Clinical similarities in siblings with schizophrenia

Three symptom groups, identified by factor analysis of schizophrenic symptoms, together with other clinical variables, were compared among 80 sibships (169 individuals), containing two or more members affected with schizophrenia. The three factors, which were labelled negative symptom, disorganization, and reality distortion, all showed a moderate but significant degree of correlation between siblings. Age at onset was also significantly correlated. Such a familial pattern of clinical heterogeneity suggests underlying common familial aetiologies that influence the clinical form of the disorder. Whether these are genetic or environmental requires further investigation. This finding confers some external validation on the three factor model. It may be feasible to develop familial symptom patterns as the basis for an a priori approach to linkage heterogeneity. © 1996 Wiley-Liss, Inc.     

Schwann cells as underestimated,major players in human skin physiology and pathology

Schwann cells (SCs) have long been recognized for their ability to support repair and promote axon regeneration following injury to the peripheral nervous system. In response to nerve injury, they rapidly dedifferentiate into a precursor-like state, secrete an array of inflammatory mediators and growth factors, proliferate, undergo epithelial-to-mesenchymal-like transformation to facilitate migration, phagocytose cellular debris and remodel the extracellular environment to promote regeneration of axons through the site of injury. However, even though a cutaneous role for SCs is becoming increasingly recognized, we argue in this Viewpoint essay that the likely complex functions of SCs in skin physiology and pathology beyond skin sensation and nerve repair deserve more attention and systemic research than they have received so far. For example, SCs promote wound healing, disseminate infection in leprosy, support the growth of neurofibromas/schwannomas and facilitate/accelerate the growth and invasion of melanoma. Despite representing a major dermal cell population, comparatively little is still known about the role of SCs in other dermatoses. To quintessentially illustrate the opportunities that promise to arise from a new skin research focus on SCs, we focus on two dermatoses that are not traditionally associated with SCs, that is, psoriasis and atopic dermatitis (AD), since both show distinct SC changes along with continuous nerve fibre degeneration and regeneration, and an impact of denervation on skin lesions. Specifically, we critically discuss the hypothesis that repeated activation of the SC repair programme occurs in and contributes to psoriasis and AD and delineate experimental approaches how to probe this clinically relevant hypothesis.     

Lung cancer incidence in young women vs. young men: A systematic analysis in 40 countries

Previous studies have reported converging lung cancer rates between sexes. We examine lung cancer incidence rates in young women vs. young men in 40 countries across five continents. Lung and bronchial cancer cases by 5-year age group (ages 30–64) and 5-year calendar period (1993–2012) were extracted from Cancer Incidence in Five Continents. Female-to-male incidence rate ratios (IRRs) and 95% confidence intervals (95%CIs) were calculated by age group and birth cohort. Among men, age-specific lung cancer incidence rates generally decreased in all countries, while in women the rates varied across countries with the trends in most countries stable or declining, albeit at a slower pace compared to those in men. As a result, the female-to-male IRRs increased among recent birth cohorts, with IRRs significantly greater than unity in Canada, Denmark, Germany, New Zealand, the Netherlands and the United States. For example, the IRRs in ages 45–49 year in the Netherlands increased from 0.7 (95% CI: 0.6–0.8) to 1.5 (95% CI: 1.4–1.7) in those born circa 1948 and 1963, respectively. Similar patterns, though nonsignificant, were found in 23 additional countries. These crossovers were largely driven by increasing adenocarcinoma incidence rates in women. For those countries with historical smoking data, smoking prevalence in women approached, but rarely exceeded, those of men. In conclusion, the emerging higher lung cancer incidence rates in young women compared to young men is widespread and not fully explained by sex differences in smoking patterns. Future studies are needed to identify reasons for the elevated incidence of lung cancer among young women.     

Testicular cancer incidence predictions in Europe 2010–2035: A rising burden despite population ageing

Testicular cancer is the most common cancer among young men of European ancestry, with about one-third of all cases occurring in Europe. With the historically increasing trends in some high-incidence populations reported to have stabilised in recent years, we aimed to assess recent trends and predict the future testicular cancer incidence burden across Europe. We extracted testicular cancer (ICD-10 C62) incidence data from Cancer Incidence in Five Continents Volumes VII–XI and complemented this with data published by registries from 28 European countries. We predicted cancer incidence rates and the number of incident cases in Europe in the year 2035 using the NORDPRED age-period-cohort model. Testicular cancer incidence rates will increase in 21 out of 28 countries over the period 2010–2035, with trends attenuating in the high-incidence populations of Denmark, Norway, Switzerland and Austria. Although population ageing would be expected to reduce the number of cases, this demographic effect is outweighed by increasing risk, leading to an overall increase in the number of cases by 2035 in Europe, and by region (21, 13 and 32% in Northern, Western and Eastern Europe, respectively). Declines are however predicted in Italy and Spain, amounting to 12% less cases in 2035 in Southern Europe overall. In conclusion, the burden of testicular cancer incidence in Europe will continue to increase, particularly in historically lower-risk countries. The largest increase in the number of testicular cancer patients is predicted in Eastern Europe, where survival is lower, reinforcing the need to ensure the provision of effective treatment across Europe.     

International trends in hepatocellular carcinoma incidence, 1978–2012

Primary liver cancer, the major histology of which is hepatocellular carcinoma (HCC), is the second leading cause of cancer death worldwide. We comprehensively examined recent international trends of primary liver cancer and HCC incidence using population-based cancer registry data. Incidence for all primary liver cancer and for HCC by calendar time and birth cohort was examined for selected countries between 1978 and 2012. For each successive 5-year period, age-standardized incidence rates were calculated from Volumes V to XI of the Cancer Incidence in Five Continents (CI5) series using the online electronic databases, CI5plus. Large variations persist in liver cancer incidence globally. Rates of liver cancer remain highest in Asian countries, specifically in the East and South-East, and Italy. However, rates in these high-risk countries have been decreasing in recent years. Rates in India and in most countries of Europe, the Americas and Oceania are rising. As the population seroprevalence of hepatitis B virus (HBV) continues to decline, we anticipate rates of HCC in many high-risk countries will continue to decrease. Treatment of hepatitis C virus (HCV) is likely to bring down rates further in some high-rate, as well as low-rate, countries with access to effective therapies. However, such gains in the control of liver cancer are at risk of being reversed by the growing obesity and diabetes epidemics, suggesting diabetes treatment and primary prevention of obesity will be key in reducing liver cancer in the longer-term.     

Review: Power of big data to improve patient care in gastroenterology

Big data is defined as being large, varied or frequently updated, and usually generated from real-world interaction. With the unprecedented availability of big data, comes an obligation to maximise its potential for healthcare improvements in treatment effectiveness, disease prevention and healthcare delivery. We review the opportunities and challenges that big data brings to gastroenterology. We review its sources for healthcare improvement in gastroenterology, including electronic medical records, patient registries and patient-generated data. Big data can complement traditional research methods in hypothesis generation, supporting studies and disseminating findings; and in some cases holds distinct advantages where traditional trials are unfeasible. There is great potential power in patient-level linkage of datasets to help quantify inequalities, identify best practice and improve patient outcomes. We exemplify this with the UK colorectal cancer repository and the potential of linkage using the National Endoscopy Database, the inflammatory bowel disease registry and the National Health Service bowel cancer screening programme. Artificial intelligence and machine learning are increasingly being used to improve diagnostics in gastroenterology, with image analysis entering clinical practice, and the potential of machine learning to improve outcome prediction and diagnostics in other clinical areas. Big data brings issues with large sample sizes, real-world biases, data curation, keeping clinical context at analysis and General Data Protection Regulation compliance. There is a tension between our obligation to use data for the common good and protecting individual patient’s data. We emphasise the importance of engaging with our patients to enable them to understand their data usage as fully as they wish.     

Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance.

We evaluated the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing elective coronary stenting. Patients (n = 150) treated with aspirin but not clopidogrel had blood samples drawn at baseline and 24 h after clopidogrel loading. Depending on the definition used, 9% to 15% were resistant to aspirin and 24% to clopidogrel. About half of the aspirin-resistant patients were also resistant to clopidogrel. As a group, aspirin-resistant patients had lower response to clopidogrel (assessed by platelet aggregation and activation markers) than aspirin-sensitive patients. Both aspirin- and clopidogrel-resistant patients had higher incidence of creatine kinase-MB elevation than the respective sensitive patients. OBJECTIVES: We sought to evaluate the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Wide variability has been reported in response to aspirin and clopidogrel. There are limited data on the simultaneous responses to both drugs. METHODS: Elective PCI patients (n = 150) who received aspirin for > or = 1 week but not clopidogrel were included. All patients received bivalirudin during PCI. Blood samples were drawn at baseline and 20 to 24 h after a 300-mg clopidogrel dose. Aspirin resistance was defined by > or = 2 of 3 criteria: rapid platelet function analyzer-ASA score > or = 550, 5 micromol/l adenosine diphosphate (ADP)-induced aggregation > or = 70%, and 0.5 mg/ml arachidonic acid-induced aggregation > or = 20%. Clopidogrel resistance was defined as baseline minus post-treatment aggregation < or = 10% in response to 5 and 20 micromol/l ADP. RESULTS: Nineteen (12.7%) patients were resistant to aspirin and 36 (24%) to clopidogrel. Nine (47.4%) of the aspirin-resistant patients were also clopidogrel resistant. Aspirin-resistant patients were more likely to be women and have diabetes than were aspirin-sensitive patients. They also had lower response to clopidogrel, assessed by platelet aggregation and activation markers (flow cytometry-determined PAC-1 binding and P-selectin expression). Elevation of creatine kinase-myocardial band after stenting occurred more frequently in aspirin-resistant versus aspirin-sensitive patients (38.9% vs. 18.3%; p = 0.04) and in clopidogrel-resistant versus clopidogrel-sensitive patients (32.4% vs. 17.3%; p = 0.06). CONCLUSIONS: Aspirin-resistant patients as a group have reduced response to clopidogrel. Furthermore, we have identified a unique group of dual drug-resistant patients who may be at increased risk for thrombotic complications after PCI.     

Differential surface marker expression in patients with CD-16+ lymphoproliferative disorders: in vivo model for NK differentiation

In this study, we report on three patients, each with a CD-16+ lymphoproliferative disorder. Peripheral blood lymphocyte from all three patients were evaluated for lymphocyte morphology, natural killer (NK) function, and surface marker expression. In addition, two-color flow cytometric analysis was performed to determine the phenotype of the CD-16+ cells. Our findings indicate that the presence of increased numbers of CD-16+ cells alone is not a good predictor of NK activity. However, we observed a differential expression of the HLA class II molecules DR and DQ on the CD-16+ cells obtained from these patients that was associated with NK function. Hence, a CD-16+, Leu-7-, Leu-19+ (NKH-1A) and HLA class II+ phenotype did correlate with NK function in contrast to a CD-16+, Leu-7+, Leu-19- (NKH-1A) and HLA class II- phenotype. Of importance was the fact that the CD-16+, HLA class II+ cells did not express CD-25 or TFR, nor did they mediate cytotoxicity against solid tumor targets, suggesting that these CD-16+ cells are not activated. Thus, in contrast to previous studies of NK ontogeny that utilized in vitro activated NK cells, studies of patients with CD-16+ lymphoproliferative disorders may provide an alternative approach for examining NK differentiation.