A gene signature for post-infectious chronic fatigue syndrome

Background: At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition. Methods: Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7). Results: Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance Conclusion: Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment

Psychosocial factors and health as determinants of quality of life in community-dwelling older adults.

PURPOSE: It is important to understand the determinants of differences in quality of life in old age and to include a wide range of possible predictors. The present study investigated the determinants of quality of life in two groups of older adults for whom there was an unusually informative set of possible predictor variables. METHOD: Participants were members of the Lothian Birth Cohorts of 1921 (n = 550) or 1936 (n = 1,091). Four facets of quality of life (QoL) and general QoL were measured using the WHOQOL-BREF. Possible determinants included personality traits, measured with the International Personality Item Pool (IPIP) scales; childhood and old age general cognitive ability, measured with the Moray House Test; minor psychological symptoms, measured with the Hospital Anxiety and Depression Scale (HADS); physical health, assessed by grip strength and cardiovascular disease history; and sociodemographic factors, assessed by interview. RESULTS: Linear regression analyses revealed that HADS depression had the greatest influence on quality of life. Personality traits, most notably Emotional Stability, also predicted quality of life to varying degrees, along with factors reflecting current life circumstances. There were differences between the two cohorts in the variables which predicted quality of life. There were different, conceptually relevant, contributions to the different QoL facets. CONCLUSIONS: Personality traits and minor depressive symptoms have an important influence on self-reported quality of life in old age. Quality of life may be influenced more by current than past circumstances, and this relationship may change with age

Predicting change in quality of life from age 79 to 90 in the Lothian Birth Cohort 1921

Purpose: Quality of life (QoL) decreases in very old age, and is strongly related to health outcomes and mortality. Understanding the predictors of QoL and change in QoL amongst the oldest old may suggest potential targets for intervention. This study investigated change in QoL from age 79 to 90 years in a group of older adults in Scotland, and identified potential predictors of that change. Method: Participants were members of the Lothian Birth Cohort 1921 who attended clinic visits at age 79 (n = 554) and 90 (n = 129). Measures at both time points included QoL (WHOQOL-BREF: four domains and two single items), anxiety and depression, objective health, functional ability, self-rated health, loneliness, and personality. Results: Mean QoL declined from age 79 to 90. Participants returning at 90 had scored significantly higher at 79 on most QoL measures, and exhibited better objective health and functional ability, and lower anxiety and depression than non-returners. Hierarchical multiple regression models accounted for 20.3–56.3% of the variance in QoL at age 90. Baseline QoL was the strongest predictor of domain scores (20.3–35.6% variance explained), suggesting that individual differences in QoL judgements remain largely stable. Additional predictors varied by the QoL domain and included self-rated health, loneliness, and functional and mood decline between age 79 and 90 years. Conclusions: This study has identified potential targets for interventions to improve QoL in the oldest old. Further research should address causal pathways between QoL and functional and mood decline, perceived health and loneliness

Comparative effectiveness of Anti-IL5 and Anti-IgE biologic classes in patients with severe asthma eligible for both.

BACKGROUND: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. METHODS: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions. RESULTS: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). CONCLUSIONS: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use

Global variability in administrative approval prescription criteria for biologic therapy in severe asthma

Background Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine. Objective To compare global differences in ease of access to biologics. Methods In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access. Results Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for anti-IgE/anti–IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower. Conclusions Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world

Simultaneous occurrence of focal nodular hyperplasia and primary sclerosing cholangitis in a young female.

We report the case of a 22-year-old female with primary sclerosing cholangitis who was found, during hepatic imaging, to have a large liver mass. Imaging techniques and histological examination confirmed the mass to be focal nodular hyperplasia. A review of the literature indicates that the simultaneous occurrence of these two hepatic pathologies is unique. The differential diagnosis of hepatic masses in primary sclerosing cholangitis is discussed. Focal nodular hyperplasia needs to be included in the differential diagnosis of hepatic lesions in primary sclerosing cholangitis

Liver transplantation for primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology that is progressive in most symptomatic patients, advancing toward cirrhosis and liver failure. Liver transplantation is the only therapeutic option for patients with end stage liver disease resulting from this disorder. The results of transplantation for PSC are excellent with one-year survival rates of 90-97% and five-year survival rates of 80-85%, but are closely related to pre-transplant Child-Pugh stage. Recurrence of PSC after liver transplantation is common, occurring in up to 20% of patients, but it appears to have little effect on patient survival, as survival of patients with recurrent PSC is similar to that of those without evidence of recurrence. Cholangiocarcinoma is a catastrophic complication of PSC and as yet no reliable screening method exists. The results of liver transplantation for patients with clinically apparent cholangiocarcinoma are extremely poor, however in patients in whom a microscopic tumour is detected in the explanted liver, survival is similar to those transplanted with PSC without cholangiocarcinoma. Activity of inflammatory bowel disease (IBD) appears to be more severe after transplantation, especially in units where steroid immunosuppression is withdrawn early. Colon cancer appears within the first few years after transplantation in approximately 7% of patients with IBD who are transplanted for PSC. Annual colonoscopy in this population seems prudent

Primary sclerosing cholangitis associated with rheumatoid arthritis and HLA DR4: is the association a marker of patients with progressive liver disease?

In four cases we describe the unique association of primary sclerosing cholangitis (PSC) and rheumatoid arthritis (RA). In three of the cases the liver disease was unusually progressive, proceeding to cirrhosis in 14, 18 and 48 months from diagnosis. The three cases with progressive liver disease and ulcerative colitis were all HLA type DR4. The fourth patient also suffered from coeliac disease in addition to PSC and RA and has remained asymptomatic over 7 years of follow-up. RA in association with PSC may serve as a clinical marker of patients at high risk of progression to cirrhosis who need to be kept under particularly close observation. In addition, PSC needs to be considered in the differential diagnosis of all patients with RA and cholestatic liver function tests. This is especially important given the link between PSC and an increased risk of colonic carcinoma, and thus the need for surveillance colonoscopy

Wilson's disease presenting with rapidly progressive visual loss: another neurologic manifestation of Wilson's disease?

Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism resulting in copper-induced tissue damage that primarily involves the liver and central nervous system. The neurologic manifestations of WD almost universally involve a derangement of basal ganglia function or psychiatric disturbance. We report the case of a 46-year-old man presenting with end-stage liver disease caused by WD who had associated rapidly progressive optic neuropathy. We also discuss the possible association between the two conditions