Risk factors for fibrosis progression in non-alcoholic steatohepatitis: Analysis of the European cohort in the real-world GAIN study.

OBJECTIVE: To better understand drivers of disease progression in non-alcoholic steatohepatitis (NASH), we assessed clinical and sociodemographic markers of fibrosis progression in adults with NASH. PATIENTS AND METHODS: Physician-reported patient demographics and clinical characteristics were utilised from the real-world Global Assessment of the Impact of NASH (GAIN) study. Factors associated with likelihood of fibrosis progression since NASH diagnosis were identified using a logistic regression model. RESULTS: Overall, 2349 patients in Europe from the GAIN study were included; mean age was 54.6 years and 41% were women. Significant covariates included age, years since diagnosis, employment status, fibrosis stage at diagnosis, type 2 diabetes mellitus, hypertension, liver transplant and liver biopsy at diagnosis. Risk of progression was 1.16 (95% confidence interval 1.12-1.20; p<0.001) times higher for each additional year since NASH diagnosis and 5.43 (2.68-11.37; p<0.001) times higher when physicians proposed a liver transplant at diagnosis. Compared with full-time employed patients, risk of progression was 1.77 (1.19-2.60; p=0.004) times higher for unemployed patients and 3.16 (1.30-7.63; p=0.010) times higher for those unable to work due to NASH. CONCLUSIONS: Disease duration, NASH severity and presence of other metabolic comorbidities could help to assess risk of progression in patients with NASH.

Clinical and sociodemographic determinants of disease progression in patients with nonalcoholic steatohepatitis in the United States.

ABSTRACT: One fifth of patients with nonalcoholic fatty liver disease (NAFLD) may progress to nonalcoholic steatohepatitis (NASH), which can increase the risk of cirrhosis, cancer, and death. To date, reported predictors of NASH progression have been heterogeneous.We identified determinants of fibrosis progression in patients with NASH in the United States using physician-reported data from the real-world Global Assessment of the Impact of NASH (GAIN) study, including demographics and clinical characteristics, NASH diagnostic information, fibrosis stage, comorbidities, and treatment. We developed a logistic regression model to assess the likelihood of fibrosis progression since diagnosis, controlling for sociodemographic and clinical variables. An iterative nested model selection approach using likelihood ratio test determined the final model.A total of 989 patients from the GAIN US cohort were included; 46% were women, 58% had biopsy-proven NAFLD, and 74% had fibrosis stage F0-F2 at diagnosis. The final multivariable model included age, years since diagnosis, sex, employment status, smoking status, obesity, fibrosis stage, diagnostic biopsy, Vitamin E, and liver transplant proposed at diagnosis. Odds of progression were 17% higher (odds ratio, 1.17 [95% CI: 1.11-1.23]; P < .001) with each year since NASH diagnosis, 41% lower (0.59 [0.38-0.90]; P = .016) for women than men, 131% higher (2.31 [1.30-4.03]; P = .004) for smokers versus non-smokers, and 89% higher (1.89 [1.26-2.86]; P = .002) with obesity. Odds of progression were also higher with part-time, retired, unemployed, and unable to work due to NASH status versus full-time employment, and when a liver transplant was proposed at diagnosis.Disease duration and severity, obesity, smoking, and lack of full-time employment were significant determinants of fibrosis progression. These findings can support clinical and health-policy decisions to improve NASH management in the US.

Perspective on Circulating Tumor Cell Clusters: Why It Takes a Village to Metastasize.

Circulating tumor cell (CTC) clusters may represent one of the key mechanisms initiating the metastasis process. However, the series of pathophysiologic events by which CTC clusters originate, enter the circulation, and reach the distant sites remain to be identified. The cellular and molecular mechanisms that provide survival advantage for CTC clusters during the transit in the blood stream are also still largely unknown. Understanding the biology of CTC clusters is critical to assess this unified scheme employed by cancer and to device strategies to overcome key pathways responsible for their improved metastatic potential. CTC clusters remain an underdeveloped area of research begging the attention of multidisciplinary cancer research teams. Here, we provide insight on existing preclinical evidence on the potential mechanisms leading to CTC cluster formation and dissemination and on processes that may offer survival advantage. We also offer our perspective on future directions to delineate the role of CTC clusters in metastatic cascade and discuss their clinical significance. Cancer Res; 78(4); 845-52. ©2018 AACR.

Association of psychological distress, quality of life and costs with carpal tunnel syndrome severity: a cross-sectional analysis of the PALMS cohort.

OBJECTIVES: The Prediciting factors for response to treatment in carpal tunnel syndrome (PALMS) study is designed to identify prognostic factors for outcome from corticosteroid injection and surgical decompression for carpal tunnel syndrome (CTS) and predictors of cost over 2 years. The aim of this paper is to explore the cross-sectional association of baseline patient-reported and clinical severity with anxiety, depression, health-related quality of life and costs of CTS in patients referred to secondary care. METHODS: Prospective, multicentre cohort study initiated in 2013. We collected baseline data on patient-reported symptom severity (CTS-6), psychological status (Hospital Anxiety and Depression Scale), hand function (Michigan Hand Questionnaire) comorbidities, EQ-5D-3L (3-level version of EuroQol-5 dimension) and sociodemographic variables. Nerve conduction tests classified patients into five severity grades (mild to very severe). Data were analysed using a general linear model. RESULTS: 753 patients with CTS provided complete baseline data. Multivariable linear regression adjusting for age, sex, ethnicity, duration of CTS, smoking status, alcohol consumption, employment status, body mass index and comorbidities showed a highly statistically significant relationship between CTS-6 and anxiety, depression and the EQ-5D (p<0.0001 in each case). Likewise, a significant relationship was observed between electrodiagnostic severity and anxiety (p=0.027) but not with depression (p=0.986) or the EQ-5D (p=0.257). National Health Service (NHS) and societal costs in the 3 months prior to enrolment were significantly associated with self-reported severity (p<0.0001) but not with electrodiagnostic severity. CONCLUSIONS: Patient-reported symptom severity in CTS is significantly and positively associated with anxiety, depression, health-related quality of life, and NHS and societal costs even when adjusting for age, gender, body mass index, comorbidities, smoking, drinking and occupational status. In contrast, there is little or no evidence of any relationship with objectively derived CTS severity. Future research is needed to understand the impact of approaches and treatments that address psychosocial stressors as well as biomedical factors on relief of symptoms from carpal tunnel syndrome.

Reasons for patient's delay in diagnosis of breast carcinoma in Pakistan.

BACKGROUND: Delay in diagnosis of breast cancer is associated with a poorer survival and a pivotal contribution to this delayed diagnosis comes from patient delay in presenting at a clinic. Reasons involved must be evaluated in order to decrease this reducible delay. OBJECTIVES: i) To evaluate the reasons for patient delay in diagnosis of breast cancer; ii) to investigate any association with other variables. MATERIALS AND METHODS: A 6 month cross sectional study (from July 2012 to Dec 2012), was carried out in Surgical and Oncology Units of Civil Hospital, Karachi. A total of 100 females diagnosed with breast cancer of any histological type were interviewed after informed consent and relevant data were collected. Due ethical clearance was obtained. RESULTS: Mean age was 47.5±12.1 years with a range from 25-77 years. Mean duration of delay was 5.13±4.8 months, from shortest 1 month to longest 36 months. Duration of delay was observed to be no delay (<1 month) in 28%, short delay (1-3 months) in 30% and long delay (>3 months) in 42% of patients. Considering the symptoms as "harmless" (39%) was the most frequent reason of delay followed by "temporary" (20%) and the "use of traditional methods" (12%). Most common reason for later approaches was an increase in the size of the lump (41%). Statistically significant association (p-value <0.05) of longer patient delay was obtained with being single, being illiterate, painless breast lump as the first symptom, negative family history of breast cancer and vague attribution of the symptoms. CONCLUSIONS: Significant delay in approach to health care facility was observed in our study due to variable reasons given by women. Sufficient awareness regarding breast cancer, its symptoms and favorable effects of a timely diagnosis on prognosis must be imparted to our general population.