriction. Data combined from all sources were synthesized and presented as a simple mean.@*Results@#Three studies were considered for final analyses of the 26 articles retrieved from structured and unstructured searches. The sample sizes for the three studies were 103, 172, and 100, respectively. The simple mean prevalence of pDPN was estimated at 26.5%. Awareness of pDPN based on a published study was 89%. According to published studies, screening and diagnosis of pDPN were 65% and 76.7%, respectively. One-third of the patients with pDPN (75%) were treated. No literature is available for adherence and control.@*Conclusion@#Limited data exist on the different management stages of patients with pDPN in the Philippines. The study analysis will help address the knowledge gaps, improve patient care and pain management, and aid decisionmaking.

A retrospective cohort study on the treatment outcome after Unilateral Adrenalectomy among patients with Aldosterone-Producing Adenoma at the University of Santo Tomas Hospital

Background@#Unilateral adrenalectomy is indicated for patients with unilateral primary aldosteronism resulting in normalization of hypokalemia and resolution of hypertension. This study aims to determine the proportion of patients with cure of hypertension and improvement of hypokalemia after unilateral adrenalectomy among patients with aldosterone-producing adenoma and assess the association of preoperative factors with these outcomes.@*Methods@#This is a retrospective cohort study among patients with aldosterone-producing adenoma who underwent unilateral adrenalectomy with at least one month follow-up after the operation. Patients were selected from admissions to the University of Santo Tomas Hospital from January 2008 to November 2018. The proportion of patients with cure of hypertension and resolution of hypokalemia were determined. Binary logistic regression was used to determine preoperative factors associated with these outcomes.@*Results@#Twenty-one patients were included in this study. Cure of hypertension was noted in 47.62% and 42.86% of patients within 24 hours of adrenalectomy and on follow-up, respectively. Improvement of hypokalemia was noted in 61.90% of patients within 24 hours of operation while all patients had improvement of hypokalemia on follow-up. Patients without preoperative hypokalemia were more likely to have cure of hypertension within 24 hours of adrenalectomy (OR=0.0250, p=0.005) and on follow-up (OR=0.0571, p=0.010).@*Conclusion@#Unilateral adrenalectomy results in improvement of hypertension and hypokalemia in the majority of patients with aldosterone-producing adenoma. Shorter duration of hypertension and absence of preoperative hypokalemia were significantly associated with cure of hypertension after unilateral adrenalectomy.

Consensus Recommendations by the Asian Pacific Society of Cardiology: Optimising Cardiovascular Outcomes in Patients with Type 2 Diabetes.

The Asian Pacific Society of Cardiology convened a consensus statement panel for optimising cardiovascular (CV) outcomes in type 2 diabetes, and reviewed the current literature. Relevant articles were appraised using the Grading of Recommendations, Assessment, Development and Evaluation system, and consensus statements were developed in two meetings and were confirmed through online voting. The consensus statements indicated that lifestyle interventions must be emphasised for patients with prediabetes, and optimal glucose control should be encouraged when possible. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are recommended for patients with chronic kidney disease with adequate renal function, and for patients with heart failure with reduced ejection fraction. In addition to SGLT2i, glucagon-like peptide-1 receptor agonists are recommended for patients at high risk of CV events. A blood pressure target below 140/90 mmHg is generally recommended for patients with type 2 diabetes. Antiplatelet therapy is recommended for secondary prevention in patients with atherosclerotic CV disease.

Approach to lower the cardiovascular risk of individuals with Type 2 Diabetes Mellitus: Evidence-based consensus statements of the Philippine Heart Association and Philippine Society of Endocrinology Diabetes and Metabolism

@#Diabetes remains as the 6th leading cause of death in the Philippines, with more than 33,000 deaths in 2016. Given this alarming prevalence, it is imperative that this public health concern be prioritized in the country and to answer such concern, a group of cardiologists and endocrinologists who are in active clinical practice and research, formed a technical working group composed of five members. Their primary objective was to develop an evidence-based consensus document for Filipino healthcare practitioners and people in the academe that would serve as a guideline on the approach to lower the CV risk of individuals with T2DM. The TWG agreed on focusing with the pharmacological approach to treatment of lowering CV risk for T2DM patients using the ADAPTE model which is a more systematic approach to guideline adaptation. The recommendations were developed using the ADAPTE framework appraising all international practice guidelines and recommendations through to 2013. The technical working group’s overall objective of guideline adaptation is to take advantage of the existing guidelines to enhance the efficient production and use of high-quality adapted guidelines specially in the local Philippine setting. Each of these articles was then assessed using the AGREE instrument. Based on the key questions that the technical working group had identified regarding the approach to lower the risk of individuals with type 2 diabetes, 9 recommendations concerning the antidiabetic drug of choice for persons with type 2 diabetes with or without established ASCVD and management of type 2 diabetes mellitus patients with hypertension and dyslipidemia were drafted and are presented in this report.

Use of SGLT-2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Abdominal Obesity: An Asian Perspective and Expert Recommendations.

The prevalence of obesity in Asia is of epidemic proportions, with an estimated 1 billion overweight/obese individuals in the region. The majority of patients with type 2 diabetes mellitus (T2DM) are overweight/obese, which increases the risk of cardiorenal outcomes in these patients; hence, sustained reductions in body weight and visceral adiposity are important management goals. However, most of the glucose-lowering therapies such as insulin, sulfonylureas, glinides, and thiazolidinediones induce weight gain, which makes the management of overweight/obese T2DM patients challenging. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the only oral glucose-lowering agents that have been shown to reduce body weight and visceral adiposity. In addition, SGLT-2 inhibitors therapy reduces ectopic fat deposition and improves adipose tissue function and weight-related quality of life. In this article, we aim to consolidate the existing literature on the effects of SGLT-2 inhibitors in Asian patients with T2DM and to produce clinical recommendations on their use in overweight or obese patients with T2DM. Recommendations from international and regional guidelines, as well as published data from clinical trials in Asian populations and cardiovascular outcomes trials are reviewed. Based on the available data, SGLT-2 inhibitors represent an evidence-based therapeutic option for the management of overweight/obese patients with T2DM.

Use of SGLT-2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Abdominal Obesity: An Asian Perspective and Expert Recommendations

The prevalence of obesity in Asia is of epidemic proportions, with an estimated 1 billion overweight/obese individuals in the region. The majority of patients with type 2 diabetes mellitus (T2DM) are overweight/obese, which increases the risk of cardiorenal outcomes in these patients; hence, sustained reductions in body weight and visceral adiposity are important management goals. However, most of the glucose-lowering therapies such as insulin, sulfonylureas, glinides, and thiazolidinediones induce weight gain, which makes the management of overweight/obese T2DM patients challenging. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the only oral glucose-lowering agents that have been shown to reduce body weight and visceral adiposity. In addition, SGLT-2 inhibitors therapy reduces ectopic fat deposition and improves adipose tissue function and weight-related quality of life. In this article, we aim to consolidate the existing literature on the effects of SGLT-2 inhibitors in Asian patients with T2DM and to produce clinical recommendations on their use in overweight or obese patients with T2DM. Recommendations from international and regional guidelines, as well as published data from clinical trials in Asian populations and cardiovascular outcomes trials are reviewed. Based on the available data, SGLT-2 inhibitors represent an evidence-based therapeutic option for the management of overweight/obese patients with T2DM.

Effect of ostarine (enobosarm/GTX024), a selective androgen receptor modulator, on adipocyte metabolism in Wistar rats.

Synthetic ligands of androgen receptor (AR) are a standard in the treatment of androgen deficiency. One of the effects of androgen deficiency is the disturbance in the homeostasis of lipid metabolism. Till date, there are no effective compounds developed to treat androgen deficiency without having any side effects. Nonsteroidal selective androgen receptor modulators (SARMs) are a promising solution for various clinical indications. In this study, we investigated the effect of ostarine (enobosarm), a nonsteroidal SARM, on the rat adipocyte metabolism using in vitro techniques. Isolated rat adipocytes were incubated in the presence of different concentrations of ostarine. Control incubation with testosterone as the natural ligand for AR was performed. AR inhibitors were used to investigate the genomic activity of ostarine. Changes in the intensity of lipolysis, lipogenesis, and the secretion of leptin and adiponectin were measured. Moreover, the gene expression of leptin and adiponectin was assessed. For the first time, we have shown that ostarine has a significant effect on the intensity of lipid metabolism. Ostarine downregulates the expression of leptin and adiponectin mRNAs, as well as decreases their release from rat adipocytes. According to our results, ostarine acts via AR with a similar effect as testosterone in the regulation of lipid metabolism and endocrine function of mature rat adipocytes in vitro. Our results indicate the need for further studies on the effects of SARM on the whole organism.

Use of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors: An Asian perspective and expert recommendations.

Diabetes mellitus in Asia accounts for more than half of the global prevalence. There is a high prevalence of cardiovascular disease (CVD) in the region among people with type 2 diabetes mellitus (T2DM) and it is often associated with multiple risk factors including hypertension, renal disease and obesity. The early onset of T2DM and the eventual long disease duration portends an increasing proportion of the population to premature CVD. In addition to lowering blood glucose, sodium-glucose co-transporter-2 (SGLT-2) inhibitors exert favourable effects on multiple risk factors (including blood pressure, body weight and renal function) and provide an opportunity to reduce the risk of CVD in patients with T2DM. In this article, we consolidated the existing literature on SGLT-2 inhibitor use in Asian patients with T2DM and established contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, published data from clinical trials in the Asian population (dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, luseogliflozin and tofogliflozin), CVD outcomes trials (EMPAREG-OUTCOME, CANVAS and DECLARE-TIMI 58) and real-world evidence studies (CVD-REAL, EASEL, CVD-REAL 2 and OBSERVE-4D). A series of clinical recommendations on the use of SGLT-2 inhibitors in Asian patients with T2DM was deliberated among experts with multiple rounds of review and voting. Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for the primary prevention of heart failure hospitalization and secondary prevention of CVD in patients with T2DM, and should be considered early on in the treatment algorithm for patients with multiple risk factors, or those with established CVD.

Expert opinion on the applicability of dyslipidemia guidelines in Asia and the Middle East.

Cardiovascular disease (CVD) is a growing burden across the world. In Asia and the Middle East, in particular, CVD is among the most prevalent and debilitating diseases. Dyslipidemia is an important factor in the development of atherosclerosis and associated cardiovascular events, and so effective management strategies are critical to reducing overall cardiovascular risk. Multiple dyslipidemia guidelines have been developed by international bodies such as the European Society of Cardiology/European Atherosclerosis Society and the American College of Cardiology/American Heart Association, which all have similarities in practice recommendations for the optimal management of dyslipidemia. However, they differ in certain aspects including pharmacological treatment, lifestyle modification and the target levels used for low-density lipoprotein cholesterol. The evidence behind these guidelines is generally based on data from Western populations, and their applicability to people in Asia and the Middle East is largely untested. As a result, practitioners within Asia and the Middle East continue to rely on international evidence despite population differences in lipid phenotypes and CVD risk factors. An expert panel was convened to review the international guidelines commonly used in Asia and the Middle East and determine their applicability to clinical practice in the region, with specific recommendations, or considerations, provided where current guideline recommendations differ from local practice. Herein, we describe the heterogeneous approaches and application of current guidelines used to manage dyslipidemia in Asia and the Middle East. We provide consensus management recommendations to cover different patient scenarios, including primary prevention, elderly, chronic kidney disease, type 2 diabetes, documented CVD, acute coronary syndromes and family history of ischemic heart disease. Moreover, we advocate for countries within the Asian and Middle East regions to continue to develop guidelines that are appropriate for the local population.

Correction to: Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

Unfortunately, the fifth author name was incorrectly published in the original publication. The correct name should read as 'Ozgur Demir'.

Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.

Detection of Experimental Swine Trichinellosis Using Commercial Elisa Test.

The aim of the study carried out on ten young (10-week old) pigs of the native Polish Large White breed experimentally infected with a low dose of 300 invasive muscle larvae (ML) of Trichinella spiralis was intravital detection of trichinellosis using the E-S ELISA test, determination of a variation level of IgG antibodies against excretory-secretory (E-S) antigens of T. spiralis muscle larvae and finally, describing the intensity of T. spiralis larvae infection in selected muscles. The pig sera were collected at 7 and 9 days prior to the experimental infection with T. spiralis and at 9, 14, 20, 23, 25, 27, 30, 33, 37, 41, 46 days post-infection (d.p.i.). The anti-T. spiralis IgG antibodies were detected by a commercial E-S ELISA test (PrioCHECK Trichinella Ab). Average intensity of the T. spiralis infection in the examined muscles of pigs ranged from 1.52 up to 43.09 larvae/g. The studies revealed that the E-S antigen in the ELISA test did not show cross-reaction with the sera of pigs infected with Oesophagostomum spp. The ELISA assay did not recognize trichinellosis in pigs until 27 days after the T. spiralis infection. The anti-T. spiralis IgG antibodies were first detected on day 30 post-infection. A statistically significant increase of IgG antibodies against T. spiralis ML E-S antigens was first observed between days 27-30 (p<0.01) post-infection, and a further significant rise in the antibody level occurred between days 27 and 33 (p<0.01); 30 and 33 (p<0.01); 33 and 37 (p<0.05) following infection.

Successful reduction in thyroid and nodule volumes in large solitary and multinodular goiters with serial 131 iodine therapy

Introduction@#131Iodine therapy is effective in nodular nontoxic goiter with enhanced effects using recombinant thyroid stimulating hormone (rTSH). The eventual fibrosis of the thyroid tissue and blood vessels ligates the vascular supply of the nodule. The study aims to show the successful reduction of thyroid and nodule volumes in large solitary and multinodular goiters using serial low dose 131iodine therapy (10mCi) at three to six months interval.@*Methods@#A retrospective analytical study was done from January 2010 to December 2012 and included twenty three patients with enlarged solitary and multinodular (nodule/s ≥2cm) non-toxic goiter (females: age range 35-65yrs) given serial 131iodine therapy (eight to10mCi) at three to six-month interval. Before each course, serum thyroid stimulating hormone (TSH) was done to document hypothyroidism while thyroid gland and nodule sizes were monitored by ultrasonographic measurements serially with each 131iodine therapy. Relief of compressive symptoms was monitored on follow-up at clinic.@*Results@#Thyroid size reduced by 38-40% from baseline after first radioactive iodine (RAI) and by 33-39% after the second RAI. Thyroid nodules reduced by 63-69% and 11-25% serially. Significant reduction was noted after the first RAI. One subject underwent third RAI with 80-85% overall reduction in nodule size. All patients developed post-RAI hypothyroidism and overall had greater than 50% increase in levothyroxine replacement dose after the last RAI. Significant relief of compressive symptoms was noted by 91% post-therapy. Four thyroid nodules disappeared which resulted in reduced total number of thyroid nodules from 29 to 25 nodules post serial RAI.@*Conclusion@#Serial 131iodine therapy proved to have thyroid and nodule size reduction by more than 70% in this study. Among patients who do not consent or have contraindications to surgery, serial 131iodine therapy may be considered a safe and effective non-surgical alternative.

Prevalence of diabetes mellitus and pre-diabetes in the Philippines: A sub-study of the 7th National Nutrition and Health Survey (2008)

INTRODUCTION: Diabetes mellitus is rapidly increasing worldwide but the greatest increase is expected in developing countries including the Philippines. It is of public health concern to monitor countrywide prevalence of diabetes as it leads to significant cardiovascular-related mortality as well as significant complications such end stage renal disease, blindness, lower leg amputations and blindness.METHODOLOGY: This is a national survey to estimate the prevalence of diabetes and pre-diabetes using the criteria of the World Health Organization through a stratified multi-stage sampling design representing each of the 17 regions in the country.RESULTS AND DISCUSSION: The national prevalence of diabetes in the year 2008 was 7.2% (6.5-7.9); impaired glucose tolerance 7.0% (6.1-7.8) and impaired fasting glucose was 2.2% (2.2-3.1). There was a greater prevalence of individuals with diabetes in the urban areas at 8.5% (7.5-9.5) compared to the rural areas at 5.7% (4.6-6.8). Diabetes is slightly more preponderant among females at 7.4% (6.4-8.3) compared to males at 7.0% (6.1-8.0).CONCLUSION: The prevalence of diabetes mellitus in the Philippines is rising with the prevalence in 2008 at 7.2%. The prevalence of pre-diabetes exceeds that of diabetes mellitus at approximately 10.2%.

[Postoperative dissection of the vertebral artery in two steps]. / Dissection postopératoire de l'artère vertébrale en deux temps.

The diagnosis of perioperative vertebral artery dissection can be difficult because of non-specific clinical signs. We report a case revealed by a tegmento-thalamic stroke after an abdominal second surgical look. The interest of this observation is related to a particular evolution in two steps separated by a 2-month-interval and an intercurrent cervical manipulation. After the second anesthesia, neck pain associated with a third cranial nerve palsy and a supranuclear ophtalmoplegia revealed a tegmento-thalamic ischemic stroke due to vertebral artery dissection. We discuss here the different factors possibly involved in the pathophysiology of postoperative vertebral artery dissection: positioning, cervical manipulation, subclavian central venous access and cisplatin toxicity. Vertebral artery dissection should be discussed in case of postoperative neck pain, especially with non-typical symptomatology.

Characterization and differential expression of cathepsin L3 alleles from Fasciola hepatica.

Fasciola hepatica infections cause significant global problems in veterinary and human medicine, including causing huge losses in cattle and sheep production. F. hepatica host infection is a multistage process and flukes express papain-like cysteine proteases, termed cathepsins, which play pivotal roles in virulence through host entry, tissue migration and immune evasion. Expression of these proteases is developmentally regulated. Recent studies indicate that excystment of infective larvae is dependent on cysteine proteases and together FhCL3 and FhCB account for over 80% of total protease activity detectable in newly excysted juvenile (NEJ) fluke. This paper focuses on members of the cathepsin L gene family, specifically those belonging to the CL3 clade. The cDNA of two novel cathepsin L3 proteases--FhCL3-1 and FhCL3-2 were cloned. The mRNA transcript expression levels for these enzymes were significantly different at various time points in life development stages obtained in vitro, from dormant metacercariae to NEJ 24h after excystment. Maximum expression levels were observed in NEJ immediately after excystment. In all stages examined by Real Time PCR, FhCL3-2 was expressed at a higher level compared to FhCL3-1 which was expressed only at very low levels. Western blot and immunohistochemical analysis also indicated higher expression of the FhCL3-2 allele and its secretory nature. The ability of antibody responses from rats and sheep challenged with F. hepatica to recognize recombinant FhCL3-1 and FhCL3-2 was shown to differ. Differences were also confirmed through the use of anti-rFhCL3-1 and anti-rFhCL3-2 sera in Western blot analysis of juvenile excretory/secretory (ES) material separated by 2D electrophoresis. These results indicate analysis of relative expression of parasite virulence factors from different populations is required, as this will likely impact the effectiveness of vaccines based on these antigens.