Side effect profile of a continuous immunosuppression following renal transplantation is well known.
Cardiovascular problems, malignancy, and infections are the main reasons for death with functioning graft and significant reasons for post-transplant morbidity.
mTOR is a 289 kDa protein kinase encoded in humans by the MTOR gene .
It interacts with several proteins to form mTORC1 and mTORC2 among eukaryotes.
There are two common proteins shared by mTORC1/mTORC2 multimeric complexes: the positive regulator mLST8 and the negative regulator Deptor.
Remember that there are unique proteins coupled to each complex (stabilizers and inhibitors).
rapamycin (sirolimus)
is well established as an immunosuppressant for use in the prevention of allograft rejection
A lipophilic agent-a fermentation product of Streptomyces hygroscopicus
1970 first investigation
1971 as an immunosuppressant
2OH ethyl chain substitution of sirolimus-everolimus better bioavailable
1999FDA approved sirolimus
2010FDA approved everolimus
mTOR is a 289 kDa protein kinase encoded in humans by the MTOR gene .
It interacts with several proteins to form mTORC1 and mTORC2 among eukaryotes.
There are two common proteins shared by mTORC1/mTORC2 multimeric complexes: the positive regulator mLST8 and the negative regulator Deptor.
Remember that there are unique proteins coupled to each complex (stabilizers and inhibitors).
rapamycin (sirolimus)
is well established as an immunosuppressant for use in the prevention of allograft rejection
A lipophilic agent-a fermentation product of Streptomyces hygroscopicus
1970 first investigation
1971 as an immunosuppressant
2OH ethyl chain substitution of sirolimus-everolimus better bioavailable
1999FDA approved sirolimus
2010FDA approved everolimus
Molecular genetics of hepatocellular carcinoma : the future is now dr_ekbalabohashem
A short review of the molecular events leading to the development of HCC due to different etiological factors , and its impact on future therapeutic modalities .
Present and Future Impact of Cytogenetics on Acute Myeloid Leukemialarriva
Cytogenetics is an advancement in which clinicians can look for specific genetic mutations of chromosomal DNA and use that information to determine patient prognosis and individualize therapy. In this presentation I cover what cytogenetics are, how they impact patient risk, what therapies to use based on risk, and how genetically targeted agents may be used in the future.
Molecular monitoring of CML patients and aims of treatment and management with illustration of the mechanism of action of different drugs (Tyrosine Kinase inhibitors) used in the management of the chronic myeloid leukemia (CML)
This presentation contains all the updated information regarding ongoing treatment protocol, HSCT, Antibiotic prophylaxis, upcoming targeted therapies related to AML
Molecular genetics of hepatocellular carcinoma : the future is now dr_ekbalabohashem
A short review of the molecular events leading to the development of HCC due to different etiological factors , and its impact on future therapeutic modalities .
Present and Future Impact of Cytogenetics on Acute Myeloid Leukemialarriva
Cytogenetics is an advancement in which clinicians can look for specific genetic mutations of chromosomal DNA and use that information to determine patient prognosis and individualize therapy. In this presentation I cover what cytogenetics are, how they impact patient risk, what therapies to use based on risk, and how genetically targeted agents may be used in the future.
Molecular monitoring of CML patients and aims of treatment and management with illustration of the mechanism of action of different drugs (Tyrosine Kinase inhibitors) used in the management of the chronic myeloid leukemia (CML)
This presentation contains all the updated information regarding ongoing treatment protocol, HSCT, Antibiotic prophylaxis, upcoming targeted therapies related to AML
Francisco M. Marty, MD, and Kathleen Mullane, DO, PharmD, FIDSA, prepared useful Practice Aids pertaining to cytomegalovirus management for this CME activity titled "Refining the Management of CMV in HCT Recipients: What Does the Future Hold?" For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2uk5G0q. CME credit will be available until April 3, 2019.
Treatment of hepatitis C in liver transplant patientApollo Hospitals
A significant proportion of patients with chronic hepatitis C virus (HCV) infection develop cirrhosis and complications of end-stage liver disease over two to three decades and require liver transplantation. However, reinfection is common and leads to further adverse events under immunosuppression. Pretransplant antiviral or pre-emptive therapy is limited to mildly decompensated patients due to poor tolerance. The main stay of management represents directed antiviral therapy after evidence of recurrence of HCV in the transplanted patient.
Roy F. Chemaly, MD, MPH, FIDSA, FACP, and Genovefa Papanicolaou, MD, prepared useful Practice Aids pertaining to cytomegalovirus for this CME activity titled "Managing CMV in the New Era of Antiviral Therapy: Practical Considerations in the HCT Setting." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2EUH2GI. CME credit will be available until March 25, 2020.
Extended Letermovir Prophylactic Therapy as CMV Prophylaxis in Graft-versus-H...Vijay Elipay
Letermovir is an antiviral with a novel mechanism of action, recently received FDA approval for prophylactic treatment against CMV in GVHD patients. In the approved use, letermovir is administered through week 14 which is about 100 days post-transplant of the allograft. This slideset discusses the subsequent study in which letermovir is investigated for its efficacy when administered beyond weak 14 or 100 days, i.e., extended course letermovir prophylaxis.
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.
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
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
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.
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.
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.
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.
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.
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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
The Role of Antiviral Effect of mTORis in Kidney Transplant Patients
1.
2. The Role of Antiviral Effect of mTORis in
Kidney Transplant Patients
Fahimeh Asgarian; MD
TUMS
3. Introduction
➨ Side effect profile of a continuous immunosuppression following
renal transplantation is well known.
➨ Cardiovascular problems, malignancy, and infections are the main
reasons for death with functioning graft and significant reasons for
post-transplant morbidity.
6. ➨Viruses remain the most common cause of infection in transplanted
patients.
➨CMV
➨BK polyomavirus virus (BKPyV)
➨EBV
7. ➨The most prominent antiviral mechanism :
➨The mTORis increase the quality, functionality and efficacy of memory T cells
in response to vaccinations as well as viral stimuli.
➨ Patients treated with everolimus had a significant increase in CMV-specific
CD8+ and CD4+ T cells.
➨ Sirolimus inhibit viral protein synthesis of pUL44 and pp65, key proteins
necessary for CMV replication in macrophages.
8. CMV
➨CMV is the most prominent viral infection after SOT.
➨The development of antiviral drug therapy has had a substantially
positive impact on CMV infection and disease; however, they have
adverse effects and risk for the development of CMV resistance.
➨Emerging evidence suggests that mTORis exhibit a protective role
against CMV reactivation and disease.
11. ➨In the first meta-analysis, CMV events after solid organ
transplantation occurred significantly more often under CNIs
(RR=2.27).
➨The second meta-analysis comparing the mTOR-I + CNI combination
with a CNI treatment in 15 trials showed again a higher CMV
incidence when patients received an mTOR-I free immunosuppression
(RR=2.45).
12. ➨mTOR-inhibitor treatment either alone or in combination with CNIs
reduces significantly the CMV incidence after organ transplantation.
➨With the use of an mTOR-inhibitor, CMV prophylaxis may be
dispensable.
13.
14. ➨The impact of mTORis on CMV in D+R− recipients is less clear.
➨CMV seropositive recipients(R+) receiving mTORis have a significantly
lower incidence of CMV infection/disease.
➨We suggest the use of mTORis as a potential approach to decrease
CMV infection and disease in CMV seropositive kidney transplant
recipients (high/strong)
15. ➨Children with recurrent CMV DNAemia or disease (at least 2
episodes) may benefit from secondary antiviral prophylaxis.
➨Conversion to mTORis based immunosuppression in pediatric kidney
transplant recipients may provide some protection against recurrent
CMV.
16.
17. Specific recommendations for ganciclovir‐ resistant CMV:
➨Cautious reduction in immunosuppression is recommended for
patients with refractory or resistant CMV infection and disease
(strong, moderate).
➨A switch to sirolimus‐containing regimen may be an option due to the
reportedly lower risk of CMV disease in patients receiving mTOR
inhibitors (weak, moderate).
18. BK polyoma virus
➨BK virus is known to cause BKV-associated nephropathy (BKVAN) and
is an important cause of graft loss in renal transplant recipients.
➨De novo mTORi may reduce the incidence of BK viremia.
19. ➨Conversion to an mTORi in patients with BKVAN may reduce BKV viral
load and improve kidney allograft function.
➨Data concerning the clearance of BKV viremia in patients without
BKVAN with the use of mTORis is limited and conflicting.
24. ➨Kidney transplant recipients should be screened for BKPyV‐ DNAemia
by QNAT to identify patients to be considered for preemptive treatment
for PyVAN [strong, moderate].
➨ Screening for BKPyV‐DNAemia by QNAT should be performed monthly
until month 9, then every 3 months until 2 years posttransplant [strong,
moderate].
25. ➨BKPyV‐DNAemia should be confirmed within 3 weeks to be sustained
as plasma BKPyV loads >1000 c/mL (probable PyVAN) [strong,
moderate], or to be increasing to plasma BKPyV loads of >10,000c/mL
(presumptive PyVAN) [strong, high]
26. ➨ The primary treatment of sustained BKPyV‐DNAemia/probable
PyVAN, presumptive PyVAN, or proven PyVAN in kidney transplant
patients without concurrent acute rejection is reducing maintenance
immunosuppression [strong, moderate].
27. ➨Tacrolimus trough levels are commonly targeted to <6 ng/mL [strong,
moderate],
➨Cyclosporine trough levels to <150 ng/mL [strong, moderate],
➨MMF daily dose equivalents of less or equal than half of the daily
maintenance dose [strong, moderate]
➨Sirolimus trough levels of <6 ng/mL [weak, very low]
28. ➨ Additional strategies:
➨Switching from tacrolimus to low‐ dose cyclosporine-A
➨Switching from the CNI to sirolimus
➨Switching from MMF to low‐dose sirolimus
➨Switching from MMF to leflunomide [weak, very low].
29. EPSTEIN-BARR VIRUS
➨Epstein- Barr virus (EBV) is implicated in the progression of many
cancers including posttransplant lymphoproliferative disorder (PTLD).
➨Overall, it appears that mTORis have minimal to no clinical benefit in
transplant recipients with EBV-associated PTLD.
30.
31. ➨We recommend reduction in immunosuppression(RIS) to the lowest
tolerated level as initial therapy for nearly all early and late B‐cell
PTLD in patients who do not have rapidly progressive disease
(strong/moderate).
➨There are insufficient data to both prescribe protocols for
immunosuppression reduction and make recommendations for or
against switching to an mTOR inhibitor.
33. mTORis and UTI
Six RCTs (SIR = 4, ERL = 2) with mTOR-I vs CNI treatment showed data on UTIs. There was no
difference for the incidence of UTIs between the treatment groups (OR 0.86, CI 0.71-1.05, P = .14).
Comparable results were seen when the mTOR-I was combined with a
CNI(n=4,SIR=2,ERL=2,OR0.89,CI0.71-1.12,P=.33)
Transpl Infect Dis. 2020;22:e13267.
34. mTORis and pneumonia
The odds ratio for pneumonia was significantly increased under
an mTOR-I therapy without a CNI compared to a CNI treatment
(OR 2.09, CI 1.41-3.12, P < .001)
35. CNI to mTORis conversion:
➨Biopsy-proven calcineurin inhibitor nephrotoxicity
➨Other serious adverse effects of CNI
➨Neurotoxicity
➨Thrombotic microangiopathy
36. mTORis to CNI conversion
➨Pregnancy:
➨mTORis are teratogenic and contraindicated in pregnancy.
➨Heavy proteinuria
➨Elective surgery:
➨Sirolimus is associated with postoperative wound complications(wound
healing).
