Atypical Clinical Manifestations of Graves' Disease: An Analysis in Depth

Over the past few decades, there has been an increase in the number of reports about newly recognized (atypical or unusual) manifestations of Graves' disease (GD), that are related to various body systems. One of these manifestations is sometimes the main presenting feature of GD. Some of the atypical manifestations are specifically related to GD, while others are also similarly seen in patients with other forms of hyperthyroidism. Lack of knowledge of the association between these findings and GD may lead to delay in diagnosis, misdiagnosis, or unnecessary investigations. The atypical clinical presentations of GD include anemia, vomiting, jaundice, and right heart failure. There is one type of anemia that is not explained by any of the known etiological factors and responds well to hyperthyroidism treatment. This type of anemia resembles anemia of chronic disease and may be termed GD anemia. Other forms of anemia that are associated with GD include pernicious anemia, iron deficiency anemia of celiac disease, and autoimmune hemolytic anemia. Vomiting has been reported as a presenting feature of Graves' disease. Some cases had the typical findings of hyperthyroidism initially masked, and the vomiting did not improve until hyperthyroidism has been detected and treated. Hyperthyroidism may present with jaundice, and on the other hand, deep jaundice may develop with the onset of overt hyperthyroidism in previously compensated chronic liver disease patients. Pulmonary hypertension is reported to be associated with GD and to respond to its treatment. GD-related pulmonary hypertension may be so severe to produce isolated right-sided heart failure that is occasionally found as the presenting manifestation of GD

Epidemiology of and Risk Factors for Type 2 Diabetes in Egypt

Background: Diabetes is a fast-growing health problem in Egypt with a significant impact on morbidity, mortality, and health care resources. Currently, the prevalence of type 2 diabetes (T2D) in Egypt is around 15.6% of all adults aged 20 to 79. Objective: To describe the epidemiology, principal causes, associated risk factors, cultural aspects, and challenges that may contribute to the rapid rise in T2D in Egypt. Methods: Review of papers in PubMed and relevant gray literature. Findings: The International Diabetes Federation (IDF) has identified Egypt as the ninth leading country in the world for the number of patients with T2D. The prevalence of T2D in Egypt was almost tripled over the last 2 decades. This sharp rise could be attributed to either an increased pattern of the traditional risk factors for T2D such as obesity and physical inactivity and change in eating pattern or other risk factors unique to Egypt. These include increased exposure to environmental risk factors like pesticides and increased prevalence of chronic hepatitis C.. Conclusions: Prevention, early identification, and effective intervention are integral components of effective T2D care in Egypt. These strategies may reduce the expanding economic burden associated with T2D care

Transcultural Diabetes Nutrition Algorithm: A Malaysian Application

Glycemic control among patients with prediabetes and type 2 diabetes mellitus (T2D) in Malaysia is suboptimal, especially after the continuous worsening over the past decade. Improved glycemic control may be achieved through a comprehensive management strategy that includes medical nutrition therapy (MNT). Evidence-based recommendations for diabetes-specific therapeutic diets are available internationally. However, Asian patients with T2D, including Malaysians, have unique disease characteristics and risk factors, as well as cultural and lifestyle dissimilarities, which may render international guidelines and recommendations less applicable and/or difficult to implement. With these thoughts in mind, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed by an international task force of diabetes and nutrition experts through the restructuring of international guidelines for the nutritional management of prediabetes and T2D to account for cultural differences in lifestyle, diet, and genetic factors. The initial evidence-based global tDNA template was designed for simplicity, flexibility, and cultural modification. This paper reports the Malaysian adaptation of the tDNA, which takes into account the epidemiologic, physiologic, cultural, and lifestyle factors unique to Malaysia, as well as the local guidelines recommendations

Diabetes-Specific Nutrition Algorithm: A Transcultural Program to Optimize Diabetes and Prediabetes Care

Type 2 diabetes (T2D) and prediabetes have a major global impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities. To mitigate this disease burden, interventions of proven effectiveness must be used. Evidence shows that nutrition therapy improves glycemic control and reduces the risks of diabetes and its complications. Accordingly, diabetes-specific nutrition therapy should be incorporated into comprehensive patient management programs. Evidence-based recommendations for healthy lifestyles that include healthy eating can be found in clinical practice guidelines (CPGs) from professional medical organizations. To enable broad implementation of these guidelines, recommendations must be reconstructed to account for cultural differences in lifestyle, food availability, and genetic factors. To begin, published CPGs and relevant medical literature were reviewed and evidence ratings applied according to established protocols for guidelines. From this information, an algorithm for the nutritional management of people with T2D and prediabetes was created. Subsequently, algorithm nodes were populated with transcultural attributes to guide decisions. The resultant transcultural diabetes-specific nutrition algorithm (tDNA) was simplified and optimized for global implementation and validation according to current standards for CPG development and cultural adaptation. Thus, the tDNA is a tool to facilitate the delivery of nutrition therapy to patients with T2D and prediabetes in a variety of cultures and geographic locations. It is anticipated that this novel approach can reduce the burden of diabetes, improve quality of life, and save lives. The specific Southeast Asian and Asian Indian tDNA versions can be found in companion articles in this issue of Current Diabetes Reports

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Diabetes-Specific Nutrition Formulas in the Management of Patients with Diabetes and Cardiometabolic Risk

Food-based dietary management, enhanced with evidence-based commercial products, such as diabetes-specific nutrition formulas (DSNFs), can help control the development, progression, and severity of certain chronic diseases. In this review, evidence is detailed on the use of DSNFs in patients with or at risk for diabetes and cardiometabolic-based chronic disease. Many DSNF strategies target glycemic excursions and cardiovascular physiology, taking into account various elements of healthy eating patterns. Nevertheless, significant research, knowledge, and practice gaps remain. These gaps are actionable in terms of formulating and testing relevant and pragmatic research questions, developing an educational program for the uniform distribution of information, and collaboratively writing clinical practice guidelines that incorporate the evidence base for DSNF. In sum, the benefits of DNSF as part of validated clinical practice algorithms include mitigation of chronic disease progression, cost-savings for the healthcare system, and applicability on a global scal

SOX2 Regulates Neuronal Differentiation of the Suprachiasmatic Nucleus

In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, orchestrating behavioral and physiological rhythms in alignment to the environmental light/dark cycle. The neurons that comprise the SCN are anatomically and functionally heterogeneous, but despite their physiological importance, little is known about the pathways that guide their specification and differentiation. Here, we report that the stem/progenitor cell transcription factor, Sex determining region Y-box 2 (Sox2), is required in the embryonic SCN to control the expression of SCN-enriched neuropeptides and transcription factors. Ablation of Sox2 in the developing SCN leads to downregulation of circadian neuropeptides as early as embryonic day (E) 15.5, followed by a decrease in the expression of two transcription factors involved in SCN development, Lhx1 and Six6, in neonates. Thymidine analog-retention assays revealed that Sox2 deficiency contributed to reduced survival of SCN neurons during the postnatal period of cell clearance, but did not affect progenitor cell proliferation or SCN specification. Our results identify SOX2 as an essential transcription factor for the proper differentiation and survival of neurons within the developing SCN

Transcultural Diabetes Nutrition Algorithm (tDNA): Venezuelan Application

Medical nutrition therapy (MNT) is a necessary component of comprehensive type 2 diabetes (T2D) management, but optimal outcomes require culturally-sensitive implementation. Accordingly, international experts created an evidence-based transcultural diabetes nutrition algorithm (tDNA) to improve understanding of MNT and to foster portability of current guidelines to various dysglycemic populations worldwide. This report details the development of tDNA-Venezuelan via analysis of region-specific cardiovascular disease (CVD) risk factors, lifestyles, anthropometrics, and resultant tDNA algorithmic modifications. Specific recommendations include: screening for prediabetes (for biochemical monitoring and lifestyle counseling); detecting obesity using Latin American cutoffs for waist circumference and Venezuelan cutoffs for BMI; prescribing MNT to people with prediabetes, T2D, or high CVD risk; specifying control goals in prediabetes and T2D; and describing regional differences in prevalence of CVD risk and lifestyle. Venezuelan deliberations involved evaluating typical food-based eating patterns, correcting improper dietary habits through adaptation of the Mediterranean diet with local foods, developing local recommendations for physical activity, avoiding stigmatizing obesity as a cosmetic problem, avoiding misuse of insulin and metformin, circumscribing bariatric surgery to appropriate indications, and using integrated health service networks to implement tDNA. Finally, further research, national surveys, and validation protocols focusing on CVD risk reduction in Venezuelan populations are necessary