This document discusses the clinical features and treatment of ANCA-associated vasculitis. It begins by defining vasculitis and describing the different types. It then focuses on ANCA-associated vasculitis, describing the characteristics of Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA), and Eosinophilic Granulomatosis with Polyangiitis (EGPA). For treatment, it recommends cyclophosphamide or rituximab combined with steroids for inducing remission of GPA and MPA. Azathioprine or methotrexate are used to maintain remission. EGPA is primarily treated with steroids, with cyclophosphamide added for more
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Pulmonary renal syndrome by Dr Bharat Rewaria Bharat Rewaria
by Dr Bharat Rewaria . 14 dec 2021
Pulmonary-renal syndrome refers to combination of diffuse alveolar hemorrhage and rapidly progressing glomerulonephritis .
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This was a review of different guidelines on lupus nephritis from ACR, EULAR, and KDIGO. Goal is appreciate similarities and differences between the different guidelines.
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Pulmonary renal syndrome by Dr Bharat Rewaria Bharat Rewaria
by Dr Bharat Rewaria . 14 dec 2021
Pulmonary-renal syndrome refers to combination of diffuse alveolar hemorrhage and rapidly progressing glomerulonephritis .
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This was a review of different guidelines on lupus nephritis from ACR, EULAR, and KDIGO. Goal is appreciate similarities and differences between the different guidelines.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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
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Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
1. The Clinical Features and Treatment
of ANCA-Associated Vasculitis
Evan Nair-Gill MD, PhD
Internal Medicine Resident, UTSW
2.
3. VASCULITIS: Inflammation of blood vessels
Vessel aneurysm,
hemorrhage
Vessel thrombosis,
ischemia and necrosis
Target tissue damage and systemic disease
(manifestations dependent on the size and distribution of affected vessels)
4. The spectrum of primary vasculitic diseases
Immune Complex Small Vessel Vasculitis
Cryoglobulinemic Vasculitis
IgA Vasculitis (HSP)
Hypocomplementemic Urticarial Vasculitis
(Anti-C1q)
Anti-GBM disease
Medium Vessel Vasculitis
Polyarteritis Nodosa
Kawasaki Disease
ANCA-Associated Small Vessel Vasculitis
Microscopic Polyangiitis
Granulomatosis with Polyangiitis
(Wegener’s)
Eosinophilic Granulomatosis with Polyangiitis
(Churg-Strauss)
Large Vessel Vasculitis
Takayasu Arteritis
Giant Cell Arteritis
Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus
Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65:1.
5. Major Features of ANCA-Associated Vasculitis
Granulomatosis with polyangiitis
(GPA, Wegener’s granulomatosis)
Microscopic polyangiitis
(MPA)
Eosinophilic GPA
(EGPA, Churg-Strauss)
(1) Necrotizing vasculitis of small and
medium-sized vessels
(2) Absence of immune deposits on
vessel pathology
(3) ANCA positive
-~30,000 people have GPA and ~10,000 people have MPA in the US.
-~2600 new cases of GPA and 900 new cases of MPA are seen annually in the United States
-EGPA is rarer and estimated to affect about 3 people per million
-68,000 to 140,000 new cases of ANCA-associated vasculitis are diagnosed per year worldwide
-Onset for AAV is typically after the 5th decade but cases have been reported for all ages.
-Majority of patients are of Caucasian ancestry
-Slight male predominance (1.5:1 male:female)
Epidemiology and demographics
6. ANCAs: Antibodies against cytoplasmic antigens in neutrophils
P-ANCA is an antibody typically directed against myeloperoxidase (MPO), associated with MPA and EGPA
http://www.unckidneycenter.org
Perinuclear staining pattern: P-ANCA Cytoplasmic staining pattern: C-ANCA
C-ANCA is an antibody typically directed against proteinase-3 (Pr-3), associated with GPA
The titer of ANCA does not correlate with disease severity
Other diseases can give ANCA positivity: eg. SLE, RA, UC, PSC, Endocarditis, meds (hydralazine, PTU)
7. A possible role for ANCA in the pathogenesis of AAV
Schönermarck U et al. Nephrol. Dial. Transplant. 2014
9. Upper Airway Disease
GPA MPA EGPA
x
GPA: epistaxis, otitis media and mastoiditis,
destructive sino-nasal disease and saddle nose
deformity, subglottic stenosis
EGPA: allergic rhinitis, recurrent sinusitis--no
destructive disease, serous otitis media, nasal
polyposis
Kelley’s Texbook of Rheumatology 8th edition
Saddle nose
Erosive sinus disease
Subglottic stenosis, s/p stent
Clinical Features of ANCA-Associated Vasculitis
10. Pulmonary Disease
GPA MPA EGPA GPA/MPA: Hemoptysis. Imaging can show fixed nodules
(+/- cavitation), diffuse infiltrates, hilar adenopathy
EGPA: History of asthma poorly responsive to therapy.
Nodules (often non-cavitary), pleural effusions
(eosinophilic), transient infiltrates on CXR
DAH: Due to pulmonary capillaritis. GPA/MPA>>EGPA
Cavitary lesion in a patient with GPA.
Thickett D R et al. Rheumatology 2006;45:261-268
Capillaritis
http://pathhsw5m54.ucsf.edu/
Clinical Features of ANCA-Associated Vasculitis
11. Renal Disease
GPA MPA EGPA
Jennette, J. C. & Falk, R. J. (2014) Nat. Rev. Rheumatol.
Crescent
Fibrinoid
Necrosis
Asymptomatic hematuria, proteinuria (usually sub-
nephrotic range), AKI, casts on UA. Can present
indolently with preserved renal function or as RPGN.
On biopsy “pauci-immune” crescentic glomerular
nephritis is the typical finding.
RBC Casts
Normal Glomerulus
Clinical Features of ANCA-Associated Vasculitis
12. Cutaneous Manifestations
GPA MPA EGPA
http://www.hopkinsvasculitis.org/
Palpable purpura
Rashes for these three diseases similar to other
small vessel vasculitides: Leukocytoclastic vasculitis
with palpable purpura typically in lower
extremities, ulceration, skin necrosis.
Urticaria, livido reticularis, tender nodules can also
occur.
Ulcerated nodule
Clinical Features of ANCA-Associated Vasculitis
13. Eye and Neurological Problems
GPA MPA EGPA
EGPA: Mononeuritis multiplex is common, rarely CNS
symptoms due to aneurysm or hemorrhage
GPA: Often initial presenting symptom: uveitis,
scleritis, conjunctivitis, corneal ulceration
Mass effect from invading adjacent sinus disease can
cause proptosis
Clinical Features of ANCA-Associated Vasculitis
14. Diagnostic Approach to Small Vessel Vasculitis
Vasculitis suspected
(pulmonary-renal syndrome, purpura, neuropathy)
ANCA associated Not ANCA associated
Granulomatous
NoYes
Asthma/eosinophilia
NoYes
EGPA GPA
MPA
IgA deposit
Yes
IgA vasculitis
(HSP)
No
Cryoglobulins
Yes No
Cryoglobulinemia Other
15. General principles of treating ANCA-associated vasculitis
Assess vasculitis severity
Remission induction (3-6 months)
Maintenance therapy and monitor for relapse
(at least 12-24 months)
16. Induction therapy: GPA and MPA
Prior to Cyc, survival of GPA was ~20% at 18 months. With Cyc this has increased to >80% after 8 years.
Cyclophosphamide (Cyc) combined with glucocorticoids is the mainstay for remission induction for
generalized and severe disease.
Toxicity of sustained Cyc: bone marrow suppression, infection, sterility, induced malignancy, bladder toxicity.
RAVE trial (2010):Rituximab was non-inferior to Cyc for inducing remission and appeared to be more
effective in treating relapsed disease. Adverse events were the same between each group.
In severe disease (RPGN, pulmonary hemorrhage) PLEX is a useful adjunctive therapy.
CYCLOPS trial (2009): IV pulse dosing Cyc was equal to daily oral dosing for inducing remission. Long-term
follow-up (median 4.3 years) showed relapse rates were higher for IV Cyc but overall morbidity and mortality
were unchanged.
Steroids are used regardless of immunosuppression regimen. Pulse dose IV steroids typically used for first 3
days (esp in setting of renal failure, alveolar hemorrhage) then transition to oral prednisone 1mg/kg/day
17. Maintenance therapy for GPA and MPA
Prednisone should be tapered down to the lowest dose to prevent symptoms then tapered off very slowly
(can argue for continuing steroids indefinitely if patient has history of prior relapses).
Methotrexate or azathioprine are the most used medications. Relapse rate ~30% for both. Azathioprine is
preferred in patients with GFR < 50.
Frequent monitoring for drug toxicity and relapse symptoms (hemoptysis, hematuria, cutaneous symptoms,
etc) is necessary.
MAINRITSAN trial (2014) compared rituximab vs. azathioprine for maintaining remission: 29% relapse rate
for azathioprine group vs 5% rituximab group. (Caveat: azathioprine group underwent a dose reduction
not typically used).
Mild relapses (no threat to organs) can be treated by increased prednisone or maintenance
immunosuppression dose. Severe relapses treated with re-induction.
18. Induction and maintenance therapies for EGPA
Five factor score (FFS) to assess severity: Cardiac involvement, Gastrointestinal disease, AKI,
proteinuria >1g/day, CNS symptoms, severe respiratory disease, age>65 all score 1 point.
Patients are usually monitored every 3 months with CBC (for eosinophilia), spirometry, serum
creatinine, UA.
Maintenance therapy with azathioprine or methotrexate + prednisone taper for 12-18 months.
>90% of patients without severe disease—FFS 0 or 1—can be induced to remission with
glucocorticoids alone, usually prednisone 0.5mg/kg-1.5 mg/kg per day.
FFS 2 or more is indication to add Cyc. Dosing protocols are similar to those for GPA/MPA.
19. Summary
AAV generally: necrotizing vasculitis of small to medium vessels, pauci-immune lesions,
predominantly ANCA positive
GPA: Destructive nasal-sinus disease, lung nodules, glomerulonephritis, granulomatous
inflammation, PR3/C-ANCA positive.
MPA: Similar to GPA but less sinus disease, no granulomatous inflammation, more associated with
MPO/P-ANCA.
EGPA: History of asthma, mononeuritis multiplex, peripheral eosinophilia (>10%), eosinophilic
granulomas, migrating or transient CXR infiltrates, MPO/P-ANCA.
Therapy for GPA/MPA: in multi-organ disease use cyclophosphamide or rituximab + steroids.
Duration usually 3-6 months. Maintenance with methotrexate, azathioprine, or rituximab. Taper
slowly off steroids. Treatment for 12-24 months.
Therapy for EGPA: primarily steroids for disease without organ failure. Otherwise Cyc + steroids.
ANCA: autoantibodies against neutrophil enzymes. Likely play pathogenic role in vasculitis. Several
conditions can lead to positive ANCA. Must consider clinical scenario when interpreting ANCA
positivity. ANCA antibody levels not correlated with disease severity.