Donesumab is a monoclonal antibody that inhibits RANKL, a protein involved in bone resorption. It is approved to treat osteoporosis and increase bone mass in high risk patients, as well as to prevent skeletal complications in patients with bone metastases or giant cell tumor of bone. Common side effects include back pain, joint pain, and hypocalcemia. While early studies found Denosumab reduced tumor giant cells and risk of recurrence in giant cell tumor patients, one case report found malignant transformation in a patient after long term use. Further research is still needed on its use for giant cell tumor.
Zoldronic acid is a treatment for certain cancers. Zoldronic acid comes in many different kinds of generic brands. You can buy Zoldronic acid from http://www.genericanticancer.com
This video explains Lumbar Disc Replacement in Detail. When degenerative disc disease begins to affect the spine this is called degenerative disc disease. This video highlights the history, epidemiology, and treatment options both conservative and surgical. If you or someone you know needs to be seen in regards to Lumbar Disc Replacement feel free to look us up online www.beverlyspine.com or www.santamonicaspine.com OR call toll free 1-8SPINECAL-1
Zoldronic acid is a treatment for certain cancers. Zoldronic acid comes in many different kinds of generic brands. You can buy Zoldronic acid from http://www.genericanticancer.com
This video explains Lumbar Disc Replacement in Detail. When degenerative disc disease begins to affect the spine this is called degenerative disc disease. This video highlights the history, epidemiology, and treatment options both conservative and surgical. If you or someone you know needs to be seen in regards to Lumbar Disc Replacement feel free to look us up online www.beverlyspine.com or www.santamonicaspine.com OR call toll free 1-8SPINECAL-1
CPR for the Foot - The approach in ScotlandDerek Jones
Presentation made at the Irish Association of Prosthetists and Orthotists meeting in Dublin featuring the work of the Scottish Foot Action Group in managing diabetic foot disease
Supplemental corticosteroids for dental patients with adrenal insufficiencyR...DrKamini Dadsena
Primary Adrenal Insufficiency:
It is caused by a progressive destruction of the adrenal cortex, usually of an idiopathic nature (most commonly autoimmune), but also results from hemorrhage, sepsis, infectious diseases (such as tuberculosis, human immunodeficiency virus, cytomegalovirus and fungal infection), malignancy, adrenalectomy, amyloidosis or drugs.
This presentation comprises of various chemotherapeutic agents used in ENT malignancies and other conditions. Its classifies the agents and briefly discusses the dosage and their common side effects.
Avascular necrosis of Hip - treatment modalities and current concepts.pptxVivek Jadawala
Slide 1 - Treatment modalities of Avascular Necrosis of Hip
JOURNAL CLUB PRESENTATION
Dr. Vivek Jadawala
PGY-3, Dept. of Orthopaedics,
JNMC, DMIHER
Slide 2 - image
slide 3 - image
slide 4 - Osteonecrosis of Hip - Osteonecrosis is death of living elements of involved bone (cells including marrow) with progressive destruction and alteration of bone architecture as a result of compromised vascularity.
Usually aseptic but may be incited by loss of vascularity from infection.
Slide 5 - Epidemiology - Male > Female
Average age group – 35 to 50 years
Bilateral Hip joints – 80 % of the cases
Most common site – Antero-lateral aspect of femoral head
Slide 6 - Blood supply of femoral head
Slide 7 - Classification of AVN: Ficat and Arlet -STAGE 0 :
X-ray : normal
MRI: normal
clinical symptoms: nil
STAGE I :
X-ray : normal or minor osteopenia
MRI: edema
bone scan: increased uptake
clinical symptoms: pain typically in the groin
Slide 8 - Stage I
Slide 9 - Stage II -
X-ray: mixed osteopenia and/or sclerosis and/or subchondral cysts, without any subchondral lucency (crescent sign)
MRI: geographic defect
Bone scan: increased uptake
clinical symptoms: pain and stiffness
Slide 10 - Stage III - X-ray: Crescent sign and eventual cortical collapse
MRI: same as plain radiograph
clinical symptoms: pain and stiffness +/- radiation to knee and limp
Slide 11 - Stage IV - X-ray: end-stage with evidence of secondary degenerative change
MRI: same as plain radiograph
clinical symptoms: pain and limp
Slide 12 - Stage IV
Slide 13 - image
Slide 14 - Steinberg staging of AVN
Slide 15 - Steinberg staging - STAGE 0:
- normal or non-diagnostic radiographs, MRI and bone scan of at risk hip (often contralateral hip involved, or patient has risk factors and hip pain)
STAGE I:
normal radiograph, abnormal bone scan and/or MRI
STAGE II:
- cystic and sclerotic radiographic changes
STAGE I AND II
A, mild: <15% head involvement as seen on radiograph or MRI
B, moderate: 15% to 30%
C, severe: >30%
Slide 16 - STAGE III:
- subchondral lucency or crescent sign
A, mild: subchondral collapse (crescent) beneath <15% of articular surface
B, moderate: crescent beneath 15% to 30%
C, severe: crescent beneath >30%
STAGE IV:
flattening of femoral head, with depression graded into
A, mild: <15% of surface has collapsed and depression is <2 mm
B, moderate: 15% to 30% collapsed or 2-4 mm depression
C, severe: >30% collapsed or >4 mm depression
Slide 17 - STAGE V:
- joint space narrowing with or without acetabular involvement
STAGE VI:
- advanced degenerative changes
Slide 18 - Association Research Circulation Osseous classification
Slide 19 - image
Slide 20 - Kerboul angle - Original classification was proposed on radiographs where he divided the necrotic region into small, medium and large regions:
Small - less than or equal to 160°
Medium - 161 to 199°
Large - 200 or more degrees.
Slide 21 - Modified Kerboul angle - based on MRI has much higher values as the MRI overestimates the necrotic region
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
3. • What is it ?
• Mechanism of action ?
• Uses ?
• Side effects ?
• Contra indications ?
• Adverse drug reactions ?
• Cost ? , availability ?
• Current recommendations ?
4. What is it ?
• Monoclonal antibody ( IgG2 )
• Developed by AMGEN
• On 2 June 2010, DENOSUMAB was approved by
(FDA) for use in postmenopausal women with risk
of osteoporosis under the trade name Prolia, and
in November 2010, as Xgeva, for the prevention of
skeleton-related events in patients with bone
metastases from solid tumors.
5. • Denosumab is the first RANKL inhibitor to be
approved by the FDA.
• On 13 June 2013, the US FDA approved
Denosumab for treatment of adults and
skeletally mature adolescents with Giant cell
tumor of bone that is unresectable or where
resection would result in significant morbidity.
10. USES
• Treatment of postmenopausal women with
osteoporosis at high risk for fracture
• Treatment to increase bone mass in men with
osteoporosis at high risk for fracture
• Treatment of glucocorticoid-induced
osteoporosis in men and women at high risk for
fracture
11. • Treatment to increase bone mass in men at
high risk for fracture receiving androgen
deprivation therapy for non-metastatic
prostate cancer
• Treatment to increase bone mass in women at
high risk for fracture receiving adjuvant
aromatase inhibitor therapy for breast cancer
12. DOSAGE AND ADMINISTRATION
• Pregnancy must be ruled out prior to
administration of Prolia
• Prolia should be administered by a healthcare
professional
• Administer injection every 6 months as a
subcutaneous injection in the upper arm,
upper thigh, or abdomen
• Instruct patients to take calcium 1000 mg
daily and at least 400 IU vitamin D daily
13. DOSAGE AND STRENGTH
• Single-use prefilled syringe containing 60 mg
in a 1 mL solution
18. WARNING AND PRECAUTIOS
• Same Active Ingredient: Patients receiving
Prolia should not receive XGEVA
• Hypersensitivity including anaphylaxis
• Hypocalcemia: Must be corrected before
initiating Prolia. May worsen, Especially in
patients with renal impairment.
• Adequately supplement Patients with calcium
and vitamin D
• Osteonecrosis of the jaw: Has been reported
with Prolia.
19. • Atypical femoral fractures
• Multiple vertebral fractures
• Serious infections including skin infections
• Dermatologic reactions: Dermatitis, rashes, and
eczema have been reported.
• Severe bone, joint, muscle pain may occur.
• Suppression of bone turnover
20. ADVERSE DRUG REACTIONS
• Postmenopausal osteoporosis: Most common adverse reactions
(> 5% and more common than placebo) were: back pain, pain in
extremity, hypercholesterolemia, musculoskeletal pain, and
cystitis. Pancreatitis has been reported in clinical trials
• Male osteoporosis: Most common adverse reactions (> 5% and
more common than placebo) were: back pain, arthralgia, and
nasopharyngitis
• Glucocorticoid-induced osteoporosis: Most common adverse
reactions (> 3% and more common than active-control group)
were: back pain, hypertension, bronchitis, and headache
• Bone loss due to hormone ablation for cancer: Most common
adverse reactions (≥ 10% and more common than placebo)
were: arthralgia and back pain. Pain in extremity and
musculoskeletal pain have also been reported in clinical trials
29. INDICATIONS AND USE
• Prevention of skeletal-related events in
patients with multiple myeloma and in
patients with bone metastases from solid
tumors.
• Treatment of adults and skeletally mature
adolescents with giant cell tumor of bone that
is unresectable or where surgical resection is
likely to result in severe morbidity.
• Treatment of hypercalcemia of malignancy
30. DOSAGE AND ADMINISTRATION
• Multiple Myeloma and Bone Metastasis from
Solid Tumors: Administer 120 mg every 4
weeks as a subcutaneous injection in the
upper arm, upper thigh, or abdomen.
• Giant Cell Tumor of Bone: Administer 120 mg
every 4 weeks with additional 120 mg doses
on Days 8 and 15 of the first month of therapy.
• Hypercalcemia of Malignancy: Administer 120
mg every 4 weeks with additional 120 mg
doses on Days 8 and 15 of the first month of
therapy.
31. DOSAGE FORMS AND STRENGTHS
• Injection: 120 mg/1.7 mL (70 mg/mL) solution
in a single-dose vial
32. WARNING SYMPTOMS AND PRECAUTIONS
• Hypersensitivity reactions including
anaphylaxis may occur.
• Hypocalcemia: Xgeva can cause severe
symptomatic hypocalcemia, and fatal cases
have been reported.
• Correct hypocalcemia prior to initiating Xgeva.
Monitor calcium levels during therapy,
especially in the first weeks of initiating
therapy, and adequately supplement all
patients with calcium and vitamin D.
33. • Osteonecrosis of the jaw (ONJ) has been
reported in patients receiving Xgeva
• Atypical femoral fracture
• Hypercalcemia Following Treatment
Discontinuation in Patients with Giant Cell
Tumor of Bone and in Patients with Growing
Skeletons: Monitor patients for signs and
symptoms of hypercalcemia, and manage as
clinically appropriate.
34. • Multiple Vertebral Fractures (MVF) Following
Treatment
• Discontinuation: When Xgeva treatment is
discontinued, evaluate the individual patient’s
risk for vertebral fractures.
• Embryo-Fetal Toxicity: Can cause fetal harm.
Advise females of reproductive potential of
potential risk to the fetus and to use effective
contraception.
35. ADVERSE REACTIONS
• Bone Metastasis from Solid Tumors: Most
common adverse reactions (≥ 25%) were
fatigue/asthenia, hypophosphatemia, and nausea.
• Multiple Myeloma: Most common adverse
reactions (≥ 10%) were diarrhea, nausea, anemia,
back pain, thrombocytopenia, peripheral edema,
hypocalcemia, upper respiratory tract infection,
rash, and headache.
36. • Giant Cell Tumor of Bone: Most common
adverse reactions (≥ 10%) were arthralgia,
headache, nausea, back pain, fatigue, and
pain in extremity.
• Hypercalcemia of Malignancy: Most common
adverse reactions (> 20%) were nausea,
dyspnea, decreased appetite, headache,
peripheral edema, vomiting, anemia,
constipation, and diarrhea.
37. DENOSUMAB IN GCT
• GCT : locally aggressive benign neoplasm
• Malignant transformation with out
radiotherapy is uncommon and occurs in less
than 1% of cases
• Decrease in activity and control of symptoms
• Malignant transformation is seen mostly
following radiation therapy
38. • To enhance surgeons ability to
perform joint preserving
intralesional surgery with an
acceptable low risk of recurrence
39.
40. • Sample : 20 adults with recurrent /
unresectable GCT
• Dosage : SC Denosumab 120 mg every 4 wks
(with additional doses on day 8 and day 15 )
• End point : 90 % or more elimination of giant
cells from tumour
• 100% subjects achieved end point .
• 65 % increased portion of RANKL- positive
stromal cells replaced by dense fibro-osseous
tissue / new owen bone
49. • Pain around knee joint diminished
• Further resection ??
• Patient refused
• Clinical improvement persisted until jan 14
• Presented with Rapidly growing painful
palpable mass
• Open biopsy : high grade sarcoma
• A/K amputation
65. RESULTS
• 54 patients with 30 primary and 25 recurrent
tumours
• 17 patients treated with out denosumab
• 6 doses before surgery ( planned arbitrarily)
• Clinical improvement in all (3 to 4 doses)
• 3 doses prior in whom surgery was planned
66. • 14 recurrences out of 37 curetted tumours(38%)
• 11 of 25 patients in donesumab-treated curettage
group had recurrences (44%) compared with 7 of
34 (21%) in the non denosumab-treated control
group : not significant
• No recurrence in the resection group
• One malignant transformation in a pt with
proximal humeral GCT.
• Denosumab reduces risk of recurrence ????
• Further trials needed !!!!!!
67.
68.
69.
70.
71. SOURCES
• Freedome trial
• Freedome extension trial
• Luis et.al case report
• Mainsh et.al article on Denosumab in GCT
• Xu et.al Denosumab in GCT review
• AMGEN annual Denosumab update