This document presents a case study of a 56-year-old male farmer who presented with abdominal pain and jaundice. Medical tests found chronic gallstones, mild liver abnormalities, and splenectomy. The document then provides an extensive overview of chronic myelomonocytic leukemia (CMML), including classification, epidemiology, clinical manifestations, diagnostic criteria, disease subtypes, genetic abnormalities, risk stratification, treatment options including hydroxyurea and azacitidine, and allogeneic stem cell transplantation as a potential cure.
MULTIPLE MYELOMA -HEMATOLOGIC MALIGNANCY-DISEASE OF BONE MARROW - PLASMA CELL DISORDER
PATHOLOGY, .CLINICAL FEATURES , AND ITS MANAGMENT REFERENCE HARRISON
MULTIPLE MYELOMA -HEMATOLOGIC MALIGNANCY-DISEASE OF BONE MARROW - PLASMA CELL DISORDER
PATHOLOGY, .CLINICAL FEATURES , AND ITS MANAGMENT REFERENCE HARRISON
Plasma cell disorders is a difficult topic where most residents and students confuse with regarding to differentiating between various types of para-proteinemias or plasma cell dyscrasias. This simple presentation will highlight the key points in differentiating, diagnosing these orders. Initial management principles are discussed as well.
Plasma cell disorders is a difficult topic where most residents and students confuse with regarding to differentiating between various types of para-proteinemias or plasma cell dyscrasias. This simple presentation will highlight the key points in differentiating, diagnosing these orders. Initial management principles are discussed as well.
Multiple myeloma(MM) is hematologic malignancy characterized by neoplastic proliferation of single clone of plasma cell in bone marrow engaged in production of monoclonal (M) protein.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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
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!
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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
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.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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.
3. 56 year old male patient from El
beheira, married , with 4 offsprings ,
farmer , smoker.
Presented with abdominal pain in Rt
hypochondrium , fatty dyspepsia &
jaundice.
He sought medical advice , US
abdomen and routine laboratory Ix were
done.
Past Hx : Splenectomy 10 years ago
4. US abdomen & pelvis
1. Chronic calcular cholecystitis, no
intra / extrahepatic biliary dilatation.
2. Mild hepatomegaly, mild periportal
fibrosis, no focal hepatic lesion.
3. Normal PV caliber with hepatopedal
blood flow.
4. Spleen surgically removed with
splenule at its bed.
13. Disease overview
The 2008 WHO classification of myeloid
neoplasms defines chronic
myelomonocytic leukemia (CMML) as a
clonal hematopoietic stem cell disorder
that is characterized by:
1. Presence of an absolute monocytosis
(>1 × 109/L) in the peripheral blood.
2. Presence of myelodysplastic and
myeloproliferative features in the
bone marrow.
14. Classification
WHO created two separate categories
of CMML:
(a) CMML-1 (<5% peripheral blasts
including promonocytes and <10%
bone marrow blasts).
(b) CMML-2 (5–19% peripheral blasts
including promonocytes or 10–19%
bone marrow blasts including
promonocytes or presence of Auer
rods).
15. Epidemiology
The incidence and prevalence of
CMML are unknown. Large population
based studies estimate CMML
constitutes ∼10% of all cases of MDS.
Median age at diagnosis varies
between 65 and 75 years, and there is
a 2:1 male predominance.
16. Clinical manifestations
The presenting symptoms of CMML are variable.
Anemia, infection and bleeding are typical.
Weight loss, night sweats, and abdominal discomfort
from splenomegaly may be the presenting
manifestations.
Vast majority of patients are discovered incidentally
when a complete blood count is obtained for
unrelated reasons.
Occasionally, skin infiltration with abnormal
monocytes (leukemia cutis) has been reported as the
initial manifestation.
Some patients may directly present in the blastic
phase of CMML as acute myeloid leukemia (AML).
17. Diagnosis
The diagnosis of CMML rests on a
combination of morphologic, histopathologic
and chromosomal abnormalities in the bone
marrow.
It is important to exclude other
myeloproliferative neoplasms and
infectious/autoimmune conditions that can
cause monocytosis.
Infectious etiologies such as tuberculosis,
chronic fungal infections, infective
endocarditis, viral, and protozoal infections;
connective tissue disorders such as
systemic lupus erythematosus and
sarcoidosis, and lipid storage disorders.
18.
19. Diagnostic Features of Chronic
Myelomonocytic Leukemia
1. Peripheral blood monocytosis of >1 × 10
9
/L
2. No Philadelphia Chromosome or BCR-
ABL1 fusion gene
3. No rearrangement of the PDGFRA
or PDGFRB
4. Less than 20% blasts in the peripheral blood
and bone marrow
5. Dysplasia present in one or more myeloid
lineages.
If myelodysplasia is minimal or absent, CMML
can still be diagnosed if: an acquired, clonal
cytogenetic or molecular cytogenetic abnormality
is demonstrated in the hematopoietic stem cell
“OR” monocytosis has persisted for greater than
20. Dysplastic versus proliferative
CMML: phenotypic and
molecular differences
In a study in Mayo clinic :
139 (53%) patients had proliferative
and 122 (47%) dysplastic subtypes.
There was no difference between the
CMML subtypes in terms of age and
gender distribution, hemoglobin level,
platelet count or BM blast content.
Patients with proliferative CMML had
higher absolute monocyte counts ,
circulating immature myeloid cells,
circulating blasts and serum LDH
levels.
21. The following gene mutations were more
common in proliferative vs dysplastic
CMML: ASXL1 (54% vs 37%,
p=0.009), JAK2 (11% vs 3%, p=0.01)
and CBL (11% vs 8%,
p=0.047); SF3B1 mutations were more common
in dysplastic CMML (8% vs 1%, p=0.02).
There was no difference in the incidence
of TET2, DNMT3A and SRSF2 mutations
whereas there was a trend towards a higher
prevalence of NRAS (p=0.06)
and CSF3R (p=0.06) mutations in proliferative
CMML.
Cytogenetic abnormalities (p=0.03), including
higher risk categories were more common in
proliferative CMML.
22. Flow cytometry
Human monocytes can be divided into
three subsets: CD14+/CD16− (classical),
CD14+/CD16+(intermediate) and
CD14low/CD16+ (nonclassical), with
different gene expression profiles,
chemokine receptor expressions and
phagocytic activities. The classical
monocytes constitute majority of the
human monocytes (∼85%) in healthy
conditions.
CMML patients demonstrate an increase
in the fraction of classical monocytes
(CD14+/CD16−) [cutoff value 94%]
23. Histopathology
The bone marrow is generally hypercellular in
the vast majority of the patients.
There is predominance of the granulocytic
lineage, with dysplasia being a defining feature
of the disease. There is also an increase in the
number of monocytes.
Eosinophilia is not as striking in patients with
CMML as it is in CML.
Erythropoiesis is generally decreased and there
may be accompanying abnormal nuclear
contours, ring sideroblasts, and megaloblastoid
changes in red cell precursors.
Megakaryocytes are generally small and may
have hypolobulated nuclei. Bone marrow
fibrosis may be present in up to 30% of patients
with CMML.
24. Immuohistochemistry
The peripheral blood and bone marrow
monocytes usually express CD33 and CD13,
the typical antigens on myelocytes. There
may be variable expression of CD68, CD14,
and CD64.
Markers of aberrant expression include CD2,
CD15, CD56 and decreased expression of
CD14, CD13, HLA-DR, CD64, or CD36. The
presence of myeloblasts can be detected by
expression of CD34.
The most reliable markers on
immunohistochemistry include CD68R and
CD163.
25. Chromosomal abnormalities
Clonal cytogenetic abnormalities are seen
in ∼20–30% of CMML patients.
Common alterations include; trisomy 8,—Y,
abnormalities of chromosome 7
(monosomy 7 and del7q), trisomy 21, and
complex karyotypes.
The Spanish cytogenetic risk stratification
system categorizes patients in to three
groups; high risk (trisomy 8, chromosome 7
abnormalities, or complex karyotype),
intermediate risk (all chromosomal
abnormalities, except for those in the high
and low risk categories), and low risk
(normal karyotype or –Y).
26. Molecular abnormalities
These can broadly be divided into the
following categories:
(a) mutations in epigenetic control of
transcription, such as histone modification
(EZH2, ASXL140%, UTX), DNA
methylation (TET2 60%, DNMT3A), or
both (IDH1, IDH2)
(b) mutations in the spliceosome machinery
(SF3B1, SRSF2 45%, U2AF1, ZRSR2)
(c) mutations in genes that regulate cytokine
signaling (JAK2, RAS 30%, CBL,
and FLT3)
(d) mutations in transcription factors and
nucleosome assembly
27. Risk stratification
Several CMML-specific prognostic
models incorporating novel mutations
have been recently reported.
28.
29. Risk-Adapted Therapy
Guidelines for supportive care measures
such as the use of erythropoietin analogs
for the treatment of anemia, prophylactic
antibiotics for isolated neutropenia and
iron chelators for Patients with heavy
transfusion burdens.
One of the earliest reported randomized
trials for CMML, Wattel et al. compared
1000 mg/day of oral hydroxyurea to 150
mg/week of oral etoposide in 105 patients
.After a median follow-up of 11 months,
60% of patients in the hydroxyurea arm
responded compared to 36% in the
etoposide arm. Median OS was
30. Hypomethylating agents
Azacitidine is the only agent approved
for the treatment of CMML without any
myeloproliferative disorder by the
European Medicine agency (EMA).
The European registration trial
included 358 patients of whom 179
received azacitidine treatment.
31. Others
A phase 1 study of lenalidomide in
patients with CMML. Ten Austrian
centers recruited 20 patients. Patients
received 5–15 mg lenalidomide daily,
with partial responses and stabilization
of the disease in about half of patients.
A phase 1 trial of ruxolitinib showed
activity in patients with CMML,
particularly in those having
a myeloproliferative disease type
32. Allogeneic stem cell
transplantation
Allogeneic stem cell transplantation (HCT)
remains the only curative option for patients
with CMML.
In general, for younger patients with higher
risk disease and an acceptable co-morbidity
index, allogeneic HCT is the preferred
treatment modality .
With the advent of reduced intensity
conditioning and alternate donor sources
(haploidentical HCT and double umbilical
cord blood units), an increasing number of
patients have access to HCT. While reduced
intensity conditioning is associated with lower
nonrelapse mortality, disease relapse rates
are higher in comparison to myeloablative
regimens