Non-Alcoholic Fatty Liver Disease (NAFLD) has become a significant health concern not only in the US but also worldwide due to the
global obesity epidemic. Although the natural course in the majority
of NAFLD patients is relatively benign, those with non-alcoholic
steatohepatitis (NASH) are at an increased risk of disease progression, leading to hepatic fibrosis, cirrhosis, end-stage liver disease
(ESLD), and hepatocellular carcinoma (HCC).
Non Alcoholic Fatty Liver Disease: A New Urban Epidemic.KETAN VAGHOLKAR
This document discusses non-alcoholic fatty liver disease (NAFLD), which has become very common in urban populations. NAFLD ranges from simple fatty liver to non-alcoholic steatohepatitis (NASH), which is characterized by fatty changes, inflammation, and fibrosis that can progress to cirrhosis. The main causes are obesity, insulin resistance, and dyslipidemia. Weight loss and improving insulin sensitivity through diet and exercise are the primary treatment approaches. Medications like vitamin E, pioglitazone, and metformin may also provide benefits, but more research is still needed on medical therapies for NAFLD.
Endpoint Selection of Non-alcoholic Steatohepatitis Clinical Trialssemualkaira
This document discusses endpoint selection for clinical trials of treatments for non-alcoholic steatohepatitis (NASH). It reviews the limitations of using hard clinical endpoints like mortality and recommends the use of histological surrogate endpoints based on paired liver biopsies. Histological improvements like resolution of NASH without worsening fibrosis or improvement in fibrosis without worsening NASH are accepted endpoints. However, histology has limitations like sampling error and inter-reader variability. The development of reliable non-invasive biomarkers that parallel drug effects and clinical outcomes could provide alternative surrogate endpoints in the future to avoid the invasiveness of biopsies. Validation of surrogate endpoints and longer term studies are still needed to prove clinical benefits.
Core Components of the Metabolic Syndrome in Nonalcohlic Fatty Liver DiseaseIOSR Journals
This study examined the association between nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in Bangladeshi patients. The study included 67 patients diagnosed with NAFLD and 50 healthy controls matched for age and BMI. Results found that NAFLD patients had higher levels of insulin resistance, triglycerides, and central obesity compared to controls. However, no significant association was found between MetS and NAFLD when defined by common diagnostic criteria. Individual components of MetS like dyslipidemia, central obesity, and high postprandial glucose were significantly associated with NAFLD on logistic regression analysis. The study concludes that while various MetS components are linked to NAFLD in
This document provides a narrative review of understanding the development of malnutrition in hemodialysis patients. It discusses malnutrition as having origins from both iatrogenic and non-iatrogenic factors. Iatrogenic factors refer to those resulting inadvertently from dialysis treatment itself, such as nutrient losses during dialysis and use of certain dialysis membranes and techniques. Non-iatrogenic factors include inadequate dietary intake due to poor appetite, diet quality issues, and psychosocial or financial barriers. Understanding the origin of factors contributing to malnutrition in dialysis patients is important for personalized patient care and determining treatment strategies.
The document discusses the potential for modulating gasotransmitters like nitric oxide, carbon monoxide, and hydrogen sulfide to treat vascular complications of diabetes. It summarizes that these gasotransmitters play roles in vasodilation and reducing oxidative stress, but their levels are reduced in diabetes. Modulating their levels may offer a novel treatment approach by targeting the pathogenesis of microvascular and macrovascular complications. However, more research is needed to validate this approach through animal and human studies before any related therapies can be used clinically.
Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, affecting up to 30% of the global population. NAFLD is closely associated with obesity and type 2 diabetes. While initially characterized by excess fat accumulation in the liver (steatosis), some patients can progress to develop more severe non-alcoholic steatohepatitis (NASH) and liver fibrosis. Accurate staging of fibrosis is important for predicting outcomes but liver biopsy is invasive and not always practical. Non-invasive tests (NITs) using blood tests or imaging can help stratify patients' risk of advanced fibrosis as an alternative to biopsy. Lifestyle modifications addressing diet and exercise are recommended for managing NAFL
This document provides guidance on indications and limitations of bariatric interventions in severely obese children and adolescents with and without nonalcoholic steatohepatitis (NASH). It finds that bariatric surgery can decrease steatosis, inflammation, and fibrosis in NASH, but uncomplicated NAFLD is not an indication. Roux-en-Y gastric bypass is considered safe and effective for adolescents with extreme obesity if long-term follow-up is provided, while laparoscopic adjustable gastric banding is still investigational. More research is needed on other procedures and temporary devices in pediatrics. NASH with significant fibrosis, type 2 diabetes, moderate-to-severe sleep apnea, and pseudot
Abstract— Non Alcoholic Fatty Liver Disease is also becoming public health impotance nowadays. So this study was aimed to determine the association of Non Alcoholic Fatty Liver Disease with metabolic syndrome and Cardio-Vascular disease along with assessment of degree of severity of NAFLD with respect to number of components of metabolic syndrome. This study includes a total of 222 subjects were enrolled as per the inclusion/exclusion criteria, out of which 110 cases who had NAFLD with hepatic steatosis on ultrasonography and 112 subjects who did not have NAFLD were considered control. These cases and controls were interrogated and investigated further. Observations were recorded and association of Non Alcoholic Fatty Liver Disease with metabolic syndrome and Cardio-Vascular disease along with assessment of degree of severity of NAFLD with respect to number of components of metabolic syndrome. Statistical methods used were unpaired student’s t-test for continuous variables, Fischer’s and chi-sq test for categorical variables using bivariate analysis by Graph Pad Instat Version 3.10. Risk was assessed in terms of Odd's Ratio. The patients with MS and NAFLD had a higher proportion of CVD compared with those who did not have NAFLD (29.1 vs 18.1 %). This study concludes that NAFLD is significantly associated with MS; most significant with WC, followed by TG and FBS and thus can be considered as hepatic component of MS. This needs more research with large multi-centric prospective studies to evaluate NAFLD as an independent risk factor for CVD.
Non Alcoholic Fatty Liver Disease: A New Urban Epidemic.KETAN VAGHOLKAR
This document discusses non-alcoholic fatty liver disease (NAFLD), which has become very common in urban populations. NAFLD ranges from simple fatty liver to non-alcoholic steatohepatitis (NASH), which is characterized by fatty changes, inflammation, and fibrosis that can progress to cirrhosis. The main causes are obesity, insulin resistance, and dyslipidemia. Weight loss and improving insulin sensitivity through diet and exercise are the primary treatment approaches. Medications like vitamin E, pioglitazone, and metformin may also provide benefits, but more research is still needed on medical therapies for NAFLD.
Endpoint Selection of Non-alcoholic Steatohepatitis Clinical Trialssemualkaira
This document discusses endpoint selection for clinical trials of treatments for non-alcoholic steatohepatitis (NASH). It reviews the limitations of using hard clinical endpoints like mortality and recommends the use of histological surrogate endpoints based on paired liver biopsies. Histological improvements like resolution of NASH without worsening fibrosis or improvement in fibrosis without worsening NASH are accepted endpoints. However, histology has limitations like sampling error and inter-reader variability. The development of reliable non-invasive biomarkers that parallel drug effects and clinical outcomes could provide alternative surrogate endpoints in the future to avoid the invasiveness of biopsies. Validation of surrogate endpoints and longer term studies are still needed to prove clinical benefits.
Core Components of the Metabolic Syndrome in Nonalcohlic Fatty Liver DiseaseIOSR Journals
This study examined the association between nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in Bangladeshi patients. The study included 67 patients diagnosed with NAFLD and 50 healthy controls matched for age and BMI. Results found that NAFLD patients had higher levels of insulin resistance, triglycerides, and central obesity compared to controls. However, no significant association was found between MetS and NAFLD when defined by common diagnostic criteria. Individual components of MetS like dyslipidemia, central obesity, and high postprandial glucose were significantly associated with NAFLD on logistic regression analysis. The study concludes that while various MetS components are linked to NAFLD in
This document provides a narrative review of understanding the development of malnutrition in hemodialysis patients. It discusses malnutrition as having origins from both iatrogenic and non-iatrogenic factors. Iatrogenic factors refer to those resulting inadvertently from dialysis treatment itself, such as nutrient losses during dialysis and use of certain dialysis membranes and techniques. Non-iatrogenic factors include inadequate dietary intake due to poor appetite, diet quality issues, and psychosocial or financial barriers. Understanding the origin of factors contributing to malnutrition in dialysis patients is important for personalized patient care and determining treatment strategies.
The document discusses the potential for modulating gasotransmitters like nitric oxide, carbon monoxide, and hydrogen sulfide to treat vascular complications of diabetes. It summarizes that these gasotransmitters play roles in vasodilation and reducing oxidative stress, but their levels are reduced in diabetes. Modulating their levels may offer a novel treatment approach by targeting the pathogenesis of microvascular and macrovascular complications. However, more research is needed to validate this approach through animal and human studies before any related therapies can be used clinically.
Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, affecting up to 30% of the global population. NAFLD is closely associated with obesity and type 2 diabetes. While initially characterized by excess fat accumulation in the liver (steatosis), some patients can progress to develop more severe non-alcoholic steatohepatitis (NASH) and liver fibrosis. Accurate staging of fibrosis is important for predicting outcomes but liver biopsy is invasive and not always practical. Non-invasive tests (NITs) using blood tests or imaging can help stratify patients' risk of advanced fibrosis as an alternative to biopsy. Lifestyle modifications addressing diet and exercise are recommended for managing NAFL
This document provides guidance on indications and limitations of bariatric interventions in severely obese children and adolescents with and without nonalcoholic steatohepatitis (NASH). It finds that bariatric surgery can decrease steatosis, inflammation, and fibrosis in NASH, but uncomplicated NAFLD is not an indication. Roux-en-Y gastric bypass is considered safe and effective for adolescents with extreme obesity if long-term follow-up is provided, while laparoscopic adjustable gastric banding is still investigational. More research is needed on other procedures and temporary devices in pediatrics. NASH with significant fibrosis, type 2 diabetes, moderate-to-severe sleep apnea, and pseudot
Abstract— Non Alcoholic Fatty Liver Disease is also becoming public health impotance nowadays. So this study was aimed to determine the association of Non Alcoholic Fatty Liver Disease with metabolic syndrome and Cardio-Vascular disease along with assessment of degree of severity of NAFLD with respect to number of components of metabolic syndrome. This study includes a total of 222 subjects were enrolled as per the inclusion/exclusion criteria, out of which 110 cases who had NAFLD with hepatic steatosis on ultrasonography and 112 subjects who did not have NAFLD were considered control. These cases and controls were interrogated and investigated further. Observations were recorded and association of Non Alcoholic Fatty Liver Disease with metabolic syndrome and Cardio-Vascular disease along with assessment of degree of severity of NAFLD with respect to number of components of metabolic syndrome. Statistical methods used were unpaired student’s t-test for continuous variables, Fischer’s and chi-sq test for categorical variables using bivariate analysis by Graph Pad Instat Version 3.10. Risk was assessed in terms of Odd's Ratio. The patients with MS and NAFLD had a higher proportion of CVD compared with those who did not have NAFLD (29.1 vs 18.1 %). This study concludes that NAFLD is significantly associated with MS; most significant with WC, followed by TG and FBS and thus can be considered as hepatic component of MS. This needs more research with large multi-centric prospective studies to evaluate NAFLD as an independent risk factor for CVD.
There is a high burden of poor cardiovascular-kidney-metabolic health in the population, which affects nearly all organ systems and has a powerful impact on cardiovascular disease incidence. More guidance is needed on definitions, staging, prediction strategies, and algorithms for prevention and treatment of cardiovascular-kidney-metabolic syndrome to optimize health. Therapies now exist that can beneficially impact metabolic risk factors, kidney function and cardiovascular outcomes.
NAFLD Patients have Limited Access to GLP1 Agonists and SGLT2 Inhibitors: NHA...JohnJulie1
This study analyzed medication use among patients with NAFLD and/or advanced fibrosis using NHANES 2017-2018 data. The following key points are summarized:
1. Patients with NAFLD or advanced fibrosis had higher rates of polypharmacy, with more medications and medication classes compared to those without these conditions.
2. While medication usage indicated higher risk of cardiovascular and metabolic issues associated with NAFLD, usage of GLP1 agonists and SGLT2 inhibitors was low among diabetics regardless of NAFLD status.
3. Diabetics with advanced fibrosis had fewer medications on average than those without advanced fibrosis, possibly due to disease progression effects, though access to beneficial therapies like G
This document summarizes a proposed study examining the effect of obesity on nonalcoholic fatty liver disease (NAFLD) and whether nutritional interventions can help. Specifically, it will investigate if obesity increases fat cell (adipocyte) infiltration and inflammation in the liver, and if polyphenolic compounds can inhibit these obesity-induced effects. The study will use a cell culture model mimicking the obese environment to test the impacts of serum from obese individuals on liver cells, with and without polyphenols. The goal is to better understand how obesity promotes NAFLD and potentially identify new treatment options through nutrition.
This document provides a 3-sentence summary of the consensus statement on the comprehensive type 2 diabetes management algorithm:
The consensus statement presents an updated algorithm for the comprehensive management of type 2 diabetes that incorporates new therapies, management approaches, and clinical data. The algorithm is intended to guide clinicians in developing individualized treatment plans considering a patient's risks, complications, and preferences. It addresses lifestyle therapy, obesity, prediabetes, glucose control, hypertension management, dyslipidemia management, and the attributes and principles for selecting antihyperglycemic therapies.
Linking uric acid metabolism to diabetic complicationsMohamedKhamis77
This document discusses the relationship between uric acid metabolism and diabetic complications. It begins by providing background on uric acid metabolism and the factors that determine serum uric acid levels. It then discusses how uric acid levels are associated with type 2 diabetes and metabolic syndrome. Higher uric acid levels have been linked to an increased risk of developing type 2 diabetes. The document also reviews evidence that elevated uric acid levels are associated with a higher risk and worsening of diabetic complications, including neuropathy, retinopathy, nephropathy, foot ulcers, and macrovascular complications. Oxidative stress from xanthine oxidoreductase activity may play a role in these relationships through vascular endothelial damage and insulin resistance.
A case presentation on severe calcific aortic stenosisM.Arumuga Vignesh
This case presentation discusses a 57-year-old male patient admitted to the hospital with dyspnea and a diabetic foot ulcer. The patient was diagnosed with severe calcific aortic stenosis along with comorbidities of hypertension, diabetes, and pleural effusion. Laboratory tests confirmed Klebsiella pneumonia as the cause of the foot ulcer. The patient is being treated with medications including amlodipine, pantoprazole, metronidazole, levofloxacin, furosemide, insulin, and N-acetylcysteine to manage his conditions while addressing any drug interactions and monitoring his health indicators.
This document provides guidelines for the management of acute pancreatitis (AP). It summarizes key recommendations regarding the diagnosis, etiology, risk stratification, and management of AP. The diagnosis of AP is usually established by abdominal pain and elevated serum amylase and/or lipase levels. Contrast-enhanced CT or MRI is only recommended if the diagnosis is unclear or the patient fails to improve. Patients should be stratified based on the presence of organ failure or systemic inflammatory response syndrome and those with organ failure admitted to intensive care. Aggressive intravenous hydration within the first 24 hours and assessment of fluid status is important. Guidelines are also provided for managing gallstone pancreatitis, infectious complications, and interventions.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western countries, affecting 17-46% of adults. NAFLD often parallels metabolic syndrome and its risk factors like obesity and diabetes. The guidelines recommend screening individuals with metabolic risk factors or obesity for NAFLD through procedures to diagnose fatty liver. A liver biopsy is needed to diagnose non-alcoholic steatohepatitis (NASH) by identifying features like steatosis, lobular inflammation and ballooning. Non-invasive markers can help identify those at high risk of fibrosis and reduce the need for biopsies. NAFLD is closely associated with insulin resistance and metabolic syndrome.
This document provides a position statement from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach to treatment that considers individual patient needs, preferences, and tolerances. The statement reviews the evidence on glycemic control and outcomes, discusses the increasing complexity of treatment options, and emphasizes the importance of shared decision making between clinicians and patients.
This document outlines a proposed research study on the prevalence, risk factors, and most common sites of lipodystrophy among type 1 diabetic patients taking subcutaneous insulin at hospitals in Addis Ababa, Ethiopia. The study aims to measure the incidence of lipodystrophy and describe associated risk factors. The retrospective cohort study will collect data from patient charts at two hospitals over the past 2 years and analyze it to compare rates of early- versus late-onset lipodystrophy and identify relationships between lipodystrophy and factors like prematurity, low birth weight, sex, and smoking. If approved, this research could help address gaps in knowledge about an emerging problem and inform policies around resource allocation for diabetic patients in Ethiopia
This document provides guidelines for managing hyperglycemia in type 2 diabetes using a patient-centered approach from the American Diabetes Association and European Association for the Study of Diabetes. It summarizes that intensive glycemic control can reduce microvascular complications but may increase mortality risk. The guidelines emphasize individualizing treatment based on patient preferences, needs, and tolerances. A patient-centered approach engages patients in medical decisions to improve adherence and outcomes for their chronic condition.
This document summarizes modern management options for the uraemic syndrome in chronic kidney disease. It discusses the pathophysiology of the uraemic syndrome and how it affects multiple organ systems. Traditional and non-traditional risk factors for cardiovascular disease are examined. Over 150 uraemic retention products have been identified and are divided into small water-soluble compounds, protein-bound compounds, and larger middle molecules. Progression of chronic kidney disease depends on the underlying cause and risk factors, leading to loss of kidney function over time. Management options aim to target modifiable factors like cardiovascular risk simultaneously.
This document discusses the shift in diabetes management from prescriptive guidelines to individualized care. It outlines several factors that have driven this change, including a lack of evidence supporting one treatment over another and recognition that lasting improvement requires considering patient preferences. The document also describes challenges in implementing individualized care within current healthcare systems. It advocates selecting treatments based on a patient's underlying pathologies and broader cardiovascular risk rather than just their diabetes type.
The document discusses the proposal to change the name of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD). It notes that NAFLD's name does not accurately capture the metabolic nature of the disease. The name change was proposed by an international panel of experts and aims to reduce stigmatization and increase consideration of the disease. If adopted, MAFLD would be used instead of NAFLD to describe fatty liver disease associated with metabolic dysfunction. The document supports the name change as a way to properly frame the growing epidemic of this liver disease.
This document presents a position statement from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs, preferences, and tolerances. Glycemic control is important but must be pursued as part of a multifactorial approach that addresses cardiovascular risk factors. Treatment should be tailored based on disease factors, patient characteristics, and constraints like age and comorbidities. The goal is to encourage shared decision making between clinicians and patients.
Prevalence and identification of fatty liver (FL) risk markers in local Pakis...Syeda Masoom Fatima
1) The study aimed to determine the prevalence of nonalcoholic fatty liver disease (NAFLD) and identify risk markers in the local Pakistani population.
2) Physical data and biochemical profiles were collected from 1366 patients visiting hospitals in Rawalpindi and Islamabad using standardized criteria to diagnose fatty liver disease.
3) Preliminary results found a high prevalence of metabolic syndrome risk factors like obesity, high blood pressure, and diabetes, which are predictors of fatty liver. Further analysis of the data aims to understand the prevalence and risk markers of NAFLD in Pakistan.
This document discusses identifying and managing advanced fibrosis due to nonalcoholic steatohepatitis (NASH). It begins by outlining the impact of advanced fibrosis, including increased risk of liver-related morbidity and mortality as well as potential for rapid progression to cirrhosis in some patients. It then examines challenges with biopsy as the reference standard for identification given sampling error and limitations. Non-invasive tests are presented as an alternative, with sequential use of two tests recommended. The document concludes by emphasizing the importance of identifying advanced fibrosis patients to prevent cirrhosis and complications.
Antihyperglycemic effects of short term resveratrol supplementation in type 2...zanet1
1) The study examined the effects of short term resveratrol supplementation in patients with type 2 diabetes who were receiving standard antidiabetic treatment. 66 patients were randomly assigned to receive either 1 g per day of resveratrol or a placebo for 45 days.
2) Resveratrol treatment significantly decreased systolic blood pressure, fasting blood glucose, HbA1c, insulin, and insulin resistance compared to baseline. HDL was also significantly increased.
3) In contrast, the placebo group had slightly increased fasting glucose and LDL compared to baseline. Liver and kidney function markers were unchanged with resveratrol treatment.
The biomarker of choice in association of dyslipidemia with osteoporosis: A c...SriramNagarajan17
This case study describes a 55-year-old male patient who presented with pain in his lower limb and was diagnosed with both dyslipidemia and osteoporosis based on his medical history and laboratory tests. He had a family history of metabolic diseases and consumed excessive alcohol. His dyslipidemia was diagnosed based on genetic predisposition and lipid profile showing low HDL and high LDL levels. His osteoporosis was diagnosed a year and a half later when he fractured his femur during a walk and was found to have low bone mineral density. The conclusion is that low HDL and high LDL levels in the lipid profile are the biomarker of choice for associating dyslipidemia with osteoporosis as these
Background: Nonalcoholic Fatty Liver Disease (NAFLD) is the most common liver disease in the developed countries. Patients with Nonalcoholic Steatohepatitis (NASH), a subset of NAFLD, are at risk for progressive liver disease and in need of effective treatment options. There is a lack of data assessing sleeve gastrectomy and their effect on NAFLD.
Objective: To assess the effects of Sleeve Gastrectomy (SG) on NAFLD.
Methods: An online search of PubMed, Medline, and Google Scholar was independently carried out by two researchers using key words like Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Steato-Hepatitis, Bariatric Surgery, Obesity Surgery, Sleeve Gastrectomy and Liver Biopsy, percutaneous liver biopsy, to identify all articles. Articles were also identified from references of relevant articles. All sleeve gastrectomies that had ntraoperative and postoperative liver biopsies were included.
Challenges and Practices in Modern Hand Surgery Nursingsemualkaira
Purpose This study aims to explore the changes in the patient spectrum and the challenges and practices in nursing brought about by
the evolution of modern hand surgery patients and medical development. Methods A retrospective study was conducted on clinical
data from 21,512 hand surgery patients in our hospital over the
past 15 years. T
The Impact Visceral Abdominal Fat and Muscle Mass Using CT on Patients with S...semualkaira
The association between abdominal visceral
fatty area (VFA) and muscle mass and mortality is not fully understood despite the fact that being overweight is an established
risk factor for the onset and severity of acute pancreatitis (AP). We
assessed the effect of VFA on severe AP (SAP) mortality
More Related Content
Similar to Future Considerations of Biological Disparities in Drug Development for NAFLD/ NASH: Trial Design and Analysis
There is a high burden of poor cardiovascular-kidney-metabolic health in the population, which affects nearly all organ systems and has a powerful impact on cardiovascular disease incidence. More guidance is needed on definitions, staging, prediction strategies, and algorithms for prevention and treatment of cardiovascular-kidney-metabolic syndrome to optimize health. Therapies now exist that can beneficially impact metabolic risk factors, kidney function and cardiovascular outcomes.
NAFLD Patients have Limited Access to GLP1 Agonists and SGLT2 Inhibitors: NHA...JohnJulie1
This study analyzed medication use among patients with NAFLD and/or advanced fibrosis using NHANES 2017-2018 data. The following key points are summarized:
1. Patients with NAFLD or advanced fibrosis had higher rates of polypharmacy, with more medications and medication classes compared to those without these conditions.
2. While medication usage indicated higher risk of cardiovascular and metabolic issues associated with NAFLD, usage of GLP1 agonists and SGLT2 inhibitors was low among diabetics regardless of NAFLD status.
3. Diabetics with advanced fibrosis had fewer medications on average than those without advanced fibrosis, possibly due to disease progression effects, though access to beneficial therapies like G
This document summarizes a proposed study examining the effect of obesity on nonalcoholic fatty liver disease (NAFLD) and whether nutritional interventions can help. Specifically, it will investigate if obesity increases fat cell (adipocyte) infiltration and inflammation in the liver, and if polyphenolic compounds can inhibit these obesity-induced effects. The study will use a cell culture model mimicking the obese environment to test the impacts of serum from obese individuals on liver cells, with and without polyphenols. The goal is to better understand how obesity promotes NAFLD and potentially identify new treatment options through nutrition.
This document provides a 3-sentence summary of the consensus statement on the comprehensive type 2 diabetes management algorithm:
The consensus statement presents an updated algorithm for the comprehensive management of type 2 diabetes that incorporates new therapies, management approaches, and clinical data. The algorithm is intended to guide clinicians in developing individualized treatment plans considering a patient's risks, complications, and preferences. It addresses lifestyle therapy, obesity, prediabetes, glucose control, hypertension management, dyslipidemia management, and the attributes and principles for selecting antihyperglycemic therapies.
Linking uric acid metabolism to diabetic complicationsMohamedKhamis77
This document discusses the relationship between uric acid metabolism and diabetic complications. It begins by providing background on uric acid metabolism and the factors that determine serum uric acid levels. It then discusses how uric acid levels are associated with type 2 diabetes and metabolic syndrome. Higher uric acid levels have been linked to an increased risk of developing type 2 diabetes. The document also reviews evidence that elevated uric acid levels are associated with a higher risk and worsening of diabetic complications, including neuropathy, retinopathy, nephropathy, foot ulcers, and macrovascular complications. Oxidative stress from xanthine oxidoreductase activity may play a role in these relationships through vascular endothelial damage and insulin resistance.
A case presentation on severe calcific aortic stenosisM.Arumuga Vignesh
This case presentation discusses a 57-year-old male patient admitted to the hospital with dyspnea and a diabetic foot ulcer. The patient was diagnosed with severe calcific aortic stenosis along with comorbidities of hypertension, diabetes, and pleural effusion. Laboratory tests confirmed Klebsiella pneumonia as the cause of the foot ulcer. The patient is being treated with medications including amlodipine, pantoprazole, metronidazole, levofloxacin, furosemide, insulin, and N-acetylcysteine to manage his conditions while addressing any drug interactions and monitoring his health indicators.
This document provides guidelines for the management of acute pancreatitis (AP). It summarizes key recommendations regarding the diagnosis, etiology, risk stratification, and management of AP. The diagnosis of AP is usually established by abdominal pain and elevated serum amylase and/or lipase levels. Contrast-enhanced CT or MRI is only recommended if the diagnosis is unclear or the patient fails to improve. Patients should be stratified based on the presence of organ failure or systemic inflammatory response syndrome and those with organ failure admitted to intensive care. Aggressive intravenous hydration within the first 24 hours and assessment of fluid status is important. Guidelines are also provided for managing gallstone pancreatitis, infectious complications, and interventions.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western countries, affecting 17-46% of adults. NAFLD often parallels metabolic syndrome and its risk factors like obesity and diabetes. The guidelines recommend screening individuals with metabolic risk factors or obesity for NAFLD through procedures to diagnose fatty liver. A liver biopsy is needed to diagnose non-alcoholic steatohepatitis (NASH) by identifying features like steatosis, lobular inflammation and ballooning. Non-invasive markers can help identify those at high risk of fibrosis and reduce the need for biopsies. NAFLD is closely associated with insulin resistance and metabolic syndrome.
This document provides a position statement from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach to treatment that considers individual patient needs, preferences, and tolerances. The statement reviews the evidence on glycemic control and outcomes, discusses the increasing complexity of treatment options, and emphasizes the importance of shared decision making between clinicians and patients.
This document outlines a proposed research study on the prevalence, risk factors, and most common sites of lipodystrophy among type 1 diabetic patients taking subcutaneous insulin at hospitals in Addis Ababa, Ethiopia. The study aims to measure the incidence of lipodystrophy and describe associated risk factors. The retrospective cohort study will collect data from patient charts at two hospitals over the past 2 years and analyze it to compare rates of early- versus late-onset lipodystrophy and identify relationships between lipodystrophy and factors like prematurity, low birth weight, sex, and smoking. If approved, this research could help address gaps in knowledge about an emerging problem and inform policies around resource allocation for diabetic patients in Ethiopia
This document provides guidelines for managing hyperglycemia in type 2 diabetes using a patient-centered approach from the American Diabetes Association and European Association for the Study of Diabetes. It summarizes that intensive glycemic control can reduce microvascular complications but may increase mortality risk. The guidelines emphasize individualizing treatment based on patient preferences, needs, and tolerances. A patient-centered approach engages patients in medical decisions to improve adherence and outcomes for their chronic condition.
This document summarizes modern management options for the uraemic syndrome in chronic kidney disease. It discusses the pathophysiology of the uraemic syndrome and how it affects multiple organ systems. Traditional and non-traditional risk factors for cardiovascular disease are examined. Over 150 uraemic retention products have been identified and are divided into small water-soluble compounds, protein-bound compounds, and larger middle molecules. Progression of chronic kidney disease depends on the underlying cause and risk factors, leading to loss of kidney function over time. Management options aim to target modifiable factors like cardiovascular risk simultaneously.
This document discusses the shift in diabetes management from prescriptive guidelines to individualized care. It outlines several factors that have driven this change, including a lack of evidence supporting one treatment over another and recognition that lasting improvement requires considering patient preferences. The document also describes challenges in implementing individualized care within current healthcare systems. It advocates selecting treatments based on a patient's underlying pathologies and broader cardiovascular risk rather than just their diabetes type.
The document discusses the proposal to change the name of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD). It notes that NAFLD's name does not accurately capture the metabolic nature of the disease. The name change was proposed by an international panel of experts and aims to reduce stigmatization and increase consideration of the disease. If adopted, MAFLD would be used instead of NAFLD to describe fatty liver disease associated with metabolic dysfunction. The document supports the name change as a way to properly frame the growing epidemic of this liver disease.
This document presents a position statement from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs, preferences, and tolerances. Glycemic control is important but must be pursued as part of a multifactorial approach that addresses cardiovascular risk factors. Treatment should be tailored based on disease factors, patient characteristics, and constraints like age and comorbidities. The goal is to encourage shared decision making between clinicians and patients.
Prevalence and identification of fatty liver (FL) risk markers in local Pakis...Syeda Masoom Fatima
1) The study aimed to determine the prevalence of nonalcoholic fatty liver disease (NAFLD) and identify risk markers in the local Pakistani population.
2) Physical data and biochemical profiles were collected from 1366 patients visiting hospitals in Rawalpindi and Islamabad using standardized criteria to diagnose fatty liver disease.
3) Preliminary results found a high prevalence of metabolic syndrome risk factors like obesity, high blood pressure, and diabetes, which are predictors of fatty liver. Further analysis of the data aims to understand the prevalence and risk markers of NAFLD in Pakistan.
This document discusses identifying and managing advanced fibrosis due to nonalcoholic steatohepatitis (NASH). It begins by outlining the impact of advanced fibrosis, including increased risk of liver-related morbidity and mortality as well as potential for rapid progression to cirrhosis in some patients. It then examines challenges with biopsy as the reference standard for identification given sampling error and limitations. Non-invasive tests are presented as an alternative, with sequential use of two tests recommended. The document concludes by emphasizing the importance of identifying advanced fibrosis patients to prevent cirrhosis and complications.
Antihyperglycemic effects of short term resveratrol supplementation in type 2...zanet1
1) The study examined the effects of short term resveratrol supplementation in patients with type 2 diabetes who were receiving standard antidiabetic treatment. 66 patients were randomly assigned to receive either 1 g per day of resveratrol or a placebo for 45 days.
2) Resveratrol treatment significantly decreased systolic blood pressure, fasting blood glucose, HbA1c, insulin, and insulin resistance compared to baseline. HDL was also significantly increased.
3) In contrast, the placebo group had slightly increased fasting glucose and LDL compared to baseline. Liver and kidney function markers were unchanged with resveratrol treatment.
The biomarker of choice in association of dyslipidemia with osteoporosis: A c...SriramNagarajan17
This case study describes a 55-year-old male patient who presented with pain in his lower limb and was diagnosed with both dyslipidemia and osteoporosis based on his medical history and laboratory tests. He had a family history of metabolic diseases and consumed excessive alcohol. His dyslipidemia was diagnosed based on genetic predisposition and lipid profile showing low HDL and high LDL levels. His osteoporosis was diagnosed a year and a half later when he fractured his femur during a walk and was found to have low bone mineral density. The conclusion is that low HDL and high LDL levels in the lipid profile are the biomarker of choice for associating dyslipidemia with osteoporosis as these
Background: Nonalcoholic Fatty Liver Disease (NAFLD) is the most common liver disease in the developed countries. Patients with Nonalcoholic Steatohepatitis (NASH), a subset of NAFLD, are at risk for progressive liver disease and in need of effective treatment options. There is a lack of data assessing sleeve gastrectomy and their effect on NAFLD.
Objective: To assess the effects of Sleeve Gastrectomy (SG) on NAFLD.
Methods: An online search of PubMed, Medline, and Google Scholar was independently carried out by two researchers using key words like Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Steato-Hepatitis, Bariatric Surgery, Obesity Surgery, Sleeve Gastrectomy and Liver Biopsy, percutaneous liver biopsy, to identify all articles. Articles were also identified from references of relevant articles. All sleeve gastrectomies that had ntraoperative and postoperative liver biopsies were included.
Similar to Future Considerations of Biological Disparities in Drug Development for NAFLD/ NASH: Trial Design and Analysis (20)
Challenges and Practices in Modern Hand Surgery Nursingsemualkaira
Purpose This study aims to explore the changes in the patient spectrum and the challenges and practices in nursing brought about by
the evolution of modern hand surgery patients and medical development. Methods A retrospective study was conducted on clinical
data from 21,512 hand surgery patients in our hospital over the
past 15 years. T
The Impact Visceral Abdominal Fat and Muscle Mass Using CT on Patients with S...semualkaira
The association between abdominal visceral
fatty area (VFA) and muscle mass and mortality is not fully understood despite the fact that being overweight is an established
risk factor for the onset and severity of acute pancreatitis (AP). We
assessed the effect of VFA on severe AP (SAP) mortality
When and Where? Hybrid Procedure after Percutaneous Coronary Interventionsemualkaira
Invasive angiography in high risk of significant disease is class A of recommendation. Myocardial infarction caused by dissection of
coronary artery is very rare complication. The infarct-related artery (IRA) should be treated during the initial intervention. If PCI of the
IRA cannot by performed coronary artery bypass (CABG) should be considered.
Incidence of VTE in the First Postoperative 24 Hours after Abdominopelvic Sur...semualkaira
A good number of research reports the incidence of postoperative venous thromboembolism (VTE) mostly
looks at longer postoperative duration, usually days after surgery.
1.2. Objective: We investigated the incidence of early asymptomatic VTE (24 hours postoperatively) to assess the relevance of generalisation of extended post-hospital discharge chemoprophylaxis
Analyses of Risk Factors of Diarrhea in Patients with Esophagectomysemualkaira
Esophageal cancer is one of the most common
cancers of the world and surgery is an effective treatment for that.
However, long-term complications, such as diarrhea, are the focus
on the postoperative quality of life. Until now, the etiologies of
diarrhea after esophagectomy are still ill-defined
Protective Effect of Essential Oil of Pelargonium Graveolens against Paraceta...semualkaira
Pelargonium graveolens is an aromatic and medicinal plant, belonging to the Geraniaceae family that grows in temperate areas of
the world, which characterized by its therapeutic proprieties. It is
widely known as one of the medicinal herbs with the highest antioxidant activity. T
Axonal Polyneuropathy with Anti-Caspr1 Igg1 Paranodal Antibodiessemualkaira
The main electrophysiological manifestation of
autoimmune paranodopathy with anti-contactin-associated protein
1 (Caspr1) positive reported previously was demyelination, with
or without axonal involvement. Here, we reported a patient with
anti-Caspr1 IgG1 positive who had severe axonal involvement accompanied less evidence of demyelination.
Laryngeal Lesion of Epidermolysis Bullosa: Topical Use of Mitomycin-Csemualkaira
Epidermolysis bullosa (EB) is a mucocutaneous genetic disease
characterized by fragility of the dermoepidermal junction. Laryngeal lesions frequently occur in junctional epidermolysis bullosa
(JEB), a subtype of EB.
The Efficacy and Safety of Convalescent Plasma for COVID-19 Patients: A Meta-...semualkaira
Convalescent plasma (CP) was demonstrated
promising benefit for clinical practice involved in efficacy and
safety in previous coronavirus pandemics, however, the efficacy of
CP from COVID-19 sufferers are still controversial and unascertainable based on current randomized controlled trials (RCTs). The
urgent needs for affirmative replies on the efficacy and safety of
CP for COVID-19 patients must be developed as soon as possible.
Borderline Ovarian Tumors – Diagnostic and Treatment Modalitiessemualkaira
Ovarian tumors occur in one third of all women gynecology organs. Out of that borderline ovarian tumors occur in 10 – 15% out
of all ovarian tumors. They are tumors with low malignant potential, which are different from benign lesions and malignancies by
its’ biological behavior and by histological structure
The human microbiota is an extremely large system with its majority inhabitin...semualkaira
Human microbiota is the system englobing more than 100 trillion
microorganisms living in symbiosis with the hosting body [1, 2].
The majority of the human microbiota inhabits the gastrointestinal
tract especially the colon
COVID-19 Infection Occurring in The Postoperative Period in A Patient Who Und...semualkaira
While the coronavirus-associated Covid-19 infection remains a
risk for people all over the world as a pandemic, it is also a major
catastrophic clinical situation for patients undergoing surgery in
hospitals. If patients encounter this infection picture, especially
after severe operations such as heart surgery, the life-threatening
rates increase gradually.
Incisional Hernia Occurring after Ventriculoperitoneal Shunt Fixationsemualkaira
Ventriculo-peritoneal shunt is the procedure of choice for hydrocephalus. Various complications of ventriculoperitoneal shunts
were reported. Abdominal complications involving the distal tip
of the catheter make the majority of the complications. In this case
report we present a case of incisional hernia occurring in a patient
who underwent fixation of ventriculoperitoneal shunt followed by
revision of the shunt after a while.
Fatal Condition of Aortic Dissection Produces Symptoms of Sudden and Tearing ...semualkaira
Aortic dissection is a very difficult condition in which the inner
sheath of the aortic wall is torn without tearing the outer sheath.
This causes blood to enter the aortic wall through the tear, which
further splits the mediastinum and creates a new channel in the
aortic wall. The serious and often fatal condition of aortic dissection produces symptoms of sudden and tearing chest pain. Although aortic dissection mostly occurs in people around the age of
60, the peak incidence in people with Marfan syndrome is between
20 and 40 years of age.
Deletion of TLR4 Ameliorates Inflammation Response and Apoptosis in Septic Ca...semualkaira
Septic cardiomyopathy (SCM) is featured by
severe myocardial dysfunction and remains one of the lethal complications in clinical sepsis. Toll-like receptor 4 (TLR4) signaling
is known as a classical innate pathway in heart diseases, whereas
the precise underlying mechanism of TLR4 in SCM remains elusive. This study was designed to examine the specific role of TLR4
in SCM with a focus on inflammation and apoptosis.
Prospective Study of Acute Appendicitis with its Clinical, Radiological Profi...semualkaira
Acute appendicitis is the most common condition encountered in general surgical practice. Alvarado and Modified Alvarado Scores (MASS) are the commonly used scoring
systems for its diagnosis, but its performance has been found to
be poor in certain populations. Hence, we compared the RIPASA
score with MASS, to find out which is a better diagnostic tool for
acute appendicitis in the Indian population.
Surgery or Endovascular Treatment, which is the Better Way to Treat Acute and...semualkaira
To investigate the influence of surgical and endovascular treatment on the prognosis of acute and chronic mesenteric ischemia and to further evaluate whether endovascular
treatment can reduce postoperative complications by performing
a meta-analysis.
Rare Case Of Primary Pulmonary Dedifferentiated Liposarcomasemualkaira
Liposarcoma is a relatively common soft tissue sarcoma, but primary pulmonary liposarcomas are extremely rare, expecially for
dedifferentiated subtype. We report the case of a 44-year-old African woman, healed from SARS-Covid, who presented with a 8
cm right lung ilary mass and underwent to a right intrapericardial pneumonectomy with diaphragmatic and pleural resections.
Histological test confirmed diagnosis of dedifferentiated primary
pulmonary liposarcoma. The patient recovered well having an uncomplicated postoperative course and was discharged after 7 days.
On four months follow up the patient was still alive and without
evidence of disease. More studies have to be conducted because
very few cases are reported in literature.
Psychological Impact and Sexual Behavior in Patients with Genital and Anal Co...semualkaira
Genital warts are benign viral tumors of the skin or mucous membranes, due to human papillomaviruses. Rare are the authors who
insist on studying the psycho-affective and sexual impact of this
condition.
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdfOsvaldo Bernardo Muchanga
GASTROINTESTINAL INFECTIONS AND GASTRITIS
Osvaldo Bernardo Muchanga
Gastrointestinal Infections
GASTROINTESTINAL INFECTIONS result from the ingestion of pathogens that cause infections at the level of this tract, generally being transmitted by food, water and hands contaminated by microorganisms such as E. coli, Salmonella, Shigella, Vibrio cholerae, Campylobacter, Staphylococcus, Rotavirus among others that are generally contained in feces, thus configuring a FECAL-ORAL type of transmission.
Among the factors that lead to the occurrence of gastrointestinal infections are the hygienic and sanitary deficiencies that characterize our markets and other places where raw or cooked food is sold, poor environmental sanitation in communities, deficiencies in water treatment (or in the process of its plumbing), risky hygienic-sanitary habits (not washing hands after major and/or minor needs), among others.
These are generally consequences (signs and symptoms) resulting from gastrointestinal infections: diarrhea, vomiting, fever and malaise, among others.
The treatment consists of replacing lost liquids and electrolytes (drinking drinking water and other recommended liquids, including consumption of juicy fruits such as papayas, apples, pears, among others that contain water in their composition).
To prevent this, it is necessary to promote health education, improve the hygienic-sanitary conditions of markets and communities in general as a way of promoting, preserving and prolonging PUBLIC HEALTH.
Gastritis and Gastric Health
Gastric Health is one of the most relevant concerns in human health, with gastrointestinal infections being among the main illnesses that affect humans.
Among gastric problems, we have GASTRITIS AND GASTRIC ULCERS as the main public health problems. Gastritis and gastric ulcers normally result from inflammation and corrosion of the walls of the stomach (gastric mucosa) and are generally associated (caused) by the bacterium Helicobacter pylor, which, according to the literature, this bacterium settles on these walls (of the stomach) and starts to release urease that ends up altering the normal pH of the stomach (acid), which leads to inflammation and corrosion of the mucous membranes and consequent gastritis or ulcers, respectively.
In addition to bacterial infections, gastritis and gastric ulcers are associated with several factors, with emphasis on prolonged fasting, chemical substances including drugs, alcohol, foods with strong seasonings including chilli, which ends up causing inflammation of the stomach walls and/or corrosion. of the same, resulting in the appearance of wounds and consequent gastritis or ulcers, respectively.
Among patients with gastritis and/or ulcers, one of the dilemmas is associated with the foods to consume in order to minimize the sensation of pain and discomfort.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
low birth weight presentation. Low birth weight (LBW) infant is defined as the one whose birth weight is less than 2500g irrespective of their gestational age. Premature birth and low birth weight(LBW) is still a serious problem in newborn. Causing high morbidity and mortality rate worldwide. The nursing care provide to low birth weight babies is crucial in promoting their overall health and development. Through careful assessment, diagnosis,, planning, and evaluation plays a vital role in ensuring these vulnerable infants receive the specialize care they need. In India every third of the infant weight less than 2500g.
Birth period, socioeconomical status, nutritional and intrauterine environment are the factors influencing low birth weight
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfrightmanforbloodline
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)MuskanShingari
Statistics- Statistics is the science of collecting, organizing, presenting, analyzing and interpreting numerical data to assist in making more effective decisions.
A statistics is a measure which is used to estimate the population parameter
Parameters-It is used to describe the properties of an entire population.
Examples-Measures of central tendency Dispersion, Variance, Standard Deviation (SD), Absolute Error, Mean Absolute Error (MAE), Eigen Value
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdfRahul Sen
Time-lapse embryo monitoring is an advanced imaging technique used in IVF to continuously observe embryo development. It captures high-resolution images at regular intervals, allowing embryologists to select the most viable embryos for transfer based on detailed growth patterns. This technology enhances embryo selection, potentially increasing pregnancy success rates.
Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
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(NASH), there is an increased risk of hepatic fibrosis progressing
to cirrhosis, end-stage liver disease (ESLD), and, in some patients,
hepatocellular carcinoma (HCC). [3] About 25-30% of patients with
NAFLD are estimated to have the progressive form of NAFLD. [4-
6] Over time, approximately 32% to 53% of patients with NASH
experience fibrosis progression. [7, 8] Until recently, viral hepatitis
(especially hepatitis C) and alcoholic liver disease were the two lead-
ing indications for liver transplants in the US. [9] However, NASH
is a rapidly growing liver transplant indication across racial/ethnic
groups. [9] NAFLD-related ESLD and HCC became a leading cause
of liver transplant consideration in the US: the second leading cause
among men and the leading cause among women. [9, 10] NAFLD is
also associated with increased risk of cardiovascular disease, cancer,
and chronic kidney disease and significantly increases overall mor-
tality. [11-14] Thus, NAFLD and its associated comorbidities pose
heavy clinical and economic burdens, with a staggering estimated
annual direct medical cost of patients with NAFLD of $103 billion
in the US and €35 billion in Europe. [15, 16] Therefore, safe and
effective treatments to mitigate the NASH progression and prevent
complications (i.e., cardiovascular diseases, chronic kidney disease,
HCC) are desperately needed.
Weight reduction and regular exercise have been proven to reverse
steatosis, NASH, and NASH fibrosis. [17] However, achieving and
sustaining therapeutic weight reduction and exercise habits is a signif-
icant challenge in patients with NAFLD. Identifying an effective, safe
pharmacological treatment to mitigate NASH activity and fibrosis is
critical to the prevention of NASH progression and liver cancer de-
velopment. During the past decades, tremendous advancement was
made in understanding the pathogenesis of NAFLD, which led to
numerous clinical trials. Despite the identified therapeutic targets and
promising candidates tested in clinical trials, no established pharma-
cological agents exist today to treat NAFLD. Many trials have been
terminated prematurely due to the lack of sufficient efficacy at the
interim analysis. The challenges in NASH/NAFLD drug develop-
ment are multifactorial. NAFLD pathogenesis is complex, involv-
ing a cascade of pathophysiologic changes. Thus, the therapeutic
approach should be formulated based on understanding the multi-
phasic NAFLD pathogenesis in patients with NAFLD (e.g., a com-
bination of drugs targeting multiple pathways, drug therapy in com-
bination with diet and/or exercise). Another limitation is the lack of
sufficient consideration of biological disparities by age and sex/gen-
der in clinical trial design and analytic planning. Robust data exists,
demonstrating sex/gender differences in human health and diseases.
[18] Many aspects of the NAFLD pathogenesis and the disease pro-
gression are regulated in sex-specific manners. [19, 20] Aging also
leads to functional senescence in adipocytes, cellular stress response,
inflammation, immune response, and regenerative capacity. [21-23]
Thus, treatment response and safety profiles may significantly vary
by sex, reproductive status, and age. Some medications may exert
sex-/age-specific therapeutic effects or safety signals. Since men and
women age differently, the effects could be age- and sex-specific. [24]
Such disparities are rarely considered in current clinical trials, prob-
ably because it would complicate the study design and increase the
required sample size. [18, 25] In this article, we will briefly summarize
the NAFLD pathogenesis, review biological disparities in NAFLD/
NASH mechanisms, discuss necessary considerations in the analysis,
and propose possible methodological solutions, including the appli-
cation of adaptive design and posthoc analysis of the trial data to
inform later phase clinical trials.
3. Overview of NASH Pathogenesis, Epidemiology, and
Disparities by Age and Sex
NAFLD is a disease caused by excess lipid accumulation in the liv-
er. Beside a few exceptions such as drug-induced NAFLD and lyso-
somal acid lipase deficiency, most NAFLD cases are associated with
metabolic derangement induced by obesity (i.e., metabolic-associated
fatty liver disease or MAFLD). The key disease drivers of NAFLD
are abdominal obesity and insulin resistance, both of which fuel the
liver with increased free fatty acids delivery, causing metabolic stress
in the hepatocytes. [3] When the increased lipid burden encounters
failed hepatocellular adaptation, it then leads to hepatocellular dam-
age, chronic liver injury (i.e., nonalcoholic steatohepatitis or NASH),
fibrosis, and tumorigenesis. [3] The disease severity and progression,
i.e., NASH and fibrosis, are considered a consequence of failed ad-
aptation to the increased metabolic stress, impaired homeostasis, and
dysregulated wound-healing process. [3] Figure 1 depicts the multi-
phasic aspects of NALFD pathogenesis.
NAFLD occurs in both sexes and spans a wide range of age groups,
from children to the elderly. However, the prevalence, clinical and
histologic features, and risk factors of NAFLD are not necessarily
homogeneous across different age groups or between sexes. [25-28]
As reviewed in a recent article, population-based studies consistently
demonstrated the prevalence of NAFLD to be higher in men than in
women during the reproductive age, while the prevalence in women
increases after the age at menopause and exceeds the prevalence in
men in older age. [25] This age-sex interaction on the NAFLD prev-
alence is partly explained by estrogen’s protective effects on visceral
obesity and insulin resistance. [25] Hormone replacement therapy
among postmenopausal women appears to be protective against liv-
er enzyme elevation presumably associated with NAFLD. [29, 30]
Similar age-sex interaction is also observed in the severity of NASH
fibrosis; premenopausal women are protected from hepatic fibrosis
compared to men and postmenopausal women, [31-33] which is like-
ly attributed to estrogen’s inhibitory effects on satellite cell prolifera-
tion and fibrogenesis. [34, 35] Of note, the prevalence of NAFLD is
positively correlated with body size (i.e., BMI), but this association is
weak among the older population [36, 37] reflecting the heterogene-
ity in the NAFLD pathogenesis; [38] This observation may suggest
that in older subjects, cellular homeostasis/senescence may more
significantly contribute to the disease progression than the upstream
disease–driving factor, i.e., increased lipid influx to the liver.
Robust evidence exists to support biological disparities in the NA-
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FLD pathogenesis. Sex differences in mechanisms involved in the
NAFLD pathogenesis are reviewed in recently published articles [19,
20], thus are not discussed here. However, there are a few crucial
points relevant to the purpose of this article. Hepatic gene expres-
sion is sexually dimorphic due to the gene regulation by estrogen,
androgen, and sex-specific growth hormone secretion patterns [39].
A recent computational modeling study demonstrated that female
and male livers are metabolically distinct organs and identified gene
regulators exerting sex-specific effects on hepatic triglycerides accu-
mulation. [40] Such regulators include peroxisome proliferator-acti-
vated receptor (Ppar)-γ, coactivator 1-a (Pgc1a), farnesoid X recep-
tor (Fxr), liver X receptor (Lxr), and Ppar-α [40], most of which are
functionally related to current therapeutic targets in NASH, [41]
reinforcing the significance of considering sex differences in evalu-
ating efficacy and safety for drugs targeting these regulators. Besides
metabolism, sexual dimorphisms are broadly observed in hepatic
gene expressions across the functions qualitatively and quantitatively.
An RNA sequence study assessed intra- and interspecies variation
in gene regulatory processes among primates and demonstrated sex
differences across the species in gene expression involved in lipid
metabolism and catabolism, steroid metabolism and biosynthesis,
ATP synthesis, RNA splicing and binding, RNA processing, immune
response, and wound healing (e.g., wnt signaling) in addition to genes
on X-chromosome. [42] Further, hepatic fibrogenesis is regulated by
sex hormones. Estradiol inhibits liver fibrosis by inhibiting stellate
cell activation via estrogen receptor-β [35, 43], while progesterone
activates stellate cells by inducing ROS generation, MAPK pathway
activation, and TGFβ1 expression. [44] Thus, physiological estrogen
levels (e.g., women vs. men, pre-menopausal vs. postmenopausal
women) and the altered ratio of estrogens to progesterone (e.g., con-
traceptives) may modulate baseline fibrogenic activities and thus in-
fluence therapeutic response to anti-fibrogenic agents. Since hepatic
lipid metabolism, inflammation, and fibrosis are frequently targeted
in the NASH treatment, proper consideration of age and sex in the
study design and analysis is critical in addressing variations in the
treatment efficacy and safety profiles.
Figure 1: NAFLD pathogenesis
4. Translating the Biological Disparities in The NAFLD
Pathogenesis into Statistical Consideration
Keeping the biological disparities in mind, we discuss a few statistical
considerations in analyzing NAFLD/NASH data. First, age and sex
are often considered covariates or variables for matching to remove
confounding effects. Given the biological effects of age and sex on
the NAFLD pathogenesis, these variables should also be considered
potential effect modifiers. Second, when analyzing sex-/age-differ-
ences in the efficacy, it is common to stratify the data by age or sex
separately. As many of the key mechanisms in NAFLD are regulated
by sex hormones, age does not equally affect the disease mechanisms
in men and women. Age-sex interaction (two-way interaction) needs
to be considered in the analysis (i.e., menopausal status). Sex-specific
analysis including all age groups is not sufficient to address sex dif-
ferences and may mask important associations.
5. Key Limitations in Current Trial Design and Analysis
In liver disease clinical development, it is recognized that there are
some limitations in the design and analysis of NAFLD/NASH clin-
ical trials. These key limitations include, but are not limited to, (i) the
lack of information on sex differences from preclinical experiments
to inform study design, (ii) the lack of blocked or stratified random-
ization, which often leads to uneven distribution of sex and age (or
treatment imbalance in sex and age), (iii) the lack of information on
women’s menopausal status and reproductive health which may have
an impact on enrollment and/or final data analysis, and (iv) there
are no considerations of potential sex/age differences and possible
sex-by-age interaction. To overcome some of the limitations, we sug-
gest the following approaches be considered: the use of adaptive trial
design and post-study subgroup analysis. In what follows, these two
approaches will be briefly described.
TG: triglyceride
VLDL: very low density lipoprotein
NASH: nonalcoholic steatohepatitis
HCC: hepatocellular carcinoma
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6. Future Considerations for NAFLD/NASH Clinical
Trials
In practice, two approaches can be employed in NAFLD/NASH
clinical trials to address the key limitations described above. The first
approach is to utilize a pre-study stratified randomization with strat-
ification factors of interest such as age and sex under a valid trial
design such as adaptive trial design. Stratified randomization allows
the assessment of possible confounding and/or interaction effect
between treatment and the stratification factors. The second ap-
proach is post-study subgroup analysis provided there are sufficient
number of subjects in the study. These two approaches are briefly
summarized below.
The Use of Adaptive Trial Design – First, we suggest employing
an adaptive trial design to address some of the limitations discussed
above. As indicated in Chow and Chang (2011), there are ten differ-
ent types of adaptive trial design (see also FDA, 2019). Selecting an
appropriate adaptive design for an intended NAFLD/NASH clinical
trial depends upon the study objectives of the intended trial. For
example, an adaptive-randomization design may be considered if the
objective is to detect potential sex and/or age differences and possi-
ble sex-by-age interaction.
We can consider a stratified randomized parallel-group design with
stratification factors such as sex, age, obesity, menopausal status (fe-
male only), and/or other key factors for the specific pathway of in-
terest and a planned interim analysis.
For instance, we can divide the target population into 4 strata using
age and gender:
a. Female patient aged over 50 (i.e., age surrogate of menopause)
b. Female patient aged 50 or below
c. Male patient aged above 50 (this age can be determined using pre-
vious knowledge about the treatment effect or just the median age of
the target male population)
d. Male patient aged 50 or below
Then we may recruit patients in each category with known ratio in
the whole target population. By randomly assign them with 1:1 ratio
to two treatment groups, we will finally result in a 2-arm parallel de-
sign in stage 1, each contains patients from all 4 strata with specific
ratio. Stage 2 should also be a 2-arm parallel design, but after interim
analysis, we may decide to drop patients from some strata if there
is no significant treatment effect or there are some considerations
about safety. (Figure 2) illustrates the proposed adaptive trial design
with stratified randomization.
Figure 2: Proposed adaptive trial design with stratified randomization
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The purposes of the planned interim analysis are multi-fold. First, it
is to verify the assumptions made upfront for power calculation of
sample size requirement based on data observed at interim. Second,
it is to perform sample size re-estimation to determine whether we
will achieve the study objective with the desired power in the end if
the observed clinically meaningful difference (treatment effect) pre-
serves till the end. Third, we may stop the trial early due to safety,
futility and/or efficacy after the review of interim data. (May drop
both the arms which are unresponsive to the treatment or adjust
safety measures if any arms exert safety concerns, and continue with
the treatment sensitive arms.) Fourth, it provides the opportunity for
adaptations to the study protocol after the review of interim data.
Adaptations could include (i) change in study endpoint, (ii) change
in randomization, (iii) change in hypothesis (e.g., from superiority
hypothesis to non-inferiority hypothesis), and etc. These adaptations
may shorten the development process and increase the probability
of success.
Under the adaptive trial design, the collected clinical data can be an-
alyzed using the method of analysis of covariance (ANCOVA) with
sex, age, and obesity as fixed effects and other demographics and
patient characteristics such as menopausal status as covariates. The
mixed effects model will allow us not only to test potential sex/age
differences, but also to assess possible sex-by-age interaction. In ad-
dition, odds ratios and their corresponding 95% confidence intervals
between the levels of class variables (fixed effects) can be obtained
for necessary adjustment of study design.
7. Post-Study Subgroup Analysis
If the study already done, one may consider post-study subgroup
analysis. A subgroup (or subpopulation) may be defined by sex, age,
obesity, and/or menopausal status (for female) if the information is
available. Subgroup analysis allow us not only to test potential sex/
age differences, but also to assess possible sex-by-age interaction.
However, subgroup analysis has been criticized that (i) sample size
is often small and hence may not have sufficient power for detection
of clinically meaningful difference, (ii) subgroup may not be repre-
sentative of the entire patient population under study and hence we
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Advantages Disadvantages
Pre-Study
1) Pre-planned study so that we may make adaptions
to sample size and endpoints so that we can maximize the
chance to achieve a desired power of the trial.
2) May use stratified sampling to avoid the problem of
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1) With dropping out unwanted strata, generalizability of the study will
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Table 1: Pros and Cons of the Two Approaches
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Under the framework of post-study subgroup analysis, data can be
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graphics and patient characteristics such as menopausal status as
covariates. The mixed effects model will allow us not only to test
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interaction. In addition, odds ratios and their corresponding 95%
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8. Summary
This article summarizes current knowledge of age-/sex- disparities
in the NAFLD pathogenesis, opportunities/challenges in investigat-
ing the disparities in clinical trials of NAFLD/NASH. As detailed
above, there are differences in biology between males and females.
Proper consideration of these variations may aid in delineating the
heterogeneity in therapeutic response in patients with NAFLD/
NASH and inform personalized therapeutic approaches in patients
with NAFLD.
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