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  Alternatives to norepinephrine in septic shock: Which agents and when? Introduction  Septic shock is one of the main causes of admission to the intensive care unit (ICU) and is associated with high mortality and morbidity. It involves life-threatening organ dysfunction, which combines hypovolemia, vasodilation, cardiac dysfunction, and microcirculatory impairment.  Macrocirculatory disorders result in an imbalance between oxygen supply and delivery, leading to inadequate tissue perfusion and cellular hypoxia. Microcirculatory disorders, however, result in impaired peripheral oxygen extraction and tissue oxygenation. Vasodilation and cardiac dysfunction are the main features of septic shock. Early vasopressor therapy is therefore the cornerstone of hemodynamic management in patients with septic shock, as fluid resuscitation alone cannot restore vascular tone and cardiac function.The numerous available vasopressors aim to counterbalance the vasodilatory effects of a sys...
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Acetaminophen, Nonsteroidal Anti-Inflammatory Drugs, and Hypertension  INTRODUCTION : Acetaminophen is widely regarded as a safe therapy for pain and fever in patients with cardiovascular disease and those taking anticoagulants. However, recent studies report that acetaminophen, like most other nonsteroidal anti-inflammatory drugs, increases blood pressure, and a formulation containing sodium increases cardiovascular risk. Those findings call into question guidelines recommending acetaminophen for patients with cardiovascular disease and pain, and those taking anticoagulants. Acetaminophen has effects in common with nonsteroidal anti-inflammatory drugs, and its influence on coagulation via effects on vitamin K metabolism. Possible alternatives to acetaminophen for patients with pain .  MECHANISMS OF ACTION OF ACETAMINOPHEN  Acetaminophen shares with NSAIDs, such as ibuprofen and naproxen, a key analgesic mechanism of action: inhibition of prostaglandin biosynthesis. Pros...
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 Important questions when managing cardiogenic acute pulmonary oedema ? What are we talking about  ? APE is usually defned by the sudden increase in pulmonary capillary wedge pressure as a result of acute and fulminant left ventricle (LV) (systolic and/or diastolic) failure or acute severe mitral regurgitation . Among the various clinical phenotypes of acute heart failure (AHF), four major clinical presentations can be described with possible overlaps between them and APE represents 30–80% of AHF clinical phenotypes . Clinical criteria  : related to lung  congestion include dyspnea with orthopnea.  increased respiratory rate.  increased work of breathing and respiratory failure .  Hypoxia is a mandatory feature of APE.  potential overlap between ARDS and APE since ARDS defnition includes “Respiratory failure not completely explained by excessive volume loading or cardiac failure. How about pathophysiology? Pathobiology of APE ...
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 Iron Metabolism Iron Intake (Dietary) :    • average North American adult diet = 10-20 mg iron daily.   • steady state absorption is 5-10% (0.5-2 mg/d); enhanced by citric acid and ascorbic acid (vitamin C); reduced by polyphenols (e.g. in tea), phytate (e.g. in bran), dietary calcium, and soy protein.   • males more likely to have positive iron balance; up to 20% of menstruating females have negative iron balance. Iron Absorption and Transport :  • dietary iron is absorbed in the duodenum (absorption impaired in IBD and celiac disease).  • in circulation, the majority of non-heme iron is bound to transferrin which transfers iron from enterocytes and storage pool sites (macrophages of the reticuloendothelial system and hepatocytes) to RBC precursors in the BM. Iron Levels :  • hepcidin is a hormone produced by hepatocytes that regulates systemic iron levels.  ■ binds to iron exporter ferroportin (on duodenal enterocytes and reticuloendot...
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  UPDATES FOR GLUCOSE TARGETS   Observational data consistently report that the association between death and hyperglycemia is markedly affected by preexisting glucose control . Moreover, the risk of treatment-induced hypoglycemia, a strong predictor of increased mortality, is greatest in those with preexisting hyperglycemia .  A recent single-center retrospective cohort study of 3,625 patients with at least four blood glucose measurements and a HbA1c measurement reported that for patients with a HbA1c  8.0% mortality was lower if the proportion of time spent with a blood glucose between 180 and 250 mg/dL (10 and 14 mmol/L) was greater . Such data support the hypothesis that glucose concentrations that are regarded as safe and desirable in those without diabetes (108–180 mg/dL) might actually be undesirable and harmful in patients with preexisting glucose intolerance, which substantiates the concept that glucose targets should be ‘personalized’ based on preexisting g...
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 New concepts in heart failure with preserved ejection fraction and hypertension With the increasing age of our population, the incidence of heart failure with preserved ejection fraction (HFpEF) continues to rise . Traditional risk factors associated with HFpEF include :  older age,  female gender,  and common medical comorbidities such as  obesity,  chronic kidney disease,  diabetes mellitus and  obstructive sleep apnea .  Hypertension (HTN) remains the strongest risk factor associated with HFpEF . In a community-based study using the H2FPEF score – an established score that aims to estimate the probability of underlying heart failure (HF) in patients with HFpEF – patients who were treated with 2 anti-HTN medication(s) were more likely to have an incident of HF hospitalization . In addition to traditional mechanisms such as left ventricular hypertrophy, ventricular stiffness and diastolic dysfunction, recent data suggest the increasing role...
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 POLYCYSTIC OVARY SYNDROME image  A. Background and classification :  1. Can be a cause of infertility in up to 20% of infertile couples  2. Mainly considered to be caused by androgen excess or hyperandrogenism   3. Underlying cause appears to be insulin resistance (in patients with and without obesity), with subsequent compensatory insulin hypersecretion or increased insulin action. This increased action stimulates androgen secretion by the ovaries or adrenal cells, leading to increased luteinizing hormone (LH) secretion but normal or low follicle-stimulating hormone (FSH) concentrations, with a subsequent decrease in follicular maturation and anovulation . 4. Has several potential comorbidities with endocrine and cardiovascular implications (e.g., T2D, obesity) 5. Can affect 6%–10% of women (or more depending on diagnostic criteria used), making it one of the most prevalent endocrine disorders in young women .  6. No clear consensus on classifyi...
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