This document summarizes recent advances in extracorporeal therapies. It discusses developments like hemofiltration, hemoperfusion with polymyxin B to remove endotoxins, high cut-off membranes that can remove cytokines, and cytokine binding therapies. It also reviews applications of extracorporeal therapies in conditions like sepsis, congestive heart failure, acute neurological injury, and liver failure. Overall, extracorporeal therapies have expanded from a focus on small solute removal to also address inflammatory mediator removal and organ support.
Hemodialysis: management of chronic kidney diseaseSapana Shrestha
Hemodialysis is a mechanical process of removing waste products (toxic nitrogenous substances) and replacing essential substances by the process of diffusion and removal of excess water from body by the process of osmosis by means of artificial kidney (made with modified cellulose or synthetic) through semi-permeable membranes.
During hemodialysis, a hemodialyzer, or artificial kidney, is used to filter fluids and wastes from a dialysis patient's blood. Reuse of a hemodialyzer means that the same hemodialyzer (filter) is used more than once for the same patient. When dialyzers are reused, they are cleaned and disinfected after each treatment.
peritoneal dialysis, management of chronic renal failureSapana Shrestha
Peritoneal dialysis is a technique of dialysis in which solute and fluid exchange occurs between peritoneal capillary blood and dialysis solution in the peritoneal cavity via peritoneal layer with the help of peritoneal catheter.
Hemodialysis: management of chronic kidney diseaseSapana Shrestha
Hemodialysis is a mechanical process of removing waste products (toxic nitrogenous substances) and replacing essential substances by the process of diffusion and removal of excess water from body by the process of osmosis by means of artificial kidney (made with modified cellulose or synthetic) through semi-permeable membranes.
During hemodialysis, a hemodialyzer, or artificial kidney, is used to filter fluids and wastes from a dialysis patient's blood. Reuse of a hemodialyzer means that the same hemodialyzer (filter) is used more than once for the same patient. When dialyzers are reused, they are cleaned and disinfected after each treatment.
peritoneal dialysis, management of chronic renal failureSapana Shrestha
Peritoneal dialysis is a technique of dialysis in which solute and fluid exchange occurs between peritoneal capillary blood and dialysis solution in the peritoneal cavity via peritoneal layer with the help of peritoneal catheter.
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Systemic Capillary Leak Syndrome complicated by severe Rhabdomyolysis: A case...Apollo Hospitals
Idiopathic systemic capillary leak syndrome is characterized by episodes of increased capillary permeability resulting in severe hypovolemic shock, hem concentration and hypoalbuminemia. Rarely, patient may develop compartment syndrome due to increased interstitial fluid resulting severe myonecrosis. Here, we are reporting a case with review of therapeutic aspects of this rare syndrome.
Provision of ideal transfusion support – The essence of thalassemia careApollo Hospitals
Thalassemia major is a major cause of transfusion dependence among patients world over. Provision of an adequate, uninterrupted and safe blood supply for these patients is the responsibility of the blood services as well as the society as a whole. Thalassemia management has evolved over a period of time and so have transfusion services. Various technological advancements have been introduced in the last few decades in order to enhance blood safety. Adoption of these newer technologies coupled with increasing awareness about voluntary blood donation in the general population can go a long way in improving the life expectancy as well the quality of life in these children.
Systemic capillary leak syndrome complicated by severe rhabdomyolysisApollo Hospitals
Idiopathic systemic capillary leak syndrome also known as
Clarkson’s disease is a potentially fatal disorder. Prompt institution
of appropriate therapy as outlined here can reduce the
morbidity and prevent complication.
Spleen is an important organ of the reticuloendothelial system. It plays a crucial role in the immunological system of the body. Understanding the consequences and diagnosis of hyposlenic and asplenic states is essential. Splenectomy is performed for a variety of indications ranging from haematological conditions to trauma. Complications of splenectomy include surgical as well as immunological. Overwhelming post splenectomy infection is one of the most dreaded complication with high mortality. The physiological basis of immunological function of the spleen, hyposplenism and complications of splenectomy are presented in this paper.
Malignant Mixed Mullerian Tumor – Case Reports and Review ArticleApollo Hospitals
Malignant mixed mullerian tumors are very rare genital tumors. They are biphasic neoplasms composed of an admixture of malignant epithelial and mesenchymal elements. In descending order of frequency they originate in the uterus, ovaries, fallopian tubes, cervix and vagina. Also they arise denovo from peritoneum. They are highly aggressive and tend to occur in postmenopausal low parity women. Because of rarity, there is as such no treatment guidelines available. Multimodality treatment in the form of radical surgery followed by adjuvant chemotherapy or radiotherapy or combined chemoradiation gives a better prognosis & outcome. Two case reports of such tumors, one from ovary and other from penitoneum are presented along with the review of literature.
Intra-Fetal Laser Ablation of Umbilical Vessels in Acardiac Twin with Success...Apollo Hospitals
To interrupt blood supply to the acardiac twin in a case of TRAP sequence of monochorionic diamniotic multiple pregnancy to allow for continuation of the normal twin.
Breast Cancer in Young Women and its Impact on Reproductive FunctionApollo Hospitals
Breast cancer is the most common cancer in women in developed countries. Chemotherapy for breast cancer is likely to negatively impact on reproductive function. We review current treatment; effects on reproductive function; breastfeeding and management of menopausal symptoms following breast cancer.
Turner syndrome (gonadal dysgenesis) is one of the most common chromosomal abnormalities occuring 1 in 2500 to 1 in 3000 live-born girls. It is an important cause of short stature in girls and primary amenorrhea in young women that is usually caused by loss of part or all of an X chromosome. This review briefly summarises the current knowledge about the syndrome and the management strategies.
Due to pregnancy thyroid economy is affected with changes in iodine metabolism, TBG and development of maternal goiter. The incidence of hypothyroidism in pregnancy is quite common with autoimmune hypothyroidism being the most important cause. Overt as well as subclinical hypothyroidism has a varied impact on maternal and neonatal outcome. After multiple studies also, routine screening in pregnancy for hypothyroidism can still not be recommended. Management mainly comprises of dosage adjustments as soon as pregnancy is diagnosed based on results of thyroid function tests. The aim should be to keep FT4 at the upper end of normal range.
Growth Hormone Deficiency (GHD) can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. Growth harmone (GH) therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks of GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual.
Advances in the management of thalassemia have led to marked improvements in the life span and quality of life of children and young adults. This poses new challenges for the treating physicians. There is now increasing recognition that thalassemics have impaired bone health which is multifactorial in etiology. This paper aims to highlight the factors that predispose these patients to osteoporosis and suggests measures to minimise the impact on bone health.
Laparoscopic Excision of Foregut Duplication Cyst of StomachApollo Hospitals
Retroperitoneal gastric duplication cysts lined by ciliated columnar epithelium are extremely rare lesions and its presentation during adulthood is a diagnostic challenge for treating clinicians. This entity often resembles cystic pancreatic neoplasm, retroperitoneal cystic lesions and sometimes as an adrenal cystic neoplasm. Correct diagnosis on the basis of radiological investigation is difficult and histopathologic analysis. We report a case of gastric duplication cyst in a 16year old girl that mimicked as a retroperitoneal /pancreatic /adrenal cystic lesion and was successfully managed by laparoscopy.
Occupational Blood Borne Infections: Prevention is Better than CureApollo Hospitals
Viral infections like HIV, hepatitis Band C virus pose a big risk to the contacts of individuals with high risk behaviour as well as to the attending health care workers. Blood, semen, vaginal and other potentially infectious materials can transmit the infection to the susceptible contacts. Universal precautions should be strictly implemented during clinical examination, laboratory work and surgical procedures to prevent transmission to the health care providers. Health care workers should receive vaccination for hepatitis B infection. An inadvertent exposure should be managed with proper first aid and infectivity of the source and severity of exposure should be assessed. Severity of exposure is based on the nature and area of exposed surface, mode of injury and volume of infective material. Post-exposure prophylaxis (PEP) should be started as soon as possible after a proper counseling about the effectiveness of post-exposure prophylaxis, side effects and risk of carrying the infection to his familial contacts and its prevention.
Evaluation of Red Cell Hemolysis in Packed Red Cells During Processing and St...Apollo Hospitals
Storage of red cells causes a progressive increase in hemolysis. Inspite of the use of additive solutions for storage and filters for leucoreduction some amount of hemolysis is still inevitable. The extent of hemolysis however should not exceed the permissible threshold for hemolysis even on the 42nd day of storage.
Efficacy and safety of dexamethasone cyclophosphamide pulse therapy in the tr...Apollo Hospitals
Various drugs used to treat pemphigus can cause remission, but none can provide permanent remission as relapses are common. With the introduction of DCP in pemphigus in 1984, patients started being in prolonged/permanent remission. This study was done to compare the efficacy of DCP to oral corticosteroids and cyclophosphamide in combination.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)Apollo Hospitals
Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30–35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5–15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. It is characterised by fever, rash and internal organ involvement. Prompt diagnosis is vital, along with identification and early withdrawal of suspect medicines and avoidance of re-exposure to the responsible agent is essential. Cross-reactivity to structurally-related syndrome caused by Carbamazepine medicines is common, thus first-degree relatives may be predisposed to developing this syndrome. We report a case of DRESS secondary to use of Carbamazepine.
Difficult Laparoscopic Cholecystectomy-When and Where is the Need to Convert?Apollo Hospitals
Laparoscopic cholecystectomy has now become the treatment of choice for the gall bladder stone. With increasing experience, surgeon has started to take more difficult cases which were considered relative contra indications for laparoscopic removal of gall bladder few years back.
We conducted this study at our hospital and included all laparoscopic cholecystectomy done from May'08 to January'10. Total time taken in surgery, conversion rate and complication rate were analysed. Factors making laparoscopic cholecystectomy difficult were also analysed. We defined difficult laparoscopic cholecystectomy when we found -dense fibrotic adhesions in and around Callot's triangle, gangrenous gall bladder, empyma, large stone impacted at gall bladder neck, contracted gall bladder, Mirrizi's syndrome, h/o biliary pancreatitis, CBD stones, acute cholecystitis of <72 hrs duration.
Out of 206 cases done during above period, 56 cases were considered difficult. Only two cases were converted to open.
With growing experience and technical advancement surgery can be completed in most of the difficult cases. This is important because recently it is shown in literature that laparoscopic cholecystectomy is associated with less morbidity than open method irrespective of duration of the surgery.
Deep vein thrombosis prophylaxis in a tertiary care center: An observational ...Apollo Hospitals
Deep vein thrombosis (DVT) is a major health problem with substantial mortality and morbidity in medically ill patients. Prevention of DVT by risk factor stratification and subsequent antithrombotic prophylaxis in moderate- to severe-risk category patients is the most rational means of reducing morbidity and mortality.
The spread of dengue and dengue haemorrhagic fever is increasing, atypical manifestations are also on the rise, although they may be under reported because of lack of awareness. We report two such cases of dengue hemorrhagic fever with hepatitis, intraocular hemorrhage, ARDS and myocarditis.
A 71-year-old male presented in ENT department with dysphagia for last three weeks, more to solids than liquids. He had a hard bony bulge in the posterior pharyngeal wall on palpation and hence was referred for an Orthopaedic opinion. Lateral radiograph of the cervical spine revealed diffuse ossification of the anterior longitudinal ligament. This ossification was extending almost half the width of the cervical body from its anterior body at C1 and C2 vertebra level.
Pediatric Liver Transplant (LT) is now an established procedure for End Stage Liver Disease (ESLD) with biliary atresia being the commonest indication. Intensive pre-transplant evaluation, nutritional buildup and immunization are the fundamental pre-requisites of a successful LT. With improvement in surgical micro-anastomotic techniques and superior immunosuppressive regimens the success rate of pediatric LT is in excess of 90%. Most of the transplants in our country however are Living related, due to which a fairly large number of children expire awaiting a donor liver. There should be a concerted effort to evolve the cadaveric donation program, so that majority of the children are benefitted.
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
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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 Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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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.
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Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/apme
Review Article
Recent advances in extracorporeal therapies
Shamik H. Shah*
ISN Fellow, Department of Nephrology, Apollo Hospitals, Gandhinagar, Ahmedabad, Gujarat 382428, India
article info abstract
Article history: Continuous renal replacement therapies (CRRT) started as continuous arterio-venous he-
Received 31 December 2012 modialysis (CAVH)2 in the 1970s. Since then, the last 4 decades have seen numerous im-
Accepted 3 January 2013 provements in extracorporeal therapies. Some of the notable improvements have been the
Available online 22 January 2013 development of veno-venous therapies, the development of special low resistance filters
with special geometry and fibers and improved machine safety with the use of micro-
Keywords: processors and sensors.
Hemoperfusion Classic extracorporeal therapies have focused on the removal of small solutes for effi-
Polymyxin B cacy. However, it is well known that the characteristics of some solutes make their removal
High cut off (HCO) membranes difficult. Also, limitations in efficiency of dialysis membranes, advances in hemadsorption
Cytokine binding therapies and the development of newer filters have led to the application of extracorporeal ther-
apies in the management of patients with multi-organ failure and sepsis, refractory con-
gestive heart failure, acute neurologic injury, liver failure and patients with various other
ailments.
Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
1. Introduction advances in hemadsorption and the development of newer
filters have led to the application of extracorporeal therapies in
Dr. Willem Kolff is considered to be the father of extrac- the management of patients with multi-organ failure and
orporeal therapies. This young Dutch physician constructed sepsis, refractory congestive heart failure, acute neurologic
the first dialyzer in 1943.1 injury, liver failure and patients with various other ailments.
Continuous renal replacement therapies (CRRT) started as In this article, we will look at some of the recent advances
continuous arterio-venous hemodialysis (CAVH)2 in the 1970s. in extracorporeal therapies in the management of such
Since then, the last 4 decades have seen numerous improve- patients.
ments in extracorporeal therapies. Some of the notable im-
provements have been the development of veno-venous
therapies, the development of special low resistance filters 2. Sepsis
with special geometry and fibers and improved machine
safety with the use of microprocessors and sensors. Sepsis is responsible for more than 20% of ICU admissions.
Classic extracorporeal therapies have focused on the Despite recent advances in therapy, the mortality remains
removal of small solutes for efficacy. However, it is well known disappointingly high.3
that the characteristics of some solutes make their removal At present, it is believed that the sepsis syndrome reflects
difficult. Also, limitations in efficiency of dialysis membranes, an imbalance of pro- and anti-inflammatory mediators,
* Tel.: þ91 9924449956.
E-mail address: shamik.shah@yahoo.com.
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http://dx.doi.org/10.1016/j.apme.2013.01.003
3. a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 e6 3
resulting in immunodysregulation. Either group of mediators have published their experience in myoglobinuric acute kid-
can be present in excess, in different compartments, and at ney injury.12 In patients with myoglobinuric acute kidney
different times.4 The abnormal “peak concentrations” of me- injury, HCO membranes have been found to reduce serum
diators is believed to be pathogenic. It is this state of systemic myoglobin levels up to 50%.13
“hyperinflammation” that is injurious to many different or-
gans, including the kidneys. This excessive response by the
2.3. Cytokine binding therapies
body is associated with the production of inflammatory mol-
ecules (“mediators”), which circulate in the blood and cause
This therapy is based on biocompatible, highly porous poly-
tissue and organ damage. These molecules are much larger in
mer beads that can actively capture and absorb cytokines in
molecular weight (approximately 5e50 kDa) than conven-
the À10 to 50 kDa range by pore capture and adsorption. The
tional uremic molecules (e.g., urea, creatinine) and are poorly
therapy is flexible as it is compatible with standard hemodi-
removed by standard high-flux membranes.
alysis machines. It also aims to reduce cytokines and mitigate
cytokine storm that is associated with multiple organ failure
2.1. Hemoperfusion with polymyxin B
and death in critical care illness.
These columns, such as CytoSorb, CYT-860-DHP, Lixelle,
Hemoperfusion is a process to remove a toxic substance from
CTR-001 and MPCF-X, have excellent adsorption rates for in-
a patient’s blood by pumping the blood over an absorbent
flammatory cytokines such as TNF-alpha, IL-1beta, IL-6 and
surface. The inside of a column is packed with polystyrene
IL-8.14
fibers coated with the antibiotic polymyxin B. This material
Various animal models have demonstrated a beneficial
has a high affinity for endotoxin and as blood passes through
effect on inflammatory response and survival.15,16
the column, endotoxin is tightly adsorbed onto the polymyxin
In addition to sepsis, these columns have been successfully
B coated fibers. This process is known as direct hemoperfu-
utilized in treatment of idiopathic thrombocytopenic pur-
sion with polymyxin (DHP-PMX) and has been certified for use
pura17 and digoxin intoxication18 and dialysis related
in Europe since 1998 and in Japan since 2004.
amyloidosis.19
Several prospective randomized controlled trials (RCTs)
have been conducted in European countries. The first RCT,
performed in six European academic medical centers in 2005,5 2.4. Coupled plasma filtration and adsorption (CPFA)
concluded that PMX-DHP is associated with improved hemo-
dynamic status and cardiac function. Coupled plasma filtrationeadsorption (CPFA) is an extrac-
Subsequently, a meta-analysis of PMX-DHP was presented orporeal therapy that uses plasma filtration associated with
in Italy in 2007.6 This systematic review found positive effects an adsorbent cartridge and hemofiltration in post dilution to
of PMX-DHP on mean arterial pressure and dopamine/dobut- remove cytokines and inflammatory mediators associated
amine use, PaO2/FiO2 ratio, endotoxin removal, and mortality. with septic shock and severe sepsis.
However, like most trials on extracorporeal therapies, none of In in-vitro studies conducted by Livigni et al, the resin used
the studies was double-blinded. The EUPHAS study,7 a multi- in the CPFA adsorptive cartridge showed higher than 80%
center randomized controlled trial (RCT) performed in ten adsorption under both static and dynamic conditions for: IL-
Italian intensive care units in 2009, found that PMX-DHP 1a, IL-6, IL-8, MIP-1a and MIP-1b, TNFa, MCP, myoglobin.20
improved 28-day survival, blood pressure, vasopressor A small randomized trial by Hu et al21 in 14 patients
requirement, and degree of organ failure. showed that CPFA could be superior to high volume hemofil-
Two more RCTs, the ABDO-MIX and EUPHRATES studies, tration (HVHF) in improving the clinical manifestations and
the primary end points of which are 28-day mortality, were eliminating inflammatory mediators.
started in Europe and the United States at the end of 2010 and In patients with severe acute pancreatitis, 1 group of pa-
will hopefully provide more answers. tients was treated with continuous veno-venous hemofiltra-
tion (CVVH). The other group received CPFA with CVVH and
2.2. High cut off (HCO) membranes was found to be superior in terms of oxygenation index (PaO2/
FiO2), mean arterial pressure, serum amylase, blood urea ni-
A new generation of hemodialysis membranes with molecular trogen and 28-day mortality.22
weight cut-offs closer to that of the native kidney (65 kDa) has Fifty-five septic patients were enrolled in an Italian
led to work assessing their potential utility across several multi-centric study.23 Every patient had four CPFA treat-
different clinical scenarios. ments. The investigators evaluated hemodynamic parame-
HCO membranes effectively remove cytokines from blood. ters, norepinephrine dosage, PaO2/FiO2 ratio, plasma IL-6,
Treatment using HCO membranes has beneficial effects on and procalcitonin (PCT). They concluded that CPFA may
immune cell function and increases survival in animal models improve hemodynamic status and respiratory function by
of sepsis. In-vitro studies have shown that high cut-off hae- plasma filtration and adsorption of proinflammatory
mofilters achieve high clearances for inflammatory mediators mediators.
like IL-6 and TNF-a.8,9 Preliminary clinical studies show that Turani et al enrolled 77 patients in a study comparing CPFA
HCO membranes decrease plasma cytokine levels and the with continuous veno-venous hemodialysis (CVVHDF). The
need for vasopressor therapy.10 authors found that CPFA was more efficient than CVVHDF in
Clinicians are now using these membranes for the treat- removing IL-6 and procalcitonin (PCT) and in improving he-
ment of myeloma kidney11 and rhabdomyolysis. Premru et al modynamic status.24
4. 4 a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 e6
treated with ultrafiltration had a more pronounced reduction
3. Extracorporeal carbon dioxide removal in signs and symptoms of HF and a significant decrease in
(ECCO2R) plasma aldosterone and NT-proBNP levels than the diuretic
group. The ultrafiltration group also showed a significant
Extracorporeal membrane carbon dioxide removal is used to improvement in stroke volume index, cardiac index, cardiac
treat respiratory failure in critically ill patients. The aim is to power output and various other criteria.
remove excess carbon dioxide from the blood. The patient will
still need to receive oxygen by mechanical ventilation. Blood is
drawn from the circulation and passed through a synthetic 6. CRRT in acute neurologic injury
membrane, where carbon dioxide is removed, before it is
returned to the circulation. Little is known about the effects of hemodialysis on the
Kolobow et al25 first described the use of veno-venous injured brain, however; concern exists over the use of inter-
carbon dioxide removal (VVCO2R) in an experimental sheep mittent hemodialysis in patients with acute brain injury (ABI)
model. Since then, a number of studies have shown that due to its hemodynamic effects and increased intracranial
ECCO2R effectively allows the decoupling of oxygenation from pressure (ICP) associated with therapy. Continuous renal
CO2 removal. replacement therapy (CRRT) has become the preferred
In a study by Terragni et al,26 VV-ECCO2R successfully method of renal support in these patients.
treated hypercapnic acidosis in all patients and allowed the CRRT is an option for the treatment of hypervolemia and in
protective ventilation strategy to continue. The study also theory may improve intracranial compliance.
demonstrated a reduction in bronchoalveolar inflammatory Fletcher et al35 report a case of traumatic brain injury with
cytokines (IL-6, IL-8, IL-1b, IL-Ra) after 72 h of ventilation. In refractory intracranial hypertension in which continuous
another study,27 the authors reported a reduction in mortality hemofiltration was found useful because of gentle removal of
in relation to a retrospective comparator group. fluid, solutes, and inflammatory cytokines.
There have been short case series and anecdotal reports of Another small case series36 also reports the beneficial ef-
use in diverse clinical scenarios like near-fatal asthma, com- fects of CRRT in patients with refractory intracranial
bined head and chest injury, as a bridge to transplant and in hypertension.
facilitating weaning and transfer of patients.
7. Liver failure
4. Cell binding therapies
An accumulation of both water-soluble and water-insoluble,
Researchers have hypothesized that exposing circulating protein-bound, metabolic waste products occurs in patients
blood to cells outside the body would add antimicrobial or with acute or acute on chronic liver failure. Conventional
inflammation modulating properties. Such bioartificial de- extracorporeal blood purification techniques based on dif-
vices may help in critical differentiated transport and improve fusion and/or convection may only eliminate small molecular
endocrine and metabolic functions of the kidney.28 weight, water-soluble compounds. In recent years, fractio-
Altrichter et al have published their experience of a pilot nated plasma separation and adsorption (FPSA) has been
study of 10 patients with septic shock in which they demon- introduced for extracorporeal liver support therapy.
strated reduced need for pressor support and improvements Oppert et al37 have published data about 23 patients trea-
in biomarkers of sepsis.29 ted with FPSA with the Prometheus system. In 40 sessions,
this therapy significantly reduced bilirubin levels and accor-
ded a survival rate of 26%. However, in another randomized
5. Hemofiltration in congestive heart failure study,38 the results were not that encouraging.
Huang et al39 conducted a prospective, randomized con-
Extracorporeal ultrafiltration (UF) is found to be useful in pa- trolled study to evaluate the effects of plasma exchange (PE)
tients with refractory congestive heart failure (rCHF). It has with molecular adsorbent re-circulating system (MARS) on
been seen that after UF, right atrial pressure and pulmonary patients with acute on chronic liver failure and hepatic en-
wedge pressure decrease, pulmonary and peripheral edema cephalopathy. They found that PE þ MARS therapy effectively
reduce, mechanical lung function improves and diuretic effi- reduces serum bilirubin levels and is more cost effective.
cacy is restored.30e32
In the UNLOAD33 trial, UF produced greater fluid reduction
and fewer heart failure (HF) rehospitalizations than IV di- 8. Conclusion
uretics in 200 hospitalized patients. The authors observed that
despite similar fluid loss with UF and continuous diuretic There have been tremendous innovations and developments
infusion, fewer HF rehospitalizations equivalents occurred in extracorporeal therapies over the past few decades. Rapid
only with UF. Removal of isotonic fluid by UF compared with strides are being made in diverse therapeutic areas. Newer
hypotonic urine by diuretics more effectively reduced total developments have made the possibility of multi-organ sup-
body sodium in congested HF patients. port therapy a reality.
In another trial,34 thirty patients with decompensated HF All of these approaches are yet to be proven in a convincing
were randomly assigned to diuretics or ultrafiltration. Patients manner. To that end, many large trials are under way. In this
5. a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 e6 5
exciting new realm of extracorporeal therapies, nephrologists endotoxin-induced shock in rats. Ther Apher Dial. 2006
should join hands with colleagues from other specialties and Feb;10(1):49e53.
lead the way. 17. Takenaka T, Suzuki H. Lixelle ameliorates idiopathic
thrombocytopenic purpura. Nephrol Dial Transplant. 2003 May
1;18(5):1032e1033.
18. Kaneko T, Kudo M, Okumura T, et al. Successful treatment of
Conflicts of interest digoxin intoxication by haemoperfusion with specific
columns for b2-microgloblin-adsorption (Lixelleä) in
The author has none to declare. a maintenance haemodialysis patient. Nephrol Dial Transplant.
2001 Jan 1;16(1):195e196.
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microglobulin adsorption column in treating dialysis-related
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