Presented at Belfast City Hospital Physician's Meeting.
Topic - A case of Focal Segmental Glomerulosclerosis with all the complications of nephrotic syndrome and transplant recurrence of FSGS.
Presented at Belfast City Hospital Physician's Meeting.
Topic - A case of Focal Segmental Glomerulosclerosis with all the complications of nephrotic syndrome and transplant recurrence of FSGS.
Nephrotic syndrome is a clinical state characterized by : Massive proteinuria ( > 40 mg /m²/hour), Hypoalbuminaemia ( < 2.5 gm/dl), Generalized edema, Hyperlipidemia ( S. cholesterol >250 mg /dl). 60%-80% present before 6 years. MCNS most commonest type of nephrotic syndrome , about 85% of idiopathic nephrotic syndrome.
Nephrotic syndrome is a clinical state characterized by : Massive proteinuria ( > 40 mg /m²/hour), Hypoalbuminaemia ( < 2.5 gm/dl), Generalized edema, Hyperlipidemia ( S. cholesterol >250 mg /dl). 60%-80% present before 6 years. MCNS most commonest type of nephrotic syndrome , about 85% of idiopathic nephrotic syndrome.
Etiology- genetic mutations, infection, toxin exposure, autoimmunity, atherosclerosis, hypertension, emboli, thrombosis, or diabetes mellitus.
Even after careful study, however, the cause often remains unknown, and the lesion is called idiopathic.
Inflammation of the glomerular capillaries is called glomerulonephritis.
Persistent glomerulonephritis that worsens renal function is always accompanied by interstitial nephritis, renal fibrosis, and tubular atrophy.
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.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
- 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
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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
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.
2. INTRODUCTION
• Major cause of idiopathic nephrotic syndrome
• Characterized by intense proteinuria leading to edema and
intravascular volume depletion
• In children >1 year of age, MCD is the most common cause of
nephrotic syndrome, accounting for 70%–90%
• In Adults-10%to15%
• Around puberty, membranous nephropathy, become more
frequent
3.
4. Most children respond to
steroid treatment, the disease
is termed “Steroid-Sensitive
Nephrotic Syndrome”
1
Lipoid Nephrosis-microscopic
lipid droplets in urine and
tubular cells
2
5. Epidemiology
10–50 cases per 1,00,000 children
More common in Asia
Male predominance (approximately 2:1)
MCD is much less frequent in adults
7. Nephrotic Syndrome
Edema
Massive proteinuria (>40 mg/m2 per h in children, >3.5 g/d in adults)
Hypoalbuminemia (<2.5 g/dl)
Remission
Resolution of edema
Normalization of serum albumin (≥3.5 g/dl)
Marked reduction in proteinuria
Complete remission (<4 mg/m2 per h or negative dipstick in children, <0.3 g/d in adults)
Partial remission (<2 g/1.73 m2 per d, decreased by 50% and serum albumin ≥2.5 g/dl in children, <3.5 g/d
and decreased by 50% in adults)
8. Relapse
Recurrence of massive proteinuria (>40 mg/m2 per h in children, >3.5 g/d in adults)
Positive urine dipstick (≥3+ for 3 d or positive for 7 d, usually applicable to children)
±Edema
Steroid-Sensitive Nephrotic Syndrome
Response to PDN 60 mg/m2 per d within 4–6 wk ±MPD boluses in children
Response to PDN 1 mg/kg per d or 2 mg/kg every other d, within 16 wk in adults
9. 50% of children achieve remission within 8 days of steroid treatment
Most patients who are going to respond to steroids do so within 4
weeks.
In contrast, in adults the median time to remission exceeds 2 months.
In both populations, MCD has a high tendency to relapse
Relapses tend to be more rapid in children
10.
11. Infrequently Relapsing Nephrotic Syndrome
<2 relapses per 6 mo (or <4 relapses per 12 mo)
Frequently Relapsing Nephrotic Syndrome
≥2 relapses per 6 mo (or ≥4 relapses per 12 mo)
Nonrelapsing Nephrotic Syndrome
No relapses for >2 yr after the end of therapy for the first episode of nephrotic syndrome (applicable to
children, not yet defined in adults)
12. Steroid-Dependent Nephrotic Syndrome
Relapse during steroid therapy or within 15 d of discontinuation
Steroid-Resistant Nephrotic Syndrome
No response to PDN 60 mg/m2 per d within 4 wk ±MPD boluses in children
No response to PDN 1 mg/kg per d or 2 mg/kg every other d, within 16 wk in adults
Multidrug-Resistant Nephrotic Syndrome
Poorly defined as absence of partial remission after 6 mo OR absence of complete remission after 2 yr
Treatment often consists of MPD boluses + oral prednisone for 6 mo + CsA and, in some cases, rituximab.
Other protocols are also used
13. RENAL BIOPSY INDICATION
In adults early
kidney biopsy is
crucial
The indications for
renal biopsy in
children are
Onset, age <1 or
>12 years
Gross hematuria Low serum C3
Marked
hypertension
Renal failure
without severe
hypovolemia
Positive history for
secondary cause
Steroid resistance
or therapy with
calcineurin
inhibitors
14. PATHOLOGY
• By LM, no glomerular lesions seen.
• Sometimes- mild focal mesangial prominence not exceeding three or four cells per
segment are seen.
• Diffuse mesangial hypercellularity variant- presence of more than four mesangial cells per
mesangial region affecting at least 80% of the glomeruli
• Hematuria and hypertension
15. • Immunofluorescence is usually negative.
• However, low-intensity mesangial IgM (sometimes accompanied
by C3 or C1q) staining can be found
• MCD is occasionally accompanied by glomerular IgA deposits-
IgA nephropathy with MCD
• Focal segmental distribution of IgM and C3 staining should
strongly suggest FSGS
• More than trace amounts of IgG and IgA suggest alternative
diagnosis
18. CLINICAL FEATURES
• Edema- Periorbital ,scrotum or labia and of the lower extremities
• Anasarca may develop with ascites and pleural and pericardial
effusion
• Severe infections such as Sepsis, Pneumonia, and
Peritonitis Ig depletion and altered T cell function
• Intravascular volume depletion and oliguria - AKI, which is more
frequently seen in adults
• Rarely, AKI with gross hematuria followed by anuria - secondary to
bilateral renal vein thrombosis.
• Gross hematuria is rare, occurring in 3% of patients
19. LAB VALUES
• Urinalysis, with urinary dipstick showing 3+/4+ proteinuria
• Nephrotic-range proteinuria
• Urine proteins >40 mg/h per m2 or
• Urine protein-to-creatinine ratio >200 mg/mmol in children and
• Urine proteins >3.5 g/d in adults
• Serum albumin<2 g/dl, with an increased α2-globulin and a reduced γ-globulin fraction
• Reduced total serum calcium, with ionized calcium usually within the normal range
• IgG is markedly decreased, IgA is slightly reduced, IgM is increased, and IgE is normal or
increased
20. • Hyperlipidemia
1. Increased hepatic synthesis of cholesterol,
triglycerides, and lipoproteins
2. Decreased activity of lipoprotein lipase
which transforms VLDL to LDL
3. Decreased LDL receptor activity and
4. Increased urinary loss of HDL and
proteins with anticoagulant properties,
such as antithrombin III
• Increase in circulating fibrinogen, factors V and
VIII, and protein C, leading to a state of
hypercoagulability
• Increased risk of thrombosis, usually venous
thrombosis (97% of patients)
24. PATHOGENESIS
• Existence of a circulating mediator produced by abnormal T cells Shalhoub(1974)
1. Remission may follow measles infection, which causes cell-mediated
immunosuppression
2. MCD may occur in Hodgkin disease, a lymphoid neoplasia;
3. MCD responds to drugs that suppress cell-mediated immunity; and
4. There is an absence of humoral (Ig and complement) deposition in glomeruli
• T cell hybridoma lines produced from patients with MCD were able to induce foot
process effacement and proteinuria in rats
• Prevalence of circulating CD8+ T suppressor cells that aggravate renal damage in
mouse models of nephrotic syndrome
25. • Prevalence of a type 2 T helper cell (Th2; IL4, IL5, IL9, IL10, and IL13)
cytokine profile in patients
• Association between MCD and atopy, as allergies are driven by Th2
responses.
• Of all Th2 cytokines, IL13 overexpression has been shown to induce
foot process effacement and proteinuria in rats
26.
27. • Effectiveness of B cell depletion via Rituximab, an anti-CD20
monoclonal antibody, in different forms of nephrotic syndrome has
suggested a role for B cells as drivers of disease
1. Total IgG and IgG subclasses display protracted alterations in
nephrotic patients during remission;
2. MCD has been observed in diseases associated with monoclonal
light chains, implicating altered Ig's in disease pathogenesis
3. Plasma soluble CD23, a classic parameter of B cell activation, is
increased during relapse
4. Measles virus also has an inhibitory effect on Ig synthesis
5. The immunosuppressors employed in the treatment of MCD have
an antiproliferative effect on B cells, as well as on T cells.
28. • Evidence against a direct role of B cells in MCD pathogenesis
1. No Ig deposition on renal biopsy.
2. In vitro, rituximab has been proven to bind directly to podocyte
SMPDL3b
3. Rituximab antiproteinuric effect may be independent of B cell
depletion
4. Moreover, after rituximab infusion, some patients maintain
prolonged remission despite reconstitution of B cells
5. the reconstitution of memory B cells predicts relapse
Targeting B cells may affect costimulatory pathways involved in T cell
activation, and this may well be one of the mechanisms involved
29. • Potential target of T cells on the Podocyte is CD80(B7–1)
• T cell costimulatory molecule expressed on antigen-
presenting cells and B cells
• Which has been found in the urine of patients with MCD
during disease relapse
• Recently, however, the presence of CD80 on human
podocytes during renal disease, including MCD and FSGS,
has been excluded
• The efficacy of recombinant CTLA4-Ig (Abatacept and
Belatacept, which downregulate CD80) in reducing
proteinuria was not confirmed by studies
30. • A plasma protein that binds sialoglycoproteins in podocytes,
• Leading to proteinuria and foot process effacement in rats and
cytoskeletal rearrangement in human cultured podocytes
Hemopexin,
• Overexpressing c-mip in podocytes develop heavy proteinuria
without any inflammatory lesions or cell infiltration.
• It interferes with podocyte signaling,
• Cytoskeletal disorganization and foot processes effacement
c-mip
• Induce proteinuria, foot process effacement, and dyslipidemia
Angiopoietin-
like 4
31. TREATMENT
• Acute management,
• Salt and fluid intake
restriction
• Steroid treatment with
prednisone or
prednisolone are the
primary drugs used at
disease onset
32. KDIGO 2012-CHILDREN
• 60 mg/m2 per d (or 2 mg/kg per d), 4–6 wk
• 40 mg/m2 every other d (or 1.5 mg/kg every other
d), 2–5 mo, taper
• Minimum duration 12 wk
PDN at onset
• 60 mg/m2 per d (or 2 mg/kg per d) until 3 d after
remission
• 40 mg/m2 every other d (or 1.5 mg/kg every other
d), 4 wk
PDN in relapse
(first relapses)
33. • 60 mg/m2 per d (or 2 mg/kg per d) until 3 d after
remission
• 40 mg/m2 every other d (or 1.5 mg/kg every other d)
• Taper over ≥3 mo
Long-term
PDN (FRNS
or SDNS)
• CPA 8–12 wk
• Chlorambucil 8 wk
• Lev>1 yr
• CsA/TAC>1 yr
• MMF>1 yr
• Rituximab
Steroid-
sparing
agents (FRNS
or SDNS)
34. Levamisole,
• An immunostimulatory drug with
an anthelmintic effect in animals,
• Is reported to increase time to
relapse in frequently relapsing NS
compared with prednisone alone
Calcineurin Inhibitor
• cyclosporin A (CsA) tacrolimus;
TAC)
• Blocks the activation of T cells,
modifying the immune response.
• CsA is easier to handle (no need
for frequent check of the blood
count and no gonadal toxicity)
• Led to a preference for CsA,
especially in steroid-dependent
NS.
• Tacrolimus - prefered in
adolescents, especially girls, as it
does not induce hypertrichosis or
gingival hypertrophy
35. Mycophenolate mofetil (MMF)
• It has an antiproliferative effect on both B and T cells.
• The main advantage of MMF compared with CsA is that it is not nephrotoxic.
• This has made it the first choice in treating steroid-dependent NS
Rituximab
• It is a chimeric monoclonal antibody
• It binds to the CD20 antigen expressed on B cells, thus inducing B cell depletion.
• Rituximab reduces drug dependency, allowing interruption of all therapy, though
often only temporarily,
• Serious side effects: fulminant myocarditis, pulmonary fibrosis, fatal Pneumocystis
jirovecii infections, severe ulcerative colitis, and severe allergic reactions
Humanized anti-CD20 monoclonal antibody, Ofatumumab
36. Steroid-Resistant Forms
• Steroid resistance is declared after 4 weeks of treatment.
• Genetic screening for genetic forms of nephrotic syndrome
and
• Performing a renal biopsy,
• Three intravenous methylprednisolone boluses followed by
the introduction of a calcineurin inhibitor, most frequently
CsA,
• Oral prednisone is usually reduced to alternate days and
gradually tapered until discontinuation within 6 months
37. ADULTS
First Episode of Nephrotic Syndrome
PDN 1 mg/kg per d or 2 mg/kg every other d (maximum 80 mg/d or 120 mg every other d) for 4–16 wk
(evidence level 2C)
Taper slowly over a total period of up to 6 mo after achieving remissionb (evidence level 2D)
Infrequent relapses
PDN 1 mg/kg per d or 2 mg/kg every other d (maximum 80 mg/d or 120 mg every other d) for 4–16 wk
(evidence level 2C)
Taper slowly over a total period of up to 6 mo after achieving remissionb (evidence level 2D)
38. Frequent relapses and steroid dependency
CPA 2–2.5 mg/kg per d for 8 wk (single course) (evidence level 2C)
If relapse occurs despite CPA or to preserve fertility:
CsA 3–5 mg/kg per d in two divided doses for 1–2 yr (evidence level 2C)
Or TAC 0.05–0.1 mg/kg per d in two divided doses until 3 mo after remission, then tapered to the
minimum efficient dose for 1–2 yr (evidence level 2C)
If intolerant to PDN, CPA, and CsA or TAC:
MMF 500–1000 mg twice daily for 1–2 yr (evidence level 2D)
39. Outcome
In children,
• After remission of the first episode of nephrosis, about 30% do not suffer relapses
for 18–24 months,
• 20%–30% progress to infrequent relapses
• The remaining 40%–50%, more frequently children <5 years of age, will have a
frequently relapsing or steroid-dependent course
• Initially steroid-sensitive disease will develop secondary steroid resistance.
• This clinical feature is highly predictive of post-transplant recurrence
In adults, relapses are frequent, occurring in about 56%–76% of
patients