Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of LDL cholesterol that can lead to premature heart disease. The underlying causes are defects in genes responsible for clearing LDL from the blood. If left untreated, high LDL levels from birth can cause heart attacks or strokes by early adulthood. Treatment involves lifestyle changes and cholesterol-lowering medications like statins. New therapies that block PCSK9 protein are helping to further lower LDL levels. For the most severe cases, liver transplantation may be considered to replace the non-functioning liver gene. Regular screening and treatment are important to manage risk and prevent early cardiovascular problems in those with FH.
Marc S. Sabatine, MD, MPH, Michelle O'Donoghue, MD, MPH, Robert S. Rosenson, MD, and James A. Underberg, MD, MS, FACPM, FACP, FNYAM, FASPC, FNLA, prepared useful Practice Aids pertaining to LDL-C lowering for this CME activity titled "Following the Evidence: LDL-C as a Path to Reducing Cardiovascular Events—How Low Do We Go?" For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2RgYhWr. CME credit will be available until December 16, 2019.
Marc S. Sabatine, MD, MPH, Michelle O'Donoghue, MD, MPH, Robert S. Rosenson, MD, and James A. Underberg, MD, MS, FACPM, FACP, FNYAM, FASPC, FNLA, prepared useful Practice Aids pertaining to LDL-C lowering for this CME activity titled "Following the Evidence: LDL-C as a Path to Reducing Cardiovascular Events—How Low Do We Go?" For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2RgYhWr. CME credit will be available until December 16, 2019.
CholesLo shows clinical significance in
helping reduce plasma cholesterol and
homocysteine levels and therefore affects
favourably the risk of subsequent development
of cardiovascular disease. Furthermore, our
findings suggest that the dose required to cause
such improvements in plasma lipid profile is
safe enough to be considered for use in general
population.
The Unmet Medical Need in Homozygous Familial Hypercholesterolemia by Dennis ...CrimsonPublishersGJEM
HoFH is a rare and life-threatening disease originally characterized by plasma cholesterol levels > 500mg/dl, extensive xanthomas, and marked premature and progressive atherosclerotic cardiovascular disease [1]. Genetic defects in the LDL receptor causing the inability to internalize LDL was first identified by Brown and Goldstein [2]. There are two types of familial hypercholesterolemia: the heterozygous and homozygous forms. The heterozygous form, in which the patient has one normal allele and one mutated allele, the most common form, is considered to have prevalence as high as of 1 out 2003. The homozygous form, in which the patient has two mutated alleles, has a prevalence as high as 1 in 160, 0003.
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This presentation will show the diagnosttic criteria of metabolic syndrome and life style modification to cope up with this common disease .
also shows some quiz for medical students
Dyslipidemia, specially high LDL cholesterol is the key risk factor for cardiovascular diseases. The presentation discusses metabolism and structure of lipoproteins, their screening and interpretation, risk assessment methods, targets for various lipoproteins and its step by step treatment.
In Pakistan, the overall prevalence of dyslipidemia in adolescents aged 10–18 years is 21.7~25.2%; prevalence is reported to be two times higher (53.1~56.1%) in obese adolescents. However, few studies have been conducted on the relationship between height and blood lipid concentrations in children and adolescents The recent emphasis on treatment of the dyslipidemia of the metabolic syndrome (hypertriglyceridemia, reduced high-density lipoprotein, and increased small, dense low-density lipoprotein particle number) has compelled practitioners to consider lipid-lowering therapy in a greater number of their patients, as one in two individuals over age 50 has the metabolic syndrome. Individuals with the metabolic syndrome typically have normal low-density lipoprotein cholesterol levels, and current lipid-lowering guidelines may underestimate their cardiovascular risk. Two subgroups of patients with the metabolic syndrome are at particularly high risk for premature CAD. One, individuals with type 2 diabetes, accounts for 20-30% of early cardiovascular disease. The second, familial combined hyperlipidemia, accounts for an additional 10-20% of premature CAD. Familial combined hyperlipidemia is characterized by the metabolic syndrome in addition to a disproportionate elevation of apolipoprotein B levels. The measurement of fasting glucose and apolipoprotein B, in addition to the fasting lipid profile, can help to estimate CAD risk in patients with the metabolic syndrome. In this research we compared allopathic medication and medicinal herb in treating hyperlipidemia.
Clinical, laboratory and histological associations in clinical, laboratory an...Dr. sreeremya S
Clinical, laboratory and histological associations in clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
2. Familial hypercholesterolemia (FH) is a most common
monogenic hereditary autosomal dominant disorder of lipid
metabolism characterized by high circulating levels of low-density
lipoprotein (LDL).
The underlying cause is mainly due to defects in genes
related to the clearance of LDL.
Chronic exposure to high levels of circulating LDL leads to
the development of premature atherosclerotic cardiovascular
disease (ASCVD).
3. • Affecting an estimated 1:250 people worldwide.
• FH is caused by mutations in 3 main genes:
1. LDL-receptor (LDLR) gene ≈ 90% of the cases,
2. Apolipoprotein (apo) B (APOB) gene ≈ 5 to 10% of the cases.
3. Proprotein convertase subtilisin/kexin type 9 (PCSK9) gene ≈ 3% of the
cases
• 20% of FH patients diagnosed by clinical criteria do not have identifiable
causative mutations in any of the known FH-associated genes
• Only < 10%of affected patients receive a formal diagnosis.
Journal of the Endocrine Society, 2021, Vol. 5, No. 1
7. Eur Heart J, Volume 34, Issue 45, 1 December 2013, Pages 3478–3490, https://doi.org/10.1093/eurheartj/eht273
ESTIMATED PER CENT OF INDIVIDUALS DIAGNOSED WITH FAMILIAL
HYPERCHOLESTEROLAEMIA IN DIFFERENT ...
11. Diagnosis and Genetic Testing
• Diagnosis of FH can be made by using either clinical and/ or molecular criteria
after ruling out secondary causes of hypercholesterolemia.
• A number of clinical diagnostic criteria have been developed over the years to
facilitate diagnosis.
• They are mainly based on lipid levels and various combinations of physical
signs and personal or family history of hyperlipidemia or premature ASCVD
12.
13. Mary P. McGowan. Journal of the American Heart Association. Diagnosis and Treatment of Heterozygous Familial Hypercholesterolemia, Volume: 8, Issue: 24, DOI:
(10.1161/JAHA.119.013225)
14.
15.
16.
17. Loukianos S. Rallidis: Journal of Cardiology Volume 76, Issue 6, December 2020, Pages 568-
18. Pedigree of a family with familial hypercholesterolaemia. Red and green colours indicate
family members with and without heterozygous familial hypercholesterolaemia
Eur Heart J, Volume 34, Issue 45, 1 December 2013, Pages 3478–3490, https://doi.org/10.1093/eurheartj/eht273
19. Cardiovascular Risk Stratification
• All adult patients with FH should receive lifestyle counseling and high
intensity statin therapy independent of additional testing; statin therapy
should be started at the lowest dose in children and titrated upwards.
• However, within the context of FH, the utility of atherosclerosis imaging is to
identify individuals who may be eligible for more aggressive management
approaches above and beyond therapeutic lifestyle changes and statin
therapy.
20. Imaging Techniques
Imaging modalities that have been studied in patients with FH include
• carotid intima-media thickness (cIMT),
• coronary artery calcium (CAC) scoring
• coronary computed tomography angiography (CCTA).
With respect to cIMT, pediatric FH patients have higher cIMT values as
compared to age-matched controls with normal lipid levels, suggesting utility
as a non-invasive marker of ASCVD risk.
Indeed, pediatric FH patients who were started on statins and followed over 20
years had decreased progression of cIMT and fewer cardiovascular events in
comparison to their parents.
Despite this observation, cIMT has not been shown to correlate with vascular
disease in the aorta or coronaries in FH patients.
21. • Higher CAC scores correlated with an increased incidence of major adverse
cardiovascular events.
• In adjusted models, CAC was found to be an independent predictor of ASCVD
events.
• Findings such as coronary calcium, the sum of stenosis, and plaque composition
sum all correlated with estimated cardiovascular risk.
• Given the heterogeneous expression of the FH phenotype, selective use of
coronary vessel imaging in the form of CAC scoring or CCTA offer a promising
method of risk stratification, despite the inherently high baseline risk of this
population.
22. Treatment
• intensive education targeting lifestyle management, including intervention on
• Smoking
• Diet
• Physical activity.
• Implementation of a healthy diet with the involvement of the whole family.
• Functional foods known to lower LDL cholesterol, such as plant sterols and
stanols, may be considered.
• Avoid overweight and to reduce the amount of food and beverages with high
cholesterol, saturated fat, and trans fat content.
• Regular physical exercise
• In adults with FH, assessment of cardiovascular function is advisable before
starting any significant exercise programme.
23. Cholesterol-lowering drugs should be initiated immediately at diagnosis in adults and
strongly considered starting at age 8–10 in childhood, along with lifestyle management.
The priority for pharmacotherapy should be as follows:
Children:
(i) Statin
(ii) Ezetimibe (>10yr age)
(iii) Bile acid-binding resin,
(iv) Lipoprotein apheresis in homozygotes.
Adults:
(i) Maximal potent statin dose
(ii) Ezetimibe
(iii) Bile acid-binding resins,
(iv) Lipoprotein apheresis in homozygotes and in treatment resistant heterozygotes
with CHD. Acute reduction in LDL-C, up to 60% to 80%, can be achieved after each
procedure
(V) anti-PCSK9 monoclonal antibody (mAb)
(VI) Liver Transplantation
26. LDLcholesterol burden in individuals with or without FH as a function of the age of initiation of
statin therapy.
27. Kaplan–Meier curve estimates of cumulativeCHD-free survival among individuals with FH according to statin
treatment (P , 0.001 for difference). Based on 413 and 1537 Dutch subjects with heterozygous FH on or off
statin treatment.
Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ 2008;337:a2423.
33. PCSK9 INHIBITORS
• PCSK9 inhibitor further reduces LDL-C by 55-60% by increasing the
number of available LDL-Receptors
• Evolocumab and Alirocumab approved in Aug 2015 is indicated as
adjunct treatment with HeFH, HoFH or clinical atherosclerotic
cardiovascular disease who require additional lowering of LDL-C
• Suggested subcutaneous dosing of Evolocumab is 140 mg every 2
weeks or 420 mg every month
• Common adverse drug reactions include respiratory and injection-site
reactions
36. SAFETY OF VERY LOW LOW-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS
WITH ALIROCUMAB: POOLED DATA FROM RANDOMIZED TRIALS
• Pooled data from 14 trials of PCSK9 inhibitors
• Follow up of 104 weeks
• LDL<25 mg% or <15 mg% were not associated with an
increase in overall adverse events or neurocognitive
events except for incidence of Cataract ( 0.8 vs 2.6 %)
Jennifer G Robinson, JACC 2017:69:471
37.
38. Liver Transplantation
•Liver transplantation has been described as a treatment for both children and
young adults with homozygous FH in the form of case series.
•LDL-C levels rapidly approach normal and xanthoma diminish in size or disappear
by 2 years.
•Most transplantations have been performed in individuals who either are
symptomatic from CAD or demonstrate significant coronary lesions despite maximal
medical therapy and apheresis.
•Reported results are generally good in the short and medium term, as late as 9
years after liver transplantation
•In patients with advanced cardiac disease, combined heart/liver transplantation has
been performed
• Maiorana A, Nobili V, Calandra S, Francalanci P, Bernabei S, El Hachem M, Monti L, Gennari F, Torre G, de Ville de Goyet J, Bartuli A. Preemptive
liver transplantation in a child with familial hypercholesterolemia. Pediatr Transplant. 2011;15:E25–E29. doi: 10.1111/j.1399-3046.2010.01383.x
• Moyle M, Tate B. Homozygous familial hypercholesterolaemia presenting with cutaneous xanthomas: response to liver transplantation. Australas
J Dermatol. 2004;45:226–228. doi: 10.1111/j.1440-0960.2004.00103
39. Liver Transplantation for Homozygous Familial Hypercholesterolemia Yasushi :Journal of Atherosclerosis and ../Volume 26 (2019) Issue
