Safety and efficacy of Empagliflozin in Pakistani Muslim patients with type 2 diabetes (SAFE-PAK); a randomized clinical trial.

BACKGROUND: Sodium-Glucose-Co-Transporter 2 (SGLT2) inhibitor (Empagliflozin) is an effective drug in controlling blood glucose through predominantly glycosuria. Glycosuria increases the risk of genitourinary infections in diabetes. This study was aimed to establish the safety and efficacy of Empagliflozin (Group-A) versus standard care (Group-B) in Pakistani Muslim individuals with type 2 diabetes. METHODS: A multicenter, randomized clinical trial was conducted in five cities across Pakistan from July 2019 to August 2020. Patients of both genders aged 18-75 years, body mass index (BMI) ≤ 45 kg/m2, glycosylated hemoglobin (HbA1c) 7-10% (53 mmol/mol to 86 mmol/mol) and treatment-naive to Empagliflozin were included. Treatment was given for 24 weeks, and allocation was done through randomization. RESULTS: Out of 745 screened patients, 333 met the eligibility criteria, and a total of 244 (73.3%) patients were enrolled. More hypoglycemic events were reported in the standard care group, whereas positive urine culture, fungal infection, dehydration, and hypotension occurrence were comparable between the two groups. The 6 months mean HbA1c reduction was significant in both groups; (Group-A: 0.91 ± 0.15; p < 0.001 vs. Group-B2: 0.79 ± 0.14; p < 0.001). Efficacy comparison at 6 months revealed a significant reduction in weight and systolic blood pressure (SBP) in Group A only (Group-A: 1.4 ± 0.4 kg; p < 0.002 vs. Group-B: 0.01 ± 0.5 kg; p < 1.00), (Group-A: 5.1 ± 1.7 mmHg; p < 0.012 vs. Group-B: 2.3 ± 1.7 mmHg; p < 0.526). CONCLUSIONS: Empagliflozin was a safe drug compared to standard care in Pakistani Muslim patients with diabetes. It was as effective as standard care in the clinical setting but achieved glycemic control by reducing weight and SBP in type 2 diabetes patients. TRIAL REGISTRATION: This study was registered in the NIH US National Library of Medicine clinical trials registry at Clinicaltrials.gov with the registration number: NCT04665284 on 11/12/2020.

Asymptomatic urinary tract infections and associated risk factors in Pakistani Muslim type 2 diabetic patients.

BACKGROUND: One of the leading long-term complications of type 2 diabetes mellitus (T2DM) includes renal dysfunction and urinary tract infections (UTI) which are considered to be prevalent in uncontrolled diabetes. Moreover, physiological factors like age, gender, duration of diabetes, other diabetic complications like neuropathy, autonomic neuropathy and glycosuria are also considered as predisposing factors for increased prevalence of UTI in diabetes which can be symptomatic or asymptomatic. METHODS: This was a cross-sectional, multi-centre study including diabetic patients from 12 clinical sites spread across major cities of Pakistan. The inclusion criteria were adult Pakistani population of age between 18 to 75 years both genders and suffering from T2DM irrespective of duration. A detailed clinical history of the past 3 months was recorded and, biochemical investigations of blood samples were conducted. Urine culture analysis performed identified the type of pathogen present and was done only for asymptomatic patients. RESULTS: A total of 745 type 2 diabetic patients were initially screened, out of 545 patients considered for final analysis 501 (91.92%) were negative and the rest 44 (8.08%) had positive urine culture. Female gender had a significantly higher proportion of positive urine culture (77.27%, p-value< 0.001). Body mass index and mean age had insignificant distribution among the two groups of positive and negative urine culture, with age 40-59 years having higher proportion (70.45%) in the positive group. Escherichia coli was detected in most of the positive samples (52.3%). All bacterial samples were found resistant to Ciprofloxacin. CONCLUSION: Diabetic Pakistani muslim female patients are identified to be at high risk of suffering from asymptomatic UTI and age more than 40 years is an important risk factor. Escherichia coli was the most common causative organism among people living in this geographical area.

Metabesity: expert panel recommendation for taking up the challenge by a multidisciplinary approach.

Metabesity refers to metabolic aberrations associated with obesity. These include low- grade inflammation, mitochondrial dysfunction, and changes in gut microbiome. Along with a genetic component, the phenotypes in metabesity are largely the result of sedentary lifestyle and unhealthy eating habits. Metabesity is associated with several co-morbidities including an increased risk for cardiovascular conditions like hypertension, heart failure, myocardial infarction, stroke, and sudden death. Insulin resistance, high blood pressure and glucose levels, visceral adiposity, progressive atherosclerosis, dyslipidaemia and fatty liver are common in obese individuals. Obesity increases the risk for and overall mortality due to cancer. Metabesity adversely impacts endocrine balances in the body and increases the risk of degenerative conditions like dementia. Metabesity is an impending epidemic of huge public health implications with enormous clinical, socioeconomic, and humanistic burden. Interventions to combat sedentary lifestyle and unhealthy eating should be introduced early in life to prevent the onset and progression of metabesity. This review also summarizes the experts' recommendation from Pakistan to manage the rising metabesity concern in their geography based on the literature evidences.

The Lipo- Phenotypic Screening Tool for Familial Hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is a common disorder of lipid metabolism. However, it is rarely diagnosed in time, leading to a high burden of preventable cardiovascular (CV) morbidity. The authors describe a lipophenotypic screening tool, which can be used by clinicians to screen for FH. This simple construct is based on history, physical examination, lipid profile and non-invasive cardioimaging. Structured as a bidirectional three column rubric, this tool should be able to improve clinical skills and teaching related to FH.

Expert Opinion: Use of sodium glucose co-transporter type-2 inhibitors in South Asian population -The Pakistan perspective.

Sodium-glucose co-transporter type 2 inhibitors (SGLT 2- i)are increasingly being used in the management of type 2 diabetes mellitus (T2DM). With the novel insulinindependent glycosuric action, these agents help to attain glycaemic goals by lowering HbA1c and fasting blood glucose. In addition, these agents improve metabolic control in diabetes and ameliorate comorbidities like obesity and hyper tension. Beneficial effec ts on cardiovascular outcomes have been a key attraction for physicians. These agents are used alone or in combination with oral antidiabetic agents and insulin to attain glycaemic and metabolic targets. A major disadvantagewith these agents is the increased risk for genital andurinary infections. When used in appropriate settings, there is no additional increased risk of hypoglycaemia or volume depletion with these agents. Available evidence suggests good efficacy and safety of these agents in diabetes management. The easy and convenient oncedaily dosing should be customized according to patient needs and glycaemic profiles.

Cardiovascular disease risk factors in Pakistani population with newly diagnosed Type 2 diabetes mellitus: A cross-sectional study of selected family practitioner clinics in four provinces of Pakistan (CardiP Study).

OBJECTIVE: To explore cardiovascular risk factors in people with newly-diagnosed type 2 diabetes mellitus. METHODS: The cross-sectional, prospective, multicentre, study was conducted from June 2014 till July 2015 at family practice clinics in 27 cities across Pakistan, and comprised individuals aged 30-50 years diagnosed with type 2 diabetes mellitus within the preceding six months. Laboratory investigations were conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, and Aga Khan University Hospital, Karachi. The 10-year absolute risk of fatal or non-fatal coronary heart disease and stroke was calculated using the United Kingdom Prospective Diabetes Study Risk Engine version 2.0. Data were analysed using SPSS 19. RESULTS: Out of 888 subjects, 362(40.8%) were women and 526(59.2%) were men. The overall mean presenting age was 42.4}5.8 years. After stratification by age, those ≥40 years were significantly associated with higher glycated haemoglobin (p=0.02) and those ≤39 years were associated with higher levels of very low density lipoprotein (p=0.001) and triglyceride (p=0.006). The mean risk estimate for CHD was 9.7% (95% Confidence Interval (CI) 9.0- 10.1)), for fatal CHD 4.4% (95% CI 4.0-4.6), for stroke 1.5% (95% CI 1.2-1.7), and for fatal stroke 0.25% (95% CI 0.24- 0.26). CONCLUSIONS: There is a need for screening cardiovascular risk factors even in younger age groups of newlydiagnosed diabetes.

A SURVEY OF CLINICAL PRACTICE PATTERNS IN MANAGEMENT OF GRAVES DISEASE IN THE MIDDLE EAST AND NORTH AFRICA.

OBJECTIVE: Graves disease (GD) is commonly seen in endocrine clinical practice. The objective of this study was to evaluate the current diagnosis and management of patients with GD in the Middle East and North Africa (MENA). METHODS: An electronic survey on GD management was performed using an online questionnaire of a large pool of practicing physicians. Responses from 352 eligible and willing physicians were included in this study. They were mostly endocrinologists (157) and internal medicine physicians (116). RESULTS: In addition to serum thyroid-stimulating hormone (TSH) and free thyroxine assays, most respondents would request serum antithyroid peroxidase antibody and TSH-receptor autoantibody (50% and 46%, respectively), whereas serum antithyroglobulin antibodies would be ordered by fewer respondents (36%). Thyroid ultra-sound would be requested by a high number of respondents (63.7%), while only a small percentage would order isotopic thyroid studies. Antithyroid drug (ATD) therapy was the preferred first-line treatment (52.7%), followed by radio-iodine (RAI) treatment (36.8%), ß-blockers alone (6.9%), thyroidectomy (3.2%), and no therapy (1.3%). When RAI treatment was selected in the presence of mild Graves orbitopathy and/or associated risk factors for its occurrence/exacerbation, steroid prophylaxis was frequently used. The preferred ATD in pregnancy was propylthiouracil in the first trimester and carbimazole in the second and third trimesters. On most issues, choices of the MENA physicians fell between European and American practices. CONCLUSION: Hybrid practices are seen in the MENA region, perhaps reflecting training and affiliations. Management approaches most suitable for patients in this region are needed. ABBREVIATIONS: ATD = antithyroid drug CBZ = carbimazole FT3 = free T3 FT4 = free T4 GD = Graves disease GO = Graves orbitopathy MENA = Middle East and North Africa MMI = methimazole RAI = radioactive iodine RAIU = RAI uptake T3 = tri-iodothyronine T4 = thyroxine TG Ab = antithyroglobulin antibodies TRAb = TSH-receptor autoantibody TSH = thyroid-stimulating hormone PTU = propylthiouracil TID = thrice daily UAE = United Arab Emirates US = ultrasound.

South Asian consensus guideline: Use of GLP-1 receptor agonists during Ramadan: Update 2016 Revised Guidelines on the use of GLP-1A in Ramadan.

This guidance is an update to the South Asian Consensus Guideline: Use of GLP1RA in Diabetes during Ramadan, published in the Indian Journal of Endocrinology and Metabolism in 2012. A five country working group has collated evidence and experience to suggest guidelines for the safe and rational use of glucagon-like peptide1 receptor agonists during Ramadan. The suggestions contained herewith are based upon recently published evidence as well as available basic pharmacological data.

Update to South Asian consensus guideline: Use of newer insulins in diabetes during Ramadan Revised Guidelines on the use of insulin in Ramadan.

This guidance is an update to the South Asian Consensus Guideline: Use of Insulin in Diabetes during Ramadan, published in the Indian Journal of Endocrinology and Metabolism in 2012. A five country working group has collated evidence and experience to suggest guidelines for the safe and rational use of insulin degludec (IDeg) and insulin degludec aspart (IDegAsp) during Ramadan. The suggestions contained herewith are based on the pharmacokinetic and pharmacodynamics properties of these novel insulins.

A systematic review of Inconel 939 alloy parts development via additive manufacturing process.

IN939 is a modern class of nickel-based superalloys designed for continuous operational sustenance at elevated temperatures owing to their excellent combination of fatigue, creep, and corrosion resistance. This unique performance of IN939 is associated with the composition of this alloy, along with specific post-processing treatments such as solution treatment and aging, giving rise to features such as the presence of γ' residues, as well as the presence of MC and M23C6 carbides. This also includes the absence of the eutectic and incipient melting phases. For this alloy, the primary part development is by the powder bed fusion process using a laser powder bed fusion machine. At the same time, a solo study highlights the use of an EB-PBF machine for the synthesis. The AM development process of these alloys is hindered by machine parameters, which have been found ineffective in isolation to obtain a fully dense structure with desired properties. The purpose of these parameters is to improve their core properties while minimizing defects associated with powder metallurgy routes, such as porosity, detrimental precipitates, grain anisotropy, etc. This study aims to provide an overview of the advancements in research related to IN939, explicitly focusing on the benchmarks achieved through additive manufacturing techniques. We have discussed the work performed in this area, compared the results of different studies, and identified the gaps in current research. By doing so, we aim to provide a comprehensive understanding of the potential of IN939 and its applications in extreme environments.

Influence of quitting smoking on diabetes-related complications: A scoping review with a systematic search strategy.

INTRODUCTION: Smoking in people with diabetes markedly elevates their risk of developing complications and increases the likelihood of cardiovascular mortality. This review is the first to specifically provide evidence-based analysis about the influence of quitting smoking on diabetes-related complications in people with type 2 diabetes. METHOD: The present review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. All human clinical studies assessing the effects of stopping smoking cessation on diabetes-related complications were included. PubMed and Embase were screened until January 2024. References of primary studies and principal peer-reviewed scientific journals in the field were manually screened. RESULTS: We identified a total of 1023 studies. Only 26 met the criteria for eligibility. In general quitting smoking is associated with decreased risks of myocardial infarction and ischemic stroke. Regarding microvascular complications, the strongest evidence for the beneficial effects of smoking cessation is observed in diabetic nephropathy. However, the relationship between smoking cessation and retinopathy, neuropathy, diabetic foot complications and diabetic-related erectile dysfunction, is poorly investigated. CONCLUSION: Quitting smoking offers significant advantages in managing diabetes-related complications, significantly lowering the risks of myocardial infarction, ischemic stroke, and diabetic nephropathy. This underscores the importance of cessation. Providing evidence-based information on the benefits of stopping smoking for people with type 2 diabetes who smoke, can bolster smoking cessation efforts in the context of diabetes management.

Global Warming and Endocrinology: The Hyderabad Declaration of the South Asian Federation of Endocrine Societies.

Global warming and endocrine disorders are intertwined issues posing significant challenges. Greenhouse gases emanating from human activities drive global warming, leading to temperature rise and altered weather patterns. South Asia has experienced a noticeable temperature surge over the past century. The sizable population residing in the region heightens the susceptibility to the impact of global warming. In addition to affecting agriculture, water resources, and livelihood, environmental changes interfere with endocrine functioning. Resulting lifestyle changes increase the risk of metabolic and endocrine disorders. Individuals with diabetes face heightened vulnerability to extreme weather due to impaired thermoregulation. A high ambient temperature predisposes to heat-related illnesses, infertility, and nephropathy. Additionally, essential endocrine drugs and medical devices are susceptible to temperature fluctuations. The South Asian Federation of Endocrine Societies (SAFES) calls for collaboration among stakeholders to combat climate change and promote healthy living. Comprehensive approaches, including the establishment of sustainable food systems, promotion of physical activity, and raising awareness about environmental impacts, are imperative. SAFES recommends strategies such as prioritizing plant-based diets, reducing meat consumption, optimizing medical device usage, and enhancing accessibility to endocrine care. Raising awareness and educating caregivers and people living with diabetes on necessary precautions during extreme weather conditions are paramount. The heat sensitivity of insulin, blood glucose monitoring devices, and insulin pumps necessitates proper storage and consideration of environmental conditions for optimal efficacy. The inter-connectedness of global warming and endocrine disorders underscores the necessity of international collaboration guided by national endocrine societies. SAFES urges all stakeholders to actively implement sustainable practices to improve endocrine health in the face of climate change.

Monitoring Endocrine Nursing in South Asia (MENSA).

Background: South Asian countries face the colossal challenge of tackling the massive burden of diabetes and other endocrine disorders. These patients grossly outnumber the specialists trained to deal with these conditions. A trained cadre of diabetes specialist nurses (DSN) and endocrine specialist nurses (ESN) might help bridge this gap. Exploring the perception of DSN/ESN among South Asian doctors will help to understand their role, responsibilities and future prospects. Methods: One hundred and seventy-four endocrinologists from South Asia participated in an online survey on their perception of DSNs and ESNs. Results: Out of the 174 respondents, 61 (35%) were currently working with DSN/ESN, 79 (45.4%) had worked in the past and 131 (75.2%) were willing to start recruiting or employ additional DSN/ESN in the future. The majority considered that the primary function of DSN and ESN is to educate on diabetes (n = 86, 96.6%) and endocrine disorders (n = 34, 57.6%), respectively, followed by anthropometry and initial work-up. Only a small minority felt they could write independent follow-up prescriptions (nurse-led clinics) [DSN - 16 (18%) and ESN - 3 (5.1%)]. Graduation with a certificate course in diabetes and basic endocrinology was considered a sufficient qualification by 68 (39.1%) respondents. Endocrinologists from countries other than India were more willing to recruit ESN/DSN in the future (89.7% vs 72.4%; P < 0.03) and approve a nurse-led clinic (62.1% vs 29.7%; P < 0.03). Upon multiple logistic regression, working in countries other than India was an independent predictor of future willingness to work with DSN/ESN (odds ratio (OR): 4.48, 95% confidence interval (CI) 1.09-18.43, P = 0.03). Conclusion: DSN and ESN could facilitate the management of healthcare-seekers with diabetes and endocrine disorders. A certification course to train nurses on diabetes and basic endocrine disorders following graduation could be helpful. Major hindrances in creating a regular cadre of DSN/ESN were limited opportunities for career progression and lack of additional remuneration for services.

South Asian Working Action Group on SARCOpenia (SWAG-SARCO) - A consensus document.

The South Asian population is rapidly ageing and sarcopenia is likely to become a huge burden in this region if proper action is not taken in time. Several sarcopenia guidelines are available, from the western world and from East Asia. However, these guidelines are not fully relevant for the South Asian healthcare ecosystem. South Asia is ethnically, culturally, and phenotypically unique. Additionally, the region is seeing an increase in non-communicable lifestyle disease and obesity. Both these conditions can lead to sarcopenia. However, secondary sarcopenia and sarcopenic obesity are either not dealt with in detail or are missing in other guidelines. Hence, we present a consensus on the screening, diagnosis and management of sarcopenia, which addresses the gaps in the current guidelines. This South Asian consensus gives equal importance to muscle function, muscle strength, and muscle mass; provides cost-effective clinical and easy to implement solutions; highlights secondary sarcopenia and sarcopenic obesity; lists commonly used biomarkers; reminds us that osteo-arthro-muscular triad should be seen as a single entity to address sarcopenia; stresses on prevention over treatment; and prioritizes non-pharmacological over pharmacological management. As literature is scarce from this region, the authors call for more South Asian research guided interventions.

Practical Guidance on Basal Insulin Initiation and Titration in Asia: A Delphi-Based Consensus.

The global health burden of diabetes is on the rise and has affected more than half a billion people worldwide, particularly in Southeast Asia, North Africa, Africa, and the Western Pacific, Middle East, and South and Central America regions of the International Diabetes Federation (IDF). Despite many new treatments being available for the management of diabetes, glycemic control remains suboptimal in Asia, compared to the rest of the world. Delay in timely insulin initiation and inadequate titration of insulin are regarded to be some of the important reasons for inadequate glycemic control. Additionally, Asian populations have a distinct phenotype, including a younger age of onset and higher glycemic excursions, suggestive of a lower beta-cell function, as compared to non-Asians. Although there are multiple local and international guidelines on insulin initiation and titration, some of these guidelines can be complex. There is an unmet need for guideline recommendations on basal insulin initiation and titration to be simplified and customized for the Asian population with type 2 diabetes mellitus (T2DM). A unified approach would increase adoption of basal insulin initiation by primary care and family medicine physicians, which in turn would help reduce the inertia to insulin initiation. With this background, a consensus-seeking meeting was conducted with 14 experts from seven Asian countries to delineate appropriate practices for insulin initiation and titration in the Asian context. The key objective was to propose a simple insulin titration algorithm, specific for the Asian population, to improve glycemic control and optimize therapeutic outcomes of people with T2DM on basal insulin. Following a detailed review of literature and current guidelines, and potential barriers to insulin initiation and titration, the experts proposed a simplified insulin titration algorithm based on both physician- and patient-led components. The consensus recommendations of the experts related to basal insulin initiation and titration have been summarized in this article, along with the proposed titration algorithm for optimizing glycemic control in the Asian population with T2DM.

Evaluation of the effectiveness and tolerability of gliclazide modified release 60 mg in patients with type 2 diabetes observing fasting during Ramadan in Pakistan: An analysis from the global DIA-RAMADAN study.

AIM: To assess safety and effectiveness of gliclazide MR 60 mg in people with controlled or suboptimal controlled T2DM treated with breakable gliclazide MR 60 mg formulation. METHOD: This study data has been extracted from an international, observational study conducted in nine Asian and Middle Eastern countries. Total 220 patients with T2DM were recruited from Pakistan. The primary endpoint was the proportion of patients reporting at least 1 symptomatic HE, whereas secondary endpoints were changes in glycosylated haemoglobin (HbA1c) %, fasting plasma glucose (FPG) mg/dL, and body weight (kg) and proportion of patients reporting any HE (confirmed or severe), between inclusion visit (V0) and end of the study visit (V1). RESULTS: During Ramadan, 3.6% (n = 8/220) patients had experienced at least one symptomatic HEs. A significant (p-value < 0.001) reduction was observed in HbA1c: (mean [SD]) (-0.4 [0.9] %), and body weight (-0.7 [4.8] kg). Thirteen adverse events (AEs) unrelated to gliclazide MR were reported during the study pre-Ramadan and post-Ramadan periods. CONCLUSION: This study shows safety and effectiveness profile of gliclazide MR 60 mg by emphasizing on the low risk of HEs, effective glycaemic control and body weight reduction in T2DM patients, who are inclined to fasting during Ramadan.

Knowledge gaps and perceptions of future research directions on management of diabetes during Ramadan fasting: An online survey of physicians.

OBJECTIVES: Current knowledge and research on diabetes and Ramadan form the basis for evidence-based clinical practice. In this context, we aimed to explore physicians' perceptions of current knowledge gaps about research fasting (RF), barriers to, and foreseeable directions for advancement of the field. METHODS: We conducted an online survey of a convenience sample of 260 physicians from 27 countries. The survey questionnaire addressed three main domains: perceived current knowledge gaps and unmet needs in research about RF and diabetes, barriers to the conduct of research, and future directions for furthering the evidence in this field. RESULTS: Majority of respondents (65.7%) were senior physicians in adult endocrinology/diabetes (45.9%) working at tertiary centers (65.2%). The majority (67.3%) reported seeing an average of 20+ patients with diabetes weekly and felt "very or fairly confident" in managing diabetes during RF (67.7%). The knowledge gaps identified were the management of high-risk patients with diabetes (54.1%), such as renal impairment (59.8%), and pregnancy (61.5%). The main barriers to research were lack of adequate funding to academic centers (75.7%) and lack of interest of institutions in the subject (64.6%). Future efforts should be directed at the conduct of large epidemiological studies (49.5%) or double-blinded, placebo-controlled clinical trials (48.6%) to address the former gaps. Research findings should be widely disseminated via hands-on workshops (recommended by 70.3% of respondents) or international conferences (61.2%). CONCLUSIONS: There is a wide agreement regarding the knowledge gaps in the management of diabetes during RF. Future efforts should focus on addressing these critical deficiencies.

Clinical and Histopathological Variables and Prognostic Factors of Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare and highly aggressive tumor with a poor prognosis. The literature on prognosis from low-income or low-middle-income countries is limited and scarce. This study aimed to determine the clinical and histopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and the factors affecting ACC's prognosis. This was a retrospective study of patients that presented with ACC to the Shaukat Khanum Memorial Cancer & Research Center, Lahore, Pakistan, between January 2011 and May 2018. Information regarding demographics and clinical and histopathological variables were extracted and analyzed. Of the 25 subjects, 16 (64%) were female. The median age of the sample was 35 years (range; 21 - 72 years). Statistically significant associations were found between RFS and functional status of the tumor (p = 0.014), cortisol overproduction (p = 0.02), androgen excess (testosterone [p = 0.03] and dehydroepiandrosterone sulfate [DHEA SO4] [p = 0.004]), Ki-67 score (p = 0.03), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.01), and composite variable of disease (p = 0.004). The OS was found to have statistical associations with cortisol hypersecretion (p = 0.02), DHEA SO4 excess (p = 0.01), Modified Weis Score (p < 0.001), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.003), and composite variable of disease (p = 0.001). Linear regression (forward-type) analysis suggested that the functional status of the tumor and the disease recurrence index statistically predicted the variance in RFS and OS, respectively. Multiple clinical and histopathological variables appear to affect the prognosis of ACC. However, based on multivariable analysis, it appears that the functional status of the tumor and the composite variable of disease recurrence are predictors of RFS and OS, respectively.

Descriptive Regional Subanalysis of a Real-World Study in Patients with Type 2 Diabetes Treated with Gliclazide MR During Fasting: DIA-RAMADAN.

INTRODUCTION: To analyse the safety and effectiveness of gliclazide modified release (MR) in adults with type 2 diabetes mellitus participating in Ramadan from three geographically and culturally different regions of the world included in the DIA-RAMADAN study. METHODS: DIA-RAMADAN was a real-world, observational, international, non-comparative study. The global study population was divided into three regional subgroups, with data gathered at inclusion 6-8 weeks prior to Ramadan (V0), during Ramadan (4.5 weeks) and 4-6 weeks after Ramadan (V1). Primary endpoint was the proportion of patients reporting ≥ 1 symptomatic hypoglycaemic events (HE), which were collected using a patient diary along with other adverse events. RESULTS: Patient numbers from the three regions were n = 564 (46.5%; Indian sub-continent), n = 354 (29.1%; Middle East) and n = 296 (24.4%; South-East Asia). Patient baseline characteristics, demographics, fasting habits and antidiabetic treatments varied between regions. There were similar proportions of symptomatic HE between regions, with no severe HE. Significant weight reductions were observed in all regions following Ramadan, along with reductions in HbA1c and fasting plasma glucose. CONCLUSION: These real-world study data indicate that gliclazide MR is safe and effective for management of type 2 diabetes during Ramadan in all three regions studied as part of DIA-RAMADAN. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04132934. INFOGRAPHIC.

Clinical Characteristics and Outcome of Patients With Pheochromocytoma: A Single Center Tertiary Care Experience.

Objective The aim of this study was to evaluate the demographic and clinical characteristics of patients with pheochromocytoma and determine the treatment outcome with overall survival rates of patients with pheochromocytoma. Methods A retrospective, cross-sectional study was performed on all the patients with histologically proven pheochromocytoma presenting to Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH & RC) Lahore, between August 2006 and July 2018. Clinical, biochemical and radiological data were collected at presentation, post-surgery, at discharge and till the last follow-up; data was retrieved from hospital records. Cure was defined as no evidence of disease biochemically, clinically, and structurally. Results This study included 29 patients, 69% were female. The three most common symptoms were abdominal pain (51.7%), hypertension (44.8%) and headache (41.4%). Most pheochromocytomas were sporadic (82.8%), all were adrenal gland tumors, and 89.7% were unilateral. All patients underwent adrenalectomy. Open adrenalectomy was performed in 25 patients whereas four underwent laparoscopic adrenalectomy. Fifteen patients experienced postoperative complications. The most frequently documented intraoperative complication was hypotension. Death occurred in two patients, one patient died of metastatic disease secondary to malignant pheochromocytoma and the other patient died from perioperative complications. Cure was documented biochemically and/or radiologically in 96.5% patients. Conclusions Abdominal pain was predominant presenting feature most likely due to large tumor size. Most patients presenting to SKMCH & RC, had large intra-abdominal tumors with high cure rate. Mortality was low despite high rate of perioperative complications.