RESUMEN
Amyloid neuropathy is caused by deposition of insoluble ß-pleated amyloid sheets in the peripheral nervous system. It is most common in: (1) light-chain amyloidosis, a clonal non-proliferative plasma cell disorder in which fragments of immunoglobulin, light or heavy chain, deposit in tissues, and (2) hereditary transthyretin (ATTRv) amyloidosis, a disorder caused by autosomal dominant mutations in the TTR gene resulting in mutated protein that has a higher tendency to misfold. Amyloid fibrils deposit in the endoneurium of peripheral nerves, often extensive in the dorsal root ganglia and sympathetic ganglia, leading to atrophy of Schwann cells in proximity to amyloid fibrils and blood-nerve barrier disruption. Clinically, amyloid neuropathy is manifested as a length-dependent sensory predominant neuropathy associated with generalized autonomic failure. Small unmyelinated nerves are involved early and prominently in early-onset Val30Met ATTRv, whereas other ATTRv and light-chain amyloidosis often present with large- and small-fiber involvement. Nerve conduction studies, quantitative sudomotor axon testing, and intraepidermal nerve fiber density are useful tools to evaluate denervation. Amyloid deposition can be demonstrated by tissue biopsy of the affected organ or surrogate site, as well as bone-avid radiotracer cardiac imaging. Treatment of light-chain amyloidosis has been revolutionized by monoclonal antibodies and stem cell transplantation with improved 5-year survival up to 77%. Novel gene therapy and transthyretin stabilizers have revolutionized treatment of ATTRv, improving the course of neuropathy (less change in the modified Neuropathy Impairment Score + 7 from baseline) and quality of life. With great progress in amyloidosis therapies, early diagnosis and presymptomatic testing for ATTRv family members has become paramount. ANN NEUROL 2024;96:423-440.
Asunto(s)
Neuropatías Amiloides Familiares , Neuropatías Amiloides , Humanos , Neuropatías Amiloides Familiares/terapia , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/fisiopatología , Neuropatías Amiloides/terapia , Neuropatías Amiloides/genética , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/genética , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/fisiopatología , Amiloidosis/terapia , Amiloidosis/genética , Prealbúmina/genéticaRESUMEN
Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple approaches have been tried to achieve adequate decongestion rapidly while minimizing adverse effects, no single diuretic strategy has shown superiority, and there is a paucity of data and guidelines to utilize in making these decisions. Observational cohort studies have shown associations between urine sodium excretion and outcomes after hospitalization for ADHF. Urine chemistries (urine sodium ± urine creatinine) may guide diuretic titration during ADHF, and multiple randomized clinical trials have been designed to compare a strategy of urine chemistry-guided diuresis to usual care. This review will summarize current literature for diuretic monitoring and titration strategies, outline evidence gaps, and describe the recently completed and ongoing clinical trials to address these gaps in patients with ADHF with a particular focus on the utility of urine sodium-guided strategies.
RESUMEN
Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care. The urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE) trial is designed to test the hypothesis that protocolized diuretic therapy guided by spot urine chemistry through completion of intravenous diuresis will be superior to usual care and improve outcomes over the 14 days following randomization. ESCALATE will randomize and obtain complete data on 450 patients with acute heart failure to a diuretic strategy guided by urine chemistry or a usual care strategy. Key inclusion criteria include an objective measure of hypervolemia with at least 10 pounds of estimated excess volume, and key exclusion criteria include significant valvular stenosis, hypotension, and a chronic need for dialysis. Our primary outcome is days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and intravenous diuresis. CLINICAL TRIAL REGISTRATION: NCT04481919.
Asunto(s)
Insuficiencia Cardíaca , Humanos , Resultado del Tratamiento , Insuficiencia Cardíaca/diagnóstico , Diuréticos/uso terapéutico , Diuresis , NatriuresisRESUMEN
OBJECTIVES: To investigate risk factors and outcomes of cardiogenic shock complicating acute myocardial infarction (AMI-CS) in young patients with AMI. BACKGROUND: AMI-CS is associated with high morbidity and mortality rates. Data regarding AMI-CS in younger individuals are limited. METHODS AND RESULTS: Consecutive patients with type 1 AMI aged 18-50 years admitted to 2 large tertiary-care academic centers were included, and they were adjudicated as having cardiogenic shock (CS) by physician review of electronic medical records using the Society for Cardiovascular Angiography and Interventions CS classification system. Outcomes included all-cause mortality (ACM), cardiovascular mortality (CVM) and 1-year hospitalization for heart failure (HHF). In addition to using the full population, matching was also used to define a comparator group in the non-CS cohort. Among 2097 patients (mean age 44 ± 5.1 years, 74% white, 19% female), AMI-CS was present in 148 (7%). Independent risk factors of AMI-CS included ST-segment elevation myocardial infarction, left main disease, out-of-hospital cardiac arrest, female sex, peripheral vascular disease, and diabetes. Over median follow-up of 11.2 years, young patients with AMI-CS had a significantly higher risk of ACM (adjusted HR 2.84, 95% CI 1.68-4.81; P < 0.001), CVM (adjusted HR 4.01, 95% CI 2.17-7.71; P < 0.001), and 1-year HHF (adjusted HR 5.99, 95% CI 2.04-17.61; Pâ¯=â¯0.001) compared with matched non-AMI-CS patients. Over the course of the study, there was an increase in the incidence of AMI-CS among young patients with MI as well as rising mortality rates for patients with both AMI-CS and non-AMI-CS. CONCLUSIONS: Of young patients with AMI, 7% developed AMI-CS, which was associated with a significantly elevated risk of mortality and HHF.
Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio , Infarto del Miocardio con Elevación del ST , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Masculino , Choque Cardiogénico/epidemiología , Choque Cardiogénico/etiología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/complicaciones , Infarto del Miocardio/complicaciones , Infarto del Miocardio/epidemiología , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/epidemiología , Factores de Riesgo , Mortalidad HospitalariaRESUMEN
BACKGROUND: Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre-direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test-positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. METHODS AND RESULTS: We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. CONCLUSIONS: These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.
RESUMEN
Allosensitization is prevalent in heart transplant candidates and is associated with prolonged waiting times and poor outcomes following transplantation. We analyzed the efficacy of a desensitization regimen consisting of plasma exchange, intravenous immunoglobulin, and bortezomib among 25 consecutive sensitized waitlisted candidates at our center from 2016 to 2021. Following desensitization therapies, all C1q negative antibodies were removed from a candidate's unacceptable antigen list. There was a significant decrease in the median number of human leukocyte antigen (HLA) class I (21-15, p = .001) but not class II antibodies (7-6.5, p = .07). There was a significant corresponding decrease in median calculated panel reactive antibodies for class I (90%-74%, p = .004) but not class II (74.5%-75.5%, p = .30). Following desensitization, 76% of patients were transplanted at a median of 91 days. One-year survival following transplant was 89% with a 33% rate of antibody-mediated rejection (AMR). In conclusion, a bortezomib desensitization protocol was modestly effective for class I antibodies and allowed successful transplant in most cases when combined with selective crossing of C1q negative antigens.
Asunto(s)
Complemento C1q , Trasplante de Corazón , Humanos , Bortezomib/uso terapéutico , Anticuerpos , Inmunoglobulinas Intravenosas/uso terapéutico , Antígenos HLA , Desensibilización Inmunológica/métodos , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , IsoanticuerposRESUMEN
Morbidity and mortality associated with COVID-19 has increased exponentially, and patients with cardiovascular (CV) disease are at risk for poor outcomes. Several lines of evidence suggest a potential role for CV therapies in COVID-19 treatment. Characteristics of clinical trials of CV therapies related to COVID-19 registered on ClinicalTrials.gov have not been described. METHODS: ClinicalTrials.gov was queried on August 7, 2020 for COVID-19 related trials. Studies evaluating established CV drugs, other fibrinolytics (defibrotide), and extracorporeal membrane oxygenation were included. Studies evaluating anti-microbial, convalescent plasma, non-colchicine anti-inflammatory, and other therapies were excluded. Trial characteristics were tabulated from study-specific entries. RESULTS: A total of 2,935 studies related to COVID-19 were registered as of August 7, 2020. Of these, 1,645 were interventional studies, and the final analytic cohort consisted of 114 studies evaluating 10 CV therapeutic categories. Antithrombotics (32.5%; n = 37) were most commonly evaluated, followed by pulmonary vasodilators (14.0%; n = 16), renin-angiotensin-aldosterone system-related therapies (12.3%; n = 14), and colchicine (8.8%; n = 10). Trials evaluating multiple CV therapy categories and CV therapies in combination with non-CV therapies encompassed 4.4% (n = 5) and 9.6% (n = 11) of studies, respectively. Most studies were designed for randomized allocation (87.7%; n = 100), enrollment of less than 1000 participants (86.8%; n = 99), single site implementation (55.3%; n = 63), and had a primary outcome of mortality or a composite including mortality (56.1%; n = 64). Most study populations consisted of patients hospitalized with COVID-19 (81.6%; n = 93). At the time of database query, 28.9% (n = 33) of studies were not yet recruiting and the majority were estimated to be completed after December 2020 (67.8%; n = 78). Most lead sponsors were located in North America (43.9%; n = 50) or Europe (36.0%; n = 41). CONCLUSIONS: A minority (7%) of clinical trials related to COVID-19 registered on ClinicalTrials.gov plan to evaluate CV therapies. Of CV therapy studies, most were planned to be single center, enroll less than 1000 inpatients, sponsored by European or North American academic institutions, and estimated to complete after December 2020. Collectively, these findings underscore the need for a network of sites with a platform protocol for rapid evaluation of multiple therapies and generalizability to inform clinical care and health policy for COVID-19 moving forward.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Enfermedades Cardiovasculares/tratamiento farmacológico , Ensayos Clínicos como Asunto/estadística & datos numéricos , National Library of Medicine (U.S.) , Sistema de Registros/estadística & datos numéricos , SARS-CoV-2 , COVID-19/complicaciones , COVID-19/mortalidad , Fármacos Cardiovasculares/uso terapéutico , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/mortalidad , Colchicina/uso terapéutico , Terapia Combinada/estadística & datos numéricos , Bases de Datos Factuales/estadística & datos numéricos , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Fibrinolíticos/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipoglucemiantes/uso terapéutico , Participación del Paciente/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Sistema Renina-Angiotensina , Resultado del Tratamiento , Estados Unidos , Vasodilatadores/uso terapéuticoRESUMEN
Importance: Atrial fibrillation (AF) is the most common heart rhythm disturbance, continues to increase in incidence, and results in significant morbidity and mortality. The marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D have been reported to have both benefits and risks with respect to incident AF, but large-scale, long-term randomized trial data are lacking. Objective: To test the effects of long-term administration of marine omega-3 fatty acids and vitamin D on incident AF. Design, Setting, and Participants: An ancillary study of a 2 × 2 factorial randomized clinical trial involving 25â¯119 women and men aged 50 years or older without prior cardiovascular disease, cancer, or AF. Participants were recruited directly by mail between November 2011 and March 2014 from all 50 US states and were followed up until December 31, 2017. Interventions: Participants were randomized to receive EPA-DHA (460 mg/d of EPA and 380 mg/d of DHA) and vitamin D3 (2000 IU/d) (n = 6272 analyzed); EPA-DHA and placebo (n = 6270 analyzed); vitamin D3 and placebo (n = 6281 analyzed); or 2 placebos (n = 6296 analyzed). Main Outcomes and Measures: The primary outcome was incident AF confirmed by medical record review. Results: Among the 25â¯119 participants who were randomized and included in the analysis (mean age, 66.7 years; 50.8% women), 24â¯127 (96.1%) completed the trial. Over a median 5.3 years of treatment and follow-up, the primary end point of incident AF occurred in 900 participants (3.6% of study population). For the EPA-DHA vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.24; P = .19). For the vitamin D3 vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.25; P = .19). There was no evidence for interaction between the 2 study agents (P = .39). Conclusions and Relevance: Among adults aged 50 years or older, treatment with EPA-DHA or vitamin D3, compared with placebo, resulted in no significant difference in the risk of incident AF over a median follow-up of more than 5 years. The findings do not support the use of either agent for the primary prevention of incident AF. Trial Registration: ClinicalTrials.gov Identifiers: NCT02178410; NCT01169259.
Asunto(s)
Fibrilación Atrial/tratamiento farmacológico , Colecalciferol/uso terapéutico , Suplementos Dietéticos , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/uso terapéutico , Vitaminas/uso terapéutico , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia del Tratamiento , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
OBJECTIVE: To compare the effect of Pakistani and American almonds on serum concentration of liver enzymes in coronary artery disease patients. METHODS: The randomised controlled trial was conducted at the Cardiology Clinics of Aga Khan University Hospital, Karachi, from February to July, 2012, and comprised patients who were randomised into intervention PA and AA groups and the control NI groups. Subjects in the intervention groups were provided Pakistani and American varieties of almonds 10g/day respectively with instructions to soak them overnight, remove the skin and eat them before breakfast for 12 weeks. The control group underwent no intervention. Serum concentrations of aspartate transaminase, Alanine transaminase and gamma-glutamyl transferase were analysed and compared. RESULTS: Of the 150 subjects, 110(73.3%) completed the study. Of them, there were 38(34.5%) in PA group, 41(37.3%) in AA, and 31(28.2%) in the NI group. Dietary almonds significantly reduced serum concentrations of aspartate transaminase, alanine transaminase and gamma-glutamyl transferase in the two intervention groups compared to the controls group (p<0.05) at 12-week follow-up. CONCLUSIONS: A low dose of almonds was found to be an effective strategy to protect the liver.
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Enfermedad de la Arteria Coronaria , Prunus dulcis , Alanina Transaminasa , Aspartato Aminotransferasas , Enfermedad de la Arteria Coronaria/prevención & control , Humanos , Hígado , Estados UnidosRESUMEN
In the management of cardiovascular disorders, medicines from herbal sources have played a vital role through centuries. The following study was commenced in order to lay possible pharmacological foundation associated with medicinal uses of edible fruit of Grewia asiatica in hypertension through in-vitro method. In this study isolated atrial preparation of Guinea pig was used where crude ethanolic extract of Grewia asiatica fruit (Ga.Cr) decreased the force and rate of spontaneous atrial contractions (0.03-10mg/kg). In isolated rat aortic ring preparations previously vasoconstricted by phenylephrine and High K+, it also resulted in dose dependent vasodilation (0.01-10 mg/kg).In the presence of L-NAME, the relaxation curve of Ga.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. The speculative analysis contemplated that Ga.Cr has blood pressure reducing potentials through inhibition of Ca++ influx via Ca++ channels, its release from intracellular stores and through other means like NO mediated pathways.
Asunto(s)
Antihipertensivos/farmacología , Frutas/química , Grewia/química , Extractos Vegetales/farmacología , Acetilcolina/farmacología , Animales , Antihipertensivos/aislamiento & purificación , Aorta/efectos de los fármacos , Aorta/fisiología , Cobayas , Atrios Cardíacos/efectos de los fármacos , Isoproterenol/farmacología , Contracción Muscular/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Extractos Vegetales/aislamiento & purificación , Ratas , Ratas Sprague-DawleyRESUMEN
Although coronavirus disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include (1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; (2) acute coronary syndrome due to acute atherothrombosis in a virally induced thrombotic and inflammatory milieu; (3) microvascular dysfunction due to diffuse microthrombi or vascular injury; (4) stress-related cardiomyopathy (Takotsubo syndrome); (5) nonischemic myocardial injury due to a hyperinflammatory cytokine storm; or (6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, D-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative nonischemic causes of injury, integrating the level of suspicion for COVID-19.
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Betacoronavirus , Enfermedades Cardiovasculares/complicaciones , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Antimaláricos/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , Biomarcadores/sangre , COVID-19 , Cloroquina/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Humanos , Hidroxicloroquina/uso terapéutico , Hipoxia/complicaciones , Pandemias , Plasma/inmunología , Neumonía Viral/tratamiento farmacológico , Receptor de Angiotensina Tipo 2/metabolismo , Factores de Riesgo , SARS-CoV-2 , Cardiomiopatía de Takotsubo/etiología , Internalización del VirusRESUMEN
OBJECTIVE: To evaluate the effectiveness of Peer Assisted Learning in teaching at undergraduate level and to assess its effects on Peer Leaders and Peer Learners. METHODS: The cross-sectional study was conducted at the Aga Khan University, Karachi, from May to October 2017, and comprised Peer Learners who were trained by faculty members in workshops and pre-run of experiments. Students were divided into two groups; Group A had Peer Learners taught by Peer Leaders, and Group B had those taught by trained lab technologists. Knowledge of the groups was assessed by a quiz using Kahoot. Post-session feedback questionnaires were also filled by the participants. Data was analysed using SPSS 23. RESULTS: There were 10 Peer Leaders with a mean age of 19.5±0.85 years, and 62 Peer Learners with a mean age of 19.08±0.81 years. Among the learners, there were 35(56.5%) males and 27(43.5%) females. Post-session assessment showed a significant difference in the test performance by the two groups (p<0.05). Feedback indicated that the learners found Peer Leaders more accessible than lab staff, leading to enhanced understanding of the subject. CONCLUSIONS: Peer-Assisted Learning was found to promote learning by creating an informal student-friendly learning environment.
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Educación de Pregrado en Medicina , Estudiantes de Medicina , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Aprendizaje , Masculino , Grupo Paritario , Enseñanza , Adulto JovenRESUMEN
We have reported the antidyslipidemic, antihypertensive, and Ca++ channel blocking activities of Viola odorata (VO) and Wrightia tinctoria (WT). This study extends our understanding of their therapeutic potential by exploring the effects on biomarkers of hepatic and vascular dysfunction together with phytochemical standardization and antioxidant potential. Total phenolic compounds, total flavonoids content, and proanthocyanins of the methanolic extracts were identified using HPLC. Antioxidant capacity was measured using the in vitro assays. Two studies of 6-week duration were conducted on a high-fat diet rat model to test the leaves and seed extracts of VO and WT (300 and 600 mg/kg) for their effect on biomarkers for hepatic and vascular dysfunction. The HPLC analysis showed high contents of total phenolic compounds, total flavonoids content, and proanthocyanins along with distinctive phenolic composition. Both extracts exhibited significant antioxidant potential in 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), fluorescence recovery after photobleaching, and total antioxidant capacity (TAC) assays, comparable with synthetic standard antioxidants. The in vivo studies indicated a significant reduction in the high-fat-diet-induced rise in serum uric acid, phosphorus, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. This study indicates the potential of VO and WT to protect from vascular and hepatic damage and an antioxidant effect, thus making these herbs strong candidates for managing cardiometabolic disorders.
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Antioxidantes/uso terapéutico , Hígado/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Animales , Antioxidantes/farmacología , Modelos Animales de Enfermedad , Femenino , Masculino , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Calcific aortic valve disease (CAVD) is a highly prevalent cardiovascular disorder accounting for a rising economic and social burden on aging populations. In spite of continuing study on the pathophysiology of disease, there remain no medical therapies to prevent the progression of CAVD. The discovery of biomarkers represents a potentially complementary approach in stratifying risk and timing of intervention in CAVD and has the advantage of providing insight into causal factors for the disease. Biomarkers have been studied extensively in atherosclerotic cardiovascular disease, with success as additive for clinical and scientific purposes. Similar research in CAVD is less robust; however, the available studies of biomarkers in CAVD show promise for enhanced clinical decision making and identification of causal factors for the disease. This comprehensive review summarizes available established and novel biomarkers in CAVD, their contributions toward an understanding of pathophysiology, their potential clinical utility, and provides an outline to direct future research in the field.
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Estenosis de la Válvula Aórtica/sangre , Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Remodelación Ósea , Calcinosis/sangre , Mediadores de Inflamación/sangre , Metabolismo de los Lípidos , Remodelación Ventricular , Animales , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/epidemiología , Estenosis de la Válvula Aórtica/terapia , Biomarcadores/sangre , Calcinosis/epidemiología , Calcinosis/terapia , Humanos , Valor Predictivo de las Pruebas , Pronóstico , Factores de RiesgoRESUMEN
To facilitate experiential learning with assistance from peers, fourteen consented first year AKUH MBBS students submitted an online application along with a written paragraph. Percentage in previous teaching module was also obtained. A training workshop was organized for all the consented students where after pretest and initial orientation, they were divided into two groups; A and B. Facilitators taught concepts of Physiology practical to PLs of Group A and of Pharmacology practical to PLs of Group B respectively. Then PLs of Group A taught PLs of Group B and vice versa with shuffling of students. Comprehension of concept was evaluated by a significant difference (p<0.05) in the pre and posttest results. Nine (64%) students labeled overall assessment of activity as excellent. Ten students were selected on the basis of paragraph writing, end of activity questionnaire and gain in knowledge as a result of comparison of pre and post-test results.
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Educación de Pregrado en Medicina , Liderazgo , Grupo Paritario , Aprendizaje Basado en Problemas , Estudiantes de Medicina , HumanosRESUMEN
Acute aortic syndromes are highly morbid conditions that require prompt diagnosis and management. Aortic dissections have rhythmic patterns, with notable peaks at certain points in every 24 hours as well as weekly and seasonal variations. Several retrospective studies have assessed the chronobiology of acute aortic dissections and there seems to be a winter seasonal peak and morning daily peak in incidence. Although the pathophysiology of this chronobiology is unclear, there are several environmental and physiologic possibilities. This article reviews the major studies examining the chronobiology of acute aortic dissection, and summarizes some theories on the pathophysiology of this phenomenon.
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Enfermedades de la Aorta/fisiopatología , Estaciones del Año , Enfermedad Aguda , Enfermedades de la Aorta/epidemiología , Salud Global , Humanos , Morbilidad/tendencias , SíndromeAsunto(s)
Enfermedades Cardiovasculares , Papillomaviridae , Infecciones por Papillomavirus , Mujeres , Pueblo Asiatico , Femenino , HumanosRESUMEN
PURPOSE OF REVIEW: A low level of plasma high density lipoprotein cholesterol (HDL-C) is a strong and independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, several large studies recently revealed that pharmacologic interventions that increase HDL-C concentration have not improved cardiovascular outcomes when added to standard therapy. In addition, specific genetic variants that raise HDL-C levels are not clearly associated with reduced risk of coronary heart disease. These observations have challenged the 'HDL hypothesis' that HDL-C is causally related to ASCVD and that intervention to raise HDL-C will reduce ASCVD events. This article will present the current data on the HDL hypothesis and provide a revised paradigm of considering HDL in the atherosclerotic pathway. RECENT FINDINGS: Recent evidence has shed light on the complex nature of HDL-C metabolism and function. There are compelling data that the ability of HDL to promote cholesterol efflux from macrophages, the first step in the 'reverse cholesterol transport' (RCT) pathway, is inversely associated with risk for ASCVD even after controlling for HDL-C. This has led to the 'HDL flux hypothesis' that therapeutic intervention that targets macrophage cholesterol efflux and RCT may reduce risk. Preclinical studies of such interventions show promise and early phase clinical studies, though small, are encouraging. SUMMARY: The role of HDL-C in modulating atherosclerotic disease is as yet uncertain. However, new findings and therapies targeting HDL-C show early promise and may provide an important intervention in attenuating the burden of ASCVD in the future.