Sarcopenia in cirrhosis: Unraveling the prevalence and relationships with liver disease severity and complications.

BACKGROUND AND OBJECTIVES: Sarcopenia in cirrhosis is associated with poor survival and adverse pre and post-transplant outcomes. The study aimed at determining the prevalence of sarcopenia and its association with the severity, complications and etiology of liver disease. METHODS: As many as 416 cirrhotic patients who met the inclusion criteria underwent muscle strength testing using a dynamometer. As many as 109 probable sarcopenia patients underwent computed tomography (CT) scan to measure skeletal muscle index (SMI) at the L3 vertebral level and gait-speed testing. The gender-specific cut-offs used to define sarcopenia were an SMI of 36.54 cm2/m2 in males and 30.21 cm2/m2 in females. A gait speed ≤ 0.8 m/s was taken as a cut-off to define severe sarcopenia in both genders. RESULTS: The mean age was 54.7 ± 9.51 years and male:female ratio was 2.2:1.The mean body mass index (BMI) was 24.2 ± 1.34 kg/m2. Alcohol and non-alcoholic steatohepatitis (NASH) were the two most common etiologies (45.9% and 31.2%). The proportion of patients belonging to Child-Pugh class A, B and C was 26.6%, 48.6% and 24.8%, respectively. Forty out of 109 (36.7%) patients had a model for end-stage liver disease (MELD) > 14. Ascites, upper gastrointestinal bleeding and hepatic encephalopathy (HE) were present in 59 (54.1%), 60 (55.0%) and 24 (22.0%) patients, respectively. The prevalence of probable sarcopenia, sarcopenia and severe sarcopenia was found to be 26.20%, 10.09% and 6.73%, respectively. Sarcopenia and severe sarcopenia were associated with Child-Pugh class (p < 0.001, p < 0.001), MELD (p = 0.007, 0.002), upper gastrointestinal bleed (p = 0.007, 0.004), ascites (p = 0.038, 0.025) and HE (0.001, < 0.001). CONCLUSION: The prevalence of sarcopenia and severe sarcopenia was found to be 10.09% and 6.73%, respectively. Sarcopenia and severe sarcopenia had a significant association with the severity and complications of cirrhosis. However, no association was observed with etiology of liver disease.

A Prospective Randomised Comparative Four-arm Intervention Study of Efficacy and Safety of Saroglitazar and Vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)-SVIN TRIAL.

Background and aim: Vitamin E is widely prescribed for non-alcoholic steatohepatitis (NASH). Saroglitazar, a novel dual peroxisome proliferator-activator receptor ɑ/γ agonist, is approved in India for non-alcoholic fatty liver disease (NAFLD). No head-to-head comparative study for vitamin E and saroglitazar is available. We studied the efficacy and safety of saroglitazar and vitamin E in NAFLD/NASH. Materials and methods: We prospectively randomised 175 NAFLD patients into four arms as Saroglitazar 4 mg daily alone (n = 44), vitamin E 800IU daily alone (n = 41), vitamin E and saroglitazar combination (n = 47), and control arm (n = 43). All the baseline variables including liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were recorded. Reassessment was done after 24 weeks of treatment. Results: The mean age and body mass index was 45 ± 11 years and 26 ± 3.6 kg/m2, respectively. Compared to control, the decrease in alanine amino transferase levels with saroglitazar, vitamin E, and combination therapy was significant (95% confidence interval [CI]: 6.27-28.25, P = 0.002, 95% CI: -3.39 to 18.88, P = 0.047 and 95% CI: 8.10-29.54, P = 0.001, respectively). The reduction in CAP was significant with saroglitazar and combination therapy (95% CI: -31.94 to 11.99, P = 0.015 and 95% CI: -10.48 to 30.51, P = 0.026, respectively). Only combination therapy shows significant reduction in LSM (95% CI: 0.41-1.68, P = 0.001). Among glycaemic parameters, both saroglitazar alone and combination therapy significantly improved glycosylated haemoglobin levels (P = 0.001 and P = 0.015, respectively), and only combination therapy significantly improved homoeostasis model assessment-estimated insulin resistance (P = 0.047). Saroglitazar alone showed significant reduction in triglyceride and low-density lipoprotein levels (P = 0.038 and P = 0.018, respectively), and combination therapy showed significant increase in high-density lipoprotein levels (P = 0.024). Conclusions: Combination of Saroglitazar and vitamin E showed statistically significant reduction of LSM and CAP along with biochemical, glycaemic, and lipid parameters. Clinical trial registry India no: CTRI/2022/01/039538.

Measuring disability in amyotrophic lateral sclerosis/motor neuron disease: the WHODAS 2.0-36, WHODAS 2.0-32, and WHODAS 2.0-12.

Aim: To investigate whether the World Health Organization Disability Assessment Schedule 2.0 (WHODAS) can provide interval level measurement of disability in Amyotrophic Lateral Sclerosis (ALS), allowing parametric analyses. Methods: Data on the WHODAS 12, 32, and 36-item versions, from 1120 patients studied at one or more time points, were fit to the Rasch model and comparisons made against ALSFRS-R, King's staging, and mortality. Trajectory modeling was undertaken for a newly diagnosed (≤6 months) cohort of 454 individuals. Results: Total scores for WHODAS 32 and 36-item versions can be converted to interval level measurement suitable for individual clinical use, and the 12-item WHODAS total for group use. The 36-item version is shown to be equivalent to the 32-item version. Expected correlations were seen with King's staging, ALSFRS-R, and EQ-5D-5L. Trajectory analysis of disability (WHODAS 2.0) showed three clearly demarcated groups with differences in King's staging, depressive symptomatology and mortality, but not age. Conclusions: The WHODAS 2.0 is a brief patient reported outcome measure which can be used to measure disability in ALS. Provided the patient answers all 36 (32 if not working) items, the conversion table produces an interval level estimate for parametric analyses. The different trajectories demonstrated from diagnosis support the concept of a prodromal period, and suggest the WHODAS 2.0 could be used for surveillance of at risk populations, such as those with genetic predisposition.

Measuring coping in multiple sclerosis: The Coping Index-MS.

BACKGROUND: Coping in multiple sclerosis (MS) refers to cognitive and behavioural efforts to manage stresses imposed by the illness. Existing generic and disease-specific coping scales do not meet modern guidelines for scale development and cannot produce interval-level metrics to allow for change scores. OBJECTIVE: The main aim of this study was to develop a brief patient-reported outcome measure for coping in MS, capable of interval-level measurement. METHODS: Qualitative work in 43 people with MS leads to a draft scale which was administered to 5747 participants, with longitudinal collection in 2290. A calibration sample of 1000 subjects split into development and validation sets was used to generate three scales consistent with Rasch model expectations. RESULTS: The total Coping Index-MS (CI-MS-T), CI-MS-Internal (CI-MS-I) and CI-MS-External (CI-MS-E) cover total, internal and externally focused coping. All three scales are capable of interval-level measurement. Trajectory analysis of 9000 questionnaires showed two trajectories in CI-MS-T: Group 1 showed a low level of coping with slight decline over 40 months, while Group 2 had a better and stable level of coping due to improving CI-MS-I which compensated for the deteriorating CI-MS-E over time. CI-MS-T < 30 identified group membership at baseline. CONCLUSION: The CI-MS-T, CI-MS-I and CI-MS-E, comprising 20 items, provide interval-level measurement and are free-for-use in not-for-profit settings.

Emerging Biomarkers for Screening and Management of Celiac Disease.

Celiac disease (CeD) is a chronic, immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals expressing HLA-DQ2 and/or HLA-DQ8. In the current clinical practice, there are many serologic studies to aid in the diagnosis of CeD which include autoantibodies like IgA antitissue transglutaminase, antiendomysium, and antideamidated forms of gliadin peptide antibodies. Small intestinal biopsy has long been considered an essential step for the diagnosis of CeD. However, in the recent era, researchers have explored the possibility of CeD screening and diagnosis without endoscopy or biopsy. The newer emerging biomarkers of CeD appear promising in diagnostic evaluation and subsequent monitoring of disease. In this review of literature, we have explored the emerging biomarker-based diagnostic evaluation and monitoring of CeD.

The four self-efficacy trajectories among people with multiple sclerosis: Clinical associations and implications.

BACKGROUND: Longitudinal studies among people with Multiple Sclerosis (pwMS) have shown that self-efficacy is linked to physical, cognitive and psychological functioning. OBJECTIVES: To determine the distribution of self-efficacy in a large sample of pwMS, examining whether there are distinct groups which show different self-efficacy trajectories over time, and the health status characteristics of any groups identified. METHODS: Participants completed serial questionnaire packs, including Unidimensional Self-efficacy-MS (USE-MS) scale, for the Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study over an average 46-month period. The resulting longitudinal data were analysed by a group-based trajectory model. RESULTS: 5887 pwMS were studied: mean age 50.2 years (SD 12.0); 73.6% female; Relapsing Remitting MS (61.8%), Secondary Progressive (22.9%), Primary Progressive (11.1%), Rapidly Evolving Relapsing Remitting MS (4.2%). Four distinct self-efficacy trajectories emerged, with declining, slightly declining, stable or improving self-efficacy, each showing different patterns of health status indicators such as EQ-5D-5L, disability and depression. USE-MS ≤ 18 at baseline detected all participants in the two declining groups. CONCLUSION: Future trials on interventions for self-efficacy should assume a priori that those with low levels of self-efficacy (USE-MS ≤ 18 at baseline) are likely to be on a declining trajectory and may need different interventions from those with stable self-efficacy.

Fatigue and anxiety mediate the effect of dyspnea on quality of life in amyotrophic lateral sclerosis.

Introduction: Dyspnea (or breathlessness) due to progressive neuromuscular respiratory failure is common in amyotrophic lateral sclerosis (ALS). It is associated with anxiety, depression and reduced quality of life (QoL). For effective treatment, it is essential to understand the relationships between dyspnea, anxiety, depression and QoL.Methods: The UK Trajectories of Outcomes in Neurological Conditions-ALS study (TONiC-ALS) collected self-report measures from patients with ALS. Ordinal scales were transformed to interval-scaled estimates by the Rasch Measurement model. They were subsequently included in a series of path models where the focal relationships were dyspnea to QoL and dyspnea to depression.Results: Path analyses using 1022 participants showed that 60.5% of the variance of QoL was explained by fatigue, anxiety, dyspnea and disability. For depression, 54.1% of the variance was explained by a model of these factors. Dyspnea played an important but mostly indirect role in influencing QoL and depressive symptoms. Disability was dominated by all other factors in the model.Discussion: Dyspnea in ALS influences quality of life and depression largely through indirect effects, principally acting via anxiety and fatigue. Recognition of this is essential for clinicians to understand where to intervene for greatest benefit. Researchers must be aware that studies of the effect of dyspnea on QoL and depression require path models, measuring both direct and indirect effects, as the impact of dyspnea is likely to be significantly miscalculated if only direct effects are assessed.

Quality of life in multiple sclerosis is dominated by fatigue, disability and self-efficacy.

BACKGROUND AND OBJECTIVE: Quality of life in multiple sclerosis (MS) reflects complex relationships between symptoms (fatigue, spasticity pain, and bladder or vision dysfunction), disability, health perceptions, and self-efficacy. METHODS: In this cross-sectional study, a self-report questionnaire pack of patient reported outcome measures was collected from 5695 people with MS (pwMS) alongside clinical data from their neurologists. Each patient reported outcome measure was converted to interval-scaled estimates following fit to the Rasch model. The patient reported outcome measures, as well as perceived health, age, disease subtype and gender, were then subject to path analysis to analyse their relationships with quality of life (QoL), guided by the Wilson and Clearly conceptual framework. RESULTS: The final model explains 81.2% of the variance of QoL. Fatigue is clearly dominant, suggesting a means to intervene and improve QoL. The next most influential factors were disability and self-efficacy, which have similar effect levels. The model can be replicated for pwMS on disease modifying therapy and is largely invariant for gender and disease subtype. Age had an insignificant effect. CONCLUSIONS: In order to promote better QoL, MS care should include management of fatigue, interventions to ameliorate disability, and support to enhance self-efficacy. The range of skills needed for these treatments will require input from medical, nursing, therapy and psychology staff, so these findings provide evidence substantiating the need for pwMS to be provided with care by comprehensive multidisciplinary teams.

Cognition and behaviour in frontotemporal dementia with and without amyotrophic lateral sclerosis.

OBJECTIVE: The precise relationship between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is incompletely understood. The association has been described as a continuum, yet data suggest that this may be an oversimplification. Direct comparisons between patients who have behavioural variant FTD (bvFTD) with and without ALS are rare. This prospective comparative study aimed to determine whether there are phenotypic differences in cognition and behaviour between patients with FTD-ALS and bvFTD alone. METHODS: Patients with bvFTD or FTD-ALS and healthy controls underwent neuropsychological testing, focusing on language, executive functions and social cognition. Behavioural change was measured through caregiver interview. Blood samples were screened for known FTD genes. RESULTS: 23 bvFTD, 20 FTD-ALS and 30 controls participated. On cognitive tests, highly significant differences were elicited between patients and controls, confirming the tests' sensitivities to FTD. bvFTD and FTD-ALS groups performed similarly, although with slightly greater difficulty in patients with ALS-FTD on category fluency and a sentence-ordering task that assesses grammar production. Patients with bvFTD demonstrated more widespread behavioural change, with more frequent disinhibition, impulsivity, loss of empathy and repetitive behaviours. Behaviour in FTD-ALS was dominated by apathy. The C9ORF72 repeat expansion was associated with poorer performance on language-related tasks. CONCLUSIONS: Differences were elicited in cognition and behaviour between bvFTD and FTD-ALS, and patients carrying the C9ORF72 repeat expansion. The findings, which raise the possibility of phenotypic variation between bvFTD and FTD-ALS, have clinical implications for early detection of FTD-ALS and theoretical implications for the nature of the relationship between FTD and ALS.

The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) in frontotemporal dementia.

OBJECTIVES: To examine the usefulness of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS) as a cognitive screening tool for the detection of behavioral variant frontotemporal dementia (bvFTD). A secondary aim was to determine whether people with FTD combined with ALS (ALS-FTD) exhibit a similar ECAS profile to that of people with bvFTD alone. Methods: Patients with ALS-FTD and bvFTD and healthy controls were recruited. Participants were administered the ECAS, which comprises tests of language, verbal fluency, executive functions, memory, and visual-spatial functions. They also carried out analogous, full-length cognitive tests that examine naming, spelling, sentence completion, and social cognition skills. Results: The study cohort comprised 20 ALS-FTD patients, 23 with bvFTD, and 30 controls. Highly significant group differences were elicited for all cognitive domains, reflecting poorer performance in patients compared to controls. No significant differences in overall test scores were found between ALS-FTD and bvFTD patients, although ALS-FTD patients showed a higher frequency of impairment on verbal fluency. Correlative analyses revealed inter-relationships in patients (but not controls) between scores in different domains, most marked in bvFTD. There were strong correlations between performance on ECAS subtests and analogous cognitive tasks. Conclusion: The ECAS is a sensitive and valuable tool for the assessment of FTD. Executive, language and behavioral breakdown may, however, compromise performance in other cognitive domains, reducing the specificity of the 'frontotemporal' cognitive profile. Subtle differences observed between ALS-FTD and bvFTD raise questions regarding the precise relationship between bvFTD with and without ALS.

Measuring quality of life in ALS/MND: validation of the WHOQOL-BREF.

Objectives: The World Health Organization Quality of Life-BREF Scale (WHOQOL-BREF) is a generic QOL measure with four domains covering Physical, Psychological, Social and Environment. Providing the opportunity to contrast QoL with other conditions, or with population norms, the current study had three aims: 1) can the established domains of the WHOQOL-BREF be validated within a large ALS/MND population; 2) can a total score be validated and 3) can they provide interval level measurement? Methods: Data were obtained from the Trajectories of Outcomes in Neurological Conditions study. Internal construct validity was determined by fit of the data to the Rasch measurement model. Results: 636 participants with ALS/MND were included. All domains, except the Social domain, showed satisfactory fit to the Rasch model. All were unidimensional, and showed no Differential Item Functioning by age, gender, or onset type. Finally, a total score was validated from a bi-factor perspective. Conclusions: The WHOQOL-BREF is valid for use in populations with ALS/MND and can be analyzed to yield interval level measurement: It offers a range of domains that reflect QOL, which can be used for parametric analysis and for comparison with other conditions or general populations, two advantages for its inclusion as a trial outcome measure and for observational studies.

The relationships between symptoms, disability, perceived health and quality of life in amyotrophic lateral sclerosis/motor neuron disease.

Objectives: Using the Wilson and Cleary model linking clinical variables to quality of life, we explored the associations between physical and psychological factors, disability, perceived health and quality of life in ALS/MND. Methods: The ongoing UK study of Trajectories of Outcomes in Neurological Conditions (TONiC) recruited participants with ALS/MND to complete a questionnaire pack including demographic factors and several patient reported outcome measures (PROMs); a clinician provided data on disease onset type and duration since diagnosis. All PROMs were transformed from ordinal raw scores to interval-scaled latent estimates via the Rasch measurement model. Results: Data from 636 patients were analyzed; mean age 65.1 years (SD 10.7), 61.3% male. Median duration since diagnosis was 11.2 months (IQR 4.6-29.9; range 0.4-295.9 months); 67.3% had limb and 27.3% bulbar onset disease. Symptoms such as breathlessness and fatigue, along with most domains of activity limitations, were shown to vary by onset type. A series of models illustrated the importance of physical functioning and anxiety upon quality of life, with breathlessness and fatigue having indirect effects. The models were invariant for gender and onset type. Conclusions: This large study highlights the importance of functional status and anxiety as key variables influencing quality of life in ALS/MND. The nature and diversity of factors, both physical and psychological, which have been shown to influence the quality of life of people with ALS/MND provide strong evidence in support of the widespread implementation of multidisciplinary care.

The clinical approach to managing herpes simplex virus encephalitis.

This article explains the approach to managing a patient with herpes simplex virus encephalitis. Acute encephalopathy is a common and often intimidating presentation in an acute general medical setting. Application of key principles will enable the generalist to take life-saving action before obtaining any specialist input. Viral infection is the most common cause (48.2%) of encephalitis; another large group is cases of autoimmune aetiology. Early diagnosis of encephalitis is crucial to ensure that the right treatment is given on time. Guidelines on the management of viral encephalitis were published by the British Association of Neurologists and British Infection Association ( Solomon et al, 2012 ), but adherence to these standards by clinicians has been found to be suboptimal ( Han and Coebergh, 2017 ). This puts lives in danger, in the context of a treatable, serious, acute presentation. Although viral infection is the most common cause of encephalitis, an awareness of rarer forms of autoimmune encephalitis is necessary. The differential diagnosis of autoimmune encephalitis is important because the disease is potentially treatable with immunosuppressive agents. Paraneoplastic limbic encephalitis may present months or years before the detection of a tumour.

Bowel sounds in the chest: An uncommon presentation of adult hernia.

We report a case of a 65-year-old male, who presented with respiratory complaints of cough and breathlessness, managed initially as respiratory tract infection. However, the patient did not improve, and a thorough examination and imaging revealed herniation of a gut segment into the thorax. The patient was operated and respiratory symptoms improved dramatically.

Discontinuity Preserving Image Registration through Motion Segmentation: A Primal-Dual Approach.

Image registration is a powerful tool in medical image analysis and facilitates the clinical routine in several aspects. There are many well established elastic registration methods, but none of them can so far preserve discontinuities in the displacement field. These discontinuities appear in particular at organ boundaries during the breathing induced organ motion. In this paper, we exploit the fact that motion segmentation could play a guiding role during discontinuity preserving registration. The motion segmentation is embedded in a continuous cut framework guaranteeing convexity for motion segmentation. Furthermore we show that a primal-dual method can be used to estimate a solution to this challenging variational problem. Experimental results are presented for MR images with apparent breathing induced sliding motion of the liver along the abdominal wall.