Comorbidity indices are often used to measure comorbidities in register-based research. We aimed to adapt the Charlson comorbidity index (CCI) to a Swedish setting.
Four versions of the CCI were ...compared and evaluated by disease-specific experts.
We created a cohesive coding system for CCI to 1) harmonize the content between different international classification of disease codes (ICD-7,8,9,10), 2) delete incorrect codes, 3) enhance the distinction between mild, moderate or severe disease (and between diabetes with and without end-organ damage), 4) minimize duplication of codes, and 5) briefly explain the meaning of individual codes in writing.
This work may provide an integrated and efficient coding algorithm for CCI to be used in medical register-based research in Sweden.
Certain autoimmune and chronic inflammatory conditions, such as Sjögren's syndrome and rheumatoid arthritis (RA), have consistently
been associated with an increased risk of malignant lymphomas, but ...it is unclear whether elevated lymphoma risk is a phenomenon
that accompanies inflammatory conditions in general. Likewise, it is debated whether the increased risk identified in association
with some disorders pertains equally to all individuals or whether it varies among groups of patients with different phenotypic
or treatment-related characteristics. It is similarly unclear to what extent the increased lymphoma occurrence is mediated
through specific lymphoma subtypes. This update reviews the many findings on risks, risk levels, and lymphoma characteristics
that have been presented recently in relation to a broad range of chronic inflammatory, including autoimmune, conditions.
Recent results clearly indicate an association between severity of chronic inflammation and lymphoma risk in RA and Sjögren's
syndrome. Thus, the average risk of lymphoma in RA may be composed of a markedly increased risk in those with most severe
disease and little or no increase in those with mild or moderate disease. The roles of immunosuppressive therapy and EBV infection
seem to be limited. Furthermore, RA, Sjögren's syndrome, systemic lupus erythematosus, and possibly celiac disease may share
an association with risk of diffuse large B-cell lymphoma, in addition to well-established links of Sjögren's syndrome with
risk of mucosa-associated lymphoid tissue lymphoma and of celiac disease with risk of small intestinal lymphoma. However,
there is also obvious heterogeneity in risk and risk mediators among different inflammatory diseases. (Cancer Epidemiol Biomarkers
Prev 2006;15(11):2069–77)
Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed ...a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Some autoimmune and chronic inflammatory disorders are associated with increased risks of non-Hodgkin lymphoma (NHL). Because different NHL subtypes develop at different stages of ...lymphocyte differentiation, associations of autoimmune and inflammatory disorders with specific NHL subtypes could lead to a better understanding of lymphomagenic mechanisms. Methods: In a population-based case–control study in Denmark and Sweden, 3055 NHL patients and 3187 matched control subjects were asked about their history of autoimmune and chronic inflammatory disorders, markers of severity, and treatment. Logistic regression with adjustment for study matching factors was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for NHL overall and for NHL subtypes. Results: Risks of all NHL were increased in association with rheumatoid arthritis (OR = 1.5, 95% CI = 1.1 to 1.9), primary Sjögren syndrome (OR = 6.1, 95% CI = 1.4 to 27), systemic lupus erythematosus (OR = 4.6, 95% CI = 1.0 to 22), and celiac disease (OR = 2.1, 95% CI = 1.0 to 4.8). All of these conditions were also associated with diffuse large B-cell lymphoma, and some were associated with marginal zone, lymphoplasmacytic, or T-cell lymphoma. Ever use of nonsteroidal anti-inflammatory drugs, systemic corticosteroids, and selected immunosuppressants was associated with risk of NHL in rheumatoid arthritis patients but not in subjects without rheumatoid arthritis. Also, multivariable adjustment for treatment had little impact on risk estimates. Psoriasis, sarcoidosis, and inflammatory bowel disorders were not associated with increased risk of NHL overall or of any NHL subtype. Conclusions: Our results confirm the associations between certain autoimmune disorders and risk of NHL and suggest that the associations may not be general but rather mediated through specific NHL subtypes. These NHL subtypes develop during postantigen exposure stages of lymphocyte differentiation, consistent with a role of antigenic drive in autoimmunity-related lymphomagenesis.
Purpose: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers.
We examined serum YKL-40 and IL-6 levels in patients with ...Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively
few tumor cells, especially in nodular sclerosis Hodgkin lymphoma.
Experimental Design: We analyzed Danish and Swedish patients with incident Hodgkin lymphoma ( N = 470) and population controls from Denmark ( n = 245 for YKL-40; n = 348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analyzed by linear
regression, adjusting for age and sex.
Results: Serum levels of YKL-40 and IL-6 increased in Hodgkin lymphoma patients compared with controls (YKL-40, 3.6-fold; IL-6, 8.3-fold;
both, P < 0.0001). In pretreatment samples from pretreatment Hodgkin lymphoma patients ( n = 176), levels were correlated with more advanced stages ( P trend , 0.0001 for YKL-40 and 0.013 for IL-6) and in those with B symptoms; however, levels were similar in nodular sclerosis and
mixed cellularity subtypes, by EBV status, and in younger (<45 years old) and older patients. Patients tested soon after treatment
onset had significantly lower levels than pretreatment patients; however, even ≥6 months after treatment onset, serum YKL-40
and IL-6 levels remained significantly increased compared with controls. In patients who died ( n = 12), pretreatment levels for YKL-40 and IL-6 were higher than in survivors, although not statistically significantly.
Conclusions: Serum YKL-40 and IL-6 levels were increased in untreated Hodgkin lymphoma patients and those with more advanced stages but
did not differ significantly by Hodgkin lymphoma histology. Following treatment, serum levels were significantly lower.
Background: The incidence of malignant lymphomas has been increasing rapidly, but the causes of these malignancies remain poorly understood. One hypothesis holds that exposure to ultraviolet (UV) ...radiation increases lymphoma risk. We tested this hypothesis in a population-based case–control study in Denmark and Sweden. Methods: A total of 3740 patients diagnosed between October 1, 1999, and August 30, 2002, with incident malignant lymphomas, including non-Hodgkin lymphoma, chronic lymphocytic leukemia, and Hodgkin lymphoma, and 3187 population controls provided detailed information on history of UV exposure and skin cancer and information on other possible risk factors for lymphomas. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. Statistical tests were two-sided. Results: Multivariable-adjusted analyses revealed consistent, statistically significant negative associations between various measures of UV light exposure and risk of non-Hodgkin lymphoma. A high frequency of sun bathing and sunburns at age 20 years and 5–10 years before the interview and sun vacations abroad were associated with 30%–40% reduced risks of non-Hodgkin lymphoma (e.g., for sunbathing four times a week or more at age 20 versus never sunbathing, OR = 0.7, 95% CI = 0.6 to 0.9; for two or more sunburns a year at age 20 versus no sunburns, OR = 0.6, 95% CI = 0.5 to 0.8). These inverse associations increased in strength with increasing levels of exposure (all Ptrend≤.01). Similar, albeit weaker, associations were observed for Hodgkin lymphoma. There were no clear differences among non-Hodgkin lymphoma subtypes, although associations were stronger for B-cell than for T-cell lymphomas. A history of skin cancer was associated with a doubling in risks of both non-Hodgkin and Hodgkin lymphoma. Conclusions: A history of high UV exposure was associated with reduced risk of non-Hodgkin lymphoma. The positive association between skin cancer and malignant lymphomas is, therefore, unlikely to be mediated by UV exposure.
•The use of RT in lymphoma has not decreased during the recent decade.•Use of RT as monotherapy is most often applied to patients aged > 80 years or with limited-stage disease.•Relative survival is ...encouraging for lymphoma patients selected for RT monotherapy.
The role of radiotherapy (RT) in lymphoma is constantly refined with the advent of novel treatments. However, RT is still an effective treatment and tolerability is high. Therefore, we aimed to describe the use of RT in primary treatment of lymphoma over calendar time, with a specific focus on older patients (age ≥ 70 years) with non-Hodgkin lymphoma (NHL) subtypes.
All adult patients diagnosed with lymphoma from 2007 to 2018 in Sweden were included and followed for survival until end of 2020. Patient characteristics and relative survival (RS) were described for patients with NHL by subtype and RT use.
In the cohort of lymphoma patients aged ≥ 70 years (n = 12,698) 11 % received RT as part of primary treatment. No decline in use of RT over calendar period was seen. Use of RT as monotherapy was associated with stage I-II disease and older age among patients with stage III-IV disease. Patients with indolent lymphomas aged ≥ 70 years who were selected for treatment with RT as monotherapy with a dose of ≥ 20 Gy had 2-year RS rate of 100 % which remained similar at five years. For patients with DLBCL, RT as monotherapy with a dose of ≥ 20 Gy was mostly administered to patients aged ≥ 85 years with a 2-year RS rate of 68 %.
The use of RT in first-line lymphoma treatment was stable over calendar time. RT monotherapy is associated with encouraging outcomes among patients with NHL aged ≥ 70 years who were selected to receive this.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: A family history of hematopoietic malignancy is associated with an increased risk of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), although the magnitude of the relative risk is ...unclear. We estimated the association between familial hematopoietic cancer and risk of lymphoma using validated, registry-based family data, and we also investigated whether associations between some environmental exposures and risk of lymphoma vary between individuals with and without such a family history. Methods: In a population-based case–control study of malignant lymphoma, 1506 case patients and 1229 control subjects were linked to the Swedish Multi-Generation Register and then to the Swedish Cancer Register to ascertain history of cancer in first-degree relatives of patients with malignant lymphoma. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with the risk of lymphoma. Results: A history of hematopoietic malignancy in any first-degree relative was associated with an increased risk of all NHL (OR = 1.8, 95% CI = 1.2 to 2.5), common B-cell NHL subtypes, and HL. Relative risks were generally stronger in association with sibling hematopoietic cancer (OR for all NHL = 3.2, 95% CI = 1.3 to 7.6) than with parental hematopoietic cancer (OR = 1.6, 95% CI = 1.1 to 2.3). A family history of NHL or chronic lymphocytic leukemia (CLL) was associated with an increased risk of several NHL subtypes and HL, whereas familial multiple myeloma was associated with a higher risk of follicular lymphoma. There was no statistically significant heterogeneity in NHL risk associations with environmental factors between individuals with and without familial hematopoietic malignancy. Conclusions: The increased risk of NHL and HL among individuals with a family history of hematopoietic malignancy was approximately twofold for both lymphoma types. There was no evidence that etiologic associations varied between familial NHL and nonfamilial NHL.
High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia del(11q), del(13q), del(17p) and ...trisomy 12, and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic profiles from sequential patients' samples allows detection of clonal evolution.
We screened samples from 369 patients with newly diagnosed chronic lymphocytic leukemia from a population-based cohort using 250K single nucleotide polymorphism-arrays. Clonal evolution was evaluated in 59 follow-up samples obtained after 5-9 years.
At diagnosis, copy-number aberrations were identified in 90% of patients; 70% carried known recurrent alterations, including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%). Additional recurrent aberrations were detected on chromosomes 2 (1.9%), 4 (1.4%), 8 (1.6%) and 14 (1.6%). Thirteen patients (3.5%) displayed recurrent copy-number neutral loss of heterozygosity on 13q, of whom 11 had concurrent homozygous del(13q). Genomic complexity and large 13q deletions correlated with inferior outcome, while the former was linked to poor-prognostic aberrations. In the follow-up study, clonal evolution developed in 8/24 (33%) patients with unmutated IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (n=10) did not acquire additional aberrations. The most common secondary event, del(13q), was detected in 6/12 (50%) of all patients with acquired alterations. Interestingly, aberrations on, for example, chromosome 6q, 8p, 9p and 10q developed exclusively in patients with unmutated IGHV.
Whole-genome screening revealed a high frequency of genomic aberrations in newly diagnosed chronic lymphocytic leukemia. Clonal evolution was associated with other markers of aggressive disease and commonly included the known recurrent aberrations.
Background
The increasing amount of molecular data and knowledge about genomic alterations from next-generation sequencing processes together allow for a greater understanding of individual patients, ...thereby advancing precision medicine. Molecular tumour boards feature multidisciplinary teams of clinical experts who meet to discuss complex individual cancer cases. Preparing the meetings is a manual and time-consuming process.
Purpose
To design a clinical decision support system to improve the multimodal data interpretation in molecular tumour board meetings for lymphoma patients at Karolinska University Hospital, Stockholm, Sweden. We investigated user needs and system requirements, explored the employment of artificial intelligence, and evaluated the proposed design with primary stakeholders.
Methods
Design science methodology was used to form and evaluate the proposed artefact. Requirements elicitation was done through a scoping review followed by five semi-structured interviews. We used UML Use Case diagrams to model user interaction and UML Activity diagrams to inform the proposed flow of control in the system. Additionally, we modelled the current and future workflow for MTB meetings and its proposed machine learning pipeline. Interactive sessions with end-users validated the initial requirements based on a fictive patient scenario which helped further refine the system.
Results
The analysis showed that an interactive secure Web-based information system supporting the preparation of the meeting, multidisciplinary discussions, and clinical decision-making could address the identified requirements. Integrating artificial intelligence
via
continual learning and multimodal data fusion were identified as crucial elements that could provide accurate diagnosis and treatment recommendations.
Impact
Our work is of methodological importance in that using artificial intelligence for molecular tumour boards is novel. We provide a consolidated proof-of-concept system that could support the end-to-end clinical decision-making process and positively and immediately impact patients.
Conclusion
Augmenting a digital decision support system for molecular tumour boards with retrospective patient material is promising. This generates realistic and constructive material for human learning, and also digital data for continual learning by data-driven artificial intelligence approaches. The latter makes the future system adaptable to human bias, improving adequacy and decision quality over time and over tasks, while building and maintaining a digital log.
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