Acute Arterial Hypertension Research Articles

Oxygenation Effects of Antihypertensive Agents in Intensive Care: A Prospective Comparative Study of Nicardipine and Urapidil.

Acute arterial hypertension within the critical care context may necessitate the administration of intravenous antihypertensive agents. Nicardipine and urapidil are notable for their application in intensive care units. Nonetheless, dihydropyridine calcium channel inhibitors (DCCIs) such as nicardipine are implicated in the impairment of hypoxic pulmonary vasoconstriction, potentially disrupting oxygenation. This study aimed to assess the differences in patient oxygenation when these antihypertensive agents are administered intravenously. This bicentric, prospective, observational investigation spanning five intensive care units evaluated patients requiring intravenous nicardipine or urapidil. Oxygenation data were recorded from the start of therapy until the 12th hour. Comparative analysis was performed between patient groups based on the antihypertensive agent administered, along with subgroup investigations to identify populations with an elevated risk of hypoxemia. From November 2021 to November 2023, 197 patients were included: 98 (50%) were treated with nicardipine, and 99 (50%) were treated with urapidil. Hypoxemia occurred in 97 (49%) patients and was more prevalent in the nicardipine cohort, affecting 65 (66%) patients, as opposed to 32 (32%) patients in the urapidil cohort (RR 2.05, 95% CI [1.48-2.82], P < 0.001). Subgroup analysis revealed a significant association between patients with pulmonary atelectasis (RR 2.30, 95% CI [1.4-3.7], P < 0.001) and obesity (RR 2.7, 95% CI [1.5-4.6], P < 0.001). Considering these findings, cautious consideration of the patient's respiratory status should be exercised when initiating intravenous DCCI treatment. However, given the limitations of this study, a controlled trial on hypertension management in the ICU is needed.

LncRNA MEG3 aggravates acute pulmonary embolism-induced pulmonary arterial hypertension by regulating miR-34a-3p/DUSP1 axis.

Acute pulmonary embolism (APE)-induced pulmonary artery hypertension (PAH) is a fatal disease. The miR-34-3p/DUSP1 has inhibitory effects on the thickening of the pulmonary arterial walls in APE rats and the proliferation of platelet-derived growth factor-BB (PDGF-BB)-induced human pulmonary arterial smooth muscle cells (hPASMCs). Herein, the lncRNAs regulating the miR-34a-3p/DUSP1 axis in APE and PAH are further explored in vitro and in vivo. MEG3 targeted miR-34a-3p. MEG3 overexpression potentiated the effects of PDGF-BB treatment on promoting the viability and proliferation of hPASMCs, as well as the mPAP level in APE rats. Also, overexpressed MEG3 strengthened PDGF-BB-induced upregulation of MEG3, NOR-1, PCNA and DUSP1, as well as downregulation of miR-34a-3p in hPASMCs and APE rats. However, shMEG3 generated opposite effects. MiR-34a-3p mimic reversed the effect of MEG3 overexpression, and DUSP1 overexpression neutralized the effect of MEG3 downregulation on PDGF-BB-induced hPASMCs and APE rats.MEG3 aggravates APE-induced PAH by regulating miR-34a-3p/DUSP1 axis, holding a great promise as a novel biomarker for PAH treatment.

Coinfections and comorbidities observed in COVID-19 during the influenza season in the pediatric patient.

To evaluate if the comorbidity and coinfections presented by SARS-CoV-2 infection vs. COVID-19 impact our Mexican children. Prospective and observational study that included the 2020-2021 peak influenza season. All patients with a diagnosis of infection by SARS-CoV-2 vs. COVID-19 who were admitted to the Hospital Infantil de Mexico were analyzed. Real-time RT-PCR for SARS-CoV-2 was performed in all patients, determining E, RdRp and RP genes and protein N, as well as RT-PCR for detection of respiratory viruses. The inclusion criteria were met by 163 patients. The group with the highest risk of becoming ill was adolescents (40.4%), followed by schoolchildren and preschoolers (21.4% and 19.6% of the cases, respectively). There were three cases with viral coinfection: two (1.2%) with parvovirus B-19 and one (0.6%) with herpes type I; another two (1.2%) showed bacterial coinfection. The main comorbidity were obesity, acute lymphoblastic leukemia and arterial hypertension. Regarding mortality, we only had four cases (2.4%). Obesity, cancer, hypertension, heart disease and diabetes are comorbidity present in our patients, as referred to in literature, but not coinfections. In our study, we did not have any associated mortality related to comorbidity.

Posterior reversible encephalopathy syndrome in autoimmune disorders

Posterior reversible encephalopathy syndrome (PRES) is characterized by nonspecific symptoms, including not only pronounced non-focal and various focal neurological signs but also specific neuroimaging features, including vasogenic edema affecting predominantly the posterior area. PRES usually develops in the setting of acute arterial hypertension. However, it is not uncommon for PRES to develop in non-hypertensive patients, including people with autoimmune disorders (multiple sclerosis, neuromyelitis optica spectrum disorder, etc). PRES could also be due to the toxic effects of drugs or other substances. The pathophysiological mechanisms of PRES include impaired autoregulation of cerebral blood flow due to acute arterial hypertension and toxic endotheliotropic effects of endogenous and exogenous factors.

Dynamin-Related Protein 1 Binding Partners MiD49 and MiD51 Increased Mitochondrial Fission In Vitro and Atherosclerosis in High-Fat-Diet-Fed ApoE-/- Mice.

Novel components of the mitochondrial fission machinery, mitochondrial dynamics proteins of 49 kDa (MiD49) and 51 kDa (MiD51), have been recently described, and their potential therapeutic targets for treating cardiovascular disease have been shown, including acute myocardial infarction (AMI), anthracycline cardiomyopathy and pulmonary arterial hypertension (PAH). Here, we examined the role of MiD49 and MiD51 in atherosclerosis. MiD49/51 expression was increased in the aortic valve endothelial cells (ECs) of high-fat diet-induced atherosclerosis in ApoE-/-mice and IL-8-induced human umbilical vein endothelial cells (HUVECs), which accelerated dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Silencing MiD49/51 reduced atherosclerotic plaque size, increased collagen content, and decreased the IL-8-induced adhesion and proliferation of HUVECs. MiD51 upregulation resulted from decreased microRNA (miR)-107 expression and increased hypoxia-inducible factor-1a (HIF-1a) expression. Treatment with miR-107 mimics decreased atherosclerotic plaque size by reducing HIF-1α and MiD51 production. Both MiD49 and MiD51 were involved in atherosclerotic plaque formation through Drp1-mediated mitochondrial fission, and the involvement of MiD51 in this process was the result of decreased miR-107 expression and increased HIF-1α expression. The miR-107-HIF-1α-MiD51 pathway might provide new therapeutic targets for atherosclerosis.

A Novel Adult Case of Recurrent Acute Pancreatitis Caused by Hypercalcemia With Concurrent Manifestation of Posterior Reversible Encephalopathy Syndrome Revealing Undiagnosed Primary Hyperparathyroidism due to an Underlying Parathyroid Adenoma.

Hypercalcemia-induced posterior reversible encephalopathy syndrome (PRES) is a rare entity primarily associated with iatrogenic vitamin D/calcium overdose, malignancy, or, infrequently, primary hyperparathyroidism. We present a novel case of an adult male from rural India who experienced recurrent acute pancreatitis caused by hypercalcemia with concurrent manifestation of PRES. Diagnostic evaluation revealed markedly elevated serum calcium levels and parathyroid hormone concentrations, consistent with primary hyperparathyroidism. Imaging studies identified a parathyroid adenoma near the right thyroid lobe, subsequently surgically excised. This case underscores the importance of considering primary hyperparathyroidism as an underlying cause of PRES, especially in the absence of acute arterial hypertension or autonomic dysfunction. Early recognition and intervention are essential in mitigating the morbidity and mortality of PRES.

Transcatheter Ductus Arteriosus Stenting for Acute Pediatric Pulmonary Arterial Hypertension is Associated with Improved Right Ventricular Echocardiography Strain.

Interventional therapies for severe pulmonary arterial hypertension (PAH) can provide right ventricular (RV) decompression and preserve cardiac output. Transcatheter stent placement in a residual ductus arteriosus (PDA) is one potentially effective option in critically ill infants and young children with PAH. We sought to assess recovery of RV function by echocardiographic strain in infants and young children following PDA stenting for acute PAH. Retrospective review of patients < 2years old who underwent PDA stenting for acute PAH. Clinical data were abstracted from the electronic medical record. RV strain (both total and free wall components) was assessed from echocardiographic images at baseline and 3, 6, and 12months post-intervention, as well as at last echocardiogram. Nine patients underwent attempted ductal stenting for PAH. The median age at intervention was 38days and median weight 3.7kg. One-third (3of 9) of patients had PAH associated with a congenital diaphragmatic hernia. PDA stents were successfully deployed in eight patients. Mean RV total strain was - 14.9 ± 5.6% at baseline and improved to - 23.8 ± 2.2% at 6 months post-procedure (p < 0.001). Mean free wall RV strain was - 19.5 ± 5.4% at baseline and improved to - 27.7 ± 4.1% at 6 months (p = 0.002). Five patients survived to discharge, and four patients survived 1 year post-discharge. PDA stenting for severe, acute PAH can improve RV function as assessed by strain echocardiography. The quantitative improvement is more prominent in the first 6 months post-procedure and stabilizes thereafter.

Clinical Significance of MicroRNAs, Long Non-Coding RNAs, and CircRNAs in Cardiovascular Diseases.

Based on recent research, the non-coding genome is essential for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases (CVDs). The microRNAs (miRNAs), lncRNAs (long ncRNAs), and circRNAs (circular RNAs) with significant regulatory and structural roles make up approximately 99% of the human genome, which does not contain proteins. Non-coding RNAs (ncRNA) have been discovered to be essential novel regulators of cardiovascular risk factors and cellular processes, making them significant prospects for advanced diagnostics and prognosis evaluation. Cases of CVDs are rising due to limitations in the current therapeutic approach; most of the treatment options are based on the coding transcripts that encode proteins. Recently, various investigations have shown the role of nc-RNA in the early diagnosis and treatment of CVDs. Furthermore, the development of novel diagnoses and treatments based on miRNAs, lncRNAs, and circRNAs could be more helpful in the clinical management of patients with CVDs. CVDs are classified into various types of heart diseases, including cardiac hypertrophy (CH), heart failure (HF), rheumatic heart disease (RHD), acute coronary syndrome (ACS), myocardial infarction (MI), atherosclerosis (AS), myocardial fibrosis (MF), arrhythmia (ARR), and pulmonary arterial hypertension (PAH). Here, we discuss the biological and clinical importance of miRNAs, lncRNAs, and circRNAs and their expression profiles and manipulation of non-coding transcripts in CVDs, which will deliver an in-depth knowledge of the role of ncRNAs in CVDs for progressing new clinical diagnosis and treatment.

PS-R03-9: PERIODIC PARALYSIS AS A PRESENTATION OF PRIMARY HYPERALDOSTERONISM: A CASE REPORT

Objective: the typical clinical presentations of patients with primary aldosteronism (PA) include generalized weakness, fatigue, high blood pressure and potassium deficiency. However, onset of PA with periodic paralysis is rare. Design and method: herein, we present the case of a 40-year-old, Caucasian women (BMI 25,6 kg/m2) with severe resistance arterial hypertension (BP 200–190/110–120 mmHg while taking antihypertensive drugs: valsartan 320 mg/day, bisoprolol 5 mg, hydrochlorthiasid 12,5 mg, amlodipin 10 mg/day, spironolacton 25 mg/day) and muscle weakness. Over the last 2 years prior to presentation, she had multiple such episodes of generalized weakness and losing the ability to stand up, move limbs, wich typically lasted for few minutes to hours/days and resolved spontaneously. Her blood pressure was uncontroled despite taking antihypertensive drugs. She was hospitalized several times because of these conditions, but there is no data on potassium levels during that period. Due to misdiagnosis, she was operated on twice (discectomy C5-C6, C6-C7 and resection of the right internal carotid artery due to pathological tortuosity), but her condition did not improve. Results: At the presentation U waves were registered in the electrocardiography the laboratory examination revealed low plasma potassium level (3,05 mmol/l). Serum TSH, cortisol level were normal. Pasma aldosteron level was 38,6ng/dl (n. 4–31). CT abdomen: adenoma of left adrenal gland. Surgical adrenalectomy was performed. Pathological diagnosis was a bening cortical adenoma. Outcomes: Patient's serum potassium level became normalized after surgical removal of adrenal adenoma. Patient's blood pressue is controlled (130/80 mmHg) by taking a fixed combination perindopril 10 mg/indapamid 2,5 mg/amlodipin 10 mg daily and there is no muscle weakness. Conclusions: Patients with periodic acute muscles weakness and arterial hypertension should monitor electrolyte levels, especially potassium, and evaluate for primary hyperaldosteronism to avoid delayed diagnosis and treatment.

HYPERTENSIVE ENCEPHALOPATHY: TO BE DIAGNOSED AND TREATED IMMEDIATELY

It is important to have a good understanding of the pat­hogenetic diagnosis and treatment features of the severe complication with high mortality – hypertensive encepha­lopathy (HE) because of the amount of people suffering from chronic arterial hypertension is constantly increa­sing. Thus, this article briefly reviews the mechanism of cerebral blood flow autoregulation, HE pathophysiology, and the main aspects of diagnosis and treatment. An HE episode is caused by a sudden and significant increase in arterial blood pressure, when the autoregulatory mecha­nism of cerebral blood flow becomes ineffective. Along with increased blood pressure, the patient gradually deve­lops neurological symptoms ranging from intense heada­che to vision loss, loss of consciousness, and convulsions. The diagnosis of HE is based on the clinical signs – acute arterial hypertension and the subsequent neurological symptoms. Also, the diagnosis of HE can be determined retrospectively when the neurological symptoms rapi­dly disappear with effective antihypertensive treatment. Computed tomography is important in differentiating HE from intracerebral hemorrhage and ischemic stroke. In management of HE it is recommended to return to the limits of cerebral blood flow autoregulation by immedi­ately reducing mean arterial blood pressure by 20-25%. In order to achieve the maximum rapid antihyperten­sive effect, it is suggested to administer the medication only intravenously. Labetalol and sodium nitroprusside are currently recommended first-line drugs for the treat­ment of HE. Patients with HE should be hospitalized in the intensive care unit for continuous control of decre­asement of arterial blood pressure while observing the cautious dynamics of the neurological condition. The outcome of patients depends on the urgency and effici­ency of treatment in returning arterial blood pressure to the limits of cerebral blood flow autoregulation, as well as on comorbidities, the severity of the condition and possible complications.

A case report on sepsis with HTN with pyelonephritis with DM 2

Introduction: Modes: Acute arterial hypertension can arise during acute sepsis in everyday practice. The most recent sepsis campaign recommendations did not include any management instructions on this topic. Arterial hypertension that develops during sepsis may go unnoticed, even though it can have serious hemodynamic effects. This report presents a clinical study of acute hypertensive response in sepsis. It demonstrates that during sepsis, At the same time, arterial hypertension, renal salt loss, and glomerular hyperfiltration can all occur. The mechanisms of sepsis-related arterial hypertension and treatment possibilities are also reviewed. Diabetes mellitus is a common cause of pyelonephritis. Acute arterial hypertension can arise during acute sepsis in everyday practice. The most recent sepsis campaign recommendations did not include any management instructions on this topic. Despite its potential for hemodynamic damage, Severe arterial hypertension that develops as a result of sepsis may be an overlooked ailment. This report presents A clinical study of sepsis-induced acute hypertension. It demonstrates that arterial hypertension, renal salt loss, and glomerular hyperfiltration can all lead to kidney failure. all happen at the same time during sepsis. The mechanisms of sepsis-related arterial hypertension and treatment possibilities are also reviewed. Pyelonephritis is frequently caused by diabetes mellitus. Patients with EPN had a lower treatment outcome than those with NEPN. However, EPN and NEPN patients had the same death rate, although EPN patients require more nephrectomy. Shock and an altered sensorium at the time of presentation were both poor prognostic factors in EPN.Patients Information: A 43-year-old woman was admitted To MICU on February 20, 2022 On fever, the patient has had chills for 5 days, vomiting for 1 day, and generalized weakness for 5 days, with a history of hypertension, sepsis, Diabetes Mellitus 2 pyelonephritis, and no history of tuberculosis.clinical findings: By physician's order, the patient had completed all essential investigations. Therapeutic Interventions: medical management was provided to the patient Iv, fluid RL, and NS were used to treat the patient. RT feed 200ml/2 hourly, pan 40 mg OD, Emmet 4 mg sos, pan 40 mg OD Lantus 8 unit HS, She was taking all treatments and the outcomes were good. The patient was taken medication as per a doctor’s order, for example, antipyretic use to treat fever Nursing Management: conclusion: A 43 -year -old woman was admitted with MICU sepsis with HTN with pyelonephritis with DM2, fever With chills for 5 days, vomiting for 1 day, and generalized weakness for 5 days, The medical treatment had a positive impact on the patient's condition. Now, the patient's symptoms have been reduced, and he was in better condition.

Nutrological and metabolic approaches to the action of the some special micronutrients in heart failure and metabolic syndrome: a systematic review

Introduction: In the heart disease scenario, heart failure (HF) is the leading cause of hospitalizations in the United States in patients over 65 years of age, and there is evidence that this pathology affects 26 million people worldwide. Dietary guidance for patients with HF has focused on sodium restriction and fluid intake, but diet quality is often poor in HF patients and can contribute to morbidity and mortality. Restrictive diets can lead to inadequate intake of macro and micronutrients by patients with HF, highlighting deficiencies in calcium, magnesium, coenzyme Q10, zinc, iron, thiamine, vitamins D, E, and K, and folate. Objective: Through a systematic literature review, the main nutrological approaches to the action of the micronutrients magnesium, coenzyme Q10, and vitamin D in heart failure and metabolic syndrome were evidenced. Methods: The present study followed a concise systematic review model (PRISMA). The literary search process was carried out from August 2022 to September 2022 and was developed based on Scopus, PubMed, Science Direct, Scielo, and Google Scholar, using scientific articles from 1998 to 2022. The low quality of evidence was attributed to reports of cases, editorials, and brief communications, according to the GRADE instrument. The risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: The total of 136 studies were found for eligibility analysis, and then 75 of the 84 total studies were selected for this systematic review. According to the GRADE instrument, most studies showed homogeneity in their results, with I2 =98.7% &gt;50%. The Funnel Plot showed a symmetrical behavior, not suggesting a significant risk of bias in studies with smaller sample sizes. Studies have shown that magnesium deficiency or changes in its metabolism are related to the pathophysiology of heart failure, hypertension, arrhythmias, preeclampsia, insulin resistance, and diabetes. Vitamin D plays an important role in innate and adaptive immune responses, cell cycle, and metabolic processes, evidenced by the reported relationship between its deficiency and the prevalence of immunity-mediated disorders, cancer, and cardiometabolic diseases. The VDR results in β cells, endothelium, cardiac myocytes, and renin production suggesting a role for vitamin D in these diseases. Coenzyme Q10 is part of the electron transport chain and is found in large concentrations in the mitochondrial, especially in the muscles, brain, and heart. Clinical studies have shown that pathologies such as acute myocardial infarction, arterial hypertension, and myopathies induced by statins, physical fatigue inherent in physical exercise, male infertility, preeclampsia, Parkinson's disease, periodontal disease, and migraine had low plasma concentrations of coenzyme Q10.

ACUTE PULMONARY HYPERTENSION AFTER BORTEZOMIB THERAPY

ACUTE PULMONARY HYPERTENSION AFTER BORTEZOMIB THERAPY

Prevalence of renal involvement among pediatric patients hospitalized due to coronavirus disease 2019: A multicenter study.

Renal involvement among pediatric patients with coronavirus disease 2019 (COVID-19) ranges between 1.2% and 44%. Given the limited information available locally, the primary objective of this study was to estimate the prevalence of renal involvement in our setting. Cross-sectional study conducted in 13 Argentine sites between March and December 2020. Patients aged 1 month to 18 years hospitalized due to COVID-19 and with at least one measurement of serum creatinine and/or a urinalysis were included. Those with a known kidney disease were excluded. Renal involvement was defined as the presence of acute kidney injury (AKI), proteinuria, hematuria, leukocyturia and/or arterial hypertension (HTN). Among 528 eligible medical records, 423 patients were included (55.0% were males; median age: 5.3 years). The clinical presentation was asymptomatic in 31%; mild, in 39.7%; moderate, in 23.9%; severe, in 1.2%; critical, in 0.7%; and 3.5% had multisystem inflammatory syndrome in children (MIS-C). Two patients (0.47%) died. The prevalence of renal involvement was 10.8% (95% confidence interval: 8.2-14.2); it was described as leukocyturia (16.9%), proteinuria (16.0%), hematuria (13.2%), HTN (3.7%), and AKI (2.3%). No patient required dialysis. Renal involvement was associated with severe forms of disease (p < 0.0001). The prevalence of renal involvement among pediatric patients hospitalized due to COVID-19 in 13 Argentine sites was 10.8%; severe forms of disease prevailed.

Atrial fibrillation and acute coronary syndromes in nonagenarians

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is the most common arrhythmia in the elderly. Age increases both thromboembolic risk and bleeding complications. However, these patients are not anticoagulated on many occasions. AF in the context of acute coronary syndrome (ACS) increases the complexity of the management of these patients and they are underrepresented in clinical trials. Purpose The objective of the study was to analyze the impact of AF in nonagenarian patients at 12 months. Other objectives were to evaluate the therapeutic strategy for ACS and AF and to compare clinical events according to AF subtype and treatment at discharge. Methods A retrospective, multicenter and observational study was carried out, in which all nonagenarian patients admitted for ACS and AF (prevalent or incident) between 2005 and 2018 were consecutively included. Patients with type 2 myocardial infarction were excluded. Baseline characteristics were analyzed and mortality at 12 months was analyzed in all patients and according to AF subtype (incident AF was considered when occurred during admission and prevalent AF was considered in patients with previous history of AF) Results 680 patients with a mean age of 92.6 ± 2.4 years were analyzed. Patients with AF more frequently presented chronic kidney disease (CKD) and non-ST-segment elevation acute coronary syndrome (Non-STEMI) and arterial hypertension (HBP) (Table 1). Mortality rate was similar in patients with previous AF and those without history of AF (Figure 1 A). 21.6% (147) of the patients had AF at admission, of which only 47.7% of the patients were previously anticoagulated. Treatment at discharge is shown in Figure 1 B. Mortality at 1 year according to discharge treatment and AF subtype are represented in figures 1C and 1D. Conclusions This is the largest registry of ACS and AF in this population. Patients with prevalent AF had more frequent Non-STEMI and comorbidities, with a similar mortality to AF subgroup at 1 year. Previous AF was no related to higher mortality in this cohort. Half of the patients were not anticoagulated at discharge. OAC was not associated with prognostic benefit in our series.

Efficacy of interatrial shunt devices: an opening window to acute pulmonary hypertensive crisis and chronic pulmonary arterial hypertension.

The current study aimed to elucidate the efficacy of interatrial shunt device (IASD) for the treatment of acute pulmonary hypertensive crisis (PHC) and chronic pulmonary arterial hypertension (PAH). After establishing chronic PAH models using dehydrogenized monocrotaline (DHMCT), PAH dogs were implanted with IASDs (group A) or received no intervention (group B). One month later, DHMCT was injected again to establish an acute PHC. The prognosis, hemodynamics, ultrasound cardiography, electrocardiogram, and lung pathology of the dogs were observed. The baseline mean pulmonary arterial pressure increased from 12.70 ± 1.03 to 19.95 ± 1.75mmHg and established a chronic PAH model 2 months after DHMCT injection (1.50mg/kg). After an additional injection of DHMCT (1.50mg/kg) in the chronic PAH model, acute PHC occurred. Mean PAP, sPAP, and pulmonary vascular resistance increased to 22.67 ± 1.80mmHg, 35.70 ± 1.66mmHg, and 12.50 ± 3.50 WOOD U, respectively. Cardiac output (CO) decreased to 1.31 ± 0.26 L/min, and the right-to-left shunt caused hypoxemia. The survival rates of the dogs with and those without IASD were 70.0% and 22.2% (P = 0.037), respectively. Six months after PHC, the CO between the dogs with and those without IASD were 1.44 ± 0.11 L/min and 1.18 ± 0.04 L/min (P = 0.028). The long-term survival rates were 50.0% and 22.2%, respectively (P = 0.21). IASD might be efficacious and beneficial for treating acute PHC and chronic PAH, as well as improving prognosis.

Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up.

Some gene polymorphisms have been previously associated individually with tacrolimus efficacy and toxicity, but no long-term study to determine the role of pharmacogene variants in the clinical evolution of liver-transplanted patients has been addressed so far. In the present work, we analyzed the relation between highly-evidenced genetic polymorphisms located in relevant pharmacogenes and the risk of suffering premature death and other comorbidities such as cancer, diabetes mellitus, arterial hypertension, graft rejection, infections and nephrotoxicities in a cohort of 87 patients (8 were excluded due to early loss of follow-up) transplanted at Hospital La Fe in Valencia (Spain) during a 12-year follow-up. Employing a logistic regression model with false discovery rate penalization and Kaplan–Meier analyses, we observed significant association between survival rates and metabolizer genes. In this sense, our results show an association between MTHFR gene variants in donor rs1801133 (HR: 7.90; p-value: 0.032) and recipient rs1801131 (HR: 7.34; p-value: 0.036) and the group of patients who died during the follow-up period, supporting the interest of confirming these results with larger patient cohorts. In addition, donor polymorphisms in UGT1A9 metabolizer gene rs6714486 (OR: 0.13; p-value: 0.032) were associated with a lower risk of suffering from de novo cancer. Genetic variants in CYP2B6 metabolizer gene rs2279343 demonstrated an association with a risk of infection. Other variants in different locations of SLCO1A2, ABCC2 and ABCB1 transporter genes were associated with a lower risk of suffering from type 2 diabetes mellitus, chronic and acute nephrotoxicities and arterial hypertension. Results suggest that pharmacogenetics-derived information may be an important support for personalized drug prescription, clinical follow-up and the evolution of liver-transplanted patients.

Mesenchymal stromal cell extracellular vesicles as therapy for acute and chronic respiratory diseases: A meta-analysis.

Preclinical studies suggest mesenchymal stromal cell extracellular vesicles (MSC‐EVs) reduce inflammation and improve organ function in lung diseases; however, an objective analysis of all available data is needed prior to translation. Using rigorous meta‐research methods, we determined the effectiveness of MSC‐EVs for preclinical respiratory diseases and identified experimental conditions that may further refine this therapy. A systematic search of MEDLINE/Embase identified 1167 records. After screening, 52 articles were included for data extraction and evaluated for risk of bias and quality of reporting in study design. A random effects meta‐analysis was conducted for acute lung injury (ALI; N = 23), bronchopulmonary dysplasia (BPD; N = 8) and pulmonary arterial hypertension (PAH; N = 7). Subgroup analyses identified EV methods/characteristics that may be associated with improved efficacy. Data is presented as standardized mean differences (SMD) or risk ratios (RR) with 95% confidence intervals (CI). For ALI, MSC‐EVs markedly reduced lung injury (SMD ‐4.33, CI ‐5.73 to ‐2.92), vascular permeability (SMD ‐2.43, CI ‐3.05 to ‐1.82), and mortality (RR 0.39, CI 0.22 to 0.68). Small EVs were more consistently effective than large EVs whereas no differences were observed between tissue sources, immunocompatibility or isolation techniques. For BPD, alveolarization was improved by MSC‐EVs (SMD ‐1.45, CI ‐2.08 to ‐0.82) with small EVs more consistently beneficial then small/large EVs. In PAH, right ventricular systolic pressure (SMD ‐4.16, CI ‐5.68 to ‐2.64) and hypertrophy (SMD ‐2.80, CI ‐3.68 to ‐1.91) were significantly attenuated by EVs. In BPD and PAH, EVs isolated by ultracentrifugation demonstrated therapeutic benefit whereas tangential flow filtration (N = 2) displayed minimal efficacy. Lastly, risk of bias and quality of reporting for experimental design were consistently unclear across all studies. Our findings demonstrate clear potential of MSC‐EVs to be developed as therapy for acute and chronic lung diseases. However, greater transparency in research design and direct comparisons of isolation technique and EV subtypes are needed to generate robust evidence to guide clinical translation.Protocol Registration: PROSPERO CRD42020145334

L'ISCHEMIE MESENTERIQUE AIGUË : PRISE EN CHARGE EN CHIRURGIE GENERALE AU CHU GABRIEL TOURE, AU MALI

Objective: to determine the frequency of acute mesenteric ischemia, to describe the diagnostic and therapeutic aspects and to analyze the results of treatment. Methodology: this was a retrospective and descriptive study conducted from January 2010 to December 2019, in the surgical department of the CHU Gabriel Touré in Bamako. were included all patients admitted for acute mesenteric ischemia, confirmed by CT-scan and / or intraoperatively. Results: in 10 years, 26 cases were collected representing 1.1% of abdominal surgical emergencies. The average age was 54 years and the sex ratio 0.85. The main risk factors were: acute arterial hypertension (11 cases), dyslipidemia (9 cases), oral contraceptive (9 cases), obesity (8 cases). The average consultation delay was 2.6 days. The main clinical signs were: abdominal pain (100%), vomiting (53.8%), gastrointestinal bleeding (38.4%), fever (76.92%), tachycardia (61.53%), hypotension (46, 15%), abdominal contracture (46.15%), abdominal distension (26.92%). The preoperative diagnosis was acute bowel obstruction in 61.5%, acute peritonitis in 34.6%. A midline laparotomy was performed in all patients. Intestinal necrosis was found in all cases, requiring extensive intestinal resection. The immediate operative consequences were simple in 30%; sepsis was observed in 66.67% and multiple organ failure in 33.33%. The mortality was 69.23%. Conclusion: acute mesenteric ischemia is a serious condition discovered intraoperatively, most often in the stage of intestinal necrosis. Early treatment could improve the prognosis. Keywords: Acute mesenteric ischemia, surgery, Emergency, Mali

Indirect autonomic nervous system activity assessment in patients with myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Abnormalities in the cardiac sympathetic nervous system have been documented in myocardial infarction (MI) and have been directly implicated in pathogenesis and progression of MI. Assessment of the autonomic nervous system activity in acute stage of MI allowed us to identify groups of high-risk patients. Purpose To investigate the sympathetic nervous system activity in patients with MI by assessing the condition of beta-adrenergic reactivity of erythrocytes. To analyze ADRB1 Arg389Gly associations with the state of beta-adrenergic reactivity of erythrocytes in patients with MI. Methods During the study period, 62 patients were enrolled. The patients were divided into 2 groups. The first group consisted of 11 patients (nine women and two men, median age of 54.0 [49.0;61.0] years) with normal beta-adrenergic reactivity of erythrocytes, the second group consisted of 51 patients (40 women and 11 man, median age of 61.0 [48.0;72.0] years) with abnormal beta-adrenergic reactivity of erythrocytes. The research of beta-adrenergic reactivity of erythrocytes was conducted by analysis of changing erythrocyte osmoresistance under the influence of beta blocker in the first 6 hours from the onset of the heart attack. The genetic research was conducted by PСR method in real time. Results Groups of patients were comparable in main clinical indicators (anamnesis of ischemic heart disease and chronic heart failure, frequency of beta blockers administration before and during of MI, electrocardiography features: elevation of ST-segment, Q-wave and etc.). The second group presented with a higher occurrence of acute left ventricular failure (33.3% vs 0%, p = 0.026) and arterial hypertension (90.2% vs 63.6%, p = 0.044). Parameters of myocardial damage were significantly higher in the second group than the first group. Primarily, this manifested in the presence of a greater number of hypokinesis zones on echocardiography (p = 0.015). In addition, patients of the second group had a lower ejection fraction according to echocardiography (51.0 [46.5;59.0]% vs 58.0 [52.0;63.0]%, p = 0.042). Levels of blood necrosis biomarkers were significantly higher in the second group, e.g. Troponin I (24.1 [9.9;68.0] ng/ml vs 1.3 [0.2;1.8] ng/ml, p = 0.001). At the same time statistically significant distinctions of the severity of coronary atherosclerosis in groups were not revealed. The analysis of ADRB1 Arg389Gly demonstrated association of CC-genotype with abnormal beta-adrenergic reactivity of erythrocytes [OR 5.9, 95% СI 1.16-30.25, p = 0.043]. Conclusion Patients with an abnormal beta-adrenergic reactivity were characterized by a greater volume of damage to the heart muscle. Moreover, association of CC-genotype of gene ADRB1 Arg389Gly with abnormal beta-adrenergic reactivity of erythrocytes was identified.