Chronic Diseases and Translational Medicine
Volume 08 · Issue 04 · 2022
Chron Dis Transl Med
- Sections
- Review
- Original Article
Cellular immunotherapy harnesses the body's own immune system to fight cancer by using engineered T cells, macrophages, or natural killer (NK) cells. Compared to chimeric antigen receptor T (CAR-T) cells that are commonly used to treat hematological malignancies, CAR-NK cells have shown remarkable therapeutic effectiveness while exhibiting enhanced safety, reduced risk of graft-versus-host disease, fewer side effects, and amplified antitumor efficacy. Preclinical trials have unveiled the high potential of adoptive CAR-NK cell therapy to curtail or even eliminate both hematological malignancies and solid tumors in animal models. We brought forth herein the design principle of CAR-NK cells, highlighted the latest progress in the preclinical testing and clinical trials of CAR-NK cells, briefly delved into discussed major roadblocks in CAR-NK therapy, and discussed potential solutions to surmount these challenges. Given the accelerated progress in both basic and translational studies on immune cell engineering, CAR-NK cell therapy promises to become a serious contender and important addition to the next-generation cell-based immunotherapy.
Over the past few decades, understanding of the pathogenesis of rheumatoid arthritis (RA) has improved substantially. Insights into the cellular and molecular mechanisms involved in RA have enabled the discovery of new therapeutic targets and led to the development of biologics and targeted synthetic disease-modifying antirheumatic drugs. In parallel with the improvement in therapies, the evolution of strategies in the management of RA has also contributed considerably to better outcomes in patients. Major changes include the development of disease activity measures, formulation of the treat-to-target principles as well as increased attention to comorbidities. The presence of comorbidities such as cardiovascular diseases may increase the mortality of RA patients, affect their treatment strategies and result in worse outcomes. Therefore, prevention and management of certain high-risk comorbidities have become increasingly important in the long-term treatment of RA. In this study, we summarized new insights into the pathogenesis and management of rheumatoid arthritis and associated comorbidities, with a special focus on the 2021 update of the American College of Rheumatology (ACR) guideline for RA and key reports presented at the 2021 ACR convergence.
Bone disease is the most common complication in patients with multiple myeloma (MM), and it may lead to skeletal-related events (SREs) such as bone pain, pathological fractures, and spinal cord compression, which impair a patients' quality of life and survival. The pathogenesis of myeloma bone disease (MBD) involves disruption of bone reconstitution balance including excessive activation of osteoclasts, inhibition of osteoblasts, and participation of osteocytes and bone marrow stromal cells. Various factors, such as the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG), dickkopf-1 (DKK-1), sclerostin, and activin-A, are involved in the development of MBD. Bisphosphonates and the anti-RANKL antibody denosumab are currently the main treatment options for MBD, delaying the onset of SREs. Denosumab is preferred in patients with MM and renal dysfunction. Although effective drugs have been approved, antimyeloma therapy is the most important method for controlling bone disease.
Glomerular disease is the leading cause of chronic kidney disease globally. No scoping review reports have focused on China's spectrum of glomerular diseases in children. This study aimed to systematically identify and describe retrospective studies on pediatric glomerular disease based on available data on sex, age, study period, and region.
Six databases were systematically searched for relevant studies from initiation to December 2021 in PubMed, Embase, Web of Science, Global Health Library, Wangfang Database, and CNKI.
Thirty-four studies were identified in the scoping review, including 40,430 patients with biopsy-proven diagnoses. The proportion of boys was significantly higher than that of girls. In this study, 28,280 (70%) cases were primary glomerular disease, 10,547 (26.1%) cases were diagnosed as secondary glomerular disease, and 1146 (2.8%) cases were hereditary glomerular disease. Minimal change disease is the most common glomerular disease among children in China, followed by mesangial proliferative glomerulonephritis, IgA nephropathy, and purpura nephritis. We observed increments in glomerular diseases in periods 2 (2001–2010) and 3 (2011–2021). The proportion of major glomerular diseases varies significantly in the different regions of China.
The spectrum of pediatric glomerular diseases varied across sex, age groups, study periods, and regions, and has changed considerably over the past 30 years.
Being able to predict with confidence the early onset of type 2 diabetes from a suite of signs and symptoms (features) displayed by potential sufferers is desirable to commence treatment promptly. Late or inconclusive diagnosis can result in more serious health consequences for sufferers and higher costs for health care services in the long run.
A novel integrated methodology is proposed involving correlation, statistical analysis, machine learning, multi-K-fold cross-validation, and confusion matrices to provide a reliable classification of diabetes-positive and -negative individuals from a substantial suite of features. The method also identifies the relative influence of each feature on the diabetes diagnosis and highlights the most important ones. Ten statistical and machine learning methods are utilized to conduct the analysis.
A published data set involving 520 individuals (Sylthet Diabetes Hospital, Bangladesh) is modeled revealing that a support vector classifier generates the most accurate early-onset type 2 diabetes status predictions with just 11 misclassifications (2.1% error). Polydipsia and polyuria are among the most influential features, whereas obesity and age are assigned low weights by the prediction models.
The proposed methodology can rapidly predict early-onset type 2 diabetes with high confidence while providing valuable insight into the key influential features involved in such predictions.
Cardiovascular disease (CVD) is the major noncommunicable disease (NCD) accounting for 17.9 million deaths. If current trends continue, the annual number of deaths from CVD will rise to 22.2 million by 2030. The United Nations General Assembly adopted a sustainable development goal (SDG) by 2030 to reduce NCD mortality by one-third. The purpose of this study was to analyze the CVD mortality trends in different countries implementing World Health Organization (WHO) NCD Action Plan and emphasize effective ways to achieve SDG.
WHO statistics, based on the Member-States unified mortality and causes-of-death reports were used for analyzing trends and different interventions.
Reduction of CVD mortality from 2000 to 2016 in 49 countries was achieved for stroke at 43% and ischemic heart disease at 30%. Smoking prevalence and raised blood pressure (RBP) decreased in 84% and 55% of the countries. Eighty-nine percent of high-income countries (HIC) demonstrated a decline in tobacco smoking against 67% in middle-income countries (MIC). Sixty-nine percent of HIC demonstrated a decline in RBP against 15% in MIC. CVD management, tobacco, and unhealthy diet reduction measures are significantly better in HIC. The air pollution level was higher in MIC.
Building partnerships between countries could enhance their efforts for CVD prevention and successful achievement of SDG.
Early body composition changes, associated with physical inactivity and disease advancement are devastating for patient-related outcomes in predialysis chronic kidney disease (CKD), thus warranting a detailed analysis of body composition beyond conventional measures.
The study included 40 subjects diagnosed with CKD; recruited between January to May 2021. Body composition was measured using the multifrequency analyzer, InBody 770. International Physical Activity Questionnaire-Short Form was used to assess physical activity. Suitable statistical analyses were performed using SPSS 21.0.
The mean age of the subjects was 58.68 ± 12.24 years. Sarcopenic obesity was prevalent in 62.5% of the subjects. Body mass index under identified obesity by 15% compared to percent body fat, especially in subjects with low muscle mass. The decline in a unit of estimated glomerular filtration rate (eGFR) significantly correlated with a decrease in weight (p = 0.02), body fat mass (p = 0.05), visceral fat area (p = 0.05), and phase angle (p = 0.01) with marginal changes in waist–hip ratio and extracellular water/total body water. The effect of physical activity on skeletal muscle mass was homogeneous between low and moderate levels, but significantly different from high activity level.
Changes in fat and fluid compartment were associated with eGFR decline, whereas higher physical activity positively affected body composition.
Pancreatitis patients are at an increased risk of malnutrition due to impaired digestion, absorption, and metabolism. The degree of malnutrition is dependent on the duration, viz. acute or chronic. Studies on nutritional status in patients with pancreatitis are limited. Prevalence of nutritional status, physical functioning, and muscle strength among the subjects are scarce globally. The main aim of this study was to screen the status of malnutrition using appropriate screening tools and to assess hand muscle strength among subjects.
A cross-sectional study was conducted on 64 subjects (18–80 years old, 59 males and 5 females) in Mysore city, Karnataka. The patients were screened for malnutrition using a standard tool Patient-Generated Subjective Global Assessment (PG-SGA) and handgrip strength on both dominant and nondominant hands.
The majority of patients (n = 44) were categorized as moderately malnourished/suspected malnutrition (Stage B) according to PG-SGA. A significant difference (p < 0.005) in handgrip strength was seen in men aged 31–40 (t = −3.287) and 41–50 (t = −5.487) years compared to healthy adults.
This study was able to identify patients at risk of malnutrition when the PG-SGA tool was used along with handgrip strength and other anthropometric parameters.
Chronic obstructive pulmonary disease (COPD) is a more prevalent chronic lung disease with a significant health burden, and the majority of these cases receive inadequate treatment.
Prospective, observational, interview (questionnaire) based complete workup COPD study, screened 12,000 cases with chronic respiratory symptoms with cough, sputum production, and shortness of breath. A total of 6000 COPD cases were enrolled after the spirometry test. COPD cases were assessed as disease knowledge and methods of treatment offered by applying questionnaires to patients and treating physicians.
In the present study, 3% of study cases were aware of their COPD illness, 54% were not having knowledge about the disease, and 43% cases were not accepting the COPD diagnosis (p < 0.0001). A total of 58% of cases received inhalation treatment as levosalbutamol monotherapy in 31% cases, levosalbutamol plus beclometasone in 18% cases, and formoterol plus budesonide or salmeterol plus fluticasone only in 9% of COPD cases (p < 0.0001). Total 42% cases received oral treatment as theophylline in 16% cases, salbutamol in 7% cases, oral steroids in 19% cases (p < 0.0001).
"Doctor–patient–drug trio" discordance clubbed as "difficult doctor, difficult patient, and difficult treatment" is a very crucial issue observed during diagnosis and management of COPD in peripheral settings in India.
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