Multimodal Imaging in Retinal Vascular Occlusions following Trauma – A Case of Sickle Cell Disease with Negative Sickling Test

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Symptomatic hypercalcemia in a patient with chronic tophaceous gout: a case report

Hypercalcemia has been widely associated with granulomatous processes. This is due to enhanced extra-renal conversion of calcidiol to calcitriol by activated macrophages within the granuloma. Symptomatic hypercalcemia due to granulomatous disorders is not common, with the incidence in sarcoidosis ranging from 10–20%. Large aggregates of monosodium urate crystals in patients with longstanding chronic tophaceous gout can serve as the inciting antigen for the development of granuloma, but hypercalcemia has not been described in this context. We report a case of symptomatic hypercalcemia due to gouty tophi induced granulomatous inflammation. Long term treatment with immunosuppressants, in addition to bisphosphonates and uric acid lowering therapy, has led to stabilization of serum calcium levels and other lab parameters indicative of granulomatous burden

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

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

Aphasic Dystextia as Presenting Feature of Ischemic Stroke in a Pediatric Patient

Aphasia is an important presenting symptom of acute stroke. With increasing reliance on electronic communication, incoherent texting or “dystextia,” which is a subset of aphasia that is reflected in text messages, can be a useful tool for symptom recognition and analysis. It can be a red flag for the family and therefore can help in early identification of an acute neurological deficit. It is also useful for providers to reliably analyze the deficit as well as establish a timeline of evolution of symptoms. There have been case reports where dystextia has been the presenting feature of stroke or complicated migraine and in one case of meningioma. We present the case of a teenage patient that in our knowledge is the youngest reported case of dystextia, whose aphasia recorded in a text message assisted with stroke localization. This also adds to the literature of dystextia which so far has only seven other cases reported

Recurrent focal seizures as a feature of status epilepticus presenting as a peri-ictal water drinking

We report a case of focal status epilepticus (SE) associated with peri-ictal water drinking (PIWD) behavior in a nine-year-old left-handed boy with epilepsy. We reviewed prior cases of epileptic peri-ictal water drinking. Only one adult patient with status epilepticus and PIWD has been reported previously. This is the first reported case of PIWD SE in a pediatric patient with frontal lobe epilepsy. We found PIWD to have no lateralizing value. Keywords: Peri-ictal water drinking, Status epilepticus, Seizur

Assessment of Indices of Vascular Involvement in Children with Idiopathic Nephrotic Syndrome: A Case-control Study

Introduction: Nephrotic Syndrome (NS) is characterised by proteinuria, oedema, hypoalbuminaemia, and hypercholesterolemia. The latter is a risk factor for atherosclerosis, suggesting a higher risk of cardiovascular disease in children with NS. Atherosclerosis is proposed to be caused by vascular endothelial dysfunction, reflecting the inflammatory response to tissue damage. Aim: To investigate indices of early vascular involvement in children with Idiopathic Nephrotic Syndrome (INS). Materials and Methods: This case-control study was conducted at a tertiary-care hospital, Pt. BD Sharma PGIMS Rohtak, Haryana, India, over a period of two years and two months. The study included 50 children aged <14 years with NS. Vascular indices, including Carotid Intima Media Thickness (CIMT), highsensitive C Reactive Protein (hs-CRP), and Atherogenic Index of Plasma (AIP), were evaluated. Analysis was performed using Statistical Package for the Social Sciences (SPSS) version 22.0 (IBM SPSS Statistics Inc., Chicago, Illinois, USA) Windows software program. The correlation of cardiovascular risk in children with NS was calculated by measuring CIMT, AIP, and CRP levels, and the relationship was analysed using the Chisquare test. A p-value of <0.05 was considered statistically significant. Results: The study found that the thickness of CIMT in group 1 was 0.67±1.39 mm, while in group 2, it was 0.31±0.04 mm. The calculated p-value was <0.001, which was statistically significant. The hs-CRP level in group 1 was 4.64±5.87 mg/L, higher than the control group (0.85±0.10 mg/L), with p-value of <0.001. Furthermore, AIP was higher in children with NS (0.80±0.19) compared to the control group (0.02±0.16). There was a statistically significant difference between both groups (p<0.001). Conclusion: Early assessment of indices of vascular involvement, such as CIMT, hs-CRP, and AIP, in children with INS can aid in the early identification and prevention of cardiovascular complications

Comparison of Interferon-Gamma Release Assay and Tuberculin Skin Test for the Screening of Latent Tuberculosis in Inflammatory Bowel Disease Patients: Indian Scenario

Background. In a country like India, where the prevalence of tuberculosis is very high, the role of screening tools for detection of latent tuberculosis infection (LTBI) like TST and IGRA is still unclear, especially in inflammatory bowel disease (IBD) patients. Our study is aimed at comparing the interferon-gamma release assay (IGRA) and tuberculin skin test (TST) to determine the prevalence of LTBI in IBD patients in the Indian subset of the population. Methods. It was a prospective observational analysis. A total of 257 participants were included in the study. Both TST and IGRA were performed in consecutive patients diagnosed with IBD (131 patients) and in 126 healthy individuals. Both tests were performed on the same day. LTBI diagnosis was considered if any one of TST or IGRA was found to be positive. Results. Out of 131 IBD patients, 121 patients had ulcerative colitis and 10 patients had Crohn’s disease. 29% of the IBD patients and 22% of the control subjects had LTBI. The study demonstrated concordance between TST and IGRA. Agreement test kappa value for IBD patients was 0.656 (CI 0.50-0.81), with a p value of <0.001, suggestive of a fair agreement. Mean IFN-γ release was lower in the immunosuppressed group as compared to non-immunosuppressed individuals (0.26±0.17 vs. 0.45±0.07, p=0.02). Cohen’s kappa coefficient values in IBD cases and control subjects were 0.66 and 0.79, respectively. TST was found to be negatively correlated to BMI. Conclusion. Agreement between TST and IGRA was fair in IBD patients. For LTBI screening in IBD patients, TST and IGRA are complementary methods