1) Hematopoietic stem cell transplantation (HSCT) can cure thalassemia patients by replacing defective bone marrow with healthy donor marrow.
2) A study of 98 thalassemia patients who received HSCT found that 94% survived with a novel reduced toxicity conditioning regimen having similar outcomes as standard regimens.
3) HSCT can cure thalassemia patients of all ages, including those over 10 years old, with survival rates over 90% found in the study. Gene therapy may also provide a cure in the future without requiring donors.
Hemophagocytic Lymphohistiocytosis (HLH) is an aggressive and life threatening syndrome which results from excessive immune activation, that can rapidly deteriorate and lead to multiple organ failure and death.
Hemophagocytic Lymphohistiocytosis (HLH) is an aggressive and life threatening syndrome which results from excessive immune activation, that can rapidly deteriorate and lead to multiple organ failure and death.
Locally advanced Ca prostate
Courtesy : NCCN , Perez, Gunderson and Tepper
Brief outline on management
ADT, Radiotherapy, Surgery indications and Standard of care
Ohio State's ASH Review 2017 - Myeloproliferative DisordersOSUCCC - James
Katherine Walsh, MD
Assistant Professor of Clinical Internal Medicine
The Ohio State University Comprehensive Cancer Center -
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINI...Alok Gupta
FACTORS AFFECTING INITIAL CYCLOSPORINE A LEVEL AND ITS CORRELATION WITH CLINICAL OUTCOME IN ACUTE LEUKEMIA PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION
CyberKnife is an option in inoperable or medically not suitable for surgery
& in patient with progression / not tolerating systemic therapy
- Initial results are impressive with low toxicity, good response rate
Pts with small tumour, no prior treatment with good performance
treated with high dose have significantly better survival
Dose >45 Gy; 15Gy/# and small vol tumour (<50cc) have better prognosis
There is minimal toxicity with CyberKnife in liver tumours
Addition of chemotherapy along with CyberKnife will be the future
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
- 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
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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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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
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
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2 Case Reports of Gastric Ultrasound
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!
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.
3. Treatments for Severe Thalassemia
Palliative treatment
Blood transfusion
Iron chelation
Splenectomy
Curative treatment
Hematopoietic stem cell transplant (HSCT)
Allogeneic HSC
Gene therapy
Autologous HSC
4. BMT in Thalassemia and Lucarelli Classification
Risk factors for BMT in thalassemia
Chelation Regular vs Irregular
Hepatomegaly Absent vs Present
Liver fibrosis Absent vs Present
Risk classes for BMT in thalassemia
Chelation Hepatomegaly Fibrosis
Class1 Regular NO NO
Class2 Reg/Irreg NO/YES NO/YES
Class3 Irregular YES YES
Lucarelli G et al. N Engl J Med 1990
6. Results of MRD in HSCT for Thal Patients
Reference Patients OS TFS
Di Bartolomeo et al. 111 90 86
Argiolu et al. 37 88 88
Clift et al. 68 94 81
Lawson et al. 54 95 82
Ghavamzadehv et al. 60 83 73
Denninson et al. 50 76 68
Lin et al. 28 86 82
Lee et al. 44 86 82
Issaragrisil et al. 21 70 53
7. HSCT in Thalassemia at Ramathibodi
Related n=28, Unrelated n=21 Total 49 patients
82%
71%
Overall survival (OS) and thalassemia free survival (TFS) in Thai children
Hongeng S et al. Biol Blood Marrow Transplant 2006
92%
82%
9. Number of Donors in
Registry
Percentage of
patients with
45%
40%
35%
30%
Donors Percent of Finding
6% 5% 6% 7%
24%
18%
18%
Percent of Finding
45%
25%
20%
15%
10%
5%
HLA-A,-B,-DR Matched Donor
HLA-A,-B,-DR Matched Donor
within 1 month
within 1 month
37%
0%
200320042005200620072008200920102011
10. New Stratification for
High Risk Class 3 Patients
Definition
Older patients
Age > 10 yrs
Hepatomegaly (liver > 3 cm below right
costal margin)
11. High Risk Class 3 Patients
(Age > 10 yrs)
Pretransplant Management Program
Hypertransfusion in order to decrease erythroid
expansion especially to decrease spleen size
Regular iron chelation for at least 6-12 months
Hydroxyurea (Hb F enhancer) in order to decrease
erythroid expansion: 20 mg/kg/day for at least
6-12 months
Sodani P et al. Blood 2004
Hongeng S et al. Am J Hematol 2007
13. Am J Hematol, 2007
2 Iannone R, et al. BBMT 2003
3 Horan JT, et al. BMT 2005
4 Jacobsohn DA, et al. Lancet 2004
5 Krishnamurti L, et al. BMT 2006
14. Outcomes of Thalassemia Patients Undergoing
Hematopoietic Stem Cell Transplant by Using
a Standard Myeloablative (MAC) Versus
a Novel Reduced Toxicity (RTC) Conditioning
Regimen According to a New Risk Stratification
Suradej Hongeng, MD
Dept of Pediatrics, Faculty of Medicine
Ramathibodi Hospital, Mahidol University
Bangkok, Thailand
15. Novel Approach for High Risk Class 3 Patients
Pre transplant management
Hypertransfusion, chelation and hydroxyurea
Pretransplant immunosuppression (PTIS)
Flu + Dex (2 cycles)
Conditioning regimen
Bu + Flu + ATG
16. Pre-transplant Immunosuppression (PTIS)
Fludarabine 40 mg/m2 x 5 days
Dexamethasone 25 mg/m2 x 5 days
1-2 cycles; 28-day cycle
PTIS is given prior to conditioning regimen
22. MAC Regimens and GVHD Prophylaxis
Related donor and age < 10 yrs
MAC regimen: Cyclo 200 mg/kg, Bu 14-16 mg/kg PO/IV
CSA + MTX
Unrelated group and < 10 yrs
MAC regimen: Cyclo 200 mg/kg, Bu 14-16 mg/kg PO/IV,
Flu 210 mg/m2 and ATG (Fresenius) 40 mg/kg
FK506 + MTX
24. Study Population
120 thalassemia patients undergoing HSCT; 1989 - 2013
Exclude cord blood transplant n = 7
Exclude previous RTC transplant n = 8
(Am J Hematol; 2007)
Exclude haploidentical transplant n = 7
Final number of patients n = 98 patients
Related n = 65; Unrelated n = 33
MAC n = 76; Novel RTC n = 22
25. Patient Characteristics
MAC
Related n= 50 , Unrelated n=26 (34%)
Mismatched HLA (1 Ag or 1 Allele) 12/76 (15%)
Novel RTC
Related n=15 , Unrelated n=7 (32%)
Mismatched HLA (1 Ag or 1 Allele) 5/22 (22%)
All received BM or PBSC.
26. Novel RTC Group
22 patients
2 out of 22 had second HSCT and 1 had third HSCT
Age; median = 16 (10-21) y/o
Male 8; Female 14
Splenectomy = 7 (Referral hospital)
All patients had liver > 5 cm below costal margin.
Ferritin level; median = 3100 (869-8350) ng/mL
Comorbidities
2 DM, 1 previous extramedullary hemopoiesis,
1 previous history of PHT
27. Novel RTC Group
21 patients received PBSC.
1 patient received BM.
Median CD34+ 9.4 (4.67-19.26) x106 cells/kg
MRD 13 MMRD 2 (DRB1)
MUD 4 MMUD 2 (C) MMUD 1 (A)
29. Outcome of All 98 Patients
Overall survival = 94% (95%CI; 86.3%-97/1%)
Event free survival = 87% (95%CI; 76.6%-91.1%)
30. Survival Rates Related (n=65) and
Unrelated (n=33) HSCT in Thalassemias
OS Related vs Unrelated = 94%
EFS Related = 88%
EFS Unrelated = 82%
31. MAC (n = 76) vs Novel RTC (n= 22)
OS MAC = 95%
RTC = 90%
EFS MAC = 88%
RTC = 93%
32. MAC vs Novel RTC
MAC RTC
Acute GVHD gr III-IV 3 (4%) 2 (10%)
Chronic GVHD
Limited 6 (8%) 3 (13%)
Extensive 2 (3%) 0
Dead 3 2
1 Graft failure 1 Fungal infection
1 Viral infection 1 Accident
1 Secondary AML
33. Haploidentical HSCT (34+ selection)
22 pts
Myeloablative
regimen; Cyclo, Bu,
Flu,Thiotepa and
ATG
GVHD prophylaxis
CSA
Sodani et al, Blood 2010
34. All Thalassemia Patients May Be Cured with HSCT?
TFS in related or unrelated for all age group
(including pts age older than 10 yrs) in our center is 90%.
Haploindentical HSCT in 12 severe patients
(9/12 age > 10 yr)
RTC plus Cyclophosphamide post transplant
All 12 pts survived without thalassemia.
No major complication except GvHD gr I-II.
Follow up time; 4-20 months
(abstract submitted to ASH 2014)
37. Overview of the clinical protocol
Testing
and Release
While Frozen
Maximize
% Transduced
HSCs
Vector
+
Cytokines
Bone Marrow
Harvest
IV Infusion
Transduced Cells
(> 4x106 CD34+/Kg)
(Spontaneous Homing)
CD34+ cells
(2x108 unsorted BM cells/Kg
kept for rescue)
38. Conclusion
Outcomes of HSCT for thal in both MRD and MUD are
favorable.
Outcomes of HSCT for all age group among thal pts are
also favorable.
Whether the novel RTC regimen should be studied in
younger thalassemia patients is needed to be
investigated.
Autologous HSC with gene addition may give a new
hope for cure for thal patients.
HF information helps the registry to calculate the probability of finding a matched donor for patients. Many studies have shown that continued recruitment of random volunteers will increase the matched probability.
Moreover, calculation of the percentage of patients for whom the donor was found was performed to evaluate unrelated donor search outcome. This figure show the percentage of patients who found matched donor when registry was grown up each year.
Comparing the percentage of patients for whom the donor was found in the TSCDR with previous calculation other registries containing
a pool of 10,000–23,000 donors, a potential HLA-A, -B,
-DR serological split antigen matched donor was found in the
TSCDR (49%), higher than the Korean Marrow Donor Program
(28%) and the Europdonor Foundation (20%).
We proposed sequential pretransplant immunosuppression, consists of fludarabine 40mg/squaremeter and dexamethasone 25 mg/squaremeter for 5 days, 28-day cylcle prior to conditioning regimen.
This graph showdecreased CD4 cell prolifereation in all three representative patients.
In the past, conditioning regimen for patients older than 10 y/o was a combination of cyclophosphamide and busulfan, which is too much alkylating agent and too toxic, therefor novel approach need to be explored
Conditioning regimen comprised of 6-day of fludarabine, 4-day of busulfex and 3-day of antithymocyte globulin.
Total eighteen patients were included in this study, two of them were second transplant. Four patients with homozygous beta thalassemia with median age at 14 y/o, seven of them were male and seven patients were undergone splenectomy. All patients had hepatomegaly, with high serum ferritin level.
Most of them received peripheral blood stem cells, at median CD34 positive 9.4 million cell per kilogram. 11 of them were matched related donor.
