impact in DLBCL. [14][15][16][17] Of the macrophages, classically activated M1 type TAM have been described as "good", acting to prevent the growth of tumor tissue, whereas the alternative M2 type TAM may have an opposite effect promoting angiogenesis and tumor development. [18][19][20] Importantly, however, studies in follicular lymphoma have demonstrated that the prognostic significance of the tumor microenvironment and especially macrophages is highly dependent on a given therapy. [21][22][23] In the present study, we investigated how the combination of rituximab with chemotherapy influences non-malignant inflammatory cell-associated clinical outcome in DLBCL. Among all studied markers for macrophages, dendritic, and lymphoid cells, we found that pretreatment gene expression of a macrophage marker CD68 and immunohistochemically defined CD68+ TAM content had a positive prognostic impact on the survival of DLBCL patients treated with chemoimmunotherapy, whereas in patients treated without rituximab, CD68 + TAM content was associated with a poor outcome. Methods Patients and samplesThe screening cohort consisted of prospectively collected DLBCL patients who were less than 65 years old and had primary high-risk (age-adjusted IPI score 2-3) disease. They were treated in the Nordic phase II NLG-LBC-04 protocol with dose-dense chemoimmunotherapy followed by systemic central nervous system prophylaxis. 24 The patients in this correlative study represent a subset of patients in the main clinical trial and were selected on the basis of DLBCL histology, the availability of fresh frozen tissue for RNA extraction and exon arrays (gene expression cohort; n=38) and formalin-fixed, paraffin-embedded lymphoma tissue containing adequate material for the preparation of tissue microarrays (TMA; immunohistochemistry cohort; n=59), and the patients' consent to correlative studies. Details of the screening cohort are provided in Table 1, the Online Supplementary Material and Online Supplementary Table S1.The clinical protocol and sampling were approved by Institutional Review Boards, National Medical Agencies and Ethics Committees in Denmark, Finland, Norway and Sweden, and the trial was registered at ClinicalTrials.gov, number NCT01502982.To validate the findings, three independent retrospective series of chemoimmunotherapy-treated DLBCL patients were used. In order to confirm gene expression data, we used RNA sequencing data from 92 patients generated by the Cancer Genome Characterization Initiative (CGCI; dbGaP database applied study accession: phs000532.v3.p1) 25,26 and oligonucleotide-based microarray data from 233 DLBCL patients generated by the Lymphoma/Leukemia Molecular Profiling Project (LLMPP; GEO dataset: GSE10846).10 Both cohorts are subsets of the original study populations treated with a R-CHOP-like regimen based on the availability of complete expression data and clinical information (Online Supplementary Table S2).In order to confirm the immunohistochemical data, an independent population-based series of ...

Male gender is an adverse prognostic factor in Hodgkin's lymphoma, but no such association has yet been established in non-Hodgkin lymphomas. Here, we have evaluated whether gender has prognostic impact on the survival of patients with B-cell non-Hodgkin lymphoma in the postrituximab era of lymphoma therapies. The study populations consisted of 217 diffuse large B-cell lymphoma (DLBCL) and 110 follicular lymphoma (FL) patients treated with immunochemotherapy. Hundred and sixty chemotherapy-treated DLBCL patients served as a control group. According to Kaplan-Meier analyses, female patients had a significantly better progression-free survival than men both in DLBCL (4 yr PFS 75% vs. 60%; P= 0.013) and in FL (4 yr PFS 68% vs. 52%, P=0.036) patients treated with immunochemotherapy. In chemotherapy-treated DLBCL patients, no difference in survival between the genders was found. The results support the idea that women seem to respond better to rituximab.

Our aim was to construct and test an intervention programme to eradicate cough and cold medicine (CCM) prescriptions for children treated in a nationwide healthcare service company. The study was carried out in the largest private healthcare service company in Finland with a centralised electronic health record system allowing for real-time, doctor-specific practice monitoring. The step-by-step intervention consisted of company-level dissemination of educational materials to doctors and families, educational staff meetings, continuous monitoring of prescriptions, and targeted feedback. Outreach visits were held in noncompliant units. Finally, those physicians who most often prescribed CCM were directly contacted. During the intervention period (2017–2020), there were more than one million paediatric visits. Prescriptions of CCMs to children were completely eradicated in 41% of units and the total number of CCM prescriptions decreased from 6738 to 744 (89%). During the fourth intervention year, CCMs containing opioid derivatives were prescribed for only 0.2% of children aged < 2 years. The decrease in prescriptions was greatest in general practitioners (5.2 to 1.1%). In paediatricians, the prescription rates decreased from 1.5 to 0.2%. The annual costs of CCMs decreased from €183,996 to €18,899 (89.7%). For the intervention, the developers used 343 h and the attended doctors used 684 h of work time during the 4-year intervention. The costs used for developing, implementing, reporting, evaluating, communicating, and data managing formed approximately 11% of total intervention costs.Conclusion: The study showed that a nationwide systematic intervention to change cough medicine prescription practices is feasible and requires only modest financial investments. What is Known:• Cough and cold medicines (CCM) are not effective or safe, especially for children aged 6 years.• Although the use of CCMs has been declining, caregivers continue to administer CCMs to children, and some physicians still prescribe them even for preschool children. What is New:• A nationwide systematic intervention can significantly and cost effectively change CCM prescription habits of paediatricians, general practitioners, and other specialists.• Electronic health records provide additional tools for operative guideline implementation and real-time quality monitoring, including recommendations of useless or harmful treatments.

Pretreatment s-VEGF level is a predictor of PFS after chemoimmunotherapy and may help to further stratify high-risk DLBCL patients into low- and high-risk groups.

Development of targeted agents for the treatment of diffuse large B-cell lymphoma includes clinical evaluation of enzastaurin, an agent that suppresses signaling through protein kinase C-b and AKT pathways. To determine whether protein kinase C-b expression has prognostic significance for diffuse large B-cell lymphoma patients treated with immunochemotherapy, we analyzed the expression of protein kinase C-b II, BCL-2 and cell of origin immunohistochemically from pretreatment samples of 95 diffuse large B-cell lymphoma patients. All patients received rituximab with CHOP or CHOEP. According to Kaplan-Meier analyses, overall survival at 3 years was better among the patients with low than high protein kinase C-b II protein levels (94 vs 76%, P ¼ 0.036). The prognostic value of protein kinase C-b II expression on survival was seen in the patients with low and high International Prognostic Index risk groups, and in all molecular entities. Gene expression data from an independent set of 233 diffuse large B-cell lymphoma patients treated with a combination of rituximab and CHOP-like chemotherapy was analyzed in comparison. Accordingly, a better 3-year overall survival was observed among the subgroup with low protein kinase C-b II mRNA levels (84 vs 68%, P ¼ 0.005). In multivariate analysis with cell of origin, protein kinase C-b II mRNA expression remained as an independent predictor for overall survival. Together, the data show that protein kinase C-b II expression has prognostic significance in diffuse large B-cell lymphoma patients treated with immunochemotherapy. Modern Pathology (2010) 23, 686-693; doi:10.1038/modpathol.2010 published online 26 February 2010 Keywords: diffuse large B-cell lymphoma; R-CHOP; protein kinase C-b II; prognosis Diffuse large B-cell lymphoma is the most common lymphoma subtype comprising 30-40% of all nonHodgkin lymphomas. It is an aggressive disease, of which only 50% of the patients can be cured with anthracyclin-based chemotherapy. However, the concurrent administration of CD20 antibody, rituximab, with different chemotherapies has resulted in a significant improvement of survival compared to chemotherapy alone.

ObjectiveTo evaluate the trajectories of acute upper respiratory tract infections (URTIs), COVID-19, and the use of antibiotics in Finland during the COVID-19 epidemic.DesignPopulation-based cohort study.SettingElectronic medical records from a nationwide healthcare chain in Finland.Participants833 444 patients from a cohort of 1 970 013 Finns who had used medical services between 2017 and 2020.Main outcome measuresNumber of weekly patients of acute URTIs, COVID-19, and the prescribed number of antibiotics in Finland between 6 January 2020 and 21 June 2020. We estimated the respective expected numbers from 1 March 2020 onward using autoregressive integrated moving average model from 1 January 2017 to 1 March 2020. We assessed the public interest in COVID-19 by collecting Google search trend frequencies.ResultsThere was a rapid increase in COVID-related internet searches between weeks 10 and 12. At the same time, there was a 106% increase in diagnoses of acute URTIs, from 410 per 100 000 inhabitants to 845 per 100 000. The first COVID-19 cases were diagnosed on week 11. Prescriptions for URTI-related antibiotics declined by 71% (403 per 100 000 to 117 per 100 000) between weeks 11 and 15 while no relevant change took place in prescriptions of antibiotics for urinary tract infections.ConclusionsAt the beginning of the epidemic, many people contacted healthcare professionals with relatively mild symptoms, as indicated by the reduced rate of URTI-antibiotics prescriptions. Our findings indicate that health service providers should be prepared for rapid variations in service demand. Securing access of true COVID-19 patients to proper diagnostics, care and isolation measures may help in preventing the spread of the disease.

Background: Respiratory infection is the 4th most common reason for absence from work in Finland. There is limited knowledge of how social distancing affects the spread of respiratory infections during respiratory epidemics. We assessed the effect of nationwide infection control strategies against coronavirus disease in 2020 on various respiratory infections (International Statistical Classification of Diseases and Related Health Problems code J06) in occupational outpatient clinics. Methods: We used occupational healthcare data of respiratory infection J06 diagnoses from 2017 to 2020 obtained from the largest health service provider in Finland. The data was divided into three 252 day-long pieces and was weekdaymatched and smoothed by 7-day-moving average. The difference in the J06 diagnosis rate between the follow-up years was measured using Pearson correlation. Possible confounding by sex, age, and region was investigated in a stratified analysis. Confounding by respiratory syncytial virus was analysed using nationwide data of confirmed cases obtained from the national registry. Results: In the second quarter of 2020, the trend in the daily number of J06 diagnoses was significantly different from the follow-up years 2019 and 2018. The number of J06 diagnoses peaked between March and April 2020 with roughly 2-fold higher count compared to normal. The timing of these peaks matched with the government issued infection control strategies and lockdowns. Based on stratified analysis, the increase in the number of J06 diagnoses was not confounded by region, age, or sex. Moreover, the rapid increase in the number of J06 diagnoses was not governed by the respiratory syncytial virus. Conclusion: Nationwide infection control strategies were effective to slow down the spread of common respiratory infectious diseases in the occupational population.

2650 Background: Tumor associated macrophages (TAM) have at least two potential roles in promoting tumor growth: suppression of immune responses and potentiation of angiogenesis. In numerous cancer types, including lymphomas, high M2 type TAM content has been associated with worse prognosis. Rarely, high TAM content correlates with better survival. We have recently shown that CD68 positive TAMs in DLBCL contribute to unfavorable survival after high dose chemotherapy. Here we have extended our analyses on M2 type macrophages and questioned how combination of rituximab with chemotherapy influences TAM-associated clinical outcome. Patients and Methods: Expression of CD163 and CCL18, which are primarily expressed in M2 type macrophages, were identified immunohistochemically from samples of 101 de novo DLBCL patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen (immunochemotherapy). With a median follow-up of 65 months, (range 16–114 months), 5-year progression free survival (PFS) was 70% and overall survival (OS) 73%. 29 DLBCL patients previously treated with up front high dose chemotherapy served as a control group. Results: Correlation between CD163 and CCL18 positive TAMs was found (rs=0.427, p<0.001). In the Kaplan-Meier analyses the cutoff level of 67% was found to best discriminate between subgroups with different outcomes. Consistent with previous data, chemotherapy-treated patients with high CD163 or CCL18 positive TAM counts displayed a significantly inferior OS and PFS than the low group (Table). In contrast, after rituximab containing regimen, the patients with high CD163 and CCL18 positive TAM content tended to have favorable survival. Among the patients with low counts in both CD163 and CCL18 positive TAMs, PFS and OS were found to be significantly worse in comparison to others. Conclusions: In contrast to data on chemotherapy treated DLBCL or other lymphoma types, M2 type TAM content is associated with favorable prognosis in DLBCL patients after immunochemotherapy. Disclosures: No relevant conflicts of interest to declare.