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Introduction The evolution of patients with obstructive sleep apnea (OSA) non-eligible for PAP-therapy at diagnosis is unknown. Currently, the severity of OSA is based on the apnea-hypopnea index (AHI), but its prognostic relevance has raised concerns. The Baveno classification may allow a better stratification of severity and therapeutic guidance in OSA. Methods Patients with AHI≥5/h in 2015, classified into Baveno groups A and B and non-eligible for PAP therapy at diagnosis and over 5 years, were analyzed. Patients were reclassified into Baveno groups (A-D) and changes in groups over 5 years were explored. Patients in Baveno groups C and D, who developed major cardiovascular comorbidities (CVC) or end-organ damage (EOD group), were compared with patients in Baveno groups A and B (non-EOD group). To identify predictors of the development of major CVC or EOD, a logistic regression analysis was performed. Results There were 76 patients, 58% male, mean age 51.9 ± 10.1 years, mean body mass index (BMI) of 30.3 ± 5.0 kg/m2 and median AHI of 8.9 (5.9–12.0) events/h. At diagnosis, 46% and 54% of patients were classified into Baveno group A and group B, respectively. In total, 21% of patients developed major CVC or EOD (Baveno group C or D); higher age (p = 0.011) and BMI (p = 0.004) and a higher percentage of central apneas (p = 0.012) at diagnosis significantly predicted it, while sex, sleepiness, insomnia, AHI, ODI and T90 were not. Conclusions A significant percentage of patients non-eligible for PAP-therapy at diagnosis of OSA developed CVC or EOD; higher age and BMI and a higher percentage of central apneas were significant predictors.

Cardiovascular complications are the leading cause of death, and elevated levels of asymmetric dimethyarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are implicated in their pathophysiology. We investigated the role of dimethylarginine dimethylaminohydrolase 1 (DDAH1), an enzyme hydrolyzing ADMA, in prevention of cardiovascular remodeling during hypertension. We hypothesized that the animals overexpressing DDAH1 will be protected from angiotensin II (ANG II)-induced end organ damage. Angiotensin II (ANG II) was infused in two doses: 0.75 and 1.5 mg/kg/day in DDAH1 transgenic mice (DDAH1 TG) and wild-type (WT) littermates for 2 or 4 wk. Echocardiography was performed in the first and fourth weeks of the infusion, systolic blood pressure (SBP) was measured weekly, and cardiac hypertrophy and vascular remodeling was assessed by histology. Increase in SBP after 1 wk of ANG II infusion was not different between the groups, whereas TG mice had lower SBP at later time points. TG mice were protected from cardiovascular remodeling after 2 wk of ANG II infusion in the high dose and after 4 wk in the moderate dose. TG mice had higher left ventricular lumen-to-wall ratio, lower cardiomyocyte cross-sectional area, and less interstitial fibrosis compared with WT controls. In aorta, TG mice had less adventitial fibrosis, lower medial thickness with preserved elastin content, lower counts of inflammatory cells, lower levels of active matrix metalloproteinase-2, and showed better endothelium-dependent relaxation. We demonstrated that overexpression of DDAH1 protects from ANG II-induced cardiovascular remodeling and progression of hypertension by preserving endothelial function and limiting inflammation.NEW & NOTEWORTHY We showed that overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1) protects from angiotensin II-induced cardiovascular damage, progression of hypertension, and adverse vascular remodeling in vivo. This protective effect is associated with decreased levels of asymmetric dimethylarginine, preservation of endothelial function, inhibition of cardiovascular inflammation, and lower activity of matrix metalloproteinase-2. Our findings are highly clinically relevant, because they suggest that upregulation of DDAH1 might be a promising therapeutic approach against angiotensin II-induced end organ damage.

The COVID-19 pandemic has highlighted racial health disparities within the United States. Although social determinants of health are the most likely drivers of this disparity, it is possible that genetic traits enriched in the black population like sickle cell trait (SCT) could worsen the morbidity and mortality of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients admitted for SARS-CoV-2 infection who identified as black or African American were included in the study (n = 166). Blood remnants were tested for SCT, and clinical data were abstracted from the chart. There was no difference in mortality between those with SCT and those without. There was no difference in respiratory complications between groups, but those without SCT had a much higher burden of chronic lung disease (P = .004). Those with SCT had higher creatinine on admission (P = .004), but no difference in in-hospital renal complications (P = .532). Notably, 12% of the cohort had SCT, which is higher than the expected 7.31% (P = .025). Our study did not show any evidence of increased end organ damage, morbidity, or mortality from SARS-CoV-2 infection among patients with SCT but did show differences in admission creatinine and preexisting lung disease., Key Points • There is no impact of SCT on respiratory, renal, or circulatory complications or mortality in patients with SARS-CoV-2 infection. • The prevalence of SCT in the hospitalized cohort was significantly higher than the prevalence in the community (12% vs 7.31%).

Morbidity and mortality risks are enhanced in preeclamptic (PE) mothers and their offspring. Here, we asked if sexual dimorphism exists in (i) cardiovascular and renal damage evolved in offspring of PE mothers, and (ii) offspring responsiveness to antenatal therapies. PE was induced by administering NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day, oral gavage) to pregnant rats for 7 days starting from gestational day 14. Three therapies were co-administered orally with L-NAME, atrasentan (endothelin ETA receptor antagonist), terutroban (thromboxane A2 receptor antagonist, TXA2), or α-methyldopa (α-MD, central sympatholytic drug). Cardiovascular and renal profiles were assessed in 3-month-old offspring. Compared with offspring of non-PE rats, PE offspring exhibited elevated systolic blood pressure and proteinuria and reduced heart rate and creatinine clearance (CrCl). Apart from a greater bradycardia in male offspring, similar PE effects were noted in male and female offspring. While terutroban, atrasentan, or α-MD partially and similarly blunted the PE-evoked changes in CrCl and proteinuria, terutroban was the only drug that virtually abolished PE hypertension. Rises in cardiorenal inflammatory (tumor necrosis factor alpha, TNFα) and oxidative (isoprostane) markers were mostly and equally eliminated by all therapies in the two sexes, except for a greater dampening action of atrasentan, compared with α-MD, on tissue TNFα in female offspring only. Histopathologically, antenatal terutroban or atrasentan was more effective than α-MD in rectifying cardiac structural damage, myofiber separation, and cytoplasmic alterations, in PE offspring. The repair by antenatal terutroban or atrasentan of cardiovascular and renal anomalies in PE offspring is mostly sex-independent and surpasses the protection offered by α-MD, the conventional PE therapy.

OBJECTIVE The study aimed to investigate the predictive power of serum corin levels for distinguishing between hypertensive urgency (HU) and hypertensive emergency (HE) in patients with hypertensive crisis (HC) admitted to the emergency department. METHODS A total of 120 consecutive consenting adult patients diagnosed with HC and 55 age- and sex-matched healthy controls were enrolled. Blood pressure measurements [(systolic, diastolic, and mean arterial pressure (MAP)] and the evidence of end-organ damage at the first admission were recorded. Patients with HC were classified as patients with HE or HU according to the presence or absence of acute end-organ damage. Serum corin levels were compared between the 2 groups. RESULTS The mean serum corin level was significantly lower in the HC group than in the control group; it was also lower in the HE group than in the HU group (p

Objective Hemorrhagic stroke (HS) and hypertensive retinopathy are known end organ damage of the brain and eye respectively, with HS having deleterious consequence to the patients. This study is to correlate between hypertensive retinopathy and HS in hypertensive disease. Methods A control group of hypertensive patients only, and an investigated group of hypertensive HS patients. Fundoscopic examination to determine the grade of retinopathy was performed and then divided into low or high severity hypertensive retinopathy. Clinical and radiological parameter included are demography, vital signs, Glasgow coma scale (GCS) on admission, clot volume, site of clot, Intracerebral hemorrhage (ICH) score and Glasgow outcome scale (GOS). Data were correlated with the severity of hypertensive retinopathy. Results Fifty patient in the control group and 51 patients in the investigated group were recruited. In the hypertensive HS group, 21 had low severity retinopathy (no or mild retinopathy) accounting for 41.2% and 30 patients had high severity (moderate or severe retinopathy). In the hypertensive patients 49 had low severity and one had high severity (p-value of 0.001). In HS group low severity showed better GCS score of 9-15 on admission (p-value of 0.003), clot volume less than 30 mL (p-value 0.001), and also a better 30 days mortality rate by using the ICH score (p-value 0.006), GOS score of 4 and 5 the low severity retinopathy fair better than the high severity retinopathy (p-value of 0.001), and the relative risk to develop HS in low severity and high severity retinopathy was 0.42 and 29.4, respectively. Conclusion Hypertensive retinopathy screening could be used as an indicator in hypertensive patient, to evaluate the risk of developing hypertensive HS in the future.

Summary The outbreak of coronavirus disease 2019 (COVID-19) has put health systems worldwide under great pressure on numerous levels. COVID-19 is a heterogeneous situation where some people experience mild symptoms for which no serious intervention is needed, while others may experience serious situations ranging from acute respiratory distress syndrome (ARDS) or even respiratory failure and end organ damage. Serious COVID-19 cases may be complicated with a cytokine storm caused by hemophagocytic lymphohistocytosis, which is a life-threatening situation. Efforts should be directed to reveal accompanying diseases that may trigger the cytokine storm. Early diagnosis leads to a better understanding of how to deal with this emergency status; however, even with early intervention, outcomes are still very poor.

Aim of the work: To investigate the relation between lymphopenia and clinical disease activity, disease associated end organ damage, laboratory markers and medications received in systemic lupus erythematosus (SLE) patients. Another objective was to investigate the prognostic value of lymphopenia. Patients and methods: The medical records of 698 SLE patients under follow-up at the Rheumatology clinics of Cairo and KafrElsheikh University hospitals were revised. Demograghic and laboratory data, SLE disease activity index (SLEDAI), damage index and drug history were assessed. Results: Mean age of 28.4 ± 8.8 years (12–60 years), they were 640 females and 58 males (F:M 11:1) and a disease duration of 6.2 ± 4.7 (0.1–31 years). The study included 674 adults and 24 juvenile cases. 280 (40%) had lymphopenia. Patients with lymphopenia had significantly consumed complement 3 (C3) (p 40 mg/day, infections, antiphospholipids for associated lymphopenia. On multivariate analysis only consumed C3 (p = 0.008) and pulse steroid therapy (p = 0.036) remained as independent risk factors for lymphopenia. Conclusion: Lymphopenia may be more than a hematological finding in SLE patients that was found to be associated with complement consumption, high steroid doses and cyclophosphamide administration, infections and antiphospholipids. The key independent risk factors for lymphopenia are pulse steroid and C3.

Introduction BRAF V600 E mutation is present in 50% cases of LCH and is associated with aggressive forms of disease-particularly liver dysfunction in infants and younger children. It is associated with increased mortality due to poorer response to chemotherapy and higher rate of relapse. Though targeted therapy with Vemurafenib shows rapid clinical response and prevents end organ related mortality, optimal duration of therapy and combination of chemotherapy needs further studies. Material & methods We discuss here follow up of 3 patients with Relapse/Refractory LCH and BRAF mutation who were salvaged with Vemurafinib. Results Three patients with Relapse/Refractory MS LCH were treated in our centre with Vemurafenib. All 3 patients showed dramatic response to Vemurafenib at initiation as well as subsequent relapse on stopping. On PET scan, 2 patients had CR at 6 weeks and 3rd patient had PR on 6 and 12th week. We then used slow taper of vemurafenib with/without addition of oral chemotherapeutic agents and continued a minimal dose successfully in all the 3 patients to prevent recurrences. Conclusion Vemurafenib is a safe and effective salvage option to be used early in refractory/relapsed disease to prevent end organ damage. Gradual taper and maintaining a minimal dose with/without addition of oral chemotherapeutic agents may help in preventing recurrences.

Background Few studies show that ambulatory blood pressure (BP) monitoring (ABPM) is superior to office BP (oBP) measurements to predict target organ damage and cardiovascular (CV) events in kidney transplant recipients (KTRs). We performed a systematic review aimed at determining the potential associations between BP recordings by different methods and renal and CV outcomes in this population. Methods Major medical databases were searched for studies enrolling adult KTRs undergoing 24-h ABPM compared with office or home BP measurements. The main outcomes were associations between different BP recordings and renal and CV outcomes. Additionally, any association between the circadian BP pattern (dipping/non-dipping status) and outcomes was assessed. Results Twenty-two studies (2078 participants) were reviewed. Among 12 studies collecting data on renal endpoints, 10 studies found that BP assessed by ABPM was a stronger predictor of renal function decline, assessed by serum creatinine and/or creatinine clearance or estimated glomerular filtration rate, than traditional office measurements. Twelve studies analysed the relation between different BP recordings and CV target organ damage and reported robust correlations between echocardiographic abnormalities (i.e. left ventricular mass index) and 24-h ABPM, but not with office BPs. Furthermore, 24-h ABPM correlated better than oBP with markers of vascular damage, such as carotid intima-media thickness, diffuse thickening and endothelial dysfunction. Additionally, an abnormal circadian BP pattern (non-dippers and reverse dippers) identified a group of kidney recipients at risk for kidney function loss and CV abnormalities. Conclusions In our systematic review, ABPM reflected target organ damage more closely than oBP in KTRs. Furthermore, an altered circadian BP profile associated with renal and CV target organ damage.

Elevated blood pressure (BP) and hypertension commonly occur in children and adolescents and increase the risk of cardiovascular disease in adulthood. The purpose of this review is to summarize recent research in pediatric hypertension including changes in defining hypertension, BP measurement techniques, hypertension epidemiology, risk factors, treatment, and BP-related target organ damage. Defining pediatric hypertension using the 2017 American Academy of Pediatrics’ updated Clinical Practice Guideline resulted in a larger proportion of children being classified as having elevated BP or hypertension compared with prior guidelines. Trends in the distribution of BP among US children and adolescents suggest that BP levels and the prevalence of hypertension may have increased from 2011–2014 to 2015–2018. Factors including a family history of hypertension, obesity, minority race/ethnicity, physical inactivity, high dietary intake of sodium, and poor sleep quality are associated with an increased prevalence of elevated BP and hypertension. Evidence of a linear relationship between systolic BP and target organ damage indicates that BP levels currently considered normal could increase the risk of target organ damage in childhood. Lifestyle changes, such as adhering to the Dietary Approaches to Stop Hypertension diet, are a central component of effectively reducing BP and have been shown to reduce target organ damage. Pharmacologic treatment using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is an effective and safe method for reducing BP among children with uncontrolled BP after implementing lifestyle changes. Research gaps in the prevention, detection, classification, and treatment of hypertension in children demonstrate opportunities for future study.

Increasing evidence indicates that hypertension and hypertensive end-organ damage are not only mediated by hemodynamic injury. Inflammation also plays an important role in the pathophysiology and contributes to the deleterious consequences of this disease. Cells of the innate immune system including monocyte/macrophages and dendritic cells can promote blood pressure elevation via effects mostly on kidney and vascular function. Moreover, convincing evidence shows that T and B cells from the adaptive immune system are involved in hypertension and hypertensive end-organ damage. Skin monocyte/macrophages, regulatory T cells, natural killer T cells, and myeloid-derived suppressor cells have been shown to exert blood pressure controlling effects. Sodium intake is undoubtedly indispensable for normal body function but can be detrimental when taken in excess of dietary requirements. Sodium levels also modulate the function of monocyte/macrophages, dendritic cells, and different T cell subsets. Some of these effects are mediated by changes in the microbiome and metabolome that can be found after high salt intake. Modulation of the immune response can reduce severity of blood pressure elevation and hypertensive end-organ damage in several animal models. The purpose of this review is to briefly summarize recent advances in immunity and hypertension as well as hypertensive end-organ damage.

Aortic mural thrombus in the absence of underlying aortic disease is rare and results in a risk of distant arterial embolization that can result in limb loss or other end organ damage. Current management involves open surgery, anticoagulation, and systemic thrombolysis; however, each carries inherent risks. We report the case of aortic thrombus with distal emboli in two patients, a 56-year-old man and a 68-year-old man, neither with underlying aortic pathology and both presenting with limb threatening ischemia. We performed percutaneous mechanical thrombectomy using the FlowTriever System (Inari Medical, Irvine, Calif) with successful removal of the aortic thrombus in both patients.

The coronavirus disease 2019 (COVID-19) pandemic is associated with significant morbidity and mortality throughout the world, predominantly due to lung and cardiovascular injury. The virus responsible for COVID-19—severe acute respiratory syndrome coronavirus 2—gains entry into host cells via ACE2 (angiotensin-converting enzyme 2). ACE2 is a primary enzyme within the key counter-regulatory pathway of the renin-angiotensin system (RAS), which acts to oppose the actions of Ang (angiotensin) II by generating Ang-(1–7) to reduce inflammation and fibrosis and mitigate end organ damage. As COVID-19 spans multiple organ systems linked to the cardiovascular system, it is imperative to understand clearly how severe acute respiratory syndrome coronavirus 2 may affect the multifaceted RAS. In addition, recognition of the role of ACE2 and the RAS in COVID-19 has renewed interest in its role in the pathophysiology of cardiovascular disease in general. We provide researchers with a framework of best practices in basic and clinical research to interrogate the RAS using appropriate methodology, especially those who are relatively new to the field. This is crucial, as there are many limitations inherent in investigating the RAS in experimental models and in humans. We discuss sound methodological approaches to quantifying enzyme content and activity (ACE, ACE2), peptides (Ang II, Ang-[1–7]), and receptors (types 1 and 2 Ang II receptors, Mas receptor). Our goal is to ensure appropriate research methodology for investigations of the RAS in patients with severe acute respiratory syndrome coronavirus 2 and COVID-19 to ensure optimal rigor and reproducibility and appropriate interpretation of results from these investigations.

Hypertension (HTN) is common in children and often associated with pathologic progression to end organ damage, specifically left ventricular hypertrophy (LVH). The primary goal of this retrospective chart review is to determine if patients with higher blood pressure were more likely to complete echocardiogram (ECHO) and more likely to have LVH, among a pediatric population referred for hypertension evaluation before the 2017 American Academy of Pediatrics (AAP) guidelines. To meet this goal, the number of patients evaluated by ECHO and prevalence of LVH was examined for independent associations with blood pressure and BMI categories by logistic regression. It was found that higher blood pressure was associated with having an ECHO evaluation (p = 0.012). Among patients evaluated by ECHO, one-third had LVH but the presence of LVH was not associated with blood pressure severity or use of anti-hypertensive medication. Instead, BMI was the only factor associated with LVH cardiac remodeling in our population (p = 0.025). Newly updated AAP practice guidelines recommend evaluation of HTN via ABPM, with ECHO performed only at the initiation of pharmaceutical therapy. It is notable that BMI, the only risk factor of LVH found in this study, is not addressed in the current AAP guidelines for ECHO evaluation among hypertensive children. This study suggests that ECHO evaluation may be warranted in a larger subset of children as is recommended by current European Society of Hypertension pediatric guidelines.

BACKGROUND Blood pressure variability (BPV) is associated with end organ damage and cardiovascular outcomes in hypertensive patients. Prehypertensive patients frequently develop hypertension (HT). The purpose of the present study was to evaluate the effect of BPV on the development of HT. METHODS Two hundred and seven prehypertensive patients from the Cappadocia cohort were monitored over 2 years, and 24-hour ambulatory blood pressure monitoring (ABPM), office BP, and home BP measurements were subsequently performed at 4- to 6-month intervals. BPV was calculated as average real variability (ARV) from 24-h ABPM data, home BP, and office BP measurements at first visit. The relationship was evaluated between baseline ARV and the development of HT. RESULTS HT was diagnosed in 25.60% of subjects. Baseline 24-hour ABPM systolic blood pressure (SBP)ARV and diastolic blood pressure (DBP)ARV and home SBPARV were significantly higher in patients who developed HT than the other patients (P 0.006, 0.001 and 0.006, respectively). Baseline 24-hour ABPM SBPARV and home SBPARV exceeding the 90th percentile were identified as parameters affecting development of HT at logistic regression analysis. CONCLUSION In conclusion, our prospective observational cohort study showed that short-term BPV in particular can predict the development of HT in the prehypertensive population.

The hypertensive emergency situation is characterized by an acute-mostly life-threatening-blood pressure derailment with the risk of acute end organ damage. It is an acute manifestation of arterial hypertension, which manifests in a variety of symptoms. The etiology is in most cases long-term (chronic) hypertension as a result of low compliance or inadequate antihypertensive therapy. It can also occur as a first manifestation of arterial hypertension. It requires timely antihypertensive drug therapy, which should be initiated in an intensive or intermediate care unit. The choice of antihypertensive therapy regimen should be based on the underlying end organ damage. Fast-acting, easily controllable and intravenously administered substances should be preferred. The most commonly used substances (groups) are urapidil, nitroglycerin, beta blockers and short-acting calcium channel blockers. With a few exceptions, a deliberate, rapid reduction in blood pressure of no more than 20-25% of the initial value is sufficient for extracerebral causes. A subsequent systolic blood pressure target of 160/100 mm Hg should be aimed for within the next 2-6 h. An overly rapid drop in blood pressure can lead to reduced blood flow to the central nervous system due to changes in autoregulation. Exceptions to this rule are acute aortic dissection and flash pulmonary edema-in these cases, prompt blood pressure normalization should be achieved. The initial acute therapy should be followed by a more detailed investigation of the cause and a long-term therapy setting based on this.

Heart failure (HF) and cancer are of the most common diseases globally, both associated with significant adverse outcomes and greatly impaired quality of life. Despite those similarities, over the last 15 years, the United States (USA) and European authorities have approved only 5 and 3 new drugs for HF respectively, none using an accelerated process and none for patients with either acute HF (AHF) or with HF and preserved ejection fraction (HFpEF). During the same period, more than 100 new drugs were approved for treatment of various cancers, several receiving accelerated approval. HF drugs in the last 15 years were mostly approved for reduction in mortality, whereas most approved cancer drugs addressed disease progression and surrogate markers. Consequently, the size of the trials in HF were far greater than those in oncology which was associated with lower probability of success. Given the larger study size and smaller probability of approval, pharma progressively reduces the necessary investments in new HF drugs. We suggest for HF drugs be developed, especially those used to treat patients with HFpEF and AHF, consideration of approval based beyond morbidity and mortality on improvements in symptoms and functional capacity and, like oncology, based on measures of disease progression and end organ damage. At the same time, HF drug development should adopt some approaches used in other diseases (such as oncology) focusing on better defining specific phenotypes and defining specific disease-related targets for new drugs.

Heart failure is characterized by pathologic hemodynamic derangements, including elevated cardiac filling pressures ("backward" failure), which may or may not coexist with reduced cardiac output ("forward" failure). Even when normal during unstressed conditions such as rest, hemodynamics classically become abnormal during stressors such as exercise in patients with heart failure. This has important upstream and downstream effects on multiple organ systems, particularly with respect to the lungs and kidneys. Hemodynamic abnormalities in heart failure are affected by processes that extend well beyond the cardiac myocyte, including important roles for pericardial constraint, ventricular interaction, and altered venous capacity. Hemodynamic perturbations have widespread effects across multiple heart failure phenotypes, ranging from reduced to preserved ejection fraction, acute to chronic disease, and cardiogenic shock to preserved perfusion states. In the lung, hemodynamic derangements lead to the development of abnormalities in ventilatory control and efficiency, pulmonary congestion, capillary stress failure, and eventually pulmonary vascular disease. In the kidney, hemodynamic perturbations lead to sodium and water retention and worsening renal function. Improved understanding of the mechanisms by which altered hemodynamics in heart failure affect the lungs and kidneys is needed in order to design novel strategies to improve clinical outcomes. Dr Verbrugge is supported by a Fellowship of the Belgian American Educational Foundation and by the Special Research Fund of Hasselt University (grant no. BOF19PD04). Dr Borlaug is supported by grants R01 HL128526 and U01 HL125205, both from the US National Heart, Lung, and Blood Institute. Borlaug, BA (corresponding author), Mayo Clin & Mayo Fdn, 200 First St SW, Rochester, MN 55905 USA. borlaug.barry@mayo.edu

Coronavirus disease (COVID-19) reached pandemic proportions at the beginning of 2020 and continues to be a worldwide concern. End organ damage and acute respiratory distress syndrome are the leading causes of death in severely or critically ill patients. The elevated cytokine levels in severe patients in comparison with mildly affected patients suggest that cytokine release syndrome (CRS) occurs in the severe form of the disease. In this paper, the significant role of pro-inflammatory cytokines, including IL-1, IL-6, and TNF-alpha, and their mechanism of action in the CRS cascade is explained. Potential therapeutic approaches involving anti-IL-6 and anti-TNF-alpha antibodies to fight COVID-19 and reduce mortality rate in severe cases are also discussed.

Hypereosinophilic syndrome is a rare entity and heterogeneous group of disorders characterized by hypereosinophilia and organ involvement. In this study, we presented a 49-year-old woman with cardiac tamponade in the context of Hypereosinophilic syndrome. Identifying hypereosinophilia as the underlying cause can have tremendous clinical implications for rapid initiation of appropriate treatment to minimize further end organ damage.

Detection of end-organ damage (EOD) in systemic hypertension is essential for the management of systemic hypertension. We aimed to evaluate subfoveal choroidal thickness (SFCT) and retinal layers' thicknesses by using spectral domain optical coherence tomography (SD‑OCT) in patients with systemic hypertension and to assess the relationship between EOD and SD-OCT parameters.A total of 189 consecutive patients with systemic hypertension and 100 controls were included. Patients were examined to detect EOD including hypertensive retinopathy (HTRP), left ventricular hypertrophy assessed by transthoracic echocardiography and microalbuminuria assessed by 24-h urine analysis. SFCT, inner plexiform-ganglion cell complex (IP-GCC), peripapillary retinal nerve fiber layer (pRNFL) and central macular thickness (CMT) were measured with SD-OCT.Patients with systemic hypertension had significantly lower SFCT and retinal layer thicknesses than controls (P˂0.001). In the dilated fundus photographic evaluation, 94 patients with systemic hypertension had HTRP and these patients had lower SFCT, CMT, IP-GCC and pRNFL thicknesses compared to hypertensive patients without HTRP and healthy controls. Patients with EOD had significantly lower SFCT, CMT, IP-GCC and pRNFL thicknesses and as the number of EOD increased, the SFCT decreased significantly. In the multivariate analysis, SFCT was found as an independent predictor of EOD (P˂0.001, odds ratio: 0.0605).Hypertensive patients, especially with EOD had significantly lower SD-OCT parameters compared to controls. It would be rational to add SD-OCT assessment to conventional hypertensive retinopathy evaluation in patients with systemic hypertension for early diagnosis of end-organ damage, burden of target organ involvement and monitoring anti-hypertensive treatment.

Necrotising soft tissue infection (NSTI) is a lethal infectious disease with rapid progression towards early hemodynamic failure, end organ damage, and death. A prospective observational study was conducted to analyse the clinical and microbiological spectrum of NSTI cases. All patients of NSTI presenting to the emergency department and consenting to participate in the study were included. Demographic details, clinical findings, laboratory parameters, operative findings, length of stay, and final outcome were noted in a study proforma. A total of 100 patients were included in the study, among whom 84 were males and 16 were females. The average age was 65.8 years with SD of 13.4. The most common presenting symptom was pain followed by redness of skin. Positive microbial culture was noted in 43 cases, and Streptococcus was the most common organism that had grown. The average length of stay was around 21 days, and patients underwent on an average 7 procedures. There were 16 fatal outcomes, and age, renal function, haemoglobin levels, bilirubin levels, and blood sugar levels were found to be significant predictors of mortality. NSTI, even in today’s era, continue to cause substantial mortality and morbidity. Aggressive debridement and broad spectrum antibiotics form the mainstay of therapy.

Cardiac hypertrophy and renal damage associated with hypertension are independent predictors of morbidity and mortality. In a model of hypertensive heart disease and renal damage, we tested the actions of continuous administration of Vastiras, a novel compound derived from the linear fragment of ANP (atrial natriuretic peptide), namely pro-ANP 31–67 , on blood pressure and associated renal and cardiac function and remodeling. Of note, this peptide, unlike the ring structured forms, does not bind to the classic natriuretic peptide receptors. Dahl/Salt–Sensitive rats fed a 4% NaCl diet for 6 weeks developed hypertension, cardiac hypertrophy, and renal damage. Four weeks of treatment with 50 to 100 ng/kg per day of Vastiras exhibited positive effects on renal function, independent of blood pressure regulation. Treated rats had increased urine excretion, natriuresis, and enhanced glomerular filtration rate. Importantly, these favorable renal effects were accompanied by improved cardiac structure and function, including attenuated cardiac hypertrophy, as indicated by decreased heart weight to body weight ratio, relative wall thickness, and left atrial diameter, as well as reduced fibrosis and normalized ratio of the diastolic mitral inflow E wave to A wave. A renal subtherapeutic dose of Vastiras (25 ng/kg per day) induced similar protective effects on the heart. At the cellular level, cardiomyocyte size and t-tubule density were preserved in Vastiras-treated compared with untreated animals. In conclusion, these data demonstrate the cardiorenal protective actions of chronic supplementation of a first-in-class compound, Vastiras, in a preclinical model of maladaptive cardiac hypertrophy and renal damage induced by hypertension.

BACKGROUND Recent studies have shown that hyperuricemia may be associated with incident hypertension (HTN). We examined whether serum uric acid (SUA) is a predictor of HTN and target organ damage (TOD) 20 years later in initially healthy middle-aged individuals. METHODS Participants from the Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) a single-center familial longitudinal cohort study (961 initially healthy adults and 570 children) underwent clinical and laboratory measurements at baseline and after approximately 20 years. Blood pressure (BP: using ambulatory BP measurements), urine albumin-to-creatinine ratio, estimated glomerular filtration rate (eGFR), left ventricular hypertrophy (LVH), diastolic dysfunction, and carotid–femoral pulse wave velocity (PWV) were measured at the end of follow-up. RESULTS In the parent population, higher baseline or last SUA levels and higher change in SUA (ΔUA) were significantly associated with an increased risk of HTN development, even after adjusting for known HTN risk factors (all P < 0.01). Higher baseline SUA was marginally associated with an increased risk of having high carotid–femoral PWV (P = 0.05). The association of SUA with BP increase was body mass index dependent (the increase in BP being greater in leaner subjects; interactionp < 0.05), and the association of SUA with eGFR decline was age dependent (the decline in eGFR being greater in older subjects; interactionp < 0.05). There was no significant association between SUA and diastolic dysfunction or LVH. In the whole population (i.e. including children), a significant association between SUA at baseline and the risk of HTN and higher carotid–femoral PWV was also found (both P < 0.02). CONCLUSIONS Increased SUA is associated with the development of HTN and vascular/renal TOD in initially healthy midlife subjects.

Cardiac arrest has a high rate of morbidity and mortality. Several advances in post‐cardiac arrest management can improve outcome, but are time‐dependent, placing the emergency physician in a critical role to both recognize the need for and initiate therapy. We present a novel perspective of both the workup and therapeutic interventions geared toward the emergency physician during the first few hours of care. We describe how the immediate care of a post‐cardiac arrest patient is resource intensive and requires simultaneous evaluation for the underlying cause and intensive management to prevent further end organ damage, particularly of the central nervous system. The goal of the initial focused assessment is to rapidly determine if any reversible causes of cardiac arrest are present and to intervene when possible. Interventions performed in this acute period are aimed at preventing additional brain injury through optimizing hemodynamics, providing ventilatory support, and by using therapeutic hypothermia when indicated. After the initial phase of care, disposition is guided by available resources and the clinician's judgment. Transfer to a specialized cardiac arrest center is prudent in centers that do not have significant support or experience in the care of these patients.

Background Although seasonal variation of home blood pressure (BP) has been reported to be higher in winter, seasonal difference in home BP (HBP) and its association with target organ damage (TOD) remains unclear. Methods This is a cross-sectional study using the dataset from the Japan Morning Surge-Home Blood Pressure (J-HOP) study to assess seasonal differences in HBP, prevalence of masked hypertension, and association of HBP with TOD. The J-HOP study is a nationwide, multicenter prospective study whose participants with cardiovascular risks underwent morning and evening HBP measurements for a 14-day period in 71 institutions throughout Japan. Urine albumin–creatinine ratio (UACR) and serum-B-type natriuretic peptide (BNP) were obtained at enrollment. Results Among 4,267 participants (mean age, 64.9 ± 10.9 years; 46.9% male; 91.4% hypertensives), 1,060, 979, 1,224, and 1,004 participants were enrolled in spring, summer, autumn, and winter, respectively. Morning and evening home systolic/diastolic BP levels, and prevalence of masked hypertension (office BP Conclusions In this study, we revealed that the prevalence of masked hypertension was higher in other seasons than in summer and found a notable association between morning home diastolic BP and TOD in winter.

OBJECTIVE(S): Few data exist relating the burden of cardiovascular (CV) risk factors over the childhood and young adult years on left ventricular mass (LVM), a known risk factor for hard CV events later in life. Racial differences exist in the development of cardiovascular Disease (CVD), with blacks adversely affected. We examined racial differences in the relationship between CV risk factors measured since age 10 and left ventricular mass index (LVMI) in adulthood in the NHLBI Growth and Health Study. STUDY DESIGN: Longitudinal investigation with CV risk factors measured throughout childhood and LVMI measured in adulthood. 556 black and white girls recruited from schools in the greater Cincinnati area. Analyses examined traditional CV risk factors at baseline, follow-up, and over time (i.e. area under the curve, AUC). LVMI was collected with 2-D guided echocardiographic imaging at a mean age of 25.7 ± 1.7 years. RESULTS: Black girls had higher adiposity and insulin and lower heart rate across time (all p < 0.05). Blacks had higher LVMI compared to whites in adulthood. Major determinants of young adult LVMI, were race, body mass index z-score AUC, systolic blood pressure z-score AUC, percent body fat by skin fold AUC, heart rate AUC, and an interaction between race and heart rate (model R(2) = 0.40, p < .0001). CONCLUSIONS: The major determinants of LVMI in young adult females are race, adiposity and systolic blood pressure. The contribution of heart rate to LVMI in whites may relate to previously noted higher sympathetic tone in obese whites.

BACKGROUND Hypertensive urgencies (HypUrg) are defined as severe elevation in blood pressure (BP) without acute target organ damage. In the office setting, treated asymptomatic patients, with severe BP elevation meeting criteria for urgency are often seen. We evaluate incident Cardiovascular (CV) events (n = 311) during follow-up (FU) in patients with HypUrg at first outpatient visit. METHODS HypUrg was defined by systolic BP ≥180 mm Hg and/or diastolic BP ≥110 mm Hg. Patients were >18 years old, with available ultrasound data, without prevalent CV disease, and no more than stage III Chronic Kidney Disease. BP control was defined as the average BP during FU RESULTS Four hundred and sixty-nine of 6,929 patients presented with HypUrg at first visit. Patients with HypUrg were more likely to be women, obese and diabetic and with higher prevalence of left ventricle (LV) hypertrophy and carotid plaque (all P < 0.05). During FU patients with HypUrg had 5-fold higher risk of uncontrolled BP (95% confidence interval (CI) 4.1–6.8, P < 0.0001). In Cox regression presenting with HypUrg was not associated with increased CV risk after adjusting for significant covariates, including age, sex, BP control, LV hypertrophy, and carotid plaque (hazard ratio (HR) 1.42, 95% CI (0.96–2.11), P = 0.08). CONCLUSIONS Patients with HypUrg have worst CV risk profile, reduced probability of BP control during FU and greater prevalence of target organ damage, but the excess CV event risk appears to be mediated through BP control, non-BP cardio-vascular disease risk factors, and demographic attributes. CLINICALTRIALS.GOV IDENTIFIER NCT02211365.

Reduced nitric oxide (NO) and a decrease in cGMP signaling mediated by soluble guanylate cyclase (sGC) has been linked to the development of several cardiorenal diseases. Stimulation of sGC is a potential means for enhancing cGMP production in conditions of reduced NO bioavailability. The purpose of our studies was to determine the effects of praliciguat, a clinical-stage sGC stimulator, in a model of cardiorenal failure. Dahl salt-sensitive rats fed a high-salt diet to induce hypertension and organ damage were treated with the sGC stimulator praliciguat to determine its effects on hemodynamics, biomarkers of inflammation, fibrosis, tissue function, and organ damage. Praliciguat treatment reduced blood pressure, improved cardiorenal damage, and attenuated the increase in circulating markers of inflammation and fibrosis. Notably, praliciguat affected markers of renal damage at a dose that had minimal effect on blood pressure. In addition, liver fibrosis and circulating markers of tissue damage were attenuated in praliciguat-treated rats. Stimulation of the NO-sGC-cGMP pathway by praliciguat attenuated or normalized indicators of chronic inflammation, fibrosis, and tissue dysfunction in the Dahl salt-sensitive rat model. Stimulation of sGC by praliciguat may present an effective mechanism for treating diseases linked to NO deficiency, particularly those associated with cardiac and renal failure. Praliciguat is currently being evaluated in patients with diabetic nephropathy and heart failure with preserved ejection fraction.