scholarly journals Application of ultrasound elastography for monitoring the effects of TβR1 shRNA therapy on hepatic fibrosis in a rat model

2019 ◽  
Author(s):  
Xiangzhou Shi ◽  
Jing-Hua Li ◽  
Ying-Bin Min ◽  
Rui-Jing Yang ◽  
Chun-Xiang He ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Portal Vein ◽  
Hepatic Fibrosis ◽  
Therapy Group ◽  
Venous Pressure ◽  
Liver Stiffness ◽  
Ultrasound Elastography ◽  
Acoustic Radiation Force Impulse ◽  
Invasive Technique ◽  
Control Group

Abstract Background: To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-β1 signaling pathway-targeted combination therapy for hepatic fibrosis. Methods: 1.Short hairpin RNA (shRNA) constructs targeted towards TβR1 were designed, synthesized, and packaged using an adeno-associated virus (AAV), and the effective target shRNA was selected based on transfection results. 2. Fifty rats were randomly allocated (n=10 per group) to the (A) control group, (B) model group, (C) 0-week therapy group, (D) 4-week therapy group, and (E) combination therapy group. At weeks 2, 4, 6, 8, 10, and 12, acoustic radiation force impulse (ARFI) elastography was used to measure the liver stiffness, inner diameter of the portal vein diameter, and blood velocity; radio frequency ultrasound imaging was used to measure the abdominal aortic elasticity parameter and pulse wave velocity (PWV) of the rats. 3. At week 12, portal vein puncture was performed to measure the portal venous pressure, and rat liver specimens were obtained for the pathological measurement of the degree of hepatic fibrosis. Conclusion: Ultrasound elastography can reflect the degree of fibrosis in moderate to severe hepatic fibrosis and the variations in the degree of fibrosis after treatment through shRNA silencing of TβR1 . Therefore, it is a potential non-invasive technique for monitoring the effects of anti-fibrosis therapy.

scholarly journals Application of ultrasound elastography for monitoring the effects of TβR1 shRNA therapy on hepatic fibrosis in a rat model

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253150
Author(s):  
Xiangzhou Shi ◽  
Jinghua Li ◽  
Binying Min ◽  
Ruijing Yang ◽  
Chunxiang He ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Hepatic Fibrosis ◽  
Therapy Group ◽  
Venous Pressure ◽  
Ultrasound Elastography ◽  
Portal Venous Pressure ◽  
Control Group ◽  
Elasticity Parameter ◽  
Aortic Elasticity ◽  
Abdominal Aortic

Background To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-β1 signaling pathway-targeted combination therapy for hepatic fibrosis. Methods 1. Short hairpin RNA (shRNA) constructs targeted towards TβR1 were designed, synthesized, and packaged using an adeno-associated virus (AAV), and the effective target shRNA was selected based on transfection results. 2. Fifty rats were randomly allocated (n = 10 per group) to the (A) control group, (B) model group, (C) 0-week therapy group, (D) 4-week therapy group, and (E) combination therapy group. At weeks 2, 4, 6, 8, 10, and 12, acoustic radiation force impulse (ARFI) elastography was used to measure the liver stiffness, inner diameter of the portal vein diameter, and blood velocity; radio frequency ultrasound imaging was used to measure the abdominal aortic elasticity parameter and pulse wave velocity (PWV) of the rats. 3. At week 12, portal vein puncture was performed to measure the portal venous pressure, and rat liver specimens were obtained for the pathological measurement of the degree of hepatic fibrosis. Results 1. An shRNA interference sequence targeted towards TβR1 was successfully designed, screened, and packaged using an AAV, and small-animal imaging results indicated expression of the specific shRNA in the liver. 2. At week 12, the ultrasound elastography results were significantly different between the experimental groups and the control group (p < 0.01); among the experimental groups, differences were significant between the therapy groups and the model group (p < 0.01). For groups C and E, the therapeutic effects on hepatic fibrosis in rats were significant, with the pathological results indicating a significant reduction in the degree of hepatic fibrosis (p < 0.01). The therapeutic effectiveness of group D was less than that of group C (p < 0.05). Significant differences existed between the portal venous pressure of the experimental groups and of the control group (p < 0.01). For the abdominal aortic elasticity parameter measured by radio frequency ultrasound imaging, differences existed between the values obtained from the experimental groups and from that of the control group (p < 0.05), while statistically significant differences were not found among the various experimental groups. 3. Continuous ultrasound examination results indicated that the elasticity value of group A was significantly different from those of the other groups after 2 weeks of model establishment (p < 0.01); after 6 weeks, the elasticity values of groups C and E were significantly different compared with those of groups B and D (p < 0.01). For the abdominal aortic elasticity parameter and pulse wave velocity (PWV), there were no significant differences among the various groups (p > 0.05). Conclusion CCl4-induced hepatic fibrosis can be treated through shRNA silencing of TβR1. Ultrasound ARFI elastography is superior to external force-assisted elastography as it can reflect the degree of fibrosis in moderate to severe hepatic fibrosis and the variations in the degree of fibrosis after treatment. Portal venous pressure was positively correlated with the degree of fibrosis; with early combination therapy, both the degree of fibrosis and portal venous pressure could be effectively reduced.

Noninvasive Assessment of Liver Diseases using 2D Shear Wave Elastography

2016 ◽  
Vol 25 (4) ◽  
pp. 525-532 ◽  
Author(s):  
Monica Lupșor-Platon ◽  
Radu Badea ◽  
Mirela Gersak ◽  
Anca Maniu ◽  
Ioana Rusu ◽  
...  
Keyword(s):  
Shear Wave ◽  
Predictive Value ◽  
Liver Diseases ◽  
Venous Pressure ◽  
Liver Stiffness ◽  
Shear Wave Elastography ◽  
Acoustic Radiation Force Impulse ◽  
Two Dimensional ◽  
Non Invasive ◽  
Examination Technique

There has been great interest in the development of non-invasive techniques for the diagnosis of liver fibrosis in chronic liver diseases, including ultrasound elastographic methods. Some of these methods have already been adequately studied for the non-invasive assessment of diffuse liver diseases. Others, however, such as two-dimensional Shear Wave Elastography (SWE), of more recent appearance, have yet to be validated and some aspects are for the moment incompletely elucidated. This review discusses some of the aspects related to two-dimensional SWE: the examination technique, the examination performance indicators, intra and interobserver agreement and clinical applications. Recommendations for a high-quality examination technique are formulated. Key words:  –  –  – Two-dimensional Shear Wave Elastography. Abbreviations: 2D- SWE: Two-dimensional Shear Wave Elastography; 3D- SWE: Three-dimensional Shear Wave Elastography; AUROC: area under the receiver operating characteristic curves; ARFI Acoustic Radiation Force Impulse Elastography; EFSUMB: European Federation of Societies for Ultrasound in Medicine and Biology; HVPG: hepatic venous pressure gradient; LS: liver stiffness; LR: likelihood ratio; NPV: negative predictive value; PPV: positive predictive value; ROI: region of interest; RT-E: Real Time-Elastography; Se: sensitivity; Sp: specificity; TE: Transient Elastography; US: ultrasound; VM: valid measurement; E: Young’s modulus

Non-invasive methods in the assessment of portal hypertension severity

2021 ◽  
Vol 75 (2) ◽  
pp. 125-133
Author(s):  
Soňa Franková ◽  
Jan Šperl
Keyword(s):  
Portal Hypertension ◽  
Liver Fibrosis ◽  
Shear Wave ◽  
Transient Elastography ◽  
Venous Pressure ◽  
Liver Stiffness ◽  
Invasive Technique ◽  
Hepatic Veins ◽  
Oesophageal Varices ◽  
Non Invasive

Portal hypertension represents a wide spectrum of complications of chronic liver diseases and may present by ascites, oesophageal varices, splenomegaly, hypersplenism, hepatorenal and hepatopulmonary syndrome or portopulmonary hypertension. Portal hypertension and its severity predicts the patient‘s prognosis: as an invasive technique, the portosystemic gradient (HPVG – hepatic venous pressure gradient) measurement by hepatic veins catheterisation has remained the gold standard of its assessment. A reliable, non-invasive method to assess the severity of portal hypertension is of paramount importance; the patients with clinically significant portal hypertension have a high risk of variceal bleeding and higher mortality. Recently, non-invasive methods enabling the assessment of liver stiffness have been introduced into clinical practice in hepatology. Not only may these methods substitute for liver biopsy, but they may also be used to assess the degree of liver fibrosis and predict the severity of portal hypertension. Nowadays, we can use the quantitative elastography (transient elastography, point shear-wave elastrography, 2D-shear-wave elastography) or magnetic resonance imaging. We may also assess the severity of portal hypertension based on the non-invasive markers of liver fibrosis (i.e. ELF test) or estimate clinically signifi cant portal hypertension using composite scores (LSPS – liver spleen stiff ness score), based on liver stiffness value, spleen diameter and platelet count. Spleen stiffness measurement is a new method that needs further prospective studies. The review describes current possibilities of the non-invasive assessment of portal hypertension and its severity.

Abstract 12308: Assessment of Liver Fibrosis Using Magnetic Resonance Elastography in Children Who Undergo the Fontan Procedure and Intracardiac Repair

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Masaya Sugimoto ◽  
Hideharu Oka ◽  
Aya Kajihama ◽  
Kouichi Nakau ◽  
Hiroshi Azuma
Keyword(s):  
Magnetic Resonance ◽  
Liver Fibrosis ◽  
Fontan Procedure ◽  
Venous Pressure ◽  
Liver Stiffness ◽  
Magnetic Resonance Elastography ◽  
Cardiac Biomarkers ◽  
Control Group ◽  
Intracardiac Repair ◽  
Significant Difference

Background: The incidence of late complications related to the liver such as fibrosis/cirrhosis is increasing in patients who have undergone the Fontan procedure and may contribute to morbidity and mortality. Recently, magnetic resonance elastography (MRE), a novel evaluation technique of liver fibrosis, has been attracting attention. However, few reports have described the use of MRE for evaluating liver fibrosis in children with congenital heart disease (CHD). Methods: Thirty-two children were examined and divided into 4 groups: 12 children with CHD who underwent intracardiac repair (ICR; median age, 13.0 years); 10 with CHD who underwent the Fontan procedure (Fontan; 15.3 years); 8 who were included in the control group (control; 15.8 years); and 2 children with cirrhosis (cirrhosis; 16.3 years). The liver stiffness (LS) was estimated by MRE. LS was measured 3 times consecutively, and the mean value was considered for further analysis. Central venous pressure (CVP) and cardiac index (C.I.) were determined by cardiac catheterization. The levels of cardiac biomarkers (NTproBNP and PIIIP) were determined at the same time. Results: Among the 4 groups, no significant differences were observed in age, C.I., and NTproBNP levels. The PIIIP levels in the cirrhosis group were significantly higher than those in the control, but no significant difference in PIIIP levels was found among the other groups (p < 0.01). LS in the Fontan and cirrhosis group was significantly higher than that in the control group (5.6, 15.3 vs. 2.4 kPa, respectively; Fig. 1). Furthermore, there was a strong correlation between LS and CVP (r = 0.802; Fig. 2). Conclusions: This study showed that LS is a direct function of CVP, which should be considered when assessing the degree of liver fibrosis in children with CHD. In particular, in the case of children who undergo the Fontan procedure, the highly sensitive MRE can be used to evaluate liver fibrosis and help detect LS earlier than cardiac biomarkers do.

scholarly journals Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Weiwei Zhang ◽  
Mujian Teng ◽  
Baochi Liu ◽  
Qiling Liu ◽  
Xin Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Liver Cirrhosis ◽  
Liver Function ◽  
Portal Vein ◽  
Liver Stiffness ◽  
Autologous Bone Marrow ◽  
Control Group ◽  
Decompensated Liver Cirrhosis ◽  
Autologous Bone ◽  
The Impact

Objective. This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. Methods. A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18 mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), α-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. Results. Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P<0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. Conclusions. Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.

scholarly journals Preliminary experience with 3T magnetic resonance elastography imaging of the liver

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Anagha Joshi ◽  
Mridula M. Muthe ◽  
Vikrant Firke ◽  
Harshal Badgujar
Keyword(s):  
Magnetic Resonance ◽  
Hepatic Fibrosis ◽  
Liver Stiffness ◽  
Stage Iv ◽  
Normal Liver ◽  
Magnetic Resonance Elastography ◽  
Invasive Technique ◽  
Non Invasive ◽  
The Waves ◽  
Identification And Quantification

Background: Magnetic resonance elastography (MRE) is a promising non-invasive technique for the identification and quantification of hepatic fibrosis. This manuscript describes our early experience with MRE for the assessment of the presence and staging of liver fibrosis on a 3T magnetic resonance imaging (MRI) system.Objectives: The purpose of this study was to describe the MRE physics, procedure, interpretation and drawbacks, along with a few recommendations as per our experience.Method: Magnetic resonance elastography was performed on 85 patients with a 3T MRI and the images were analysed both qualitatively and quantitatively. Liver stiffness was assessed by drawing freehand geographic regions of interest on the elastograms to cover the maximum portion of the hepatic parenchyma within the 95% confidence maps on each slice. Correlation with histopathology was performed whenever available.Results: Of the 80 patients who met the inclusion criteria, 41 patients displayed a normal liver stiffness measurement (LSM) and 39 patients had a raised LSM. In the patients who had a raised LSM, 14 patients had Stage I–II fibrosis, 8 patients had Stage II–III fibrosis, 6 patients had Stage III–IV fibrosis, 4 patients had Stage IV fibrosis or cirrhosis and 7 patients had non-alcoholic steatohepatitis. The mean thickness of the waves increased with increasing stages of fibrosis. The waves became gradually darker medially in patients with normal LSM as compared to the patients with raised LSM. Histopathology with METAVIR scoring was available in 46 patients, which agreed with the MRE findings in all except two patients.Conclusion: Magnetic resonance elastography is a suitable non-invasive modality for the identification and quantification of hepatic fibrosis.

IFN-α, IFN-γ, IL-2 combined with TNF-α for predicting efficacy of PD-1 inhibitors combination therapy in patients with solid cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2584-2584
Author(s):  
Penghui Xing ◽  
Jinyan Zhang ◽  
Rongfeng Liu ◽  
Junyan Wang ◽  
Ming Ma ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Therapy Group ◽  
Control Group ◽  
Coincidence Rate ◽  
Advanced Malignancies ◽  
Tnf Α ◽  
Significant Difference ◽  
Group A ◽  
Ifn Γ ◽  
Group B

2584 Background: PD-1 inhibitors have transformed the treatment landscape for patients (pts) with many advanced malignancies. Combination therapy with PD-1 inhibitors for cancer is a trend. However, Biomarkers for the efficacy of combination therapy remains unknown. In order for the benefited population to be screened out, biomarkers need to be established. we will conduct the following study, to explore the IFN-α, IFN-γ, IL-2 combined with TNF-α for predicting efficacy of PD-1 inhibitors combination therapy. Methods: Using postoperative without lesions as control group (n=7). Pts with lesions as the experimental group (n=66). 27 of 66 pts received chemoradiotherapy (group A), 39 of 66 pts received PD-1 inhibitors combined with therapy (group B). IFN-α, IFN-γ, IL-2, TNF-α in peripheral blood of all pts were measured using flow cytometry. Results: 1) There was significant difference in proportion above normal concentrations (ANCs) of IFN-α between two groups (57.1% vs 43.5%, P<0.05), but there was no significant difference in IFN-γ, IL-2 and TNF-α between two groups (IFN-γ 57.1% vs 52.2%, IL-2 14.3% vs 5.8%, TNF-α 42.9% vs 43.5%, P>0.05). 2) The normal ratios of IFN-α, IFN-γ and TNF-α in group B was significantly higher than that in group A (IFN-α 64.1% vs 51.9%, IFN-γ 59% vs 37%, TNF-α 69.2% vs 44.4%, P<0.05). The proportion ANCs of IFN-α, IFN-γ, and TNF-α were lower in group A (IFN-α 35.9% vs 63%, P>0.05; IFN-γ 41% vs 63%, P<0.05; TNF-α 30.8% vs 55.6%, P<0.05). However, the proportion ANCs of IL-2 detection was lower (7.4% vs 5.1%). 3) In group B, 21 of 39 pts were evaluable. ORR was 52.4% (11/21) and DCR was 85.7% (18/21). The proportion ANCs of IFN-α, IFN-γ and TNF-α in the pts with PR was higher than that with SD (IFN-α 37.5% vs 28.6%, IFN-γ 37.5% vs 28.6%, TNF-α 50% vs 38.8%, P<0.05). 4) We found that the coincidence rate of IFN-α+ IFN-γ and IFN-α+ IFN-γ+TNF-α was higher in group B (Table). Conclusions: Our results suggest that the proportion ANCs of IFN-α, IFN-γ, and TNF-α in the pts with lesions were lower than that without lesions, it may be the decrease of immune function with lesions. There was positive correlation between proportion ANCs of IFN-α, IFN-γ and TNF-α and efficacy in these pts. IL-2 was not used as a routine detection indicator. The coincidence rate of IFN-α, IFN-γ combined with TNF-α was higher, it may help predict the outcome of PD-1 inhibitors combination therapy in pts with solid cancers, and helpful to screen the benefit population. Further study is needed.[Table: see text]

The Etiology of Portal Hypertension in Egyptian Children and Adolescents

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Lerine B El-Din Ahmed ◽  
Asmaa W Abd Elaziz ◽  
Reham I Abdelmegeed ◽  
Mayada Abd El-Rahman F Battah
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Pressure Gradient ◽  
Portal Vein Thrombosis ◽  
Hepatic Fibrosis ◽  
Venous Pressure ◽  
Vena Cava ◽  
Clinical Manifestations ◽  
Vein Thrombosis ◽  
Egyptian Children

Abstract Background Portal hypertension is a clinical syndrome in which the portal venous pressure gradient between portal vein and inferior vena cava exceeding 5mmHg. Clinically significant portal hypertension is diagnosed when clinical manifestations of the disease appear or the portal pressure gradient exceeding 10 mmHg. For better management, it is important to determine the underlying cause. Objective To evaluate the aetiology of portal hypertension in pediatric who attending the hepatology clinic at El-Demerdash hospital, Ain Shams University. Materials and Methods This cross sectional study was done in the department of pediatric hepatology clinic at El-Demerdash hospital, Ain Shams University on 91 consecutive cases of portal hypertension enrolled from 2016 to 2019. All pediatric patients were subjected to full history, clinical examination, investigations and questionnaire about effect of portal hypertension and its complications on QOL. Results Age of children and adolescent was 5 months to 16 years with mean age of 5.55±4.30y and male to female ration was 1.5:1. Out of 91 children (51, 56.1%) developed portal hypertension due to extrahepatic causes and (39, 42.9%) due to hepatic causes. In extrahepatic causes (portal vein thrombosis was found 36, (39.6%) and Budd Chiari syndrome 15(16.5%)). On the other hand, hepatic causes (cong. hepatic fibrosis (CHF) was found in 21(23.1%), cases, hepatic cirrhosis 12(13.2%), extrahepatic biliary atresia 3(3.3%) and autoimmune hepatitis with secondary hepatic fibrosis 3(3.3%)). In extrahepatic cases first variant bleed much earlier than hepatic cases. Conclusion Extrahepatic disease were the most common aetiology of portal hypertension in studied cases. Portal vein thrombosis in extrahepatic cases and congenital hepatic fibrosis in intrahepatic cases were the most common causes.

Acoustic Radiation Force Impulse Elastometry (ARFI Elastometry) in Chronic Viral Hepatitis

2017 ◽  
pp. 82-93
Author(s):  
A. A. Megroyan ◽  
Ju. R. Kamalov ◽  
A. V. Filin ◽  
A. V. Semenkov ◽  
M. M. Morozova ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Fibrosis ◽  
Viral Hepatitis ◽  
Acoustic Radiation ◽  
Liver Stiffness ◽  
Radiation Force ◽  
Chronic Viral Hepatitis ◽  
Acoustic Radiation Force Impulse ◽  
Control Group ◽  
History Of

Purpose:the aim of this study was to evaluate the reliabilityof ARFI elastometry for diagnosis of fibrosis severity stages in patients with chronic viral hepatitis.Material and methods.ARFI elastometry measurements were  done in 103 patients. Mean age of patients was 39.2 ± 10.8 years.  The study included 11 patients with HBV chronic hepatitis, 87  patients with HCV chronic hepatitis and 5 patients with В+D chronic  hepatitis. Liver stiffness was measured using ARFI elastometry with  following liver biopsy which was made 1–2 after US study and  assessed according to the METAVIR score. Control group included 32  patients (20 (62.5%) volunteers and 12 (37.5%) potential liver  fragment donors). Mean age of patients was 26.9 ± 5.3 years. None  of the healthy subjects had a history of gastrointestinal, pancreatic or hepatic disease; all patients had a normal results of laboratory tests.Results.Significant correlation (r = 0.74, р < 0.001) was found  between ARFI measurements and liver fibrosis stages. The values of  ARFI elastometry for various stages of fibrosis were: F ≥ 2 – cut-off  > 1.36 m/s (AUROC – 77%, sensitivity – 65.9%, specificity – 79%),  F ≥ 3 – cut-off > 1.36 m/s (AUROC = 95%, sensitivity – 95,5%,  specificity – 81.5%), F = 4 – cut-off > 1.66 m/s (AUROC – 97%, sensitivity – 93.3%, specificity – 100%). Liver stiffness  measurements in stages F0–F2 reliably differ from stages F3–F4 (1.25 ± 0.18 m/s vs 2.0 ± 0.52 m/s, р < 0.05).Conclusion. ARFI elastometry is reliable diagnostic method for liver  fibrosis detection in stages F ≥ 2. The best performance of this  method was shown for the prediction of severe fibrosis and cirrhosis.

scholarly journals A combination of cognitive training and physical exercise for elderly with the mild cognitive impairment

2019 ◽  
Vol 33 (6) ◽  
pp. 504-516 ◽  
Author(s):  
Ida Untari ◽  
Achmad Arman Subijanto ◽  
Dyah Kurnia Mirawati ◽  
Ari Natalia Probandari ◽  
Rossi Sanusi
Keyword(s):  
Combination Therapy ◽  
Physical Exercise ◽  
Cognitive Training ◽  
Therapy Group ◽  
Meta Analysis ◽  
Control Group ◽  
Combination Therapy Group ◽  
National Library ◽  
Content Type ◽  
Treatment Services

Purpose The purpose of this paper is to conduct systematic reviews on Indonesian papers, to examine the most recent evidence of the efficacy of the combination of cognitive training and physical exercise, and to make recommendations in order to improve prevention, care and treatment services in elderly patients with mild cognitive impairment (MCI). Design/methodology/approach The databases of Cochrane, Medline, NIH (US National Library Medicine), ProQuest, EbscoHost, Clinical Key, EMBASE, Medical Librarian (TWE) in Ovid, Science Direct, Scopus, The Lancet Global Health, PubMed, Emerald, Indonesian National Library, Google Scholar, Google Indonesia, and Garuda Portal were systematically searched using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to obtain empirical papers published between June 1976 and January 2018. Findings Out of the 3,293 articles collected, 10 were included in this analysis. The result of this combined meta-analysis compares the combination therapy group (cognitive therapy and physical exercise) with a control group. It shows that the control group was likely to experience MCI 1.65 times more often than the combination therapy group. According to the result acquired from the synthesized meta-analysis, the control group experienced MCI 1.65 times higher than the combination therapy. The finding is proven to be statistically significant (95% CI= 1.42–1.93). Research limitations/implications The research considers only English and Indonesian articles. Practical implications It is important to explore the most effective training characteristics in a special combined intervention differentiated by the duration, frequency, intervention, type and combination mode. There is a need for further investigation that focuses on the physiological mechanisms underlying the positive effects, by inserting a more comprehensive neuro-imaging measurement to assess specifically the domain that benefits in terms of cognitive functions and molecular markers. Finally, exploratory studies are definitely required, which will specifically examine maintenance and treatment effects as well as derive theoretical explanations related to the interventions and predictors. Social implications A combination of cognitive training and physical exercise intervention may improve the global health or cognitive functions. Originality/value A combination of cognitive training and physical exercise has been found to improve prevention, care and treatment services in elderly patients with MCI. There is an increase in value in comparison to the study of Karssemeijer, which considered five Indonesian articles.

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