Anger and disgust shape judgments of social sanctions across cultures, especially in high individual autonomy societies.

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

UV-Induced Spectral and Morphological Changes in Bacterial Spores for Inactivation Assessment.

The ability to detect and inactivate spore-forming bacteria is of significance within, for example, industrial, healthcare, and defense sectors. Not only are stringent protocols necessary for the inactivation of spores but robust procedures are also required to detect viable spores after an inactivation assay to evaluate the procedure's success. UV radiation is a standard procedure to inactivate spores. However, there is limited understanding regarding its impact on spores' spectral and morphological characteristics. A further insight into these UV-induced changes can significantly improve the design of spore decontamination procedures and verification assays. This work investigates the spectral and morphological changes to Bacillus thuringiensis spores after UV exposure. Using absorbance and fluorescence spectroscopy, we observe an exponential decay in the spectral intensity of amino acids and protein structures, as well as a logistic increase in dimerized DPA with increased UV exposure on bulk spore suspensions. Additionally, using micro-Raman spectroscopy, we observe DPA release and protein degradation with increased UV exposure. More specifically, the protein backbone's 1600-1700 cm-1 amide I band decays slower than other amino acid-based structures. Last, using electron microscopy and light scattering measurements, we observe shriveling of the spore bodies with increased UV radiation, alongside the leaking of core content and disruption of proteinaceous coat and exosporium layers. Overall, this work utilized spectroscopy and electron microscopy techniques to gain new understanding of UV-induced spore inactivation relating to spore degradation and CaDPA release. The study also identified spectroscopic indicators that can be used to determine spore viability after inactivation. These findings have practical applications in the development of new spore decontamination and inactivation validation methods.

Higher cyclosporine-A concentration increases the risk of relapse in AML following allogeneic stem cell transplantation from unrelated donors using anti-thymocyte globulin.

Cyclosporine-A (CsA) is used to prevent acute graft-versus-host disease (aGvHD). European Society for Blood and Marrow transplantation (EBMT) recommends a CsA target serum concentration of 200-300 µg/L during the first month after allogeneic hematopoietic stem cell transplantation (HSCT). With this study, we investigated whether a median CsA concentration > 200 µg/L (CsAhigh) the first month after HSCT, compared to ≤ 200 µg/L (CsAlow), increased the relapse risk of acute myloid leukemia (AML), using unrelated donors (URD) and antithymocyte globulin (ATG). Data was collected from 157 patients with AML, transplanted 2010-2016. The cumulative incidence of relapse (CIR) at 60 months was 50% in the CsAhigh versus 32% in the CsAlow group (p = 0.016). In univariate analysis, CsAhigh versus CsAlow (p = 0.028), 10-unit increase of CsA as a continuous variable (p = 0.017) and high risk disease (p = 0.003) were associated with higher CIR. The results remained after adjusting for disease risk. Death following relapse occurred more frequently in the CsAhigh group (p = 0.0076). There were no significant differences in rates of aGvHD, chronic GvHD (cGvHD), EBV/CMV-infections or overall survival (OS) between the two groups. In conclusion, we found that a median CsA concentration > 200 µg/L, the first month after HSCT, results in higher CIR of AML when combined with ATG.

Despite warnings, co-medication with proton pump inhibitors and dasatinib is common in chronic myeloid leukemia, but XS004, a novel oral dasatinib formulation, provides reduced pH-dependence, minimizing undesirable drug-drug interactions.

BACKGROUND: Dasatinib and other tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML). However, as a lipophilic weak base, crystalline monohydrate, dasatinib (Sprycel®) is poorly soluble, rendering a pH-dependent absorption and a highly variable bioavailability. Thus, co-medication with proton pump inhibitors (PPI) profoundly impairs dasatinib uptake and is clearly recommended against. XS004 is a novel oral immediate release and amorphous solid dispersion (ASD) formulation of dasatinib and is bioequivalent to the original crystalline dasatinib at 30% lower dosages. XS004 is designed to mitigate gastric pH dependency, thus optimizing absorption and bioavailability. METHODS: We investigated the prevalence of dasatinib and PPI co-medication among chronic-phase CML patients in a real-world setting and assessed the plasma pharmacokinetics (PK) of XS004 with and without PPI co-medication (omeprazole) in healthy volunteers. RESULTS: Using the Swedish CML and Prescribed Drug Registers, we identified 676 TKI-treated CML patients; 320 (47%) had been prescribed PPI at some point after CML diagnosis. Among dasatinib-treated patients, the 2-year cumulative PPI co-medication was 24%. Interestingly, the 5-year overall survival was significantly lower for TKI-treated CML patients with versus without PPI co-medication (79% vs. 94%; hazard ratio 3.5; 95% confidence interval, 2.1-5.3; p < .0001). When assessing PK of XS004, neither Cmax nor area under the plasma concentration curve levels in plasma were significantly altered by the PPI co-medication. CONCLUSION: In conclusion, despite warnings, PPI co-medication is common among dasatinib-treated CML patients in a real-world setting. The new XS004 ASD formulation of dasatinib provided, in contrast to original crystalline dasatinib, superior pH independence with stable bioavailability, thereby minimizing drug-drug interactions. This may improve the long-term efficacy and tolerability of dasatinib in CML.

Outcomes in patients with chest pain in emergency departments using high-sensitivity versus conventional troponins.

Objectives. There is a paucity of data regarding the association between the use of high-sensitivity troponin (hs-cTn) compared with conventional troponin (cTn) and outcomes in chest pain patients in emergency departments (EDs). This study examined the impact of hs-cTnT on prognosis in chest pain patients in EDs. Design. In an observational cohort study, we included chest pain patients visiting the EDs of 14 hospitals in Sweden from 2011 to 2016. The study population was retrieved from each hospital, and information on characteristics and outcomes was collected from nationwide registries. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals (HR, 95% CI) for (1) 1-year all-cause mortality, (2) missed acute coronary syndromes (ACSs), (3) use of coronary angiography, and (4) revascularizations within 30 days. Results. We included 170461 patients with chest pain where 62669 patients were tested with cTn while 107792 patients were tested with hs-cTnT. We found 4149 (4.6%) deaths in the cTn group and 6087 (3.7%) deaths in the hs-cTnT group. Patients in the hs-cTnT group had 9% lower mortality (0.91, 0.87-0.94), and were 14% more likely to undergo coronary angiography (1.14, 1.10-1.17), and 12% more likely to be revascularized (1.12, 1.08-1.17) than patients in the cTn group. Conclusions. Patients with chest pain visiting EDs using hs-cTnT had lower mortality and a higher likelihood of undergoing coronary angiographies and revascularizations than those using cTn. There may be a survival benefit of being tested with hs-cTnT compared with cTn in patients seeking medical attention for chest pain.

Artificial Intelligence Increases the Agreement among Physicians Classifying Focal Skeleton/Bone Marrow Uptake in Hodgkin's Lymphoma Patients Staged with [18F]FDG PET/CT-a Retrospective Study.

Purpose: Classification of focal skeleton/bone marrow uptake (BMU) can be challenging. The aim is to investigate whether an artificial intelligence-based method (AI), which highlights suspicious focal BMU, increases interobserver agreement among a group of physicians from different hospitals classifying Hodgkin's lymphoma (HL) patients staged with [18F]FDG PET/CT. Methods: Forty-eight patients staged with [18F]FDG PET/CT at Sahlgenska University Hospital between 2017 and 2018 were reviewed twice, 6 months apart, regarding focal BMU. During the second time review, the 10 physicians also had access to AI-based advice regarding focal BMU. Results: Each physician's classifications were pairwise compared with the classifications made by all the other physicians, resulting in 45 unique pairs of comparisons both without and with AI advice. The agreement between the physicians increased significantly when AI advice was available, which was measured as an increase in mean Kappa values from 0.51 (range 0.25-0.80) without AI advice to 0.61 (range 0.19-0.94) with AI advice (p = 0.005). The majority of the physicians agreed with the AI-based method in 40 (83%) of the 48 cases. Conclusion: An AI-based method significantly increases interobserver agreement among physicians working at different hospitals by highlighting suspicious focal BMU in HL patients staged with [18F]FDG PET/CT.

Survival by First-line Treatment Type and Timing of Progression Among Follicular Lymphoma Patients: A National Population-based Study in Sweden.

In follicular lymphoma (FL), progression of disease ≤24 months (POD24) has emerged as an important prognostic marker for overall survival (OS). We aimed to investigate survival more broadly by timing of progression and treatment in a national population-based setting. We identified 948 stage II-IV indolent FL patients in the Swedish Lymphoma Register diagnosed 2007-2014 who received first-line systemic therapy, followed through 2020. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by first POD at any time during follow-up using Cox regression. OS was predicted by POD using an illness-death model. During a median follow-up of 6.1 years (IQR: 3.5-8.4), 414 patients experienced POD (44%), of which 270 (65%) occurred ≤24 months. POD was represented by a transformation in 15% of cases. Compared to progression-free patients, POD increased all-cause mortality across treatments, but less so among patients treated with rituximab(R)-single (HR = 4.54, 95% CI: 2.76-7.47) than R-chemotherapy (HR = 8.17, 95% CI: 6.09-10.94). The effect of POD was similar following R-CHOP (HR = 8.97, 95% CI: 6.14-13.10) and BR (HR = 10.29, 95% CI: 5.60-18.91). The negative impact of POD on survival remained for progressions up to 5 years after R-chemotherapy, but was restricted to 2 years after R-single. After R-chemotherapy, the 5-year OS conditional on POD occurring at 12, 24, and 60 months was 34%, 46%, and 57% respectively, versus 78%, 82%, and 83% if progression-free. To conclude, POD before but also beyond 24 months is associated with worse survival, illustrating the need for individualized management for optimal care of FL patients.

Bone marrow expression of CD68/CD163 macrophages, IL-17 and FOXP3 cells in aplastic anemia and their relation to prognosis.

OBJECTIVES: The primary mechanism for bone marrow failure in aplastic anemia (AA) is autoimmune hematopoietic stem cell destruction. AA can be cured with antithymocyte globulin (ATG) treatment, and some smaller studies have indicated that the number of regulatory T cells (Tregs) may be predictive of response. Additionally, AA patients appear to have elevated numbers of Th17 cells and bone marrow macrophages, but outcome data are missing. METHODS: We performed immunohistochemistry on bone marrow biopsies from 121 ATG-treated AA patients and 14 healthy controls, using antibodies against FOXP3 (for Tregs), IL-17 (for Th17), CD68 (for pan-macrophages) and CD163 (for M2 type macrophages) to study their possible relation to ATG response and AA prognosis. RESULTS: AA patients had significantly fewer Tregs and Th17 cells but significantly more macrophages compared with controls. Treg, Th17 and pan-macrophage cell numbers were not associated with ATG response or differences in survival. Patients with higher levels of M2 macrophages had improved 5-year overall survival: 79.6% versus 57.4% (p = .017), and this benefit was primarily seen in AA patients with non-severe disease. CONCLUSIONS: We found that Treg and Th17 cell numbers did not predict ATG response or survival, whereas M2 macrophages may be associated with improved survival.

The effect of herd immunity thresholds on willingness to vaccinate.

Throughout the COVID-19 pandemic, media and policymakers openly speculated about the number of immune citizens needed to reach a herd immunity threshold. What are the effects of such numerical goals on the willingness to vaccinate? In a large representative sample (N = 1540) of unvaccinated Swedish citizens, we find that giving a low (60%) compared to a high (90%) threshold has direct effects on beliefs about reaching herd immunity and beliefs about how many others that will get vaccinated. Presenting the high threshold makes people believe that herd immunity is harder to reach (on average about half a step on a seven-point scale), compared to the low threshold. Yet at the same time, people also believe that a higher number of the population will get vaccinated (on average about 3.3% more of the population). Since these beliefs affect willingness to vaccinate in opposite directions, some individuals are encouraged and others discouraged depending on the threshold presented. Specifically, in mediation analysis, the high threshold indirectly increases vaccination willingness through the belief that many others will get vaccinated (B = 0.027, p = 0.003). At the same time, the high threshold also decreases vaccination willingness through the belief that the threshold goal is less attainable (B = -0.053, p < 0.001) compared to the low threshold condition. This has consequences for ongoing COVID-19 vaccination and future vaccination campaigns. One message may not fit all, as different groups can be encouraged or discouraged from vaccination.

Outcomes of relapsed/refractory diffuse large B-cell lymphoma and influence of chimaeric antigen receptor T trial eligibility criteria in second line-A population-based study of 736 patients.

Several recently published trials investigate novel therapies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). To estimate the benefit of these therapies in the real-world setting, comprehensive data on patients treated in clinical routine are needed. We report outcomes for 736 R/R DLBCL patients identified among all curatively treated DLBCL patients in Sweden in the period 2007-2014. Survival and associations with disease characteristics, second-line treatment and fulfilment of chimaeric antigen receptor (CAR) T-cell trial criteria were assessed. Median overall survival (OS) was 6.6 months (≤70 years 9.6 months, >70 years 4.9 months). Early relapse (≤12 months) was strongly associated with selection of less intensive treatment and poor survival. Among patients of at most 70 years of age, 63% started intensive second-line treatment and 34% received autologous stem cell transplantation (ASCT). Two-year OS among transplanted patients was 56% (early relapse ≤12 months 40%, late relapse >12 months 66%). A minority of patients 76 years (n = 178/506, 35%) fitted CAR T trial criteria. Median progression-free survival (PFS) for patients with early relapse fitting trial criteria was 4.8 months. In conclusion, most R/R DLBCL manifest early and are often ineligible for or cannot complete intensive regimens resulting in dismal survival. Real-world patients eligible for CAR T trials also did poorly, providing a benchmark for efficacy of novel therapies.

Impact of treatment with immunomodulators and tumour necrosis factor antagonists on the incidence of infectious events in patients with inflammatory bowel disease.

BACKGROUND: Corticosteroids, immunomodulators (IM) and tumour necrosis factor antagonists (anti-TNF) are commonly used in the treatment of inflammatory bowel disease (IBD) but they also supress the defence against infectious disease. The aim of this study was to analyse the incidence of infectious events in patients with IBD and the association to concomitant medical therapy. METHODS: We performed a retrospective medical chart review of patients with IBD aged 18-65 years included in the Swedish Registry of Inflammatory Bowel Disease in the catchment area of Umeå University Hospital, Sweden. Data were collected from the period 01 January 2006, to 31 January 2019. An infectious event was defined as an outpatient prescription of antimicrobials or a positive diagnostic test for infection. RESULTS: During a period of 5,120 observation-years, we observed 1,394 events in 593 patients. The mean number of infectious events per 100 person-years was 27.2 (standard deviation [SD]: 0.46). There were no differences in mean incidence rates between patients treated with no immunosuppression (23.0 events per 100 person-years, SD: 50.4), patients treated with IM monotherapy (27.6 events per 100 person-years, SD: 49.9), patients treated with anti-TNF monotherapy (34.3 events per 100 person-years, SD: 50.1) and patients on combination therapy (22.5 events per 100-person-years, SD: 44.2). In a multivariate logistic regression, female gender (adjusted odds ratio [AOR]: 2.24; 95% confidence interval [CI]: 1.49-3.37) and combination therapy (AOR: 3.46; 95% CI: 1.52-7.85) were associated with higher risks of infection (>32 events per 100 person years). Also, patients treated with any immunosuppression treatment for 25-75% (AOR: 2.29; 95% CI: 1.21-4.34) and for >75% (AOR: 1.93; 95% CI: 1.19-3.12) of the observation period were at higher risks compared to patients treated with immunosuppression <25% of the observation period. CONCLUSION: We observed no significant difference in risk for infections between patients on monotherapy with IM or anti-TNF and patients with low use of immunosuppression, but there was a significant risk for combination therapy.

pH-induced changes in Raman, UV-vis absorbance, and fluorescence spectra of dipicolinic acid (DPA).

Dipicolinic acid (DPA) is an essential component for the protection of DNA in bacterial endospores and is often used as a biomarker for spore detection. Depending upon the pH of the solution, DPA exists in different ionic forms. Therefore, it is important to understand how these ionic forms influence spectroscopic response. In this work, we characterize Raman and absorption spectra of DPA in a pH range of 2.0-10.5. We show that the ring breathing mode Raman peak of DPA shifts from 1003 cm-1 to 1017 cm-1 and then to 1000 cm-1 as pH increases from 2 to 5. The relative peak intensities related to the different ionic forms of DPA are used to experimentally derive the pKa values (2.3 and 4.8). We observe using UV-vis spectroscopy that the changes in the absorption spectrum of DPA as a function of pH correlate with the changes observed in Raman spectroscopy, and the same pKa values are verified. Lastly, using fluorescence spectroscopy and exciting a DPA solution at between 210-330 nm, we observe a shift in fluorescence emission from 375 nm to 425 nm between pH 2 and pH 6 when exciting at 320 nm. Our work shows that the different spectral responses from the three ionic forms of DPA may have to be taken into account in, e.g., spectral analysis and for detection applications.

Transcriptome sequencing of archived lymphoma specimens is feasible and clinically relevant using exome capture technology.

Formalin-fixed, paraffin-embedded (FFPE) specimens are an underutilized resource in medical research, particularly in the setting of transcriptome sequencing, as RNA from these samples is often degraded. We took advantage of an exome capture-based RNA-sequencing protocol to explore global gene expression in paired fresh-frozen (FF) and FFPE samples from 16 diffuse large B-cell lymphoma (DLBCL) patients. While FFPE samples generated fewer mapped reads compared to their FF counterparts, these reads captured the same library complexity and had a similar number of genes expressed on average. Furthermore, gene expression demonstrated a high correlation when comparing housekeeping genes only or across the entire transcriptome (r = 0.99 for both comparisons). Differences in gene expression were primarily seen in lowly expressed genes and genes with small or large coding sequences. Using cell-of-origin classifiers and clinically relevant gene expression signatures for DLBCL, FF, and FFPE samples from the same biopsy paired nearly perfectly in clustering analysis. This was further confirmed in a validation cohort of 50 FFPE DLBCL samples. In summary, we found the biological differences between tumors to be far greater than artifacts created as a result of degraded RNA. We conclude that exome capture transcriptome sequencing data from archival samples can confidently be used for cell-of-origin classification of DLBCL samples.

Laser induced degradation of bacterial spores during micro-Raman spectroscopy.

Micro-Raman spectroscopy combined with optical tweezers is a powerful method to analyze how the biochemical composition and molecular structures of individual biological objects change with time. In this work we investigate laser induced effects in the trapped object. Bacillus thuringiensis spores, which are robust organisms known for their resilience to light, heat, and chemicals are used for this study. We trap spores and monitor the Raman peak from CaDPA (calcium dipicolinic acid), which is a chemical protecting the spore core. We see a correlation between the amount of laser power used in the trap and the release of CaDPA from the spore. At a laser power of 5 mW, the CaDPA from spores in water suspension remain intact over the 90 min experiment, however, at higher laser powers an induced effect could be observed. SEM images of laser exposed spores (after loss of CaDPA Raman peak was confirmed) show a notable alteration of the spores' structure. Our Raman data indicates that the median dose exposure to lose the CaDPA peak was ∼60 J at 808 nm. For decontaminated/deactivated spores, i.e., treated in sodium hypochlorite or peracetic acid solutions, the sensitivity on laser power is even more pronounced and different behavior could be observed on spores treated by the two chemicals. Importantly, the observed effect is most likely photochemical since the increase of the spore temperature is in the order of 0.1 K as suggested by our numerical multiphysics model. Our results show that care must be taken when using micro-Raman spectroscopy on biological objects since photoinduced effects may substantially affect the results.

Synthetic NAC 71-82 Peptides Designed to Produce Fibrils with Different Protofilament Interface Contacts.

Alpha-synucleinopathies are featured by fibrillar inclusions in brain cells. Although α-synuclein fibrils display structural diversity, the origin of this diversity is not fully understood. We used molecular dynamics simulations to design synthetic peptides, based on the NAC 71-82 amino acid fragment of α-synuclein, that govern protofilament contacts and generation of twisted fibrillar polymorphs. Four peptides with structures based on either single or double fragments and capped or non-capped ends were selected for further analysis. We determined the fibrillar yield and the structures from these peptides found in the solution after fibrillisation using protein concentration determination assay and circular dichroism spectroscopy. In addition, we characterised secondary structures formed by individual fibrillar complexes using laser-tweezers Raman spectroscopy. Results suggest less mature fibrils, based on the lower relative ß-sheet content for double- than single-fragment peptide fibrils. We confirmed this structural difference by TEM analysis which revealed, in addition to short protofibrils, more elongated, twisted and rod-like fibril structures in non-capped and capped double-fragment peptide systems, respectively. Finally, time-correlated single-photon counting demonstrated a difference in the Thioflavin T fluorescence lifetime profiles upon fibril binding. It could be proposed that this difference originated from morphological differences in the fibril samples. Altogether, these results highlight the potential of using peptide models for the generation of fibrils that share morphological features relevant for disease, e.g., twisted and rod-like polymorphs.

Proteomic analysis in diffuse large B-cell lymphoma identifies dysregulated tumor microenvironment proteins in non-GCB/ABC subtype patients.

The complexity of the activated B-cell like (ABC) diffuse large B-cell lymphoma (DLBCL) subtype is probably not only explained by genetic alterations and methods to measure global protein expression could bring new knowledge regarding the pathophysiology. We used quantitative proteomics to analyze the global protein expression of formalin-fixed paraffin-embedded (FFPE) tumor tissues from 202 DLBCL patients. We identified 6430 proteins and 498 were significantly regulated between the germinal center B-cell like (GCB) and non-GCB groups. A number of proteins previously not described to be upregulated in non-GCB or ABC DLBCL was found, e.g. CD64, CD85A, guanylate-binding protein 1 (GBP1), interferon-induced proteins with tetratricopeptide repeat (IFIT)2, and mixed lineage kinase domain-like protein (MLKL) and immunohistochemical staining showed higher expression of GBP1 and MLKL. A cluster analysis revealed that the most prominent cluster contained proteins involved in the tumor microenvironment and regulation of the immune system. Our data suggest that the therapeutic focus should be expanded toward the tumor microenvironment in non-GCB/ABC subtype patients.

Age is the most important predictor of survival in diffuse large B-cell lymphoma patients achieving event-free survival at 24 months: a Swedish population-based study.

Routine follow-up for diffuse large B-cell lymphoma have been shortened to 2 years when event-free survival at 24 months (EFS24) emerged as a new milestone. In the present study, we aimed to determine whether the achievement of this milestone affected overall survival (OS). We compared OS to that of an age- and sex-matched population, analysed other factors governing OS, and reviewed the causes of death. Data were collected from the Swedish Cancer Registry and from individual patient's records. We included 1169 adult patients from five counties between the years 2001 and 2014. The median (range) age was 64·6 (18-91) years, 56·6% were men and the median follow-up was 82·3 months. For early stages, the achievement of EFS12 did not improve OS. More than two-thirds of the patients (n = 837, 71·6%) achieved EFS24, of which 190 (22·7%) died during follow-up. Lymphoma (20%), cardiovascular disease (22·4%) and malignancies (16%) contributed to causes of death. Patients aged <60 years had an OS that matched the standard population. In multivariate analysis, only age >60 years significantly affected OS after EFS24 compared with the standard population. We concluded that follow-up beyond EFS24 should be considered for patients aged >60 years.

[Precision diagnostics and therapy in hematological malignancies]. / Precisionsmedicin standard vid flera hematologiska sjukdomar.

Precision diagnostics and therapy have been implemented rather early in clinical hematology due to the easy accessibility of blood and bone marrow, allowing not only for consecutive genetic analysis at diagnosis, remission and relapse, but also for culturing these cells and testing new drugs in vitro. One contributing factor has also been the relatively low number of ¼driver« mutations in hematologic malignancies and that some of them are gain of function mutations that are relatively easy to target by drugs. Examples of this development are ABL1-, JAK2-, and FLT3-inhibitors for the treatment of chronic myeloid leukemia, myeloproliferative neoplasms, and acute myeloid leukemia, respectively. More recently, gene panel sequencing has been introduced in clinical routine to identify genetic alterations with diagnostic, prognostic and predictive impact, and more sensitive techniques to monitor minimal residual disease are emerging. Whole genome and transcriptome sequencing are currently evaluated as the next diagnostic tool. Finally, a large number of targeted therapies are currently under development and/or undergoing clinical trials.

Artificial intelligence could alert for focal skeleton/bone marrow uptake in Hodgkin's lymphoma patients staged with FDG-PET/CT.

To develop an artificial intelligence (AI)-based method for the detection of focal skeleton/bone marrow uptake (BMU) in patients with Hodgkin's lymphoma (HL) undergoing staging with FDG-PET/CT. The results of the AI in a separate test group were compared to the interpretations of independent physicians. The skeleton and bone marrow were segmented using a convolutional neural network. The training of AI was based on 153 un-treated patients. Bone uptake significantly higher than the mean BMU was marked as abnormal, and an index, based on the total squared abnormal uptake, was computed to identify the focal uptake. Patients with an index above a predefined threshold were interpreted as having focal uptake. As the test group, 48 un-treated patients who had undergone a staging FDG-PET/CT between 2017-2018 with biopsy-proven HL were retrospectively included. Ten physicians classified the 48 cases regarding focal skeleton/BMU. The majority of the physicians agreed with the AI in 39/48 cases (81%) regarding focal skeleton/bone marrow involvement. Inter-observer agreement between the physicians was moderate, Kappa 0.51 (range 0.25-0.80). An AI-based method can be developed to highlight suspicious focal skeleton/BMU in HL patients staged with FDG-PET/CT. Inter-observer agreement regarding focal BMU is moderate among nuclear medicine physicians.