Breast Carcinoma; Human Epidermal Growth Factor Receptor-2 (HER-2) and Grading Correlation

Introduction: Overexpression of Human Epidermal Growth factor Receptor-2 (HER-2) is one of the most important prognostic and predictive factors of breast cancer, observed in 25% - 30% of breast carcinoma patients leading to poor prognosis and feasible anti HER-2 antibody drugs. The objective of this study was to evaluate the HER-2 frequency in target population and its correlation with histologic grade as well as tumor pathology, estrogen receptor (ER) and P53 in our patients. Methods: A total of 300 cases (all female) aged 24- 80 year, were randomly selected from patients who were admitted in two of the Tehran University of Medical Sciences affiliated centers (Emam Khomeini Cancer Institute and Shariati hospital) over a 2-year period (2013-2014). Assessment of tumors for HER-2, P53, ER, pathological type and histologic grade was performed. HER-2 over expression defined as three plus (+++) in immunohistochemistry (IHC). Results: The mean age was 49.6±11 years. HER-2 over expression was seen in 34% of the patients. Significant correlations were found between HER-2+, P53+ and high histologic grade and ER (PConclusion: Co-expression of several poor prognostic biomarkers in breast cancer (HER-2 +, P53 +, ER- , high grade) may predict more aggressive phenotype, worse disease and lower overall survival in these patients

The wound healing effect of Iris forentina on full thickness excisional skin wounds: A histomorphometrical study

Iris florentina is an ancient herbal remedy which was prescribed by many physicians due to its positive effects on dermatological problems, specifically skin wounds. Hence, we aimed to investigate the effects of this agent on full-thickness excisional skin wounds in laboratory rats. Three groups of rats (180 ± 20 g; n=8) with 1 cm diameter full-thickness excisional skin wound received daily treatment with I. florentina 10% ointment, and a group with no treatment. By using histomorphometrical methods, the amount of fibroblast population, collagen bundle synthesis, and vascularization (length density, mean diameter and volume density of the vessels) were estimated. Outcome of the study exhibited that the increase in fibroblast proliferation rate, collagen bundle synthesis, vascular density and vascular mean diameter in I. florentina-treated group were significant in comparison to the untreated group (p<0.05). Results indicated that I. florentina can be prescribed as a herbal medicine for treatment of skin wounds or be used as an additional agent for today's common medicines

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health 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

Genetic susceptibility to hereditary non-medullary thyroid cancer

Abstract Non-medullary thyroid cancer (NMTC) is the most common type of thyroid cancer. With the increasing incidence of NMTC in recent years, the familial form of the disease has also become more common than previously reported, accounting for 5–15% of NMTC cases. Familial NMTC is further classified as non-syndromic and the less common syndromic FNMTC. Although syndromic NMTC has well-known genetic risk factors, the gene(s) responsible for the vast majority of non-syndromic FNMTC cases are yet to be identified. To date, several candidate genes have been identified as susceptibility genes in hereditary NMTC. This review summarizes genetic predisposition to non-medullary thyroid cancer and expands on the role of genetic variants in thyroid cancer tumorigenesis and the level of penetrance of NMTC-susceptibility genes

A Review of the Clinical Implications of Breast Cancer Biology

Background: Histologically similar tumors may have different prognoses and responses to treatment. These differences are due to molecular differences. Hence, in this review, the biological interaction of breast cancer in several different areas is discussed. In addition, the performance and clinical application of the most widelyrecognized biomarkers, metastasis, and recurrences from a biological perspective and current global advances in these areas are addressed. Objective: This review provides the performance and clinical application of the most widely-recognized biomarkers, metastasis, and recurrences from the biological perspective and current global advances in these areas. Methods: PubMed, Scopus, and Google Scholar were searched comprehensively with combinations of the following keywords: “breast cancer,” “biological markers,” and “clinical.” The definition of breast cancer, diagnostic methods, biological markers, and available treatment approaches were extracted from the literature. Results: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER- 2), and Ki-67 are the most well-known biological markers that have important roles in prognosis and response to therapeutic methods. Some studies showed the response of ER-positive and PR-negative tumors to anti- estrogenic treatment to be lower than ER-positive and PR-positive tumors. Patients with high expression of HER- 2 and Ki-67 had a poor prognosis. In addition, recent investigations indicated the roles of new biomarkers, such as VEGF, IGF, P53 and P21, which are associated with many factors, such as age, race, and histological features. Conclusion: The objective of scientists, from establishing a relationship between cancer biology infrastructures with clinical manifestations, is to find new ways of prevention and progression inhibition and then possible introduction of less dangerous and better treatments to resolve this dilemma of human society

Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 on L-Arginine-Induced Acute Pancreatitis in Rat

This study was aimed at evaluating the protective effect of coenzyme Q10 on L-arginine-induced acute pancreatitis in rats regarding biomarkers and morphologic changes. Thirty-two male Sprague-Dawley rats were divided into 4 equal groups. Control group received intraperitoneal normal saline, while in sham and experimental groups 1 and 2 pancreatitis was induced with L-arginine. E1 and E2 groups were treated with a single dose of 100 and 200 mg/kg Q10, respectively. Serum lipase and amylase, along with pancreas IL-10, IL-1β, and TNF-α, were measured. For evaluation of oxidative stress, pancreatic superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) were assessed. Histopathological examination for morphologic investigation was conducted. Serum amylase and lipase, as well as TNF-α and IL-1β cytokines, reverted with administration of Q10 in consistence with dosage. In contrast, Q10 assisted in boosting of IL-10 with higher dosage (200 mg/kg). A similar pattern for oxidative stress markers was noticed. Both MDA and MPO levels declined with increased dosage, contrary to elevation of SOD and GSH. Histopathology was in favor of protective effects of Q10. Our findings proved the amelioration of pancreatic injury by Q10, which suggest the anti-inflammatory and antioxidant property of Q10 and its potential therapeutic role

Low Serum Trypsin Levels Predict Deep Pancreatic Cannulation Failure during ERCP in Patients with Chronic Pancreatitis

Background: Deep pancreatic cannulation failure (DPCF) during ERCP in patients with chronic pancreatitis (CP) can occur in the presence of duct obstruction due to strictures and/or stones. There are currently no simple preprocedure clinical or laboratory tests that can predict DPCF during ERCP. Since low serum trypsin levels have been correlated with advanced chronic pancreatitis and exocrine insufficiency, we hypothesized that it might be a useful preprocedure test for predicting DPCF. Aim: To assess whether low serum trypsin levels predict DPCF failure of deep pancreatic duct cannulation during ERCP in patients with chronic pancreatitis. after adjusting for obstructing strictures and/or stones. Method: All adult (\u3e18 year of age) patients with definite CP who were referred to a multidisciplinary pancreatitis clinic between 2010-2015 and underwent a serum trypsin level measurement prior to ERCP for the management of abdominal pain were evaluated. Serum trypsin levels are obtained in all CP patients as part of their evaluation for exocrine insufficiency. Exclusion criteria included chronic kidney disease, prior pancreatic resection, and/or type 1 diabetes mellitus as these conditions can affect serum trypsin levels independent of CP. Definite CP was defined as abdominal pain and/or acute recurrent pancreatitis in the presence of calcification(s) on CT scan and endoscopic ultrasound EUS and/or moderate to severe ductal changes based on the MANNHEIM criteria. Low serum trypsin was defined as values \u3c 19 ng/mL or \u3c10 ng/mL based on laboratory assay. Failure of deep cannulation during ERCP was defined as the inability to advance any accessory (sphincterotome guidewire, cannula, and/or guidewire sphincterotome) upstream of an obstructing stricture and/or stone which would be necessary for the completion of therapeutic maneuvers (stone extraction, stricture dilation, stone extraction and stent placement). Heavy smoking and alcohol use was defined per NAPS2 study. Serum trypsin levels, pancreatic stone(s) and duct stricture were evaluated as Ffactors associated with DPCF during ERCP were evaluated using univariable and multivariable logistic regression analysis. Results: Among 213 patients diagnosed with definite CP, 104 patients underwent trypsin measurements and ERCP, of whom 42 (40.4%) had low/undetectable serum trypsin levels and 37 (35.6%) had DPCF during ERCP. There were no significant differences between patients with and without DPCF low/ undetectable and normal trypsin levels with regards to age, gender, etiology, smoking, and pancreas divisum. Patients with DPCF were more likely to have low trypsin levels (68% vs. 25%, p\u3c0.0001), obstructing stones (86% vs. 57%, p=0.02), and strictures (69%% vs. 30.9%, p=0.001) compared to those without DPCF. Patients with low/undetectable trypsin had significantly higher rates of heavy alcohol use (61.1%) (p=0.006) and calcifications (51.4%) (p=0.002) detected on CT scan or EUS. A total of 6 (54.5%) out of 11 patients who underwent ESWL after failure of ERCP, had successful deep pancreatic cannulation on subsequent ERCP. A low /undetectable serum trypsin level was significantly associated with DPCF in the both the univariable (OR: 6.13; 95% CI: 2.5-14.8; P\u3c0.001) and multivariable (OR: 5.99; 95%CI: 2.13-16.83; P=0.001) analysis after adjusting for obstructing stones and stricture. Conclusion: Preprocedural low serum trypsin levels independently predict DPCF during ERCP in patients with chronic pancreatitis. Consideration of ESWL prior to ERCP may increase successful deep pancreatic cannulation rates