The Genetic Profile of Large B-Cell Lymphomas Presenting in the Ocular Adnexa.

To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL) presenting in the ocular adnexa. Pathogenic variants and copy number variations in 128 B-cell lymphoma-relevant genes were analyzed by targeted next-generation sequencing. Genetic subtypes were determined with the LymphGen algorithm. Primary ocular adnexal DLBCL-NOS constituted 50% (n = 14) and was generally characterized by non-germinal center B-cell origin (non-GCB) (n = 8, 57%), and LymphGen MCD subtype (n = 5, 36%). Primary ocular adnexal DLBCL-NOS presented pathogenic variants in genes involved in NF-κB activation and genes which are recurrently mutated in other extranodal lymphomas of non-GCB origin, including MYD88 (n = 4, 29%), CD79B (n = 3, 21%), PIM1 (n = 3, 21%), and TBL1XR1 (n = 3, 21%). Relapsed DLBCL-NOS presenting in the ocular adnexa (n = 6) were all of non-GCB origin and frequently of MCD subtype (n = 3, 50%), presenting with a similar genetic profile as primary ocular adnexal DLBCL-NOS. These results provide valuable insights into genetic drivers in ocular adnexal DLBCL-NOS, offering potential applications in future precision medicine.

Specific location of ocular adnexal lymphoma and mortality: an international multicentre retrospective study.

AIMS: To examine whether the specific location of ocular adnexal lymphoma (OAL) and the American Joint Committee on Cancer (AJCC) TNM tumour stage are prognostic factors for mortality in the main OAL subtypes. METHODS: Clinical and survival data were retrospectively collected from seven international eye cancer centres. All patients from 1980 to 2017 with histologically verified primary or secondary OAL were included. Cox regression was used to compare the ocular adnexal tumour locations on all-cause mortality and disease-specific mortality. RESULTS: OAL was identified in 1168 patients. The most frequent lymphoma subtypes were extranodal marginal zone B-cell lymphoma (EMZL) (n=688, 59%); follicular lymphoma (FL) (n=150, 13%); diffuse large B-cell lymphoma (DLBCL) (n=131, 11%); and mantle cell lymphoma (MCL) (n=89, 8%). AJCC/TNM tumour-stage (T-stage) was significantly associated with disease-specific mortality in primary ocular adnexal EMZL and increased through T-categories from T1 to T3 disease. No associations between AJCC/TNM T-stage and mortality were found in primary ocular adnexal FL, DLBCL, or MCL. EMZL located in the eyelid had a significantly increased disease-specific mortality compared with orbital and conjunctival EMZL, in both primary EMZL and the full EMZL cohort. In DLBCL, eyelid location had a significantly higher disease-specific mortality compared with an orbital or lacrimal gland location. CONCLUSION: Disease-specific mortality is associated with AJCC/TNM T-stage in primary ocular adnexal EMZL patients. Lymphoma of the eyelid has the highest disease-specific mortality in primary EMZL, and in the full cohort of EMZL and DLBCL patients.

Lymphoma of the Lacrimal Gland - An International Multicenter Retrospective Study.

PURPOSE: To characterize the clinical features of subtype-specific lacrimal gland lymphoma and their effect on patient survival. DESIGN: Multicenter retrospective interventional case series. METHODS: Patient data were collected from 6 international eye cancer centers from January 1, 1980, through December 31, 2017. All patients with histologically verified primary or secondary lymphoma of the lacrimal gland were included. Primary endpoints were overall survival (OS) and disease-specific survival (DSS). RESULTS: A total of 260 patients with lacrimal gland lymphoma were identified. The median age was 58 years and 52% of patients were men. Non-Hodgkin B-cell lymphomas constituted 99% (n = 258) and T-cell lymphomas constituted 1% (n = 2). The most frequent lymphoma subtypes were extranodal marginal zone B-cell lymphoma (EMZL) (n = 177, 68%), follicular lymphoma (FL) (n = 26, 10%), diffuse large B-cell lymphoma (DLBCL) (n = 25, 10%), and mantle cell lymphoma (MCL) (n = 17, 7%). Low-grade lymphomas (EMZL and FL) were most commonly treated with external beam radiotherapy (EBRT), whereas high-grade lymphomas (DLBCL and MCL) were treated with chemotherapy in combination with rituximab and/or EBRT. The prognosis was relatively good with a 5-year OS and DSS of 73.8% and 87.5%, respectively. Lymphoma subtype was a statistically significant predictor for DSS, with EMZL (5-year DSS: 93.4%) having the best prognosis and DLBCL (5-year DSS: 52.6%) having the poorest. CONCLUSIONS: This is the largest reported collection of data of subtype-specific lacrimal gland lymphoma. The subtype distribution of lacrimal gland lymphoma resembles that of the ocular adnexa. Prognosis is good and the histologic subtype is a significant predictor for disease-specific survival.

Plasma free fatty acid concentration is closely tied to whole body peak fat oxidation rate during repeated exercise.

Plasma free fatty acids (FFA) are a major contributor to whole body fat oxidation during exercise. However, the extent to which manipulating plasma FFA concentrations will influence whole body peak fat oxidation rate (PFO) during exercise remains elusive. In this study we aimed to increase plasma FFA concentrations through a combination of fasting and repeated exercise bouts. We hypothesized that an increase in plasma FFA concentration would increase PFO in a dose-dependent manner. Ten healthy young (31 ± 6 yr) (mean ± SD) well-trained (maximal oxygen uptake 65.9 ± 6.1 ml·min-1·kg-1) men performed four graded exercise tests (GXTs) on 1 day. The GXTs were interspersed by 4 h of bed rest. This was conducted either in a fasted state or with the consumption of a standardized carbohydrate-rich meal 3.5 h before each GXT. Fasting and previous GXTs resulted in a gradual increase in PFO from 0.63 ± 0.18 g/min after an overnight fast (10 h) to 0.93 ± 0.17 g/min after ∼22 h of fasting and three previous GXTs. This increase in PFO coincided with an increase in plasma FFA concentrations (r2 = 0.73, P < 0.0001). Ingestion of a carbohydrate-rich meal 3.5 h before each GXT resulted in unaltered PFO. This was also reflected in unchanged plasma FFA, glucose, and insulin concentrations. In this study we show that plasma FFA availability is closely tied to whole body PFO and that the length of fasting combined with previous exercise are robust stimuli toward increasing plasma FFA concentration, highlighting the importance for preexercise standardization when conducting GXTs measuring substrate oxidation. NEW & NOTEWORTHY We show that peak fat oxidation is increased in close relationship with plasma free fatty acid availability after combined fasting and repeated incremental exercise tests in healthy highly trained men. Therefore it may be argued that whole body fat oxidation rate measured in most cases after an overnight fast indeed does not represent whole body maximal fat oxidation rate but a whole body peak fat oxidation rate within the context of the preexercise standardization obtained in the study design.

Peak Fat Oxidation is not Independently Related to Ironman Performance in Women.

The aim of the present study was to investigate if peak fat oxidation rate (PFO) is related to Ironman performance in female athletes. Thirty-six female Ironman athletes (age: 34±1 yrs, [21-45 yrs.] SEM [Range]) with a BMI of 22.1±2.0 kg/m2 [18.8-28.4 kg/m2], a body fat percentage of 24.8±1.0% [9.0-37.0%] and a V̇O2peak of 53.0±1.3 ml/min/kg [36.5-70.5 ml/min/kg] were tested in the laboratory prior to the Ironman Copenhagen 2017. Race time ranged from 9:17:07 to 15:23:48 with mean race time being 11:57:26 h:min:s (717 min). By simple linear regression analyses we found associations between race time and P FO (r2=0.22, p<0.005), V̇O2peak (r2=0.65, p<0.0001) and the relative exercise intensity eliciting PFO (Fatmax) (r2=0.35, p=0.0001). Furthermore, associations were found between race time and body fat percentage (r2=0.44, p<0.0001) and age (r2=0.16, p<0.05). By means of multiple regression analysis, V̇O2peak was the only statistically significant variable explaining 64% of the variation in race time (adj. r2=0.64, p<0.005). In conclusion, these results demonstrate that PFO is not independently related to Ironman performance in a heterogeneous group of female athletes. Interestingly, V̇O2peak alone was able to predict 64% of the variation in Ironman race times.

Maximal Fat Oxidation is Related to Performance in an Ironman Triathlon.

The aim of the present study was to investigate the relationship between maximal fat oxidation rate (MFO) measured during a progressive exercise test on a cycle ergometer and ultra-endurance performance. 61 male ironman athletes (age: 35±1 yrs. [23-47 yrs.], with a BMI of 23.6±0.3 kg/m2 [20.0-30.1 kg/m2], a body fat percentage of 16.7±0.7% [8.4-30.7%] and a VO2peak of 58.7±0.7 ml/min/kg [43.9-72.5 ml/min/kg] SEM [Range]) were tested in the laboratory between 25 and 4 days prior to the ultra-endurance event, 2016 Ironman Copenhagen. Simple bivariate analyses revealed significant negative correlations between race time and MFO (r2=0.12, p<0.005) and VO2peak (r2=0.45, p<0.0001) and a positive correlation between race time and body fat percentage (r2=0.27, p<0.0001). MFO and VO2peak were not correlated. When the significant variables from the bivariate regression analyses were entered into the multiple regression models, VO2peak and MFO together explained 50% of the variation observed in race time among the 61 Ironman athletes (adj R2=0.50, p<0.001). These results suggests that maximal fat oxidation rate exert an independent influence on ultra-endurance performance (>9 h). Furthermore, we demonstrate that 50% of the variation in Ironman triathlon race time can be explained by peak oxygen uptake and maximal fat oxidation.