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Aims Formylpeptide receptors (FPRs) play a critical role in the regulation of inflammation, an important driver of hypertension-induced end-organ damage. We have previously reported that the biased FPR small-molecule agonist, compound17b (Cmpd17b), is cardioprotective against acute, severe inflammatory insults. Here, we reveal the first compelling evidence of the therapeutic potential of this novel FPR agonist against a longer-term, sustained inflammatory insult, i.e. hypertension-induced end-organ damage. The parallels between the murine and human hypertensive proteome were also investigated. Methods and results The hypertensive response to angiotensin II (Ang II, 0.7 mg/kg/day, s.c.) was attenuated by Cmpd17b (50 mg/kg/day, i.p.). Impairments in cardiac and vascular function assessed via echocardiography were improved by Cmpd17b in hypertensive mice. This functional improvement was accompanied by reduced cardiac and aortic fibrosis and vascular calcification. Cmpd17b also attenuated Ang II-induced increased cardiac mitochondrial complex 2 respiration. Proteomic profiling of cardiac and aortic tissues and cells, using label-free nano-liquid chromatography with high-sensitivity mass spectrometry, detected and quantified ∼6000 proteins. We report hypertension-impacted protein clusters associated with dysregulation of inflammatory, mitochondrial, and calcium responses, as well as modified networks associated with cardiovascular remodelling, contractility, and structural/cytoskeletal organization. Cmpd17b attenuated hypertension-induced dysregulation of multiple proteins in mice, and of these, ∼110 proteins were identified as similarly dysregulated in humans suffering from adverse aortic remodelling and cardiac hypertrophy. Conclusion We have demonstrated, for the first time, that the FPR agonist Cmpd17b powerfully limits hypertension-induced end-organ damage, consistent with proteome networks, supporting development of pro-resolution FPR-based therapeutics for treatment of systemic hypertension complications. [ABSTRACT FROM AUTHOR]

Sickle cell disease is an orphan disease affecting ethnic minorities and characterized by profound systemic manifestations. Although around 100,000 individuals with SCD are living in the US, the exact number of individuals is unknown, and it is considered an orphan disease. This single-gene disorder leads to red blood cell sickling and the deoxygenation of hemoglobin, resulting in hemolysis. SCD is associated with acute complications such as vaso-occlusive crisis, infections, and chronic target organ complications such as pulmonary disease and renal failure. While genetic therapy holds promise to alter the fundamental disease process, the major challenge in the field remains the target end organ damage and ways to mitigate or reverse it. Here, we provide an overview of the clinical manifestations and pathogenesis with a focus on end-organ damage and current therapeutic options, including recent FDA-approved stem cell and gene editing therapies. [ABSTRACT FROM AUTHOR]

Abstract Background Invasive fungal infection (IFI) has become an increasing problem in NICU neonates, and end-organ damage (EOD) from IFI is one of the leading causes of morbidity and mortality in neonates. This study was conducted to summarize clinical data on epidemiology, risk factors, causative pathogens, and clinical outcomes of IFI-associated EOD among neonates in a center in China for the sake of providing references for prevention and treatment of fungal infections in neonates in future. Methods The clinical data of IFI neonates who received treatment in a tertiary NICU of China from January 2009 to December 2022 were retrospectively analyzed, including causative pathogens and the incidence of EOD. The neonates were divided into EOD group and non-EOD (NEOD) group. The general characteristics, risk factors and clinical outcomes of the two groups were compared. Results Included in this study were 223 IFI neonates (137 male and 86 female) with a median gestational age (GA) of 30.71 (29,35) weeks and a median birth weight (BW) of 1470 (1120,2150) g. Of them, 79.4% were preterm infants and 50.2% were born at a GA of ≥ 28,

Background: The extensive variability and conflicting information in Coronavirus Disease 2019 (COVID-19) patient data have made it difficult for the medical community to gain a comprehensive understanding and develop clear, reliable guidelines for managing COVID-19 cases. As the world uncovers the diverse side effects of the pandemic, the pursuit of knowledge about COVID-19 has become crucial. The present study aimed to evaluate some clinically relevant serum proteins, providing analysis of the obtained results to employ them in the diagnosis, prognosis, and disease monitoring among COVID-19 patients. Methods: Samples were collected from 262 COVID-19 unvaccinated hospitalized patients. Measurement of certain serum proteins, namely C-reactive protein (CRP), ferritin, D-dimer, procalcitonin, interleukin-6 (IL-6), serum creatinine (SCr), alanine transaminase (ALT), aspartate transaminase (AST) was done using standard methods. Statistical analysis was performed on the obtained data and the results were correlated to the severity and prognosis. Results: The calculated Mortality rate was found to be 30% with a higher percentage observed among females. The results showed elevation in serum CRP, ferritin, D-dimer, and procalcitonin in most of the patients, also some patients had elevated SCr, ALT, and AST levels indicating end-organ damage. The statistical analysis displayed a strong correlation between serum levels of CRP and ferritin, between D-dimer and ferritin, and between ferritin and procalcitonin. No significant difference was observed between male and female patients' serum levels of the tested serum proteins. A significant correlation between increased serum procalcitonin and mortality was observed. Conclusion: The levels of measured serum proteins were impacted by SARS-CoV-2 infection. Serum ferritin, CRP, D-dimer, and procalcitonin are good predicting tools for end-organ damage and acute kidney impairment in COVID-19. Procalcitonin is a strong indicator of severity and mortality in hospitalized COVID-19 patients. [ABSTRACT FROM AUTHOR]

Asymptomatic severe hypertension is defined as systolic blood pressure of ≥ 180 mmHg or diastolic blood pressure of ≥ 120 mmHg without signs and symptoms of end-organ damage or dysfunction. Literature shows that around 5% of the patients with severe asymptomatic hypertension had acute hypertension-related end-organ damage. This study aimed to determine the clinical utility of routine investigations and risk factors of end-organ damage in patients presented to the emergency department with asymptomatic severe hypertension. This single-center, cross-sectional study was conducted at the emergency department of the Aga Khan University Hospital, Karachi, Pakistan, from January 2018 to December 2020. All adult patients (age ≥ 18 years) presented to the emergency department with a systolic blood pressure of ≥ 180 or diastolic blood pressure of ≥ 120 mmHg without any signs and symptoms of end-organ damage (e.g., chest pain, unilateral limb or facial weakness, or hemiplegia, altered mental status, shortness of breath, decreased urine output, and sudden-onset of severe headache) were included. Routine investigations were analyzed to detect end-organ damage, including complete blood count, basic metabolic panel, urine detailed report, electrocardiogram, and troponin-I. Multivariable binary logistic regression was applied to identify the risk factors of end-organ damage considering the significant p value of ≤ 0.05. A total of 180 patients were presented to the emergency department with asymptomatic severe hypertension during the study period. Among the total patients, 60 patients (33.3%) had abnormal investigation findings; out of them, new-onset end-organ damage was diagnosed in 15 patients (8.3%). The most common end-organ damage was the kidney (73.3%) followed by the heart (26.6%). The multivariable binary logistic regression showed that age of more than 60 years, past medical history of diabetes, ischemic heart disease, and cerebrovascular accident were significantly associated with a higher risk of end-organ damage (p < 0.05). The study identified a higher prevalence of abnormal routine investigations and acute end-organ damage in emergency department patients with asymptomatic severe hypertension compared to high-income countries and suggested a lower threshold for end-organ damage screening in these patients. The current recommendations of foregoing further workup in patients with asymptomatic severe hypertension may need modification for emergency departments in low–middle-income countries if similar associations are replicated in other settings. [ABSTRACT FROM AUTHOR]

Maternal sepsis is a significant cause of maternal morbidity and mortality, and is a potentially preventable cause of maternal death. This Consult aims to summarize what is known about sepsis and provide guidance for the management of sepsis during pregnancy and the postpartum period. Most studies cited are from the nonpregnant population, but where available, pregnancy data are included. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend that clinicians consider the diagnosis of sepsis in pregnant or postpartum patients with otherwise unexplained end-organ damage in the presence of a suspected or confirmed infectious process, regardless of the presence of fever (GRADE 1C); (2) we recommend that sepsis and septic shock in pregnancy be considered medical emergencies and that treatment and resuscitation begin immediately (Best Practice); (3) we recommend that hospitals and health systems use a performance improvement program for sepsis in pregnancy with sepsis screening tools and metrics (GRADE 1B); (4) we recommend that institutions develop their own procedures and protocols for the detection of maternal sepsis, avoiding the use of a single screening tool alone (GRADE 1B); (5) we recommend obtaining tests to evaluate for infectious and noninfectious causes of life-threatening organ dysfunction in pregnant and postpartum patients with possible sepsis (Best Practice); (6) we recommend that an evaluation for infectious causes in pregnant or postpartum patients in whom sepsis is suspected or identified includes appropriate microbiologic cultures, including blood, before starting antimicrobial therapy, as long as there are no substantial delays in timely administration of antibiotics (Best Practice); (7) we recommend obtaining a serum lactate level in pregnant or postpartum patients in whom sepsis is suspected or identified (GRADE 1B); (8) in pregnant or postpartum patients with septic shock or a high likelihood of sepsis, we recommend administration of empiric broad-spectrum antimicrobial therapy, ideally within 1 hour of recognition (GRADE 1C); (9) after a diagnosis of sepsis in pregnancy is made, we recommend rapid identification or exclusion of an anatomic source of infection and emergency source control when indicated (Best Practice); (10) we recommend early intravenous administration (within the first 3 hours) of 1 to 2 L of balanced crystalloid solutions in sepsis complicated by hypotension or suspected organ hypoperfusion (GRADE 1C); (11) we recommend the use of a balanced crystalloid solution as a first-line fluid for resuscitation in pregnant and postpartum patients with sepsis or septic shock (GRADE 1B); (12) we recommend against the use of starches or gelatin for resuscitation in pregnant and postpartum patients with sepsis or septic shock (GRADE 1A); (13) we recommend ongoing, detailed evaluation of the patient's response to fluid resuscitation guided by dynamic measures of preload (GRADE 1B); (14) we recommend the use of norepinephrine as the first-line vasopressor during pregnancy and the postpartum period with septic shock (GRADE 1C); (15) we suggest using intravenous corticosteroids in pregnant or postpartum patients with septic shock who continue to require vasopressor therapy (GRADE 2B); (16) because of an increased risk of venous thromboembolism in sepsis and septic shock, we recommend the use of pharmacologic venous thromboembolism prophylaxis in pregnant and postpartum patients in septic shock (GRADE 1B); (17) we suggest initiating insulin therapy at a glucose level >180 mg/dL in critically ill pregnant patients with sepsis (GRADE 2C); (18) if a uterine source for sepsis is suspected or confirmed, we recommend prompt delivery or evacuation of uterine contents to achieve source control, regardless of gestational age (GRADE 1C); and (19) because of an increased risk of physical, cognitive, and emotional problems in survivors of sepsis and septic shock, we recommend ongoing comprehensive support for pregnant and postpartum sepsis survivors and their families (Best Practice). [ABSTRACT FROM AUTHOR]

Sickle cell disease is an orphan disease affecting ethnic minorities and characterized by profound systemic manifestations. Although around 100,000 individuals with SCD are living in the US, the exact number of individuals is unknown, and it is considered an orphan disease. This single-gene disorder leads to red blood cell sickling and the deoxygenation of hemoglobin, resulting in hemolysis. SCD is associated with acute complications such as vaso-occlusive crisis, infections, and chronic target organ complications such as pulmonary disease and renal failure. While genetic therapy holds promise to alter the fundamental disease process, the major challenge in the field remains the target end organ damage and ways to mitigate or reverse it. Here, we provide an overview of the clinical manifestations and pathogenesis with a focus on end-organ damage and current therapeutic options, including recent FDA-approved stem cell and gene editing therapies.

Objective: To assess the prevalence of hypertension in children with infrequently relapsing nephrotic syndrome (IRNS) and its association with dyslipidemia, and end organ damage including left ventricular hypertrophy (LVH), at relapse and after steroid induced remission. Methods: Prospective observational study conducted in 83 children aged 1–12 years with IRNS, presenting in relapse. Blood pressure, fundus examination, blood and urine investigations were done at relapse and then at 4 weeks of therapy. Echocardiography at 4 weeks was performed for assessment of LVH and relative wall thickness (RWT) for concentric geo-metry (CG). Results: 27 patients (32.5%) developed hypertension, out of which 21 patients (25.3%) had stage I hypertension. Hypertension in first episode (63.0%, P<0.01) and in previous relapses (87.5%, P<0.001) was significantly associated with hypertension in the current episode. 12 patients had a positive family history of hypertension, of which 8 (66.7%) were classified under the hypertensive group (P=0.016). Concentric geometry (CG) was found in 28% of hypertensive and 5.5% of non-hypertensive children (P=0.011). On regres-sion analysis, a lower Up:Uc at the time of relapse was found to have a protective role for development of hypertension. Conclusion: One third children with IRNS had hypertension at relapse and a high proportion of hypertensive patients had CG pattern on echocardiography. [ABSTRACT FROM AUTHOR]

Background: Microalbuminuria (MA) is an independent risk factor in association with fatal cardiovascular and cerebrovascular outcomes among patients with hypertension (HTN). Methods: An observational study was conducted among 100 randomly selected hypertensive patients January 2013 to January 2014 to observe the proportion of MA among hypertensive patients and the proportion of presence of various target organ damages (TODs) in them. Results: The frequency of MA was 36% among participants. The frequency in males was slightly more than females (38.2% vs. 33.3%). The frequency of MA increased linearly with the duration and severity of HTN. It was more commonly found in smokers than in non-smokers. Diastolic dysfunction (42%) and Grade 2 hypertensive retinopathy (60.7%) were associated with MA. TOD was frequently observed in MA-positive patients. Conclusions: The proportion of patients with MA was in increasing trend with increasing age of hypertensive participants and duration of history of HTN. Hypertensive retinopathy, regional wall motion abnormality and neurological deficit emerged to be sensitive surrogate markers for MA in patients with HTN.

Depending on end-organ involvement, hypertensive crisis is classified as hypertensive urgency or hypertensive emergency. The recognition of a hypertensive crisis will lead to the adequate reduction of blood pressure to ameliorate the incidence of end-organ damage. Hypertensive crises result from dysfunction in the renin-angiotensin-aldosterone system and damage to the vascular bed. They occur commonly in the emergency department setting and can lead to increased mortality rates if not treated. Registered nurses play a vital role in assessing patients and administering medications during hypertensive crises. This article will outline the assessment strategies that registered nurses should implement in critical care units while patients are receiving antihypertensive drugs. We will also underscore the significance of monitoring specific laboratory values to mitigate the potential side effects of these drugs and exclude them when contraindicated. [ABSTRACT FROM AUTHOR]

Inflammation and immunity play a major role in the development of hypertension, and a potential correlation between host mucosal immunity and inflammatory response regulation. We explored the changes of intestinal mucosal microbiota in hypertensive rats induced by high-salt diet and the potential link between the intestinal mucosal microbiota and inflammation in rats. Therefore, we used PacBio (Pacific Bioscience) SMRT sequencing technology to determine the structure of intestinal mucosal microbiota, used enzyme-linked immunosorbent assay (ELISA) to determined the proinflammatory cytokines and hormones associated with hypertension in serum, and used histopathology methods to observe the kidney and vascular structure. We performed a potential association analysis between intestinal mucosal characteristic bacteria and significantly different blood cytokines in hypertensive rats induced by high-salt. The results showed that the kidney and vascular structures of hypertensive rats induced by high salt were damaged, the serum concentration of necrosis factor-α (TNF-α), angiotensin II (AngII), interleukin-6 (IL-6), and interleukin-8 (IL-8) were significantly increased (p < 0.05), and the coefficient of immune organ spleen was significantly changed (p < 0.05), but there was no significant change in serum lipids (p > 0.05). From the perspective of gut microbiota, high-salt diet leads to significant changes in intestinal mucosal microbiota. Bifidobacterium animalis subsp. and Brachybacterium paraconglomeratum were the dominant differential bacteria in intestinal mucosal, with the AUC (area under curve) value of Bifidobacterium animalis subsp. and Brachybacterium paraconglomeratum were 1 and 0.875 according to ROC (receiver operating characteristic) analysis. Correlation analysis showed that Bifidobacterium animalis subsp. was correlated with IL-6, IL-8, TNF-α, and Ang II. Based on our results, we can speculated that high salt diet mediated chronic low-grade inflammation through inhibited the growth of Bifidobacterium animalis subsp. in intestinal mucosa and caused end-organ damage, which leads to hypertension. [ABSTRACT FROM AUTHOR]

Cisplatin is a widely used and efficacious chemotherapeutic agent for treating solid tumors, yet it causes systemic end-organ damage that is often irreversible and detrimental to quality of life. This includes severe sensorineural hearing loss, hepatotoxicity, and renal injury. Based on the hard-soft acid-base theory, we recently developed two acetophenone-derived, enol-based compounds that directly interfere with the side effects of cisplatin. We investigated organ-specific and generalized toxicity in order to define dose-dependent responses in rodents injected with cisplatin with or without the protective compounds. All metrics that were used as indicators of toxicity showed retention of baseline or control measurements when animals were pre-treated with acetophenones prior to cisplatin administration, while animals injected with no protective compounds showed expected elevations in toxicity measurements or depressions in measurements of organ function. These data support the further investigation of novel acetophenone compounds for the prevention of cisplatin-induced end-organ toxicity.

Summary: The definition of multiple myeloma (MM) was updated in 2014, with the intent to enable earlier treatment and thereby avoid appearance of end‐organ damage at progression from smouldering multiple myeloma (SMM) to MM. The purpose of this study was to investigate to which extent the development of end‐organ damage at progression to MM was reduced under the updated guidelines. In this prospective observational cohort study (ClinicalTrials.gov Identifier: NCT01374412), between 2014 and 2020, 96 SMM patients prospectively underwent whole‐body magnetic resonance imaging (wb‐MRI) and serological follow‐up at baseline and every 6 months thereafter. A total of 22 patients progressed into MM during follow‐up, of which seven (32%) showed SLiM‐criteria only but no end‐organ damage. Four (57%) of the seven patients who progressed by SLiM‐criteria only progressed with >1 focal lesion (FL) or a growing FL, and three (43%) due to serum free light‐chain‐ratio ≥100. Fifteen (68%) out of 22 patients who progressed still suffered from end‐organ damage at progression. The updated disease definition reduced the proportion of SMM patients suffering from end‐organ damage at progression to MM by one third. wb‐MRI is an important tool for detection of SMM patients who progress to MM without end‐organ damage. [ABSTRACT FROM AUTHOR]

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Introduction Chronic hypertension is associated with left ventricular hypertrophy. Recent evidence suggests that secondhand smoke (SHS) exposure is associated with chronic hypertension, so we sought to examine the relationship between secondhand smoke exposure and electrocardiographic left ventricular (LV) mass among non-smokers. Methods This analysis included 4982 non-smoker participants from the Third National Health and Nutrition Examination (NHANES-III). Non-smoking was defined by self-report and serum cotinine ≤10 ng/mL, a biomarker for tobacco exposure. SHS exposure was defined as serum cotinine level ≥1 ng/mL. LV mass was estimated using an electrocardiographic model developed and applied in NHANES-III then validated in the Cardiovascular Health Study. Multivariable linear regression was used to examine the cross-sectional association between SHS exposure (vs no exposure) with estimated LV mass index. In similar models, we also examined the associations of LV mass index across quartiles of serum cotinine (reference group, 1st quartile) and in subgroups stratified by age, race, sex, hypertension, and obesity. Results About 9.8% (n=489) of the participants were exposed to SHS. Exposure to SHS was associated with an estimated 2.9 g/m 2 increase in LV mass index, with a dose-response relationship between higher serum cotinine and LV mass index. These results were consistent in men and women, Whites and non-Whites, elderly and non-elderly, and those with and without hypertension. Significant effect modification was present among obese individuals with an estimated 4.8 g/m 2 increase in LV mass index (interaction p=0.01). Conclusions In a racially diverse sample of non-smokers, SHS is associated with increased LV mass with a dose-response relationship between level of exposure and LV mass. Effect modification was present among obese individuals. These findings underscore the harmful effect of passive smoking on the cardiovascular system and highlight the need for more restrictions on smoking in public areas, especially in countries or regions with less-stringent public health policies.

Current guidelines emphasize the use of 100% oxygen during cardiopulmonary resuscitation after cardiac arrest. When patients are ventilated for variable periods after return of spontaneous circulation (ROSC), hyperoxia causes increased morbidity and mortality by overproduction of reactive oxygen species. Various patient, volunteer, and animal studies have shown the harmful effects of hyperoxia. This mini-review article aims to expand the potential clinical spectrum of hyperoxia on individual organ systems leading to organ dysfunction. A framework to achieve and maintain normoxia after ROSC is proposed. Despite the harmful considerations of hyperoxia in critically ill patients, additional safety studies including dose-effect, level and onset of the reactive oxygen species effect, and safe hyperoxia applicability period after ROSC, need to be performed in various animal and human models to further elucidate the role of oxygen therapy after cardiac arrest. [ABSTRACT FROM AUTHOR]

Background: The American College of Cardiology and American Heart Association define hypertensive emergency (HTN-E) as a systolic blood pressure greater than 180 mmHg or a diastolic blood pressure greater than 120 mmHg with evidence of end-organ damage (EOD). Based on expert opinion, current guidelines recommend antihypertensive therapy to reduce blood pressure (BP) at specific hourly rates to reduce progression of EOD, outlined by four criteria. Our goal was to describe compliance with guideline recommendations for early management of HTN-E and to analyze safety outcomes related to pharmacologic intervention.Methods: This was a retrospective chart review including patients presenting to the emergency department with HTN-E between September 2016 and August 2020. We excluded patients with a compelling indication for altered therapeutic goals (e.g. acute aortic dissection, hemorrhagic or ischemic stroke, and pheochromocytoma). The primary outcome was complete adherence with guideline recommendations in the first 24 h.Results: Of 758 screened records, 402 were included. Mean age was 54 years and majority Black race (72%). Overall, total adherence was poor (<1%): 30% received intravenous therapy within 1 h, 64% achieved 1-h BP goals, 44% achieved 6-h goals, and 9% had appropriate 24-h maintenance BP. Hypotensive events (N = 67) were common and antihypertensive-associated EOD (N = 21) did occur. Predictors of hypotension include treatment within 1 h and management with continuous infusion medication.Conclusions: Current practice is poorly compliant with guideline criteria and there are risks associated with recommended treatments. Our results favor relaxing the expert opinion-based recommendations. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • OSA is a progressive disease. • Some patients with OSA not treated with PAP at diagnosis have poor long-term outcome. • Higher age and BMI and a higher percentage of central apneas were significant predictors of major CVC. • AHI was a poor predictor of cardiovascular comorbidities. • Baveno classification allows a better stratification of the OSA patients. [ABSTRACT FROM AUTHOR]

Purpose 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. Methods 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. Results 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). Conclusion 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.

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. [ABSTRACT FROM AUTHOR]

BackgroundIt is unclear whether antihypertensive treatment can restore cardiovascular disease risk to the risk level of persons with ideal blood pressure (BP) levels.Methods and resultsData from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA) study were analyzed. Outcomes were compared among participants without or with antihypertensive treatment at 3 BP levels: 100, and twice the incident cardiovascular disease rate over 9.5 years of follow-up than those with BP 3000 mm Hg-years in 25 years), the increase in left ventricular mass index accelerated.ConclusionsThe data suggest that based on the current approach, antihypertensive treatment cannot restore cardiovascular disease risk to ideal levels. Emphasis should be placed on primordial prevention of BP increases to further reduce cardiovascular disease morbidity and mortality.

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. [ABSTRACT FROM AUTHOR]

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<0.001 for all). In the HE group, clinical features associated with end-organ damage included ST-elevation myocardial infarction (n=28, 46.7%), hemorrhagic stroke (n=11, 18.3%), ischemic stroke (n=11, 18.3%), and non-ST-elevation myocardial infarction (n=10, 16.7%). The receiving operator characteristic (ROC) analysis identified a serum corin cutoff value of 45 pg/mL for distinguishing patients with HE from patients with HU with 98.3% sensitivity and 95% specificity. Conclusion: Our findings suggest that serum corin levels play an important role in regulating blood pressure and are involved in the pathogenesis of HC. Low serum corin levels may predict end-organ damage and serve as a guide for diagnostic decision making in patients with HC. [ABSTRACT FROM AUTHOR]

1. The aim of the present study was to test the hypothesis that increasing kidney tissue concentrations of epoxyeicosatrienoic acids (EETs) by preventing their degradation to the biologically inactive dihydroxyeicosatrienoic acids (DHETEs) using blockade of soluble epoxide hydrolase (sEH) would attenuate the progression of chronic kidney disease (CKD). 2. Ren-2 transgenic rats (TGR) after 5/6 renal mass reduction (5/6 NX) served as a model of CKD associated with angiotensin (Ang) II-dependent hypertension. Soluble epoxide hydrolase was inhibited using cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid (c-AUCB; 3 mg/L drinking water) for 20 weeks after 5/6 NX. Sham-operated normotensive transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. 3. When applied in TGR subjected to 5/6 NX, c-AUCB treatment improved survival rate, prevented the increase in blood pressure, retarded the progression of cardiac hypertrophy, reduced proteinuria and the degree of glomerular and tubulointerstitial injury and reduced glomerular volume. All these organ-protective actions were associated with normalization of the intrarenal EETs:DHETEs ratio, an index of the availability of biologically active EETs, to levels observed in sham-operated HanSD rats. There were no significant concurrent changes of increased intrarenal AngII content. 4. Together, these results show that 5/6 NX TGR exhibit a profound deficiency of intrarenal availability of active epoxygenase metabolites (EETs), which probably contributes to the progression of CKD in this model of AngII-dependent hypertension, and that restoration of intrarenal availability of EETs using long-term c-AUCB treatment exhibits substantial renoprotective actions.

Background: Data on prevalence and burden of end-organ damage in fibrocalculous pancreatic diabetes (FCPD) from eastern India is scant. This study investigated the burden of end-organ damage and exocrine pancreatic defect in FCPD patients in Eastern India. Materials and Methods: Consecutive FCPD patients underwent evaluation of glycemic control, C-peptide, fecal elastase, body fat percent, tests for cardiac autonomic neuropathy (CAN), neuropathy, nephropathy, and retinopathy which were compared with data from type-1 diabetes (T1DM) and type-2 diabetes (T2DM). Results: Data from 101 FCPD, 41 T1DM, 40 T2DM, and 40 controls were analyzed. Body fat percent was lowest in FCPD and T1DM. Similarly, fasting and stimulated C-peptide was significantly lowest in T1DM, followed by FCPD. Significant elevations in stimulated C-peptide were observed in FCPD. Fecal elastase was lowest in FCPD. Exocrine pancreas defect in FCPD, T1DM, and T2DM was 100%, 53.66%, 27.5%, respectively. HbA1c was worst in FCPD. About 40% of FCPD patients had CAN while 13.33% had borderline CAN. Isolated parasympathetic dysfunction was the commonest (66.67%) among them. FCPD patients with CAN had lower fecal elastase, higher HbA1c, microalbuminuria, steatorrhea, neuropathy, retinopathy, and nephropathy, compared to those without CAN. On binary logistic regression, diabetes duration was a significant predictor of end-organ damage in FCPD. Fecal elastase and body fat percent were independent predictors for insulin therapy in FCPD. Conclusion: CAN is common in FCPD while exocrine pancreas defect is most severe in FCPD followed by T1DM and T2DM. Fecal elastase has an important prognostic role for insulinization in FCPD. Role of pancreatic enzyme replacement on glycemic control in diabetes with exocrine pancreas defect needs investigation.

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. [ABSTRACT FROM AUTHOR]

Hypertensive crisis is a relatively rare condition in children. However, if not treated, it might be life-threatening and lead to irreversible damage of vital organs. Clinical presentation of patients with hypertensive crisis can vary from very mild (hypertensive urgency) to severe symptoms (hypertensive emergency) despite similarly high blood pressure (BP). Individualized assessment of patients presenting with high BP with emphasis on the evaluation of end-organ damage rather than on the specific BP number is a key in guiding physician's initial management of a hypertensive crisis. The main aim of the treatment of hypertensive crisis is the prevention or treatment of life-threatening complications of hypertension-induced organ dysfunction, including neurologic, ophthalmologic, renal, and cardiac complications. While the treatment strategy must be directed toward the immediate reduction of BP to reduce the hypertensive damage to these organs, it should not be at a too fast rate to cause hypoperfusion of vital organs by an excessively rapid reduction of BP. Thus, intravenous continuous infusions rather than intravenous boluses of antihypertensive medications should be the preferable mode of initial treatment of children with hypertensive emergency. [ABSTRACT FROM AUTHOR]

The rat has classically been the species of choice for pharmacological studies and disease modeling, providing a source of high-quality physiological data on cardiovascular and renal pathophysiology over many decades. Recent developments in genome engineering now allow us to capitalize on the wealth of knowledge acquired over the last century. Here, we review rat models of hypertension, diabetic nephropathy, and acute and chronic kidney disease. These models have made important contributions to our understanding of renal diseases and have revealed key genes, such as Ace and P2rx7, involved in renal pathogenic processes. By targeting these genes of interest, researchers are gaining a better understanding of the etiology of renal pathologies, with the promised potential of slowing disease progression or even reversing the damage caused. Some, but not all, of these target genes have proved to be of clinical relevance. However, it is now possible to generate more sophisticated and appropriate disease models in the rat, which can recapitulate key aspects of human renal pathology. These advances will ultimately be used to identify new treatments and therapeutic targets of much greater clinical relevance.

Background: Data on prevalence and burden of end-organ damage in fibrocalculous pancreatic diabetes (FCPD) from eastern India is scant. This study investigated the burden of end-organ damage and exocrine pancreatic defect in FCPD patients in Eastern India. Materials and Methods: Consecutive FCPD patients underwent evaluation of glycemic control, C-peptide, fecal elastase, body fat percent, tests for cardiac autonomic neuropathy (CAN), neuropathy, nephropathy, and retinopathy which were compared with data from type-1 diabetes (T1DM) and type-2 diabetes (T2DM). Results: Data from 101 FCPD, 41 T1DM, 40 T2DM, and 40 controls were analyzed. Body fat percent was lowest in FCPD and T1DM. Similarly, fasting and stimulated C-peptide was significantly lowest in T1DM, followed by FCPD. Significant elevations in stimulated C-peptide were observed in FCPD. Fecal elastase was lowest in FCPD. Exocrine pancreas defect in FCPD, T1DM, and T2DM was 100%, 53.66%, 27.5%, respectively. HbA1c was worst in FCPD. About 40% of FCPD patients had CAN while 13.33% had borderline CAN. Isolated parasympathetic dysfunction was the commonest (66.67%) among them. FCPD patients with CAN had lower fecal elastase, higher HbA1c, microalbuminuria, steatorrhea, neuropathy, retinopathy, and nephropathy, compared to those without CAN. On binary logistic regression, diabetes duration was a significant predictor of end-organ damage in FCPD. Fecal elastase and body fat percent were independent predictors for insulin therapy in FCPD. Conclusion: CAN is common in FCPD while exocrine pancreas defect is most severe in FCPD followed by T1DM and T2DM. Fecal elastase has an important prognostic role for insulinization in FCPD. Role of pancreatic enzyme replacement on glycemic control in diabetes with exocrine pancreas defect needs investigation. [ABSTRACT FROM AUTHOR]

The contributions of T lymphocytes to the pathogenesis of salt-sensitive hypertension has been well established. Under hypertensive stimuli, naive T cells develop into different subsets, including Th1, Th2, Th17, Treg, and cytotoxic CD8+ T cells, depending on the surrounding microenviroment in organs. Distinct subsets of T cells may play totally different roles in tissue damage and hypertension. The underlying mechanisms by which hypertensive stimuli activate naive T cells involve many events and different organs, such as neoantigen presentation by dendritic cells, high salt concentration, and the milieu of oxidative stress in the kidney and vasculature. Infiltrating and activated T subsets in injured organs, in turn, exert considerable impacts on tissue dysfunction, including sodium retention in the kidney, vascular stiffness, and remodeling in the vasculature. Therefore, a thorough knowledge of T-cell actions in hypertension may provide novel insights into the development of new therapeutic strategies for patients with hypertension. [ABSTRACT FROM AUTHOR]

Abstract Background Hypertension is established to cause vascular end-organ damage. Other forms of dysregulated blood pressure (BP) behaviour, such as orthostatic hypotension have also been associated with cardiovascular (CV) events. The eye is potentially vulnerable to dysregulated systemic BP if ocular circulation autoregulation is impaired. We investigated whether phenotypes of abnormal BP stabilisation after orthostasis, an autonomic stressor, had a relationship with contrast sensitivity (CS), an outcome measure of subtle psychophysical visual function. Methods This was a cross-sectional study from wave 1 of The Irish Longitudinal Study on Ageing (TILDA). From beat-to-beat orthostatic BP (BP), measured by digital photoplethysmography during active stand, 4 phenotypes have been defined 1) normal stabilisation 2) orthostatic hypotension, 3) orthostatic hypertension 4) BP variability. Contrast sensitivity was measured using a Functional Visual Analyzer. Multivariable linear regression models investigated the relationship between orthostatic BP phenotypes and contrast sensitivity in 4289 adults aged ≥50 years adjusting for, demographics, cardiovascular risk factors, self-reported eye pathologies, objective hypertension and antihypertensives. A sensitivity analysis adjusted for age-related macular degeneration, glaucoma, diabetic retinopathy and maculopathy identified on retinal photographs. Finally models were compared, adjusting for alternative measures of cataract versus not, to examine the potential effect of cataract on any associations. Results Systolic orthostatic BP variability was associated with worse contrast sensitivity, in the primary and the sensitivity analysis. Adjusting for alternative measures of clinical cataract attenuated the association by 18%. Conclusions Orthostatic BP variability is associated with worse contrast sensitivity, independent of hypertension and retinal pathology and may be a cardiovascular biomarker of early ocular pathology. Highlights • Orthostatic hypotension, orthostatic hypertension and some forms of blood pressure variability have been associated with increased risk of cardiovascular events. • On a population level, one in four individuals aged over 50 years demonstrated this phenotype of blood pressure variability. • Orthostatic blood pressure variability was associated with lower visual contrast sensitivity. • Blood pressure variability may influence target-organ damage. [ABSTRACT FROM AUTHOR]

HIV infection leads to severe B cell dysfunction, which manifests as impaired humoral immune response to infection and vaccinations and is not completely reversed by otherwise effective antiretroviral therapy (ART). Despite its inability to correct HIV-induced B cell dysfunction, ART has led to significantly increased lifespans in people living with HIV/AIDS. This has in turn led to escalating prevalence of non-AIDS complications in aging HIV-infected individuals, including malignancies, cardiovascular disease, bone disease, and other end-organ damage. These complications, typically associated with aging, are a significant cause of morbidity and mortality and occur significantly earlier in HIV-infected individuals. Understanding the pathophysiology of these comorbidities and delineating clinical management strategies and potential cures is gaining in importance. Bone loss and osteoporosis, which lead to increase in fragility fracture prevalence, have in recent years emerged as important non-AIDS comorbidities in patients with chronic HIV infection. Interestingly, ART exacerbates bone loss, particularly within the first couple of years following initiation. The mechanisms underlying HIV-induced bone loss are multifactorial and complicated by the fact that HIV infection is linked to multiple risk factors for osteoporosis and fracture, but a very interesting role for B cells in HIV-induced bone loss has recently emerged. Although best known for their important antibody-producing capabilities, B cells also produce two cytokines critical for bone metabolism: the key osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL) and its physiological inhibitor osteoprotegerin (OPG). Dysregulated B cell production of OPG and RANKL was shown to be a major contributor to increased bone loss and fracture risk in animal models and HIV-infected humans. This review will summarize our current knowledge of the role of the OPG/RANK–RANKL pathway in B cells in health and disease, and the contribution of B cells to HIV-induced bone loss. Data from mouse studies indicate that RANKL and OPG may also play a role in B cell function and the implications of these findings for human B cell biology, as well as therapeutic strategies targeting the OPG/RANK–RANKL pathway, will be discussed.

By 2030, sub-Saharan Africa is forecast to see the steepest rise in the number of people with hypertension of any world region. Hypertensive retinopathy is known to be a common complication of hypertension in developed countries and some studies suggest it is associated with the presence of other hypertension-related end-organ damage (EOD) such as stroke and cardiovascular disease. In Tanzania hypertension is relatively more common than in other parts of sub-Saharan Africa, especially in the older population; however, the prevalence of hypertensive retinopathy and its association with EOD remain unknown. The authors conducted a cross-sectional study of elderly, community-dwelling, rural Tanzanians to determine the prevalence of hypertensive retinopathy and its association with hypertension and other forms of EOD. Hypertensive retinopathy was diagnosed based on retinal imaging. In a cohort of 61 patients with gradable images, the authors found the overall prevalence of hypertensive retinopathy to be 64% (n = 39), which was strongly associated with hypertension (X2 [1] = 4.207, P = .004), with a significant trend towards more severe retinopathy with more severe hypertension (r = .377, P = .003). The authors did not find hypertensive retinopathy to be associated with other forms of EOD. Hypertensive retinopathy is highly prevalent in this population and is associated in most but not all cases with hypertension. These findings do not suggest that it could be used as a screening tool for EOD, but it is important to identify and educate patients with retinopathy about possible complications of the condition. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent complication of diabetes, obesity and hypertension. Since it is typically undetected for long periods, it often progresses to end-stage renal disease. CKD is characterized by the development of progressive glomerulosclerosis, interstitial fibrosis and tubular atrophy along with a decreased glomerular filtration rate. This is associated with podocyte injury and a progressive rise in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin receptor type A (ETA) promotes renal cell injury, inflammation, and fibrosis which finally lead to proteinuria, it is not surprising that ETA receptors antagonists have been proven to have beneficial renoprotective effects in both experimental and clinical studies in diabetic and non-diabetic CKD. Unfortunately, fluid retention encountered in large clinical trials in diabetic CKD led to the termination of these studies. Therefore, several advances, including the synthesis of new antagonists with enhanced pharmacological activity, the use of lower doses of ET antagonists, the addition of diuretics, plus simply searching for distinct pathological states to be treated, are promising targets for future experimental studies. In support of these approaches, our group demonstrated in adult subtotally nephrectomized Ren-2 transgenic rats that the addition of a diuretic on top of renin-angiotensin and ETA blockade led to a further decrease of proteinuria. This effect was independent of blood pressure which was normalized in all treated groups. Recent data in non-diabetic CKD, therefore, indicate a new potential for ETA antagonists, at least under certain pathological conditions. [ABSTRACT FROM AUTHOR]

HIV infection leads to severe B cell dysfunction, which manifests as impaired humoral immune response to infection and vaccinations and is not completely reversed by otherwise effective antiretroviral therapy (ART). Despite its inability to correct HIVinduced B cell dysfunction, ART has led to significantly increased lifespans in people living with HIV/AIDS. This has in turn led to escalating prevalence of non-AIDS complications in aging HIV-infected individuals, including malignancies, cardiovascular disease, bone disease, and other end-organ damage. These complications, typically associated with aging, are a significant cause of morbidity and mortality and occur significantly earlier in HIV-infected individuals. Understanding the pathophysiology of these comorbidities and delineating clinical management strategies and potential cures is gaining in importance. Bone loss and osteoporosis, which lead to increase in fragility fracture prevalence, have in recent years emerged as important non-AIDS comorbidities in patients with chronic HIV infection. Interestingly, ART exacerbates bone loss, particularly within the first couple of years following initiation. The mechanisms underlying HIV-induced bone loss are multifactorial and complicated by the fact that HIV infection is linked to multiple risk factors for osteoporosis and fracture, but a very interesting role for B cells in HIV-induced bone loss has recently emerged. Although best known for their important antibody-producing capabilities, B cells also produce two cytokines critical for bone metabolism: the key osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL) and its physiological inhibitor osteoprotegerin (OPG). Dysregulated B cell production of OPG and RANKL was shown to be a major contributor to increased bone loss and fracture risk in animal models and HIV-infected humans. This review will summarize our current knowledge of the role of the OPG/RANK–RANKL pathway in B cells in health and disease, and the contribution of B cells to HIV-induced bone loss. Data from mouse studies indicate that RANKL and OPG may also play a role in B cell function and the implications of these findings for human B cell biology, as well as therapeutic strategies targeting the OPG/RANK–RANKL pathway, will be discussed. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a monogenetic disorder due to a single base-pair point mutation in the β-globin gene resulting in the substitution of the amino acid valine for glutamic acid in the β-globin chain. Phenotypic variation in the clinical presentation and disease outcome is a characteristic feature of the disorder. Understanding the pathogenesis and pathophysiology of the disorder is central to the choice of therapeutic development and intervention. In this special edition for newborn screening for haemoglobin disorders, it is pertinent to describe the genetic, pathologic and clinical presentation of sickle cell disease as a prelude to the justification for screening. Through a systematic review of the literature using search terms relating to SCD up till 2019, we identified relevant descriptive publications for inclusion. The scope of this review is mainly an overview of the clinical features of pain, the cardinal symptom in SCD, which present following the drop in foetal haemoglobin as young as five to six months after birth. The relative impact of haemolysis and small-vessel occlusive pathology remains controversial, a combination of features probably contribute to the different pathologies. We also provide an overview of emerging therapies in SCD.

BACKGROUND There are no comprehensive guidelines on management of hypertensive emergency (HTNE) and complications. Despite advances in antihypertensive medications HTNE is accompanied with significant morbidity and mortality. METHODS We queried the 2002-2012 nationwide inpatient sample database to identify patients with HTNE. Trends in incidence of HTNE and in-hospital mortality were analyzed. Logistic regression analysis was used to assess the relationship between end-organ complications and in-hospital mortality. RESULTS Between 2002 and 2012, 129,914 admissions were included. Six hundred and thirty (0.48%) patients died during their hospital stay. There was an increase in the number of HTNE admissions (9,511-15,479; Ptrend < 0.001) with concurrent reduction of in-hospital mortality (0.8-0.3%; Ptrend < 0.001) by the year 2012 compared to 2002. Patients who died during hospitalization were older, had longer length of stay, higher cost of stay, more comorbidities, and higher risk scores. Presence of acute cardiorespiratory failure [adjusted odds ratio (OR), 15.8; 95% confidence interval (CI), 13.2-18.9], stroke or transient ischemia attack (TIA) (adjusted OR, 7.9; 95% CI, 6.3-9.9), chest pain (adjusted OR, 5.9; 95% CI, 4.4-7.7), stroke/TIA (adjusted OR, 5.9; 95% CI, 4.5-7.7), and aortic dissection (adjusted OR, 5.9; 95% CI, 2.8-12.4) were most predictive of higher in-hospital mortality in addition to factors such as age, aortic dissection, acute myocardial infarction, acute renal failure, and presence of neurological symptoms. CONCLUSION A rising trend in hospitalization for HTNE, with an overall decrease in in-hospital mortality was observed from 2002 to 2012, possibly related to changes in coding practices and improved management. Presence of acute cardiorespiratory failure, stroke/TIA, chest pain, and aortic dissection were most predictive of higher hospital mortality. [ABSTRACT FROM AUTHOR]

Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and end-organ damage in intact Cyp1b1-/-, ovariectomized female, and Cyp1b1+/+ male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II-induced increases in systolic blood pressure, water consumption, urine output, and proteinuria in intact female Cyp1b1-/- and ovariectomized mice. 2-Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water intake, urine output, and proteinuria in Cyp1b1+/+ male mice. Treatment with 2-methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1-/- and ovariectomized Cyp1b1+/+ and Cyp1b1-/- female mice and Cyp1b1+/+ male mice. 2-Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of angiotensinogen in intact Cyp1b1-/- and ovariectomized Cyp1b1+/+ and Cyp1b1-/- female mice but not in Cyp1b1+/+ male mice. The G protein-coupled estrogen receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood pressure and renal function in Cyp1b1+/+ female mice. These data suggest that 2-methoxyestradiol reduces Ang II-induced hypertension and associated end-organ damage in intact Cyp1b1-/-, ovariectomized Cyp1b1+/+ and Cyp1b1-/- female mice, and Cyp1b1+/+ male mice independent of G protein-coupled estrogen receptor 1. Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating hypertension and associated pathogenesis in postmenopausal females, and in males. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to investigate the association between plasma homocysteine (Hcy) levels and carotid, cardiac, and renal end-organ damage in newly diagnosed type 2 diabetes mellitus (T2DM) patients.Methods: Newly diagnosed normotensive T2DM patients (n= 390) were enrolled in this study. The patients were not taking any medications over the duration of the study. The left ventricular mass index (LVMI), carotid intima media thickness (CIMT), and creatinine levels and 24-h microalbuminuria were used to determine cardiac, carotid, and kidney end-organ diseases, respectively.Results: Using univariate logistic regression analysis; age, 24-h microalbuminuria, fasting blood glucose, CIMT, creatinine level, and LVMI were found to be significantly associated with the Hcy level. When those six variables were included in a multivariate regression model, CIMT, LVMI, and creatinine were found to be significantly associated with the Hcy level. We determined that an Hcy level >12.5 µmol/L was predictive of high LVMI, with a sensitivity of 70.1% and a specificity of 68%. An Hcy level >13.5 µmol/L was predictive of high CIMT, with a sensitivity of 67.5% and a specificity of 63.1%.Conclusion: In this study, LVMI, CIMT, and creatinine level were positively correlated with the Hcy level. We believe that the Hcy level may be a useful predictor of end-organ damage, including cardiac, carotid, and renal diseases, in newly diagnosed T2DM patients. [ABSTRACT FROM AUTHOR]