Common Target Organ Research Articles

Abstract P347: Association between Blood Pressure, Left Ventricular Structure and Cognitive Function: Evidence from a Cohort Study in Preschool-aged Children

Objective: Serving as a common hypertensive target organ damage, left ventricular (LV) structure alteration has been found to be associated with cognition decline in the elderly. However, its mediating role in the association between decreased cognitive function and elevated blood pressure (BP) remains controversial, owing to several inherent confounder in adults that could distort observed associations. The study was first known conducted to examine the association between LV structure, BP and cognitive function in preschool-aged children, a population without disturbance of various cardiovascular risk factors. Methods: This study included 1279 children from Shanghai Birth Cohort (SBC) during 2018 to 2021. Using the Wechsler Preschool and Primary Scales of Intelligence-Fourth Edition (WPPSI-IV), children’s intelligence quotient (IQ) was evaluated at 4-year-old. Detailed anthropometrics and BP measurements and echocardiography were conducted during follow-up. Multivariable linear regression models and restricted cubic spline were applied to estimate the association between individual BP, LV structure parameters and IQ scores. Results: There was no significant association found between cognitive function and LV structure in preschool-aged children, while higher BP levels was found to be correlated with lower scores in cognitive function. Children in the elevated BP and non-LVH group tended to have lower full-scale IQ (FSIQ). In detail, children with elevated BP tended to have lower scores in FSIQ (β: -2.95, 95%CI: -4.65, -1.25), processing speed index (β: -1.77, 95%CI: -3.41, -0.14), working memory index (β: -2.79, 95%CI: -4.70, -0.88) and visual spatial index (β: -2.64, 95%CI: -4.74, -0.55), and these associations were independent of LV structure. Conclusion: Higher BP levels was related to poor cognitive development during childhood as early as four, while LV structure alteration was not. The associations between BP and children’s decreased cognitive function was independent of LV structure.

The Role of Interferon-Induced Proteins with Tetratricopeptide Repeats 1 and 2 in Sepsis-Induced Acute Liver Injury.

Sepsis refers to a life-threatening organ dysfunction which can be resulted from the infection-induced dysregulated host response. A large number of inflammatory cytokines are released to act on the liver, making the liver one of the common target organs for the development of multiple organ dysfunction syndrome (MODS) in patients with sepsis. Sepsis-induced acute liver injury (SALI) can aggravate systemic disease. As a result, it is of great clinical significance to comprehend the molecular biological mechanism of SALI and to identify the markers for evaluating SALI. Interferon-induced proteins with tetratricopeptide repeats 1 and 2 (IFIT1, IFIT2) have been recognized as the anti-inflammatory factors that are widely expressed in various organs. The present study was aimed at clarifying the roles of IFIT1 and IFIT2 in the development of SALI. A two-sample Mendelian randomization (MR) analysis was employed. Summary statistics datas were obtained from GWAS for inflammatory factors [tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], IFIT2, and sepsis as well as liver injury. Independent SNPs were selected as instrumental variables (IVs). Inverse variance weighted (IVW) in the MR analysis was adopted as the primary method for estimating the causal associations of inflammatory factors and IFIT2 with two diseases, and the associations of inflammatory factors with IFIT2. Additionally, weighted median method, MR-Egger and sensitivity analyses were applied in assessing the robustness of the results and ensure the result reliability. Subsequently, 119 healthy volunteers, 116 patients with sepsis and 116 SALI patients were recruited. The ELISA method was employed to quantify the expression levels of TNF-α, IL-1β, and IL-6. Additionally, qRT-PCR was conducted to measure the expression of IFIT1 and IFIT2. Furthermore, the correlations of IFIT1 and IFIT2 with inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were explored. As shown by the MR analysis, the genetically predisposed sepsis was significantly associated with the risk of IL-1β, with an odds ratio (OR) of 1.069 (95% confidence interval (CI), 1.015-1.127, p = 0.0119), and negatively associated with the risk of IL-6, with an OR of 0.880 (95% CI: 0.792-0.979, p= 0.0184). Meanwhile, there were positive causal effects of IL-6 (OR = 1.269, 95% CI: 1.032-1.561, p= 0.0238), IL-1β (OR = 1.106, 95% CI: 1.010-1.211, p = 0.0299) and IFIT2 (OR = 1.191, 95% CI: 1.045-1.359, p = 0.0090) on liver injury. Additionally, there was a positive causal effect of IFIT2 (OR = 1.164, 95% CI: 1.035-1.309, p= 0.0110) on IL-1β. Upon sensitivity analyses, there was weak evidence of such effects, indicating that the findings of this study were robust and reliable. Our results revealed the elevated levels of TNF-α, IL-1β, and IL-6 in the blood samples of sepsis and SALI patients (p < 0.0001). Conversely, IFIT1 and IFIT2 demonstrated the significantly decreased levels in peripheral blood mononuclear cells (PBMCs) of SALI patients (p < 0.0001). Furthermore, the expression levels of IFIT1 and IFIT2 were both negatively correlated with ALT activity (r = -0.3426, p = 0.0002; r = -0.3069, p = 0.0008) and AST activity (r = -0.2483, p = 0.0072; r = -0.3261, p = 0.0004), respectively. Moreover, the expression of IFIT1 and IFIT2 was both negatively related to the levels of TNF-α (r = -0.5027, p < 0.0001; r = -0.4218, p < 0.0001), IL-1β (r = -0.3349, p = 0.0002; r = -0.4070, p < 0.0001) and IL-6 (r = -0.2734, p = 0.0030; r = -0.3536, p < 0.0001), respectively. IFIT1 and IFIT2 can serve as the diagnostic markers for sepsis-related liver injury, and IFIT1 and IFIT2 may participate in the pathological process of sepsis-related liver injury by regulating inflammation and liver function.

Estimating the Lifetime Cost of Managing Hypertension in Ghana: A Modelling Study.

Over the last decade, hypertension (HPT) is among the leading causes of death and morbidity in Ghana. In recent past, most health policy research in Ghana and Africa focussed on communicable diseases. In recent times, Ghana and other developing nations have shifted their attention to non-communicable diseases because most of these countries are going through an epidemiologic transition where there is a surge in the prevalence of HPT. This paper was therefore set out to estimate the cost of treating HPT in Ghana from the patients' and health system's perspectives. We used a cost of illness framework to simulate the cost of HPT management in Ghana taking into account 4 of the common target organ complications with the most mortality implication. A decision analytic model (DAM) was developed in Microsoft® Excel to simulate the progression of HPT patients and the Markov model was employed in simulating the lifetime cost of illness. The results show that by 10 years from diagnosis, the probability of death from any of the 4 complications (ie, stroke, myocardial infarction, heart failure, and chronic kidney disease) is roughly 41.03%. By 20 years (or 243 months) from diagnosis, the probability of death is estimated to be 69.61%. However, by the 30th anniversary, the probability of death among the cohort is 82.3%. Also, the lifetime discounted cost of treating HPT is about GHS 869 106 which could range between GHS 570 239 and GHS 1.202 million if wide uncertainty is taken into account. This is equivalent to USD 119 056 (range: USD 78 115-164 723). By highlighting the lifetime cost of treating HPT in Ghana, policies can be formulated regarding the cost of treating HPT by the non-communicable disease unit and National Health Insurance Authority (NHIA) of the Ministry of Health.

The Depiction of Hypertension in Heart Imaging Examinations: An Up-to-Date Review of the Evidence.

Hypertension is one of the main preventable cardiovascular (CV) risk factors all over the years, closely related to CV morbidity and mortality. One of the most common hypertensive target organ damages is hypertensive heart disease (HHD), including left ventricular hypertrophy, which progresses gradually and leads to systolic or diastolic dysfunction of the left ventricular, and finally to end-stage heart failure. Regarding its prevalence and the need for early diagnosis, assessment of heart imaging examination is of major importance. Echocardiography has been used as the standard imaging technique to evaluate HHD for years, providing an accurate evaluation of the left ventricular geometry, along with the systolic and diastolic function. However, nowadays there is a growing interest in cardiovascular magnetic resonance (CMR). Despite the importance of the use of echocardiography in everyday clinical practice, numerous studies have shown the superiority of CMR as an imaging technique for clinical and research purposes, mainly due to its strength to provide an unlimited area of view, as well as the identification and quantification of the type and extent of myocardial fibrosis. Hence, this review aims to analyze the importance of heart imaging in the hypertensive population, with a special interest in CMR imaging.

Resection of giant sigmoid cancer metastasis in the skull bone with extra-, intracranial distribution

The most common secondary target organs in patients with colorectal cancer are the liver and lungs. Cranial metastases from sigmoid colon cancer are rare. Giant cranial metastases are currently diagnosed in exceptional cases.The article presents a clinical case of a secondary extra‑intracranial lesion with a stable primary tumor focus in the sigmoid colon in a young patient with a high functional status.

The Relationship Between Serum Angiotensin Converting Enzyme Level and the Decision to Escalate Treatment of Sarcoidosis.

We performed a retrospective analysis of a sarcoidosis cohort who had sACE obtained at their initial clinic visit, but the treating physician was blinded to the results. We examined the relationship between sACE and the treating physician's decision to escalate sarcoidosis treatment. Treatment was considered escalated if the prednisone dose was increased or if the prednisone dose was not changed but an additional anti-sarcoidosis drug was added or the dose was increased. 561 sarcoidosis patients were analyzed. The most common target organ was the lung (84%). Using a cut-off of > 82 units/L for an elevated sACE, 31/82 (38%) with an elevated sACE had treatment escalation whereas 91/497 (18%) had treatment escalation with a normal sACE (p < 0.0001). For the need of treatment escalation, a sACE (cut-off of > 82) had sensitivity 0.25, specificity 0.89, positive predictive value 0.38, negative predictive value 0.81. These results were not appreciably different using other sACE cut-off values such as 70, 80, 90, or 100. A multivariable logistic regression model that included demographics, the target organ, spirometry results estimated that sACE level and lower FVC were significantly associated with the likelihood of treatment escalation. These findings held when sACE > 82 replaced sACElevel in the multivariable logistic regression model. Although there was a strong correlation between sACE at the initial sarcoidosis clinic visit and subsequent treatment escalation of sarcoidosis, the predictive power was such that sACE is not adequately reliable to be used in isolation to make this determination.

Deficiency of Tregs in hypertension-associated left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is the most common target organ damage in hypertension. Abnormal numbers or functions of CD4+ CD25+ Foxp3+ regulatory T lymphocytes (Tregs) can cause immune disorders, which participates in LVH. This study aimed to explore the role of Tregs in LVH by investigating circulating Tregs and associated cytokine levels in hypertensive patients with or without LVH. Blood samples were collected from 83 hypertensive patients without LVH (essential hypertension group, EH), 91 hypertensive patients with LVH (left ventricular hypertrophy group, LVH), and 69 normotensive controls without LVH (control group, CG). Tregs and cytokines were measured by flow cytometry and enzyme-linked immunosorbent assays. We found that circulating Tregs were significantly lower in hypertensive patients than in CG subjects. It was lower in LVH than in EH patients. No correlation between blood pressure regulation and Tregs was found in EH or LVH patients. Furthermore, Tregs in older females were lower than those in older males among LVH patients. Additionally, serum interleukin-10 (IL-10) and transforming growth factor beta 1 (TGFβ1) decreased in hypertensive patients, and interleukin-6 (IL-6) increased in LVH patients. Tregs were negatively correlated with creatine kinase, low-density lipoprotein cholesterol, apoprotein B, high-sensitivity C-reactive protein, and left ventricular mass index (LVMI) values. In general, our study demonstrates significantly decreased circulating Tregs in hypertensive LVH patients. Decreased circulating Tregs in LVH is independent of blood pressure regulation. IL-6, IL-10, and TGF-β1 are related with LVH in hypertension.

Macrophage transcription factor TonEBP promotes systemic lupus erythematosus and kidney injury via damage-induced signaling pathways

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by autoreactive B cells and dysregulation of many other types of immune cells including myeloid cells. Lupus nephritis (LN) is a common target organ manifestations of SLE. Tonicity-responsive enhancer-binding protein (TonEBP, also known as nuclear factor of activated T-cells 5 (NFAT5)), was initially identified as a central regulator of cellular responses to hypertonic stress and is a pleiotropic stress protein involved in a variety of immunometabolic diseases. To explore the role of TonEBP, we examined kidney biopsy samples from patients with LN. Kidney TonEBP expression was found to be elevated in these patients compared to control patients - in both kidney cells and infiltrating immune cells. Kidney TonEBP mRNA was elevated in LN and correlated with mRNAs encoding inflammatory cytokines and the degree of proteinuria. In a pristane-induced SLE model in mice, myeloid TonEBP deficiency blocked the development of SLE and LN. In macrophages, engagement of various toll-like receptors (TLRs) that respond to damage-associated molecular patterns induced TonEBP expression via stimulation of its promoter. Intracellular signaling downstream of the TLRs was dependent on TonEBP. Therefore, TonEBP can act as a transcriptional cofactor for NF-κB, and activated mTOR-IRF3/7 via protein-protein interactions. Additionally, TonEBP-deficient macrophages displayed elevated efferocytosis and animals with myeloid deficiency of TonEBP showed reduced Th1 and Th17 differentiation, consistent with macrophages defective in TLR signaling. Thus, our data show that myeloid TonEBP may be an attractive therapeutic target for SLE and LN.

Abstract P1-11-03: VRN101099, Brain Permeable HER2 Kinase Inhibitor, Shows the Anti-tumor Activity in Preclinical Models of HER2-positive Cancers

Abstract The brain is a common target organ for breast cancer metastasis, and the risk of brain metastasis is usually high for patients with HER2-positive breast cancer. While T-DXd showed positive results in HER2-positive breast cancer brain metastasis (BCBM), its activity and blood-brain barrier (BBB) permeability in active BCBM need to be further validated (TUXEDO-1 included 15 patients with active brain metastasis). Tucatinib plus Trastuzumab and Capecitabine triplet showed efficacy in patients with brain metastasis, but Tucatinib alone has poor BBB penetration. There is still an unmet medical need for active HER2-positive BCBM. VRN101099 is a highly selective kinase inhibitor of HER2 (Eurofins scanMAX Kinase Profiling, S-score (35) of 0.01). VRN101099 has single- to double-digit nanomolar (IC50) cellular potency in HER2-dependent cancer cells, and Ba/F3 cells expressing HER2 wild type or mutations with selectivity over wildtype EGFR. VRN101099 inhibited proliferation of BT474 with 3.6 nM IC50 but HaCaT with 829.2 nM IC50. VRN101099 binds HER2 kinase by forming a covalent bond to the Cys805 and its irreversible inhibition resulted in a longer target resident time than Tucatinib, confirmed by in vitro washout experiments. Robust in vivo activity of VRN101099 was observed in HER2-positive BT474 xenograft models. Moreover, once daily oral administration of VRN101099 significantly regressed intracranial BT474 tumor, demonstrating greater efficacy than twice daily oral administration of Tucatinib. These results were well explained by the superior brain to plasma exposure of VRN101099 to Tucatinib. Also, VRN101099 showed high exposure in the target organ, the fat pad, which potentiated better clinical translation. These anti-tumor efficacies are correlated with pharmacodynamic responses, as confirmed by decreased HER2, AKT, and ERK phosphorylation. In summary, VRN101099 is a brain penetrant, orally bioavailable, irreversible, and highly selective inhibitor of HER2 with therapeutic potential in HER2-positive BCBM. These data support the clinical development of VRN101099 in HER2-driven cancers. Citation Format: Yikyung Ko, Jihye yoo, Hong-ryul Jung, Hyerim Lim, YeongDeok Lee, Se Hyuk Kim, Dong Guk Shin, Serin Cho, Myung hoe Heo, Haelee Kim, Ha Yeon Cho, Ah Reum Han, Eunhwa Ko, Hwan Geun Choi, Deakwon Kim, Sunghwan Kim. VRN101099, Brain Permeable HER2 Kinase Inhibitor, Shows the Anti-tumor Activity in Preclinical Models of HER2-positive Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-03.

Hypertriglyceridemic waist phenotype is associated with left ventricular hypertrophy in Chinese hypertension patients

Left ventricular hypertrophy (LVH), the most common target organ damage in patients with hypertension, is closely related to excessive visceral adipose tissue (VAT) accumulation in the body. The hypertriglyceridemic waist (HTHW) phenotype can act as a surrogate marker of excessive VAT. However, the relationship between the HTHW phenotype and LVH in patients with hypertension remains unknown. The present study aimed to investigate whether the HTHW phenotype is associated with LVH, using echocardiography in a cross-sectional study involving 4470 middle-aged and older Chinese patients with hypertension. Logistic regression analysis revealed that patients with the HTHW phenotype were 1.52-fold more likely to experience LVH than those with normal triglyceride levels and normal waist circumference. This association was independent of age, sex, and other potentially confounding factors. In the stratified analysis, a stronger correlation was found among women, people of at least 70years of age, and people with hyperuricemia. These results suggest that distinguishing the HTHW phenotype in patients with hypertension could serve as a simple and effective screening strategy for identifying people with a higher risk of developing LVH.

Identifying chemicals based on receptor binding/bioactivation/mechanistic explanation associated with potential to elicit hepatotoxicity and to support structure activity relationship-based read-across

The liver is the most common target organ in toxicology studies. The development of chemical structural alerts for identifying hepatotoxicity will play an important role in in silico model prediction and help strengthen the identification of analogs used in structure activity relationship (SAR)- based read-across. The aim of the current study is development of an SAR-based expert-system decision tree for screening of hepatotoxicants across a wide range of chemistry space and proposed modes of action for clustering of chemicals using defined core chemical categories based on receptor-binding or bioactivation. The decision tree is based on ∼ 1180 different chemicals that were reviewed for hepatotoxicity information. Knowledge of chemical receptor binding, metabolism and mechanistic information were used to group these chemicals into 16 different categories and 102 subcategories: four categories describe binders to 9 different receptors, 11 categories are associated with possible reactive metabolites (RMs) and there is one miscellaneous category. Each chemical subcategory has been associated with possible modes of action (MOAs) or similar key structural features. This decision tree can help to screen potential liver toxicants associated with core structural alerts of receptor binding and/or RMs and be used as a component of weight of evidence decisions based on SAR read-across, and to fill data gaps.

Cardiac damage in autoimmune diseases: Target organ involvement that cannot be ignored.

Autoimmune diseases are diseases that cause damage to the body's own tissues as a result of immune dysfunction, often involving multiple organs and systems. The heart is one of the common target organs of autoimmune diseases. The whole structure of the heart can be affected, causing microcirculatory disorders, arrhythmias, pericardial damage, myocarditis, myocardial fibrosis, and impaired valvular function. However, early clinical manifestations of autoimmune heart damage are often overlooked because they are insidious or have no typical features. The damage is often severe and irreversible when symptoms are apparent, even life-threatening. Therefore, early detection and treatment of heart damage in autoimmune diseases is particularly important. Herein, we review the clinical features and mechanisms of cardiac damage in common rheumatic diseases.

Diagnosis and treatment of liver metastases of parathyroid carcinoma.

IntroductionParathyroid carcinoma (PC) is a very rare endocrine malignancy occurring in less than 1% of all cases of primary hyperparathyroidism (pHPT). The liver is the second most common target organ for distant metastases of PC, but no guidelines are available for the diagnosis and treatment of liver metastases. In this study, we attempted to summarize the characteristics of the diagnosis and treatment of liver metastases based on our patients and other cases reported in the literature.Materials and methodsThe files of all patients diagnosed with PC with liver metastases summarized at our center between 2000 and 2022 were reviewed, and three datasets from Medline, Web of Science, and Embase were systematically searched to identify relevant articles.ResultsThree patients with liver metastases from our center and 11 patients from the literature were included in the study. All patients had pHPT with borderline remission of hypercalcemia after each operation. A total of 71.4% of the patients’ liver lesions were found by abdominal CT scans, while 35.7% were found by MRI, PET-CT, and fine-needle aspiration biopsy (FNAB), which were also helpful for diagnosis. Eight of nine patients (88.9%) who underwent surgery, radiofrequency ablation (RFA), or transcatheter arterial embolization (TAE) were alive, and only one postoperative patient died after a follow-up of 60 months.ConclusionsPC is a rare malignant tumor prone to recurrence and metastasis, and postoperative reviews should be carried out routinely. Abnormally elevated parathyroid hormone (PTH) and serum calcium can indicate recurrence or metastasis. Enhanced CT and MRI can provide valuable support for the diagnosis of liver metastases, but whether [18F]FDG-PET-CT, [18F]FCH-PET-CT, or [11C]choline-PET-CT can be used as a diagnostic basis requires further study. Resection of liver metastases, segmental hepatectomy, or RFA can significantly improve patients’ symptoms.

S2416 A Case of Severe Undifferentiated Ulcerative Esophagitis as an AIDS-Defining Illness in Acute HIV Infection

Introduction: The esophagus is a common target organ in acute HIV infection (fungal or viral agents). Idiopathic esophageal ulcers are less common and we present a case of severe idiopathic ulcerative esophagitis in acute HIV infection. Case Description/Methods: 29-year-old male with no prior medical history presented with symptoms of odynophagia, dysphagia and limited oral intake for 2 weeks. Due to his symptoms, he lost 25lbs at presentation. Esophagogastroduodenoscopy (EGD) revealed long cratered ulcerations with friability to the edges in the mid and distal esophagus (Figure 1a). The mucosa between the ulcers appeared normal. Closer to the gastroesophageal junction (GEJ), there was evidence of healing ulcers without friability or cratered appearance (Figure 1b). These lesions were biopsied (edges and base). The mucosa of the proximal esophagus, stomach and duodenum appeared normal. Due to endoscopic assessment concerning for viral infection, serology (HSV, CMV and HIV) were ordered. The patient was treated with empiric Valgancyclovir for presumed CMV esophagitis. The biopsy stained positive for undifferentiated hyphae type mold elements and viral stains were negative. His viral serology were normal but HIV RNA testing was positive. With infectious disease engagement, additional tests were done to rule out any opportunistic infection and results were negative. He was started on HAART therapy. Two weeks after initiating Valgancyclovir and HAART therapy, a repeat EGD showed significant improvement in the mid and distal esophageal mucosa ulceration with only one clean base cratered ulcer noted (Fig 2a). There were new and enlarged scattered white plaques throughout the entire esophagus up to the level of the GEJ (Fig. 2b). Several biopsies obtained from the ulcer and the white plaques were consistent with candida esophagitis, see Figure 2b. He was treated with a course of fluconazole. Currently, patient is well controlled on HAART therapy with excellent immunologic and virologic response. Discussion: Idiopathic esophageal ulcers occur in about 10% of patients with acute HIV infection or AIDS. Prior reports have described giant (greater than 5cm) ulcers with profound depth usually located in the mid esophagus. The exact pathophysiology is unknown. Gastroenterologists should maintain a low index suspicion for an immunocompromised state in all patients presenting with odynophagia or dysphagia. Upon diagnosis, compliance with HAART therapy is key for treatment of HIV related esophageal ulcers.Figure 1

Glomerular filtration in the aging population.

In the last decades, improvements in the average life expectancy in the world population have been associated with a significant increase in the proportion of elderly people, in parallel with a higher prevalence of non-communicable diseases, such as hypertension and diabetes. As the kidney is a common target organ of a variety of diseases, an adequate evaluation of renal function in the approach of this population is of special relevance. It is also known that the kidneys undergo aging-related changes expressed by a decline in the glomerular filtration rate (GFR), reflecting the loss of kidney function, either by a natural senescence process associated with healthy aging or by the length of exposure to diseases with potential kidney damage. Accurate assessment of renal function in the older population is of particular importance to evaluate the degree of kidney function loss, enabling tailored therapeutic interventions. The present review addresses a relevant topic, which is the effects of aging on renal function. In order to do that, we analyze and discuss age-related structural and functional changes. The text also examines the different options for evaluating GFR, from the use of direct methods to the implementation of several estimating equations. Finally, this manuscript supports clinicians in the interpretation of GFR changes associated with age and the management of the older patients with decreased kidney function.

Hypertensive emergencies in Asia: A brief review.

Hypertensive emergency is one of the most challenging conditions to treat in the emergency department (ED). From previous studies, about 1%–3% of hypertensive individuals experienced hypertensive emergencies. Its prevalence varied by country and region throughout Asia. Asian populations have more different biological and cultural backgrounds than Caucasians and even within Asian countries. However, there is a scarcity of research on clinical features, treatment, and outcomes in multinational Asian populations. The authors aimed to review the current evidence about epidemiology, clinical characteristics and outcomes, and practice guidelines in Asia.Five observational studies and nine clinical practice guidelines across Asia were reviewed. The prevalence of hypertensive emergencies ranged from .1% to 1.5%. Stroke was the most common target organ involvement in Asians who presented with hypertensive emergencies. Although most hypertensive emergency patients required hospitalization, the mortality rate was low. Given the current lack of data among Asian countries, a multinational data repository and Asian guidelines on hypertensive emergency management are mandatory.

Protective effect of Astragalus membranaceus and Astragaloside IV in sepsis-induced acute kidney injury.

Background: Acute kidney injury (AKI) is the most common target organ damage in sepsis. Sepsis-associated AKI (SA-AKI) may be characterized by damage to the renal tubular epithelium. In this study, the pharmacological mechanisms of Astragalus membranaceus and its active monomer Astragaloside IV (AS-IV) were predicted based on a network pharmacology approach and validated both in vitro and in vivo using the SA-AKI model.Method: We constructed an in vivo sepsis model using a mouse cecum ligation puncture (CLP) and HK-2 cells were treated with lipopolysaccharide (LPS) to mimic Gram (–) induced sepsis to assess the renal-protective efficacy of Astragalus membranaceus and AS-IV.Results: The findings demonstrated that Astragalus membranaceus and AS-IV attenuate renal tubular injury in mice with polymicrobial sepsis, including vacuolization, loss of brush border, mitochondrial ultrastructural changes, and increased staining of kidney injury molecule-1 (KIM-1). AS-IV protected human proximal tubular epithelial (HK-2) cells against LPS induced cell viability loss. Both Astragalus membranaceus and AS-IV activated the PI3K/AKT pathway both in vitro and in vivo, as shown by Western blot and immunohistochemistry analysis.Conclusion: The findings demonstrate that Astragalus membranaceus and AS-IV protect against sepsis-induced kidney tubular injury by activating the PI3K/AKT pathway.

Combined Exposure to Multiple Mycotoxins: An Example of Using a Tiered Approach in a Mixture Risk Assessment.

Humans are exposed to mycotoxins on a regular basis. Exposure to a mixture of mycotoxins may, therefore, result in a combination of adverse effects, or trigger the same effects. This should be accounted for when assessing the combined risk of multiple mycotoxins. Here, we show the outcome of using different approaches in assessing the risks related to the combined exposure to mycotoxins. We performed a tiered approach using assessment groups with a common target organ (kidney, liver and haematologic system), or a common adverse effect (phenomenon) (reduced white blood cell count), to combine the exposure to mycotoxins. The combined exposure was calculated for the individuals in this assessment, using the Monte Carlo Risk Assessment (MCRA) tool. The risk related to this combined exposure was assessed using toxicological reference values, e.g., health based guidance values. We show that estimating the combined risk by adding the single compounds’ risk distributions slightly overestimates the combined risk in the 95th percentile, as compared to combining the exposures at an individual level. We also show that relative potency factors can be used to refine the mixture risk assessment, as compared to ratios of toxicological reference values with different effect sizes and assessment factors.

Review on Coexistence of Hypertension with Diabetes Mellitus

The coexistence of both diabetes mellitus and hypertension affect the some major target organs. Their common target organ is heart and kidney. The primary goal in the management of the hypertensive diabetic patients is lowering blood pressure to less than 130/80mm Hg Beta- blockers have been reported to adversely affect the overall risk factor profile in the diabetic patient. Initially ACE inhibitors and ARB are initially can be given to diabetic hypertensive. Beta blockers also show great effects in preventing further cardiovascular diseases in diabetic hypertensive. Although combined drug therapy is usually required to achieve goal but in addition to drug therapy some other precautions should also plays effective role like exercise، low sodium chloride intake, lower lipids in diet, maintaining glucose level, stress less patients environment.&#x0D; Calcium channels blockers and diuretics in combination with ACE inhibitors and antidiabetic drugs will also exerts beneficial effects.

Insights into COVID-19 Vaccine Development Based on Immunogenic Structural Proteins of SARS-CoV-2, Host Immune Responses, and Herd Immunity.

The first quarter of the 21st century has remarkably been characterized by a multitude of challenges confronting human society as a whole in terms of several outbreaks of infectious viral diseases, such as the 2003 severe acute respiratory syndrome (SARS), China; the 2009 influenza H1N1, Mexico; the 2012 Middle East respiratory syndrome (MERS), Saudi Arabia; and the ongoing coronavirus disease 19 (COVID-19), China. COVID-19, caused by SARS-CoV-2, reportedly broke out in December 2019, Wuhan, the capital of China’s Hubei province, and continues unabated, leading to considerable devastation and death worldwide. The most common target organ of SARS-CoV-2 is the lungs, especially the bronchial and alveolar epithelial cells, culminating in acute respiratory distress syndrome (ARDS) in severe patients. Nevertheless, other tissues and organs are also known to be critically affected following infection, thereby complicating the overall aetiology and prognosis. Excluding H1N1, the SARS-CoV (also referred as SARS-CoV-1), MERS, and SARS-CoV-2 are collectively referred to as coronaviruses, and taxonomically placed under the realm Riboviria, order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae, genus Betacoronavirus, and subgenus Sarbecovirus. As of 23 September 2021, the ongoing SARS-CoV-2 pandemic has globally resulted in around 229 million and 4.7 million reported infections and deaths, respectively, apart from causing huge psychosomatic debilitation, academic loss, and deep economic recession. Such an unprecedented pandemic has compelled researchers, especially epidemiologists and immunologists, to search for SARS-CoV-2-associated potential immunogenic molecules to develop a vaccine as an immediate prophylactic measure. Amongst multiple structural and non-structural proteins, the homotrimeric spike (S) glycoprotein has been empirically found as the most suitable candidate for vaccine development owing to its immense immunogenic potential, which makes it capable of eliciting both humoral and cell-mediated immune responses. As a consequence, it has become possible to design appropriate, safe, and effective vaccines, apart from related therapeutic agents, to reduce both morbidity and mortality. As of 23 September 2021, four vaccines, namely, Comirnaty, COVID-19 vaccine Janssen, Spikevax, and Vaxzevria, have received the European Medicines Agency’s (EMA) approval, and around thirty are under the phase three clinical trial with emergency authorization by the vaccine-developing country-specific National Regulatory Authority (NRA). In addition, 100–150 vaccines are under various phases of pre-clinical and clinical trials. The mainstay of global vaccination is to introduce herd immunity, which would protect the majority of the population, including immunocompromised individuals, from infection and disease. Here, we primarily discuss category-wise vaccine development, their respective advantages and disadvantages, associated efficiency and potential safety aspects, antigenicity of SARS-CoV-2 structural proteins and immune responses to them along with the emergence of SARS-CoV-2 VOC, and the urgent need of achieving herd immunity to contain the pandemic.